gebhart/patrepeval huggingface dataset:
Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases (2007)

The two primary human inflammatory bowel diseases, Crohn's disease (CD) and ulcerative colitis (UC), are idiopathic relapsing disorders characterized by chronic inflammation of the intestinal tract. Although several lines of reasoning suggest that gastrointestinal (GI) microbes influence inflammatory bowel disease (IBD) pathogenesis, the types of microbes involved have not been adequately described. Here we report the results of a culture-independent rRNA sequence analysis of GI tissue samples obtained from CD and UC patients, as well as non-IBD controls. Specimens were obtained through surgery from a variety of intestinal sites and included both pathologically normal and abnormal states. Our results provide comprehensive molecular-based analysis of the microbiota of the human small intestine. Comparison of clone libraries reveals statistically significant differences between the microbiotas of CD and UC patients and those of non-IBD controls. Significantly, our results indicate that a subset of CD and UC samples contained abnormal GI microbiotas, characterized by depletion of commensal bacteria, notably members of the phyla Firmicutes and Bacteroidetes. Patient stratification by GI microbiota provides further evidence that CD represents a spectrum of disease states and suggests that treatment of some forms of IBD may be facilitated by redress of the detected microbiological imbalances.
Oral Salmonella: malaria circumsporozoite recombinants induce specific CD8+ cytotoxic T cells. (1990)

Oral immunization with an attenuated Salmonella typhimurium recombinant containing the full-length Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I-restricted CD8+ cytotoxic T cells that are directed against the P. berghei CS peptide epitope spanning amino acids 242-253. This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. falciparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences. Both of these vaccines were able to induce CD8+ CTL directed against P. falciparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8+ CTL in immunity to malaria.
Serial cardiovascular variables in survivors and nonsurvivors of human septic shock (1987)

Forty-eight septic shock patients with positive blood cultures had conventional serial hemodynamic evaluations until recovery or death to identify early cardiovascular variables that predicted outcome. There were 19 (40%) survivors and 29 nonsurvivors. At the initial evaluation, both survivors and nonsurvivors demonstrated an elevated cardiac index (CI), low systemic vascular resistance index (SVRI), and normal stroke volume index. However, only an initial heart rate (HR) less than 106 beat/min significantly predicted survival. Twenty-four hours after the onset of shock, both an HR less than 95 beat/min and an SVRI greater than 1529 dyne.sec/cm5.m2 predicted survival. Comparing the hemodynamic profiles from the initial to the 24 h time point, a decrease in HR greater than 18 beat/min or a decrease in CI greater than 0.5 L/min.m2 predicted survival. Twenty-two deaths occurred in the first week of study, of which 18 (82%) were due primarily to low SVRI and four (18%) to low CI. Seven deaths occurred after 1 wk, all of which were due to multiple organ failure.
Therapeutic intervention in dementia. (1993)

The search for novel therapeutics for human cognitive disorders has intensified. Neurotransmitter replacement therapies represent a short-term hope for treating cognitive dysfunction associated with Alzheimer's disease (AD). AD, however, is clearly a neurodegenerative disease and is characterized by a loss of synaptic elements. Ultimately, synaptic loss must be halted to alter the disease course. Agents mimicking or modulating the actions of neurotrophic factors may be useful. They may restore lost function and exert anabolic effects on existing neurons, making treated cells less susceptible to neurotoxic insult (i.e., excitotoxicity, oxidative stress, etc.). Intervening in the biogenesis of amyloid plaques and blunting local inflammatory responses may provide the ultimate treatment for AD. The success of any treatment, however, rests on early diagnosis. Early intervention in the neurodegenerative disease process will be required. Without early intervention, the risk of maintaining patients in a premorbid state is high. Therefore, it is likely that no single approach will provide optimal therapy for the AD patient and multifactorial treatment strategies may be required.
The Association of Dietary l-Arginine Intake and Serum Nitric Oxide Metabolites in Adults: A Population-Based Study (2016)

