gebhart/patrepeval huggingface dataset:
Oral proteases: a new approach to managing coeliac disease (2006)

A life-long but constraining gluten-free diet is the only treatment currently available for coeliac disease. The human gastrointestinal tract does not possess the enzymatic equipment to efficiently cleave the gluten-derived proline-rich peptides driving the abnormal immune intestinal response in patients with coeliac disease. Oral therapy by exogenous prolylendopeptidases able to digest ingested gluten was therefore propounded as an alternative treatment to the diet. The feasibility of this approach is discussed by reviewing recent data on the intestinal transport of gliadin peptides, properties of available enzymes and preliminary clinical assays. Development of new enzymes or enzymatic cocktails offers potentially more potent therapeutic tools that, however, need meticulous evaluation based on clinical, biological and histological criteria.
CROSS-REACTIONS OF GLUCOSE-CONTAINING POLYSACCHARIDES IN ANTIPNEUMOCOCCAL SERA. VII. THE PRECIPITATION OF TYPE IX ANTISERA BY ISOLICHENIN, AND OTHER REACTIONS. (1963)

Isolichenin, which consists of α-1, 3- and α-1, 4-linked glucose, partly, at least, in pairs, precipitates type IX anti-pneumococcal sera very strongly at 0°. Quantitative data are given on this reaction and the precipitation of other antipneumococcal sera by isolichenin, other polyglucoses, and natural polysaccharides containing glucose. The data are discussed in terms of a quantitative theory of the precipitin reaction (5) and, where possible, in terms of the linkages of glucose involved.
Nucleotide sequence preservation of human mitochondrial DNA. (1985)

Recombinant DNA techniques have been used to quantitate the amount of nucleotide sequence divergence in the mitochondrial DNA population of individual normal humans. Mitochondrial DNA was isolated from the peripheral blood lymphocytes of five normal humans and cloned in M13 mp11; 49 kilobases of nucleotide sequence information was obtained from 248 independently isolated clones from the five normal donors. Both between- and within-individual differences were identified. Between-individual differences were identified in approximately 1/200 nucleotides. In contrast, only one within-individual difference was identified in 49 kilobases of nucleotide sequence information. This high degree of mitochondrial nucleotide sequence homogeneity in human somatic cells is in marked contrast to the rapid evolutionary divergence of human mitochondrial DNA and suggests the existence of mechanisms for the concerted preservation of mammalian mitochondrial DNA sequences in single organisms.
Effects of System Pressure and Nozzle Type on Spray Application of Avian Vaccines (2008)

Optimization of vaccine delivery via spray application of live Mycoplasma gallisepticum (MG) vaccine to commercial caged layer chickens is impacted by many factors. One of these factors is the pressure utilized to dispense the vaccine, which affects both application rate and droplet size. MG vaccine was applied using a self-propelled, constant speed vaccinator operated at two different pressures and using three different nozzles. Droplet size and as-applied coverage and deposition were measured to determine the effects of system pressure and nozzle type on spray characteristics. Vaccine viability was also assessed to determine how viability is affected by the spray application process.
Diversity of Endonuclease V: From DNA Repair to RNA Editing (2015)

Deamination of adenine occurs in DNA, RNA, and their precursors via a hydrolytic reaction and a nitrosative reaction. The generated deaminated products are potentially mutagenic because of their structural similarity to natural bases, which in turn leads to erroneous nucleotide pairing and subsequent disruption of cellular metabolism. Incorporation of deaminated precursors into the nucleic acid strand occurs during nucleotide synthesis by DNA and RNA polymerases or base modification by DNA- and/or RNA-editing enzymes during cellular functions. In such cases, removal of deaminated products from DNA and RNA by a nuclease might be required depending on the cellular function. One such enzyme, endonuclease V, recognizes deoxyinosine and cleaves 3' end of the damaged base in double-stranded DNA through an alternative excision repair mechanism in Escherichia coli, whereas in Homo sapiens, it recognizes and cleaves inosine in single-stranded RNA. However, to explore the role of endonuclease V in vivo, a detailed analysis of cell biology is required. Based on recent reports and developments on endonuclease V, we discuss the potential functions of endonuclease V in DNA repair and RNA metabolism.
The Major Histocompatibility Complex Class II AllelesMamu-DRB1*1003and -DRB1*0306Are Enriched in a Cohort of Simian Immunodeficiency Virus-Infected Rhesus Macaque Elite Controllers (2007)

The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.
Instability of Helios-deficient Tregs is associated with conversion to a T-effector phenotype and enhanced antitumor immunity (2016)

