gebhart/patrepeval huggingface dataset:
Degradation of fibrinogen and collagen by staphopains, cysteine proteases released from Staphylococcus aureus (2010)

Staphylococcus aureus is the most frequently isolated pathogen in gram-positive sepsis often complicated by a blood clotting disorder, and is the leading cause of infective endocarditis induced by bacterial destruction of endocardial tissues. The bacterium secretes cysteine proteases referred to as staphopain A (ScpA) and staphopain B (SspB). To investigate virulence activities of staphopains pertinent to clotting disorders and tissue destruction, we examined their effects on collagen, one of the major tissue components, and on plasma clotting. Both staphopains prolonged the partial thromboplastin time of plasma in a dose- and activity-dependent manner, with SspB being threefold more potent than ScpA. Staphopains also prolonged the thrombin time of both plasma and fibrinogen, indicating that these enzymes can cause impaired plasma clotting through fibrinogen degradation. Whereas SspB cleaved the fibrinogen Aα-chain at the C-terminal region very efficiently, ScpA degraded it rather slowly. This explains the superior ability of the former enzyme to impair fibrinogen clottability. Enzymically active staphopains, at concentrations as low as 10 nM, degraded collagen with comparable efficiency. These results show novel virulence activities of staphopains in degrading fibrinogen and collagen, and suggest an involvement of staphopains in the clotting impairment and tissue destruction caused by staphylococcal infection.
A molecular compendium of genes expressed in multiple myeloma (2002)

We have created a molecular resource of genes expressed in primary malignant plasma cells using a combination of cDNA library construction, 5' end single-pass sequencing, bioinformatics, and microarray analysis. In total, we identified 9732 nonredundant expressed genes. This dataset is available as the Myeloma Gene Index (www.uhnres.utoronto.ca/akstewart_lab).Predictably, the sequenced profile of myeloma cDNAs mirrored the known function of immunoglobulin-producing, high-respiratory rate, low-cycling, terminally differentiated plasma cells. Nevertheless, approximately 10% of myeloma-expressed sequences matched only entries in the database of Expressed Sequence Tags (dbEST) or the high-throughput genomic sequence (htgs) database. Numerous novel genes of potential biologic significance were identified. We therefore spotted 4300 sequenced cDNAs on glass slides creating a myeloma-enriched microarray. Several of the most highly expressed genes identified by sequencing, such as a novel putative disulfide isomerase (MGC3178), tumor rejection antigen TRA1, heat shock 70-kDa protein 5, and annexin A2, were also differentially expressed between myeloma and B lymphoma cell lines using this myeloma-enriched microarray. Furthermore, a defined subset of 34 up-regulated and 18 down-regulated genes on the array were able to differentiate myeloma from nonmyeloma cell lines. These not only include genes involved in B-cell biology such as syndecan, BCMA, PIM2, MUM1/IRF4, and XBP1, but also novel uncharacterized genes matching sequences only in the public databases. In summary, our expressed gene catalog and myeloma-enriched microarray contains numerous genes of unknown function and may complement other commercially available arrays in defining the molecular portrait of this hematopoietic malignancy. GenBank Accession numbers include BF169967-BF176369, BF185966-BF185969, and BF177280-BF177455.
Biomarkers for the early diagnosis of hepatocellular carcinoma (2015)

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the 5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α-fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers, such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article, we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.
A structural support vector method for extracting contexts and answers of questions from online forums (2009)

This paper addresses the issue of extracting contexts and answers of questions from post discussion of online forums. We propose a novel and unified model by customizing the structural Support Vector Machine method. Our customization has several attractive properties: (1) it gives a comprehensive graphical representation of thread discussion. (2) It designs special inference algorithms instead of general-purpose ones. (3) It can be readily extended to different task preferences by varying loss functions. Experimental results on a real data set show that our methods are both promising and flexible.
Retinal detachment in the cat: the pigment epithelial-photoreceptor interface. (1983)

