gebhart/patrepeval huggingface dataset:
IFN Induces miR-21 through a Signal Transducer and Activator of Transcription 3–Dependent Pathway as a Suppressive Negative Feedback on IFN-Induced Apoptosis (2010)

The microRNA miR-21 is overexpressed in many human cancers, wherein accumulating evidence indicates that it functions as an oncogene. Here, we report that the cytokine IFN rapidly induces miR-21 expression in human and mouse cells. Signal transducer and activator of transcription 3 (STAT3) was implicated in this pathway based on the lack of IFN effect on miR-21 expression in prostate cancer cells with a deletion in the STAT3 gene. STAT3 ablation abrogated IFN induction of miR-21, confirming the important role of STAT3 in regulating miR-21. Chromatin immunoprecipitation analysis showed that STAT3 directly bound the miR-21 promoter in response to IFN. Experiments in mouse embryo fibroblasts with a genetic deletion of the p65 NF-κB subunit showed that IFN-induced miR-21 expression was also dependent on NF-κB. STAT3 silencing blocked both IFN-induced p65 binding to the miR-21 promoter and p65 nuclear translocation. Thus, IFN-induced miR-21 expression is coregulated by STAT3 and NF-κB at the level of the miR-21 promoter. Several cell death regulators were identified as downstream targets of miR-21, including PTEN and Akt. Functional experiments in prostate cancer cells directly showed that miR-21 plays a critical role in suppressing IFN-induced apoptosis. Our results identify miR-21 as a novel IFN target gene that functions as a key feedback regulator of IFN-induced apoptosis.
Epitope Mapping of Human Luteinizing Hormone Using Monoclonal Antibodies (1988)

To establish structure-function relationships for human (h) LH, 14 murine monoclonal antibodies (MABs) to hLH were characterized in terms of their affinity of binding (Ka), their specificity for intact glycoproteins and their subunits, their paratopic relationships, and their ability to interfere with the biological activity of hLH. The Ka values obtained ranged between 2.4 x 10(6) and 1.0 x 10(10) for intact hLH and between 2.3 x 10(6) and 7.5 x 10(8) liters/M for the free alpha- and beta-subunits, indicating that, in general, the antibodies showed higher avidity for the intact hormone. Six MAB recognized both the intact and free alpha-subunit of hLH, cross-reacted with intact hCG, hFSH, and hTSH, and thus appeared to be alpha-directed. Four MAB were beta-directed, recognizing both intact hLH and its free beta-subunit. One of these beta-directed MABs also cross-reacted with intact hCG, hFSH, and hTSH, while two others recognized both intact and free beta-subunits of hLH and hCG. The fourth beta-directed MAB was quite specific for intact hLH and its beta-subunit. The remaining four MABs recognized epitopes only on the intact hormone; three recognized intact hLH and hCG, and the fourth was specific for intact hLH. Their paratopic relationships tested in competitive binding studies resulted in either mutual competition or complementarity, sometimes with cooperativity. Biointerference, defined as the ability to inhibit hLH-induced testosterone biosynthesis in dispersed rat Leydig cells, indicated that three of the alpha- and one of the beta-directed antibodies neutralized the biological response of hLH in this bioassay in a dose-responsive manner. Their ability to inhibit hLH bioactivity largely paralleled their affinity constants. Our data have allowed us to establish a tentative topographic relationship of epitopes to the biological region of the molecule of hLH, foreshadowing (in additive binding studies) some of the possible combinations of antibodies that might allow us to design two- or multiple-site immunometric assays in which measurement of immunoactive LH reflects biological activity. In addition, these studies suggest that both the alpha- and beta-subunits participate in LH receptor binding and/or biological activity.
A Mutational Analysis of the Baculovirus Inhibitor of Apoptosis Op-IAP (1998)

