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Subcorp \Filename ID Start End
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Subcorp \Filename ID Start End
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Subcorp \Filename ID Start End
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Subcorp \Filename ID Start End
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Subcorp \Filename ID Start End
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Subcorp \Filename ID Start End
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Subcorp \Filename ID Start End
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Subcorp \Filename ID Start End
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0-100 abstractIndiv00091.txt 110 1569 1582
0-100 abstractIndiv00091.txt 111 1586 1593
0-100 abstractIndiv00091.txt 112 1594 1603
0-100 abstractIndiv00091.txt 113 1607 1610
0-100 abstractIndiv00091.txt 114 1624 1632
0-100 abstractIndiv00091.txt 115 1660 1670
0-100 abstractIndiv00091.txt 116 1695 1702
0-100 abstractIndiv00091.txt 117 1734 1743
0-100 abstractIndiv00091.txt 118 1745 1749
0-100 abstractIndiv00091.txt 119 1751 1755
0-100 abstractIndiv00091.txt 120 1761 1770
0-100 abstractIndiv00091.txt 121 1771 1793
0-100 abstractIndiv00091.txt 122 1771 1781
0-100 abstractIndiv00091.txt 123 1801 1806
Text Comment
VALIDATION
STATISTICAL ANALYSIS
COMPUTER MODELING METHOD
QUANTITATIVE ANALYSIS
RADIO LIGAND BINDING DATA
RADIO LIGAND BINDING
RADIO LIGAND
MIXTURES
PHARMACOLOGICAL RECEPTOR SUBTYPES
Accurate and reliable assessment
mixtures
pharmacological receptor subtypes
pharmacological
optimally quantitative data analysis
optimally quantitative
radioligand binding
radioligand
competition
selective drugs
validity
statistically tested
limits
computer modeling method
analysis
heterogeneous receptor populations
heterogeneous receptor
heterogeneous
study
.alpha.- and .beta.-adrenergic receptor subtypes
method
testing
accurate estimates
accurate
analysis of binding data
analysis
binding data
experimentally derived and simulated
.beta.-adrenergic receptor subtype mixtures
mixtures
receptor subtypes
created
various proportions
various
previously characterized
previously
pure .beta.1- and .beta.2-adrenergic receptor preparations
turkey and frog erythrocyte membranes
turkey
frog
Monte Carlo simulation methods
methods
currently available .beta.-adrenergic ligands
resolution limit
method
mixture
about 90%/10% or 10%/90%
about
high- and low-affinity receptor subtypes
high- and low-affinity
high
low
mixtures
computer analysis
competition curves
competition
tritiated dihydroalprenolol ([3H]DHA) binding
tritiated dihydroalprenolol ([3H]DHA)
Zinterol
MJ9184
200-fold .beta.2-adrenergic-selective
200-fold
norepinephrine
70-fold .beta.1-adrenergic selective
70-fold
.beta.1-adrenergic
observation
significant discrimination
2 sites
2
2/3
experiments
Simultaneous analysis
Simultaneous
competition curves
same experiment
same
ligands
different selectivities
different
more accurate estimates
more accurate
each component
each
receptor mixture
affinity constant
ligands
receptor subtype
ideal mixture
ideal
equal proportions
equal
each receptor subtype
each
competition curves
drugs
6-fold selectivity
6-fold
document
both receptor subtypes
both
computer modeling method
analyzing
mixtures
adrenergic receptor subtypes
same validation approach
same
other receptor subtype systems
other
estimate
resolution limit
resolution
development
new selective drugs
new
selective
Text Comment
SPIN LABELED NARCOTICS
SPIN LABELED
series
spin-labeled derivatives
spin-labeled
morphine
codeine
synthesized
ESR spectroscopy
examine
molecular interactions
molecular
Animal studies
Animal
conducted
determine
relative analgesic potencies
analgesic
drugs
One
spin-labeled drugs
spin-labeled
isolated
rat brains
ESR
showed
enzymatic hydrolysis
enzymatic
drug
relatively slow process
relatively slow
pharmacological effects
pharmacological
drugs
spin-labeled molecules
spin-labeled
hydrolysis product
hydrolysis
morphine
codeine
ESR
demonstrate
spin-labeled drugs
isolated synaptic membrane preparations
isolated
synaptic membrane
synaptic
ESR
valuable tool
study
interaction
spin-labeled analgesic drugs
spin-labeled
analgesic
membranes
Text Comment
human and veterinary health
trends
directions
initiatives
objective
overview
harmonization efforts
animal health community
scientific networks
interdisciplinary communication
interdisciplinary
organizations
animal-related public health
animal
role
veterinary pharmaceutical scientist
veterinary pharmaceutical
human health-oriented professional organizations
recent publications
veterinary pharmacology, pharmaceutics and therapeutics
role
global networking
veterinary product
research and development
Text Comment
Activation
antitumor agent aminoflavone
antitumor
NSC 686288
mediated
induction
tumor cell cytochrome P450 1A1/1A2
tumor cell cytochrome
present studies
present
mechanism
cytotoxicity
aminoflavone analog
(5-amino-2,3-fluorophenyl)- 6,8-difluoro-7-methyl-4H-1-benzopyran-4-one
AF; NSC 686288
novel flavone
novel
in vitro
in vivo
antiproliferative activity
antiproliferative
number
human tumor cell lines
unique pattern
unique
antiproliferative activity
antiproliferative
National Cancer Institute
tumor cell line screen
tumor cell line
AF
metabolized
cytochrome P450 (P450) 1A1 and 1A2
P450
several metabolites
several
one
identified
mass spectrometry
potentially reactive hydroxylamine
potentially reactive
potentially
Radiolabeled AF
Radiolabeled
converted
rat and human microsomes
recombinant CYP1A1 and CYP1A2
sensitive human tumor cell lines
sensitive
species
covalently bound
macromolecules
Treatment
sensitive human MCF7 cells
sensitive
AF
increased CYP1A1 mRNA and CYP1A1/1A2 protein
increased
covalent binding
AF metabolite
DNA
phosphorylation
stabilization
p53
increased
increased expression
p53 transcriptional target
transcriptional
p21
Covalent binding
AF metabolite
increased
pretreatment
CYP1A inducer 3-methylcholanthrene
CYP1A inducer
CYP1A
decreased
coincubation
CYP1A inhibitor
CYP1A
alpha-naphthoflavone
induction
CYP1A1
covalent binding
AF metabolite
AF-resistant M14-MEL cells
AF-resistant
observations
AF
induce
metabolic activation
CYP1A1/1A2 induction
CYP1A1/1A2
cytotoxic DNA-damaging
cytotoxic DNA-damaging species
tumor cells
AF
other agents
treatment strategy
tumors
CYP1A1/1A2 induction
CYP1A1/1A2
breast, ovarian, and renal cancers
breast
ovarian
renal
Text Comment
Aerosolization
lipoplexes
AERx Pulmonary Delivery System
AERx
Pulmonary Delivery
Pulmonary
lung
attractive target
delivering
gene therapy
gene
local and potentially systemic delivery
local
potentially systemic
gene products
objective
study
AERx
AERx Pulmonary Delivery System
delivering
nonviral gene therapy formulations
nonviral gene therapy
gene
lung
naked"" DNA
naked""
degradation
aerosolization
AERx nozzle system
AERx
DNA
formulated
molar excess
molar
cationic lipids
lipoplexes
no loss
no
integrity
lipoplexes
no significant change
no
particle size
particle
zeta (zeta) potential
degree
complexation
extrusion
data
complexation
cationic lipids
protective effect
formulation
extrusion
no significant change
no
potency
formulation
transfection study
transfection
A-549 cells
culture
DNA formulations
DNA
lactose
aerosolized poorly
poorly
Significant improvements
aerosolization efficiency
aerosolization
electrolytes
NaCl
added
formulation
data
delivery
lipoplexes
AERx Pulmonary Delivery System
AERx
pulmonary gene therapy
pulmonary
Text Comment
Bioerodible injectable poly(ortho ester)
Bioerodible
injectable
tetracycline controlled delivery
tetracycline controlled
tetracycline
periodontal pockets
Preliminary trial
humans
semisolid consistency
poly(ortho esters)
POEs
tetracycline free base
direct injection
periodontal pocket
periodontal
sustained and almost constant in vitro release
sustained and almost constant
in vitro
phosphate
phosphate buffer
pH 7.4
37degreesC
14 days
Total polymer degradation
Total
polymer
concomitant
drug
drug release
Formulations
10% or 20% (wt/wt) tetracycline
10% or 20% (wt/wt)
10%
20%
wt/wt
12 patients
12
severe and recurrent periodontitis
severe and recurrent
6
patients
single-rooted teeth
molar teeth
furcations
treated immediately
scaling and root planing
Patients
formulations
no pain
no
application
irritation or discomfort
observation period
retention
formulation
minimal
first
first study
improved clinical protocol
second study
second
stopping bleeding
scaling and root planning
retention
formulations
inflamed periodontal pockets
11 days
tetracycline concentrations
tetracycline
gingival crevicular fluid
gingival crevicular
higher
minimum inhibitory concentration
minimum
tetracycline
most
most periodontal pathogens
periodontal
Text Comment
Characterization
two pharmacophores
two
multidrug transporter
P-glycoprotein
multidrug transporter
P-glycoprotein
plasma membrane protein
cell and tissue detoxification
cell
tissue
multidrug resistance (MDR) phenotype
multidrug resistance
MDR
actively expels
actively
cells
number
cytotoxic molecules
cytotoxic
all amphiphilic
all
chemically unrelated
investigated
molecular characteristics
binding selectivity
binding
P-glycoprotein
molecular modeling approach
various substrates
various
combined
enzymological study
enzymological
substrates
native membrane vesicles
native
prepared
MDR cells
MDR
affinities
mutual relationships
changes
P-glycoprotein ATPase activity
P-glycoprotein ATPase
cyclic peptides
cyclic
peptide-like compounds
peptide-like
alone
combination
Modeling
intramolecular distribution
intramolecular
hydrophobic and polar surfaces
this series
molecules
superimpose
surface elements
molecular alignments
correlated
observed
mutual exclusions
binding
P-glycoprotein
characterization
two different, but partially overlapping, pharmacophores
two different
two
partially overlapping
partially
pharmacophores
ligands
compete
each other
each
typical MDR-associated molecules
typical
MDR-associated
verapamil
cyclosporin A
actinomycin D
bound
pharmacophore 1
vinblastine
bound
pharmacophore 2
multispecific binding pocket
multispecific
P-glycoprotein
sites
one another
bind
ligands
distribution
hydrophobic and polar elements
hydrophobic
polar
chemical motifs
existence
two pharmacophores
two
increases
multiple chemical structure recognition
multiple
chemical structure
size
ligands
compete
ligands
binding
P-glycoprotein
Text Comment
Comparison
formulation requirements
formulation
dosator and dosing disc automatic capsule filling machines
dosator
dosing disc
automatic
capsule filling
capsule
objective
study
'semi-quantitative' or 'rigorous' definitions
semi-quantitative
rigorous
fluidity, lubricity and compactibility requirements
fluidity
lubricity
compactibility
formulation
representative dosator and dosing disc capsule filling machines
dosator
dosing disc
capsule filling
capsule
model formulations
developed
properties
Carr's compressibility index
ejection force
ejection
plug breaking force
plug
breaking
specified compression force
compression
gauge
fluidity
lubricity
compactibility
formulations
encapsulated
Hofliger-Karg
Hofliger-Karg GKF400 dosing disc machine
dosing disc
Zanasi LZ-64 dosator machine
Zanasi
dosator
machine
measure
plug compression and ejection forces
plug compression and ejection
plug
encapsulation process
% CV
fill-weight
ejection force
ejection
plug breaking force
plug breaking
plug
dissolution
marker drugs
marker
formulations
f(2) metric
dissolution profiles
dissolution
results
formulations
flow criteria
flow
successful encapsulation
successful
two machines
two
relatively lower level
relatively lower
lubricant
dosing disc machine
dosing disc
higher degree
higher
formulation compactibility
formulation
dosator machine
dosator
transferring
formulations
machine types
same class
same
different subclass
different
FDA's SUPAC-IR/MR Manufacturing Equipment Addendum
FDA's
SUPAC-IR/MR
challenging
dissolution profiles
dissolution
formulation
two machines
two
equivalent
compression force
f(2) < 50
f(2)
<
50
results
study
range
formulation characteristics
formulation
transferring
formulations
two types
two
machines
Text Comment
MDR1
single nucleotide polymorphisms
C3435T
G2677T
real-time polymerase chain reaction
real-time
MDR1
single nucleotide polymorphism
genotyping assay
objective
study
real-time polymerase chain reaction (PCR) method
real-time
polymerase chain reaction
PCR
MDR1
human multidrug resistance gene
single nucleotide polymorphisms
SNPs
C3435T
G2677T
C3435T
G2677T
MDR1*2
associated
enhanced efflux activity
enhanced
efflux
in vitro
Smart Cycler
allele-specific real-time PCR-based genotyping method
allele-specific
real-time
PCR-based
PCR
detect
C3435T
G2677T
MDR1
genotype
human genomic DNA templates
human genomic DNA
direct DNA sequencing
direct
DNA
PCR reactions
PCR
genotyping
C3435T
G2677T
allele-specific primers
allele-specific
separate tubes
separate
additional nucleotide mismatch
additional
nucleotide
third position
third
3' end
3'
allele-specific primer
allele-specific
abrogate
nonspecific PCR amplification
nonspecific
PCR
fluorescence
SYBR Green I
monitored
detect
formation
specific PCR products
specific
PCR
PCR growth curves
PCR
threshold cycle
positive
Fluorescence melt-curve analysis
Fluorescence
melt-curve
corroborate
results
PCR growth curves
PCR
PCR growth curves
PCR
assay
accurately determined
hetero- and homozygosity
C3435T
G2677T
Genotype assignments
Genotype
PCR growth curve
PCR
melt-curve analysis
melt-curve
agarose gel electrophoresis
agarose gel
agarose
direct DNA sequencing
direct
DNA
results
PCR products
PCR
perfect agreement
rapid MDR1 genotyping method
rapid
MDR1
MDR1*2
pharmacokinetic and pharmacodynamic variability
pharmacokinetic
pharmacodynamic
P-glycoprotein substrates
Text Comment
Discovery
novel targets
quinoline drugs
quinoline
human purine binding proteome
purine binding
purine
quinolines
treatment
malaria
arthritis
lupus
many years
precise mechanism
precise
action
unclear
functional proteomics approach
functional proteomics
functional
structural similarities
quinoline compounds
purine ring
ATP
identify
quinoline-binding proteins
quinoline-binding
quinoline drugs
quinoline
screened
displacement affinity chromatography
displacement affinity
displacement
purine binding proteome
purine binding
purine
captured
gamma-phosphate-linked ATP-Sepharose
gamma-phosphate-linked
Screening
human red blood cell purine binding proteome
purine binding
purine
two human proteins
two
aldehyde dehydrogenase 1
ALDH1
quinone reductase 2
QR2
contrast
no proteins
no
screening
Plasmodium falciparum purine binding proteome
purine binding
purine
quinolines
complementary approach
complementary
cell lysates
mice
red blood cells
P. falciparum
hydroxychloroquine- or primaquine-Sepharose
displacement affinity chromatography screen
displacement affinity
displacement
ALDH
QR2
proteins
recovered
mice and human red blood cell lysate
no proteins
no
P. falciparum
activity
QR2
potently inhibited
several
quinolines
in vitro
results
ALDH1
QR2
selective targets
quinolines
insights
mechanism
action
drugs
Text Comment
Dissolution test development
Dissolution
complex veterinary dosage forms
complex
Oral boluses
Oral
Fundamental aspects
electrolyte chemistry
electrolyte
design
dissolution medium
dissolution
capacity
maintain
sink conditions
test
Dissolution
various bolus dosage forms
various
bolus
USP Apparatus II
USP
Complete dissolution
Complete
each drug
each
designed medium
designed
achieved
evidence
dissolution test
dissolution
discriminating
review
development
potentially discriminating in vitro dissolution tests
potentially discriminating
in vitro
dissolution
veterinary boluses
veterinary
USP Apparatus II
USP
examines
potential role
testing
product quality assessments
product quality
product
evaluation
postapproval manufacturing changes
manufacturing
establishment
generic equivalence
veterinary products
veterinary
Text Comment
Effects
obesity
pharmacodynamics
nitroglycerin
conscious rats
conscious
Literature reports
hemodynamic response
hemodynamic
organic nitrates
organic
obese patients
obese
effect
studied
compared
mean arterial pressure
mean
arterial
MAP
responses
single doses
single
nitroglycerin
NTG
0.5-50 mug
conscious Zucker obese (ZOB), Zucker lean (ZL), and Sprague-Dawley (SD) rats
Zucker obese
ZOB
Zucker lean
ZL
Sprague-Dawley
SD
NTG tolerance development
NTG tolerance
NTG
animal groups
separately examined
separately
Rats
1 and 10 pg/min
NTG or vehicle infusion
NTG
vehicle
maximal MAP response
maximal
MAP
hourly 30 mug NTG IV challenge dose
30 mug
NTG IV
CD
measured
Steady-state
NTG plasma concentrations
NTG
plasma
measured
10 mug/min NTG infusion
10 mug/min
NTG
E (max,) and ED (50) values
E (max,)
ED (50)
33.9 +/- 3.6 and 3.5 +/- 1.7 mug
SD rats
SD
33.2 +/- 4.1 and 3.0 +/- 1.4 mug
ZL rats
ZL
34.8 +/- 3.9 and 5.3 +/- 2.8 mug
ZOB rats
ZOB
respectively
No difference
No
found
dose-response curves
dose-response
3 groups
3
P > .05
P
.05
2-way ANOVA
2-way
dynamics
NTG tolerance development
NTG tolerance
NTG
steady-state NTG plasma concentrations
steady-state
NTG
plasma
3 animal groups
3
results
ZOB rats
ZOB
not more resistant
not more
hemodynamic effects
hemodynamic
organic nitrates
organic
compared
lean controls
lean
acute and chronic hemodynamic effects
acute and chronic
hemodynamic
induced
NTG
not sensitively affected
not
obesity
conscious animal model
animal
genetic obesity
Text Comment
Flurbiprofen release
Flurbiprofen
Eudragit RS and RL aqueous nanosuspensions
Eudragit RS and RL
aqueous
kinetic study
kinetic
DSC
dialysis experiments
dialysis
present work
present
Flurbiprofen
FLU
Eudragit RS100 (RS) and Eudragit RL100 (RL) nanosuspensions
Eudragit RS100
RS
Eudragit RL100
RL
biological model membrane
Dimyristoylphosphatidylcholine (DMPC) multilamellar vesicles (MLV)
Dimyristoylphosphatidylcholine
DMPC
MLV
release
compared
observed
solid drug particles
solid
dialysis experiments
dialysis
Nanosuspensions
prepared
modification
Quasi-Emulsion Solvent Diffusion technique
Solvent
Drug release
Drug
monitored
Differential Scanning Calorimetry
DSC
FLU
MLV
transition temperature
T(m)
DMPC liposomes
DMPC
shift
lower values
lower
temperature shift
temperature
modulated
drug fraction
drug
aqueous lipid bilayer suspension
aqueous
lipid bilayer
DSC
increasing incubation periods
increasing
incubation
37 degrees C
suspensions
blank liposomes
blank
fixed amounts
fixed
unloaded and FLU-loaded nanosuspensions
unloaded
FLU-loaded
FLU
powdered free drug
powdered
free
T(m) shifts
T(m)
drug released
drug
polymeric system
polymeric
free-drug dissolution
free-drug
incubation cycles
incubation
free drug
free
increasing
molar fractions
dispersed directly
directly
membrane
preparation
results
compared
drug release
drug
classical dialysis technique
classical
dialysis
suitability
2 different techniques
2
different
drug release
drug
differences
2 RL and RS polymer systems
2
RL
RS
polymer
confirm
efficacy
DSC
studying
release
polymeric nanoparticulate systems
polymeric nanoparticulate
classical"" release test
classical""
dialysis
different rate
different
kinetic release
kinetic
void liposomes
void
better uptaking system
aqueous solution
aqueous
dialysis experiments
dialysis
Text Comment
Identification
ligand-binding regions
ligand-binding
ligand
P-glycoprotein
activated-pharmacophore
photoaffinity labeling
photoaffinity
matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry
matrix-assisted laser desorption/ionization-time-of-flight
laser
mass
Energy dependent efflux pumps
Energy dependent
Energy
efflux
resistance
anticancer, antimicrobial, and antiparasitic drugs
anticancer
antimicrobial
antiparasitic
P-glycoprotein
Pgp, ABCB1
mediates
resistance
broad spectrum
broad
antitumor drugs
antitumor
Compounds
nontoxic
cells
shown
inhibitors
Pgp
mechanism
binding
transport
low-molecular-mass ligands
low-molecular-mass
Pgp
incompletely understood
incompletely