Twenty-six cat retinae were surgically detached by injecting fluid into the subretinal space (SRS). The retinae were then studied by light and electron microscopy at detachment intervals ranging from 1/2 hr to 14 months. Degenerative and proliferative changes occur at the retinal pigment epithelial (RPE)-photoreceptor interface very soon after detachment, and the severity of these changes depends upon both the duration and height of the detachment. The specialized apical RPE processes that ensheath the outer segments are replaced by a uniform fringe of short, undifferentiated processes. The apical RPE surface becomes mounded, and this mounding becomes more pronounced at longer detachment durations. Labeling experiments with 3H-thymidine showed that some cat RPE cells enter a phase of stimulated DNA synthesis 12-24 hrs after detachment; RPE mitotic figures are first apparent 48 hrs after detachment. In the cat, discrete regions of proliferated RPE cells usually appear in one of several configurations. A number of different cell types, including polymorphonuclear neutrophils, monocytes at various maturational stages, photoreceptor cells, Müller cells, and RPE cells, appear in the expanded SRS of detached retinae. Rod and cone outer segments degenerate rapidly and become membrane bound sacs by 3 days postdetachment; the assembly of new outer segment membrane apparently does not stop completely even at moderately long detachment intervals (ie, 2 months). Degenerative changes in the inner segments do not take place with the same rapidity as those in the outer segments. The changes that occur at the RPE-photoreceptor interface are rapid, progressive, and sometimes irreversible events that have significant implications for photoreceptor recovery following retinal reattachment surgery.
Coronary vascular reserve in humans: A critical review of methods of evaluation and of interpretation of the results (1995)

The concept of coronary vascular reserve stems from the description of coronary autoregulation by Mosher in 1964. Schematically, the coronary blood flow at rest depends on the determinants of myocardial oxygen demand (heart rate, contractility and ventricular load). If maximal coronary vasodilation is produced, it results in a linear and steep pressure-flow relationship. The increment of coronary flow above its basal value is called the coronary flow reserve, which indicates the flow added to the basal flow for a given coronary perfusion pressure when the coronary vascular bed is maximally dilated. Thus, in the absence of epicardial coronary artery stenosis, the maximal coronary flow is a function of the coronary perfusion pressure and of the maximal surface area of the coronary circulation at the resistance vessel level. Evaluation of the coronary reserve in humans raises three major concerns: (1) methods for measuring or evaluating coronary flow are imprecise and inconvenient (diffusible indicators), invasive (coronary sinus thermodilution, intracoronary Doppler), expensive and require sophisticated technology (ultrafast computed tomography, positron emission tomography), or in the process of being validated (contrast echocardiography, transoesophageal Doppler echocardiography, myocardial scintigraphy: (2) the compounds used to produce maximal coronary vasodilation are administered either by the intracoronary route (papaverine) or intravenously (dipyridamole, adenosine); (3) how to interpret the data: is the alteration of the coronary reserve due to a modification of the basal coronary flow or/and of the maximal coronary flow? Thus, each method has its own limitations and constraints that must be taken into account in order to avoid crude misinterpretations. In conclusion, the measurement of coronary reserve may be an important means of understanding coronary physiology and pathophysiology. Recently developed non-invasive methods (ultrafast computed tomography, positron emission tomography, echography) and the ability to produce maximal coronary vasodilation by the intravenous route are promising.
The use of chipcards for electronic signatures and encryption (2003)

The intelligent chipcard as a personal security device is being introduced in many application fields. If a document has to be concealed in order to provide confidentiality, it has to be encrypted. The user's instrument for producing an electronic signature and for decryption of an encrypted message is an intelligent chipcard. The main characteristics of such a chipcard are outlined. Particular attention is given to cards based on the RSA encryption algorithm of R. Rivest et al. (1978).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Saposins: structure, function, distribution, and molecular genetics. (1992)

