gebhart/patrepeval huggingface dataset:
Cochlear supporting cells (2010)

This article deals with the anatomy of cochlear supporting cell types, their molecular specializations, and their functional or physiological roles during normal hearing and during damage or overstimulation. It begins with explaining the cellular organization of the cochlea, focusing on the supporting cell types in the mature organ of corti. It also describes the functional roles of the supporting cells, which include, homeostasis in the cochlea, providing structural support, and few functions depending on the molecular specialization of supporting cells. Furthermore, it also details the functions of cochlear supporting cells during development, damage, repair, and regeneration. Finally, it gives a brief description on what lies in the future of cochlear supporting cells. It states that research into the function of supporting cells in the normal, damaged, and ageing ear will provide better understanding of cochlear physiology alleviate cochlear pathophysiology.
Multi-style training for robust isolated-word speech recognition (2005)

A new training procedure called multi-style training has been developed to improve performance when a recognizer is used under stress or in high noise but cannot be trained in these conditions. Instead of speaking normally during training, talkers use different, easily produced, talking styles. This technique was tested using a speech data base that included stress speech produced during a workload task and when intense noise was presented through earphones. A continuous-distribution talker-dependent Hidden Markov Model (HMM) recognizer was trained both normally (5 normally spoken tokens) and with multi-style training (one token each from normal, fast, clear, loud, and question-pitch talking styles). The average error rate under stress and normal conditions fell by more than a factor of two with multi-style training and the average error rate under conditions sampled during training fell by a factor of four.
Production of a suppressor factor by CD8+ lymphocytes activated by mycobacterial components (1991)

The lipid component present in high-molecular-mass fractions with molecular masses of greater than 200 kDa derived from Mycobacterium tuberculosis extracts passaged through Sephacryl S.200 columns activate CD8+ lymphocytes to suppress lymphocyte blastogenesis. Suppression is mediated by the release of suppressor molecules by these CD8+ lymphocytes. Release of suppressor molecules occurs as early as 2 h following pulsing with the high-molecular-mass mycobacterial components and is maximal at 24 h, after which their release declines rapidly. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblotting indicates that the active components are carbohydrate moieties with approximate molecular masses of 122 to 148 kDa. Our results suggest a mechanism of interaction between mycobacteria and host mononuclear cells such that mycobacterial lipids, once exposed, activate CD8+ suppressor lymphocytes. Activation of these lymphocytes results in the release of carbohydrate-containing molecules that ultimately inhibit the blastogenesis of other lymphocytes.
2′-O-(2-Methoxy)ethyl-modified Anti-intercellular Adhesion Molecule 1 (ICAM-1) Oligonucleotides Selectively Increase the ICAM-1 mRNA Level and Inhibit Formation of the ICAM-1 Translation Initiation Complex in Human Umbilical Vein Endothelial Cells (1997)

Little is known about the mechanisms that account for inhibition of gene expression by antisense oligonucleotides at the level of molecular cell biology. For this purpose, we have selected potent 2'-O-(2-methoxy)ethyl antisense oligonucleotides (IC50 = 2 and 6 nM) that target the 5' cap region of the human intercellular adhesion molecule 1 (ICAM-1) transcript to determine their effects upon individual processes of mRNA metabolism in HUVECs. Given the functions of the 5' cap structure throughout mRNA metabolism, antisense oligonucleotides that target the 5' cap region of a target transcript have the potential to modulate one or more metabolic stages of the message inside the cell. In this study we found that inhibition of protein expression by these RNase H independent antisense oligonucleotides was not due to effects on splicing or transport of the ICAM-1 transcript, but due instead to selective interference with the formation of the 80 S translation initiation complex. Interestingly, these antisense oligonucleotides also caused an increase in ICAM-1 mRNA abundance in the cytoplasm. These results imply that ICAM-1 mRNA turnover is coupled in part to translation.
Structure of von Willebrand Factor-cleaving Protease (ADAMTS13), a Metalloprotease Involved in Thrombotic Thrombocytopenic Purpura (2001)

