gebhart/patrepeval huggingface dataset:
Role of heat shock proteins in the exercise response. (1999)

Heat shock proteins (HSP) are a characteristic set of highly conserved proteins that are synthesized shortly after the organism is exposed to external stress, including physical activity. HSP help to maintain cellular homeostasis and protein conformation, reactivate denatured or malformed proteins, and provide "housekeeping," translocase, and chaperone functions. Some of the conditions known to elicit the cellular stress reaction are similar to those experienced by cells in response to physical exercise. Hyperthermia, ischemia, oxidative, cytokine and muscular stress, glucose deprivation, and alterations in calcium and pH are potent inducers of HSP expression in different types of cells and tissues. This review provides an overview of the cellular heat shock response to exercise. The presently known exercise related HSP are introduced. Their possible roles in response to acute exercise, thermotolerance, adaptation to training, aging, and immunological reactions are discussed.
A novel method for rapid isolation of plasmid DNA. (1988)

A new disposable chromatographic column, pZ523, has been developed for separating plasmid DNA from bacterial chromosomal DNA. Use of pZ523 spun columns eliminates the need for ethidium bromide-cesium chloride density gradients which require long centrifugation times. pZ523 purified plasmids have been shown to be of purity suitable for restriction analysis, ligation, transfection of mammalian cells and transformation of bacteria. Unlike the traditional ultracentrifugation method, pZ523 offers an extremely rapid alternative method for purifying large amounts of plasmid DNA (2.5 mg to 4.5 mg) from cleared bacterial lysates in only 25 minutes.
Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by the Eastern Cooperative Oncology Group (E1996) (2009)

This phase 3 prospective randomized trial evaluated the efficacy and long-term safety of erythropoietin (EPO) with or without granulocyte colony-stimulating factor plus supportive care (SC; n = 53) versus SC alone (n = 57) for the treatment of anemic patients with lower-risk myelodysplastic syndromes. The response rates in the EPO versus SC alone arms were 36% versus 9.6%, respectively, at the initial treatment step, 47% in the EPO arm, including subsequent steps. Responding patients had significantly lower serum EPO levels (45% vs 5% responses for levels < 200 mU/mL vs > or = 200 mU/mL) and improvement in multiple quality-of-life domains. With prolonged follow-up (median, 5.8 years), no differences were found in overall survival of patients in the EPO versus SC arms (median, 3.1 vs 2.6 years) or in the incidence of transformation to acute myeloid leukemia (7.5% and 10.5% patients, respectively). Increased survival was demonstrated for erythroid responders versus nonresponders (median, 5.5 vs 2.3 years). Flow cytometric analysis showed that the percentage of P-glycoprotein(+) CD34(+) marrow blasts was positively correlated with longer overall survival. In comparison with SC alone, patients receiving EPO with or without granulocyte colony-stimulating factor plus SC had improved erythroid responses, similar survival, and incidence of acute myeloid leukemia transformation.
Discovery of 1,4-Disubstituted 3-Cyano-2-pyridones: A New Class of Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor (2012)

The discovery and characterization of compound 48, a selective and in vivo active mGlu2 receptor positive allosteric modulator (PAM), are described. A key to the discovery was the rational exploration of the initial HTS hit 13 guided by an overlay model built with reported mGlu2 receptor PAM chemotypes. The initial weak in vitro activity of the hit 13 was quickly improved, although compounds still had suboptimal druglike properties. Subsequent modulation of the physicochemical properties resulted in compounds having a more balanced profile, combining good potency and in vivo pharmacokinetic properties. Final refinement by addressing cardiovascular safety liabilities led to the discovery of compound 48. Besides good potency, selectivity, and ADME properties, compound 48 displayed robust in vivo activity in a sleep-wake electroencephalogram (sw-EEG) assay consistent with mGlu2 receptor activation, in accordance with previous work from our laboratories.
Enhanced optical properties in porous silicon microcavities (1995)