study
series
propafenone-related photoaffinity ligands
propafenone-related
propafenone
photoaffinity
combine
high specificity and selectivity
high
Pgp
high labeling efficiency
high
labeling
Molecules
intrinsically photoactivatable
intrinsically
arylcarbonyl group
pharmacophoric substructure
pharmacophoric
group
ligand molecules
ligand
detailed study
detailed
structure-activity relationship
structure
activity
type
photoligand
subsequent experiments
subsequent
ligands
characterize
drug-binding domain
drug-binding
drug
propafenone-type
propafenone-type analogs
propafenone
Matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry
Matrix-assisted laser desorption/ionization-time-of-flight
laser
MALDI-TOF
propafenone-type ligands
propafenone-type
propafenone
preferentially label
preferentially
fragments
putative transmembrane segments 3, 5, 6, 8, 10, 11, and 12
3, 5, 6, 8, 10, 11, and 12
Labeled fragments
identified
highly charged region
highly
15 amino acids
15
second cytoplasmic loop
second
cytoplasmic
region
EAA-like motif
EAA-like
EAA
proposed
interaction
transmembrane domain
nucleotide binding domain
nucleotide binding
nucleotide
peroxisomal ATP-binding cassette transporters
peroxisomal
ATP-binding
region
cytoplasmic loop 3
cytoplasmic
TM12
N terminus
Walker A sequence
NBD2
labeled
ligands
number
confined protein regions
protein
drug-binding domain
drug-binding
drug
propafenone-type analogs
propafenone-type
Text Comment
Impact
antimicrobial resistance
antimicrobial
regulatory policies
veterinary medicine
Status report
Increasing resistance
Increasing
antimicrobial agents
antimicrobial
growing concern
growing
public health officials
public health
worldwide
concern
infections
hospitals
community infections
outpatient care settings
resistant foodborne disease
foodborne
drug use
drug
food-producing animals
food-producing
United States
significant source
antimicrobial-resistant foodborne infections
antimicrobial-resistant
foodborne
humans
acquisition
resistant bacteria
resistant
animals
US Food and Drug Administration's (FDA's) goal
US Food and Drug Administration's
US
FDA's
public health impact
public health
antimicrobial drugs
antimicrobial
food-producing animals
food-producing
significant human antimicrobial therapies
significant
human
not compromised or lost
not
antimicrobials
food animals
FDA's approach
FDA's
problem
multipronged
innovative
strategy
revision
pre-approval safety assessment
new animal drug applications
new
animal drug
risk assessment
risk
human health effect
human health
human
antimicrobials
food animals
robust monitoring
susceptibilities
foodborne pathogens
foodborne
drugs
human and veterinary medicine
human
veterinary
research
risk management
risk
Text Comment
Inflammation
modulates
interaction
heterogeneous nuclear ribonucleoprotein
hnRNP) I
polypyrimidine tract binding protein
binding
hnRNP L
3 ' untranslated region
3'
murine inducible nitric-oxide synthase mRNA
murine inducible
murine
nitric-oxide
two members
two
heterogeneous nuclear ribonucleoprotein (hnRNP) family
heterogeneous nuclear ribonucleoprotein
hnRNP
3' untranslated region
3'
UTR
murine inducible nitric-oxide synthase (iNOS) mRNA
murine inducible nitric-oxide synthase
nitric-oxide
iNOS
mRNA
study
iNOS
RNA-protein complex
protein extracts
untreated and septic shock treated mouse liver
untreated and septic shock treated
UV cross-linking
UV
complex
two proteins
two
molecular masses
60 and 70 kDa
60-kDa protein binding site
60-kDa protein
60-kDa
112-nt pyrimidine-rich sequence
112
160 nt
160
coding sequence
RNA-protein complex
precipitated
monoclonal antibody
hnRNP I
polypyrimidine tract binding protein
PTB
70-kDa protein
70-kDa
binds
43-nt sequence
43-nt
43
3' end
3'
3' UTR
3'
immunoprecipitated
monoclonal antibody
hnRNP L
computer-simulated conformation
computer-simulated
3' UTR
3'
binding sites
regions
protein
Supershifts
native RNA-protein complex
native
anti-hnRNP L
multiprotein RNA complex
hnRNP L
exposed
antibodies
hnRNP I
PTB
interaction
mRNA
Up-regulation
iNOS
septic shock
RNA-protein complex formation
RNA-protein complex
hnRNP I
PTB
hnRNP L
iNOS mRNA
modulated
inflammation
novel function
two
proteins
regulators
iNOS gene
Text Comment
Inhibition
protein tyrosine/mitogen-activated protein kinase phosphatase activity
protein tyrosine
mitogen-activated protein kinase phosphatase
associated
D-2 dopamine receptor supersensitivity
D-2 dopamine receptor
dopamine
rat model
rat
Parkinson's disease
Previous work
Previous
stimulation
D-2 dopamine receptors
dopamine
D(2)DRs
unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat
6-hydroxydopamine
6-OHDA
extracellular signal-regulated kinase (ERK) activity
extracellular signal-regulated kinase
ERK
ipsilateral
lesion
present work
designed
explore
mechanism
activation
ERK
denervated striatum
D2DR
60% inhibition
60%
protein tyrosine phosphatase (PTP) activity
protein tyrosine phosphatase
PTP
PSP activity
lesioned striata
D2DR antagonist spiperone
D2DR antagonist
D2DR
spiperone
blocked
quinpirole-elicited PTP inhibition
PTP
D-1 receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
D-1 receptor agonist
D-1 receptor
SKF38393
did not inhibit
PTP activity
PTP
PTP inhibition
PTP
specific effect
mediated
stimulation
D2DR
discovered
striatal mitogen-activated protein kinase phosphatase
MKP
protein phosphatase
ERK dephosphorylation
ERK
inhibited
D2DR stimulation
D2DR
6-OHDA-lesioned rats
6-OHDA-lesioned
6-OHDA
MKP1
identified
isozyme
D2DR stimulation
D2DR
PC12 cells
express D2DR
D2DR
quinpirole
PTP or MKP activity
PTP
MKP
ERK
activated
D-2 dopamine receptor stimulation
D-2 dopamine receptor
dopamine
6-OHDA-induced
6-OHDA
striatal denervation
striatal
D2DR
PTP/MKP pathway
PTP
MKP
unilateral inhibition
unilateral
striatal PTP
striatal
intrastriatal injection
intrastriatal
vanadate
contralateral rotation
contralateral
control rats
control
D2DR stimulation
D2DR
response observed
unilateral 6-OHDA-lesioned rat
unilateral
6-OHDA
results
attenuation
PTP/MKP pathway
PTP
MKP
development
D2DR supersensitivity
D2DR
Text Comment
Interspecies considerations
evaluation
human food safety
human
veterinary drugs
veterinary
Residues
parent drug
parent
metabolites
interspecies comparisons
interspecies
xenobiotic metabolism
xenobiotic
focus
article
residue studies
establish
human food safety
human
interspecies pharmacokinetic differences and similarities
interspecies
pharmacokinetic
impact
drug residues
animal- derived foods
factors
comparisons
2 drugs
2
ivermectin
fenbendazole
activities
2 US programs
2
US
Food Animal Residue Avoidance Databank
FARAD
NRSP-7 (National Research Support Project Number 7) Minor Use Animal Drug Program
NRSP-7
National Research Support Project Number 7
presented
strategies
employed
study
species differences
Text Comment
Special Animal Health Issue
AAPS PharmSci
goal
special volume
veterinary scientists
veterinary
state-of-the art reviews
animal health
human health scientists
human health
challenges and collaborative opportunities
animal health counterparts
animal health
contributors
highly respected experts
current issues and state-of-the-art advances
veterinary medicine
Text Comment
Maleimide
potent inhibitor
topoisomerase II
in vitro
in vivo
new mode
new
catalytic inhibition
Maleimide
N-ethyl-maleimide
NEM
N-methyl-maleimide
NMM
potent catalytic inhibitors
potent
catalytic
purified human topoisomerase IIalpha
purified
ring-saturated analog
ring-saturated
succinimide
completely inactive
completely
Catalytic inhibition
abrogated
topoisomerase II mutations
topoisomerase II
totally abolish
totally
bisdioxopiperazine compounds
catalytic inhibition
different mode
different
action
maleimides
DNA cleavage assay
DNA
maleimide
NEM
antagonize
etoposide-induced DNA double-strand breaks
etoposide-induced
etoposide
DNA
maleimide
antagonize
topoisomerase II poisons
topoisomerase II
three different in vivo assays
three different
in vivo
alkaline elution assay
alkaline
elution
maleimide
etoposide-induced DNA damage
etoposide-induced
etoposide
DNA
band depletion assay
band depletion
maleimide
etoposide-induced trapping
etoposide-induced
etoposide
topoisomerase IIalpha and beta
DNA
clonogenic assay
maleimide
antagonized
cytotoxicity
etoposide
daunorubicin
four different cell lines
four different
human and murine origin
human
murine
at-MDR cell lines
reduced nuclear topoisomerase IIalpha content
reduced
nuclear topoisomerase IIalpha
fully sensitive
fully
maleimide
topoisomerase II poison
topoisomerase II
in vivo
finding
topoisomerase II
sensitive
maleimide
NMM
NEM
insensitive
succinimide
strict requirement
strict
unsaturated ring bond
activity
observed
antagonism
in vitro
in vivo
covalent modification
covalent
topoisomerase II cysteine residues
cysteine
amount
catalytically active enzyme
catalytically active
sensitive
action
topoisomerase II poisons
topoisomerase II
Text Comment
Model system
study
classical nuclear export signals
classical
nuclear export
Signal-mediated protein transport
Signal-mediated
protein
nuclear pore complex
pore
field
molecular pharmaceutics
Nuclear localization signals
Nuclear localization
target
genes
antisense delivery systems
antisense
delivery
nucleus
Studying
nuclear export
enhancing
expression
efficiency
action
therapeutic agents
therapeutic
mechanism
nuclear import
well studied
well
proteins
mechanism
identified
subject
nuclear export
initial stages
initial
considerable amount
uncertainty
Two main
Two main export receptors
Two
export
identified
Exportin 1
Crm1
Calreticulin
Crm1
leucine-rich amino acid sequences
leucine
amino acid
proteins
exports
classical nuclear export signals
nuclear export
paper
model system
study
identify
establish
classical nuclear export signals
nuclear export
green fluorescent protein
green fluorescent
GFP
Two putative export signals
Two putative
Two
export
human progesterone receptor
human progesterone
PR
strongest nuclear export signal
strongest
nuclear export
mitogen activated protein kinase kinase
mitogen activated
MAPKK
studied
model system
Text Comment
Modulation
mouse and human phenobarbital-responsive enhancer module
phenobarbital-responsive
phenobarbital
nuclear receptors
constitutive androstane receptor
CAR
regulates
mouse and human CYP2B genes
binding
direct repeat-4 (DR4) motifs
phenobarbital-responsive enhancer module
phenobarbital-responsive
phenobarbital
PBREM
PBREM elements
PBREM
nuclear receptors
extent
cross-talk
CAR
other nuclear receptors
currently unknown
transient transfection and DNA binding experiments
transient transfection
DNA binding
DNA
binding
DR4 motifs
not correlate
not
activation response
mouse and human PBREM
efficiently 'insulated'
effects
other nuclear receptors
other
substantial affinity
DR4 motifs
Certain nuclear receptors
Certain
not bind
not
DR4 motifs
peroxisome proliferator-activated receptor-alpha
peroxisome
proliferator-activated
farnesoid X receptor
suppress
PBREM function
PBREM
coactivator-dependent process
coactivator
relevance
in vivo
competition experiments
competition
mouse PBREM
more selective
more
CAR
human PBREM
Pregnane X, vitamin D, and thyroid hormone receptors
vitamin D
thyroid hormone
human CAR
human PBREM
selective nature
PBREM
CYP3A enhancers
highly and comparably responsive
highly
comparably
CAR
pregnane X receptor
vitamin D receptor
ligand specificities
ligand
human and mouse CAR
defined
mammalian cotransfection
mammalian
yeast two-hybrid techniques
yeast
two
results
new mechanistic explanations
new mechanistic
several previously unresolved aspects
several
CYP2B and CYP3A gene regulation
CYP2B
CYP3A
Text Comment
Molecular Modeling
site-specific mutagenesis
site-specific
histamine-binding site
histamine-binding
histamine
histamine H-4 receptor
histamine
histamine H-4 receptor
histamine
novel G-protein-coupled receptor
novel
G-protein-coupled
G-protein
unique pharmacological profile
distribution
H4 mRNA
role
regulation
immune function
immune
allergy
asthma
define
histamine-binding site
histamine-binding
histamine
receptor
molecular modeling
site-directed mutagenesis
site-directed
predict
alter
amino acids
residing
histamine-binding pocket
histamine-binding
histamine
effects
alterations
histamine binding
receptor activation
assessed
results
Asp(94) (3.32)
transmembrane region (TM) 3
Glu(182) (5.46)
TM5
critically involved
critically
histamine binding
histamine
Asp(94)
counter-anion
anion
cationic amino group
histamine
Glu(182) (5.46)
interacts
N-tau nitrogen atom
N-tau
histamine imidazole ring
histamine
imidazole
ion pair
Thr(178) (5.42)
Ser(179) (5.43)
TM5
not significantly involved
not significantly
histamine binding
histamine
receptor
receptor activation
results
those
analogous residues
analogous
H-1 histamine receptor
histamine
findings
H-2 histamine receptor
histamine
results
Asn(147) (4.57)
TM4
Ser(320) (6.52)
TM6
role
receptor activation
receptor
not involved
not
histamine binding
histamine
data
indicate
histamine
bind
H-4 receptor
similar
predicted
other histamine receptor subtypes
important differences
exploited
discovery
novel
novel H-4-selective compounds
H-4-selective
Text Comment
Molecular basis
voltage-dependent potassium currents
voltage-dependent
voltage
potassium
porcine granulosa cells
major objective
major
study
elucidate
molecular bases
K+
K+ current diversity
K+ current
porcine granulosa cells
GC
Two delayed rectifier K+ currents
Two delayed rectifier
Two
K+ currents
K+
electrophysiological and pharmacological properties
electrophysiological
pharmacological
recorded
porcine GC
whole-cell patch clamp
whole-cell
cell
slowly activating, noninactivating current
I-Ks
antagonized
clofilium
293B
L-735,821
L-768,673
ultrarapidly activating, slowly inactivating current
I-Kur
antagonized completely
completely
clofilium
4-aminopyridine
partially
tetraethylammonium
charybdotoxin
dendrotoxin
kaliotoxin
molecular identity
K+ channel genes
K+
I-Ks
I-Kur
examined
reverse transcription-polymerase chain reaction
reverse transcription
immunoblotting
detect
K+ channel transcripts
K+
proteins
GC
express
multiple voltage-dependent K+ (Kv) channel subunits
multiple
voltage-dependent
K+
KCNQ1
KCNE1
Kv1.1
Kv1.2
Kv1.3
Kv1.4
Kv1.5
Kv1.6
Kvbeta1.3
Kvbeta2
Coimmunoprecipitation
establish
hetero-oligomeric nature
granulosa cell Kv channels
KCNE1
KCNQ1
coassociated
GC
expression
coincided
expression
I-Ks
Extensive coassociation
Extensive
various Kv alpha- and beta-subunits
various
documented
diverse electrophysiological and pharmacological properties
diverse
electrophysiological and pharmacological
I-Kur currents
variation
composition
stoichiometry
channel assemblies
differences
post-translational modification
post-translational
contributing
Kv channel subunits
findings
essential background
experimental definition
experimental
granulosa K+ channel function(s)
granulosa K+ channel
functional roles
specific GC K+ channels
specific
proteins
novel targets
novel
assisted reproduction
potential sites
potential
drug toxicity
drug
Text Comment
Multiple interference
Multiple
anthracyclines
mitochondrial creatine kinases
creatine
Preferential damage
Preferential
cardiac isoenzyme
cardiac
implications
drug cardiotoxicity
drug
Anthracyclines
most efficient drugs
most efficient
most
cancer chemotherapy
limited
significant risk
significant
cardiotoxicity
understood
This study
This
investigates
impairment
mitochondrial creatine kinase
creatine
MtCK
key
key enzyme
cellular energy metabolism
anthracycline cardiotoxicity
anthracycline
analyzed
effects
three anthracyclines
three
doxorubicin
daunorubicin
idarubicin
two MtCK isoenzymes
two
sarcomeric/cardiac sMtCK
ubiquitous uMtCK
human
chicken
surface plasmon resonance
surface
gel filtration
gel
enzyme assays
quantified properties
quantified
basic importance
basic
MtCK
functioning
in vivo
membrane binding
membrane
octameric state
enzymatic activity
enzymatic
Anthracyclines
impaired
three properties
three
differences
dose-, time-, and drug-dependence
Membrane binding
Membrane
enzymatic activity
enzymatic
low
low anthracycline concentrations
anthracycline
5-100 muM
high clinical relevance
high
clinical
Effects
membrane binding
membrane
immediate
competitive binding
competitive
drug
cardiolipin
dissociation
MtCK octamers
dimers
enzymatic inactivation
enzymatic
cross-linking
occurred
hours
days
Different protection assays
Different
deleterious effects
oxidative damage
highly susceptible MtCK cysteines
highly susceptible
highly
generation
free oxygen radicals
higher drug concentrations
higher
drug
Enzymatic inactivation
Enzymatic
occurred
mainly
active site
active
involved
Cys278
experiments
protective agents
sMtCK mutant C278G
All anthracycline effects
All
anthracycline
more pronounced
more
sMtCK
uMtCK
in vitro results
sMtCK damage
sMtCK
role
anthracycline cardiotoxicity
anthracycline
Text Comment
Near-infrared spectral imaging
Near-infrared
quality assurance
quality
pharmaceutical products
analysis
tablets
assess
powder blend homogeneity
powder blend
objective
study
evaluate
near-infrared (NIR) spectroscopic imaging
near-infrared
NIR
tool
assess
pharmaceutical quality assurance problem
quality assurance
quality
blend uniformity
final dosage product
dosage
system
array detector technology
rapidly collect
rapidly
high-contrast NIR images
high-contrast
NIR
furosemide tablets
furosemide
varying
mixing
5 grades
experimental tablets
experimental
containing
same amount
furosemide
microcrystalline cellulose
microcrystalline
produced
well blended
unblended
comparison
tablets
analyzed
traditional NIR spectroscopy
NIR
both
both approaches
evaluate
drug product homogeneity
drug product
NIR spectral imaging
NIR
clearly differentiating
clearly
each grade
each
blending
qualitatively
quantitatively
spatial distribution
spatial
components
variation
contrast
pixel intensity
pixel
NIR spectral contribution
NIR spectral
each pixel
each
chemical nature
chemical
each pixel
each
identified
localized
localized spectrum
each pixel
each
Both univariate and partial least squares (PLS) images
Both
univariate
partial least squares
PLS
evaluated
suboptimal blends
suboptimal
regions
heterogeneity
visual inspection
visual
images
quantitative measure
quantitative
blending
determined
calculating
standard deviation
distribution
pixel intensities
PLS score images
PLS
score
percent standard deviation
percent
increased progressively
11%
240%
well blended to unblended tablets
well blended
unblended
NIR spectral imaging system
NIR spectral imaging
NIR
rapid approach
acquiring
spatial and spectral information
spatial
spectral
pharmaceuticals
technique
potential
variety
applications
product quality assurance
control
manufacturing processes
Text Comment
Novel system
investigate
effects
inhaled volume
inhaled
rates
rise
simulated
simulated inspiratory air flow
simulated inspiratory
air
fine particle output
fine particle
fine
dry powder inhaler
dry powder
dry
study
evaluated
effect
inhaled volume
inhaled
simulated inspiratory flow rate ramps
simulated
flow rate
flow
fine
fine particle output
fine particle
dry powder inhalers
dry powder
dry
DPIs
simple, robust system
developed
rate of rise""
rise"" (ramp) effects
maintaining
constant air flow
constant
air
multi-stage liquid impinger
multi-stage
liquid
MSLI
sizing
emitted particles
emitted
Ramps
programmed
30 and 60 L/min
over
100 milliseconds
500 milliseconds
1, 2, and 3 seconds
Rotahaler
test DPI
test
Testing
simulated inhalation volumes
simulated
inhalation
2L
4L
Testing
USP apparatus 4
USP
30 L/min
2 L volume
2L
amount
drug
exiting
device
fine particle fraction
particle
FPF
increased
2.33 mug
6.04 mug
3-second ramp
3-second
100-millisecond ramp
100-millisecond
11.64 mug
FPF
USP (no ramp) method
USP
same flow rate
same
4 L volume
4L
FPF
increased
2.23 mug
8.45 mug
10.25 mug
USP method
USP
60 L/min
similar trends
observed
both flow rates
both
flow
increase
FPF
shallowest to the steepest ramp
shallowest
steepest
no significant differences
no
FPF
2 L inhaled volume
2L
inhaled
