gebhart/patrepeval huggingface dataset:
Annexin 1 and the biology of the neutrophil (2004)

This overview will focus on one aspect of neutrophil biology, which is the selective activation of the annexin 1 system in relation to the process of cell extravasation. Besides the current view about the biochemistry of annexin 1 and annexin 1 receptor(s) up-regulation within the microenvironment of the adherent neutrophils, we will also comment on the final result achieved by activation of the system, which is inhibition of neutrophil recruitment. In view of the historical link between annexin 1 and glucocorticoids, the potential for the annexin 1 system in mediating at least some of the anti-inflammatory actions of these powerful drugs is also discussed.
Trichosarcina polymorpha Gen. et Sp. Nov. (1965)

SUMMARY Trichosarcina polymorpha gen. et sp. nov. is newly described as a member of the Ulvales, Schizo‐meridaceae. The life cycle includes a uniseriate, Hormidiuzn‐like phase; a pluriseriate stage, and, finally, a chain of sarcinoidpackets which may dissociate. The cells are uninucleate, with a parietal cbloroplast and single pyrenoid. Quadriflagellate zoospores are produced singly by cells of the pluriseriate and sarcinoid stages. Sexual reproduction was not observed.
The Design and Implementation of a Smart e-Receptionist (2013)

A smart e-Receptionist is a computer application that is capable of sensing approaching visitors, orally greeting them, picking up their voice and understanding their questions, and then talking back to them appropriately. It may also have a limited self-learning capability of accumulating “knowledge” through its interactions with visitors. In this article, we present the recently developed smart e-Receptionist that integrates video-based motion detection (for sensing a nearby visitor), natural speech recognition (for understanding a visitor's language), a question-answer (Q-A) knowledge database (for storing and managing information), and text-to-speech (TTS) (for a machine talking back to visitors). This e-Receptionist system can be easily converted into various information kiosks with slight modifications and configurations.
Applications and statistics for multiple high-scoring segments in molecular sequences. (1993)

Score-based measures of molecular-sequence features provide versatile aids for the study of proteins and DNA. They are used by many sequence data base search programs, as well as for identifying distinctive properties of single sequences. For any such measure, it is important to know what can be expected to occur purely by chance. The statistical distribution of high-scoring segments has been described elsewhere. However, molecular sequences will frequently yield several high-scoring segments for which some combined assessment is in order. This paper describes the statistical distribution for the sum of the scores of multiple high-scoring segments and illustrates its application to the identification of possible transmembrane segments and the evaluation of sequence similarity.
Novel markers for heart failure diagnosis and prognosis (2005)

Purpose of review This paper reviews recent advances in heart failure biomarkers for identification of disease precursors, subclinical disease, and onset or progression of overt disease. Recent findings Heart failure biomarkers can be categorized empirically as neurohormonal mediators, markers of myocyte injury and remodeling, and indicators of systemic inflammation. Brain natriuretic peptide is the most widely studied, with a potentially important but evolving role for determining prognosis and as a surrogate endpoint in clinical trials. Strong evidence exists for use of brain natriuretic peptide in the diagnosis of acute heart failure and for improved clinical outcomes with a brain natriuretic peptide-guided approach to heart failure care. The use of brain natriuretic peptide as a screening tool for asymptomatic left ventricular systolic dysfunction, or to distinguish systolic from diastolic heart failure, is not supported by current data. Markers of myocyte injury, including troponins, heart-type fatty acid binding protein, and myosin light chain-1, may further improve heart failure prognostication in conjunction with plasma brain natriuretic peptide. Biomarkers of matrix remodeling and inflammation have emerged as potential preclinical indicators to identify individuals at risk of developing clinical heart failure. A role for cellular adhesion molecules may also emerge in identifying those at risk for cardiovascular thrombotic complications, such as stroke. Summary The spectrum of heart failure biomarkers and their potential clinical applications continues to grow. Ongoing research on multimarker strategies will likely identify biomarker combinations that are optimal at various stages during the evolution of heart failure, ranging from their use for screening, diagnosis, determining prognosis, and guiding management.
Fast methods for the CELP speech coding algorithm (1990)