We report the experimental investigation of the optical properties of porous silicon embedded in a planar microcavity structure in which both the active layer and the two Bragg reflectors are fabricated by electrochemical processing of a p-type porous silicon wafer. By tuning the cavity resonance energy around the maximum of the porous silicon emission we have observed photoluminescence linewidths as narrow as 18--25 meV and an intensity enhancement of more than one order of magnitude. The experimental results are clarified by theoretical calculations performed with the standard transfer-matrix approach in the framework of a porous silicon quantum-box model.
From Sugar to Fat (2009)

Lipogenesis occurs primarily in the liver, where dietary carbohydrates control the expression of key enzymes in glycolytic and lipogenic pathways. We have recently discovered that the transcription factor XBP1, best known as a key regulator of the unfolded protein response (UPR), is required for de novo fatty acid synthesis in the liver, a function unrelated to its role in the UPR.(1) XBP1 protein expression is induced in the liver by a high carbohydrate diet and directly controls the induction of critical genes involved in fatty acid synthesis. Specific deletion of XBP1 in adult liver using an inducible approach results in profound hypocholesterolemia and hypotriglyceridemia, which could be attributed to diminished production of lipids in the liver. Notably, this phenotype is not associated with fatty liver (hepatic steatosis) or significant compromise in protein secretion. XBP1 joins an already rich field of transcriptional regulatory proteins in the control of hepatic lipogenesis. Its function in lipogenesis appears to be highly significant as evidenced by the phenotype of the genetic mutant strain. A more complete understanding of the mechanisms by which XBP1 accelerates de novo fatty acid synthesis in the liver while preserving normal hepatic lipid composition is highly relevant to the treatment of diseases such as atherosclerosis and metabolic syndrome that are associated with dyslipidemia. Since excess fat accumulation in the liver could result from increased hepatic fatty acid synthesis, compounds that inhibit XBP1 activation may also be useful therapeutics for the treatment of human alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), increasingly common causes of morbidity and mortality in the United States.
A novel suicide vector and its use in construction of insertion mutations: osmoregulation of outer membrane proteins and virulence determinants in Vibrio cholerae requires toxR (1988)

The toxR gene of Vibrio cholerae encodes a transmembrane, DNA-binding protein that activates transcription of the cholera toxin operon and a gene (tcpA) for the major subunit of a pilus colonization factor. We constructed site-directed insertion mutations in the toxR gene by a novel method employing the chromosomal integration of a mobilizable suicide plasmid containing a portion of the toxR coding sequence. Mutants containing these new toxR alleles had an altered outer membrane protein profile, suggesting that two major outer membrane proteins (OmpT and OmpU) might be under the control of toxR. Physiological studies indicated that varying the concentration of the amino acids asparagine, arginine, glutamate, and serine caused coordinate changes in the expression of cholera toxin, TcpA, OmpT, and OmpU. Changes in the osmolarity of a tryptone-based medium also produced coordinate changes in the expression of these proteins. Other environmental signals (temperature and pH) had a more pronounced effect on the expression of cholera toxin and TcpA than they did on the outer membrane proteins. These results suggest that certain environmental signals (i.e., osmolarity and the presence of amino acids) are tightly coupled to the expression of toxR-regulated proteins and therefore may be signals that are directly sensed by the ToxR protein.
Stem Cell Transplantation in Chronic Lymphocytic Leukemia (2009)

