gebhart/patrepeval huggingface dataset:
Packet synchronization and identification for incremental redundancy transmission in FH-CDMA systems (2003)

Incremental redundancy transmission is an efficient data communication technique in a frequency hopping code division multiple access system. However, there are some difficulties in practical implementation of this technique such as synchronization of packets of different sizes and identification between regular and subpackets. This paper describes these problems and suggests practical solutions to avoid the loss of synchronization and decoding ambiguity during transmission of messages.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mutation of amino acids within the gibbon ape leukemia virus (GALV) receptor differentially affects feline leukemia virus subgroup B, simian sarcoma-associated virus, and GALV infections (1993)

The three type C retroviruses, gibbon ape leukemia virus (GALV), simian sarcoma-associated virus (SSAV), and feline leukemia virus subgroup B (FeLV-B), infect human cells by interacting with the same cell surface receptor, GLVR1. Using LacZ retroviral pseudotypes and murine cells transfected with mutant GLVR1 expression vectors, we show that the same 9-amino-acid region of human GLVR1 is critical for infection by the three viruses. Rat cells were not susceptible to infection by LacZ (FeLV-B) pseudotypes because of a block at the receptor level. We found multiple amino acid differences from human GLVR1 in the 9-amino-acid critical region of rat GLVR1. Expression of a human-rat chimeric GLVR1 in murine cells demonstrated that rat GLVR1 could function as a receptor for GALV and SSAV but not for FeLV-B. Substitution of human GLVR1 amino acids in the critical region of rat GLVR1 identified three amino acids as responsible for resistance to FeLV-B infection; two of these affect SSAV infection, but none affects GALV infection.
Quantitative Determination of 3,3?-Diindolylmethane inUrine of Individuals Receiving Indole-3-Carbinol (2001)

Indole-3-carbinol (I3C) or, more correctly, its acid condensation products act as chemoprotective agents via several mechanisms. It induces the expression of cytochrome P-450 1A1, which shifts the estrogen metabolic pathway in favor of C-2 hydroxylation and away from the formation of 16 alpha-hydroxyestrone, a suspected endogenous carcinogen. Increased 16 alpha-hydroxylation of estrogen is associated with greater risk of cancer of the cervix, breast, endometrium, and larynx. The production of 4-hydroxyestrone is also inhibited by I3C. I3C can induce a G1 cell cycle arrest in human MCF-7 breast cancer cells. It can suppress aberrant crypt foci. I3C significantly inhibits the cell adhesion, spreading, and invasion associated with an upregulation of PTEN (a tumor suppressor gene) and E-cadherin (a regulator of cell-cell adhesion) expression in T47-D human breast cancer cells. Thus I3C exhibits anticancer activities by suppressing breast tumor cell growth and metastatic spread. A gas chromatography-mass spectrometry method for the quantitation of diindolylmethane, the principal acid condensation product of I3C, has been developed for use in determining compliance in subjects who have been treated with I3C. The method utilizes a 1-ml urine sample. We have used this method to correlate I3C ingestion with regression of cervical intraepithelial neoplasia in a population of women at risk for cervical cancer. The assay provides an objective marker of consumption using a noninvasive biological fluid and illustrates that diindolylmethane may be used as a marker of compliance in I3C dietary intervention studies.
The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungusHistoplasma capsulatum (2008)

The PD-1 costimulatory receptor inhibits T cell receptor signaling upon interacting with its ligands PD-L1 and PD-L2. The PD-1/PD-L pathway is critical in maintaining self-tolerance. In this study, we examined the role of PD-1 in a mouse model of acute infection with Histoplasma capsulatum, a major human pathogenic fungus. In a lethal model of histoplasmosis, all PD-1-deficient mice survived infection, whereas the wild-type mice died with disseminated disease. PD-L expression on macrophages and splenocytes was up-regulated during infection, and macrophages from infected mice inhibited in vitro T cell activation. Of interest, antibody blocking of PD-1 significantly increased survival of lethally infected wild-type mice. Thus, our studies extend the role of the PD-1/PD-L pathway in regulating antimicrobial immunity to fungal pathogens. The results show that the PD-1/PD-L pathway has a key role in the regulation of antifungal immunity, and suggest that manipulation of this pathway represents a strategy of immunotherapy for histoplasmosis.
Bendamustine Plus Rituximab Is Effective and Has a Favorable Toxicity Profile in the Treatment of Mantle Cell and Low-Grade Non-Hodgkin's Lymphoma (2005)

