gebhart/patrepeval huggingface dataset:
Hepatitis C virus non-structural protein NS4B can modulate an unfolded protein response. (2005)

Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing alpha-mannosidase-like protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.
Identification, cloning, and characterization of an immune activation gene. (1988)

We have identified an immune activation gene, denoted Act-2, by differential hybridization screening of an activated T-cell library. The gene is induced rapidly after T-cell activation with phytohemagglutinin, B-cell activation with Staphylococcus aureus Cowan I, and monocyte activation with lipopolysaccharide. We have isolated a cDNA containing the full-length coding region. The deduced amino acid sequence predicts an open reading frame of 92 amino acids, including a very hydrophobic N terminus, which by weight matrix score is predicted to be a signal peptide. Using a baculovirus expression system, we have shown that this gene encodes a secreted product. It is therefore possible that Act-2 represents a newly discovered cytokine.
Nanometer Silica Particles Encapsulating Active Compounds:  A Novel Ceramic Drug Carrier (1998)

Novel, injectable, and sprayable nanometer size hydrated silica particles encapsulating high molecular weight compounds such as [125I]tyraminylinulin (mol wt 5 kD), FITC-dextran (mol wt 19.6 kD), and horse radish peroxidase (mol wt 40 kD) have been prepared and characterized. The size of these particles is always below 100 nm in diameter and the entrapment efficiency was found to be as high as 80%. The entrapped compounds show practically zero leachability for more than 45 days. Enzymes entrapped in these particles show Michaelis−Menten kinetics and the catalytic reaction takes place only after the diffusion of substrate molecules into the particles through the pores of the silica matrix. Peroxidase entrapped into silica nanoparticles shows higher stability toward temperature and pH changes compared to free enzyme molecules.
Improved Perioperative Antibiotic Use and Reduced Surgical Wound Infections Through Use of Computer Decision Analysis (1989)

A prospective study was performed over a two-year period to determine whether computer-generated reminders of perioperative antibiotic use could improve prescribing habits and reduce postoperative wound infections. During the first year, baseline patterns of antibiotic use and postoperative infection rates were established. During the second year, computer-generated reminders regarding perioperative antibiotic use were placed in the patient's medical record prior to surgery and patterns of antibiotic use and postoperative wound infections monitored. Hospitalized patients undergoing non-emergency surgery from June to November 1985 (3,263 patients), and from June to November 1986 (3,568) were monitored with respect to indications for perioperative antibiotic use, timing of antibiotic use and postoperative infectious complications. Perioperative antibiotic use was considered advisable for 1,621 (50%) patients in the 1985 sample and for 1,830 (51%) patients in the 1986 sample. Among these patients, antibiotics were given within two hours before the surgical incision in 638 (40%) of the 1985 sample and 1,070 (58%) of the 1986 sample (p less than 0.001). Overall, postoperative wound infections were detected in 28 (1.8%) of 1,621 patients in 1985 compared with 16 (0.9%) of 1,830 such patients in 1986 (p less than 0.03). We conclude that computer-generated reminders of perioperative antibiotic use improved prescribing habits with a concurrent decline in postoperative wound infections.
Helpful hints in flow cytometry and sorting (1985)

Most users of flow cytometers and sorters become proficient in their use through direct operation of the instruments. There are no text books or operation manuals that describe all of the problems that will be encountered and that may not be apparent. We have discovered many of these problems through finding an explanation for unexpected data and in resolving difficulties in achieving and maintaining high resolution and stable operation of the instruments. This paper presents a summary of problems encountered and solutions found at this laboratory and others.
Rituximab: an insider's historical perspective. (2000)

Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a unique monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human antibody was discovered in 1991 at IDEC Pharmaceuticals' laboratories, where the antibody was genetically engineered and produced utilizing high-yield expression systems. It is a human IgG1 kappa antibody with mouse variable regions isolated from a murine anti-CD20 antibody, IDEC-2B8, that binds with high affinity to cells expressing the CD20 antigen found on the surface of malignant and normal B cells, but not on other normal tissues. It mediates complement-dependent cell lysis in the presence of human complement, and antibody-dependent cellular cytotoxicity with human effector cells. Also, it has been shown to induce apoptosis and to sensitize chemoresistant human lymphoma cell lines in vitro. Clinical development was expedited (3 years) with the first patient entered in phase I trials in March 1993 and the last patient entered in the phase III study in March 1996. IDEC Pharmaceuticals began a collaboration with Genentech, Inc in March 1995 and with F. Hoffman-LaRoche (Nutley, NJ) shortly thereafter. Marketing approval was granted by the US Food and Drug Administration on November 26, 1997 (and by the European Union on June 2, 1998) for the indication of relapsed or refractory, CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma. Rituximab is the first therapeutic monoclonal antibody approved for the treatment of cancer and the first single agent approved specifically for therapy for a lymphoma. Substantial research has been performed over the past 8 years to further the understanding of this novel therapeutic. Nevertheless, much remains to be accomplished in key areas such as mechanism of action and resistance, combinations with chemotherapy, biologics and radiotherapy/radioimmunotherapy, role within multimodality regimens, and nonmalignant applications. Research conducted in the coming years should be targeted toward resolving these important issues.
Pharmacological uses and perspectives of heavy water and deuterated compounds (1999)