This study was conducted to investigate whether regular dietary intake of l-arginine is associated with serum nitrate + nitrite (NOx). In this cross-sectional study, 2771 men and women, who had participated in the third examination of the Tehran Lipid and Glucose Study (2006-2008), were recruited. Demographics, anthropometrics and biochemical variables were evaluated. Dietary data were collected using a validated 168-food item semi-quantitative food frequency questionnaire and dietary intake of l-arginine was calculated. To determine any association between dietary l-arginine and serum NOx, linear regression models with adjustment for potential confounders were used. Mean age of participants (39.2% men) was 45.9 ± 15.9 years. After adjustment for all potential confounding variables, a significant positive association was observed between l-arginine intake and serum NOx concentrations in the fourth quartile of l-arginine (β = 6.63, 95% CI = 4.14, 9.12, p for trend = 0.001), an association stronger in women. Further analysis, stratified by age, body mass index and hypertension status categories, showed a greater association in middle-aged and older adults (β = 9.12, 95% CI = 3.99, 13.6 and β = 12.1, 95% CI = 6.48, 17.7, respectively). l-arginine intakes were also strongly associated with serum NOx levels in overweight and obese subjects in the upper quartile (β = 10.7, 95% CI = 5.43, 16.0 and β = 11.0, 95% CI = 4.29, 17.5); a greater association was also observed between l-arginine intakes and serum NOx in non-hypertensive (HTN) compared to HTN subjects (β = 2.65, 95% CI = 2.1-3.2 vs. β = 1.25, 95% CI = -1.64-4.15). Dietary l-arginine intakes were associated to serum NOx and this association may be affected by sex, age, body mass index, and hypertension status.
Learning a Similarity Metric Discriminatively, with Application to Face Verification (2005)

We present a method for training a similarity metric from data. The method can be used for recognition or verification applications where the number of categories is very large and not known during training, and where the number of training samples for a single category is very small. The idea is to learn a function that maps input patterns into a target space such that the L/sub 1/ norm in the target space approximates the "semantic" distance in the input space. The method is applied to a face verification task. The learning process minimizes a discriminative loss function that drives the similarity metric to be small for pairs of faces from the same person, and large for pairs from different persons. The mapping from raw to the target space is a convolutional network whose architecture is designed for robustness to geometric distortions. The system is tested on the Purdue/AR face database which has a very high degree of variability in the pose, lighting, expression, position, and artificial occlusions such as dark glasses and obscuring scarves.
Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction (2012)

These data are consistent with a causal association between elevated levels of remnant cholesterol in hypertriglyceridaemia and an increased risk of MI. Limitations include that remnants were not measured directly, and that APOA5 genetic variants may influence other lipoprotein parameters.
Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase (1995)

We have identified recessive overproliferation mutations by screening and examining clones of mutant cells in genetic mosaics of the fruitfly Drosophila melanogaster. This type of screen provides a powerful approach for identifying and studying potential tumor suppressors. One of the identified genes, lats, has been cloned and encodes a putative protein kinase that shares high levels of sequence similarity with three proteins in budding yeast and Neurospora that are involved in regulation of the cell cycle and growth. Mutations in lats cause dramatic overproliferation phenotypes and various developmental defects in both mosaic animals and homozygous mutants.
The vesicular stomatitis virus matrix protein inhibits transcription from the human beta interferon promoter (1997)

In cells infected by wild-type (wt) vesicular stomatitis virus (VSV) Indiana, host transcription is severely inhibited. DNA cotransfection studies have implicated the VSV matrix (M) protein in this process (B. L. Black and D. S. Lyles, J. Virol. 66:4058-4064, 1992). The M protein inhibited transcription not only from viral promoters in plasmids but also from the chromosomally integrated human immunodeficiency virus type 1 (HIV-1) provirus promoter (S.-Y. Paik, A. C. Banerjea, G. G. Harmison, C.-J. Chen, and M. Schubert, J. Virol. 69:3529-3537, 1995). In this study, we investigated the effect of wt VSV M protein on expression of a reporter gene under control of a cellular promoter (beta-interferon [IFN-beta] promoter), using double transient transfections in BHK and COS-1 cells. The cellular IFN-beta promoter was as susceptible to the inhibitory effect of the M protein as the viral promoters used previously. Viral proteins N, P, and G had no significant effect on reporter gene expression. The M protein gene from VSV mutant T1026R1, which is defective in host transcription inhibition, was cloned and sequenced, and its effect on reporter gene expression was tested. The mutant M protein had a methionine-to-arginine change at position 51 in the protein sequence and did not inhibit transcription from either the IFN-beta promoter or viral promoters. This VSV mutant is a good inducer of IFN, as opposed to the wt virus, which suppresses IFN induction. These results show that the M protein inhibits transcription from cellular as well as viral promoters and that the M protein does not regulate the IFN promoter any differently from viral promoters. While the M protein may play a role in IFN gene regulation, other viral or cellular factors that provide specificity to the induction process must also be involved.
Multiprotocol transport networking: a general internetworking solution (2002)

The multiprotocol transport networking (MPTN) architecture proposed in this paper is a general solution to providing interconnectivity for applications. The MPTN architecture provides a protocol-independent system interface that includes most functions provided by existing transport protocols. As a result, the MPTN architecture decouples higher-layer protocols, application programming interfaces, and applications from protocols at the transport layer and below. Using the MPTN architecture, current and new applications can function unmodified over any transport supported under the MPTN interface. In addition, MPTN transport-layer gateways provide an end-to-end communication facility across a number of networks running different protocols. Therefore, a collection of networks running different protocols can serve as a single logical network.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Inhibition of HIV infectivity by a natural human isolate of Lactobacillus jensenii engineered to express functional two-domain CD4 (2003)

