gebhart/patrepeval huggingface dataset:
A monoclonal antibody to factor IX that inhibits the factor VIII:Ca potentiation of factor X activation. (1985)

A murine monoclonal antibody (IgG1k, Kd approximately 10(-8) M) specific for an epitope located on the heavy chain of human factor IXa was used to study structure-function relationships of factor IX. The antibody inhibited factor IX clotting activity but did not impair activation of factor IX either by factor XIa/calcium or by factor VIIa/tissue factor/calcium. The antibody also did not impair the binding of factor IXa to antithrombin III. Moreover, the antibody did not prevent calcium and phospholipid (PL) from inhibiting the binding of factor IXa to antithrombin III. The antibody also failed to impair activation of factor VII by factor IXa/calcium/PL. Furthermore, the antibody did not interfere with the very slow activation of factor X by factor IXa/calcium/PL. In contrast, the antibody did interfere with factor X activation when reaction mixtures also contained factor VIII:Ca/von Willebrand factor. The marked acceleration of factor X activation observed in control mixtures was not observed in mixtures containing the antibody. Similar results were obtained in reaction mixtures containing the Fab portion of the antibody and factor VIII:Ca free of von Willebrand factor. In additional experiments, factor VIII:Ca/von Willebrand factor was found to inhibit the binding of the antibody to 125I-factor IXa as determined using an immunosorbent assay. Moreover, the antibody displaced factor VIII:Ca from the factor X activator complex (IXa/calcium/PL/VIII:Ca) as evidenced by an altered elution pattern on gel filtration chromatography. From these observations, we conclude that the antibody impairs the clotting activity of factor IXa through interference with its binding of factor VIII:Ca. This suggests a significant role for the heavy chain (residues of 181-415) of factor IXa in binding factor VIII:Ca.
Identification of Bases in 16 S rRNA Essential for tRNA Binding at the 30 S Ribosomal P Site (1995)

Previous studies suggest that the mechanism of action of the ribosome in translation involves crucial transfer RNA (tRNA)-ribosomal RNA (rRNA) interactions. Here, a selection scheme was developed to identify bases in 16S rRNA that are essential for tRNA binding to the P site of the small (30S) ribosomal subunit. Modification of the N-1 and N-2 positions of 2-methylguanine 966 and of the N-7 position of guanine 1401 interfered with messenger RNA (mRNA)-dependent binding of tRNA to the P site. Modification of the same positions as well as of the N-1 and N-2 positions of guanine 926 interfered with mRNA-independent binding of tRNA at high magnesium ion concentration. These results suggest that these three bases are involved in intermolecular contacts between ribosomes and tRNA.
Radiation colitis is another mimic of chronic inflammatory bowel disease. (1992)

results originate in two independent centres.Leary et al suggest that as HPV DNA is not always present in glandular neoplasia' that HPV might be a cofactor rather than an initiator of endocervical glandular neoplasia.If this is so then HPV DNA need not necessarily be detected, possibly explaining the discrepant results from the United Kingdom and elsewhere.To summarise, results from the United Kingdom37 suggest that infection with HPV types 6, 11, 16, 18 and 31 does not necessarily have a major role in cervical glandular neoplasia.
Prospective Study of Fluoxetine Treatment and Suicidal Behavior in Affectively Ill Subjects (1999)

The results do not support the speculation that fluoxetine increases the risk of suicide. Rather, there was a nonsignificant reduction in risk of suicidal behavior among patients treated with fluoxetine, even though those subjects were more severely ill before treatment with fluoxetine.
Oral health is impaired in Behcet's disease and is associated with disease severity (2004)

Oral health is impaired in BD and associated with disease severity. Improvement of the oral health of BD patients may affect their disease course, leading to a better prognosis.
Statistics : methods and applications : a comprehensive reference for science, industry, and data mining (2006)