Special fast procedures for the code excited linear predictive coding (CELP) algorithm have been developed to make implementation on modest hardware possible. The advantages, as well as the disadvantages, of the various fast procedures are discussed. A general formalism for the algorithm is developed, followed by the discussion of the individual procedures which are grouped according to their features. Along with the computational complexity of each procedure, its storage requirement and numerical accuracy are discussed. A large number of the fast procedures are designed to search through a particular type of codebook (most of the codebooks are stochastic in character, while a few are deterministic). Other fast procedures can be used for arbitrary codebooks and are thus also applicable to trained codebooks. Some of the fast procedures designed for stochastic codebooks can also be used for the computation of the closed pitch loop parameters, which can be interpreted as a search through a time-dependent codebook.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Anaphylaxis caused by repetitive doses of a GITR agonist monoclonal antibody in mice (2014)

Immunotherapy for cancer using antibodies to enhance T-cell function has been successful in recent clinical trials. Many molecules that improve activation and effector function of T cells have been investigated as potential new targets for immunomodulatory antibodies, including the tumor necrosis factor receptor superfamily members GITR and OX40. Antibodies engaging GITR or OX40 result in significant tumor protection in preclinical models. In this study, we observed that the GITR agonist antibody DTA-1 causes anaphylaxis in mice upon repeated intraperitoneal dosing. DTA-1-induced anaphylaxis requires GITR, CD4(+) T cells, B cells, and interleukin-4. Transfer of serum antibodies from DTA-1-treated mice, which contain high levels of DTA-1-specific immunoglobulin G1 (IgG1), can induce anaphylaxis in naive mice upon administration of an additional dose of DTA-1, suggesting that anaphylaxis results from anti-DTA-1 antibodies. Depletion of basophils and blockade of platelet-activating factor, the key components of the IgG1 pathway of anaphylaxis, rescues the mice from DTA-1-induced anaphylaxis. These results demonstrate a previously undescribed lethal side effect of repetitive doses of an agonist immunomodulatory antibody as well as insight into the mechanism of toxicity, which may offer a means of preventing adverse effects in future clinical trials using anti-GITR or other agonist antibodies as immunotherapies.
Recoding the Genetic Code with Selenocysteine (2013)

Selenocysteine (Sec) is naturally incorporated into proteins by recoding the stop codon UGA. Sec is not hardwired to UGA, as the Sec insertion machinery was found to be able to site-specifically incorporate Sec directed by 58 of the 64 codons. For 15 sense codons, complete conversion of the codon meaning from canonical amino acid (AA) to Sec was observed along with a tenfold increase in selenoprotein yield compared to Sec insertion at the three stop codons. This high-fidelity sense-codon recoding mechanism was demonstrated for Escherichia coli formate dehydrogenase and recombinant human thioredoxin reductase and confirmed by independent biochemical and biophysical methods. Although Sec insertion at UGA is known to compete against protein termination, it is surprising that the Sec machinery has the ability to outcompete abundant aminoacyl-tRNAs in decoding sense codons. The findings have implications for the process of translation and the information storage capacity of the biological cell.
A Subset of Latency-Reversing Agents Expose HIV-Infected Resting CD4+ T-Cells to Recognition by Cytotoxic T-Lymphocytes (2016)

Resting CD4+ T-cells harboring inducible HIV proviruses are a critical reservoir in antiretroviral therapy (ART)-treated subjects. These cells express little to no viral protein, and thus neither die by viral cytopathic effects, nor are efficiently cleared by immune effectors. Elimination of this reservoir is theoretically possible by combining latency-reversing agents (LRAs) with immune effectors, such as CD8+ T-cells. However, the relative efficacy of different LRAs in sensitizing latently-infected cells for recognition by HIV-specific CD8+ T-cells has not been determined. To address this, we developed an assay that utilizes HIV-specific CD8+ T-cell clones as biosensors for HIV antigen expression. By testing multiple CD8+ T-cell clones against a primary cell model of HIV latency, we identified several single agents that primed latently-infected cells for CD8+ T-cell recognition, including IL-2, IL-15, two IL-15 superagonists (IL-15SA and ALT-803), prostratin, and the TLR-2 ligand Pam3CSK4. In contrast, we did not observe CD8+ T-cell recognition of target cells following treatment with histone deacetylase inhibitors or with hexamethylene bisacetamide (HMBA). In further experiments we demonstrate that a clinically achievable concentration of the IL-15 superagonist 'ALT-803', an agent presently in clinical trials for solid and hematological tumors, primes the natural ex vivo reservoir for CD8+ T-cell recognition. Thus, our results establish a novel experimental approach for comparative evaluation of LRAs, and highlight ALT-803 as an LRA with the potential to synergize with CD8+ T-cells in HIV eradication strategies.
Reliable prediction of Drosha processing sites improves microRNA gene prediction (2006)