The predominant mode of HIV transmission worldwide is via heterosexual contact, with the cervico-vaginal mucosa being the main portal of entry in women. The cervico-vaginal mucosa is naturally colonized with commensal bacteria, primarily lactobacilli. To address the urgent need for female-controlled approaches to block the heterosexual transmission of HIV, we have engineered natural human vaginal isolates of Lactobacillus jensenii to secrete two-domain CD4 (2D CD4) proteins. The secreted 2D CD4 recognized a conformation-dependent anti-CD4 antibody and bound HIV type 1 (HIV-1) gp120, suggesting that the expressed proteins adopted a native conformation. Single-cycle infection assays using HIV-1 HxB2 carrying a luciferase reporter gene demonstrated that Lactobacillus -derived 2D CD4 inhibited HIV-1 entry into target cells in a dose-dependent manner. Importantly, coincubation of the engineered bacteria with recombinant HIV-1 HxB2 reporter virus led to a significant decrease in virus infectivity of HeLa cells expressing CD4–CXCR4–CCR5. Engineered lactobacilli also caused a modest, but statistically significant, decrease in infectivity of a primary isolate, HIV-1 JR-FL . This represents an important first step toward the development of engineered commensal bacteria within the vaginal microflora to inhibit heterosexual transmission of HIV.
Algebraic Codes for Data Transmission (2003)

The need to transmit and store massive amounts of data reliably and without error is a vital part of modern communications systems. Error-correcting codes play a fundamental role in minimising data corruption caused by defects such as noise, interference, crosstalk and packet loss. This book provides an accessible introduction to the basic elements of algebraic codes, and discusses their use in a variety of applications. The author describes a range of important coding techniques, including Reed-Solomon codes, BCH codes, trellis codes, and turbocodes. Throughout the book, mathematical theory is illustrated by reference to many practical examples. The book was first published in 2003 and is aimed at graduate students of electrical and computer engineering, and at practising engineers whose work involves communications or signal processing.
Growth requirements of pyruvate-decarboxylase-negativeSaccharomyces cerevisiae (1999)

Pyruvate-decarboxylase (Pdc)-negative Saccharomyces cerevisiae has been reported to grow in batch cultures on glucose-containing complex media, but not on defined glucose-containing media. By a combination of batch and chemostat experiments it is demonstrated that even in complex media, Pdc- S. cerevisiae does not exhibit prolonged growth on glucose. Pdc- strains do grow in carbon-limited cultures on defined media containing glucose-acetate mixtures. The acetate requirement for glucose-limited growth, estimated experimentally by continuously decreasing the acetate feed to chemostat cultures, matched the theoretical acetyl-CoA requirement for lipid and lysine synthesis, consistent with the proposed role of pyruvate decarboxylase in the synthesis of cytosolic acetyl-CoA.
Protein-tyrosine-phosphatase-mediated epidermal growth factor (EGF) receptor transinactivation and EGF receptor-independent stimulation of mitogen-activated protein kinase by bradykinin in A431 cells (2000)

Transactivation of the epidermal growth factor (EGF) receptor (EGFR) has been proposed to represent an essential link between G-protein-coupled receptors and the mitogen-activated protein kinase (MAPK) pathway in various cell types. In the present work we report, in contrast, that in A431 cells bradykinin transinactivates the EGFR and stimulates MAPK activity independently of EGFR tyrosine phosphorylation. Both effects of bradykinin are mediated by a pertussis-toxin-insensitive G-protein. Three lines of evidence suggest the activation of a protein tyrosine phosphatase (PTP) by bradykinin: (i) treatment of A431 cells with bradykinin decreases both basal and EGF-induced EGFR tyrosine phosphorylation, (ii) this effect of bradykinin can be blocked by two different PTP inhibitors, and (iii) bradykinin significantly increased the PTP activity in total A431 cell lysates when measured in vitro. The transmembrane receptor PTP σ was identified as a putative mediator of bradykinin-induced downregulation of EGFR autophosphorylation. Activation of MAPK in response to bradykinin was insensitive towards AG 1478, a specific inhibitor of EGFR tyrosine kinase, but was blocked by wortmannin or bisindolylmaleimide, inhibitors of phosphatidylinositol 3-kinase (PI3-K) and protein kinase C (PKC) respectively. These results also suggest that the bradykinin-induced activation of MAPK is independent of EGFR and indicate a pathway involving PI3-K and PKC. In addition, bradykinin evokes a rapid and transient increase in Src kinase activity. Although Src does not participate in bradykinin-induced stimulation of PTP activity, inhibition of Src by 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine leads to an increase in MAPK activation by bradykinin. Our results suggest that in A431 cells the Gq/11-protein-coupled bradykinin B2 receptor may stimulate PTP activity and thereby transinactivate the EGFR, and may simultaneously activate MAPK by an alternative signalling pathway which can bypass EGFR.
[Effect of glycerol, mannitol, and lasix on cerebrospinal fluid pressure in the acute period of a stroke]. (1981)