Saposins A, B, C, and D are small heat-stable glycoproteins derived from a common precursor protein, prosaposin. These mature saposins, as well as prosaposin, activate several lysosomal hydrolases involved in the metabolism of various sphingolipids. All four saposins are structurally similar to one another including placement of six cysteines, a glycosylation site, and conserved prolines in identical positions. In spite of the structural similarities, the specificity and mode of activation of sphingolipid hydrolases differs among individual saposins. Saposins appear to be lysosomal proteins, exerting their action upon lysosomal hydrolases. Prosaposin is a 70 kDa glycoprotein containing four domains, one for each saposin, placed in tandem. Prosaposin is proteolytically processed to saposins A, B, C and D, apparently within lysosomes. However, prosaposin also exists as an integral membrane protein not destined for lysosomal entry and exists uncleaved in many biological fluids such as seminal plasma, human milk, and cerebrospinal fluid, where it appears to have a different function. The physiological significance of saposins is underlined by their accumulation in tissues of lysosomal storage disease patients and the occurrence of sphingolipidosis due to mutations in the prosaposin gene. This review presents an overview of the occurrence, structure and function of these saposin proteins.
Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. (1988)

In contrast to mouse epidermal cells, human skin keratinocytes are rather resistant to transformation in vitro. Immortalization has been achieved by SV40 but has resulted in cell lines with altered differentiation. We have established a spontaneously transformed human epithelial cell line from adult skin, which maintains full epidermal differentiation capacity. This HaCaT cell line is obviously immortal (greater than 140 passages), has a transformed phenotype in vitro (clonogenic on plastic and in agar) but remains nontumorigenic. Despite the altered and unlimited growth potential, HaCaT cells, similar to normal keratinocytes, reform an orderly structured and differentiated epidermal tissue when transplanted onto nude mice. Differentiation-specific keratins (Nos. 1 and 10) and other markers (involucrin and filaggrin) are expressed and regularly located. Thus, HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. On karyotyping this line is aneuploid (initially hypodiploid) with unique stable marker chromosomes indicating monoclonal origin. The identity of the HaCaT line with the tissue of origin was proven by DNA fingerprinting using hypervariable minisatellite probes. This is the first demonstration that the DNA fingerprint pattern is unaffected by long-term cultivation, transformation, and multiple chromosomal alterations, thereby offering a unique possibility for unequivocal identification of human cell lines. The characteristics of the HaCaT cell line clearly document that spontaneous transformation of human adult keratinocytes can occur in vitro and is associated with sequential chromosomal alterations, though not obligatorily linked to major defects in differentiation.
Phylogenomic analysis of the cystatin superfamily in eukaryotes and prokaryotes (2009)

This study challenges the current view on the classification, origin and evolution of the cystatin superfamily and provides valuable insights into their functional diversification. The findings of this comprehensive study provide guides for future structural and evolutionary studies of the cystatin superfamily as well as of other protease inhibitors and proteases.
Human CD38, a cell‐surface protein with multiple functions (1996)

Human CD38 is a nonlineage-restricted type II transmembrane glycoprotein that has emerged as a multifunctional protein in recent years. It can serve as an ectoenzyme that catalyzes the synthesis and hydrolysis of cyclic ADP-ribose, a recently identified Ca2+ mobilizing agent that acts independently of inositol triphosphate. The enzymatic functions of CD38 probably contribute to an array of its immunoregulatory functions. The release of soluble CD38 and the ability of membrane-bound CD38 to become internalized in response to appropriate stimuli suggest that extracellular and intracellular roles for this protein are equally plausible. Ligation of CD38 with agonistic antibodies induces diverse effects in hematopoietic cells that range from growth stimulation to induction and prevention from apoptosis, induction of cytokines, activation of kinases, and phosphorylation of certain proteins. These observations suggest that CD38 may serve as receptor for an as yet unidentified ligand. Other molecules that share significant structural and functional homology to CD38 have been identified in humans and mice, suggesting that these molecules may represent a new family of proteins. Understanding the role of CD38 in certain pathological conditions such as myeloma, X-linked agammaglobulinemia, and HIV infection may provide insight into its physiological functions.
On-Line Archives Let Biologists Interrogate the Genome (1995)