Since the discovery of D20 (heavy water) and its use as a moderator in nuclear reactors, its biological effects have been extensively, although seldom deeply, studied. This article reviews these effects on whole animals, animal cells, and microorganisms. Both "solvent isotope effects," those due to the special properties of D20 as a solvent, and "deuterium isotope effects" (DIE), which result when D replaces H in many biological molecules, are considered. The low toxicity of D20 toward mammals is reflected in its widespread use for measuring water spaces in humans and other animals. Higher concentrations (usually >20% of body weight) can be toxic to animals and animal cells. Effects on the nervous system and the liver and on formation of different blood cells have been noted. At the cellular level, D20 may affect mitosis and membrane function. Protozoa are able to withstand up to 70% D20. Algae and bacteria can adapt to grow in 100% D2O and can serve as sources of a large number of deuterated molecules. D2O increases heat stability of macromolecules but may decrease cellular heat stability, possibly as a result of inhibition of chaperonin formation. High D2O concentrations can reduce salt- and ethanol-induced hypertension in rats and protect mice from gamma irradation. Such concentrations are also used in boron neutron capture therapy to increase neutron penetration to boron compounds bound to malignant cells. D2O is more toxic to malignant than normal animal cells, but at concentrations too high for regular therapeutic use. D2O and deuterated drugs are widely used in studies of metabolism of drugs and toxic substances in humans and other animals. The deuterated forms of drugs often have different actions than the protonated forms. Some deuterated drugs show different transport processes. Most are more resistant to metabolic changes, especially those changes mediated by cytochrome P450 systems. Deuteration may also change the pathway of drug metabolism (metabolic switching). Changed metabolism may lead to increased duration of action and lower toxicity. It may also lead to lower activity, if the drug is normally changed to the active form in vivo. Deuteration can also lower the genotoxicity of the anticancer drug tamoxifen and other compounds. Deuteration increases effectiveness of long-chain fatty acids and fluoro-D-phenylalanine by preventing their breakdown by target microorganisms. A few deuterated antibiotics have been prepared, and their antimicrobial activity was found to be little changed. Their action on resistant bacteria has not been studied, but there is no reason to believe that they would be more effective against such bacteria. Insect resistance to insecticides is very often due to insecticide destruction through the cytochrome P450 system. Deuterated insecticides might well be more effective against resistant insects, but this potentially valuable possibility has not yet been studied.
Systemic abnormalities of psoriatic patients: a retrospective study (2016)

This study is the first report in relation to a detailed assessment of systemic abnormalities in psoriatic patients prior to onset of systemic treatment. The systemic condition of psoriatic patients should be observed by clinicians before systemic therapy.
Bioabsorbable metal stents for percutaneous treatment of critical recoarctation of the aorta in a newborn (2006)

In neonates and infants with critical aortic coarctation, balloon angioplasty is considered for rescue therapy of heart failure. The use of conventional stents is limited because of further vessel growth, the need of redilation, and later surgical removal. However, a novel bioabsorbable magnesium stent (AMS) might overcome such restrictions of vessel stenting in newborns. Presented is the first use of an AMS for acute treatment of a newborn with severely impaired heart function due to a long segment recoarctation after a complex surgical repair. We hypothesize that bioabsorbable stents will dramatically change the treatment of coarctation and recoarctation in newborns.
Enzyme replacement therapy for murine mucopolysaccharidosis type VII. (1994)

Recombinant mouse beta-glucuronidase administered intravenously to newborn mice with mucopolysaccharidosis type VII (MPS VII) is rapidly cleared from the circulation and localized in many tissues. Here we determine the tissue distribution of injected enzyme and describe its effects on the histopathology in 6-wk-old MPS VII mice that received either one injection of 28,000 U recombinant beta-glucuronidase at 5 wk of age or received six injections of 28,000 U given at weekly intervals beginning at birth. These mice were compared with untreated 6-wk-old MPS VII mice. The single injection decreased lysosomal distention in the fixed tissue macrophage system. MPS VII mice that received multiple injections had 27.8, 3.5, and 3.3% of normal levels of beta-glucuronidase in liver, spleen, and kidney, respectively. Brain had detectable beta-glucuronidase, ranging from 2.0-12.1% of normal. Secondary elevations of alpha-galactosidase and beta-hexosaminidase in brain, spleen, liver, and kidney were decreased compared with untreated MPS VII mice. Although no improvement was observed in chondrocytes, glia, and some neurons, the skeleton had less clinical and pathological evidence of disease and the brain had reduced lysosomal storage in meninges and selected neuronal groups. These data show that recombinant beta-glucuronidase treatment begun in newborn MPS VII mice provides enzyme to most tissues and significantly reduces or prevents the accumulation of lysosomal storage during the first 6 wk of life. Whether therapy begun later in life can achieve this level of correction remains to be established.
Relationship between exposure to tobacco smoke and bronchial asthma in children: a review. (1998)

