gebhart/patrepeval huggingface dataset:
A Breast and Melanoma-Shared Tumor Antigen: T Cell Responses to Antigenic Peptides Translated from Different Open Reading Frames (1998)

Infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Here, we report that screening a cDNA library from the 586mel cell line using CTL clones derived from TIL586 resulted in the isolation of a gene, CAG-3 (cancer Ag gene 3). Sequence analysis revealed that CAG-3 encodes an open reading frame identical to NY-ESO-1, which was recently reported to be recognized by autologous serum from a patient with esophageal cancer. Thus, NY-ESO-1 appears to be an immune target for both Ab- and T cell-mediated responses. Significantly, NY-ESO-1-specific CTL clones were capable of recognizing two HLA-A31-positive fresh and cultured breast tumors. To our knowledge, this represents the first direct demonstration that tumor-specific CTL clones can recognize both breast and melanoma tumor cells. A 10-mer antigenic peptide ESO10-53 (ASGPGGGAPR) was identified from the normal open reading frame of NY-ESO-1 based on its ability to sensitize HLA-A31-positive target cells for cytokine release and specific lysis. Interestingly, two additional CTL clones that were sensitized with NY-ESO-1 recognized two overlapping antigenic peptides derived from an alternative open reading frame of the same gene. These findings indicate that CTLs simultaneously responded to two different gene products translated from the normal and alternative reading frames of the same gene. Understanding of this mechanism by which the alternative reading frame is translated may have important implications in tumor immunology.
Control of feeding behavior in C. elegans by human G protein-coupled receptors permits screening for agonist-expressing bacteria (2008)

G protein-coupled receptors (GPCRs) have a key role in many biological processes and are important drug targets for many human diseases. Therefore, understanding the molecular interactions between GPCRs and their ligands would improve drug design. Here, we describe an approach that allows the rapid identification of functional agonists expressed in bacteria. Transgenic Caenorhabditis elegans expressing the human chemokine receptor 5 (CCR5) in nociceptive neurons show avoidance behavior on encounter with the ligand MIP-1alpha and avoid feeding on Escherichia coli expressing MIP-1alpha compared with control bacteria. This system allows a simple activity screen, based on the distribution of transgenic worms in a binary food-choice assay, without a requirement for protein purification or tagging. By using this approach, a library of 68 MIP-1alpha variants was screened, and 13 critical agonist residues involved in CCR5 activation were identified, four of which (T8, A9, N22, and A25) have not been described previously, to our knowledge. Identified residues were subsequently validated in receptor binding assays and by calcium flux assays in mammalian cells. This approach serves not only for structure/function studies as demonstrated, but may be used to facilitate the discovery of agonists within bacterial libraries.
A fast square rooter combining algorithmic and lookup table techniques (2003)

It is noted that lookup table implementations of a square root are very inefficient in terms of hardware, while algorithmic techniques are inefficient in terms of speed. The author considers square-root implementations combining both techniques, which are a compromise between speed and complexity. The proposed technique speeds up the algorithmic implementation by using a PLA (programmable logic array) lookup table to determine both the MSBs (most significant bits) of the square root and the square of these bits. The square is subtracted form the original number to obtain a partial remainder, and the remaining square-root bits are determined algorithmically. >
Amyloid Deposits and Amyloidosis (1980)

Redefinition of Amyloid Fibrils and Classification of the β-FibrillosesThe diversity of the major protein component of amyloid fibrils from classically accepted sites of amyloid deposition negates the unitary concept that all amyloid proteins are derived from a single source and of the same nature. Although this chemical heterogeneity of amyloid and the generic basis of the term was predicted before the definitive chemical data were presented,29, 119 the great variation subsequently found was not anticipated.6 The amyloid fibril, the abortive effort of the vertebrate to rival the silkworm, represents the final common pathway for a diverse array of proteins in . . .
The kinetic resolution of allylic alcohols by a non-enzymatic acylation catalyst; application to natural product synthesis (2000)

