gebhart/patrepeval huggingface dataset:
Brain‐Derived Neurotrophic Factor Induces Excitotoxic Sensitivity in Cultured Embryonic Rat Spinal Motor Neurons Through Activation of the Phosphatidylinositol 3‐Kinase Pathway (2000)

Neurotrophic factors (NTFs) can protect against or sensitize neurons to excitotoxicity. We studied the role played by various NTFs in the excitotoxic death of purified embryonic rat motor neurons. Motor neurons cultured in brain-derived neurotrophic factor, but not neurotrophin 3, glial-derived neurotrophic factor, or cardiotrophin 1, were sensitive to excitotoxic insult. BDNF also induces excitotoxic sensitivity (ES) in motor neurons when BDNF is combined with these other NTFs. The effect of BDNF depends on de novo protein and mRNA synthesis. Reagents that either activate or inhibit the 75-kDa NTF receptor p75NTR do not affect BDNF-induced ES. The low EC50 for BDNF-induced survival and ES suggests that TrkB mediates both of these biological activities. BDNF does not alter glutamate-evoked rises of intracellular Ca2+, suggesting BDNF acts downstream. Both wortmannin and LY294002, which specifically block the phosphatidylinositol 3-kinase (PI3K) intracellular signaling pathway in motor neurons, inhibit BDNF-induced ES. We confirm this finding using a herpes simplex virus (HSV) that expresses the dominant negative p85 subunit of PI3K. Infecting motor neurons with this HSV, but not a control HSV, blocks activation of the PI3K pathway and BDNF-induced ES. Through the activation of TrkB and the PI3K signaling pathway, BDNF renders developing motor neurons susceptible to glutamate receptor-mediated cell death.
Recent advances in liquid-phase combinatorial chemistry. (1999)

In combination with high throughput screening, combinatorial organic synthesis of large numbers of pharmaceutically interesting compounds may revolutionize the drug discovery process. Although combinatorial organic synthesis on solid supports is a useful approach, several groups are focusing their research efforts on liquid-phase combinatorial synthesis by the use of soluble polymer supports to generate libraries. This macromolecular carrier, in contrast to an insoluble matrix, is soluble in most organic solvents and has a strong tendency for precipitation in particular solvents. Liquid-phase combinatorial synthesis is a unique approach since homogeneous reaction conditions can be applied, but product purification similar to the solid-phase method can be carried out by simple filtration and washing. This method combines the positive aspects of classical solution-phase chemistry and solid-phase synthesis. This review examines the recent applications (1995-1999) of soluble polymer supports in the synthesis of combinatorial libraries.
Dual Transforming Activities of the FUS (TLS)-ERG Leukemia Fusion Protein Conferred by Two N-Terminal Domains of FUS (TLS) (1999)

The FUS (TLS)-ERG chimeric protein associated with t(16;21)(p11;q22) acute myeloid leukemia is structurally similar to the Ewing's sarcoma chimeric transcription factor EWS-ERG. We found that both FUS-ERG and EWS-ERG could induce anchorage-independent proliferation of the mouse fibroblast cell line NIH 3T3. However, only FUS-ERG was able to inhibit the differentiation into neutrophils of a mouse myeloid precursor cell line L-G and induce its granulocyte colony-stimulating factor-dependent growth. We constructed several deletion mutants of FUS-ERG lacking a part of the N-terminal FUS region. A deletion mutant lacking the region between amino acids 1 and 173 (exons 1 to 5) lost the NIH 3T3-transforming activity but retained the L-G-transforming activity. On the other hand, a mutant lacking the region between amino acids 174 and 265 (exons 6 and 7) lost the L-G-transforming activity but retained the NIH 3T3-transforming activity. These results indicate that the N-terminal region of FUS contains two independent functional domains required for the NIH 3T3 and L-G transformation, which we named TR1 and TR2, respectively. Although EWS intrinsically possessed the TR2 domain, the EWS-ERG construct employed lacked the EWS sequence containing this domain. Since the TR2 domain is always found in chimeric proteins identified from t(16;21) leukemia patients but not in chimeric proteins from Ewing's sarcoma patients, it seems that the TR2 function is required only for the leukemogenic potential. In addition, we identified three cellular genes whose expression was altered by ectopic expression of FUS-ERG and found that these are regulated in either a TR1-dependent or a TR2-dependent manner. These results suggest that FUS-ERG may activate two independent oncogenic pathways during the leukemogenic process by modulating the expression of two different groups of genes simultaneously.
Chitinophaga oryziterrae sp. nov., isolated from the rhizosphere soil of rice (Oryza sativa L.) (2012)