The classifiers are publicly available at https://demo1.interagon.com/miRNA/
Physical Principles and Visual-OMP Software for Optimal PCR Design (2007)

The physical principles of DNA hybridization and folding are described within the context of how they are important for designing optimal PCRs. The multi-state equilibrium model for computing the concentrations of competing unimolecular and bimolecular species is described. Seven PCR design "myths" are stated explicitly, and alternative proper physical models for PCR design are described. This chapter provides both a theoretical framework for understanding PCR design and practical guidelines for users. The Visual-OMP (oligonucleotide modeling platform) package from DNA Software, Inc. is also described.
Regulatory B Cells Limit CNS Inflammation and Neurologic Deficits in Murine Experimental Stroke (2011)

Evaluation of infarct volumes and infiltrating immune cell populations in mice after middle cerebral artery occlusion (MCAO) strongly implicates a mixture of both pathogenic and regulatory immune cell subsets in stroke pathogenesis and recovery. Our goal was to evaluate the contribution of B cells to the development of MCAO by comparing infarct volumes and functional outcomes in wild-type (WT) versus B-cell-deficient μMT(-/-) mice. The results clearly demonstrate larger infarct volumes, higher mortality, more severe functional deficits, and increased numbers of activated T cells, macrophages, microglial cells, and neutrophils in the affected brain hemisphere of MCAO-treated μMT(-/-) versus WT mice. These MCAO-induced changes were completely prevented in B-cell-restored μMT(-/-) mice after transfer of highly purified WT GFP(+) B cells that were detected in the periphery, but not the CNS. In contrast, transfer of B cells from IL-10(-/-) mice had no effect on infarct volume when transferred into μMT(-/-) mice. These findings strongly support a previously unrecognized activity of IL-10-secreting WT B cells to limit infarct volume, mortality rate, recruitment of inflammatory cells, and functional neurological deficits 48 h after MCAO. Our novel observations are the first to implicate IL-10-secreting B cells as a major regulatory cell type in stroke and suggest that enhancement of regulatory B cells might have application as a novel therapy for this devastating neurologic condition.
Th1 cytokines and NK cells participate in the development of murine syngeneic graft-versus-host disease. (1999)

Syngeneic graft-vs-host disease (SGVHD) is induced by reconstituting lethally irradiated mice with syngeneic bone marrow cells followed by a short course of therapy with the immunosuppressive agent cyclosporine A. Following cessation of cyclosporine A therapy, animals develop clinical symptoms of SGVHD: weight loss, runting, and diarrhea. While it has been suggested that T cells are responsible for the induction and effector phases of SGVHD, the role of nonspecific effector cells and cytokine mediators has yet to be examined in the disease process. Mice with SGVHD had increased levels of message for IL-12p40, IFN-gamma, and TNF-alpha in the target organs of SGVHD as compared with transplant controls and asymptomatic cyclosporine A-treated mice. Concomitant with the increase in Th1 cytokines was an enhanced cellular infiltrate in the target organs of SGVHD mice as determined by histological analysis. To directly examine the role of IL-12 in the development of SGVHD, in vivo neutralization of IL-12 was performed. Treatment of mice with Abs to IL-12 inhibited SGVHD-mediated tissue pathology and mortality. Because IL-12 has been shown to activate both T cells and NK cells to secrete IFN-gamma and to become more cytolytic, studies were initiated to ascertain which lymphocyte populations play a role in the development of murine SGVHD. Depletion of NK cells inhibited clinical symptoms of SGVHD. In contrast, T cell depletion did not alter the disease process. Therefore, these findings collectively demonstrate a role for IL-12 and NK cells in the effector phase of murine SGVHD.
Nonalcoholic Steatohepatitis and Noncirrhotic Hepatocellular Carcinoma: Fertile Soil (2012)