Expression of the transcription factor Helios by Tregs ensures stable expression of a suppressive and anergic phenotype in the face of intense inflammatory responses, whereas Helios-deficient Tregs display diminished lineage stability, reduced FoxP3 expression, and production of proinflammatory cytokines. Here we report that selective Helios deficiency within CD4 Tregs leads to enhanced antitumor immunity through induction of an unstable phenotype and conversion of intratumoral Tregs into T effector cells within the tumor microenvironment. Induction of an unstable Treg phenotype is associated with enhanced production of proinflammatory cytokines by tumor-infiltrating but not systemic Tregs and significantly delayed tumor growth. Ab-dependent engagement of Treg surface receptors that result in Helios down-regulation also promotes conversion of intratumoral but not systemic Tregs into T effector cells and leads to enhanced antitumor immunity. These findings suggest that selective instability and conversion of intratumoral CD4 Tregs through genetic or Ab-based targeting of Helios may represent an effective approach to immunotherapy.
Comparison of a physical model and principal component analysis for the diagnosis of epithelial neoplasias in vivo using diffuse reflectance spectroscopy (2007)

We explored the use of diffuse reflectance spectroscopy in the ultraviolet-visible (UV-VIS) spectrum for the diagnosis of epithelial precancers and cancers in vivo. A physical model (Monte Carlo inverse model) and an empirical model (principal component analysis, (PCA)) based approach were compared for extracting diagnostic features from diffuse reflectance spectra measured in vivo from the dimethylbenz[alpha]anthracene-treated hamster cheek pouch model of oral carcinogenesis. These diagnostic features were input into a support vector machine algorithm to classify each tissue sample as normal (n=10) or neoplastic (dysplasia to carcinoma, n=10) and cross-validated using a leave one out method. There was a statistically significant decrease in the absorption and reduced scattering coefficient at 460 nm in neoplastic compared to normal tissues, and these two features provided 90% classification accuracy. The first two principal components extracted from PCA provided a classification accuracy of 95%. The first principal component was highly correlated with the wavelength-averaged reduced scattering coefficient. Although both methods show similar classification accuracy, the physical model provides insight into the physiological and structural features that discriminate between normal and neoplastic tissues and does not require a priori, a representative set of spectral data from which to derive the principal components.
Incremental Decoding for Phrase-Based Statistical Machine Translation (2010)

In this paper we focus on the incremental decoding for a statistical phrase-based ma-chine translation system. In incremental decoding, translations are generated incre-mentally for every word typed by a user, instead of waiting for the entire sentence as input. We introduce a novel modifi-cation to the beam-search decoding algo-rithm for phrase-based MT to address this issue, aimed at efficient computation of fu-ture costs and avoiding search errors. Our objective is to do a faster translation dur-ing incremental decoding without signifi-cant reduction in the translation quality. 1
Improved Medium for Lactic Streptococci and Their Bacteriophages (1975)

Incorporation of 1.9% beta-disodium glycerophosphate (GP) into a complex medium resulted in improved growth by lactic streptococci at 30 C. The medium, called M17, contained: Phytone peptone, 5.0 g; polypeptone, 5.0 g; yeast extract, 2.5 g; beef extract, 5.0 g; lactose, 5.0 g; ascorbic acid, 0.5 g; GP, 19.0 g; 1.0 M MgSO(4).7H(2)O, 1.0 ml; and glass-distilled water, 1,000 ml. Based on absorbance readings and total counts, all strains of Streptococcus cremoris, S. diacetilactis, and S. lactis grew better in M17 medium than in a similar medium lacking GP or in lactic broth. Enhanced growth was probably due to the increased buffering capacity of the medium, since pH values below 5.70 were not reached after 24 h of growth at 30 C by S. lactis or S. cremoris strains. The medium also proved useful for isolation of bacterial mutants lacking the ability to ferment lactose; such mutants formed minute colonies on M17 agar plates, whereas wild-type cells formed colonies 3 to 4 mm in diameter. Incorporation of sterile GP into skim milk at 1.9% final concentration resulted in enhanced acid-producing activity by lactic streptococci when cells were inoculated from GP milk into skim milk not containing GP. M17 medium also proved superior to other media in demonstrating and distinguishing between lactic streptococcal bacteriophages. Plaques larger than 6 mm in diameter developed with some phage-host combinations, and turbid plaques, indicative of lysogeny, were also easily demonstrated for some systems.
Soft tissue coverage for lower-extremity trauma: current practice and techniques. A review. (1988)

The development and refinement of the free flap have revolutionized lower limb salvage. Excellent fixation of lower extremity fractures is often marred by the lack of adequate soft tissue coverage. In this article, we discuss the indications for and techniques of soft tissue coverage procedures for the exposed lower extremity fracture.
DNA Topoisomerase I Is a Cofactor for c-Jun in the Regulation of Epidermal Growth Factor Receptor Expression and Cancer Cell Proliferation (2005)