A novel bacterial strain, YC7001(T), was isolated from the rhizosphere soil of rice collected at Jinju, Korea, and was characterized using a polyphasic approach. Cells of strain YC7001(T) were Gram-negative-staining, yellow-pigmented, rod-shaped, aerobic, heterotrophic and non-motile. Strain YC7001(T) grew optimally at 25-30 °C, pH 5.0-8.0 and degraded gelatin, cellulose and chitin. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain YC7001(T) belonged to the genus Chitinophaga in the family Chitinophagaceae. The most closely related species were Chitinophaga sancti NBRC 15057(T) (96.9%), Chitinophaga ginsengisoli Gsoil 052(T) (95.9%), Chitinophaga pinensis DSM 2588(T) (95.7%), Chitinophaga filiformis IFO 15056(T) (95.7%) and Chitinophaga niabensis JS13-10(T) (95.0%). The DNA-DNA relatedness value of strain YC7001(T) with C. sancti NBRC 15057(T) was 15.2 ± 0.6%. Strain YC7001(T) contained MK-7 as the major menaquinone and homospermidine as the major polyamine. The major fatty acids of strain YC7001(T) were C(15:0) iso, C(16:1)ω5c and C(17:0) iso 3-OH. The polar lipids were phosphatidylethanolamine, unknown aminolipids and unknown lipids. The total genomic DNA G+C content was 41.3 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain YC7001(T) represents a novel species of the genus Chitinophaga, in the family Chitinophagaceae, for which the name Chitinophaga oryziterrae sp. nov. is proposed. The type strain is YC7001(T) ( = KACC 14533(T) = JCM 16595(T)).
Heat Shock Protein–Peptide Complexes, Reconstituted In Vitro, Elicit Peptide-specific Cytotoxic T Lymphocyte Response and Tumor Immunity (1997)

Heat shock protein (HSP) preparations derived from cancer cells and virus-infected cells have been shown previously to elicit cancer-specific or virus-specific immunity. The immunogenicity of HSP preparations has been attributed to peptides associated with the HSPs. The studies reported here demonstrate that immunogenic HSP-peptide complexes can also be reconstituted in vitro. The studies show that (a) complexes of hsp70 or gp96 HSP molecules with a variety of synthetic peptides can be generated in vitro; (b) the binding of HSPs with peptides is specific in that a number of other proteins tested do not bind synthetic peptides under the conditions in which gp96 molecules do; (c) HSP-peptide complexes reconstituted in vitro are immunologically active, as tested by their ability to elicit antitumor immunity and specific CD8+ cytolytic T lymphocyte response; and (d) synthetic peptides reconstituted in vitro with gp96 are capable of being taken up and re-presented by macrophage in the same manner as gp96- peptides complexes generated in vivo. These observations demonstrate that HSPs are CD8+ T cell response-eliciting adjuvants.
Integrated Computer Systems for Monitoring of the Critically Ill (1977)

An integrated computer system utilizing distributed minicomputers with a central data base-decision making system is described. Up to 57 critically ill patients can be monitored with the system at one time. Evaluation of elements of the system implemented in the last five years and the new features being implemented are discussed. Major new features include use of distributed minicomputers and computerized diagnostic and treatment protocols.
Isolation and characterization of temperature-sensitive and thermostable mutants of the human receptor-like protein tyrosine phosphatase LAR (1991)

Human LAR is a transmembrane receptor-like protein whose cytoplasmic region contains two tandemly duplicated domains homologous to protein tyrosine phosphatases (PTPases). Whereas the membrane-proximal domain I has enzymatic activity, the membrane-distal domain II has no apparent catalytic activity but seems to have a regulatory function. In order to study structure-function relationships of the LAR PTPase, LAR domain I was expressed in Escherichia coli, and mutants that have reduced catalytic activity or reduced thermostability were isolated and characterized. We isolated 18 unique hydroxylamine-induced missense mutations in the LAR domain I segment, of which three were temperature-sensitive. Five additional temperature-sensitive mutations were isolated using N-methyl-N'-nitro-N-nitrosoguanidine. All eight temperature-sensitive mutations are confined within a short segment of the LAR domain I sequence between amino acid positions 1329 and 1407. To examine whether this region is particularly prone to temperature-sensitive mutations, tyrosine at amino acid position 1379 was changed to a phenylalanine by oligonucleotide-directed mutagenesis. This mutant, Y1379-F, was indeed temperature-sensitive. We also isolated a revertant of a temperature-sensitive mutant. The revertant contained a second-site mutation (C1446-Y) that suppresses several temperature-sensitive mutations and also enhances the folding of LAR protein produced in E. coli.
The Theoretical Treatment of Chemical Reactions Produced by Ionization Processes Part I. The Ortho-Para Hydrogen Conversion by Alpha-Particles (1936)