4 L volume
4L
each flow rate
each
flow
data
existing USP apparatus
existing
USP
overestimate
FPF
flow rates
flow
lower
recommended
USP
Text Comment
Oxidative stress
Oxidative
G protein-coupled receptor kinase 2
G protein-coupled
lymphocytes
calpain-dependent mechanism
calpain
G protein-coupled receptor kinase (GRK) 2
G protein-coupled
crucial role
regulating
desensitization
resensitization
G protein-coupled receptors
G protein-coupled
GPCRs
expression level
GRK2
lymphocytes
decreases
inflammatory diseases
arthritis
Reactive oxygen species
Reactive
important role
variety
inflammatory conditions
inflammatory
arthritis
demonstrate
oxidative stress
oxidative
exposure
lymphocytes
H2O2
50% reduction
50%
GRK2 protein levels
GRK2 protein
GRK activity
GRK
no changes
no
mRNA expression
mRNA
Treatment
lymphocytes
tyrosine kinase inhibitor
tyrosine
genistein
partially reverses
partially
effect
H2O2
GRK2 levels
GRK2
not detect
not
direct tyrosine phosphorylation
direct
tyrosine
GRK2
Inhibition
nonproteasomal protease
nonproteasomal
calpain
calpeptin
prevent
H2O2-induced
H2O2
GRK2 decrease
GRK2
In vitro experiments
In vitro
GRK2
partially digested
partially
m-calpain
calcium-dependent way
calcium
H2O2-induced decrease
H2O2-induced
H2O2
GRK2 levels
GRK2
70% decrease
70%
agonist-induced beta(2)-adrenergic receptor sequestration
agonist-induced
agonist
beta(2)-adrenergic receptor
oxidative stress
oxidative
novel mechanism
novel
regulation
intracellular level
intracellular
GRK2
inflammatory processes
inflammatory
data
demonstrate
oxidative stress
oxidative
GPCRs
calpain-dependent regulation
calpain
GRK2 levels
GRK2
Text Comment
Pharmaceutical impurities
Pharmaceutical
mini-review
mini
control
pharmaceutical impurities
pharmaceutical
critical issue
pharmaceutical industry
pharmaceutical
International Conference on Harmonization
ICH
formulated
workable guideline
control
impurities
review
description
different types and origins
different
impurities
relation
ICH guidelines
ICH
degradation routes
degradation
specific examples
presented
article
measures
control
impurities
pharmaceuticals
Text Comment
Pharmacogenomics
implementation phase
implementation
Pharmacogenomics
genetic and genomic principles
genetic
genomic
facilitate
drug discovery and development
drug
improve
drug therapy
drug
goal
optimal therapy
optimal
individual
individual patient
article
analyzes
current trends
current
pharmacogenomics
new science
new
affects
drug development
drug
pharmaceutical industry
clinical use
clinical
drugs
Text Comment
Protein binding predictions
Protein binding
Protein
infants
Plasma binding protein levels
Plasma binding protein
Plasma binding
lower
newborn
adult
gradually increase
age
birth
human serum albumin (HSA) concentrations
human serum albumin
HSA
close
adult levels
adult
75%
80%
alpha 1-acid glycoprotein
AAG
initially half
initially
adult concentration
adult
result
extent
drug binding
drug
HSA
closer
adult
those drugs
those
bound
largely
AAG
model
fraction unbound
fraction
adults
ratio
binding protein concentration
binding protein
binding
infants
adults
predicted
fraction unbound
fraction
infants
children
Text Comment
Statistical modeling
Statistical
protein spray drying
protein
lab scale
lab
objective
study
examine
effects
formulation
process variables
particle size
particle
other characteristics
spray-dried model protein
spray-dried
spray
model
bovine serum albumin
BSA
partial factorial design
partial factorial
experiments
Formulation variables
tested
concentration
zinc:protein complexation ratio
zinc
protein
ratio
Process variables
explored
inlet temperature
liquid feed rate
liquid
drying air flow rate
drying air
drying
atomizing nitrogen pressure
atomizing nitrogen
atomizing
lab-scale
lab-scale spray dryer
spray
Statistical data analysis
Statistical
data
determine
F ratios
each
inputs
provided
ranking
importance
variables
each powder characteristic
each
protein concentration
protein
atomizing nitrogen pressure
atomizing nitrogen
atomizing
greatest effects
greatest
particle size
particle
protein powder
protein
product yield
results
protein concentration
protein
critical variable
critical
outlet temperature
mostly influenced
mostly
inlet temperature
liquid feed
liquid feed rate
liquid
Mathematical models
based
these input-output relationships
these
constructed
models
insight
controllable variables
spray-drying process
Text Comment
Stereospecific activation
Stereospecific
cardiac ATP-sensitive K+ channels
ATP-sensitive
K+
epoxyeicosatrienoic acids
structural determinant study
structural determinant
structural
heart
richly endowed
richly
K-ATP channels
function
biological sensors
biological
regulating
membrane potentials
membrane
electrical excitability
electrical
response
metabolic alterations
metabolic
recently reported
recently
cytochrome P450 metabolites
arachidonic acid
epoxyeicosatrienoic acids
EETs
potently activate
potently
cardiac K-ATP channels
reducing
channel sensitivity
channel
ATP
present study
present
further demonstrate
further
11(S), 12(R)-EET
activated
cardiac K-ATP channels
EC50
39.5 nM
11(R), 12(S)-EET
totally inactive
totally
11(S), 12(R)-EET
11(R), 12(S)-EET
hyperpolarized
resting membrane potentials
membrane
shortened
duration
cardiomyocyte action potentials
cardiomyocyte action
cardiomyocyte
studying
homologs
analogs
11,12-EET
all four EET regioisomers
all four
equipotent activators
equipotent
K-ATP channels
reducing
ATP sensitivity
ATP
more than
10-fold
neither
altered chain length
double bond number
epoxide position
epoxide
methylation
carboxyl group
affected
channel inhibitions
channel
ATP
All
fatty epoxides
fatty
studied
potent K-ATP channel activators
potent
K-ATP channel
omega-3 homolog
potent
reducing
ATP sensitivity
ATP
27-fold
results
epoxide group
particular three-dimensional configuration
particular
critical determinant
critical
K-ATP channel activation
K-ATP channel
effect
augmented
double bond
omega-3 position
omega-3
results
fatty epoxides
fatty
important modulators
important
cardiac
cardiac electrical excitability
electrical
Text Comment
Structurally and functionally important amino acids
Structurally
functionally
agonistic conformation
agonistic
human vitamin D receptor
vitamin D
crystal structures
ligand binding domain
ligand
human vitamin D receptor
vitamin D
VDR
complexed
natural ligand
natural
superagonists
MC1288
KH1060
recently
reported
crystallized ligand binding domain
ligand
LBD
VDR
differs
full-length VDR
full-length
deletion
50 amino acids
50
its helices 2 and 3
its
this
this study
investigated
structurally and functionally important amino acid interactions
structurally
functionally
amino acid
ligand binding pocket
ligand
full-length VDR
full-length
several synthetic vitamin D-3 analogs
several synthetic
several
vitamin D-3
site-directed mutagenesis scanning
site-directed
site
combined
limited proteolytic digestion
limited
proteolytic
electrophoretic mobility shift assay
electrophoretic mobility
reporter gene assay
reporter gene
correlated
findings
crystal structures
truncated VDR LBD
VDR
results
structurally different agonists
structurally different
structurally
distinct ligand-receptor interactions
distinct
ligand
receptor
amino acid residues
H229
D232
E269
F279
Y295
agonistic conformation
agonistic
VDR
biological data
biological
full-length VDR
full-length
crystal structure
truncated VDR LBD
VDR
removal
insertion domain
helices 2 and 3
receptor
not markedly influence
not
functionality
VDR
Text Comment
Study
novel rosin-based biomaterials
novel rosin-based
rosin
pharmaceutical coating
pharmaceutical
coating
film forming
film
coating properties
coating
Glycerol ester
maleic rosin
GMR
Pentaerythritol ester
maleic rosin
PMR
investigated
2 rosin-based biomaterials
2 rosin-based
2
rosin
initially characterized
initially
physicochemical properties
physicochemical
molecular weight
Mw
glass transition temperature
Tg
Films
produced
solvent evaporation technique
solvent
mercury substrate
mercury
Dibutyl sebacate plasticized and nonplasticized films
Dibutyl sebacate
plasticized
nonplasticized
characterized
mechanical
tensile zzzz strength
percentage elongation
percentage
Young's modulus
water vapor transmission
water vapor
vapor
transmission
WVT
moisture absorption parameters
moisture absorption
moisture
Plasticization
increase
film elongation
film
decrease
Young's modulus
films
flexible
reducing
brittleness
Poor rates
Poor
WVT
percentage moisture absorption
percentage
moisture
demonstrated
various film formulations
various
Diclofenac sodium-layered pellets
Diclofenac
sodium-layered
sodium
GMR and PMR film formulations
sustained drug release
sustained
drug
10 hours
release rate
release
influenced
extent
plasticization
coating level
results
obtained
study
demonstrate
utility
novel rosin-based biomaterials
novel rosin-based
novel
rosin
pharmaceutical coating
pharmaceutical
sustained-release drug delivery systems
sustained-release drug delivery
sustained
drug
Text Comment
Synthesis
evaluation
new class
new
nifedipine analogs
T-type calcium channel blocking activity
T-type calcium channel
calcium
synthesized
novel series
novel
18 dialkyl 1,4-dihydro-4(2'-alkoxy-6'-pentadecylphenyl)-2,6-dimethyl-3,5 pyridine dicarboxylates
18
anacardic acid
natural compound
natural
cashew nut shells
investigated
blocking action
L- and T-type calcium channels
transiently expressed
transiently
tSA-201 cells
IC50 values
IC50
L-type calcium channel block
L-type calcium channel
calcium
obtained
series
ranged
1 to similar to 40 muM
similar
higher affinities
higher
increasing
size
alkoxy group
4-phenyl ring
ester substituent
3,5 positions
3,5
detailed analysis
strongest L-type channel blocker
series
PPK-12
block
poorly reversible
poorly
mediated
apparent speeding
time course
inactivation
PPK-12
midpoint
steady state inactivation curve
steady state inactivation
20 mV
hyperpolarized potentials
increase
blocking efficacy
depolarized holding potentials
depolarized
PPK-12 blocked T- and L-type calcium channels
PPK-12 blocked
PPK-12
calcium
similar affinities
similar
weakest L-type channel inhibitors
weakest
L-type channel
PPK-5
T-type channel affinity
T-type channel
similar
PPK-12
resulting
40-fold selectivity
40-fold
PPK-5
T- over L-type channels
over
dialkyl 1,4-dihydro-4-(2'alkoxy-6'-pentadecylphenyl)-2,6-dimethyl-3,5 pyridine dicarboxylates
excellent candidates
development
T-type calcium-channel specific blockers
T-type calcium-channel specific
T-type calcium-channel
Text Comment
role
clinical pharmacologist
clinical
animal health
animal
most scientific disciplines
most
pharmacology
subspecialties
most scientists
most
value
animal studies
animal
drug development
drug
human pharmaceuticals
human
animals
target species
target
major focus
major
investigation
recent estimates
recent
United States
year 2000
98.1 million cattle
98.1 million
59.8 million pigs
59.8 million
1.5 billion chickens
1.5 billion
estimate
companion animals
companion
4 million horses
4 million
59 million cats
59 million
52.9 million dogs
52.9 million
estimate
minor""
minor"" species
7 million sheep
7 million
320 000 acres
freshwater fish production
freshwater fish
medical needs
animals
addressed
human medicine
human
distinct differences
distinct
human counterpart
veterinary clinical pharmacology
Text Comment
Translocation
liposomes
cancer cells
cell-penetrating peptides
cell-penetrating
penetratin
TAT
kinetic and efficacy study
kinetic
efficacy
conventional liposomes
conventional
sterically stabilized liposomes
sterically stabilized
smaller volume
smaller
distribution
reduced clearance
reduced
encapsulated drugs
encapsulated
tumor sites
tumor
intracellular
intracellular delivery
stable drug retention
drug
liposomes
diminishes
efficacy
liposomal drug
liposomal
uptake
liposomal drugs
liposomal
cells
two cell-penetrating peptides
two
cell-penetrating
penetratin
PEN
TAT
HIV-1 TAT protein
studied
control peptides
control
TAT
PEN
enhanced
translocation efficiency
translocation
liposomes
proportion
number
peptides
liposomal surface
liposomal
peptide number
peptide
five
enhance
intracellular delivery
intracellular
liposomes
kinetics
uptake
peptide- and cell-type dependent
peptide- and cell-type
peptide
cell
Intracellular accumulation
Intracellular
TAT-liposomes
increased
incubation time
incubation
PEN-liposomes
1h
declined gradually
treatment
1 mug/ml doxorubicin equivalents
1 mug/ml
doxorubicin
liposome
2h
TAT
increased
doxorubicin uptake
doxorubicin
A431 cells
12-fold
improvement
uptake
liposomal doxorubicin
liposomal
not reflected
not
cytotoxicity
in vitro
tumor control
tumor
in vivo
results
adding
CPP
liposome encapsulating
liposome encapsulating anticancer drug
liposome
anticancer
inadequate
improving
antitumor activity
antitumor
additional approach
additional
enhance
intracellular release
intracellular
encapsulated drug
encapsulated
Text Comment
Vascular-targeted overexpression
G protein-coupled receptor kinase-2
G protein-coupled
transgenic mice
transgenic
beta-adrenergic receptor signaling
beta-adrenergic receptor
resting blood pressure
resting
blood
Cardiovascular regulation
Cardiovascular
controlled
signaling
G protein-coupled receptors
GPCRs
beta-Adrenergic receptors
ARs
GPCRs
regulate
inotropy
chronotropy
heart
mediate
vasodilation
critically influences
critically
systemic vascular resistance
vascular
GPCR kinases
GRKs
GRK2
betaARK1
phosphorylate
desensitize
agonist-activated betaARs
agonist-activated
Myocardial GRK2 levels
Myocardial GRK2
increased
heart failure
heart
data
suggest
vascular levels
vascular
elevated
hypertension
generated
transgenic mice
transgenic
vascular smooth muscle
VSM
overexpression
GRK2
SM22alpha promoter
determine
vascular betaAR regulation
vascular betaAR
VSM betaAR signaling
VSM betaAR
adenylyl cyclase and mitogen-activated protein (MAP) kinase activation assays
adenylyl cyclase and mitogen-activated protein (MAP) kinase activation
adenylyl cyclase
mitogen-activated protein
MAP
attenuated
GRK2
overexpressed
2- to 3-fold
In vivo vasodilation
In vivo
response
betaAR stimulation
betaAR
isoproterenol
attenuated
conscious resting mean arterial blood pressure
conscious resting
mean
arterial blood
arterial
elevated
96 +/- 2 mm Hg
nontransgenic littermate control (NLC) mice
nontransgenic littermate control
nontransgenic
NLC
n=9
=
9
112 +/- 3 mm Hg
117 +/- 2 mm Hg
two different lines
two different
SM22alpha-GRK2 transgenic mice
n=7
=
7
n=5
=
5
p < 0.05
<
0.05
medial VSM thickness
medial
VSM
increased
30%
29.8 +/- 1.6 &mu;m
NLC mice
NLC
n=6
=
6
39.4 +/- 1.6 &mu;m
SM22&alpha;-GRK2 mice
n=7
=
7
p < 0.05
<
0.05
vascular GRK2 overexpression
vascular GRK2
sufficient
cardiac
cardiac hypertrophy
data
developed
unique mouse model
unique
mouse
hypertension
insight
contribution
vascular betaAR signaling
vascular betaAR
resting blood pressure
resting
blood
overall cardiovascular regulation
overall
cardiovascular
they
GRK2
important role
vascular control
vascular
novel therapeutic target
novel
therapeutic
hypertension
Text Comment
Inhibition
human insulin gene transcription
human insulin gene
immunosuppressive drugs
immunosuppressive
cyclosporin A
tacrolimus
primary, mature islets
primary, mature
transgenic mice
transgenic
Cyclosporin A
tacrolimus
clinically important immunosuppressive drugs
clinically important
clinically
immunosuppressive
diabetogenic action
diabetogenic
most serious adverse effects
most
underlying mechanism
Previous studies
Previous
shown
tacrolimus
inhibit
insulin gene transcription
insulin gene
high concentrations
high
tumor cell lines
study
insulin gene transcription
insulin gene
normal, mature pancreatic islet cells
normal
mature
novel approach
novel
present study
present
Transgenic mice
Transgenic
human insulin promoter-reporter gene
generated
human insulin promoter directed transcription
human insulin promoter directed
human insulin promoter
pancreatic islets
normal, physiological glucose response
glucose
reporter gene
reporter gene expression
isolated islets
isolated
stimulation
glucose
human insulin promoter-mediated gene expression
human insulin promoter-mediated
human insulin promoter
gene
inhibited
normal, mature islet cells
normal
mature
both
tacrolimus
cyclosporin A
large extent
large
approximately 70%
approximately
high potency
high
concentrations
inhibit
calcineurin phosphatase activity
calcineurin phosphatase
IC50 values
IC50
1 and 35 nM
glucose stimulated calcineurin phosphatase activity
glucose stimulated
glucose
calcineurin phosphatase
mouse pancreatic islets
further supporting
further
calcineurin phosphatase activity
calcineurin phosphatase
essential part
glucose signaling
glucose
human insulin gene
high potency
high
cyclosporin A
tacrolimus
normal islets
normal
inhibition
insulin gene transcription
insulin gene
cyclosporin A
tacrolimus
clinically important
clinically
one mechanism
one
diabetogenic effect
diabetogenic
immunosuppressive drugs
immunosuppressive
Text Comment
Possible involvement
small oligomers
small
amyloid-beta peptides
15-deoxy-Delta(12,14) prostaglandin
J(2)-sensitive microglial activation
J(2)-sensitive microglial
J(2)-sensitive
Alzheimer's disease
fibrillar amyloid-beta (Abeta) peptides
fibrillar
form
senile plaques
senile
microglia
relationship
Abeta peptides
microglia
not fully understood
not fully
study
incubation
Abeta1-40
Abeta40
small oligomers
small
incubation
Abeta1-42
Abeta42
large molecular aggregates
large molecular
Microglial production
Microglial
nitrite
interleukin-6
tumor necrosis factor-a
tumor necrosis
induced
Abeta40
Abeta42
production
significantly reduced
15-deoxy-Delta(12,14) prostaglandin J(2)
completely suppressed
completely
beta-sheet breaker peptide
beta-sheet breaker
Leu-Pro-Phe-Phe-Asp
results
small oligomers
small
large molecular aggregates
large molecular
mediate
microglial activation
microglial
induced
Abeta peptides
Text Comment
new and simple method
new
simple
delivering
clamped nitric oxide concentrations
nitric oxide
physiological range
physiological
activation
guanylyl cyclase-coupled nitric oxide receptors
guanylyl cyclase-coupled
nitric oxide
signaling molecule nitric oxide
signaling
NO
engage
multiple pathways
multiple
influence
cellular function
cellular
relative biological importance
biological
not been possible
not been
administer
NO
steady-state conditions
normally axiomatic
analyzing
ligand-receptor interactions
ligand
receptor
downstream signal transduction
problem
chemical method
generating
constant NO concentrations
constant
NO
derived
balancing
NO release
NO
NONOate donor
NO consumption
NO
sink
theoretical grounds
2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
CPTIO
selected
sink
mixture
contained
urate
convert
unwanted product
unwanted
reaction
NO(2)
nitrite ions
method
enabled
NO concentrations
NO
covering
physiological range
physiological
0-100 nM
formed
approximately 1 s
approximately
concentrations
sufficiently stable
sufficiently
several minutes
biological purposes
biological
applied
activation
guanylyl cyclase-coupled NO receptors
guanylyl cyclase-coupled
NO
method
EC(50)
1.7 nM NO
1.7 nM
protein
purified
bovine lung
lower
estimated previously
previously
biological NO sink
biological
NO
red blood cells
corresponding values
alpha1beta1 and alpha2beta1 isoforms
0.9 nM
0.5 nM
slopes
concentration-response curves
concentration-response
concentration
more shallow
more
Hill coefficient
1
2
questioning
consider
binding
one NO molecule
one
receptor activation
receptor
discrepancies
limitations
earlier method
biological problems
biological
addressed
adaptations
new method
new
Text Comment
new method
new
predict
flowability
microscale fluid bed
microscale fluid
microscale
purpose
research
new method
new
predict
flow behavior
flow
pharmaceutical powders
pharmaceutical
multichamber microscale fluid bed
multichamber
microscale fluid
microscale
Different amounts
poorly flowing paracetamol
poorly flowing
poorly
added
various grades
various
microcrystalline celluloses