These results demonstrate that the BR combination is a highly active regimen in the treatment of low-grade lymphomas and mantle cell lymphomas.
Fibulin-5 Antagonizes Vascular Endothelial Growth Factor (VEGF) Signaling and Angiogenic Sprouting by Endothelial Cells (2004)

Fibulin-5 (FBLN-5) is a widely expressed, integrin-binding extracellular matrix protein that mediates endothelial cell adhesion and scaffolds cells to elastic fibers. It is also a gene target of TGF-beta in fibroblasts and endothelial cells that regulates cell proliferation and motility in a context-specific manner. Whereas FBLN-5 expression is low in adult vasculature, its expression is high in developing and injured vasculature, implicating FBLN-5 in regulating angiogenesis and endothelial cell function. We show here that TGF-beta stimulates FBLN-5 expression in endothelial cells, and that this response was inhibited by coadministration of the proangiogenic factor, VEGF. FBLN-5 expression was downregulated significantly during endothelial cell tubulogenesis, implying that FBLN-5 expression antagonizes angiogenesis. Accordingly, FBLN-5 overexpression in or recombinant FBLN-5 treatment of endothelial cells abrogated their ability to undergo angiogenic sprouting, doing so by inhibiting endothelial cell proliferation and invasion through Matrigel matrices. Moreover, FBLN-5 antagonized VEGF signaling in endothelial cells, as well as enhanced their expression of the antiangiogenic factor, thrombospondin-1. Finally, the ability of FBLN-5 to antagonize angiogenic processes was determined to be independent of its integrin-binding RGD motif. Collectively, our findings establish FBLN-5 as a novel antagonist of angiogenesis and endothelial cell activities, and offer new insights into why tumorigenesis downregulates FBLN-5 expression.
Investigations into resting-state connectivity using independent component analysis (2005)

Inferring resting-state connectivity patterns from functional magnetic resonance imaging (fMRI) data is a challenging task for any analytical technique. In this paper, we review a probabilistic independent component analysis (PICA) approach, optimized for the analysis of fMRI data, and discuss the role which this exploratory technique can take in scientific investigations into the structure of these effects. We apply PICA to fMRI data acquired at rest, in order to characterize the spatio-temporal structure of such data, and demonstrate that this is an effective and robust tool for the identification of low-frequency resting-state patterns from data acquired at various different spatial and temporal resolutions. We show that these networks exhibit high spatial consistency across subjects and closely resemble discrete cortical functional networks such as visual cortical areas or sensory–motor cortex.
Amantadine in the Treatment of Parkinson's Disease (1969)

Sixty-six percent of a group of 163 patients with Parkinson's disease exhibited subjective or objective improvement of their akinesia, rigidity, and tremor while receiving amantadine hydrochloride. Of those showing improvement, benefits were sustained in 58% for a period of three to eight months. The maximum daily dose was 200 mg. Side effects occurred in 22% and consisted of increased jitteriness, insomnia, abdominal uneasiness, dizziness, depression, confusion, and, in a few cases, hallucinations. Convulsions have been reported with large doses of 800 mg per day. In most cases, side effects were controlled by adjustment of dosage of [ill] hydrochloride or the patient's concomitant medication.
High yield bacterial expression of active c‐Abl and c‐Src tyrosine kinases (2005)

The Abl and Src tyrosine kinases are key signaling proteins that are of considerable interest as drug targets in cancer and many other diseases. The regulatory mechanisms that control the activity of these proteins are complex, and involve large-scale conformational changes in response to phosphorylation and other modulatory signals. The success of the Abl inhibitor imatinib in the treatment of chronic myelogenous leukemia has shown the potential of kinase inhibitors, but the rise of drug resistance in patients has also shown that drugs with alternative modes of binding to the kinase are needed. The detailed understanding of mechanisms of protein-drug interaction and drug resistance through biophysical methods demands a method for the production of active protein on the milligram scale. We have developed a bacterial expression system for the kinase domains of c-Abl and c-Src, which allows for the quick expression and purification of active wild-type and mutant kinase domains by coexpression with the YopH tyrosine phosphatase. This method makes practical the use of isotopic labeling of c-Abl and c-Src for NMR studies, and is also applicable for constructs containing the SH2 and SH3 domains of the kinases.
nos-1 and nos-2, two genes related to Drosophila nanos, regulate primordial germ cell development and survival in Caenorhabditis elegans (1999)