The possible individual processes that may occur in a gaseous system under irradiation from alpha-particles have been examined from the theoretical standpoint. The ionization, clustering and the fate of the ions have been studied. The ortho-para hydrogen conversion under the influence of alpha-particles has been chosen as an example with which to illustrate the method of treatment. Recent experimental data by Capron have been analyzed to confirm his conclusion that atomic hydrogen is responsible for the large ratio of molecules converted to ions produced (M/N = (700 to 1000)/1). It is also shown that clustering is unimportant in this case and that the paramagnetism of the ions is of negligible importance in producing the spin-isomerization. The role of mercury atoms in removing atomic hydrogen from the system is found to be negligible. Removal of atoms by three body collision of two atoms with molecular hydrogen is slow compared with removal at the walls of the reaction vessel. Analysis of this latter process shows excellent agreement with the experimental data on the conversion efficiency of the system.
Statistical approaches to DDoS attack detection and response (2004)

The nature of the threats posed by distributed denial of service (DDoS) attacks on large networks, such as the Internet, demands effective detection and response methods. These methods must be deployed not only at the edge but also at the core of the network This paper presents methods to identify DDoS attacks by computing entropy and frequency-sorted distributions of selected packet attributes. The DDoS attacks show anomalies in the characteristics of the selected packet attributes. The detection accuracy and performance are analyzed using live traffic traces from a variety of network environments ranging from points in the core of the Internet to those inside an edge network The results indicate that these methods can be effective against current attacks and suggest directions for improving detection of more stealthy attacks. We also describe our detection-response prototype and how the detectors can be extended to make effective response decisions.
Regulation of Myosin Heavy Chain Expression during Rat Skeletal Muscle Development In Vitro (2001)

Signals that determine fast- and slow-twitch phenotypes of skeletal muscle fibers are thought to stem from depolarization, with concomitant contraction and activation of calcium-dependent pathways. We examined the roles of contraction and activation of calcineurin (CN) in regulation of slow and fast myosin heavy chain (MHC) protein expression during muscle fiber formation in vitro. Myotubes formed from embryonic day 21 rat myoblasts contracted spontaneously, and approximately 10% expressed slow MHC after 12 d in culture, as seen by immunofluorescent staining. Transfection with a constitutively active form of calcineurin (CN*) increased slow MHC by 2.5-fold as determined by Western blot. This effect was attenuated 35% by treatment with tetrodotoxin and 90% by administration of the selective inhibitor of CN, cyclosporin A. Conversely, cyclosporin A alone increased fast MHC by twofold. Cotransfection with VIVIT, a peptide that selectively inhibits calcineurin-induced activation of the nuclear factor of activated T-cells, blocked the effect of CN* on slow MHC by 70% but had no effect on fast MHC. The results suggest that contractile activity-dependent expression of slow MHC is mediated largely through the CN-nuclear factor of activated T-cells pathway, whereas suppression of fast MHC expression may be independent of nuclear factor of activated T-cells.
Genesis: cluster analysis of microarray data (2002)

A versatile, platform independent and easy to use Java suite for large-scale gene expression analysis was developed. Genesis integrates various tools for microarray data analysis such as filters, normalization and visualization tools, distance measures as well as common clustering algorithms including hierarchical clustering, self-organizing maps, k-means, principal component analysis, and support vector machines. The results of the clustering are transparent across all implemented methods and enable the analysis of the outcome of different algorithms and parameters. Additionally, mapping of gene expression data onto chromosomal sequences was implemented to enhance promoter analysis and investigation of transcriptional control mechanisms.
Clinical and Biochemical Manifestations of Depression (1988)