A planar-chiral DMAP derivative is shown to serve as an effective catalyst for the kinetic resolution of allylic alcohols; to illustrate its practical utility, the catalyst is applied to the resolution of two alcohols that have been employed as intermediates in recent natural product total syntheses.
Silencing ataxin-3 mitigates degeneration in a rat model of Machado–Joseph disease: no role for wild-type ataxin-3? (2010)

Machado-Joseph disease or spinocerebellar ataxia type 3 (MJD/SCA3) is a fatal, autosomal dominant disorder caused by a cytosine-adenine-guanine expansion in the coding region of the MJD1 gene. RNA interference has potential as a therapeutic approach but raises the issue of the role of wild-type ataxin-3 (WT ATX3) in MJD and of whether the expression of the wild-type protein must be maintained. To address this issue, we both overexpressed and silenced WT ATX3 in a rat model of MJD. We showed that (i) overexpression of WT ATX3 did not protect against MJD pathology, (ii) knockdown of WT ATX3 did not aggravate MJD pathology and that (iii) non-allele-specific silencing of ataxin-3 strongly reduced neuropathology in a rat model of MJD. Our findings indicate that therapeutic strategies involving non-allele-specific silencing to treat MJD patients may be safe and effective.
Kinetics and mechanism of the DNA double helix invasion by pseudocomplementary peptide nucleic acids (2002)

If adenines and thymines in two mutually complementary mixed-base peptide nucleic acid (PNA) oligomers are substituted with diaminopurines and thiouracils, respectively, so-called pseudocomplementary PNAs (pcPNAs) are created. Pairs of pcPNAs have recently demonstrated an ability to highly selectively target essentially any designated site on double-stranded DNA (dsDNA) by forming very stable PNA-DNA strand-displacement complexes via double duplex invasion (helix invasion). These properties of pcPNAs make them unique and very promising ligands capable of denying the access of DNA-binding proteins to dsDNA. To elucidate the sequence-unrestricted mechanism of sequence-specific dsDNA recognition by pcPNAs, we have studied the kinetics of formation of corresponding PNA-DNA complexes at various temperatures by the gel-shift assay. In parallel, the conditions for possible self-hybridization of pcPNA oligomers have been assayed by mixing curve (Job plot) and thermal melting experiments. The data indicate that, at physiological temperatures ( approximately 37 degrees C), the equilibrium is shifted toward the pairing of corresponding pcPNAs with each other. This finding explains a linear concentration dependence, within the submicromolar range, of the pcPNA invasion rate into dsDNA at 37 degrees C. At elevated temperatures (>50 degrees C), the rather unstable pcPNA duplexes dissociate, yielding the expected quadratic dependence for the rate of pcPNA invasion on the PNA concentration. The polycationic character of pcPNA pairs, carrying the duplicated number of protonated terminal PNA residues commonly used to increase the PNA solubility and binding affinity, also explains the self-inhibition of pcPNA invasion observed at higher PNA concentrations. Melting of pcPNA duplexes occurs with the integral transition enthalpies ranged from -235 to -280 kJ.mol(-1), contributing to an anomalously high activation energy of approximately 150 kJ.mol(-1) found for the helix invasion of pcPNAs carrying four different nucleobases. A simplified kinetic model for pcPNAs helix invasion is proposed that interprets all unusual features of pcPNAs binding to dsDNA. Our findings have important implications for rational use of pcPNAs.
An energetic tale of AMPK-independent effects of metformin (2010)

Metformin has become a mainstay in the modest therapeutic armamentarium for the treatment of the insulin resistance of type 2 diabetes mellitus. Although metformin functions primarily by reducing hepatic glucose output, the molecular mechanism mediating this effect had remained elusive until recently. Metformin impairs ATP production, activating the conserved sensor of nutritional stress AMP-activated protein kinase (AMPK), thus providing a plausible and generally accepted model for suppression of gluconeogenic gene expression and glucose output. In this issue of the JCI, Foretz et al. refute this hypothesis by showing that AMPK is dispensable for the effects of metformin on hepatic glucose output in primary hepatocytes; rather, their data suggest that the antidiabetic effects of metformin in the liver are mediated directly by reducing energy charge.
Genetic diversity and evolution of hepatitis C virus – 15 years on (2004)