In Drosophila, the posterior determinant nanos is required for embryonic patterning and for primordial germ cell (PGC) development. We have identified three genes in Caenorhabditis elegans that contain a putative zinc-binding domain similar to the one found in nanos, and show that two of these genes function during PGC development. Like Drosophila nanos, C. elegans nos-1 and nos-2 are not generally required for PGC fate specification, but instead regulate specific aspects of PGC development. nos-2 is expressed in PGCs around the time of gastrulation from a maternal RNA associated with P granules, and is required for the efficient incorporation of PGCs into the somatic gonad. nos-1 is expressed in PGCs after gastrulation, and is required redundantly with nos-2 to prevent PGCs from dividing in starved animals and to maintain germ cell viability during larval development. In the absence of nos-1 and nos-2, germ cells cease proliferation at the end of the second larval stage, and die in a manner that is partially dependent on the apoptosis gene ced-4. Our results also indicate that putative RNA-binding proteins related to Drosophila Pumilio are required for the same PGC processes as nos-1 and nos-2. These studies demonstrate that evolutionarily distant organisms utilize conserved factors to regulate early germ cell development and survival, and that these factors include members of the nanos and pumilio gene families.
Interfacial Effects on the Reinforcement Properties of Polymer−Organoclay Nanocomposites (1996)

Interfacial effects play a major role in the formation of organic polymer−smectite clay nanocomposites. As little 2 mol % Na+ cations on the exchange sites of a short-chain alkylammonium smectite clay completely inhibits exfoliation of the silicate nanolayers in an epoxy matrix.
Experimental demonstration of resonant interband tunnel diode with room temperature peak-to-valley current ratio over 100 (1993)

This letter reports a recent experiment on resonant interband tunneling (RIT) diodes and the measured room temperature peak-to-valley (P/V) current ratio of 104:1 which represents the highest P/V ratio ever reported in any tunneling device. The RIT diode studied in this work consists of an InGaAs/InAlAs double-quantum well system embedded in a pn junction structure grown on InP.
Reactive Oxygen Species Drives Myocardial Angiogenesis? (2006)

Neovascularization, the natural physiological process of formation of new blood vessels, is extremely important for ameliorating the function of the heart that undergoes ischemic stress. This process is potentially important for the treatment of ischemic heart and limb diseases, which includes formation of capillaries (angiogenesis) and collateral arteries. Ischemia or coronary artery occlusion induces vascular endothelial growth factor (VEGF) in the experimental rat myocardial infarction model, and this molecule encourages development of coronary collateral circulation and retention of the blood supply to the ischemic area. Restoration of the blood supply to the ischemic area prevents cardiomyocyte death and cardiac remodeling. Among the various triggers and enhancers of angiogenesis, hypoxic or ischemic preconditioning, as well as pharmacologic agents such as statin and resveratrol, have been identified as important stimuli for the induction of new vessel growth. It has already been demonstrated that the VEGF family and its receptor system is the fundamental regulator in the redox cell signaling of angiogenesis. This review article will focus on the role of reactive oxygen species in the process of myocardial angiogenesis.
Pharmacological properties of some aminoalkanolic derivatives of xanthone. (2001)

A series of appropriate aminoisopropanoloxy derivatives of 2-, 3- or 6-xanthone was synthesized and evaluated for anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole seizure threshold (ScMet) assays and for neurotoxicity (TOX). The most interesting result was the anticonvulsant activity of (+/-)-3-(2-propylamino)-1- [(2-methyl)-6-xanthonoxy]-2-propanol hydrochloride (10), which displayed anti-MES activity with a protective index (TD50/ED50) of 0.80. Some of the obtained compounds were also tested for their effect on the circulatory system (influence on the non-working heart perfusion, protection against adrenaline induced-arrhythmia) and acute toxicity.
Mapping of antigenic and functional epitopes on the alpha- and beta-subunits of two related mouse glycoproteins involved in cell interactions, LFA-1 and Mac-1. (1983)