microcrystalline
silicified microcrystalline cellulose powders
silicified microcrystalline cellulose
silicified microcrystalline
Magnesium stearate
lubricant
Experimental minimum fluidization velocities
minimum
fluidization
u(mf)
defined
2 to 4 g
equal to
10 mL
material
Video 1
reference flowability
powders
determined
specific flow meter
specific
flow
weight variation
weight
compressed powders
compressed
single-punch press
single-punch
single
measured
amount
paracetamol
excipients
increased
experimental umf
increased
fluidization behavior
fluidization
Video 2
Principal component analysis
PCA
established
pressure difference
bed
function
fluidization velocity
fluidization
characterize
behavior
powders
increase
poor fluidization behavior
poor
fluidization
powders
increasing amount
increasing
paracetamol
increasing weight variation
weight
tablets
angle of repose
flow rate
silicified microcrystalline cellulose powders
silicified microcrystalline cellulose
silicified microcrystalline
predicted
partial least squares (PLS) model
partial least squares
developed method
predict
flowability
promising approach
preformulation and formulation stages
preformulation
formulation
new drug candidates
new
Text Comment
photo-crosslinked poly(vinyl alcohol) hydrogel growth factor release vehicle
photo-crosslinked poly(vinyl alcohol) hydrogel growth factor
photo-crosslinked
poly(vinyl alcohol)
wound healing applications
objective
study
develop
evaluate
hydrogel vehicle
sustained release
sustained
growth factors
wound healing applications
Hydrogels
fabricated
ultraviolet photo-crosslinking
ultraviolet
acrylamide-functionalized nondegradable poly(vinyl alcohol)
acrylamide-functionalized
nondegradable
PVA
Protein permeability
Protein
initially assessed
trypsin inhibitor
TI
21 000 MW model protein drug
21 000 MW
model
protein
TI permeability
TI
altered
changing
solids content
gel
adding
hydrophilic PVA fillers
hydrophilic
PVA content
PVA
increased
10%
20%
protein flux
protein
decreased
no
TI
permeating
20% PVA hydrogels
20%
PVA
increase
model drug release
model
drug
incorporating
hydrophilic PVA fillers
hydrophilic
hydrogel
filler molecular weight
filler
increased
TI flux
TI
increased
mechanism
alteration
protein/gel interactions
protein
gel
transient variations
transient
water content
water
percent protein released
protein released
protein
altered
varying
protein loading concentration
protein loading
protein
Release studies
Release
conducted
growth factor
vehicles
hydrophilic filler
hydrophilic
sustained release
sustained
platelet-derived growth factor
platelet-derived
PDGF-beta,beta
3 days
less than 24 hours
less than
controls
In vitro
bioactivity
demonstrated
doubling
normal human dermal fibroblast numbers
human dermal fibroblast
exposed
growth factor-loaded vehicle
growth factor-loaded
growth factor
compared
control
release vehicle
release
developed
study
rapid and simple fabrication method
rapid and simple
fabrication
protein release
protein
tailored
modifying
solid content
incorporating
biocompatible hydrophilic fillers
biocompatible hydrophilic
varying
protein loading concentration
protein loading
protein
Text Comment
semiautomated approach
gene discovery
gene
expressed sequence tag data mining
expressed sequence tag
expressed sequence
Discovery
new human transporter genes
new
Identification
functional characterization
genes
human genome
major challenge
principal source
principal
publicly available information
purpose
National Center for Biotechnology Information
database
expressed sequence tags
dbEST
4 million human ESTs
4 million
human
extract
information
data
developed
semiautomated method
mine
dbEST
uncharacterized human genes
uncharacterized
single protein input sequence
single
input
family
related proteins
related
all species
all
compiled
entire
entire family
human EST database
human EST
human
new gene candidates
new
Evaluation
putative new gene candidates
putative
new
gene
family
characterized proteins
characterized
inference
structure
function
new genes
new
applied
test data set
28 families
28
major facilitator superfamily
major facilitator
major
MFS
membrane transporters
protocol
73 previously characterized human MFS genes
73
previously characterized
43 new MFS gene candidates
43
new
Development
approach
provided
insights
problems
pitfalls
automated data mining
automated
public databases
Text Comment
AAPS/RAPS/CAPRA collaborative program
AAPS
RAPS
CAPRA
exploring
challenges
drug regulation
drug
global environment
clinical concerns
Globalization
pharmaceutical industry
harmonize
regulatory requirements
governing
marketing
medicinal products
minimize
barriers
global drug product registration
global
drug product
International Conference on the Harmonization of Technical Requirements of Pharmaceuticals for Human Use
Pharmaceuticals
Human
ICH
established
1990
ICH
developed
series
guidelines
reflect
agreements
reached
participating nations
participating
aspects
chemistry
clinical technical sections
fulfill
regulatory requirements
various jurisdications
various
continue
points
divergent perspectives
barriers
impede
foreign clinical data
importance
issues
Regulatory Science
Regulatory Science (RS) section
RS
American Association of Pharmaceutical Scientists
AAPS
conjunction
Regulatory Affairs Professional Society
RAPS
Canadian Association of Professional Regulatory Affairs
CAPRA
cosponsored
public forum
topic
manuscript
summary
speaker presentations
speaker
audience discussions
audience
design
clinical trials
clinical
extrapolation
results
trials
support
international drug registration
international
drug
Text Comment
Akt
molecular target
molecular
signal transduction therapy
signal transduction
signal
brain ischemic insult
brain
Growth factors
insulin-like
insulin-like growth factor-1
IGF-1
promote
cell survival
cell
ischemic brain injury
brain
Stimulation
IGF-1 receptor
coupled
tyrosine kinase
activates
phosphatidylinositol 3-kinase
subsequently
protein kinase B
Akt
hippocampal neurons
hippocampal
introduce
new approach
new
signal transduction therapy
signal transduction
signal
brain damage
brain
ischemic insult
shown
IGF-1
intracerebroventricular injection
intracerebroventricular
sodium orthovanadate
protein tyrosine phosphatase inhibitor
protein tyrosine phosphatase
prior
ischemic insult
blocked
delayed neuronal death
delayed
CA1 region
CA1
neuroprotective effects
neuroprotective
orthovanadate
IGF-1
associated
increased
Akt activity
CA1 region
CA1
potential targets
Akt
neuroprotective activity
neuroprotective
findings
lead
conclusion
Akt activity
Akt
potential target
neuroprotective drugs
neuroprotective
brain ischemic insult
brain
other episodes
other
excitotoxic neuronal apoptosis
excitotoxic neuronal
seizure
Huntington's and Parkinson's diseases
Text Comment
Amphiphilic star-like macromolecules
Amphiphilic star-like
novel carriers
topical delivery
topical
nonsteroidal anti-inflammatory drugs
nonsteroidal anti-inflammatory
objective
study
evaluate
amphiphilic star-like macromolecules
amphiphilic star-like
ASMs
topical drug delivery system
topical
drug delivery
Indomethacin
piroxicam
ketoprofen
individually encapsulated
individually
ASMs
coprecipitation
effects
ASMs
percutaneous permeation
percutaneous
nonsteroidal anti-inflammatory drugs
nonsteroidal anti-inflammatory
NSAIDs
full thickness, hairless mouse skin
full thickness
hairless
evaluated
in vitro
modified Franz diffusion cells
modified
diffusion
solubility and in vitro release experiments
solubility
in vitro
performed
characterize
ASMs behavior
ASMs
aqueous media
aqueous
Poly(ethylene glycol)
PEG
Pluronic P-85
used
polymer controls
polymer
compare
role
PEG
amphiphilic behavior
amphiphilic
ASMs
In vitro release experiments
In vitro
indicated
ASMs
delay
drug release
drug
P < .05
<
.05
solubility measurements
solubility
ASMs
increase
NSAIDs aqueous solubility
NSAIDs
P < .05
<
.05
Percutaneous permeation studies
Percutaneous
revealed
ASMs
decreased
both
flux
Q(24)
drugs
compared
control
P < .10
<
.10
Skin pretreatment studies
Skin
ASM-containing solution
ASM-containing
ASM
drug application
drug
demonstrated
pretreatment
similarly influenced
similarly
NSAID percutaneous permeation
NSAID
percutaneous
conclusion
ASMs
slow drug permeation
slow
drug
2 mechanisms
2
delayed drug diffusion
delayed
drug
its core
skin dehydration
skin
its shell
ASMs
delayed dermal delivery
delayed
dermal
prevention
compound permeation
compound
skin
sunscreens
N,N-diethyl-m-toluamide
DEET
aqueous formulations
aqueous
Text Comment
Apoptosis
induced
(E)-5-(2-bromovinyl)-2 '-deoxyuridine
varicella zoster virus thymidine kinase-expressing cells
thymidine kinase-expressing
driven
activation
c-Jun
activator protein-1
fas ligand
caspase-8
molecular mode
molecular
cell killing
cell
antiviral drug (E)-5-(2-bromovinyl-2'-deoxyuridine
antiviral
drug
BVDU
studied
Chinese hamster ovary (CHO) cells
Chinese
stably transfected
stably
thymidine kinase gene
tk
varicella zoster virus
CHO-VZVtk
colony-forming ability
cells
reduced
<1%
<
concentration
&SIM;1 &mu;M BVDU
&SIM;1 &mu;M
&SIM;
nontransfected cells
nontransfected
cells
transfected
tk gene
herpes simplex virus type 1
CHO-HSVtk
1000-fold higher dose
1000-fold
higher
required
achieve
same response
same
BVDU
inhibited
thymidylate synthase
CHO-VZVtk
not
CHO-HSVtk
control cells
control
drug
incorporated
DNA
VZVtk- and HSVtk-expressing cells
VZVtk- and HSVtk-expressing
equal amounts
equal
coexposure
CHO-VZVtk cells
exogenous thymidine
exogenous
protected
BVDU-induced cell killing
BVDU-induced
BVDU
cell
cells
die
thymidine depletion
thymidine
highly cytotoxic BVDU doses
highly cytotoxic
highly
50 &mu;M
longer exposure times
longer
24-48 h
VZVtk cells
blocked
some extent
some
S and G2/M phase
apoptosis
48-72 h
apoptosis
necrosis
induced
findings
show
drug
induction
c-Jun
activation
activator protein-1
resulting
increased level
increased
Fas ligand
FasL
caspase-8/-3 activation
caspase-8/-3
Bid
poly(ADP-ribose) polymerase
cleaved
caspases
Expression
Bax
increased
Bcl-2/Bcl-x(L)
remained
unchanged
Transfection
dominant-negative Fas-associated death domain
Fas-associated
Fas
death
inhibition
caspase-8
N-benzyloxycarbonyl-IETD-fluoromethyl ketone
strongly abrogated
BVDU-induced apoptosis
BVDU-induced
BVDU
indicating
Fas/FasL
crucially involved
BVDU-triggered apoptosis
BVDU-triggered
BVDU
differs significantly
significantly
induced
ganciclovir
induces
same cellular background
same
mitochondrial damage pathway
mitochondrial damage
Text Comment
Ascorbic acid
promising memory-enhancer
memory
mice
Alzheimer's disease
progressive neurodegenerative disorder
characterized
gradual decline
gradual
memory
occurrence
Alzheimer's disease
commonplace
Asian population
senior citizens
senior
present study
present
undertaken
assess
potential
ascorbic acid
memory-enhancer
Swiss mice
either sex
either
employed
present investigation
present
Elevated plus-maze
Elevated
passive-avoidance apparatus
passive-avoidance
served
exteroceptive behavioral models
exteroceptive behavioral
diazepam-, scopolamine-, and aging-induced amnesia
diazepam-, scopolamine-, and aging-induced
diazepam
scopolamine
served
interoceptive behavioral models
interoceptive behavioral
Ascorbic acid
60, 120 mg/kg
injected
3 and 8 consecutive days
consecutive
improved
learning
memory
aged mice
aged
indicated
decreased-transfer-latency
decreased
transfer
increased
step-down latency
step-down
ascorbic acid
provided
protection
young animals
young
scopolamine- and diazepam-induced impairment
scopolamine
diazepam
memory
Ascorbic acid
found
more potent
more
piracetam
reflected
smaller dose
smaller
more pronounced effect
more
quicker onset
quicker
action
Ascorbic acid
shown promise
powerful memory-improving agent
powerful
memory-improving
memory
particularly effective
aged animals
aged
ascorbic acid
memory-restorative agent
memory-restorative
memory
treatment
dementia
elderly individuals
elderly
underlying mechanism
action
ascorbic acid
attributed
antioxidant property
Text Comment
Carbamoylcholine homologs
Novel and potent agonists
Novel and potent
agonists
neuronal nicotinic acetylcholine receptors
neuronal
nicotinic acetylcholine
classic muscarinic acetylcholine receptor (mAChR) agonist
classic
mAChR
carbamoylcholine
carbachol
most obvious lead
most
development
selective ligands
selective
nicotinic acetylcholine receptors
nicotinic acetylcholine
nAChRs
N-methylations
carbachol
provided
N-methylcarbamoylcholine
N,N-dimethylcarbamoylcholine
DMCC
predominantly display
nicotinic activity
nicotinic
study
12 homologous analogs
12
homologous
DMCC
its corresponding tertiary amine
corresponding tertiary
N, N-dimethylcarbamoyl-N,N-dimethylaminoethanol
synthesized
binding affinities
native mAChR and nAChR sites
mAChR
nAChR
estimated
3-N,N-dimethylaminobutyl-N,N-dimethylcarbamate
displayed
low nanomolar binding affinity
low nanomolar
low
binding
nAChRs
400-fold selectivity
400-fold
nAChRs
mAChRs
new series
new
compounds
synthesized
alkyl and aryl groups
alkyl
aryl
different ring systems
different
ring
introduced
carbamate moiety
7
[H-3]epibatidine binding assay
[H-3]epibatidine
K-i values
K-i
7
analogs
rat alpha2beta2, alpha4beta2, alpha2beta4, alpha3beta4, and alpha4beta4 nAChRs
stably expressed
stably
mammalian cell lines
mammalian
ranged
low nanomolar
low
midmicromolar concentrations
midmicromolar
compounds
displayed
weak binding
weak
alpha7/5-HT3 chimera
native mAChRs
Compound 7
its analogs
determined
agonists
alpha3beta4 nAChR subtype
series
most potent and selective nicotinic agonists
most
potent and selective nicotinic
agonists
structurally derived
structurally
ACh
compounds
tertiary amines
implying
some advantages
some
bioavailability
future in vivo pharmacological studies
future
in vivo
pharmacological
observations
study
promising perspectives
future development
future
ligands
selective
specific nAChR subtypes
specific
Text Comment
Changes
blood viscosity
blood
synthetic protease inhibitors
synthetic
protease
examined
effects
whole blood viscosity
whole
blood
coagulation time
coagulation
various dosages
various
synthetic low-molecular protease inhibitors
synthetic
low-molecular
protease
gabexate mesilate
nafamostat mesilate
oscillation-type viscometer
oscillation-type
oscillation
either agent
either
added
blood viscosity
blood
decreased
dose-dependently
dose
sigmoid-like curve
sigmoid-like
coagulation time
coagulation
shorter
gabexate mesilate
nafamostat mesilate
differences
half-life
human blood
Thrombin generation
Thrombin
results
activation
coagulation factors
coagulation
inhibited
synthetic protease inhibitors
subsequently decreases
subsequently
blood viscosity
blood
dose-dependently
dose
Text Comment
Closure
gap junction channels
gap junction
arylaminobenzoates
determined
effect
flufenamic acid
FFA
related derivatives
related
gap junction channel currents
gap junction channel
gap junction
applying
dual whole-cell patch-clamp technique
dual
whole-cell
whole
patch-clamp
pairs
N2A neuroblastoma cells
transfected
various connexins
various
FFA
reduced
gap junction channel currents
gap junction channel
gap junction
reversible
concentration-dependent manner
concentration
Half-maximal concentrations
Half-maximal
FFA-induced reduction
FFA-induced
FFA
junctional conductance
cell pairs
coupled
different connexins
different
similar
20 to 60 muM
FFA
not greatly discriminate
not greatly
connexin subtypes
Hill coefficients
blockade
approximately 3
approximately
indicating
high degree
high
cooperativity
Analogs
FFA
reduced
junctional conductance
junctional
similar potencies
similar
other unrelated chloride channel blockers
other
unrelated
chloride channel
chloride
no effect
Inhibition
gap junction channels
gap junction
FFA
pK(a)
similar
3.8
increased
low external pH
suggesting
uncharged form
drug
blockade
effect
FFA
mediated
direct binding
direct
drug
pore
gap junction channel
gap junction
Internal application
Internal
high concentrations
high
FFA
addition
patch pipettes
inhibition
channel currents
channel
magnitude
inhibition
neither
voltage-dependent
influenced
nature
permeant ion
permeant
Single-channel recordings
Single-channel
Single
indicated
FFA
reduced
channel-open probability
channel
modifying
current amplitude
current
induced
slow transitions
open and closed states
propose
FFA
inhibits
gap junctions
inducing
conformational change
conformational
protein
binding
site
located
membrane
Text Comment
Colonic drug delivery
Colonic
drug
updated review
Specific targeting
drug
colon
recognized
several therapeutic advantages
several
Drugs
destroyed
acidic environment
stomach
metabolized
pancreatic enzymes
slightly affected
slightly
colon
Sustained colonic delivery
Sustained
colonic
drugs
treatment
nocturnal asthma
angina
arthritis
Treatment
colonic diseases
ulcerative colitis
Crohn's disease
colorectal cancer
more effective
more
direct delivery
direct
drugs
colon
article
aimed
providing
insight
design considerations
design
evaluation
colonic
colonic drug delivery systems
drug delivery
drug
anatomy
physiology
lower
lower gastrointestinal tract
discussed
biopharmaceutical aspects
biopharmaceutical
considered
drug absorption
drug
colon
Various approaches
Various
colon-specific drug delivery
colon-specific
colon
drug
discussed
Text Comment
Critical role
Akt1
modulation
apoptotic phosphatidylserine exposure
apoptotic
phosphatidylserine
microglial activation
microglial
Biological targets
Biological
neurodegenerative disease
intrinsic maintenance
cellular integrity
cellular
extrinsic prevention
phagocytic cellular disposal
phagocytic cellular
greatest promise
greatest
therapeutic intervention
therapeutic
Protein kinase B
Akt1
serine-threonine kinase
serine
threonine
closely involved
cell growth
cell
survival
offers
strong potential
both intrinsic and extrinsic mechanisms
both
neuronal injury
demonstrate
overexpression
constitutively active form
constitutively active
Akt1
myristoylated Akt1
myristoylated
differentiated SH-SY5Y neuronal cells
differentiated
intrinsic cellular protection
cellular
apoptotic genomic DNA destruction
apoptotic genomic
DNA
membrane phosphatidylserine (PS) exposure
membrane
phosphatidylserine
PS
Transfection
SH-SY5Y cells
plasmid
encoding
kinase-deficient dominant-negative Akt1
eliminates
cytoprotection
suggesting
activation
Akt1
necessary and sufficient
prevent
apoptotic destruction
apoptotic
Apoptotic neuronal membrane PS exposure
Apoptotic
neuronal membrane
PS
provides
unique pathway
Akt1
extrinsic cellular protection
extrinsic
cellular
block
microglial activation
microglial
independent cotreatment
anti-PS receptor neutralizing antibody
PS
neutralizing
prevent
microglial proliferation
microglial
Akt1
maintains
nuclear DNA integrity
DNA
membrane PS exposure
PS
specific inhibition
specific
caspase 3-, 8-, and 9-like activities
caspase
linked
mitochondrial membrane potential
mitochondrial membrane
cytochrome c release
cytochrome c
work
novel capacity
Akt1
maintain
cellular integrity
series
cysteine protease pathways
cysteine protease
uniquely regulate
uniquely
microglial activation
microglial
modulation
membrane PS residue externalization
membrane
PS residue
PS
Text Comment
Effect
TTC-909
cerebral infarction
cerebral
permanent occlusion
permanent
middle cerebral artery
middle
cerebral
stroke prone spontaneously hypertensive rats
stroke prone
spontaneously hypertensive
investigated
effect
TTC-909
drug preparation
stable prostaglandin I-2 analogue
stable
prostaglandin I-2
clinprost
isocarbacyclin methylester
methyl 5-{(1S,5S,6R,7R)-7-hydroxy-6-[(E)-(S)-3-hydroxy-1-octenyl] bicyclo[3.3.0]oct-2-en-3-yl} pentanoate
incorporated
lipid microspheres
cerebral infarction
cerebral
7 days
permanent occlusion
permanent
middle cerebral artery
middle
cerebral
MCA
stroke prone spontaneously hypertensive rats
stroke prone
spontaneously hypertensive
SHRSP
anesthesia
MCA
permanently occluded
permanently
rhinal fissure
schedule 1
vehicle
TTC-909
injected
i.v.