Thrombotic thrombocytopenic purpura is associated with acquired or congenital deficiency of a plasma von Willebrand factor-cleaving protease (VWFCP). Based on partial amino acid sequence, VWFCP was identified recently as a new member of the ADAMTS family of metalloproteases and designated ADAMTS13. The 4.6-kilobase pair cDNA sequence for VWFCP has now been determined. By Northern blotting, full-length VWFCP mRNA was detected only in liver. VWFCP consists of 1427 amino acid residues and has a signal peptide, a short propeptide terminating in the sequence RQRR, a reprolysin-like metalloprotease domain, a disintegrin-like domain, a thrombospondin-1 repeat, a Cys-rich domain, an ADAMTS spacer, seven additional thrombospondin-1 repeats, and two CUB domains. VWFCP apparently is made as a zymogen that requires proteolytic activation, possibly by furin intracellularly. Sites for Zn(2+) and Ca(2+) ions are conserved in the protease domain. The Cys-rich domain contains an RGDS sequence that could mediate integrin-dependent binding to platelets or other cells. Alternative splicing gives rise to at least seven potential variants that truncate the protein at different positions after the protease domain. Alternative splicing may have functional significance, producing proteins with distinct abilities to interact with cofactors, connective tissue, platelets, and von Willebrand factor.
Mycobacterium tuberculosis 16-kDa Antigen (Hsp16.3) Functions as an Oligomeric Structure in Vitro to Suppress Thermal Aggregation (1996)

Tuberculosis continues to be a major disease threatening millions of lives worldwide. Several antigens of Mycobacterium tuberculosis, identified by monoclonal antibodies, have been cloned and are being exploited in the development of improved vaccines and diagnostic reagents. We have expressed and purified the 16-kDa antigen, an immunodominant antigen with serodiagnostic value, which has been previously cloned and shown to share low sequence homology with the alpha-crystallin-related small heat shock protein family. Sedimentation equilibrium analytical ultracentrifugation and dynamic light scattering demonstrate the formation of a specific oligomer, 149 +/- 8 kDa, consisting of approximately nine monomers. In 4 M urea, a smaller oligomer of 47 +/- 6 kDa (or trimer) is produced. Analysis by electron cryomicroscopy reveals a triangular shaped oligomeric structure arising from the presence of three subparticles or globules. Taken together, the data suggest an antigen complex structure of a trimer of trimers. This antigen, independent of ATP addition, effectively suppresses the thermal aggregation of citrate synthase at 40 degrees C, indicating that it can function as a molecular chaperone in vitro. A complex between the antigen and heat-denatured citrate synthase can be detected and isolated using high performance liquid chromatography. We propose to rename the 16-kDa antigen Hsp16.3 to be consistent with other members of the small heat shock protein family.
The tumor necrosis factor-α promoter −1031C polymorphism is associated with decreased risk of endometriosis in a Japanese population (2004)

The variability of the -1031T/C polymorphism of the TNF-alpha gene may be associated with susceptibility to (AUTHOR: as meant?) endometriosis.
Paullones, a Series of Cyclin-Dependent Kinase Inhibitors:  Synthesis, Evaluation of CDK1/Cyclin B Inhibition, and in Vitro Antitumor Activity (1999)