Mouse Mac-1, a complement receptor-associated surface structure on macrophages, and LFA-1, a function-associated structure on lymphocytes, comprise a novel family of leukocyte differentiation antigens participating in adhesive cell interactions. Mac-1 and LFA-1 contain alpha-subunits of 170,000 and 180,000 Mr, respectively, and beta-subunits of 95,000 Mr noncovalently associated in alpha 1 beta 1 complexes. The structural relation between the alpha- and between the beta-subunits, and the location of functionally important sites on the molecules, have been probed with antibodies. Both non-cross-reactive and cross-reactive monoclonal antibodies (MAb) and antisera prepared to the purified molecules or the LFA-1 alpha-subunits were used. Reactivity with individual subunits was studied by immunoprecipitation after dissociation induced by high pH treatment, or by immunoblotting after SDS-PAGE. Cross-reactive epitopes on Mac-1 and LFA-1 were found to be present on the beta-subunits, which were immunologically identical. Non-cross-reactive epitopes that are distinctive for Mac-1 or LFA-1 were localized to the alpha-subunits. MAb to LFA-1 alpha-subunit epitopes inhibited CTL-mediated killing. Two MAb to Mac-1 alpha-subunit epitopes but not a third MAb to a spatially distinct alpha-epitope inhibited complement receptor function. Neither function was inhibited by a MAb binding to a common beta-subunit epitope. Therefore, sites of Mac-1 and LFA-1 involved in their respective adhesion-related functions, as well as distinctive structural features, have been localized to the alpha-subunits.
Information-seeking strategies of novices using a full-text electronic encyclopedia (1989)

An exploratory study was conducted of elementary school children searching a full-text electronic encyclopedia on CD-ROM. Twenty-eight third and fourth graders and 24 sixth graders conducted two assigned searches, one open-ended, the other one closed, after two demonstration sessions. Keystrokes captured by the computer and observer notes were used to examine user information-seeking strategies from a mental model perspective. Older searchers were more successful in finding required information, and took less time than younger searchers. No differences in total number of moves were found. Analysis of search patterns showed that novices used a heuristic, highly interactive search strategy. Searchers used sentence and phrase queries, indicating unique mental models for this search system. Most searchers accepted system defaults and used the AND connective in formulating queries. Transition matrix analyses showed that younger searchers generally favored query refining moves and older searchers favored examining title and text moves. Suggestions for system designers were made and future research questions were identified. © 1989 John Wiley & Sons, Inc.
Targeting voltage-gated sodium channels for pain therapy (2009)

Drugs inhibiting voltage-gated sodium channels have long been used as analgesics, beginning with the use of local anaesthetics for sensory blockade and then with the discovery that Nav-blocking anticonvulsants also have benefit for pain therapy. These drugs were discovered without knowledge of their molecular target, using traditional pharmacological methods, and their clinical utility is limited by relatively narrow therapeutic windows. Until recently, attempts to develop improved inhibitors using modern molecular-targeted screening approaches have met with limited success. However, in the last few years there has been renewed activity following the discovery of human Nav1.7 mutations that cause striking insensitivity to pain. Together with recent advances in the technologies required to prosecute ion channels as drug targets, this has led to significant progress being made. This article reviews these developments and summarises current findings with these emerging new Nav inhibitors, highlighting some of the unanswered questions and the challenges that remain before they can be developed for clinical use.
Interferon Resistance of Hepatitis C Virus Genotype 1b: Relationship to Nonstructural 5A Gene Quasispecies Mutations (1998)