Chronic lymphocytic leukemia (CLL) remains incurable with standard therapy. Most patients with CLL have an indolent clinical course, but it is possible to identify patients with high-risk disease. Younger patients with adverse risk factors will die from their disease, and are therefore candidates for clinical trials exploring hematopoietic stem cell transplantation (HSCT). Autologous SCT is feasible and has low treatment-related mortality (TRM); but it is not curative. Myeloablative allogeneic SCT is associated with high treatment-related mortality and, TRM few late relapses, but is applicable to only a small number of CLL patients. The major focus of SCT in CLL has been with reduced-intensity conditioning (RIC) allogeneic SCT, which is applicable to the more elderly patient population with this disease and which attempts to exploit the graft-versus-leukemia (GVL) effect that exists in CLL. Steps to further decrease the morbidity and mortality of the RIC SCT, and, in particular, to reduce the incidence of extensive chronic graft-versus-host disease (cGVHD) remain the major focus. Many potential treatments are available for CLL, and appropriate patient selection and the timing of SCT remain controversial and the focus of ongoing clinical trials. The use of SCT must always be weighed against the risk of the underlying disease, particularly in a setting where improvements in treatment are leading to improved outcome.
OBJECT MOTION IDENTIFICATION FOR OBJECT RECOGNITION (1990)

This review describes current methods of protein immunoanalysis: radioimmunoanalysis, ELISA, immuno-PCR, electrochemical analysis and chromatin immunoprecipitation, as well as main areas of their application.
Luminescence of nanocrystalline ZnSe:Cu (2001)

A chemical synthesis is described in which ZnSe:Cu particles slowly grow to a final size of ∼3.5 nm radius in 4 h reaction time. During particle growth, samples are extracted to study the luminescence as a function of particle size and temperature. Quantum size effects are observed to influence both the ZnSe and the Cu2+ luminescence. Temperature-dependent measurements on the luminescence intensity, lifetime, and peak positions are reported and discussed.
Molecular basis of MAP kinase regulation (2013)

Mitogen-activated protein kinases (MAPKs; ERK1/2, p38, JNK, and ERK5) have evolved to transduce environmental and developmental signals (growth factors, stress) into adaptive and programmed responses (differentiation, inflammation, apoptosis). Almost 20 years ago, it was discovered that MAPKs contain a docking site in the C-terminal lobe that binds a conserved 13-16 amino acid sequence known as the D- or KIM-motif (kinase interaction motif). Recent crystal structures of MAPK:KIM-peptide complexes are leading to a precise understanding of how KIM sequences contribute to MAPK selectivity. In addition, new crystal and especially NMR studies are revealing how residues outside the canonical KIM motif interact with specific MAPKs and contribute further to MAPK selectivity and signaling pathway fidelity. In this review, we focus on these recent studies, with an emphasis on the use of NMR spectroscopy, isothermal titration calorimetry and small angle X-ray scattering to investigate these processes.
Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes. (1990)

fms genes encoding either wild-type or constitutively activated colony-stimulating factor 1 receptors (CSF-1R) were introduced by retroviral infection into long-term mouse lymphoid cultures. Four early pre-B-cell lines transformed by the feline v-fms oncogene underwent spontaneous and irreversible differentiation to macrophages when transferred from RPMI 1640 to Iscove modified Dulbecco medium. Expression of wild-type human CSF-1R in early pre-B cells conferred no proliferative advantage unless human CSF-1 was added to the culture medium. A clonal, factor-dependent early pre-B-cell line (D1F9), selected for continuous growth on NIH 3T3 cell feeder layers producing human CSF-1, could be maintained in RPMI 1640 medium containing interleukin-7 (IL-7) but also differentiated to macrophages when grown in Iscove modified Dulbecco medium containing human CSF-1. The macrophages retained parental immunoglobulin gene rearrangements and proviral insertions, lost B-cell antigens, expressed butyrate esterase and MAC-1, were actively phagocytic, and no longer survived in IL-7. Unlike factor-independent v-fms transformants, the irreversible commitment of D1F9 cells to differentiate in the macrophage lineage could be suppressed by IL-7, depended on human (but not mouse) CSF-1, and was inhibited by an antibody to human CSF-1R. Signals mediated by transduced CSF-1R can therefore play a deterministic role in cell differentiation.
Effective sounds in complex systems (1991)