This article describes the management of a fast growing, enormous volume of gene sequencing data both for humans and other species. As a result, major biomentical archives have found themselves on the cutting edge of database management. The history of GenBank and the Genomen Sequence Data Base (GSDB), a former nucleotide database, is described and how it works now is detailed. Other databases discussed are the European Molecular Biology Laboratory and the DNA Data Bank of Japan. The use of specifically designed software and the developing future of database use in this area is also covered.
IL-2, IL-4, and IFN-gamma gene expression versus secretion in superantigen-activated T cells. Distinct requirement for costimulatory signals through adhesion molecules. (1994)

In the complete absence of APCs staphylococcal superantigens induced IL-2, IL-4, IL-5, IFN-gamma, and IL-2R gene transcripts in both highly purified human T cells and FACs sorted CD4+ memory (CD45RA-) T cells. Secretion of IL-2, IL-4, and IFN-gamma, as well as DNA synthesis, on the other hand, required the presence of monocytes. At cytokine gene transcript level, three patterns of expression were noted after superantigen activation of T cells in the presence vs the absence of APC. mRNA levels for IL-2 were markedly up-regulated in the presence of monocytes, IL-4 and IFN-gamma transcripts increased only modestly, and IL-5 and IL-2R mRNA levels were unaffected. Blocking mAbs against LFA-1 and LFA-3 added to staphylococcal enterotoxin B (SEB)-activated cultures of T cells and autologous monocytes, reproducibly decreased both T cell proliferation and genetic expression of IL-2, IL-4, IL-5, and IL-2R, although having little or no effect on IFN-gamma transcripts. Further, under those conditions of blocking, secretion of IL-2 and IL-4 was dramatically decreased, whereas IFN-gamma secretion remained essentially unchanged. In contrast, LFA-1 and LFA-3 mAbs completely abrogated IFN-gamma secretion from PHA-activated T cell-monocyte mixtures, although having no inhibitory effect on T cell proliferation. These results indicate a characteristic and differential involvement of adhesion molecule-mediated signals in superantigen-induced T cell proliferation, differential cytokine gene expression, and cytokine secretion.
First pass metabolism of ethanol is strikingly influenced by the speed of gastric emptying (1998)

FPM of ethanol is strikingly modulated by the speed of GE. Delayed GE increases the time of exposure of ethanol to gastric ADH and may therefore increase gastric FPM of ethanol. In addition, hepatic FPM of ethanol may also be enhanced as the result of slower absorption of ethanol from the small intestine. Thus a knowledge of GE time is a major prerequisite for studying FPM of ethanol in humans.
Dorsal column stimulation: optimization of application. (1975)

Although the basic efficacy of dorsal column stimulation (DCS) has been shown, its optimal use remains to be defined. Since 1970, a program designed to maximize clinical success with DCS has been under way at Temple University Health Sciences Center. This article reviews patients screening, operative technique, new instrumentation and postoperative adjustment in DCS. Clinical results and long-term impressions of 90 implants in 75 patients are reported.
Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism. (1987)