DNA topoisomerase I (Topo I) is a molecular target for the anticancer agent topotecan in the treatment of small cell lung cancer and ovarian carcinomas. However, the molecular mechanisms by which topotecan treatment inhibits cancer cell proliferation are unclear. We describe here the identification of Topo I as a novel endogenous interaction partner for transcription factor c-Jun. Reciprocal coimmunoprecipitation analysis showed that Topo I and c-Jun interact in transformed human cells in a manner that is dependent on JNK activity. c-Jun target gene epidermal growth factor receptor (EGFR) was identified as a novel gene whose expression was specifically inhibited by topotecan. Moreover, Topo I overexpression supported c-Jun-mediated reporter gene activation and both genetic and chemical inhibition of c-Jun converted cells resistant to topotecan-elicited EGFR downregulation. Topotecan-elicited suppression of proliferation was rescued by exogenously expressed EGFR. Furthermore, we demonstrate the cooperation of the JNK-c-Jun pathway, Topo I, and EGFR in the positive regulation of HT-1080 cell proliferation. Together, these results have identified transcriptional coactivator Topo I as a first endogenous cofactor for c-Jun in the regulation of cell proliferation. In addition, the results of the present study strongly suggest that inhibition of EGFR expression is a novel mechanism by which topotecan inhibits cell proliferation in cancer therapy.
Exploring the Limits of Transfer Learning with a Unified Text-to-Text Transformer (2019)

Transfer learning, where a model is first pre-trained on a data-rich task before being fine-tuned on a downstream task, has emerged as a powerful technique in natural language processing (NLP). The effectiveness of transfer learning has given rise to a diversity of approaches, methodology, and practice. In this paper, we explore the landscape of transfer learning techniques for NLP by introducing a unified framework that converts all text-based language problems into a text-to-text format. Our systematic study compares pre-training objectives, architectures, unlabeled data sets, transfer approaches, and other factors on dozens of language understanding tasks. By combining the insights from our exploration with scale and our new ``Colossal Clean Crawled Corpus'', we achieve state-of-the-art results on many benchmarks covering summarization, question answering, text classification, and more. To facilitate future work on transfer learning for NLP, we release our data set, pre-trained models, and code.
New algorithms for processing and peak detection in liquid chromatography/mass spectrometry data (2002)

Two new algorithms for automated processing of liquid chromatography/mass spectrometry (LC/MS) data are presented. These algorithms were developed from an analysis of the noise and artifact distribution in such data. The noise distribution was analyzed by preparing histograms of the signal intensity in LC/MS data. These histograms are well fit by a sum of two normal distributions in the log scale. One new algorithm, median filtering, provides increased performance compared to averaging adjacent scans in removing noise that is not normally distributed in the linear scale. Another new algorithm, vectorized peak detection, provides increased robustness with respect to variation in the noise and artifact distribution compared to methods based on determining an intensity threshold for the entire dataset. Vectorized peak detection also permits the incorporation of existing algorithms for peak detection in ion chromatograms and/or mass spectra. The application of these methods to LC/MS spectra of complex biological samples is described.
Cd20 (pan‐B cell) antigen is expressed at a low level on a subpopulation of human T lymphocytes (1993)

Despite the previous description of the leukocyte differentiation antigen CD20 as B cell restricted, the findings reported here indicate that a small subset of human T cells expresses low levels of CD20 or a cross-reacting antigen. Three different CD20 monoclonal antibodies (mAb), Leu16, B1, and 1F5, reacted with the T cell subset. B cells that expressed CD20 were CD20bright and constituted an average of 9.2 +/- 3.3% of adult PBL. Meanwhile, T cells that expressed CD20 were CD20dim and represented 2.4 +/- 1.5% of the PBL. This population may have been overlooked in previous studies due to the low level of CD20 expression per T cell and the small size of the subset in most individuals. Blocking studies indicated that CD20 mAb binding to CD3+ cells was due to the antigen-reactive regions of the CD20 antibodies and was not a result of Fc receptor binding, or non-specific fluorochrome or protein binding. The T cell nature of the CD20dim CD3+ cells was confirmed by the rapid rise in the intracellular calcium concentration ([Ca2+]i) of CD20dim cells observed following treatment with CD3 mAb but not following treatment with anti-human immunoglobulin (Ig). Extensive three-color immunophenotypic analyses indicated that CD20dim T cells were phenotypically heterogeneous and displayed a leukocyte differentiation profile that was slightly different than that of CD20- T cells. Thus, the CD20dim T cells were more likely than CD20- T cells to be gamma/delta T cell antigen receptor positive (14% vs. 3.4%), CD8+ (57% vs. 33%), and CD45RO+ (82% vs. 51%); fewer were CD38+ (5% vs. 24%) or CD4+ (35% vs. 61%).(ABSTRACT TRUNCATED AT 250 WORDS)
SMRT isoforms mediate repression and anti-repression of nuclear receptor heterodimers. (1996)