In the 15 years since the discovery of hepatitis C virus (HCV), much has been learned about its role as a major causative agent of human liver disease and its ability to persist in the face of host-cell defences and the immune system. This review describes what is known about the diversity of HCV, the current classification of HCV genotypes within the family Flaviviridae and how this genetic diversity contributes to its pathogenesis. On one hand, diversification of HCV has been constrained by its intimate adaptation to its host. Despite the >30 % nucleotide sequence divergence between genotypes, HCV variants nevertheless remain remarkably similar in their transmission dynamics, persistence and disease development. Nowhere is this more evident than in the evolutionary conservation of numerous evasion methods to counteract the cell's innate antiviral defence pathways; this series of highly complex virus-host interactions may represent key components in establishing its 'ecological niche' in the human liver. On the other hand, the mutability and large population size of HCV enables it to respond very rapidly to new selection pressures, manifested by immune-driven changes in T- and B-cell epitopes that are encountered on transmission between individuals with different antigen-recognition repertoires. If human immunodeficiency virus type 1 is a precedent, future therapies that target virus protease or polymerase enzymes may also select very rapidly for antiviral-resistant mutants. These contrasting aspects of conservatism and adaptability provide a fascinating paradigm in which to explore the complex selection pressures that underlie the evolution of HCV and other persistent viruses.
A brief guide to nucleic acid chemistry (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA brief guide to nucleic acid chemistryPaul S. MillerCite this: Bioconjugate Chem. 1990, 1, 3, 187–191Publication Date (Print):May 1, 1990Publication History Published online1 May 2002Published inissue 1 May 1990https://pubs.acs.org/doi/10.1021/bc00003a002https://doi.org/10.1021/bc00003a002research-articleACS PublicationsRequest reuse permissionsArticle Views240Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Genetic Predictors of Weight Loss and Weight Regain After Intensive Lifestyle Modification, Metformin Treatment, or Standard Care in the Diabetes Prevention Program (2011)

Genetic information may help identify people who require additional support to maintain reduced weight after clinical intervention.
Ubiquitous Access through the Integration of Mobile Ad-hoc Networks (2007)

The increasing requirement for ubiquitous access of the users, enable the seamless support of different networks, with different technologies, and also with different types, such as moving networks and ad-hoc networks. This paper describes the ad-hoc network integration architecture being developed inside the IST project Daidalos II. The main purpose of this architecture is to seamlessly support the movement of nodes between ad-hoc and infrastructure networks, maintaining in the ad-hoc networks all the features being supported in the infrastructure, such as, efficient routing for unicast and multicast flows, distributed QoS mechanisms, security, and seamless mobility, including multihoming support.
Programmed necrosis induced by asbestos in human mesothelial cells causes high-mobility group box 1 protein release and resultant inflammation (2010)

Asbestos carcinogenesis has been linked to the release of cytokines and mutagenic reactive oxygen species (ROS) from inflammatory cells. Asbestos is cytotoxic to human mesothelial cells (HM), which appears counterintuitive for a carcinogen. We show that asbestos-induced HM cell death is a regulated form of necrosis that links to carcinogenesis. Asbestos-exposed HM activate poly(ADP-ribose) polymerase, secrete H 2 O 2 , deplete ATP, and translocate high-mobility group box 1 protein (HMGB1) from the nucleus to the cytoplasm, and into the extracellular space. The release of HMGB1 induces macrophages to secrete TNF-α, which protects HM from asbestos-induced cell death and triggers a chronic inflammatory response; both favor HM transformation. In both mice and hamsters injected with asbestos, HMGB1 was specifically detected in the nuclei, cytoplasm, and extracellular space of mesothelial and inflammatory cells around asbestos deposits. TNF-α was coexpressed in the same areas. HMGB1 levels in asbestos-exposed individuals were significantly higher than in nonexposed controls ( P &lt; 0.0001). Our findings identify the release of HMGB1 as a critical initial step in the pathogenesis of asbestos-related disease, and provide mechanistic links between asbestos-induced cell death, chronic inflammation, and carcinogenesis. Chemopreventive approaches aimed at inhibiting the chronic inflammatory response, and especially blocking HMGB1, may decrease the risk of malignant mesothelioma among asbestos-exposed cohorts.
Neonatal Facial Pain Detection Using NNSOA and LSVM. (2008)