once daily
once
7 days
immediately
MCA occlusion
MCA
schedule 2
vehicle
TTC-909
infused
3h
immediately
MCA occlusion
MCA
schedule 3
vehicle
TTC-909
infused
3h
immediately
MCA occlusion
MCA
bolus injection
bolus
once daily
once
6 days
Seven days
infarct volume
infarct
estimated
hematoxylin and eosin staining
hematoxylin
eosin
Cerebral infarction
Cerebral
produced
permanent occlusion
permanent
MCA
limited
cerebral cortex
volume
reduced significantly
schedule 3
infarct volume
infarct
not reduced significantly
not
schedules I and 2
Ozagrel
thromboxane A(2) synthetase
thromboxane A(2) synthetase inhibitor
no effect
no
infarct volume
infarct
schedule 3
results
suggest
cerebral infarction
cerebral
developed progressively
first few hours
first few
permanent occlusion
permanent
MCA
SHRSP
TTC-909
inhibited
cerebral infarction
cerebral
improving
cerebral blood flow
cerebral
blood
protecting
neuronal damage
neuronal
Text Comment
Effects
muscarinic receptor antagonists
muscarinic receptor
M-2 antagonist activity
M-2 antagonist
cholinergic reflex bronchoconstriction
cholinergic reflex
ovalbumin-sensitized and -challenged mice
ovalbumin-sensitized and -challenged
investigate
inhibition
muscarinic M-2 receptors
muscarinic
results
enhancement
reflex bronchoconstriction
reflex
airway hyperresponsiveness
airway
evaluated
effects
muscarinic antagonists
muscarinic
M-2 antagonist activity
M-2 antagonist
methacholine (MCh)- and SO2-induced airway responses
methacholine
MCh
SO2
airway
ovalbumin (OVA)-sensitized and -challenged mice
ovalbumin (OVA)-sensitized and -challenged
model
similar airway hyperresponsiveness
similar
airway
MCh
12 mg/ml
observed
Days 31 and 37
31
37
2.2-fold
2.7-fold
airway hyperresponsiveness
airway
SO2
0.05 1/min
Day 37
37
Day 31
31
4.0- and 2.7-fold
Days 31 and 37
31
37
reflex bronchoconstriction
reflex
enhanced
Day 31
31
comparison
Day 37
37
Ipratropium
0.03 - 0.3 mg/ml
inhalation
Compound A
0.1 - 3 mg/kg
MCh-induced responses
MCh
Days 31 and 37
31
37
ipratropium
0.03 - 1 mg/ml
dose-dependently inhibited
SO2-induced responses
SO2
Day 31
ipratropium
dose
0.1 mg/ml
significantly increased
SO2-induced responses
SO2
Day 37
37
162.2%
corresponding control
Compound A
0.03 - 0.3 mg/kg
inhibited
SO2-induced responses
SO2
increases
Days 31 and 37
31
37
results
suggest
two different conditions
two
different
reflex bronchoconstriction
reflex
presented
model
SO2-induced responses
SO2
enhanced
dysfunctional M-2 receptors
dysfunctional
Day 31
31
dysfunctional M-2 receptors
dysfunctional
partially restored
partially
Day 37
37
inhibition
restored M-2 receptors
restored
further enhance
reflex bronchoconstriction
reflex
Text Comment
Expression
human organic anion transporters
organic anion
choroid plexus
interactions
neurotransmitter metabolites
neurotransmitter
purpose
present study
present
elucidate
expression
human organic anion transporter 1
organic anion
hOAT1
hOAT3
choroid plexus
human brain
their interactions
neurotransmitter metabolites
neurotransmitter
stable cell lines
stable
Immunohistochemical analysis
Immunohistochemical
revealed
hOAT1
hOAT3
expressed
cytoplasmic membrane
cytoplasm
human choroid plexus
Neurotransmitter metabolites
Neurotransmitter
5-methoxyindole-3-acetic acid
5-MI-3-AA
homovanillic acid
HVA
vanilmandelic acid
VMA
3,4-dihydroxyphenylacetic acid
DOPAC
5 -hydroxyindole-3-acetic acid
5-HI-3-AA
N-acetyl-5-hydroxytryptamine
NA-5-HTT
melatonin
5-methoxytryptamine
5-MTT
3,4-dihidroxymandelic acid
DHMA
5-hydroxytryptophol
5-methoxytryptophol
5-MTP
not
methanephrine
MN
normethanephrine
NMN
3-methyltyramine
3-MT
2 mM
inhibited
para-aminohippuric acid uptake
para-aminohippuric acid
mediated
hOAT1
melatonin
5-MI-3-AA
NA-5-HTT
5-MTT
5-MTP
HVA
5-HI-3-AA
VMA
DOPAC
5-hydroxytryptophol
MN
not
3-MT
DHMA
NMN
2 mM
inhibited
estrone sulfate uptake
estrone sulfate
mediated
hOAT3
Differences
IC50 values
hOAT1
hOAT3
observed
DHMA
DOPAC
HVA
5-HI-3-AA
melatonin
5-MI-3-AA
5-MTP
5-MTT
VMA
HOAT1
hOAT3
mediated
transport
VMA
not
HVA
melatonin
results
hOAT1
hOAT3
involved
efflux
various neurotransmitter metabolites
various
cerebrospinal fluid
cerebrospinal
blood
choroid plexus
Text Comment
High-affinity partial agonists
High-affinity
partial
vanilloid receptor
vanilloid
vanilloid receptor
vanilloid
VR1
polymodal nociceptor
sensitive
capsaicin
protons
heat
VR1
attractive therapeutic target
attractive
therapeutic
conditions
ranging
long-term pain
long-term
bladder hyperreflexia
bladder
we and other groups
develop
novel ligands
novel
enhanced potencies
enhanced
novel pharmacological properties
novel
pharmacological
characterize
two compounds
two
N-[2-(3,4-dimethylbenzyl)-3-(pivaloyloxy)propyl]-N'-[4-(methylsulfonylamino) benzyl] thiourea
JYL827
N-(4-tert-butylbenzyl)N'-[3-methoxy-4-(methylsulfonylamino) benzyl] thiourea
JYL1511
function
partial agonists
partial
rat VR1
heterologously expressed
heterologously
Chinese hamster ovary cells
Chinese
Both compounds
Both
substantially enhanced potency
substantially enhanced
substantially
inhibiting
[H-3] resiniferatoxin binding
[H-3] resiniferatoxin
K-i values
K-i
29.3 +/- 7.6 and 50.4 +/- 16.5 nM
compared
1810 +/- 270 nM
capsaicin
compounds
showed
different extents
different
partial agonism
partial
6.8 +/- 0.7%
17.4 +/- 0.6%
expected corresponding degrees
expected corresponding
partial antagonism
partial
93.9 +/- 0.9
84.1 +/- 3.2%
IC50 values
IC50
antagonism
Ca-45(2+) uptake
Ca-45(2+)
response
capsaicin
67.3 +/- 24.9 nM
3.4 +/- 0.5 nM
Protons
temperature
protein kinase C
function
coactivators
modulators
rVR1
enhanced
extent
partial agonism
partial
JYL827
JYL1511
pH 5.5
extents
partial agonism
partial
increased
54.9 +/- 2.5%
90.7 +/- 1.7%
response
300 nM capsaicin
300 nM
extents
partial antagonism
partial
decreased
correspondingly
Compounds
JYL827
JYL1511
exploration
potential utility
partial agonists
partial
rVR1
animal models
animal
results
emphasize
strong dependence
strong
partial agonists
partial
other modulators
rVR1
predict
biological behavior
biological context
biological
Text Comment
Integrity
actin-network
involved
uridine 5 '-triphosphate evoked store-operated Ca2+ entry
uridine 5 '-triphosphate evoked
uridine 5 '-triphosphate
store-operated
Ca2+
bovine adrenocortical fasciculata cells
Store-operated Ca2+ entry channels
Ca2+
SOCs
important role
regulation
diverse non-excitable cell functions
diverse
non-excitable
cell
precise mechanism
precise
SOCs activation
SOCs
controversial
Uridine 5'-triphosphate
UTP
induce
Ca2+ entry
Ca2+
dihydropyridines-insensitive manner
dihydropyridines
accelerated
steroidogenesis
bovine adrenocortical fasciculata cells
BAFCs
Gq/11 protein-coupled P2Y2 receptor
Gq/11 protein-coupled
investigated
UTP
involved
SOCs activation
SOCs
mechanism
UTP-induced SOCs activation
UTP-induced
UTP
SOCs
Fura 2-loaded BAFCs
Fura 2-loaded
Fura 2
measurement
intracellular concentration
Ca2+ ([Ca2+](i)) mobilization
Ca2+
[Ca2+](i)
Extracellular UTP
Extracellular
evoked
Ca2+ release
Ca2+
intracellular stores
intracellular
increase
Ca2+ entry
Ca2+
Ca2+ influx
Ca2+
elicited
UTP
inhibited
nifedipine
Zn2+
Cd2+
Ni2+
potency order
potency
Zn2+ > Cd2+ much greater than Ni2+
Zn2+
>
Cd2+
much greater than
Ni2+
effect
UTP
attenuated
phospholipase C inhibitor
U73122
results
indicate
UTP
activates
SOCs
BAFCs
increase
[Ca2+](i)
UTP
attenuated
ML-9
myosin-light chain kinase inhibitor
myosin-light chain
calmodulin inhibitors
W-7 and E6 berbamine
concentration-dependent manner
concentration
reagents
depolymerized
actin filaments
rhodamine staining
rhodamine
BAFCs
Cytochalasin D
inhibited
UTP-activated SOCs
UTP-activated
UTP
depolymerized
actin filaments
results
proposed
calcium/calmodulin dependent myosin-light chain kinase
calcium/calmodulin dependent
calcium
myosin-light chain
involved
mobilization
actin filaments
integrity
actin-network
important role
UTP-induced SOCs activation
UTP-induced
UTP
SOCs
BAFCs
Text Comment
Lipid-based supramolecular systems
Lipid-based
Lipid
supramolecular
topical application
preformulatory study
preformulatory
article
describes
production
characterization
monoglyceride-based supramolecular systems
monoglyceride-based
monoglyceride
supramolecular
simple processing technique
avoiding
time-consuming procedures
high energy input
high energy
high
use
organic solvents
organic
preformulatory study
preformulatory
performed
study
influence
experimental parameters
production
monoglyceride-based disperse systems
monoglyceride-based
monoglyceride
effects
stirring speed
type
concentration
monoglyceride mixture
type
concentration
surfactant
investigated
recovery
fraction
larger particles
larger
mean diameter
mean
shape
smaller particles
smaller
nanosomes ???
Dispersions
first characterized
first
optical microscopy
optical
freeze-fracture electron microscopy
freeze-fracture
electron
mean diameter
mean
standard nanosomes
standard
analyzed
photon correlation spectroscopy
photon
correlation
PCS
elimination
larger particles
larger
filtration
193.5 nm
Cryotransmission electron microscopy studies
Cryotransmission electron microscopy
Cryotransmission
electron
conducted
investigate
structure
dispersions
vesicles
particles
characterized
cubic organization
X-ray diffraction data
X-ray diffraction
X-ray
revealed
2 different cubic phases
2
different
first
bicontinuous cubic phase
spatial symmetry
Im3m
Q229
second
Pn3m spatial symmetry
Pn3m
study
stability
monoglyceride-based dispersions
monoglyceride-based
monoglyceride
based
macroscopical analysis
macroscopical
organoleptic properties
organoleptic
dimensional analysis
dimensional
time
performed
elimination
larger particles
larger
filtration
Organoleptic and morphological features
Organoleptic
not change
not
time
phase-separation phenomena
1 year
production
PCS studies
nanosomes
initial increase
mean diameter
mean
first month
first
production
generally maintain
generally
dimensions
next 4 months
next
Text Comment
Macroprolactinemia
new cause
new
hyperprolactinemia
Hyperprolactinemia
not
seen
pregnancy
several pathological conditions
several
prolactin
PRL
secreting
pituitary adenoma
prolactinoma
intracranial tumors
compressing
pituitary stalk
hypothalamus
PRL stimulative drugs
PRL
stimulative
patients
hyperprolactinemia
diagnosed
idiopathic hyperprolactinemia
causes
unknown
subjected
repeated radiological examinations
repeated
radiological
microadenoma
long-term treatment
long-term
long
bromocriptine
surgical intervention
surgical
accumulating evidence
accumulating
macroprolactinemia
most circulating PRL
most
circulating
forms
large protein complexes
large
150 kDa
idiopathic hyperprolactinemia
patients
macroprolactinemia
clinically characterized
clinically
lack
hyperprolactinemia-related symptoms
hyperprolactinemia
amenorrhea
galactorrhea
anti-PRL autoantibody
anti-PRL
PRL
leading cause
leading
macroprolactinemia
heterogeneous
nature
patients
anti-PRL autoantibodies
anti-PRL
PRL
symptom-free
pregnancy
hyperprolactinemia
Identification
macroprolactinemia
clinically important
clinically
unnecessary examinations and treatments
unnecessary
patients
idiopathic hyperprolactinemia
Text Comment
Molecular modeling
interactions
dihydropyridines
phenylalkylamines
inner pore
L-type Ca2+ channel
Ca2+
Domains IIIS5, IIIS6, and IVS6 transmembrane segments
L-type Ca2+ channels
Ca2+
participate
dihydropyridine (DHP) and phenylalkylamine (PAA) binding
dihydropyridine
DHP
phenylalkylamine
PAA
inner pore structure
Ca(v)1.2 channel
reconstructed
coordinates
transmembrane alpha-helices
KcsA channel
S6s
M2
comparative analysis
comparative
pore-facing M2 side chains
M2
drug binding
drug
Two neighboring tilted S6 helices
Two
domains III and IV
selectivity filter
selectivity
formed
interdomain crevice
Docking
DHPs
inside
crevice
DHP ring
DHP
Phe-1159
1159
IIIS6
Ala-1467
1467
IVS6
parallel
pore axis
4-aryl ring
aromatic and polar interactions
aromatic
polar
side chains
Tyr-1152
1152
Tyr-1463
1463
Nonpolar interactions
Nonpolar
port side ester group
port side
hydrophobic side chains
Ile-1156
1156
Ile-1163
1163
Ile-1471
1471
bottom
binding cavity
formed
crossover
IIIS6
IVS6
stabilize
channel's closed/inactivated state
channel's
Similar arrangements
Similar
DHP agonist drugs
DHP
agonist
absence
hydrophobic interactions
hydrophobic
helical crossing
arrangement
DHPs
not physically block
not
pore
central amine group
central
desmethoxyverapamil
selectivity filter domain III
selectivity
glutamic acid
one aromatic ring
one
CH2CH2 linker
CH2CH2
interact
side chain
Tyr-1463
1463
DHP binding site
DHP binding
DHP
opposite aromatic ring
opposite
in contact
side chain
Ile-1470
1470
IVS6
blocking
pore
Text Comment
Monomeric and dimeric byproducts
Monomeric
dimeric
principal functional elements
principal
functional
higher
higher order P2X(1) concatamers
higher order
Heteromultimeric assembly
Heteromultimeric
ion channel subunits
ion
generates
high diversity
high
ion channel subtypes
ion
distinct pharmacological and functional properties
distinct
pharmacological
functional
determine
subunit stoichiometry
order
ion channels
ion
constructs
several concatenated subunits
several
widely used
widely
electrophysiological studies
electrophysiological
primarily biochemical techniques
primarily
biochemical
analyze
synthesis
assembly
surface expression
P2X(1) concatamers
full-length concatamers
full-length
full
consisting
two to six contiguous copies
two
six
P2X(1) subunit
readily synthesized
readily
Xenopus laevis oocytes
retained
aggregates
endoplasmic reticulum
endoplasmic
minute levels
minute
lower order byproducts
lower order
lower
monomers
dimers
inherently
inherently formed
concatamers
combined
form
defined protein complexes
defined
equal
mass
homotrimeric P2X(1) receptor
assembled
P2X(1) monomers
complexes
three monomers
three
one monomer
one
plus
one concatenated dimer
one
concatenated
small amounts
small
concatenated P2X(1) trimers
concatenated
plasma membrane
Complexes
comprising
three
three subunits
not observed
not
plasma membrane
byproduct complexes
account
ATP-gated currents
ATP-gated
ATP
expression
concatenated P2X(1) subunits
concatenated
results
strongly corroborate
strongly
trimeric architecture
P2X receptors
indicate
formation
lower order by-products
lower order
lower
concatamer approach
concatamer
Text Comment
New methods
New
evaluate
endothelial function
endothelial
search
marker
nitric oxide
NO
in vivo
Re-evaluation
NOx
plasma
red blood cells
trial
detect
nitrosothiols
plasma NOx
plasma
NO2-
NO3-
index
nitric oxide (NO) formation
nitric oxide
NO
in vivo
unreasonable results
appeared
after
active elimination
NOx contamination
NOx
laboratory ware
example
plasma NOx concentrations
plasma NOx
plasma
not increase
not
vasodilation
mediated
NO/cGMP pathway
NO
cGMP
after
organ perfusion
organ
possible shift
NOx
plasma
erythrocytes
RBCs
cause
phenomena
excluded
leaving
destination
NOx
after
leaving
plasma
unknown
Kinetic analyses
Kinetic
revealed
steady state NOx concentrations
steady state
NOx
plasma
whole blood
whole
correlate
NOx formation rate
NOx formation
NOx
NOx elimination rate
NOx elimination
NOx
supposition
NO status
NO
directly reflected
plasma NOx concentrations
plasma NOx
plasma
untenable
nitrosothiols
R-SNOs
possible carriers
possible
NO bioactivity
NO
flagged
alternative indices
alternative
NO status
NO
in vivo
efforts
detect
substances
interference
ultrafiltration
eliminated
low molecular weight R-SNOs
low molecular weight
low
nitrosocystein
nitrosogluthathione
undetectable
high-molecular weight R-SNO
high-molecular weight
high
nitrosoalbumin
detected
human blood
Further research
Further
significance
practical use
nitrosoalbumin
marker
NO
in vivo
Text Comment
Optical bioimaging
Optical
living tissue
living
single molecule
single
Calcium imaging
Calcium
blood vessel
in situ
employing
two-photon excitation fluorescence microscopy
two
photon
fluorescence
Recent developments
optoelectronics
real-time Ca2+ imaging
real-time
Ca2+
thin planes
cells
utilizing
laser scanning confocal microscopy
laser
confocal
LSCM
major complication
major
associated
imaging system
imaging
increased phototoxicity
increased
improved
spatiotemporal resolution
Two-photon excitation microscopy
Two
photon
TPEM
minimize
phototoxicity
restriction
technique
volume
proximal
geometric focus
geometric
light
study
capability
Ca2+ imaging
Ca2+
investigated
employing
recently developed real-time TPEM
recently developed
real-time
RTS2000MP
Bio-Rad
Tokyo
mode-locked Ti-sapphire laser
mode-locked
Z-axis resolution
RTS2000MP
high NA objectives
high
defined
full-width
full
half maximum
FWHM
0.5-mum fluorescent bead
0.5-mum
fluorescent
provided
values
nearly identical
obtained
LSCM
small pinhole
small
0.2 mm
approximately 0.6 mum
approximately
serial sectioning
serial
21 sequential images
21
sequential
0.3-mum intervals
0.3-mum
cultured endothelial cells
cultured endothelial
loaded
calcein
tetramethyl-rhodamine methylester
performed
TPEM
z-axis resolution
higher
observed
LSCM
photobleaching rate
photobleaching
significantly lower
obtained
LSCM
Maximum fluorescence intensities
Maximum
detected
780 nm
excitation spectra
excitation
fluo-3 and fluo-4 Ca2+-sensitive probes
fluo-3
3
fluo-4
4
Ca2+-sensitive
Ca2+
TPEM
Fluorescence images
Fluorescence
mouse arterial endothelial cells
arterial endothelial
loaded
fluo-4
4
clearly visualized
clearly
TPEM
in situ
Application
acetylcholine
oscillatory increase
[Ca2+](i)
endothelial cells
endothelial
relaxation
major axis
smooth muscle cells
consecutive long-lasting
consecutive long-lasting experiments
long
repeated
identical response
identical
same microscopic field
same
fluorescence imaging
fluorescence
employing
TPEM
Ca2+ imaging
Ca2+
blood vessels
in situ
Text Comment
Optical bioimaging
Optical
living tissue
living
single molecule
single
Imaging
functional analysis
functional
blood flow
blood
organic microcirculation
organic
Activity
blood cells
erythrocytes
leucocytes
platelets
microcirculation
observed
using
intravital microscope
intravital
confocal laser scanning microscope
confocal
laser
scanning
connected
image processing system
including
fluorescence and phosphorescence emission methods
fluorescence
phosphorescence
Dynamic functions
blood flow
blood
mainly observed
mesentery, brain, and liver tissues
rats
results
summarized
Deformability
diabetic erythrocytes
diabetic
significantly lower
significantly
healthy controls
healthy
high shear rate
high
shear
spring constant
Young's modulus
diabetic erythrocytes
diabetic
stiffened
hard
deform
capillary
hemorrhagic shock
thrombosis
flow velocity
flow
oxygen partial pressure
oxygen
blood
decreased
brain and liver tissues
visualized
FITC stained erythrocytes
FITC stained
FITC
Pd-porphyrin derivative
pO(2) probe
pO(2)
Platelet adhesion
Platelet
thrombus
thrombus formation
micro-vessels
accelerated
photodynamic reaction
photodynamic
diabetic platelets
diabetic
augmented adhesion and aggregation
augmented
vessel wall
vessel
followed
acute thromboembolism
Active oxygen radicals
Active
thrombus formation
thrombus
adhesion
activated leucocytes
activated
Fluorescent dye probes
Fluorescent dye
Fluorescent
rhodamine G
acridine orange
visualization
flow behavior
flow
platelets
leucocytes
Text Comment
Optical bioimaging
Optical
living tissue
living
single molecule
single
Optical detection
Optical
synaptically induced glutamate transporter activity
synaptically induced
glutamate transporter
hippocampal slices
hippocampal
voltage-sensitive dyes
voltage-sensitive
VSDs
optical properties
optical
response
membrane potential changes
membrane potential
membrane
non-invasive optical measurements
non-invasive optical
optical
membrane excitation
membrane
VSDs
applied
various types
various
excitable tissue
excitable
article
authors' recent work
authors' recent
authors'
technique
addition
basic and technical information
VSD imaging
VSD
applying
technology
hippocampal brain slices
brain
found
astrocytes
indispensable roles
sequestering
glutamate
maintenance
synaptic transmission
synaptic
neuronal survival
potential
VSD imaging
VSD
drug development
drug
discussed
Text Comment
Pharmacokinetics
paclitaxel-containing liposomes
paclitaxel-containing
paclitaxel
rats
animal models
animal
liposomal formulations
liposomal
paclitaxel
possess
lower
lower toxicity
equal antitumor efficacy
equal
antitumor
compared
clinical formulation
clinical
Taxol
goal
study
determine
formulation dependence
formulation
paclitaxel pharmacokinetics
paclitaxel
rats
test
hypothesis
altered biodistribution
altered
paclitaxel
modifies
exposure
critical normal tissues
critical normal
Paclitaxel
administered intravenously
intravenously
multilamellar (MLV) liposomes