A family of antiapoptotic regulators known as inhibitors of apoptosis (IAPs) was initially identified and functionally described in baculoviruses, and IAP homologues are now known in insects, birds, and mammals. Baculovirus and Drosophila IAPs inhibit apoptosis induced by Drosophila proapoptotic proteins Reaper, HID, and GRIM and physically interact with them through their baculovirus IAP repeat (BIR) region. Here we examined the functional importance of BIR and RING finger motifs of Orgyia pseudotsugata nuclear polyhedrosis virus Op-IAP and D-IAP1 in binding to and inhibiting HID. In the absence of both the BIR1 and RING motifs, the BIR2 regions of Op-IAP and D-IAP1 were able to associate with HID and block HID-induced apoptosis. Mutation of conserved amino acid residues within the BIR and RING finger motifs revealed that the conserved residues within BIR2 were essential for Op-IAP to inhibit apoptosis. However, most of the conserved residues of the BIR2 were not required for HID binding. A region at the carboxy-proximal end of BIR2 was essential for the association of Op-IAP with HID. Thus binding to HID is necessary but not sufficient to block HID-induced apoptosis: the conserved residues within BIR2 must have an additional role in blocking apoptosis. These findings demonstrate that the region encompassing a single BIR of Op-IAP and D-IAP1 can be sufficient for physical interaction with and inhibition of apoptosis induced by HID.
FLT3 internal tandem duplication mutations in adult acute myeloid leukaemia define a high‐risk group (2000)

Genomic DNA from 106 cases of adult de novo acute myeloid leukaemia (AML) was screened by polymerase chain reaction (PCR) and gel electrophoresis for FLT3 internal tandem duplication (ITD) mutations within the juxtamembrane (JM) domain. FLT3 mutations were detected in 14 cases (13·2 % ) and occurred in FAB types M1 (4 out of 14 cases), M3 (1 out of 10 cases), M4 (5 out of 37 cases) and M5 (4 out of 11 cases). Sequence analysis of four cases with abnormal PCR electrophoretic patterns revealed in frame duplications in the region of exon 11 of between 27 and 111 base pairs. Three are predicted to result in the tandem duplication of adjacent amino acid residues and one to result in a tandem duplication plus insertion of a novel amino acid motif. Statistical analysis showed the FLT3 mutations to be a strong prognostic factor, with patients lacking the mutation surviving significantly longer from diagnosis (mean 29·1 months) than those with an ITD (mean 12·8 months; P = 0·0002). Thirteen of the 14 patients with FLT3 mutations died within 18 months of diagnosis. FLT3 mutations were of prognostic significance in good risk disease ( P = 0·04), as well as in patients with standard risk disease ( P = 0·0096). This study demonstrates that the FLT3 ITD mutation occurs in a significant percentage of adult AML cases and is an important adverse prognostic factor that appears independent of conventional karyotypic findings.
Addition of Kerberos Cipher Suites to Transport Layer Security (TLS) (1999)

This document proposes the addition of new cipher suites to the TLS protocol [1] to support Kerberos-based authentication. Kerberos credentials are used to achieve mutual authentication and to establish a master secret which is subsequently used to secure client-server communication.
Noninvasive biochemical monitoring of physiological stress by Fourier transform infrared saliva spectroscopy (2010)

Physical stress affects the immune system, activates the sympathetic (SNS) and parasympathetic (PNS) subsystems of autonomic nervous system (ANS), and increases the activity of the hypothalamic-pituitary-adrenal axis (HPA). The specific response of the major regulatory systems depends on the human functional state. Saliva is a unique diagnostic fluid, the composition of which immediately reflects the SNS, PNS, HPA and immune system response to stress. A new method of saliva biomarker determination by Attenuated Total Reflection Fourier-Transform Infrared (ATR FTIR) spectroscopy has been developed to monitor the exercise induced metabolic changes in saliva from male endurance athletes. The method has been tested using a group of professional athletes by analysing saliva samples collected before and after the exercise, and the saliva composition monitoring by ATR FTIR spectroscopy was shown to be suitable for real-time checking of response to stress.
Mapping the site(s) of MgATP and MgADP interaction with the nitrogenase of Azotobacter vinelandii. Lysine 15 of the iron protein plays a major role in MgATP interaction. (1992)