Abstract- We report classification experiments using the pilot Infant COPE database of neonatal facial expressions. Two sets of DCT coeffiecents were used to train a neural network simultaneous algorithm (NNSOA) and a linear support vector machine (LSVM) to classify neonatal expressions into the two categories of pain and nonpain. In the first set (VAR) only 80 of the coefficients with the highest variance were included. In the second set (SFFS), 15 DCT coefficients were selected by applying Sequential Forward Floating Selection (SFFS) [1]. We found that NNSOA+VAR produced the best classification score of 95.38 % accuracy, but with no statistical difference compared with the DCT sets. However, NNSOA using the DCT coefficients outperformed with statistical significance previous experiments reported in [2] that used PCA components. It is surmised that NNSOA, an algorithm that eliminates unnecessary weights, is more stable than LSVM and may be better than SFFS at identifying relevant features.
The pathogenicity of cytomegalovirus (1999)

Human cytomegalovirus is ubiquitous, yet causes little illness in immunocompetent individuals. Disease is evident in immunodeficient groups such as neonates, transplant recipients and AIDS patients either following a primary infection or reactivation of a latent infection. Little is known of the mechanisms underlying the pathogenicity of the virus. The recent determination of the nucleotide sequence of both human cytomegalovirus (strain AD169) and murine cytomegalovirus (murine cytomegalovirus strain Smith) has allowed an analysis of the biological importance of several virus genes. Studies with human cytomegalovirus have indicated that many viral genes are non-essential for replication in vitro which are thus assumed to be important in the pathogenesis of the virus. This is being examined in the murine model where the role of the gene and its product in disease can be directly examined in vivo using viral mutants in which the relevant gene has been interrupted or deleted. Current information on the role of cytomegalovirus genes in tissue tropism, immune evasion, latency, reactivation from latency and damage is described.
Late Complications After Gastric Reservoir Reduction With External Wrap (1987)

Numerous surgical procedures have been introduced to facilitate weight loss in morbidly obese individuals. Gastric reservoir reduction, wrapping the stomach with an inert fabric, is one such procedure. Nissen fundoplication has been performed in conjunction with this approach to prevent postoperative gastroesophageal reflux. Gastric perforation and functional gastroesophageal obstruction occurring as late as 71 months after this operation represent late complications. Perforation has developed in 14.6% of stomachs wrapped with polypropylene mesh. Nissen fundoplication may contribute to this complication.
Progressive Familial Intrahepatic Cholestasis in Korea: A Clinicopathological Study of Five Patients (2019)

PFIC is not rare in patients with neonatal cholestasis of unknown origin. Proper clinicopathologic correlation and genetic testing can enable early detection and management.
<title>Four-kiloframe 14-bit 128x128 digital imaging spectrometer</title> (2002)

A digital readout for a 128 by 128 MWIR focal plane using InSb detectors was developed for imaging spectrometry. There are a total of 16,384 oversample A/D converters on the chi p that provide a 14 bit linear data output at a nominal frame rate of 4,000 samples per second. An early prototype design was completed and tested without detectors and found to meet all requirements. A second iteration is in final hybrid assembly for demonstration where it will be mounted in a dewar with optics. The device is designed to work with a 3.3 volt power supply with on chip A/D power consumption of under 50 milliwatts. This technology was developed under a SBIR program sponsored by US Air Force, Arnold Air Force Base.
Glyoxalase System in Clinical Diabetes Mellitus and Correlation with Diabetic Complications (1994)