Elementary concepts in statistics -- Basic statistics and tables -- ANOVA/MANOVA -- Association rules -- Boosting trees -- Canonical analysis -- CHAID analysis -- Classification and regression trees (CART) -- Classification trees -- Cluster analysis -- Correspondence analysis -- Data mining techniques -- Discriminant function analysis -- Distribution fitting -- Experimental design (Industrial DOE) -- Factor analysis and principal components -- General discrimination analysis (GDA) -- General linear models (GLM) -- General regression models (GRM) -- Generalized additive models (GAM) -- Generalized linear/nonlinear models (GLZ) -- Log linear analysis of frequency tables -- Machine learning -- Multivariate adaptive regression splines (MARSplines) -- Multidimensional scaling (MDS) -- Multiple linear regression -- Neural networks -- Nonlinear estimation -- Nonparametric statistics -- Partial least squares (PLS) -- Power analysis -- Process analysis -- Quality control charts -- Reliabilty/item analysis -- Structural equation modeling -- Survival/failure time analysis -- Text mining -- Time series/forecasting -- Variance components and mixed model ANOVA/ANCOVA.
Regulation of free and bound magnesium in rat hepatocytes and isolated mitochondria. (1986)

Null point titration techniques have been developed for measurements of cytosolic free Mg2+ in isolated cells and matrix free Mg2+ in isolated mitochondria using antipyrylazo III as a spectrophotometric Mg2+ indicator. A cytosolic free Mg2+ of 0.37 +/- 0.02 mM was obtained with hepatocytes. This represented about 6% of the total cytosolic magnesium content (activity coefficient of 5.8 X 10(-2). Nondiffusable Mg2+-binding sites in the cytosol were equal to 11.1 nmol/mg cell dry weight with an apparent dissociation constant of 0.71 mM and accounted for binding of 32% of the cytosolic magnesium. The null point method gave a value of 0.35 +/- 0.01 mM for the mitochondrial matrix free Mg2+ concentration (activity coefficient of 8.8 X 10(-3). Nondiffusable Mg2+ binding sites in the mitochondria were estimated at 25.7 nmol/mg mitochondrial protein with an apparent dissociation constant of 0.22 mM, compared with an apparent dissociation constant of 1.66 microM for bound calcium. These data demonstrate the absence of a significant gradient of free Mg2+ between the cytosolic and mitochondrial compartments. They also demonstrate a high ligand binding capacity for magnesium in both compartments with relatively low affinity resulting in a constant value for free Mg2+ when total cell magnesium is constant. This maintains a ratio between free Mg2+ and free Ca2+ of about 2000 in the cytosol and 100 in the mitochondria. The high concentration and low affinity of Mg2+ binding sites results in rather large changes of free Mg2+ with small variations in total cell magnesium. This is apparent in hepatocytes isolated from streptozotocin diabetic rats which had a decreased total magnesium content and a cytosolic free Mg2+ of 0.16 +/- 0.02 mM.
Acquired resistance to bile increases fructose-6-phosphate phosphoketolase activity in Bifidobacterium (2004)

Two Bifidobacterium strains with acquired resistance to bile were used in this study. Significant differences on membrane-associated protein profiles were found between the bile resistant derivatives and their corresponding original strains. One of the major species detected in one of the resistant derivatives had an apparent denatured molecular mass of approximately 90 kDa, and was identified as xylulose-5-phosphate/fructose-6-phosphate phosphoketolase, the key enzyme of Bifidobacterium carbohydrate catabolism. Phosphoketolase activity was considerably higher in membrane preparations and cell-free extracts of the two bile resistant derivatives. This correlated to a greater consumption rate of glucose in resistant strains. Fructose-6-phosphate phosphoketolase activity in the strain Bifidobacterium bifidum CECT4549 and its resistant derivative was found to be partially associated with the cytoplasmic membrane through weak interactions.
Ribosomal Synthesis of Unnatural Peptides (2005)