Nitrogenase binds and hydrolyzes 2MgATP yielding 2MgADP and 2Pi for each electron that is transferred from the iron protein to the MoFe protein. The iron protein alone binds but does not hydrolyze 2MgATP or 2MgADP and the binding of these nucleotides is competitive. Iron protein amino acid sequences all contain a putatitive mononucleotide-binding region similar to a region found in other mononucleotide-binding proteins. To examine the role of this region in MgATP interaction, we have substituted glutamine and proline for conserved lysine 15. The amino acid substitutions, K15Q and K15P, both yielded a non-N2-fixing phenotype when the genes coding for them were substituted into the Azotobacter vinelandii chromosome in place of the wild-type gene. The iron protein from the K15Q mutant was purified to homogeneity, whereas the protein from the K15P mutant could not be purified in its native form. Unlike wild-type iron protein, the purified K15Q iron protein showed no acetylene reduction, H2 evolution, or ATP hydrolysis activities when complemented with wild-type MoFe protein. The K15Q iron protein and the normal iron protein had a similar total iron content and both proteins showed the characteristic rhombic EPR signal resulting from the reduced state of the single 4Fe-4S cluster bridging the two subunits. Unlike the wild-type iron protein, addition of MgATP to the K15Q iron protein did not result in the perturbation necessary to change the EPR signal of its 4Fe-4S center from a rhombic to an axial line shape. Also unlike the wild-type iron protein, addition of MgATP to K15Q iron protein in the presence of the iron chelator, alpha,alpha'-dipyridyl, did not result in a time-dependent transfer of iron to the chelator. Thus, even though the K15Q iron protein contains a normal 4Fe-4S center, it does not respond to MgATP like the wild-type protein. Examination of the ability of the K15Q iron protein to bind MgADP showed no change from the wild-type iron protein, but its ability to bind MgATP decreased to 35% of the wild-type protein. Thus, in A. vinelandii iron protein, lysine 15 is not needed for interaction with MgADP but is involved in the binding of ATP, presumably through charge-charge interaction with the gamma-phosphate. Based on the above data, this lysine appears to be essential for the MgATP induced conformational change of wild-type iron protein that is required for activity.(ABSTRACT TRUNCATED AT 400 WORDS)
The Internet and the New Biology : Tools for Genomic and Molecular Research (1997)

Introduction to the Internet E-mail, Gopher and the Web An Internet Server Primer Molecular and Genomic Databases Search and Retrieval Structure and Function Software, News and Information Other Tools: Gopher and the Web The Future of the New Biology and its Tools Appendixes - Server Addresses, Domains and Usage, Computer Hardware and Software Requirements, Nucleic Acid and Amino Acid Codes and Properties, Glossary of Terms
Endocytosis of chimeric influenza virus hemagglutinin proteins that lack a cytoplasmic recognition feature for coated pits. (1996)

The influenza virus A/Japan/305/57 hemagglutinin (HA) can be converted from a protein that is essentially excluded from coated pits into one that is internalized at approximately the rate of uptake of bulk membrane by replacing the HA transmembrane and cytoplasmic sequences with those of either of two other glycoproteins (Roth et al., 1986. J. Cell Biol. 102:1271-1283). To identify more precisely the foreign amino acid sequences responsible for this change in HA traffic, DNA sequences encoding the transmembrane (TM) or cytoplasmic (CD) domains of either the G glycoprotein of vesicular stomatitis virus (VSV) or the gC glycoprotein of herpes simplex virus were exchanged for those encoding the analogous regions of wild type HA (HA wt). HA-HA-G and HA-HA-gC, chimeras that contain only a foreign CD, resembled HA wt in having a long residence on the cell surface and were internalized very slowly. HA-HA-gC was indistinguishable from HA in our assays, whereas twice as much HA-HA-G was internalized as was HA wt. However, HA-G-HA, containing only a foreign TM, was internalized as efficiently as was HA-G-G, a chimeric protein with transmembrane and cytoplasmic sequences of VSV G protein. Conditions that blocked internalization through coated pits also inhibited endocytosis of the chimeric proteins. Although the external domains of the chimeras were less well folded than that of the wild type HA, denaturation of the wild type HA external domain by treatment with low pH did not increase the interaction of HA with coated pits. However, mutation of four amino acids in the TM of HA allowed the protein to be internalized, indicating that the property that allows HA to escape endocytosis resides in its TM. These results indicate that possession of a cytoplasmic recognition feature is not required for the internalization of all cell surface proteins and suggest that multiple mechanisms for internalization exist that operate at distinctly different rates.
Development of an adhesive bonding system. (1992)