Asthma is a common chronic childhood disease yet not much is known about factors that determine its outcome. Cigarette smoke has been associated with lung cancer in adults but its effects on children has hitherto been underestimated and not well studied. Cigarette smoke has been noted through various research studies to influence the development and or the exacerbation of asthma in childhood. Furthermore the prevalence of childhood asthma is higher among the children of smoking parents, more so when both parents are smokers as compared to those of non-smoking parents. Corroborative evidence indicates elevated urine cotinine levels amongst children of smoking parents than those of non-smoking parents. There is a corresponding increase in prevalence and exacerbation of asthma symptoms among children with raised urine cotinine levels than those with low levels. The presence of other risk factors increases the risk of development and exacerbation of bronchial asthma in children exposed to tobacco smoke than those not exposed. Cigarette smoking is on the increase, especially in developing countries due to aggressive advertising and exportation by the tobacco industry from developed countries. International legislation is needed to regulate the production and exportation of tobacco products. However, this may be resisted by the influential tobacco industry and may not get the support from the developing countries due to economic gains from the sale of tobacco products. This scenario poses major health problems for the developing countries in the future.
Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation (1998)

Dendritic cells (DC) migrate into inflamed peripheral tissues where they capture antigens and, following maturation, to lymph nodes where they stimulate T cells. To gain insight into this process we compared chemokine receptor expression in immature and mature DC. Immature DC expressed CCR1, CCR2, CCR5 and CXCR1 and responded to their respective ligands, which are chemokines produced at inflammatory sites. Following stimulation with LPS or TNF-alpha maturing DC expressed high levels of CCR7 mRNA and acquired responsiveness to the CCR7 ligand EBI1 ligand chemokine (ELC), a chemokine produced in lymphoid organs. Maturation also resulted in up-regulation of CXCR4 and down-regulation of CXCR1 mRNA, while CCR1 and CCR5 mRNA were only marginally affected for up to 40 h. However, CCR1 and CCR5 were lost from the cell surface within 3 h, due to receptor down-regulation mediated by chemokines produced by maturing DC. A complete down-regulation of CCR1 and CCR5 mRNA was observed only after stimulation with CD40 ligand of DC induced to mature by LPS treatment. These different patterns of chemokine receptors are consistent with "inflammatory" and "primary response" phases of DC function.
Specific Inhibition of Nuclear RNA Polymerase II by α-Amanitin (1970)

alpha-Amanitin, a toxic substance from the mushroom Amanita phalloides, is a potent inhibitor of DNA-dependent RNA polymerase II (the nucleoplasmic form) from sea urchin, rat liver, and calf thymus. This compound exerts no effect on the activity of polymerase I (nucleolar form) or polymerase III (also nucleoplasmic). The inhibition is due to a specific interaction with polymerase II or with a complex of DNA and polymerase II.
Neural GPUs Learn Algorithms (2015)

Learning an algorithm from examples is a fundamental problem that has been widely studied. Recently it has been addressed using neural networks, in particular by Neural Turing Machines (NTMs). These are fully differentiable computers that use backpropagation to learn their own programming. Despite their appeal NTMs have a weakness that is caused by their sequential nature: they are not parallel and are are hard to train due to their large depth when unfolded. We present a neural network architecture to address this problem: the Neural GPU. It is based on a type of convolutional gated recurrent unit and, like the NTM, is computationally universal. Unlike the NTM, the Neural GPU is highly parallel which makes it easier to train and efficient to run. An essential property of algorithms is their ability to handle inputs of arbitrary size. We show that the Neural GPU can be trained on short instances of an algorithmic task and successfully generalize to long instances. We verified it on a number of tasks including long addition and long multiplication of numbers represented in binary. We train the Neural GPU on numbers with upto 20 bits and observe no errors whatsoever while testing it, even on much longer numbers. To achieve these results we introduce a technique for training deep recurrent networks: parameter sharing relaxation. We also found a small amount of dropout and gradient noise to have a large positive effect on learning and generalization.
Experimental Streptococcus pneumoniae infection in mice for studying correlation of in vitro and in vivo activities of penicillin against pneumococci with various susceptibilities to penicillin (1995)