On giving a dose of glycerol (orally), mannitol or lasix (intravenously) to patients with a cerebral stroke in the acute period the cerebrospinal fluid (CSF) pressure in them dropped, on the average, by 70-80%, 65-70%, and 25-30%, respectively. However in 6.5 to 7.5 hours it rose again and the after-effect phenomenon appeared. The effects of the drugs having been over, the CSF pressure was found to exceed the initial level by 50-60% after the glycerol intake; by 75 to 80% after the mannitol, an by 4 to 6% after the lasix injections. When glycerol, mannitol, and lasix were given rectally the CSF pressure dropped, respectively, by 35-45%, 35-40%, and 20-25% below the initial level, and did not rise throughout the whole period of the observation.
The Conquest file system (2006)

Modern file systems assume the use of disk, a system-wide performance bottleneck for over a decade. Current disk caching and RAM file systems either impose high overhead to access memory content or fail to provide mechanisms to achieve data persistence across reboots.The Conquest file system is based on the observation that memory is becoming inexpensive, which enables all file system services to be delivered from memory, except for providing large storage capacity. Unlike caching, Conquest uses memory with battery backup as persistent storage, and provides specialized and separate data paths to memory and disk. Therefore, the memory data path contains no disk-related complexity. The disk data path consists of optimizations only for the specialized disk usage pattern.Compared to a memory-based file system, Conquest incurs little performance overhead. Compared to several disk-based file systems, Conquest achieves 1.3x to 19x faster memory performance, and 1.4x to 2.0x faster performance when exercising both memory and disk. Conquest realizes most of the benefits of persistent RAM at a fraction of the cost of a RAM-only solution. It also demonstrates that disk-related optimizations impose high overheads for accessing memory content in a memory-rich environment.
Activated T cells in an animal model of allergic conjunctivitis. (1993)

The aim of this study has been to determine whether the presence of lymphocytic infiltrates observed in the histology of ocular allergic conditions in humans or in the late phase of ocular anaphylactic reactions in experimental animals is a non-specific event dependent only on the degranulation of mast cells, or is conditioned by a specific response to antigen. With this in mind, responses to antigen and to a non-immunological mast cell degranulator (compound 48/80) were compared in an experimental model of allergic conjunctivitis. Rats were sensitised to ovalbumin and challenged topically in the left conjunctival sac either with ovalbumin or compound 48/80. The presence of T cells and activated T cells in the infiltrate was studied by immunohistochemical staining on conjunctival tissue obtained at 4, 24, and 48 hours after challenge. Ovalbumin sensitised and challenged rats showed increased numbers of T cells in the conjunctival infiltrate, statistically significant when compared with compound 48/80 challenged rats at 48 hours and with controls at 4, 24, and 48 hours. The number of T cells was significantly higher in compound 48/80 challenged rats only at 48 hours when compared with controls. As for the number of activated T cells, only ovalbumin sensitised and challenged rats showed significantly increased levels of these cells compared with both sensitised animals challenged with compound 48/80 and controls at 4 and 24 hours after challenge. These results suggest that the infiltration of the conjunctiva by activated T lymphocytes is, at least in part, dependent on a specific response to antigen.
Biogenesis pathways of RNA guides in archaeal and bacterial CRISPR-Cas adaptive immunity (2015)

CRISPR-Cas is an RNA-mediated adaptive immune system that defends bacteria and archaea against mobile genetic elements. Short mature CRISPR RNAs (crRNAs) are key elements in the interference step of the immune pathway. A CRISPR array composed of a series of repeats interspaced by spacer sequences acquired from invading mobile genomes is transcribed as a precursor crRNA (pre-crRNA) molecule. This pre-crRNA undergoes one or two maturation steps to generate the mature crRNAs that guide CRISPR-associated (Cas) protein(s) to cognate invading genomes for their destruction. Different types of CRISPR-Cas systems have evolved distinct crRNA biogenesis pathways that implicate highly sophisticated processing mechanisms. In Types I and III CRISPR-Cas systems, a specific endoribonuclease of the Cas6 family, either standalone or in a complex with other Cas proteins, cleaves the pre-crRNA within the repeat regions. In Type II systems, the trans-acting small RNA (tracrRNA) base pairs with each repeat of the pre-crRNA to form a dual-RNA that is cleaved by the housekeeping RNase III in the presence of the protein Cas9. In this review, we present a detailed comparative analysis of pre-crRNA recognition and cleavage mechanisms involved in the biogenesis of guide crRNAs in the three CRISPR-Cas types.