Combinatorial libraries of non-biological polymers and drug-like peptides could in principle be synthesized from unnatural amino acids by exploiting the broad substrate specificity of the ribosome. The ribosomal synthesis of such libraries would allow rare functional molecules to be identified using technologies developed for the in vitro selection of peptides and proteins. Here, we use a reconstituted E. coli translation system to simultaneously re-assign 35 of the 61 sense codons to 12 unnatural amino acid analogues. This reprogrammed genetic code was used to direct the synthesis of a single peptide containing 10 different unnatural amino acids. This system is compatible with mRNA-display, enabling the synthesis of unnatural peptide libraries of 10(14) unique members for the in vitro selection of functional unnatural molecules. We also show that the chemical space sampled by these libraries can be expanded using mutant aminoacyl-tRNA synthetases for the incorporation of additional unnatural amino acids or by the specific posttranslational chemical derivitization of reactive groups with small molecules. This system represents a first step toward a platform for the synthesis by enzymatic tRNA aminoacylation and ribosomal translation of cyclic peptides comprised of unnatural amino acids that are similar to the nonribosomal peptides.
Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate (2009)

We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing, decreased tolerance to delays, poor temporal foresight and steeper temporal discounting. A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder (ADHD). Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD. We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal, cingulate, striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds, motor timing to seconds and temporal discounting of longer time intervals. Given that impulsiveness, timing abnormalities and more specifically ADHD have been related to dopamine dysregulation, we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice, methylphenidate. This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor.
Human thrombopoietin structure–function relationships: identification of functionally important residues (1998)

Thrombopoietin (TPO) is a haematopoietic growth factor responsible for megakaryocyte progenitor proliferation and differentiation. It belongs to the four-helix-bundle cytokine family and exerts its biological effects through binding to a specific receptor, c-Mpl. With the use of site-directed mutagenesis we have generated 20 TPO mutants. Each of the TPO mutants was produced in a eukaryotic expression system and the mutants' ability to induce the proliferation of factor-dependent c-Mpl-expressing megakaryoblastic M-O7e cells was compared with that of wild-type TPO. Among the mutations studied, 10 lead to a significant decrease in TPO bioactivity. Of these ten residues, three are located in helix A of the protein (Arg10, Lys14 and Arg17) and four in helix D (His133, Gln132, Lys138 and Phe141), indicating that in TPO, as in other cytokines, these two helices are important for functional cytokine/receptor interactions. Surprisingly, mutant Arg10-->Ala (R10A) lacked any proliferative activity, despite the fact that this mutation was recently reported to have no effect on TPO/c-Mpl binding in a TPO phage ELISA [Pearce, Potts, Presta, Bald, Fendly and Wells (1997) J. Biol. Chem. 272, 20595-20602]. The lack of M-O7e proliferation is probably due to an inability of R10A mutant to promote receptor dimerization and thus receptor activation. Moreover we found that the Arg10 and Arg17 residues of TPO seem to be specific determinants for TPO/c-Mpl recognition. We also demonstrate that the O-glycosylation site located at position 110 of TPO is not necessary for the bioactivity of the cytokine.
Spreading and focal contact formation of human melanoma cells in response to the stimulation of both melanoma-associated proteoglycan (NG2) and alpha 4 beta 1 integrin. (1995)

In this study, we evaluated the potential role for a specific melanoma-associated chondroitin sulfate proteoglycan core protein, termed NG2, to collaborate with alpha 4 beta 1 integrin in focal contact formation in human melanoma cells. Although melanoma cells adhered to substrata coated with either the alpha 4 beta 1 integrin binding fibronectin synthetic peptide CS1-OVA or anti-NG2 mAbs, no spreading or focal contact formation was observed on either substratum. However, melanoma cells spread and formed focal contacts on "chimeric substrata" coated with CS1-OVA and the anti-NG2 mAb, 9.2.27, indicating that engaging both adhesion receptors changes the adhesion phenotype of melanoma cells by reorganizing the cytoskeleton. The collaboration between the two receptors is specific to fibronectin, since cells adherent on substrata coated with low concentrations of either laminin and 9.2.27 or type IV collagen and 9.2.27 failed to spread, while cells adherent on low concentrations of fibronectin and 9.2.27 exhibited a fully spread morphology. Two selective tyrosine kinase inhibitors, genistein and herbimycin A, totally inhibited cell spreading on the substrata coated with CS1-OVA and 9.2.27, indicating that tyrosine kinase(s) is important for cell spreading and focal contact formation. When cells were cultured on substrata coated with CS1-OVA and 9.2.27, two proteins (M(r) 130,000 and 120,000) were tyrosine phosphorylated in a genistein- and herbimycin A-sensitive fashion. These proteins were not immunologically related to pp125FAK or alpha 4 beta 1 integrin. Importantly, when melanoma cells were cultured on substrata coated with CS1 and then stimulated with 9.2.27-conjugated microsphere beads, formation of focal contacts and stress fibers was also observed, indicating that NG2 can collaborate with alpha 4 beta 1 integrin when each receptor is engaged on distinct and separate substrata. These results demonstrate that NG2 acts as a coreceptor for spreading and focal contact formation in association with alpha 4 beta 1 integrin in melanoma cells and suggest a model in which the NG2 core protein communicates to alpha 4 beta 1 integrin by an inside-out signaling mechanism.
<title>Application of neural networks to computer-aided pathology detection in mammography</title> (1993)