Building on findings concerning adhesion to enamel, R L Bowen and his colleagues at the Paffenbarger Research Center, National Institute of Standards and Technology began addressing and solving problems associated with (1) silicate cements and unfilled resins, (2) bonding in an aqueous environment, and (3) the development of an adhesion system for both dentin and enamel that could withstand various stresses. This article reviews the development of an adhesion system for bonding dental composites to dentin and enamel.
Granuloerythropoietic colonies in human bone marrow, peripheral blood, and cord blood (1978)

Colonies that contain granulopoietic and erythropoietic cells can be grown in specimens of human bone marrow, peripheral blood, and cord blood. Growth of these colonies is promoted by media conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM) and the addition of erythropoietin on days 4 or 5 to the cultures. Sedimentation velocity profiles for these granuloerythrocytic colonies suggest their origin from single cells (CFU-G/E) rather than from doublets or clumps. This hypothesis is supported by cocultivation of male and female specimens. Cells in granuloerythrocytic colonies that developed in such mixing experiments were either uniformly female by Y- chromatin analysis or contained Y-chromatin bodies in both the granulocytic and erythroid cells.
Effect of Enalapril on Mortality and the Development of Heart Failure in Asymptomatic Patients with Reduced Left Ventricular Ejection Fractions (1992)

The angiotensin-converting--enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations, as compared with the rates in the group given placebo, among patients with asymptomatic left ventricular dysfunction. There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril.
Stream-based Translation Models for Statistical Machine Translation (2010)

Typical statistical machine translation systems are trained with static parallel corpora. Here we account for scenarios with a continuous incoming stream of parallel training data. Such scenarios include daily governmental proceedings, sustained output from translation agencies, or crowd-sourced translations. We show incorporating recent sentence pairs from the stream improves performance compared with a static baseline. Since frequent batch retraining is computationally demanding we introduce a fast incremental alternative using an online version of the EM algorithm. To bound our memory requirements we use a novel data-structure and associated training regime. When compared to frequent batch retraining, our online time and space-bounded model achieves the same performance with significantly less computational overhead. 1
Ghrelin Is Present in Pancreatic α-Cells of Humans and Rats and Stimulates Insulin Secretion (2002)

Ghrelin, a novel growth hormone-releasing peptide isolated from human and rat stomach, is a 28-amino acid peptide with a posttranslational acylation modification that is indispensable for stimulating growth hormone secretion by increasing intracellular Ca(2+) concentration. It also functions in the regulation of feeding behavior, energy metabolism, and gastric acid secretion and motility. Using two different antibodies against the NH(2)- and COOH-terminal regions of ghrelin, we studied its localization in human and rat pancreas by immunohistochemistry. Ghrelin-immunoreactive cells were identified at the periphery of pancreatic islets in both species. Ghrelin co-localized exclusively with glucagon in rat islets, indicating that it is produced in alpha-cells. We identified ghrelin and des-acyl ghrelin in the rat pancreas using reverse-phase high-performance liquid chromatography combined with two radioimmunoassays. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets. Ghrelin increased the cytosolic free Ca(2+) concentration in beta-cells and stimulated insulin secretion when it was added to isolated rat pancreatic islets. These findings indicate that ghrelin may regulate islet function in an endocrine and/or paracrine manner.
Interferon alpha regulates MAPK and STAT1 pathways in human hepatoma cells (2011)

IFN alpha up-regulates MAPK and STAT1 pathways in human hepatoma cells, and may provide useful information for understanding the IFN signaling.
Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis (2004)