A 40-amino-acid sequence located in the nonstructural 5A (NS5A) protein of hepatitis C virus genotype 1b (HCV-1b) was recently suggested to be the interferon sensitivity-determining region (ISDR), because HCV-1b strains with an ISDR amino acid sequence identical to that of the prototype strain HCV-J were found to be resistant to alpha interferon (IFN-alpha) whereas strains with amino acid substitutions were found to be sensitive (N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, N. Izumi, F. Marumo, and C. Sato, J. Clin. Invest. 96:224-230, 1995; N. Enomoto, I. Sakuma, Y. Asahina, M. Kurosaki, T. Murakami, C. Yamamoto, Y. Ogura, N. Izumi, F. Marumo, and C. Sato, N. Engl. J. Med. 334:77-81, 1996). We used single-strand conformation polymorphism (SSCP) analysis, combined with cloning and sequencing strategies, to characterize NS5A quasispecies in HCV-1b-infected patients and determine the relationships between pre- and posttreatment NS5A quasispecies mutations and the IFN-alpha sensitivity of HCV-1b. The serine residues involved in phosphorylation of NS5A protein were highly conserved both in the various patients and in quasispecies in a given patient, suggesting that phosphorylation is important in NS5A protein function. A hot spot for amino acid substitutions was found at positions 2217 to 2218; it could be the result of either strong selection pressure or tolerance to these amino acid replacements. The proportion of synonymous mutations was significantly higher than the proportion of nonsynonymous mutations, suggesting that genetic variability in the region studied was the result of high mutation rates and viral replication kinetics rather than of positive selection. Sustained HCV RNA clearance was associated with low viral load and low nucleotide sequence entropy, suggesting (i) that the replication kinetics when treatment is started plays a critical role in HCV-1b sensitivity to IFN-alpha and (ii) that HCV-1b resistance to IFN-alpha could be conferred by numerous and/or related mutations that could be patient specific and located at different positions throughout the viral genome and could allow escape variants to be selected by IFN-alpha-stimulated immune responses. No NS5A sequence appeared to be intrinsically resistant or sensitive to IFN-alpha, but the HCV-J sequence was significantly more frequent in nonresponder quasispecies than in sustained virological responder quasispecies, suggesting that the balance between NS5A quasispecies sequences in infected patients could have a subtle regulatory influence on HCV replication.
Antibiotic acyldepsipeptides activate ClpP peptidase to degrade the cell division protein FtsZ (2011)

The worldwide spread of antibiotic-resistant bacteria has lent urgency to the search for antibiotics with new modes of action that are devoid of preexisting cross-resistances. We previously described a unique class of acyldepsipeptides (ADEPs) that exerts prominent antibacterial activity against Gram-positive pathogens including streptococci, enterococci, as well as multidrug-resistant Staphylococcus aureus. Here, we report that ADEP prevents cell division in Gram-positive bacteria and induces strong filamentation of rod-shaped Bacillus subtilis and swelling of coccoid S. aureus and Streptococcus pneumoniae. It emerged that ADEP treatment inhibits septum formation at the stage of Z-ring assembly, and that central cell division proteins delocalize from midcell positions. Using in vivo and in vitro studies, we show that the inhibition of Z-ring formation is a consequence of the proteolytic degradation of the essential cell division protein FtsZ. ADEP switches the bacterial ClpP peptidase from a regulated to an uncontrolled protease, and it turned out that FtsZ is particularly prone to degradation by the ADEP-ClpP complex. By preventing cell division, ADEP inhibits a vital cellular process of bacteria that is not targeted by any therapeutically applied antibiotic so far. Their unique multifaceted mechanism of action and antibacterial potency makes them promising lead structures for future antibiotic development.
Extensions of recurrent neural network language model (2011)

We present several modifications of the original recurrent neural network language model (RNN LM).While this model has been shown to significantly outperform many competitive language modeling techniques in terms of accuracy, the remaining problem is the computational complexity. In this work, we show approaches that lead to more than 15 times speedup for both training and testing phases. Next, we show importance of using a backpropagation through time algorithm. An empirical comparison with feedforward networks is also provided. In the end, we discuss possibilities how to reduce the amount of parameters in the model. The resulting RNN model can thus be smaller, faster both during training and testing, and more accurate than the basic one.
Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder (2014)

Fasting ammonia correlates strongly and positively with daily ammonia exposure and with the risk and rate of hyperammonemic crises, suggesting that patients with urea cycle disorder may benefit from tight ammonia control.