The pineal gland constitutes a major neuroendocrine organ in the brain. It transduces exogenous signals such as circadian and seasonal variations of light and temperature into proper hormonal changes which adjust and adapt internal endocrine functions. These pineal activities seem to be exerted via circadian synthesis and release of the indoleamine melatonin, a neurohormone secreted by the pineal itself. Alteration of circadian rhythms have been associated with affective disorders, psychosomatic diseases, cancer and many other pathologies. We have reported that functional and pharmacologic inhibition of melatonin synthesis results in depressed immune functions in vivo and that exogenous, evening administration of melatonin enhances antibody formation via an antigen-activated process and also antagonizes the immunosuppressive effects of corticosterone. We communicate here findings demonstrating that (a) three different inbred strains of mice possess a clear-cut cycle of melatonin levels in serum, (b) that melatonin administered in the evening enhances primary antibody response (IgM and IgG immunoglobulins) in vivo according to a dose-response behaviour and that (c) the opioid receptors blocker naltrexone antagonizes the immunostimulatory effect of melatonin. These findings point to a fundamental immunoregulatory role of circadian melatonin and to an activity of the neurohormone via opioid peptides.
Ablation of Systemic Phosphate‐Regulating Gene Fibroblast Growth Factor 23 (Fgf23) Compromises the Dentoalveolar Complex (2010)

Fibroblast growth factor-23 (FGF23) is a hormone that modulates circulating phosphate (P(i)) levels by controlling P(i) reabsorption from the kidneys. When FGF23 levels are deficient, as in tumoral calcinosis patients, hyperphosphatemia ensues. We show here in a murine model that Fgf23 ablation disrupted morphology and protein expression within the dentoalveolar complex. Ectopic matrix formation in pulp chambers, odontoblast layer disruption, narrowing of periodontal ligament space, and alteration of cementum structure were observed in histological and electron microscopy sections. Because serum P(i) levels are dramatically elevated in Fgf23(-/-), we assayed for apoptosis and expression of members from the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, both of which are sensitive to elevated P(i) in vitro. Unlike X-linked hypophosphatemic (Hyp) and wild-type (WT) specimens, numerous apoptotic osteocytes and osteoblasts were detected in Fgf23(-/-) specimens. Further, in comparison to Hyp and WT samples, decreased bone sialoprotein and elevated dentin matrix protein-1 protein levels were observed in cementum of Fgf23(-/-) mice. Additional dentin-associated proteins, such as dentin sialoprotein and dentin phosphoprotein, exhibited altered localization in both Fgf23(-/-) and Hyp samples. Based on these results, we propose that FGF23 and (P(i)) homeostasis play a significant role in maintenance of the dentoalveolar complex.
Alterations in pancreatic, biliary, and breast carcinomas support MKK4 as a genetically targeted tumor suppressor gene. (1998)

Mitogen-activated protein kinase (MAPK) kinase 4 (MKK4) is a component of a stress and cytokine-induced signal transduction pathway involving MAPK proteins. The MKK4 protein has been implicated in activation of JNK1 and p38 MAPK on phosphorylation by conserved kinase pathways. A recent report on the deletion and mutation of the MKK4 gene in human pancreatic, lung, breast, testicle, and colorectal cancer cell lines suggests an additional role for MKK4 in tumor suppression. Both the gene function and the infrequency of mutations might be considered atypical for many human tumor suppressor genes, and constitutional DNA was not previously available to determine whether the reported sequence variants had preceded tumor development. Here, we report that homozygous deletions are detected in 2 of 92 pancreatic adenocarcinomas (2%), 1 of 16 biliary adenocarcinomas (6%), and 1 of 22 breast carcinomas (when combined with reported sequence alterations, 3 of 22 or 14%). In addition, in a panel of 45 pancreatic carcinomas prescreened for loss of heterozygosity, one somatic missense mutation of MKK4 is observed and confirmed in the primary tumor (2%). Mapping of the homozygous deletions further indicated MKK4 to lie at the target of deletion. The finding of a somatic missense mutation in the absence of any other nucleotide polymorphisms or silent nucleotide changes continues to favor MKK4 as a mutationally targeted tumor suppressor gene. Coexistent mutations of other tumor suppressor genes in MKK4-deficient tumors suggest that MKK4 may participate in a tumor suppressive signaling pathway distinct from DPC4, p16, p53, and BRCA2.