Digitized mammograms are used as input to a system of feedforward neural networks for determining the presence of clusters of microcalcifications. Rather than presenting the locations of detected suspected pathologies on the digital image itself, the intent is to produce a transparent overlay marking these possible pathologies for later diagnosis by the radiologist. Current results indicate that this method will in general be more efficient than human observers in locating low contrast objects and clusters of small microcalcifications (down to 50 micron diameter).
Applied Nonparametric Statistical Methods. (1990)

PREFACEINTRODUCING NONPARAMETRIC METHODSBasic StatisticsSamples and PopulationsHypothesis TestsEstimationEthical IssuesComputers and Nonparametric MethodsFurther ReadingCENTRALITY INFERENCE FOR SINGLE SAMPLESUsing Measurement DataInferences about Medians Based on RanksThe Sign TestTransformation of RanksAsymptotic ResultsRobustnessOTHER SINGLE-SAMPLE INFERENCEInferences for Dichotomous DataTests Related to the Sign TestMatching Samples to DistributionsAngular DataA Runs Test for RandomnessMETHODS FOR PAIRED SAMPLESComparisons in PairsA Less Obvious Use of the Sign TestPower and Sample SizeMETHODS FOR TWO INDEPENDENT SAMPLESCentrality Tests and EstimatesRank Based TestsThe Median TestNormal ScoresTests for Survival DataAsymptotic ApproximationPower and Sample SizeTests for Equality of VarianceTests for a Common DistributionTHREE OR MORE SAMPLESComparisons with Parametric MethodsCentrality Tests for Independent SamplesCentrality Tests for Related SamplesMore Detailed Treatment ComparisonsTests for Heterogeneity of VarianceSome MiscellaneousConsiderationsCORRELATION AND CONCORDANCECorrelation and Bivariate DataRanked Data for Several VariablesAgreementREGRESSIONBivariate Linear RegressionMultiple RegressionNonparametric Regression ModelsOther Multivariate Data ProblemsCATEGORICAL DATACategories and CountsNominal Attribute CategoriesOrdered Categorical DataGoodness-of-Fit Tests for Discrete DataExtension of McNemar'sTestASSOCIATION IN CATEGORICAL DATAThe Analysis of AssociationSome Models for Contingency TablesCombining and Partitioning of TablesPowerROBUST ESTIMATIONWhen Assumptions Break DownOutliers and InfluenceThe BootstrapM-Estimators and Other Robust EstimatorsAPPENDIXREFERENCESSOLUTIONS TO ODD-NUMBERED EXERCISESINDEXEach chapter also includes Fields of Application, Summary, and Exercises
Search for the optimal sequence of the ribosome binding site by random oligonucleotide-directed mutagenesis (1988)

Synthetic DNA duplexes corresponding to the ribosome binding site (RBS) were synthesized through the phosphite method on solid support. The synthetic RBS DNA with partial random sequences was inserted into an appropriate site between the lpp-lac promoter and the beta-galactosidase structural gene in plasmid pMKT2. The level of beta-galactosidase expression was correlated with the color intensity of the recombinant colonies on X-gal plates. The bluest colonies were isolated and characterized with respect to beta-galactosidase enzyme activity and RBS sequence. There was good correlation between color intensity and the level of the enzyme activity, and this provided a reliable phenotypic screening method in the search for the optimal regulatory sequences. Novel RBS sequences obtained here show not only the unique nucleotide distribution, but also strong complemetarity to the 3' end region of 16S rRNA, from which could be deduced a generalized RBS sequence, the position of the SD region, and the 16S rRNA position mediated during translation initiation.
Caffedymine from Cocoa Has COX Inhibitory Activity Suppressing the Expression of a Platelet Activation Marker, P-Selectin (2007)