Nonalcoholic fatty liver disease (NAFLD) is easily the most common cause of chronic liver disease in the United States (U.S.) as the hepatic manifestation of the metabolic syndrome. Although only 5 to 20% of patients with NAFLD are generally considered to meet criteria for nonalcoholic steatohepatitis (NASH), with its inherent risk for progression to cirrhosis, this still represents an alarmingly large number of individuals. The exponentially growing rates of hepatocellular carcinoma (HCC) in the U.S. may be partially attributable to increased numbers of NASH cirrhotics, although recent evidence has suggested that NAFLD may directly promote hepatic carcinogenesis independent of cirrhosis. This review focuses on HCC in noncirrhotic NASH with an emphasis on clinical presentation, pathogenesis, and implications for screening.
Design and rationale of the ODYSSEY DM-DYSLIPIDEMIA trial: lipid-lowering efficacy and safety of alirocumab in individuals with type 2 diabetes and mixed dyslipidaemia at high cardiovascular risk (2017)

ODYSSEY DM-DYSLIPIDEMIA will provide information on the efficacy and safety of alirocumab versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk using non-HDL-C as the primary efficacy endpoint. Trial registration NCT02642159 (registered December 24, 2015).
Transcription Factor ATF2 Cooperates with v-Jun To Promote Growth Factor-Independent Proliferation In Vitro and Tumor Formation In Vivo (1998)

ATF2 belongs to the bZIP family of transcription factors and controls gene expression via 8-bp ATF/CREB motifs either as a homodimer or as a heterodimer-for instance, with Jun-but has never been shown to be directly involved in oncogenesis. Experiments were designed to evaluate a possible role of ATF2 in oncogenesis in chick embryo fibroblasts (CEFs) in the presence or absence of v-Jun. We found that (i) forced expression of ATF2 cannot alone cause transformation, (ii) overexpression of ATF2 plus v-Jun specifically stimulates v-Jun-induced growth in medium with a reduced amount of serum, and (iii) the efficiency of low-serum growth correlates with the activity of a Jun-ATF2-dependent model promoter in stably transformed CEFs. Analysis of ATF2 and Jun dimerization mutants showed that the growth-stimulatory effect of ATF2 is likely to be mediated by v-Jun-ATF2 heterodimers since (i) v-Jun-m1, a mutant with enhanced affinity for ATF2, induces growth in low-serum medium much more efficiently than v-Jun, when expressed alone or in combination with ATF2; and (ii) ATF2/fos, a mutant that efficiently binds to v-Jun but is unable to form stable homodimers, shows enhanced oncogenic cooperation with v-Jun. In addition, we examined the role of ATF2 in tumor formation by subcutaneous injection of CEFs into chickens. In contrast to v-Jun, v-Jun-m1 gave rise to numerous fibrosarcomas while coexpression of ATF2 and v-Jun-m1 led to a dramatic development of fibrosarcomas visible within 1 week. Together these data demonstrate that overexpressed ATF2 potentiates the ability of v-Jun-transformed CEFs to grow in low-serum medium in vitro and contributes to the formation of tumors in vivo.
An analysis on the lift generation for Coand&#x0103; micro air vehicles (2014)

A mathematical model for lift generation on a doughnut-shaped Coandă micro air vehicle is developed and an analysis on the lift generation due to Coandă effect is carried out utilizing basic principles. A degenerate two-dimensional case is also developed. The results are discussed in view of related analytical and experimental work in the literature.
The case for an ancestral genetic system involving simple analogues of the nucleotides. (1987)