The purpose of the study was to investigate the correlation of in vitro activity with the in vivo effect and the pharmacokinetics of penicillin in the treatment of infections with pneumococci with various susceptibilities to penicillin. We used 10 pneumococcal strains for which penicillin MICs ranged from 0.016 to 8 micrograms/ml. Time-kill curve experiments were performed with all strains. We found that the effect of penicillin in vitro is concentration independent, with a maximum effect at two to four times the MIC for penicillin-susceptible as well as penicillin-resistant pneumococci. The mouse peritonitis model with an inoculum of approximately 10(6) CFU, to which mucin was added, resulted in a reproducible lethal infection with the pneumococci. The 50% effective dose was determined for each strain, and we found a highly significant correlation between the log MIC and the log 50% effective dose of penicillin against these strains (P < 0.01). Furthermore, it was shown that the most important pharmacokinetic parameter determining the effect of penicillin in vivo was the time that the concentration of penicillin in serum was greater than the MIC.
Mucosal Immunity in Asthma and Chronic Obstructive Pulmonary Disease: A Role for Immunoglobulin A? (2004)

Despite our knowledge on the role of IgA in mucosal homeostasis and host defense and clinical evidence suggesting deficient first-line defense mechanisms in chronic airway disorders, little is known regarding its role in asthma and chronic obstructive pulmonary disease (COPD). Studies suggest that the mucosal IgA response is impaired in COPD, and a deficient transport of IgA across the bronchial epithelium in COPD has been identified, possibly involving neutrophil proteinases, which may degrade the Ig receptor mediating this transepithelial routing. In contrast, the IgA response to allergens in patients with asthma may play a pathogenic role through eosinophil activation. Thus, secretory IgA can induce eosinophil degranulation in vitro, a feature in keeping with the correlations observed in vivo between airway IgA levels and eosinophil cationic protein during late asthmatic responses. Selective IgA deficiency is associated with an increased prevalence of atopy, and a protective role of IgA has been seen in murine models of asthma, delineating the complexity of the IgA system in the airway mucosa. Future studies will hopefully yield better knowledge of IgA biology and lung mucosal immunity and help to use more efficiently the mucosal route for immunotherapy or target specific genes in inflamed airways.
Molecular Population Genetics ofXdhand the Evolution of Base Composition in Drosophila (2002)

Few loci have been measured for DNA polymorphism and divergence in several species. Here we report such data from the protein-coding region of xanthine dehydrogenase (Xdh) in 22 species of Drosophila. Many of our samples were from closely related species, allowing us to confidently assign substitutions to individual lineages. Surprisingly, Xdh appears to be fixing more A/T mutations than G/C mutations in most lineages, leading to evolution of higher A/T content in the recent past. We found no compelling evidence for selection on protein variation, though some aspects of the data support the notion that a significant fraction of amino acid polymorphisms are slightly deleterious. Finally, we found no convincing evidence that levels of silent heterozygosity are associated with rates of protein evolution.
Digital-Analog-Hybrid Neural Simulator: A Design-Aid For Custom-VLSI Neurochips (1989)

A high speed neural network simulator and its use for the dynamics and performance analysis of feedback neural architectures are described. The simulator is based on a semi-parallel, analog-digital hybrid architecture which utilizes digital memories to store synaptic weights and analog hardware for high speed computation. A breadboard system with 8-bit gray scale synapses, designed and built at JPL, is successfully serving as a valuable design test-bed for the development of fully parallel, analog, custom VLSI neurochips, currently underway at JPL. The breadboard hybrid simulator indeed allows a detailed evaluation of hardware potential and limitations in implementing full analog operations in such chips. As an example, the paper presents an analysis of the stability and convergence behavior of a feedback neural network applied to the &quot;Concentrator Assignment Problem&quot; in combinatorial optimization, as studied on the analog-digital hybrid simulator. This has already resulted in a VLSI custom design of a fully parallel, analog neuroprocessor with a powerful &quot;analog prompting&quot; feature, for the high-speed, multiparameter optimization function.
A voltage gradient‐induced arrest of circular DNA during agarose gel electrophoresis (1987)

Abstract During the gel electrophoresis of double‐stranded DNA, interaction with the gel fractionates the DNA by molecular weight and conformation. Here, it is shown that open circular bacteriophage λ DNA ( M r 32.1 × 10 6 ) migrates into a 0.2% agarose gel during a first electrophoresis at 0.34 V/cm, but does not migrate when the voltage gradient is subsequently raised to 6.0 V/cm for a second, orthogonal electrophoresis. Linear DNA of the same molecular weight does migrate at 6.0 V/cm. The data suggest that the arrest observed at 6.0 V/cm is caused by threading of circular DNA by gel fibers. These observations have produced a procedure of two‐dimensional agarose gel electrophoresis capable of detecting comparatively small amounts of circular DNA. The concept of threading is potentially useful for understanding of DNA fractionations obtained with pulsed electrical fields.