We designed an ecology of auditory icons which worked together to convey information about a complex, demanding simulation task, and observed users collaborating on it with and without sound. Our observations suggest that audio cues can provide useful information about processes and problems, and support the perceptual integration of a number of separate processes into one complex one. In addition, they can smooth the transition between division of labour and collaboration by providing a new dimension of reference. These results suggest that auditory icons can play a significant role in future multiprocessing and collaborative systems.
Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers (1999)

Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.
Identification of Functionally Important Domains in the N-Terminal Region of Telomerase Reverse Transcriptase (2000)

Telomerase is a ribonucleoprotein reverse transcriptase responsible for the maintenance of one strand of telomere terminal repeats. The key protein subunit of the telomerase complex, known as TERT, possesses reverse transcriptase-like motifs that presumably mediate catalysis. These motifs are located in the C-terminal region of the polypeptide. Hidden Markov model-based sequence analysis revealed in the N-terminal region of all TERTs the presence of four conserved motifs, named GQ, CP, QFP, and T. Point mutation analysis of conserved residues confirmed the functional importance of the GQ motif. In addition, the distinct phenotypes of the GQ mutants suggest that this motif may play at least two distinct functions in telomere maintenance. Deletion analysis indicates that even the most N-terminal nonconserved region of yeast TERT (N region) is required for telomerase function. This N region exhibits a nonspecific nucleic acid binding activity that probably reflects an important physiologic function. Expression studies of various portions of the yeast TERT in Escherichia coli suggest that the N region and the GQ motif together may constitute a stable domain. We propose that all TERTs may have a bipartite organization, with an N-GQ domain connected to the other motifs through a flexible linker.
The design of the 88000 RISC family (1989)

The design and implementation of the RISC (reduced-instruction-set computer) 88000 system in high-speed, complementary metal-oxide semiconductor (HCMOS) technology is described. The total system consists of the 88100 processor and two 88200 cache memory management units (CMMUs). The various features and components of the 88000 are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An update on sleep disorders and their treatment (2010)

Abstract Over the past year, Progress in Neurology and Psychiatry has been running a series of articles on the major psychiatric drug groups, produced in association with the College of Mental Health Pharmacy. In the final article in the series, Michele Sie describes the main types of sleep disorder and their features, and provides an overview of their treatment. Copyright © 2010 Wiley Interface Ltd
Spline Neural Networks for Blind Separation of Post-Nonlinear-Linear Mixtures (2004)

In this paper, a novel paradigm for blind source separation in the presence of nonlinear mixtures is presented. In particular, the paper addresses the problem of post-nonlinear mixing followed by another instantaneous mixing system. This model is called here the post-nonlinear-linear model. The method is based on the use of the recently introduced flexible activation function whose control points are adaptively changed: a neural model based on adaptive B-spline functions is employed. The signal separation is achieved through an information maximization criterion. Experimental results and comparison with existing solutions confirm the effectiveness of the proposed architecture.
Reduced Secondary Cytokine Induction by BAY 50-4798, a High-Affinity Receptor-Specific Interleukin-2 Analog (2006)

Recombinant interleukin-2 (IL-2) (aldesleukin, Proleukin, Chiron, Emeryville, CA) is approved for treatment of cancer patients and under investigation in HIV-infected individuals. However, treatment with aldesleukin is associated with toxicity, which may be due to its elicitation of inflammatory mediators from cells that express the intermediate-affinity IL-2 receptor. BAY 50-4798, a novel IL-2 analog, is a selective agonist for the high-affinity receptor. It induces the proliferation of activated T cells with a potency similar to that of aldesleukin but has reduced activity on cells expressing the intermediate-affinity receptor. In the current study, we compared cytokine responses elicited in peripheral blood mononuclear cell (PBMC) cultures stimulated with BAY 50-4798 or aldesleukin. BAY 50-4798 induced approximately 5-fold lower mean levels of endogenous IL-2 than aldesleukin, and at least 50% lower levels of proinflammatory cytokines, such as tumor necrosis fctor-alpha (TNF-alpha), IL-1beta, IL-6, and interferon-gamma (IFN-gamma). Furthermore, statistically significant reductions in the levels of IL-5, IL-8, IL-10, IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were observed in response to BAY 50-4798. These findings increase our understanding of the biologic action of BAY 50-4798 and suggest a mechanism by which it may exhibit better safety than aldesleukin in humans.
Analyzing a Portion of the ROC Curve (1989)