multilamellar
MLV
composed
phosphatidylglycerol
phosphatidylcholine
L-pac
Cremophor EL
ethanol vehicle
used
Taxol formulation
Taxol
Cre-pac
dose
40 mg/kg
infusion time
infusion
8 to 9 minutes
to
Animals
killed
various times
various
pharmacokinetic parameters
determined
blood and tissue distribution
blood
tissue
paclitaxel
area
concentration vs time curve
concentration
vs
time
AUC
blood
similar
2 formulations
2
L-pac
38.1 +/- 3.32 microg-h/mL
Cre-pac
34.5 +/- 0.994 microg-h/mL
AUC
various tissues
various
formulation-dependent
formulation
bone marrow, skin, kidney, brain, adipose, and muscle tissue
AUC
statistically higher
Cre-pac
spleen
tissue
reticuloendothelial system
reticuloendothelial
clearance
liposomes
AUC
statistically higher
L-pac
Apparent tissue partition coefficients
Apparent
tissue
K(p)
calculated
bone marrow
tissue
paclitaxel
exerts
significant toxicity
significant
K(p)
5-fold greater
5-fold
paclitaxel
Cre-pac
data
paclitaxel release
paclitaxel
circulating liposomes
circulating
efflux
delayed sufficiently
sufficiently
retain
drug
greater extent
greater
central (blood) compartment
blood
reduce
penetration
peripheral tissues
peripheral
effects
contribute
reduced toxicity
reduced
liposomal formulations
liposomal
paclitaxel
Text Comment
Pharmacology
airway goblet cell mucin release
airway
goblet cell mucin
Airway mucus hypersecretion
Airway
mucus
one
major clinical manifestations
major
clinical
patients
suffering
various pulmonary diseases
various
no drugs
no
available
control
airway mucus hypersecretion
airway
mucus
15 years
plethora
information
amassed
pharmacology
airway goblet cell mucin secretion
airway
goblet cell mucin
various primary cell culture systems
various
primary cell culture
primary
recent discovery
recent
various MUC genes
various
greatly stimulated
greatly
research
field
heterogeneity
oligosaccharide structure
oligosaccharide
mucin molecules
mucin
assess
significance
information
pharmacological studies
pharmacological
understand
roles
individual mucins
individual
conjunction
normal airway physiology and pathology
normal
airway
future research directions
research
studying
airway goblet cell mucin pharmacology
airway
goblet cell mucin
Text Comment
Physical properties and compact analysis
Physical properties
compact
commonly used direct compression binders
commonly used
direct compression
direct
study
investigated
basic physico-chemical property
physico-chemical
binding functionality
binding
commonly used commercial direct compression binders/fillers
commonly used
commercial
direct compression
direct
compressibility
materials
compression parameters
compression
derived
Heckel, Kawakita, and Cooper-Eaton equations
Five classes
Five
excipients
evaluated
microcrystalline cellulose
microcrystalline
MCC
starch
lactose
dicalcium phosphate
DCP
sugar
starch category
starch
exhibited
highest moisture content
highest
moisture
followed by
MCC
DCP
lactose
sugar
DCP
highest density
highest
followed by
sugar
lactose
starch
MCC
material particle size
material particle
highly processing dependent
highly
processing
data
demonstrated
MCC
moderate flowability
moderate
excellent compressibility
excellent
extremely good compact hardness
extremely good
exceptions
starch
lactose
sugar
generally exhibited
moderate flowability, compressibility, and hardness
moderate
DCP
excellent flowability
excellent
poor compressibility and hardness
poor
research
additionally confirmed
binding mechanism
binding
well documented
well
MCC
performs
binder
plastic deformation
plastic
pressure
fragmentation
predominant mechanism
predominant
lactose
DCP
starch
sugar
perform
both mechanisms
both
Text Comment
Platelets
anti-platelet therapy
anti-platelet
platelet
Platelets
central role
hemostatic process
hemostatic
similarly involved
similarly
pathological counterpart
pathological
thrombosis
adhere
various subendothelial proteins
various
subendothelial
exposed
injury
disease
subsequently
activated
thrombogenic surface
thrombogenic
locally produced agonists
locally
produced
activated platelets
activated
aggregate
form
platelet plug
release
agonists
recruit
more platelets
more
growing thrombus
growing
provide
catalytic surface
catalytic
thrombin generation
thrombin
fibrin formation
fibrin
platelet-rich thrombi
platelet-rich
responsible
acute occlusion
acute
stenotic vessels
stenotic
ischemic injury
heart
brain
range
anti-platelet drugs
anti-platelet
platelet
currently used
prophylactically
therapeutically
regimens
manage
thrombo-embolic disorders
thrombo-embolic
include
inhibitors
generation
effects
locally produced agonists
locally
produced
several large clinical trials
several
large
clinical
supported
roles
cyclooxygenase inhibitors
cyclooxygenase
prevent
thromboxane generation
thromboxane
thienopyridine derivatives
antagonize
ADP receptors
ADP
intravenous alphaIIbbeta3 antagonists
intravenous
alphaIIbbeta3
shown
effective
anti-thrombotics
highly selective situations
highly
studies
oral counterparts
oral
Recent advances
Recent
understanding
platelet physiology
platelet
novel, if yet untested, targets
novel, if yet untested
anti-platelet therapy
anti-platelet
platelet
include
thrombin receptor
serotonin handling system
serotonin handling
serotonin
leptin receptor
Text Comment
Preparation
biodegradable microspheres
biodegradable
matrix devices
containing
naltrexone
study
use
biodegradable
biodegradable polymers
microencapsulation
naltrexone
solvent evaporation technique
solvent evaporation
solvent
investigated
use
naltrexone microspheres
naltrexone
preparation
matrix devices
studied
purpose
poly(L-lactide) (PLA) microspheres
poly(L-lactide)
PLA
containing
naltrexone
prepared
solvent evaporation technique
solvent evaporation
solvent
compressed
temperatures
Tg
polymer
effect
different process parameters
different
drug/polymer ratio
drug
polymer
stirring rate
stirring
preparation
microspheres
morphology
size distribution
size
in vitro
drug release
drug
microspheres
studied
stirring rate
stirring
influenced
particle size distribution
particle size
particle
microspheres
drug release profiles
drug release
drug
increasing
stirring speed
stirring
400 to 1200 rpm
mean diameter
mean
microspheres
decreased
251 microm
104 microm
drug release rate
drug release
drug
smaller microspheres
smaller
faster
larger
larger microspheres
drug release
drug
microspheres
low drug content
low
drug
20% wt/wt
not affected
not
particle size
particle
microspheres
Increasing
drug content
drug
microspheres
20% to 50% wt/wt
significantly faster
drug release
drug
microspheres
shown
drug release
drug
matrix devices
prepared
compression
naltrexone microspheres
naltrexone
slower
microspheres
No burst release
No
burst
observed
matrix devices
Applying
higher compression force
higher
compression
compressing
microspheres
produce
tablets
resulted
lower drug release
lower
drug
matrix devices
results
suggest
regulating
different variables
different
desired release profiles
release
naltrexone
achieved
PLA microparticulate system
PLA
microparticulate
matrix devices
Text Comment
Preservation
caspase-3 subunits
caspase-3
degradation
contributes
apoptosis
evoked
lactacystin
single lysine
single
lysine pair
pair
small subunit
small
sufficient
ubiquitination
Procaspase-3
p32
processed
upstream caspases
upstream
p12 and p20 subunits
heterodimerize
Concomitant
formation
active heterotetramer
active
p20
autoprocessed
p17
Treatment
HL-60 cells
lactacystin
selective inhibitor
selective
proteasome
exponentially increased
caspase-3-like hydrolytic activity
caspase-3
induced
apoptosis
little or no effect
little or no
activity
upstream caspase-8, caspase-9, or granzyme B
upstream
Lactacystin treatment
Lactacystin
decreased
p32 zymogen
evoked
accumulation
p17 and p12 subunits
Treatment
transfected human retinoblast 911 cells
transfected
proteasome inhibitor
evoked
accumulation
epitope-tagged p12, p17, and p20
epitope-tagged
no
no effect
p32 zymogen
result
caspase-3 subunits
zymogen
unstable
degradation
ubiquitin-proteasome system
Ubiquitin
conjugates
p12
p17
accumulated
cells
cotransfected
p12
caspase inactive mutant
caspase
inactive
p17
Substitution
arginine
all eight lysines
all
eight
p12
abolished
ubiquitination
single lysine
single
lysine pair
pair
sufficient
p12 ubiquitination
p12
Lactacystin treatment
Lactacystin
HL-60 cells
induced
proteolytic processing
proteolytic
X-linked inhibitor
X-linked
apoptosis
XIAP
decreased
full-length XIAP
full-length
known
ubiquitin-protein ligase activity
ubiquitin-protein ligase
active caspase-3
active
findings
indicate
caspase-3 subunits
degraded
ubiquitin-proteasome system
suggest
lactacystin
induces
apoptosis
disabling
ubiquitin-protein ligase function
ubiquitin-protein ligase
XIAP
stabilizing
active caspase-3 subunits
active
Text Comment
Properties
microcrystalline cellulose
microcrystalline
powder cellulose
powder
extrusion/spheronization
studied
Fourier transform Raman spectroscopy
Fourier transform
Raman
environmental scanning electron microscopy
environmental
electron
study
effect
powder cellulose
powder
PC
2 types
2
microcrystalline cellulose
microcrystalline
MCC 101
MCC 301
pellet properties
pellet
extrusion/spheronization process
investigated
different investigated types
different
investigated
cellulose
different behavior
different
extrusion/spheronization process
Pure PC
Pure
extrusion
too much
too much water
added water
added
partly
partly squeezed
extrusion process
MCC 101
MCC 301
extrudable
wide range
water content
water
quality
resulting products
resulting
varied
extrusion/spheronization process
MCC 101
best substance
best
easy
easy handling
acceptable product properties
acceptable
product
properties
extrudates
pellets
determined
Fourier transform (FT) Raman spectroscopy
Fourier transform
FT
Raman
environmental scanning electron microscopy
environmental
electron
ESEM
FT-Raman spectroscopy
distinguish
original substances
original
also
wet and dried extrudates
wet
dried
particle sizes
particle
raw material
extrudates
determined
ESEM
without
additional preparation
MCC
size
resulting particles
resulting
extrudate
pellet
smaller
extrudates
PC
changes
particle size
particle
not
observed
Text Comment
Protection
hypothermia
hypoxia-induced inhibition
hypoxia
neurogenic vasodilation
neurogenic
porcine cerebral arteries
porcine cerebral
Porcine cerebral arterial strips
denuded
endothelium
responded
transmural electrical stimulation
5 Hz
40 s
relaxation
abolished
tetrodotoxin
N-G-nitro-L-arginine
NO synthase inhibitor
NO synthase
Lowering
temperature
bathing media
bathing
37degreesC
33degreesC
25degreesC
potentiated
response
nerve stimulation
nerve
not affect
not
relaxations
induced
NO
applied
exogenously
Hypoxia
suppressed
stimulation-induced relaxation
37degreesC
hypothermia
blunted
inhibitory effect
hypoxia
temperature-dependent manner
concluded
hypothermia
augments
vasodilatation
associated
nitroxidergic (nitrergic) nerve activation
nitroxidergic
nitrergic
nerve
increasing
production
NO
L-arginine
prevents
impairment
NO production
NO
hypoxia
These mechanisms
These
hypothermia
protects
nerve cells
hypoxia
Inhibitions
cyclic GMP phosphodiesterase
superoxide production
superoxide
hypoxia
not
participate
action
hypothermia
Mechanisms
protective action
ascertained
Text Comment
Rheology
stability
water
water-in-oil-in-water multiple emulsions
oil
water
multiple
Span 83
Tween 80
Multiple emulsions
Multiple
often stabilized
combination
hydrophilic and hydrophobic surfactants
hydrophilic
hydrophobic
ratio
these surfactants
these
important
stable multiple emulsions
stable
multiple
objective
this study
this
evaluate
long-term stability
long-term
water-in-oil-in-water (W/O/W) multiple emulsions
water
oil
water
multiple
concentrations
Span 83
Tween 80
effect
surfactant and electrolyte concentration
surfactant
electrolyte
emulsion bulk rheological properties
emulsion
investigated
Light microscopy
Light
creaming volume
rheological properties
assess
emulsion stability
observed
optimal surfactant concentrations
optimal
surfactant
W/O/W emulsion long-term stability
W/O/W emulsion
W/O/W
long-term
20% wt/vol Span 83
20%
wt
vol
oil phase
oil
0.1% wt/vol Tween 80
0.1%
wt
vol
continuous phase
Higher concentrations
Higher
Tween 80
destructive effect
W/O/W emulsion stability
W/O/W emulsion
W/O/W
correlated
observation
interfacial film strength
film
oil/water interface
oil
water
decreased
Tween 80 concentration
Tween 80
increased
High Span 83 concentrations
High
Span 83
increased
storage modulus G' (solidlike) values
storage modulus
solidlike
enhanced
multiple emulsion stability
multiple
emulsion
30% wt/vol Span 83
30%
wt
vol
incorporated
viscosity
primary W/O emulsion
primary
W/O
increased considerably
emulsion droplets
shape
Salt
inner aqueous phase
inner aqueous
exerted
osmotic pressure
diffusion
water
inner aqueous phase
inner aqueous
increased
W/O/W emulsion viscosity
W/O/W emulsion
increase
volume fraction
primary W/O emulsion
primary
W/O
type
viscosity increase
viscosity
destabilizing effect
likelihood
rupture
inner and multiple droplets
inner
multiple
Text Comment
Roles
substance p
NK1 receptor
NK1
brainstem
development
emesis
emetic response
emetic
response
primarily
protective reflex
protective
occurring
wide
variety
vertebrates
response
ingestion
toxic compounds
toxic
role
nuclei
brainstem
including
area postrema
nucleus tractus solitarius
dorsal motor nucleus
dorsal motor
nucleus
vagus
central pattern generator
central pattern
vomiting
involvement
abdominal visceral innervation
abdominal visceral
emetic reflex
emetic
reflex
discussed
many
researchers
introduction
serotonin
serotonin 5-HT3-receptor antagonists
5-HT3-receptor
clinical practice
allowed
dramatic
improvement
management
vomiting
vomiting
significant
problem
mechanism
emetic response
emetic
more
complicated
review
evidence
roles
substance P
receptor
neurokinin NK1 receptor
neurokinin NK1
brainstem nuclei
brainstem
emesis
NK1-receptor antagonists
NK1-receptor
NK1
novel drugs
management
major types
emesis
Text Comment
Roxatidine- and cimetidine-induced angiogenesis inhibition
Roxatidine- and cimetidine-induced angiogenesis
Roxatidine
cimetidine
suppresses
growth
colon cancer implants
colon cancer
colon
syngeneic mice
syngeneic
Cimetidine
suppress
growth
several
tumors
gastrointestinal cancer
gastrointestinal
humans
animals
histamine H-2-receptor antagonists
histamine H-2-receptor
histamine
H-2-receptor antagonists
tumor suppressive effects
tumor
effect
roxatidine acetate hydrochloride (roxatidine)
H-2-receptor antagonist
H-2-receptor
growth
colon cancer
colon
mice
examined
compared
cimetidine
Drugs
orally
delivered
26 - 29 days
implantation
syngeneic colon cancer (Colon 38)
syngeneic
colon cancer
C57BL/6 mice
Tumor volume
Tumor
determined
histochemical analysis
histochemical
performed
Tumor tissue
Tumor
serum vascular endothelial growth factor (VEGF) levels
serum vascular endothelial growth factor (VEGF)
serum vascular endothelial
measured
In vitro cell
In vitro cell growth
assessed
MTT assay
roxatidine
cimetidine
suppressed
growth
Colon 38 tumor implants
Colon 38 tumor
Colon 38
Histologic analysis
Histologic
revealed
antagonists
increased
necrotic areas
decreased
density
microvessels
tumor tissue
tumor
H-2-receptor antagonists
H-2-receptor
suppressed
VEGF
VEGF levels
tumor tissue
decreased
serum VEGF levels
VEGF levels
VEGF
Colon 38-bearing mice
Colon 38-bearing
drugs
failed
suppress
in vitro growth
in vitro
cell line
conclusion
roxatidine
cimetidine
exert
suppressive effects
suppressive
growth
colon cancer implants
colon cancer
colon
mice
inhibiting
angiogenesis
reducing
VEGF expression
VEGF
Text Comment
Stargazin
controls
trafficking
alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionate
kainate receptors
kainate
Synaptic plasticity
Synapti
excitatory synapses
excitatory
brain
largely
rapid changes
number
synaptic alpha-amino-3- hydroxyl-5-methyl-4-isoxazolepropionate ( AMPA) receptors
synaptic
alpha-amino-3- hydroxyl-5-methyl-4-isoxazolepropionate ( AMPA)
Stargazin
membrane protein
membrane
interacts
AMPA receptors
AMPA
pivotal role
trafficking
AMPA receptors
AMPA
plasma membrane
plasma
targeting
synapse
trafficking
kainate receptors
structurally
very similar
AMPA receptors
AMPA
also
dependent
stargazin
cerebellar granule cells
cerebellar granule
Xenopus laevis oocytes expression system
Xenopus laevis oocytes
Xenopus laevis
surface delivery
kainate receptor
kainate
independent
stargazin
results
stargazin
highly selective
AMPA receptors
AMPA
Text Comment
Studies
interaction of water with ethylcellulose
water
ethylcellulose
effect
polymer particle size
polymer
purpose
research
investigate
interaction of water with ethylcellulose
water
ethylcellulose
samples
assess
effect
particle size
interaction
distribution
water
coarse particle
coarse particle ethylcellulose
CPEC
average particle size
310 micro m
310
fine particle ethylcellulose
fine particle
FPEC
average particle size
9.7 micro m
9.7
7 cps
viscosity grade
assessed
differential scanning calorimetry
differential
DSC
dynamic vapor sorption analysis
nonfreezing
freezing
water
hydrated samples
determined
n
enthalpy of fusion
enthalpy
water
two particle size fractions
particle size fractions
EC
nonfreezable water
nonfreezable
change
particle size
low water contents
Exposure
ethylcellulose
water
30 minutes
sufficient
equilibration
hydrated polymer
47% wt/wt
water content
water
moisture sorption profiles
analyzed
Guggenheim-Anderson-de Boer
GAB
Young and Nelson equations
moisture distribution
physical forms
amount
externally adsorbed moisture
externally adsorbed
greater
FPEC
Internally absorbed moisture
Internally absorbed
CPEC
success
FPEC
wet-granulation methods
wet-granulation
CPEC
not successful
Text Comment
3-D model
time plasticity
time
represent
influence
tableting speed
tableting
objective
study
test
hypothesis
time plasticity
parameter d
3-D modeling
influenced
tableting speed
Tablets
produced
different maximum relative densities
different
maximum
densities (rho(rel, max))
instrumented eccentric tableting machine
tableting
linear rotary tableting machine replicator
3-D data plots
pressure
normalized time
porosity
according
Heckel
fitting
twisted plane
resulting parameters
resulting
analyzed
3-D parameter plot
materials
dicalcium phosphate dihydrate (DCPD)
spray-dried lactose
spray-dried
microcrystalline cellulose (MCC)
hydroxypropyl methylcellulose (HPMC)
kappa-carrageenan (CAR)
theophylline monohydrate (TheoM)
results
tableting speed
influences
parameter d
time plasticity
3-D model
plastically
viscoelastically
deforming materials
MCC
HPMC
CAR
TheoM
more
plastically deforming materials
plastically
MCC
HPMC
TheoM
influence
omega
stages
higher densification
higher
affected
more
stages
lower densification
lower
Brittle materials
Brittle
DCPD
exhibit
no influence
tableting speed
influence
speed
spray-dried lactose
spray-dried
minor
results
valid
data
obtained
eccentric tableting machine
data
linear rotary tableting machine replicator
empirically derived parameter time plasticity d
time plasticity
influence
time
Text Comment
use
artificial neural networks
artificial
selection
most appropriate formulation
most
appropriate
processing variables
processing
predict
in vitro dissolution
sustained release minitablets
sustained release
objective
work
apply
artificial neural networks
ANNs
examine
importance
various
factors
formulation
process
governing
in-vitro dissolution
enteric-coated sustained release (SR) minitablets
enteric-coated
sustained release
SR
Input feature selection (IFS) algorithms
Input feature selection
used
estimate
relative importance
various
formulation
processing variables
determining
minitablet dissolution rate
minitablet
dissolution
forward
backward stepwise algorithms
backward
stepwise
used
genetic algorithms
Networks
trained
back propagation algorithm
back propagation
check
IFS process
IFS
correctly
located
unimportant inputs
unimportant
IFS
consistent rankings
consistent
importance
formulation
processing variables
processing
determining
release
drug
minitablets
Consistent
ranking
achieved
both
indices
release process
release
time taken
release
commence
enteric coat
T(lag)
drug
diffuse
SR matrix
minitablet
dissolution medium
T(lag) phase
main
coating parameters
coating
original
batch blend size
batch blend
blend time
lubricant
found
most
influence
T(90-10 phase)
amounts
matrix forming polymer
matrix forming
matrix
direct compression filler
direct compression
important
training
ANNs
removal
less
important
improved
network performance
network
ANNs
ranking
relative importance
various
formulations
processing variables
processing