1. The metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. The glyoxalase system was characterized in blood samples from patients with insulin-dependent diabetes mellitus (n = 43), patients with non-insulin-dependent diabetes mellitus (n = 107) and 21 normal healthy control subjects. 2. The concentrations of glyoxalase metabolites, methylglyoxal, S-D-lactoylglutathione and D-lactate, were increased in diabetic patients, relative to normal control subjects: methylglyoxal [median, range (n) pmol/g], insulin-dependent patients, 470.7, 85.6-1044.3 (42), P < 0.001, non-insulin-dependent patients, 286.8, 54.7-2370 (105), P < 0.001, control subjects, 79.8, 25.3-892.9 (21); S-D-lactoylglutathione [mean +/- SD (n)pmol/10(6) erythrocytes], combined diabetic patients, 3.37 +/- 0.85 (24), control subjects 4.76 +/- 1.95 (8) P < 0.05; D-lactate [mean +/- SD or median, range (n)nmol/g], insulin dependent patients, median 18.3, 5.7-57.4 (42), P < 0.001, non-insulin-dependent patients, 20.0 +/- 8.9, 2.6-48.4 (105), P < 0.001, control subjects 9.7 +/- 4.3, 1.8-19.7 (21). The reduced glutathione concentrations in blood samples from the insulin-dependent and non-insulin-dependent diabetic patient groups were not different from the control group values (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Fluctuation of endogenous TNF alpha concentration in plasma in advanced cancer patients. (1997)

Serum TNF alpha levels were substantially increased in patients with advanced cancer as compared to healthy subjects. Peak value appeared at 3 a.m., and gradually declined to very low levels in the afternoon (3 p.m.). Using cosinor least square methods we could not find the circadian rhythm of TNF alpha.
Structural properties and evolutionary relationships of PspA, a surface protein of Streptococcus pneumoniae, as revealed by sequence analysis (1992)

Analysis of the sequence for the gene encoding PspA (pneumococcal surface protein A) of Streptococcus pneumoniae revealed the presence of four distinct domains in the mature protein. The structure of the N-terminal half of PspA was highly consistent with that of an alpha-helical coiled-coil protein. The alpha-helical domain was followed by a proline-rich domain (with two regions in which 18 of 43 and 5 of 11 of the residues are prolines) and a repeat domain consisting of 10 highly conserved 20-amino-acid repeats. A fourth domain consisting of a hydrophobic region too short to serve as a membrane anchor and a poorly charged region followed the repeats and preceded the translation stop codon. The C-terminal region of PspA did not possess features conserved among numerous other surface proteins, suggesting that PspA is attached to the cell by a mechanism unique among known surface proteins of gram-positive bacteria. The repeat domain of PspA was found to have significant homology with C-terminal repeat regions of proteins from Streptococcus mutans, Streptococcus downei, Clostridium difficile, and S. pneumoniae. Comparisons of these regions with respect to functions and homologies suggested that, through evolution, the repeat regions may have lost or gained a mechanism for attachment to the bacterial cell.
Genome‐wide monitoring of wine yeast gene expression during alcoholic fermentation (2003)

The transcriptome of a wine yeast was monitored throughout an alcoholic fermentation under conditions mimicking an enological environment. Major changes in gene expression occurred during fermentation, affecting more than 2000 genes, as the yeast adapted to changing nutritional, environmental and physiological conditions. The genes of many pathways are regulated in a highly coordinated manner, and genes involved in the key metabolic pathways of fermentation are strongly expressed. We showed that, during fermentation of a synthetic medium mimicking a natural must in which growth arrest was caused by nitrogen exhaustion, entry into the stationary phase triggered major transcriptional reprogramming. Many TOR target genes involved in nitrogen utilization or other functions are induced at this stage, suggesting that this signalling pathway plays a critical role in changes in gene expression in response to nitrogen depletion. Entry into stationary phase is a key physiological event and is followed by a general stress response. The superimposition of multiple stresses, including starvation and ethanol stress, gives rise to a unique stress response, involving hundreds of genes encoding proteins involved in various cellular processes, many of unknown function.