Transcriptional repression represents an important component in the regulation of cell differentiation and oncogenesis mediated by nuclear hormone receptors. Hormones act to relieve repression, thus allowing receptors to function as transcriptional activators. The transcriptional corepressor SMRT was identified as a silencing mediator for retinoid and thyroid hormone receptors. SMRT is highly related to another corepressor, N-CoR, suggesting the existence of a new family of receptor-interacting proteins. We demonstrate that SMRT is a ubiquitous nuclear protein that interacts with unliganded receptor heterodimers in mammalian cells. Furthermore, expression of the receptor-interacting domain of SMRT acts as an antirepressor, suggesting the potential importance of splicing variants as modulators of thyroid hormone and retinoic acid signaling.
A Survey of Neural Computation on Graphics Processing Hardware (2007)

Modern graphics processing units (GPU) are used for much more than simply 3D graphics applications. From machine vision to finite element analysis, CPU's are being used in diverse applications, collectively called general purpose graphics processor utilization. This paper explores the capabilities and limitations of modern GPU's and surveys the neural computation technologies that have been applied to these devices.
Human monoclonal anti-keyhole limpet hemocyanin antibody-secreting hybridoma produced from peripheral blood B lymphocytes of a keyhole limpet hemocyanin-immune individual. (1982)

A human IgMk monoclonal antibody, 2F7, of predetermined specificity, has been produced by the fusion of human peripheral blood lymphocytes with the nonsecreting mouse myeloma line SP-1. The heterohybridoma has remained stable for over 8 mo, with culture supernatants containing up to 30 micrograms/ml of specific IgM. The antibody has been shown to be capable of inducing a blastogenic response in the absence of antigen in the peripheral blood lymphocytes of normal subjects immune to the antigen. The ability to choose an antigen, immunize a human subject to that antigen, and then use the peripheral blood lymphocytes from that subject to produce antigen-specific human monoclonal antibodies should be of great value in a wide variety of investigative, diagnostic, and therapeutic endeavors.U
A 1000-MIPS/W microprocessor using speed adaptive threshold-voltage CMOS with forward bias (2002)

Substrate bias is continuously controlled from -1.5 V (backward bias) to 0.5 V (forward bias) to compensate for fabrication fluctuation, supply voltage variation, and operating temperature variation. A speed-adaptive threshold-voltage (SA-Vt) CMOS with forward bias is used in a 4.3M transistor microprocessor. The SA-Vt CMOS with forward bias occupies 320/spl times/400 /spl mu/m/sup 2/ and consumes 4 mA. The processor provides 400 VAX MIPS at 1.5 to 1.8 V with 320 to 380mW dissipation. It achieves >1000-MIPS/W performance.
BET bromodomain inhibition suppresses TH17-mediated pathology (2013)

Interleukin (IL) 17-producing T helper (T(H)17) cells have been selected through evolution for their ability to control fungal and bacterial infections. It is also firmly established that their aberrant generation and activation results in autoimmune conditions. Using a characterized potent and selective small molecule inhibitor, we show that the bromodomain and extra-terminal domain (BET) family of chromatin adaptors plays fundamental and selective roles in human and murine T(H)17 differentiation from naive CD4(+) T cells, as well as in the activation of previously differentiated T(H)17 cells. We provide evidence that BET controls T(H)17 differentiation in a bromodomain-dependent manner through a mechanism that includes the direct regulation of multiple effector T(H)17-associated cytokines, including IL17, IL21, and GMCSF. We also demonstrate that BET family members Brd2 and Brd4 associate with the Il17 locus in T(H)17 cells, and that this association requires bromodomains. We recapitulate the critical role of BET bromodomains in T(H)17 differentiation in vivo and show that therapeutic dosing of the BET inhibitor is efficacious in mouse models of autoimmunity. Our results identify the BET family of proteins as a fundamental link between chromatin signaling and T(H)17 biology, and support the notion of BET inhibition as a point of therapeutic intervention in autoimmune conditions.
Inflammatory Cytokines in Diabetic Nephropathy (2015)

Probably, the most paradigmatic example of diabetic complication is diabetic nephropathy, which is the largest single cause of end-stage renal disease and a medical catastrophe of worldwide dimensions. Metabolic and hemodynamic alterations have been considered as the classical factors involved in the development of renal injury in patients with diabetes mellitus. However, the exact pathogenic mechanisms and the molecular events of diabetic nephropathy remain incompletely understood. Nowadays, there are convincing data that relate the diabetes inflammatory component with the development of renal disease. This review is focused on the inflammatory processes that develop diabetic nephropathy and on the new therapeutic approaches with anti-inflammatory effects for the treatment of chronic kidney disease in the setting of diabetic nephropathy.