Caffedymine (N-caffeoyldopamine) is a clovamide-type phenylpropenoic acid amide found in plants. Previous studies indicate that caffedymine inhibits P-selectin expression via increasing cAMP through beta-2 adrenoceptors, but the inhibition was only partially repressed by beta-2 adrenoceptor antagonists, suggesting additional mechanisms underlying the inhibitory effect. Therefore, in this study, the effect of caffedymine and its analogues (N-caffeoyltyramine, N-feruloyltyramine, N-coumaroyltyramine, N-cinnamoyltyramine) on COX enzymes (I and II) was investigated, because COX enzymes are deeply involved in regulating P-selectin expression on human platelets. The decreasing order of COX-I inhibitory activity was caffedymine>N-caffeoyltyramine>N-feruloyltyramine>N-coumaroyltyramine>N-cinnamoyltyramine. Caffedymine was the most potent compound tested, able to inhibit COX-I enzyme activity by 43% (P<0.013) at the concentration of 0.01 microM. At the same concentration, caffedymine was also able to inhibit COX-II enzyme activity by 36% (P<0.015), and the decreasing order of COX-II inhibitory activity was similar as that of COX-I. As a result of the COX inhibition, the production of thromboxane B2 (thromboxane A2 derivative) also decreased significantly in mouse blood treated with caffedymine and its analogues (0.05 microM). Caffedymine and N-caffeoyltyramine, both with potent COX inhibitory activity, were also able to inhibit P-selectin expression and platelet-leukocyte interactions. These data indicate that COX inhibition is likely to be another mechanism for caffedymine to inhibit P-selectin expression on platelets.
Type II Secretion by Aeromonas salmonicida : Evidence for Two Periplasmic Pools of Proaerolysin (2001)

Aeromonas salmonicida containing the cloned gene for proaerolysin secretes the protein via the type II secretory pathway. Here we show that altering a region near the beginning of aerA led to a dramatic increase in the amount of proaerolysin that was produced and that a large amount of the protein was cell associated. All of the cell-associated protein had crossed the cytoplasmic membrane, because the signal sequence had been removed, and all of it was accessible to processing by trypsin during osmotic shock. Enlargement of the periplasm was observed by electron microscopy in overproducing cells, likely caused by the osmotic effect of the very large concentrations of accumulated proaerolysin. Immunogold electron microscopy localized nearly all of the proaerolysin in the enlarged periplasm; however, only half of the protoxin was released from the cells by osmotic shocking. Cross-linking studies showed that this fraction contained normal dimeric proaerolysin but that proaerolysin in the fraction that was not shockable had not dimerized, although it appeared to be correctly folded. Both periplasmic fractions were secreted by the cells; however, the nonshockable fraction was secreted much more slowly than the shockable fraction. We estimated a rate for maximal secretion of proaerolysin from the bacteria that was much lower than the rates that have been estimated for inner membrane transit, which suggests that transit across the outer membrane is rate limiting and may account for the periplasmic accumulation of the protein. Finally, we show that overproduction of proaerolysin inhibited the release of the protease that is secreted by A. salmonicida.
High-numerical-aperture effects in photoresist (1997)

Two-beam and three-beam vector interference in thin photoresist films is used to illustrate the striking differences between s -polarized and p-polarized high-numerical-aperture illumination. Both simulations and experiments are performed for several cases, including undyed photoresist on silicon, dyed photoresist on silicon, and the addition of an antireflective layer between the photoresist and the silicon. A 0.85 numerical-aperture system is examined. The major differences between s- and p-polarized illumination include elliptical versus rectangular features and lower contrast for p-polarized images.