Haemorrhagic shock (60 min) in the anaesthetized rat resulted in a prolonged fall in the mean arterial blood pressure (MAP) and heart rate (HR). Pre-treatment (30 min before shock) or post-treatment (60 min after shock) with inhibitors of cystathionine gamma lyase (CSE; converts cysteine into hydrogen sulphide (H(2)S)), dl-propargylglycine or beta-cyanoalanine (50 mg kg(-1), i.v.), or glibenclamide (40 mg kg(-1), i.p.), produced a rapid, partial restoration in MAP and HR. Neither saline nor DMSO affected MAP or HR. Plasma H(2)S concentration was elevated 60 min after blood withdrawal (37.5+/-1.3 microM, n=18 c.f. 28.9+/-1.4 microM, n=15, P<0.05). The conversion of cysteine to H(2)S by liver (but not kidney) homogenates prepared from animals killed 60 min after withdrawal of blood was significantly increased (52.1+/-1.6 c.f. 39.8+/-4.1 nmol mg protein(-1), n=8, P<0.05), as was liver CSE mRNA (2.7 x). Both PAG (IC(50), 55.0+/-3.2 microM) and BCA (IC(50), 6.5+/-1.2 microM) inhibited liver H(2)S synthesizing activity in vitro. Pre-treatment of animals with PAG or BCA (50 mg kg(-1), i.p.) but not glibenclamide (40 mg kg(-1), i.p., K(ATP) channel inhibitor) abolished the rise in plasma H(2)S in animals exposed to 60 min haemorrhagic shock and prevented the augmented biosynthesis of H(2)S from cysteine in liver. These results demonstrate that H(2)S plays a role in haemorrhagic shock in the rat. CSE inhibitors may provide a novel approach to the treatment of haemorrhagic shock.
Step-emulsification in a microfluidic device (2014)

We present a comprehensive study of the step-emulsification process for high-throughput production of colloidal monodisperse droplets. The 'microfluidic step emulsifier' combines a shallow microchannel operating with two co-flowing immiscible fluids and an abrupt (step-like) opening to a deep and wide reservoir. Based on Hele-Shaw hydrodynamics, we determine the quasi-static shape of the fluid interface prior to transition to oscillatory step-emulsification at low capillary numbers. The theoretically derived transition threshold yields an excellent agreement with experimental data. A closed-form expression for the size of the droplets generated in the step-emulsification regime and derived using geometric arguments also shows a very good agreement with the experiment.
A Real-Time Beat Tracking System for Audio Signals (1995)

This paper presents a beat tracking system that processes musical acoustic signals and recognizes temporal positions of beats in real time. Most previous systems were not able to deal with audio signals that contained sounds of various instruments, especially drums. Our system deals with popular music in which drums maintain the beat. To examine multiple hypotheses of beats in parallel, our system manages multiple agents that predict beats by using autocorrelation and cross-correlation according to different strategies. In our experiment with eight pre-registered drum patterns, the system implemented on a parallel computer correctly tracked beats in 42 out of 44 commercially distributed popular songs.
Lessons learned from biosimilar epoetins and insulins (2010)

Patients with diabetes and renal failure may already be receiving biosimilar epoetin and may receive biosimilar insulin in the near future. Because these biosimilar pharmaceuticals (or follow-on biologics) are complex protein molecules manufactured in lengthy and inherently variable processes involving living organisms, they have the potential to induce an immunogenic, rather than a therapeutic, response. This response is dependent as much on the method of manufacture and formulation, as on the protein itself. Apparently small and innocuous differences in manufacture and formulation can lead to unforeseen clinical consequences. This article discusses two case studies illustrating this principle, that of three insulin formulations which were physicochemically similar to comparator insulins, but with pharmacokinetic and pharmacodynamic profiles sufficiently different to have potentially serious clinical consequences and that of Eprex, for which an apparently minor change in one formulation caused an upsurge of cases of pure red cell aplasia which resulted in fatalities or complete transfusion dependence. Comprehensive and rigorous testing and long-term pharmacovigilance programmes are essential to detect and forestall such consequences.
<title>Apple color management system (ColorSyncTM)</title> (1993)

Before ColorSync, the QuickDraw graphics model had no specific means to define device independent color. That is, colors in QuickDraw were defined in terms of RGB values without reference to a specific, objective definition of RGB. This means that devices have no way of knowing how to interpret the incoming RGB values. When QuickDraw asks for a red value of 300, say, it asks the device to output 300 / 65536 of full red. The problem is that the full red has not been defined, so the color is relative to the full red of the destination device. The end result is that the same color triplet imaged on different output devices looks different. Without the capability of device independent color definition, achieving consistent color across varying devices is impossible.