release rate
drug
minitablets
done
main stages
main
release process
release
Subsequent
training
ANN
verified
removal
less
relevant inputs
relevant
training process
training
improved
performance
ANN
Text Comment
combination of iontophoresis and the chelating agent 1,10 phenanthroline
iontophoresis
chelating agent
1,10 phenanthroline
act synergistically
penetration enhancers
peroxovanadium compound
VO(O-2)(2) 1,10 phenanthroline (bpV(phen))
capable
lowering blood glucose levels
oral form
effective
delivered transdermally
Iontophoresis
significantly reduce
lag time
in vivo
compared
passive penetration
mimic in vivo insulin release
insulin
explored
effects of various iontophoretic current durations
various
iontophoretic current durations
dermal penetration of bpV(phen)
bpV(phen)
Iontophoretic transport
not related to total applied charge
total applied charge
steady-state flux
15 minutes
9 hours
hypothesized
unexpectedly large transport
15 minutes
current
increase
passive penetration
bpV(phen)
induced by iontophoresis
Iontophoretic pretreatment
chelating agent
1,10 phenanthroline
increased
passive penetration
bpV(phen)
neither
nonchelating isomer
1,7 phenanthroline
less potent
chelator
EDTA
effective
use of 1,10 phenanthroline
1,10 phenanthroline
penetration enhancer
other chemicals
examined
amino acids
alanine
leucine
Fifteen minutes
1,10 phenanthroline
iontophoresis
alanine transport
11.4-fold
1,7 phenanthroline
increased
transport
factor of 4.6
iontophoretic control
ethanol
1.9
phenanthroline
not enhance
H-3 leucin
H-3 leucine penetration
reasons
selectivity
not clear
data
suggest
chelating agents
1,10 phenanthroline
penetration enhancers
delivery of certain compounds
compounds
Text Comment
ATP
agonist
rat P2Y(4) receptor
antagonist
human P2Y(4) receptor
nucleotide selectivities
human P2Y(4) (hP2Y(4))
rat P2Y(4) (rP2Y(4)) receptor
stably expressed
1321N1 human astrocytoma cells
determined by measuring increases
intracellular [Ca2+]
conditions
minimized
metabolism
bioconversion
endogenous nucleotide release
endogenous nucleotide
cells expressing the hP2Y4 receptor
UTP
GTP
ITP
increased
intracellular [Ca2+]
rank order of potency
UTP (0.55) > GTP (6.59) = ITP (7.38)
UTP
0.55
GTP
6.59
ITP
7.38
(EC50
mu M
ATP
CTP
xanthine 5'-triphosphate (XTP)
diadenosine 5',5'''-P-1,P-4-tetraphosphate (Ap(4)A)
100 mu M
inactive
hP2Y4 receptor
cells expressing the rP2Y4 receptor
all seven nucleotides
nucleotides
increased
intracellular [Ca2+]
similar maximal effects
rank order of potency
UTP (0.20) > ATP (0.51) > Ap4(A) (1.24)
UTP
0.20
ATP
0.51
Ap4(A)
1.24
ITP
1.82
GTP (2.28) > CTP (7.24) > XTP (22.9)
ATP
inactive
hP2Y(4) receptor
assessed
ATP
displayed antagonist activity
ATP
shifted the concentration-response curve to UTP rightward in a concentration-dependent manner
concentration-response curve
UTP
no change in the maximal response
Schild plot
Schild
derived from these data
pA(2) value
6.15
708 nM
slope near unity
CTP
Ap(4)A
100 mu M
inhibited the response
EC50 concentration
UTP
40%
50%
XT
no effec
inhibitory effects
AT
CT
Ap(4)
reversible on washou
AT
potent agonis
poten
rP2Y(4) recepto
competitive antagonis
competitive
moderate potenc
hP2Y(4) recepto
Text Comment
Pharmacological properties
Pharmacological
Y-27632
specific inhibitor
Rho-associated kinases
kinases
Y-27632 [(+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl)cyclohexanecarboxamide dihydrochloride]
used
specific inhibitor
Rho-associated coiled-coil
protein serine/threonine kinase (ROCK) family
protein
serine
threonine
protein kinases
protein
kinases
study
examined
inhibition mechanism
inhibition
profile of actions
Y-27632
Y-30141 [(+)-(R)-trans-4-(1-aminoethyl)-N-(1H-pyrrolo[2,3-b]pyridin-4-yl)cyclohexanecarboxamide dihydrochloride]
Y-27632
Y-30141
inhibited
kinase activity
kinase
ROCK-I
ROCK-II
in vitro
inhibition
reversed
ATP
competitive manner
suggests
compounds
inhibit
kinases
binding
catalytic site
affinities
ROCK kinases
determined
K-i values
20 to 30 times higher
Rho effector kinases
kinases
citron kinase
kinase
protein kinase PKN
kinase
[H-3]Y-30141
cells
temperature- and time-dependent
saturable
uptake
competed
unlabeled Y-27632
Y-27632
No concentrated accumulation
found
suggesting
uptake
carrier-mediated facilitated diffusion
carrier-mediated
Y-27632
abolished
stress fibers
Swiss 3T3 cells
10 mu M
G(1)-S phase transition
cell cycle
cytokinesis
affected
concentration
Y-30141
10 times more potent
10 times
Y-27632
inhibiting
kinase activity
kinase
stress fiber formation
significant delay
G(1)-S transition
inhibition
cytokinesis
10 mu M
Text Comment
Polyanionic
polysulfonate
dendrimers
inhibit
replication
human immunodeficiency virus
human immunodeficiency
interfering
virus adsorption
virus
steps
Reverse transcriptase/integrase
virus replicative cycle
virus
Polyanionic dendrimers
Polyanionic
synthesized
evaluated
antiviral effects
antiviral
Phenyldicarboxylic acid (BRI6195) and naphthyldisulfonic acid (BRI2923) dendrimers
Phenyldicarboxylic acid (BRI6195)
naphthyldisulfonic acid (BRI2923)
found
inhibit
replication
human immunodeficiency virus type 1 (HIV-1; strain III(B))
human immunodeficiency virus
MT-4 cells
EC(50)
0.1 and 0.3 mu g/ml
dendrimers
not toxic
MT-4 cells
highest concentrations
tested
250 mu g/ml
compounds
effective
HIV- 1 strains
HIV- 1
clinical isolates
HIV-2 strains
HIV-2
simian immunodeficiency virus
SIV
strain MAC(251)
HIV-1 strains
HIV-1
resistant
reverse transcriptase inhibitors
transcriptase
HIV strains
HIV
mutations
envelope glycoprotein gp120
glycoprotein
engendering resistance
resistance
adsorption inhibitors
reduced
sensitivity
dendrimers
compounds
inhibited
binding
wild-type
wild-type virus
recombinant virus
wild-type gp120
wild-type
gp120
MT-4 cells
concentrations
comparable
inhibited
replication
HIV- 1(III(B))
cells
Cellular uptake studies
Cellular uptake
BRI2923
BRI6195
permeates
MT-4
CEM cells
naphtyldisulfonic acid dendrimer (BRI2923)
naphtyldisulfonic acid
able
inhibit
steps
replication cycle
HIV
reverse transcriptase
transcriptase
integrase
NL4.3 strains
NL4.3
resistant
BRI2923
selected
passage
virus
presence
increasing concentrations
BRI2923
virus mutants
virus
showed
15-fold
reduced
sensitivity
BRI2923
cross-resistance
adsorption inhibitors
adsorption
virus mutants
virus
not cross-resistant
reverse transcriptase inhibitors
reverse transcriptase
protease inhibitors
protease
several
mutations
envelope glycoprotein gp120 gene
glycoprotein gp120
BRI2923-resistant
BRI2923
NL4.3 strains
not present
wild-type NL4.3 strain
NL4.3 strain
no mutations
found
reverse transcriptase
transcriptase
integrase genes
integrase
Text Comment
Regulation
cell proliferation
cell
gene expression
production of cytokines
cytokines
cell cycle progression
cell cycle
cell
primary
human
T lymphocytes
piperlactam S
isolated
Piper kadsura
piperlactam S
C17H13NO4
isolated
Piper kadsura
phytohemagglutinin
PHA
stimulated
cell proliferation
cell
studied
primary culture
primary
human T cells
human
showed
piperlactam S
suppressed
T cell proliferation
T cell
0
12 h
12
stimulation
PHA
Synthesis
total cellular proteins
cellular
RNA
activated cell cultures
activated
cell
suppressed
inhibitory action
piperlactam S
direct cytotoxicity
direct
Cell cycle analysis
Cell cycle
piperlactam S
arrested
cell cycle progression
cell cycle
activated T cells
activated
G(1) transition
S phase
attempt
localize
cell cycle
arrest
regulatory events
regulatory
G(1)/S boundary
gene expression
gene
cytokines
c-Fos protein synthesis
c-Fos protein
examined
Piperlactam S
suppressed
activated T lymphocytes
activated
production
mRNA expression
cytokines
interleukin-2 (IL-2)
IL-4
interferon-gamma
dose-dependent manner
dose-dependent
Western blot analysis
indicated
c-Fos protein
expressed
activated T lymphocytes
activated
decreased
piperlactam S
kinetic study
kinetic
indicated
inhibitory effects
inhibitory
piperlactam S
IL-2 mRNA
expressed
T cells
blocking
c-Fos protein synthesis
c-Fos protein
suppressant effects
suppressant
piperlactam S
proliferation
T cells
activated
PHA
mediated
inhibition
T cells
cytokines
IL-2
IL-4
arresting
cell cycle progression
cell cycle
cells
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 1 0 0
1 1 0 0
1 1 0 0
1 0 0 1
5 1 1 0 0
7 1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
1 0 1 0
1 0 1 0
12 1 0 0 1
1 1 0 0
14 1 0 0 1
1 1 0 0
16 1 0 1 0
1 0 0 1
1 0 1 0
1 0 0 1
1 1 0 0
1 0 0 1
1 1 0 0
1 1 0 0
1 0 0 1
13 1 0 1 0
22 1 0 0 1
1 1 0 0
1 0 1 0
1 0 0 1
1 1 0 0
1 1 0 0
25 1 0 0 1
1 1 0 0
27 1 1 0 0
27 1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 0 1
35 1 0 0 1
1 1 0 0
40 1 0 0 1
1 0 1 0
1 0 1 0
39 1 0 1 0
39 1 0 1 0
1 1 0 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
52 1 0 0 1
1 0 1 0
49 1 0 0 1
50 1 0 0 1
50 1 0 0 1
1 0 1 0
1 1 0 0
1 0 0 1
55 1 0 0 1
1 1 0 0
57 1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
59 1 0 0 1
1 0 0 0
1 0 0 1
63 1 0 0 1
63 1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
98 1 0 0 1
1 0 0 1
1 1 0 0
1 1 0 0
66 1 0 0 1
1 0 0 1
1 1 0 0
70 1 0 0 1
1 0 1 0
1 0 0 1
72 1 0 0 1
 1 1 0 0
77 1 0 0 1
1 0 0 1
76 1 0 0 1
1 0 1 0
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
79 1 0 0 1
1 0 0 1
80 1 0 0 1
1 0 1 0
82 1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
85 1 0 0 1
1 0 0 1
1 0 1 0
87 1 0 0 1
1 1 0 0
1 1 0 0
1 0 1 0
1 0 1 0
1 1 0 0
92 1 0 0 1
1 0 1 0
93 1 0 0 1
1 1 0 0
1 0 0 1
94 1 0 0 1
1 1 0 0
1 0 1 0
96 1 0 0 1
96 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
1 1 0 0 1
1 0 0 0
1 0 1 0
2 1 0 0 1
1 0 1 0
1 0 1 0
1 1 0 0
 1 1 0 0
1 1 0 0
1 1 0 0
8 1 0 0 1
1 1 0 0
9 1 0 1 0
1 1 0 0
1 0 0 1
1 0 0 1
10 1 0 1 0
1 0 1 0
1 0 0 1
1 0 1 0
12 1 0 0 1
1 1 0 0
1 0 1 0
1 1 0 0
1 0 0 1
1 1 0 0
16 1 0 0 1
1 0 1 0
1 1 0 0
18 1 0 0 1
1 0 0 1
19 1 0 0 1
1 0 1 0
1 0 1 0
21 1 0 0 1
1 0 1 0
22 1 1 0 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 0 1
1 0 1 0
1 0 1 0
27 1 0 0 1
27 1 0 1 0
45 1 0 0 1
1 1 0 0
1 0 0 1
1 1 0 0
1 0 0 1
1 0 1 0
30 1 0 0 1
 30 1 0 0 1
1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 1 0 0
9 1 0 0 1
1 0 1 0
1 0 0 1
11 1 0 1 0
1 0 0 1
1 0 1 0
13 1 0 0 1
1 0 1 0
1 0 1 0
1 0 0 1
1 0 0 1
1 1 0 0
1 0 1 0
1 1 0 0
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
1 0 1 0
2 1 0 0 1
1 0 1 0
1 1 0 0
1 1 0 0
1 0 1 0
5 1 0 1 0
1 1 0 0
6 1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
12 1 0 0 1
 1 0 0 1
1 0 0 1
1 0 0 1
14 1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
86 1 0 0 1
1 0 0 1
16 1 0 0 1
1 0 1 0
1 1 0 0
18 1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
23 1 0 1 0
1 0 1 0
24 1 0 0 1
1 0 0 1
1 1 0 0
1 1 0 0
1 0 1 0
26 1 0 0 1
27 1 0 0 1
1 0 1 0
29 1 0 0 1
1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
93 1 0 0 1
1 0 1 0
1 1 0 0
1 0 1 0
1 0 0 1
1 0 1 0
99 1 0 0 1
1 0 1 0
1 0 1 0
32 1 0 0 1
1 1 0 0
1 0 1 0
1 0 1 0
1 1 0 0
 1 1 0 0
1 0 1 0
1 0 0 1
1 1 0 0
1 0 1 0
44 1 0 0 1
1 0 1 0
1 1 0 0
1 0 1 0
1 0 0 1
1 1 0 0
1 0 1 0
48 1 0 0 1
49 1 0 1 0
1 0 0 1
1 1 0 0
1 0 0 1
53 1 0 1 0
1 0 1 0
1 1 0 0
1 0 0 0
1 1 0 0
1 0 1 0
1 0 1 0
59 1 0 0 1
1 0 0 1
1 0 1 0
1 1 0 0
1 1 0 0
1 1 0 0
64 1 0 1 0
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
1 0 1 0
1 1 0 0
77 1 0 1 0
1 0 0 1
76 1 0 1 0
76 1 0 1 0
76 1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
 1 1 0 0
1 0 1 0
1 0 1 0
3 1 0 1 0
3 1 1 0 0
5 1 0 0 1
1 0 1 0
1 0 0 1
1 1 0 0
1 0 0 1
8 1 0 1 0
1 1 0 0
9 1 0 0 1
9 1 0 0 1
1 0 1 0
1 0 0 1
1 1 0 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
16 1 0 0 1
15 1 0 1 0
1 0 1 0
1 0 1 0
19 1 0 0 1
1 1 0 0
1 1 0 0
1 0 1 0
21 1 0 1 0
1 0 1 0
1 1 0 0
1 0 0 1
26 1 0 0 1
1 0 1 0
1 0 1 0
1 0 0 1
71 1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
41 1 0 0 1
1 0 0 1
31 1 0 1 0
1 0 0 1
 1 0 0 1
1 1 0 0
1 1 0 0
1 0 0 1
1 1 0 0
1 0 1 0
1 0 0 1
1 0 1 0
1 1 0 0
1 0 0 1
42 1 0 0 1
1 0 0 1
1 0 1 0
1 1 0 0
45 1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
47 1 0 1 0
1 0 1 0
1 1 0 0
49 1 0 0 1
1 0 0 1
1 0 0 1
51 1 1 0 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
1 0 0 1
1 1 0 0
1 0 1 0
1 0 1 0
59 1 0 1 0
1 0 0 1
61 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
2 1 0 0 1
2 1 0 0 1
1 1 0 0
4 1 0 0 1
72 1 0 1 0
1 0 1 0
1 1 0 0
 1 0 1 0
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
13 1 0 0 1
1 1 0 0
15 1 0 0 1
15 1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 1 0 0
22 1 0 0 1
22 1 0 1 0
1 0 0 1
1 0 1 0
1 1 0 0
1 0 1 0
1 0 1 0
32 1 0 0 1
66 1 0 0 1
66 1 0 0 1
66 1 0 0 1
1 0 1 0
34 1 0 0 1
1 0 0 1
35 1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
1 0 0 1
1 1 0 0
1 0 1 0
1 0 1 0
1 0 0 1
47 1 0 0 1
1 1 0 0
1 0 0 1
 1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 1 0 0
1 0 0 1
1 1 0 0
55 1 0 0 1
1 0 0 1
1 1 0 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
64 1 0 1 0
1 0 1 0
65 1 0 1 0
1 0 0 1
1 0 0 1
69 1 0 0 1
1 0 1 0
1 0 0 1
1 0 1 0
71 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
1 0 0 1
3 1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
11 1 0 1 0
11 1 0 1 0
1 0 0 1
13 1 0 0 1
13 1 0 0 1
1 1 0 0
16 1 0 0 1
1 0 1 0
1 0 0 1
 1 0 1 0
17 1 0 0 1
1 0 0 1
18 1 0 0 1
1 0 0 1
1 1 0 0
1 0 0 1
1 0 0 1
23 1 1 0 0
1 0 1 0
1 1 0 0
1 0 1 0
26 1 0 0 1
1 1 0 0
1 1 0 0
28 1 0 0 1
1 0 1 0
1 0 1 0
30 1 0 0 1
1 1 0 0
1 0 1 0
31 1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
36 1 0 1 0
1 0 1 0
37 1 0 0 1
1 0 1 0
38 1 0 0 1
1 0 0 1
1 0 0 1
1 1 0 0
1 0 0 1
40 1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
1 0 0 1
1 1 0 0
1 0 0 1
1 0 0 1
 1 1 0 0
1 0 1 0
1 1 0 0
1 0 0 1
58 1 0 0 1
56 1 0 0 0
58 1 0 0 1
57 1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
62 1 0 0 1
1 0 1 0
64 1 0 0 1
64 1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 0 1
1 0 1 0
1 1 0 0
1 0 0 1
1 0 0 1
74 1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 1 0 0
1 0 1 0
1 0 0 1
1 0 1 0
82 1 0 0 1
82 1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
84 1 0 0 1
1 0 0 1
1 0 0 1
90 1 0 0 1
90 1 0 0 1
1 0 0 1
1 0 1 0
 1 0 0 1
1 0 1 0
1 1 0 0
1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 0 1
2 1 0 1 0
1 0 1 0
7 1 0 1 0
7 1 0 1 0
7 1 0 0 1
7 1 1 0 0
6 1 0 1 0
1 0 0 1
1 1 0 0
1 0 0 1
14 1 0 0 1
14 1 0 0 1
1 0 0 1
18 1 0 0 1
18 1 0 0 1
18 1 0 0 1
1 1 0 0
1 0 1 0
21 1 0 1 0
21 1 0 1 0
21 1 1 0 0
4 1 0 1 0
1 0 0 1
1 1 0 0
1 0 0 1
1 0 0 1
1 0 0 1
29 1 1 0 0
1 0 0 1
30 1 0 1 0
30 1 1 0 0
1 0 0 1
34 1 1 0 0
1 1 0 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
 1 1 0 0
1 0 1 0
1 0 1 0
43 1 0 1 0
1 0 1 0
45 1 0 1 0
45 1 0 1 0
1 0 1 0
1 1 0 0
1 0 0 1
52 1 1 0 0
49 1 0 1 0
1 1 0 0
1 0 0 1
1 0 0 1
1 0 0 1
59 1 1 0 0
1 0 0 1
62 1 1 0 0
65 1 0 1 0
1 1 0 0
1 0 1 0
68 1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
71 1 1 0 0
1 0 0 1
1 0 1 0
1 0 0 1
75 1 1 0 0
1 1 0 0
74 1 0 0 1
1 0 1 0
78 1 0 0 1
1 0 0 1
79 1 0 0 1
1 0 1 0
1 0 1 0
81 1 0 1 0
1 0 0 1
82 1 0 0 1
1 0 0 1
83 1 0 1 0
1 0 1 0
 84 1 0 1 0
1 1 0 0
1 0 1 0
1 0 1 0
1 0 0 1
88 1 0 0 1
1 0 0 1
89 1 0 0 1
1 0 1 0
92 1 0 1 0
92 1 0 1 0
1 0 0 1
1 0 0 1
94 1 1 0 0
1 0 1 0
1 0 1 0
96 1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
119 1 0 0 1
119 1 0 0 1
119 1 0 0 1
1 0 0 1
1 1 0 0
1 0 0 1
1 0 0 1
106 1 0 1 0
1 1 0 0
1 0 1 0
1 0 0 1
111 1 0 0 1
1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
6 1 0 0 1
1 0 1 0
1 0 0 0
1 1 0 0
1 0 0 1
1 1 0 0
 1 1 0 0
16 1 0 0 1
16 1 1 0 0
16 1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
1 0 0 1
27 1 0 0 1
27 1 1 0 0
1 0 0 1
1 0 1 0
1 1 0 0
33 1 0 0 1
33 1 0 0 1
33 1 0 0 1
32 1 1 0 0
1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
40 1 0 1 0
1 1 0 0
41 1 0 0 1
41 1 0 1 0
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44 1 1 0 0
1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
50 1 0 0 1
1 0 1 0
51 1 0 0 1
1 0 0 1
60 1 0 0 1
60 1 0 1 0
1 0 0 1
54 1 0 0 1
1 0 0 1
56 1 0 0 1
1 0 1 0
58 1 0 0 1
1 0 0 1
1 1 0 0
64 1 0 0 1
64 1 1 0 0
1 0 0 1
1 0 1 0
1 1 0 0
1 0 0 1
1 1 0 0
1 0 1 0
69 1 0 0 1
69 1 1 0 0
1 0 0 1
72 1 1 0 0
1 0 0 1
1 0 0 1
1 1 0 0
77 1 0 0 1
77 1 0 0 1
1 1 0 0
1 0 0 1
1 0 0 1
81 1 1 0 0
1 0 0 1
83 1 1 0 0
1 1 0 0
1 1 0 0
1 0 0 1
1 0 1 0
1 0 1 0
1 0 0 1
89 1 0 0 1
1 0 0 1
92 1 1 0 0
1 1 0 0
94 1 0 0 1
1 1 0 0
95 1 0 1 0
 96 1 0 1 0
1 1 0 0
98 1 0 0 1
98 1 0 1 0
1 0 0 1
1 0 1 0
102 1 1 0 0
1 0 0 1
1 1 0 0
107 1 0 0 1
107 1 0 1 0
1 0 1 0
1 0 0 1
111 1 0 0 1
111 1 0 0 1
1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
1 0 0 1
1 0 1 0
4 1 0 1 0
1 0 1 0
9 1 1 0 0
8 1 0 1 0
1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
17 1 0 0 1
1 1 0 0
1 0 0 1
1 0 0 1
5 1 1 0 0
20 1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
27 1 0 0 1
1 0 1 0
30 1 0 1 0
1 1 0 0
1 1 0 0
35 1 0 0 1
33 1 1 0 0
1 0 1 0
39 1 0 0 1
40 1 0 1 0
1 1 0 0
1 0 1 0
43 1 0 0 1
1 1 0 0
1 0 1 0
50 1 0 0 1
48 1 0 1 0
1 0 1 0
52 1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
1 0 1 0
57 1 0 0 1
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60 1 0 0 1
62 1 0 1 0
1 0 1 0
1 1 0 0
23 1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
75 1 0 0 1
74 1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
1 0 1 0
 82 1 0 0 1
1 0 1 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 1 0 0
1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
1 1 1 0 0
1 0 0 1
2 1 0 0 1
1 0 1 0
4 1 0 0 1
1 0 0 1
1 0 0 1
6 1 0 1 0
1 1 0 0
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1 0 0 1
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1 1 0 0
1 0 0 1
17 1 0 0 1
17 1 0 1 0
1 0 1 0
18 1 0 1 0
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20 1 0 0 1
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22 1 0 0 1
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 23 1 0 0 1
1 0 0 1
1 0 0 1
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26 1 1 0 0
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1 0 0 1
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31 1 0 0 1
31 1 0 0 1
31 1 1 0 0
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32 1 0 0 1
1 0 1 0
33 1 0 1 0
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1 1 0 0
38 1 0 0 1
54 1 0 1 0
1 1 0 0
1 0 0 1
41 1 1 0 0
1 0 0 1
1 0 0 1
1 0 1 0
42 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
6 1 0 0 1
1 0 0 1
1 0 0 1
8 1 0 0 1
1 0 1 0
9 1 0 0 1
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11 1 0 0 1
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15 1 0 0 1
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1 0 1 0
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27 1 0 0 1
27 1 0 0 1
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37 1 0 0 1
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53 1 0 0 1
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1 1 0 0
1 0 0 1
1 0 0 1
55 1 0 1 0
55 1 0 1 0
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1 1 0 0
57 1 0 0 1
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67 1 0 0 1
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64 1 0 0 1
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71 1 0 0 1
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76 1 0 0 1
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97 1 0 1 0
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101 1 0 0 1
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105 1 0 0 1
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110 1 0 0 1
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1 0 0 1
1 0 1 0
1 0 0 1
115 1 0 0 1
1 0 0 1
1 0 0 1
117 1 0 1 0
1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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1 0 1 0
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4 1 0 0 1
1 1 0 0
7 1 0 0 1
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1 1 0 0
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18 1 0 1 0
18 1 0 1 0
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25 1 0 1 0
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61 1 0 0 1
61 1 0 0 1
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62 1 0 0 1
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1 0 1 0
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95 1 0 1 0
95 1 0 1 0
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1 0 0 1
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1 1 0 0
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103 1 0 0 1
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106 1 0 0 1
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109 1 0 0 1
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111 1 0 0 1
1 0 1 0
113 1 0 0 1
1 0 0 1
1 0 1 0
115 1 0 0 1
1 1 0 0
119 1 1 0 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 0 1
2 1 1 0 0
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1 0 1 0
1 0 0 1
1 1 0 0
7 1 0 0 1
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10 1 0 0 1