The paullones represent a novel class of small molecule cyclin-dependent kinase (CDK) inhibitors. To investigate structure-activity relationships and to develop paullones with antitumor activity, derivatives of the lead structure kenpaullone (9-bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, 4a) were synthesized. Paullones with different substituents in the 2-, 3-, 4-, 9-, and 11-positions were prepared by a Fischer indole reaction starting from 1H-[1]benzazepine-2,5(3H,4H)-diones 5. Selective substitutions at either the lactam or the indole nitrogen atom were accomplished by treating kenpaullone with alkyl halides in the presence of sodium hydride/THF or potassium hydroxide/acetone, respectively. S-Methylation of the kenpaullone-derived thiolactam 18 yielded the methylthioimidate 19, which gave the hydroxyamidine 20 upon reaction with hydroxylamine. The new paullones were tested both in a CDK1/cyclin B inhibition assay and in the in vitro antitumor cell line-screening program of the National Cancer Institute (NCI). With respect to the CDK1/cyclin B inhibition, electron-withdrawing substituents in the 9-position as well as a 2,3-dimethoxy substitution on the paullone basic scaffold turned out to be favorable. A 9-trifluoromethyl substituent was found to be equivalent to the 9-bromo substituent of kenpaullone. Replacement of the 9-bromo substituent of kenpaullone by a 9-cyano or 9-nitro group produced a substantial increase in enzyme-inhibiting potency. Substitutions in other positions or the replacement of the lactam moiety led to decreased CDK1 inhibition. Noteworthy in vitro antitumor activities (GI(50) values between 1 and 10 microM) were found with the 9-bromo-2,3-dimethoxy-7,12-dihydroindolo[3, 2-d][1]benzazepin-6(5H)-one (4t), its 9-trifluoromethyl analogue 4u, the 12-Boc-substituted paullone15, and the methylthioimidate 19, respectively. The 9-nitro-7,12-dihydroindolo[3, 2-d][1]benzazepin-6(5H)-one (4j, named alsterpaullone) showed a high CDK1/cyclin B inhibitory activity (IC(50) = 0.035 microM) and exceeded the in vitro antitumor potency of the other paullones by 1 order of magnitude (log GI(50) mean graph midpoint = -6.4 M).
Sodium Borohydride, Its Hydrolysis and its Use as a Reducing Agent and in the Generation of Hydrogen1 (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSodium Borohydride, Its Hydrolysis and its Use as a Reducing Agent and in the Generation of Hydrogen1H. I. Schlesinger, Herbert C. Brown, A. E. Finholt, James R. Gilbreath, Henry R. Hoekstra, and Earl K. HydeCite this: J. Am. Chem. Soc. 1953, 75, 1, 215–219Publication Date (Print):January 1, 1953Publication History Published online1 May 2002Published inissue 1 January 1953https://pubs.acs.org/doi/10.1021/ja01097a057https://doi.org/10.1021/ja01097a057research-articleACS PublicationsRequest reuse permissionsArticle Views9655Altmetric-Citations876LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Representation of Biochemistry for Modeling Organisms (1994)

Before one makes a database, one must needs understand the fundamental structure of that portion of the "real world" the database is intended to model. This understanding inevitably guides decisions on representation and implementation, so its fidelity to reality is critical: an accurate model is easier to change as knowledge evolves, and appropriate representational choices simplify the process of database revision. In this paper I describe the basic representational principles we have reached in our attempt to model portions of cellular biochemistry, and sketch some of their consequences for representation and our implementations.
Lentiviral Hematopoietic Stem Cell Gene Therapy in Patients with Wiskott-Aldrich Syndrome (2013)

Wiskott-Aldrich syndrome (WAS) is an inherited immunodeficiency caused by mutations in the gene encoding WASP, a protein regulating the cytoskeleton. Hematopoietic stem/progenitor cell (HSPC) transplants can be curative, but, when matched donors are unavailable, infusion of autologous HSPCs modified ex vivo by gene therapy is an alternative approach. We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen. All three patients showed stable engraftment of WASP-expressing cells and improvements in platelet counts, immune functions, and clinical scores. Vector integration analyses revealed highly polyclonal and multilineage haematopoiesis resulting from the gene-corrected HSPCs. Lentiviral gene therapy did not induce selection of integrations near oncogenes, and no aberrant clonal expansion was observed after 20 to 32 months. Although extended clinical observation is required to establish long-term safety, lentiviral gene therapy represents a promising treatment for WAS.
Electrophilic Peroxisome Proliferator–Activated Receptor-γ Ligands Have Potent Antifibrotic Effects in Human Lung Fibroblasts (2009)