The idea that the first living systems on earth were based on self-replicating RNA molecules has recently become popular as a result of the discovery of ribozymes. However, there are several major problems associated with the prebiotic synthesis of ribonucleotides. In addition, there is the newly recognized problem of enantiomeric cross-inhibition, whereby template-directed polymerization involving one enantiomer of RNA is inhibited strongly by the presence of the other enantiomer. Here we propose that RNA was preceded in the evolution of life by a polymer constructed from flexible, acyclic, probably prochiral nucleotide analogues that were synthesized readily on the primitive earth. Several potentially prebiotic nucleotide analogues are considered in this context, and some of the consequences of this proposal are discussed.
Characterization of Genes Associated with Different Phenotypes of Human Bladder Cancer Cells (2006)

To identify genes associated with morphological phenotypes of human bladder transitional cell carcinoma, we used suppression subtractive hybridization (SSH) to create a subtractive cDNA library of two established cell lines, BLZ-211 and BLS-211, derived from a patient with transitional cell carcinoma of the bladder, then to screen for differentially expressed genes. Real-time reverse transcription-polymerase chain reaction was used to further confirm the selected differentially expressed genes. Forward and reverse subtractive cDNA libraries yielded 168 and 305 putative clones, and among them more than 90% contained the inserts. After differential screening, 36 different transcripts were obtained from 64 cDNA clones of a forward and reverse subtraction library. Among them, 17 were identified as known genes by homology, for example, Vimentin, Keratin7, DDH and UCH-L1. The remaining 19 were unknown expressed genes, and were collected as new expressed sequence tags by the GenBank dbEST database. Their function will be studied further. Thus, SSH appears to be a useful technique for identifying differentially expressed genes between cell lines or clones. Our results, as revealed by SSH, also suggest that differences in gene expression of cytoskeletal proteins might contribute to the different morphologies in BLZ-211 and BLS-211 cells.
Lymphotoxin α induces apoptosis, necroptosis and inflammatory signals with the same potency as tumour necrosis factor (2013)

Both of the TNF superfamily ligands, TNF and LTα, can bind and signal through TNFR1 and TNFR2, yet mice mutant for each have different phenotypes. Part of this difference is because LTα but not TNF can activate Herpes Virus Entry Mediator and also heterotrimerise with LTβ to activate LTβR, which is consistent with the similar phenotypes of the LTα and LTβR deficient mice. However, it has also been reported that the LTα3 homotrimer signals differently than TNF through TNFR1, and has unique roles in initiation and exacerbation of some inflammatory diseases. Our modeling of the TNF/TNFR1 interface compared to the LTα3/TNFR1 structure revealed some differences that could affect signalling by the two ligands. To determine whether there were any functional differences in the ability of TNF and LTα3 to induce TNFR1-dependent apoptosis or necroptosis, and if there were different requirements for cIAPs and Sharpin to transmit the TNFR1 signal, we compared the ability of cells to respond to TNF and LTα3. Contrary to our hypothesis, we were unable to discover differences in signalling by TNFR1 in response to TNF and LTα3. Our results imply that the reasons for the conservation of LTα are most likely due either to differential regulation, the ability to signal through Herpes Virus Entry Mediator or the ability of LTα to form heterotrimers with LTβ.
Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain (2004)

Based on limited information, topically applied rubefacients containing salicylates may be efficacious in the treatment of acute pain. Trials of musculoskeletal and arthritic pain suggested moderate to poor efficacy. Adverse events were rare in studies of acute pain and poorly reported in those of chronic pain. Efficacy estimates for rubefacients are unreliable owing to a lack of good clinical trials.
Expression and immunohistochemical localization of galectin‐3 in various mouse tissues (2006)

The expression and immunohistochemical localization of galectin-3, a beta-galactoside-binding protein, was studied in several mouse tissues. Galectin-3 expression was low in the cerebrum, heart, and pancreas, and moderate in the liver, ileum, kidney, and adrenal gland. High expression of galectin-3 was found in the lung, spleen, stomach, colon, uterus, and ovary. The results of Western blot analysis largely matched the immunohistochemical findings for galectin-3. These findings suggest that galectin-3 is differentially expressed in a variety of organs in the mouse. This study provides valuable information for research on galectin-3.