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129 1 0 0 1
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1 0 1 0
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66 1 0 1 0
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73 1 0 1 0
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1 0 0 1
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1 0 0 1
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92 1 0 0 1
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1 0 0 1
97 1 0 0 1
95 1 0 1 0
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1 0 0 1
1 0 0 1
1 0 0 1
101 1 1 0 0
102 1 0 1 0
1 0 1 0
104 1 0 0 1
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1 0 0 1
1 0 0 1
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1 0 0 1
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1 1 0 0
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1 0 0 1
1 0 0 1
116 1 0 1 0
1 0 0 1
119 1 0 0 1
121 1 0 1 0
1 0 1 0
124 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 0 1
2 1 0 0 1
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1 0 0 1
1 0 0 1
1 0 0 1
6 1 0 0 1
1 0 1 0
8 1 0 0 1
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1 0 0 1
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21 1 0 1 0
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1 0 0 1
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31 1 0 0 1
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36 1 0 1 0
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36 1 0 1 0
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79 1 0 1 0
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56 1 0 0 1
56 1 0 1 0
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57 1 0 1 0
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68 1 0 0 1
1 0 1 0
1 0 0 1
70 1 0 1 0
 70 1 0 0 1
1 1 0 0
1 0 0 1
74 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 1 0 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 1 0
6 1 1 0 0
1 0 0 1
1 0 0 1
10 1 0 0 1
1 0 1 0
11 1 0 0 1
12 1 0 1 0
11 1 0 1 0
1 0 1 0
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1 0 1 0
17 1 0 1 0
17 1 0 0 1
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26 1 0 1 0
21 1 0 1 0
26 1 0 1 0
26 1 0 1 0
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1 0 1 0
1 0 1 0
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32 1 0 0 1
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37 1 0 0 1
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54 1 0 0 1
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1 0 0 1
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1 0 1 0
64 1 0 0 0
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1 0 0 1
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89 1 0 1 0
1 0 0 1
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1 0 1 0
1 1 0 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 0 1
4 1 0 1 0
4 1 0 1 0
1 0 0 1
1 0 0 1
6 1 0 1 0
7 1 0 1 0
1 0 0 1
9 1 0 1 0
1 0 0 1
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12 1 0 0 1
1 0 0 1
1 0 1 0
15 1 0 1 0
1 0 1 0
1 0 0 0
20 1 0 1 0
20 1 0 1 0
1 0 0 0
22 1 0 1 0
22 1 0 1 0
1 0 0 1
1 0 0 1
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1 1 0 0
 1 1 0 0
1 0 0 1
1 0 0 1
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1 0 1 0
1 0 1 0
1 0 0 1
35 1 0 0 1
1 0 0 1
38 1 0 1 0
38 1 0 1 0
1 0 0 1
1 0 1 0
1 0 1 0
41 1 0 0 1
44 1 0 1 0
41 1 0 1 0
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1 0 0 1
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1 0 1 0
50 1 0 0 1
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1 0 1 0
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66 1 0 1 0
1 0 0 1
1 0 0 1
68 1 0 1 0
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70 1 0 0 1
71 1 0 1 0
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1 0 0 1
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77 1 0 1 0
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80 1 0 1 0
1 0 1 0
1 0 0 1
84 1 0 1 0
84 1 0 1 0
1 0 1 0
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89 1 0 1 0
87 1 0 1 0
1 0 0 1
91 1 0 1 0
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92 1 0 0 1
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96 1 0 1 0
96 1 0 1 0
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102 1 0 0 1
1 0 1 0
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105 1 0 0 1
1 0 1 0
107 1 0 0 1
1 0 0 1
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112 1 0 0 1
112 1 0 1 0
1 0 0 1
1 0 0 1
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 119 1 0 1 0
119 1 0 1 0
1 0 0 1
1 0 0 1
122 1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 0
1 1 0 0
1 0 0 1
5 1 0 1 0
1 0 1 0
6 1 0 0 0
1 0 1 0
1 0 1 0
20 1 0 0 1
1 0 1 0
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45 1 0 0 1
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43 1 0 1 0
1 0 0 1
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34 1 0 1 0
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37 1 0 0 1
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1 0 1 0
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26 1 0 0 1
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1 1 0 0
16 1 0 0 1
16 1 0 0 1
1 0 0 1
1 0 0 1
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 8 1 0 0 1
8 1 0 0 1
1 1 0 0
1 0 0 1
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1 1 0 0
1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
 1 0 0 1
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88 1 0 1 0
88 1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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105 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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1 0 1 0
3 1 0 0 1
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1 0 1 0
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1 0 0 1
1 0 0 1
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1 0 0 1
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23 1 0 0 1
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25 1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
30 1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
34 1 0 1 0
1 0 1 0
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37 1 0 0 1
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1 0 1 0
1 1 0 0
1 0 1 0
1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
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1 0 1 0
1 0 1 0
1 1 0 0
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51 1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
55 1 0 0 1
56 1 0 1 0
1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
59 1 0 0 1
1 0 0 1
61 1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
64 1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
71 1 0 1 0
1 1 0 0
1 0 1 0
1 1 0 0
1 0 0 1
76 1 0 1 0
1 0 1 0
1 0 0 1
1 0 1 0
79 1 0 0 1
1 1 0 0
1 0 0 1
81 1 0 0 1
81 1 0 1 0
1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
87 1 0 1 0
1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
92 1 0 0 1
1 0 0 1
94 1 0 0 1
1 0 0 1
96 1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
101 1 0 1 0
1 0 0 1
1 0 1 0
103 1 0 0 1
1 0 0 1
105 1 0 0 1
 1 0 0 1
1 0 0 1
107 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
1 1 0 0 1
1 1 0 0 1
1 0 0 1
5 1 0 0 1
1 0 1 0
7 1 0 1 0
1 0 0 1
1 0 0 1
10 1 0 1 0
1 0 1 0
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1 0 1 0
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1 0 1 0
17 1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
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1 0 0 1
24 1 0 1 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 1 0
30 1 0 0 1
1 0 0 1
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34 1 0 0 1
1 0 0 1
35 1 0 0 1
1 0 0 1
1 1 0 0
1 0 0 1
1 1 0 0
38 1 0 0 1
38 1 0 0 1
38 1 0 1 0
1 0 0 1
43 1 0 1 0
1 0 1 0
46 1 0 0 1
1 0 1 0
48 1 0 0 1
51 1 0 0 1
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1 1 0 0
52 1 0 0 1
53 1 0 0 1
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1 1 0 0
56 1 0 0 1
56 1 0 0 1
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59 1 0 0 1
1 1 0 0
61 1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
65 1 0 1 0
1 0 0 1
1 0 1 0
69 1 0 0 1
70 1 0 0 1
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72 1 0 0 1
72 1 0 1 0
72 1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 0 1
81 1 0 0 1
1 0 1 0
1 0 0 1
84 1 0 0 1
1 0 1 0
86 1 0 0 1
1 0 0 1
 1 0 0 1
89 1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
96 1 0 0 1
1 0 0 1
1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
1 0 1 0
2 1 0 0 1
3 1 0 1 0
1 0 1 0
5 1 0 0 1
5 1 0 0 1
1 1 0 0
8 1 0 1 0
1 0 0 1
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1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 0 1 0
1 1 0 0
1 0 1 0
19 1 0 0 1
20 1 0 0 1
20 1 0 1 0
1 0 0 1
22 1 0 0 1
1 0 0 1
24 1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 1 0 0
1 0 0 1
31 1 0 1 0
 1 0 1 0
33 1 0 1 0
1 0 1 0
35 1 0 1 0
35 1 0 0 1
35 1 0 0 1
1 1 0 0
1 0 0 1
1 0 0 1
1 0 0 1
41 1 0 0 1
1 0 0 1
1 0 0 1
44 1 0 1 0
46 1 0 0 1
44 1 1 0 0
1 0 0 1
1 0 0 1
49 1 1 0 0
50 1 0 1 0
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1 0 0 1
53 1 0 1 0
1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
62 1 0 0 1
1 0 0 1
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64 1 0 0 1
64 1 0 1 0
1 1 0 0
1 0 1 0
68 1 0 0 1
1 0 1 0
70 1 0 1 0
70 1 0 0 1
73 1 0 1 0
1 0 1 0
1 1 0 0
 79 1 0 0 1
79 1 0 1 0
1 0 0 1
1 0 0 1
83 1 1 0 0
1 0 0 1
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1 1 0 0
1 0 0 1
1 0 0 1
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1 1 0 0
1 1 0 0
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91 1 0 0 1
92 1 0 0 1
92 1 0 1 0
1 0 1 0
94 1 0 0 1
1 0 0 1
96 1 1 0 0
98 1 0 0 1
98 1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
1 1 0 0
1 0 0 1
2 1 0 0 1
1 0 1 0
1 0 0 1
6 1 0 1 0
8 1 0 1 0
1 1 0 0
1 0 0 1
11 1 0 0 1
1 0 1 0
13 1 0 0 1
1 0 1 0
1 0 1 0
15 1 0 0 1
1 0 1 0
1 1 0 0
1 1 0 0
1 0 1 0
 1 0 0 1
21 1 0 0 1
1 0 1 0
1 0 0 1
24 1 0 0 1
1 0 0 1
26 1 0 1 0
27 1 0 1 0
1 1 0 0
1 0 0 1
1 0 0 1
1 0 0 1
29 1 0 0 1
1 0 0 1
30 1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
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36 1 0 0 1
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1 0 1 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
43 1 0 0 1
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1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
50 1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
1 0 0 1
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58 1 0 0 1
 59 1 0 1 0
58 1 0 1 0
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62 1 0 0 1
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1 0 0 1
64 1 0 1 0
1 0 0 1
1 0 1 0
1 0 0 1
1 0 0 1
67 1 0 0 1
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1 0 1 0
71 1 0 0 1
1 0 1 0
1 0 0 1
1 1 0 0
1 0 1 0
76 1 0 0 1
89 1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 1 0
2 1 0 0 1
1 0 0 1
4 1 0 1 0
1 0 0 1
6 1 0 0 1
1 0 0 1
1 0 0 1
1 0 1 0
9 1 0 0 1
1 0 0 1
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10 1 0 1 0
1 1 0 0
12 1 0 1 0
1 0 1 0
14 1 0 1 0
1 0 1 0
1 0 1 0
 16 1 0 0 1
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57 1 0 0 1
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1 0 0 1
1 0 1 0
24 1 0 0 1
1 0 1 0
25 1 0 0 1
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28 1 0 0 1
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29 1 0 0 1
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31 1 0 0 1
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33 1 0 0 1
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35 1 0 0 1
1 0 0 1
1 0 0 1
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1 0 1 0
38 1 0 1 0
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41 1 0 1 0
1 0 0 1
1 0 1 0
1 1 0 0
1 0 0 1
45 1 0 1 0
1 0 0 1
47 1 0 0 1
1 0 1 0
1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
1 0 1 0
1 0 1 0
1 0 1 0
4 1 0 0 1
1 0 1 0
1 0 1 0
1 1 0 0
8 1 0 0 1
8 1 0 0 1
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11 1 0 0 1
1 0 1 0
12 1 0 0 1
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18 1 0 0 1
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28 1 0 0 1
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30 1 0 0 1
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34 1 0 0 1
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1 0 1 0
1 0 1 0
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41 1 0 0 1
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55 1 0 1 0
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58 1 0 0 1
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63 1 0 0 1
118 1 0 1 0
118 1 0 1 0
1 0 0 1
66 1 0 0 1
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1 0 0 1
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83 1 0 1 0
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94 1 0 1 0
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1 0 0 1
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1 0 0 1
1 0 1 0
100 1 0 1 0
100 1 0 0 1
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1 0 0 1
1 0 0 1
106 1 0 0 1
1 0 0 1
108 1 0 0 1
1 0 0 1
1 1 0 0
109 1 0 0 1
1 0 1 0
112 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 1 0
2 1 0 0 1
1 0 1 0
4 1 0 0 1
1 0 0 1
6 1 0 1 0
1 0 0 1
8 1 0 0 1
8 1 0 1 0
1 0 0 1
12 1 0 0 1
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1 0 1 0
1 0 1 0
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7 1 0 0 1
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143 1 0 0 1
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33 1 0 0 1
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38 1 0 1 0
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63 1 0 1 0
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69 1 0 0 1
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78 1 0 0 1
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82 1 0 0 1
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104 1 0 0 1
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1 0 0 1
1 0 0 1
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127 1 0 1 0
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129 1 0 0 1
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1 0 0 1
132 1 0 0 1
132 1 0 0 1
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1 0 0 1
1 0 0 1
137 1 0 0 1
1 0 1 0
139 1 0 0 1
139 1 0 0 1
 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 1 0 0
1 1 0 1 0
1 0 1 0
4 1 0 0 1
1 0 1 0
1 0 1 0
1 0 1 0
8 1 0 0 1
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14 1 0 0 1
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22 1 0 0 1
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27 1 0 1 0
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32 1 0 1 0
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35 1 0 0 1
35 1 0 0 1
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39 1 0 0 1
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45 1 0 0 1
109 1 0 1 0
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92 1 0 0 1
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1 0 0 1
99 1 0 0 1
1 0 0 1
101 1 0 0 1
1 0 0 1
103 1 0 0 1
1 0 1 0
105 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 0 1 0
3 1 0 0 1
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1 0 1 0
1 0 0 1
7 1 0 0 1
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1 0 0 1
1 0 1 0
11 1 0 0 1
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52 1 0 0 1
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54 1 0 0 1
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1 0 0 1
56 1 0 0 1
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1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
1 1 0 0 1
1 1 0 0 1
1 1 0 0
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4 1 0 1 0
1 0 0 1
5 1 0 0 1
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42 1 0 1 0
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46 1 0 1 0
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1 0 0 1
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121 1 0 0 1
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1 0 0 1
1 0 0 1
124 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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1 0 0 1
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1 0 1 0
4 1 0 1 0
5 1 0 0 1
1 0 0 1
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1 0 0 1
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16 1 0 0 1
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111 1 0 0 1
1 0 0 1
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20 1 1 0 0
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26 1 0 0 1
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28 1 0 1 0
31 1 0 0 1
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1 0 0 1
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1 0 0 1
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66 1 1 0 0
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76 1 1 0 0
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95 1 0 1 0
98 1 0 0 1
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1 0 0 1
1 0 0 1
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108 1 1 0 0
108 1 1 0 0
1 0 1 0
109 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
5 1 0 1 0
2 1 0 0 1
2 1 0 1 0
1 0 0 1
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27 1 0 1 0
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32 1 0 0 1
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1 0 0 1
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97 1 0 0 1
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1 0 1 0
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124 1 0 1 0
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130 1 0 0 1
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133 1 0 0 1
134 1 0 1 0
Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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1 0 0 1
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 88 1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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1 0 0 1
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39 1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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1 0 1 0
131 1 0 0 1
Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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Role ParentID doc_completeness rootclasslayer action object concept
 1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
 1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
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Role ParentID doc_completeness rootclasslayer action object concept
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 1 0 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 1 0
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
 1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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Role ParentID doc_completeness rootclasslayer action object concept
1 0 0 1
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 1 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 1 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 1 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
1 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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0 0 1 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 1 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 1 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 1 0
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0 0 0 0 0
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 1 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
0 0 0 0 0
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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physical-process mathematical-process experiment computer-algorithm analytical-process
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0-100 abstractIndiv00071.txt 62 779 805
0-100 abstractIndiv00075.txt 37 496 502
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Text
norepinephrine
series
CYP1A1
single nucleotide polymorphism
unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rat
extracellular signal-regulated kinase (ERK) activity
Interspecies considerations
Two delayed rectifier K+ currents
diverse electrophysiological and pharmacological properties
phosphatidylinositol 3-kinase
addition
phototoxicity
brain and liver tissues
pharmacokinetic parameters
effect
MCC