Pulmonary fibrosis is a progressive scarring disease with no effective treatment. Transforming growth factor (TGF)-beta is up-regulated in fibrotic diseases, where it stimulates differentiation of fibroblasts to myofibroblasts and production of excess extracellular matrix. Peroxisome proliferator-activated receptor (PPAR) gamma is a transcription factor that regulates adipogenesis, insulin sensitization, and inflammation. We report here that a novel PPARgamma ligand, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO), is a potent inhibitor of TGF-beta-stimulated differentiation of human lung fibroblasts to myofibroblasts, and suppresses up-regulation of alpha-smooth muscle actin, fibronectin, collagen, and the novel myofibroblast marker, calponin. The inhibitory concentration causing a 50% decrease in aSMA for CDDO was 20-fold lower than the endogenous PPARgamma ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2) (15 d-PGJ(2)), and 400-fold lower than the synthetic ligand, rosiglitazone. Pharmacologic and genetic approaches were used to demonstrate that CDDO mediates its activity via a PPARgamma-independent pathway. CDDO and 15 d-PGJ(2) contain an alpha/beta unsaturated ketone, which acts as an electrophilic center that can form covalent bonds with cellular proteins. Prostaglandin A(1) and diphenyl diselenide, both strong electrophiles, also inhibit myofibroblast differentiation, but a structural analog of 15 d-PGJ(2) lacking the electrophilic center is much less potent. CDDO does not alter TGF-beta-induced Smad or AP-1 signaling, but does inhibit acetylation of CREB binding protein/p300, a critical coactivator in the transcriptional regulation of TGF-beta-responsive genes. Overall, these data indicate that certain PPARgamma ligands, and other small molecules with electrophilic centers, are potent inhibitors of critical TGF-beta-mediated profibrogenic activities through pathways independent of PPARgamma. As the inhibitory concentration causing a 50% decrease in aSMA for CDDO is 400-fold lower than that in rosiglitazone, the translational potential of CDDO for treatment of fibrotic diseases is high.
The Lipoprotein Receptor LR11 Regulates Amyloid β Production and Amyloid Precursor Protein Traffic in Endosomal Compartments (2006)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and neuropathological changes, including the deposition of amyloid beta (Abeta) in senile plaques. The mechanisms causing the disease and Abeta accumulation are not well understood, but important genetic associations with apolipoprotein E genotype and involvement of lipoprotein receptors have become apparent. LR11 (also known as SorLA), a member of the low-density lipoprotein receptor family, has been identified previously as an altered transcript in microarray analyses of samples from human AD cases. Here, we show neuronal expression of the lipoprotein receptor LR11 in control brain in regions vulnerable to AD neuropathology and marked reduction of LR11 expression in these regions in AD brains before cell death. Overexpression of LR11 drastically reduces levels of extracellular Abeta and also lowers levels of total cellular amyloid precursor protein (APP). LR11 colocalizes with APP and regulates its trafficking in endocytic compartments, which are important intracellular sites for APP processing and Abeta generation. Endogenous LR11 localizes to neuronal multivesicular bodies in both rat and human brain. The robust correlation between reduced LR11 expression and AD neuropathology and its potent effects on extracellular Abeta levels suggest that this neuronal lipoprotein receptor could play an important role in AD pathogenesis.
Zigzag defect free alignment and good bistability of surface stabilized Sc*cells (1991)

Abstract Both zigzag defect free alignment and good bistability of Scc * cells with a rubbed polymer film are obtained by a study on the influence of ferroelectric liquid crystal's phase transition sequences and enthalpy changes on the alignment and the bistability properties in the naphthalene containing liquid crystals system.
Age-specific effects of juvenile rheumatoid arthritis-associated HLA alleles (1999)

These data define at what age and for how long various HLA alleles influence susceptibility and protection (window-of-effect) in patients with JRA. In addition, these data establish more clearly the boundaries of ages-at-onset for 2 of the subtypes of the disease.
Comparative lesion sequencing provides insights into tumor evolution (2008)