The area under the ROC curve is a common index summarizing the information contained in the curve. When comparing two ROC curves, though, problems arise when interest does not lie in the entire range of false-positive rates (and hence the entire area). Numerical integration is suggested for evaluating the area under a portion of the ROC curve. Variance estimates are derived. The method is applicable for either continuous or rating scale binormal data, from independent or dependent samples. An example is presented which looks at rating scale data of computed tomographic scans of the head with and without concomitant use of clinical history. The areas under the two ROC curves over an a priori range of false-positive rates are examined, as well as the areas under the two curves at a specific point.
Photochromic Spiropyrans. I. The Effect of Substituents on the Rate of Ring Closure (1959)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochromic Spiropyrans. I. The Effect of Substituents on the Rate of Ring ClosureElliot Berman, Richard E. Fox, and Francis D. ThomsonCite this: J. Am. Chem. Soc. 1959, 81, 21, 5605–5608Publication Date (Print):November 1, 1959Publication History Published online1 May 2002Published inissue 1 November 1959https://doi.org/10.1021/ja01530a021RIGHTS & PERMISSIONSArticle Views974Altmetric-Citations103LEARN 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 InReddit PDF (445 KB) Get e-Alerts Get e-Alerts
Site-directed mutagenesis of arginine 103 and lysine 185 in the proposed glycosaminoglycan-binding site of heparin cofactor II. (1990)

Inhibition of thrombin by heparin cofactor (HCII) is accelerated approximately 1000-fold by heparin or dermatan sulfate. We found recently that the mutation Arg189----His decreases the affinity of HCII for dermatan sulfate but not for heparin (Blinder, M. A., Andersson, T. R., Abildgaard, U., and Tollefsen, D. M. (1989) J. Biol. Chem. 264, 5128-5133). Other investigators have implicated Arg47 and Lys125 of anti-thrombin (homologous to Arg103 and Lys185 of HCII) in heparin binding. To investigate the corresponding residues in HCII, we have constructed amino acid substitutions (Arg103----Leu, Gln, or Trp; Lys185----Met, Asn, or Thr) by oligonucleotide-directed mutagenesis of the cDNA and expressed the products in Escherichia coli. The recombinant HCII variants were assayed for binding to heparin-Sepharose and for inhibition of thrombin in the presence of various concentrations of heparin or dermatan sulfate. All of the Arg103 variants bound to heparin with normal affinity. Furthermore, inhibition of thrombin by the Arg103----Leu variant occurred at a normal rate in the absence of a glycosaminoglycan and was accelerated by normal concentrations of heparin and dermatan sulfate. These results indicate that HCII, unlike anti-thrombin, does not require a positive charge at this position for the interaction with heparin or dermatan sulfate. The Arg103----Gln and Arg103----Trp variants inhibited thrombin at about one-third of the normal rate in the absence of a glycosaminoglycan, suggesting that these mutations exert an effect on the reactive site (Leu444-Ser445) of HCII. All of the Lys185 variants bound to heparin with decreased affinity but inhibited thrombin at approximately the normal rate in the absence of a glycosaminoglycan. These variants required greater than 10-fold higher concentrations of heparin to accelerate inhibition of thrombin and were not stimulated significantly by dermatan sulfate, suggesting that heparin and dermatan sulfate interact with Lys185 of HCII. These results provide evidence that the glycosaminoglycan-binding site in HCII includes Lys185 but not Arg103, both of which were predicted to be involved by homology to anti-thrombin.