We show that the times separating the birth of benign, invasive, and metastatic tumor cells can be determined by analysis of the mutations they have in common. When combined with prior clinical observations, these analyses suggest the following general conclusions about colorectal tumorigenesis: (i) It takes approximately 17 years for a large benign tumor to evolve into an advanced cancer but <2 years for cells within that cancer to acquire the ability to metastasize; (ii) it requires few, if any, selective events to transform a highly invasive cancer cell into one with the capacity to metastasize; (iii) the process of cell culture ex vivo does not introduce new clonal mutations into colorectal tumor cell populations; and (iv) the rates at which point mutations develop in advanced cancers are similar to those of normal cells. These results have important implications for understanding human tumor pathogenesis, particularly those associated with metastasis.
Functional abnormalities in P0-deficient mice resemble human hereditary neuropathies linked to P0 gene mutations (1996)

Mutations in the gene encoding the transmembranous cell adhesion molecule, myelin protein zero (P0), have been reported in patients with Charcot-Marie-Tooth disease types 1B and 3 (Déjérine-Sottas disease). We have previously shown that the targeted deletion of the P0 gene in mice results in impairment of sciatic nerve conduction, and we now extend our detailed electrophysiologic investigation to the facial nerve. In concordance with histologic investigations which revealed severe hypomyelination in peripheral nerves we found the typical electrophysiologic signs of severe dysmyelination in both the facial and sciatic nerves in mice homozygously deficient for the expression of P0 (P0 -/- mice). As compared to control mice (P0+/+), nerve conduction velocities were reduced to below 10% and compound muscle action potential (CMAP) amplitudes to below 25%, while CMAP duration and excitation thresholds were markedly increased. Surprisingly, nerve conduction changes in mice heterozygously deficient for P0 (P0+/-) were only mild, were detected only in the sciatic nerve, and occurred not before 5-7 months of age. They were more prominent at age 12-13 months. Thus, P0 -/- mice resemble severe human inherited neuropathies like Charcot-Marie-Tooth disease type 3 (Déjérine-Sottas disease) with onset early in life, whereas the P0 +/- mice may resemble the milder form, CMT1B.
The Central Role of Anti-IL-1 Blockade in the Treatment of Monogenic and Multi-Factorial Autoinflammatory Diseases (2013)

Inherited autoinflammatory diseases are secondary to mutations of proteins playing a pivotal role in the regulation of the innate immunity leading to seemingly unprovoked episodes of inflammation. The understanding of the molecular pathways involved in these disorders has shed new lights on the pattern of activation and maintenance of the inflammatory response and disclosed new molecular therapeutic targets. Cryopyrin-associated periodic syndrome (CAPS) represents the prototype of an autoinflammatory disease. The study of the pathophysiological consequence of mutations in the cryopyrin gene (NLRP3) allowed the identification of intracellular pathways responsible for the activation and secretion of the potent inflammatory cytokine interleukin-1β (IL-1β). It became clear that several multi-factorial inflammatory conditions display a number of pathogenic and clinical similarities with inherited autoinflammatory diseases. The dramatic effect of interleukin-1 (IL-1) blockade in CAPS opened new perspectives for the treatment of other inherited and multi-factorial autoinflammatory disorders. Several IL-1 blockers are now available on the market. In this review we outline the more recent novelties in the treatment with different IL-1 blockers in inherited and multi-factorial autoinflammatory diseases.
The Microsoft Multiperson Location Survey (2005)

The Microsoft Multiperson Location Survey (MSMLS) is an ongoing research project aimed at surveying the travel patterns of regular people. We loan to our volunteer subjects a GPS receiver capable of measuring and storing time-stamped (latitude, longitude) data. Nominally, we expect our subjects to leave the GPS in their car for about two weeks, during which time the GPS will record everywhere the car goes. When the subject returns the GPS, we upload the stored data to our server. With this data we are pursuing research projects for generating efficient driving directions and predicting a driver’s destination. This evolving technical report describes the project and the data gathered so far.