Thousands of studies have been conducted of the functioning of the many neurotransmitter systems in order to explore the biologic basis of major depressive disorder. Instead of reviewing this literature exhaustively, we have attempted to propose a model that accommodates the clinical observation that chronic stress early in life in vulnerable persons predisposes them to major depression with contemporary observations of the potential consequences of repeated central nervous system exposure to effectors of the stress response. This model accords with current clinical judgment that major depression is best treated with a combination of psychopharmacologic agents and psychotherapy. Accordingly, whereas psychopharmacologic intervention may be required to resolve an active episode of major depression and to prevent recurrences, psychotherapy may be equally important to lessen the burden of stress imposed by intense inner conflict and counterproductive defenses.
Bridging the gap. Joining of nonhomologous ends by DNA polymerases. (1994)

DNA double strand breaks with noncomplementary ends can be joined by mechanisms of nonhomologous recombination. In some systems a DNA end with a 3'-protruding single strand (PSS), which does not have a recessed 3'-hydroxyl that can allow for fill-in DNA synthesis, is joined to a blunt end with preservation of the 3'-PSS. It has been proposed that this process occurs via single strand ligation or is facilitated by an alignment protein. We were interested in testing the hypothesis that a DNA polymerase could function as this putative alignment protein. To characterize polymerase activities in this type of reaction, we incubated short double-stranded oligonucleotides that had an excess of one of the strands with an exonuclease-free Klenow fragment of Escherichia coli polymerase I, Taq DNA polymerase from Thermus aquaticus, or an exonuclease-free Stoffel fragment of Taq DNA polymerase. Products were analyzed by using biotinylated oligonucleotides separated by denaturing polyacrylamide gel electrophoresis. To further assess the effect of DNA polymerases on the joining of 3'-PSS ends to blunt ends, we incubated linear plasmid DNA with the polymerases and subjected the DNA to Southern blot and sequence analysis. We determined that these DNA polymerases can use a 3'-PSS end as a template after priming off the 3'-hydroxyl of a blunt end. This implies that the joining of noncomplementary ends in eukaryotic cells could proceed by a similar mechanism.
Cytosine methylation can induce local distortions in the structure of duplex DNA (1992)

Methyl groups at the C5 position of pyrimidines located within oligopurine-oligopyrimidine tracts in DNA have been shown previously to modulate curvature generated by those tracts. However, it was not known whether the influence of such methyl groups is consequent to the altered helical structure within the tracts themselves. In the current study, it is demonstrated that methylation of cytosines up to three base pairs away from a (dA)5.(dT)5 tract (A-tract) can still result in alterations of the net curvature of the A-tract-containing DNA, as measured by alterations in electrophoretic mobility. This latter effect depends strongly on both the sequence of the non-A-tract DNA and the positions of the methylated C residues. The current results lend further support to the notion that the biological consequences of cytosine methylation may be effected through local alterations in DNA structure as well as through direct protein-DNA interactions.
STATISTICAL PROCESS CONTROL USING (2008)

SPC is a practical approach to continuous control of quality (and safety) that uses various tools to monitor, analyse, evaluate and control a process and is based on the philosophical concept that it is essential to use the best available data in order to optimise process effi ciency. In this context, the term ‘ process ’ is any activity that is subject to variability and includes not just production, storage and distribution within an industry, such as food processing, but also other operations where it is necessary to ensure that day-to-day operations are in control. It is therefore relevant also to laboratory monitoring and testing activities, where ‘ process ’ describes the production of analytical data and to other forms of quantifi able activity. The concept was introduced in the late 1920s by Dr William Shewhart whose work helped to improve effi ciency in the United States manufacturing industry by moving from traditional quality control to one based on quality assurance. Hence, SPC is based on the concept of
HIV‐1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity (2001)

Toxic effects of HIV-1 proteins contribute to altered function and decreased survival of select populations of neurons in HIV-1-infected brain. One such HIV-1 protein, Tat, can activate calcium release from IP3-sensitive intracellular pools, induce calcium influx in neural cells, and, as a result, can increase neuronal cell death. Here, we provide evidence that Tat potentiates excitatory amino acid (glutamate and NMDA) triggered calcium flux, as well as glutamate- and staurosporine-mediated neurotoxicity. Calcium flux in cultured rat hippocampal neurons triggered by the transient application of glutamate or NMDA was facilitated by pre-exposure to Tat. Facilitation of glutamate-triggered calcium flux by Tat was prevented by inhibitors of ADP-ribosylation of G(i)/G(o) proteins (pertussis toxin), protein kinase C (H7 and bisindolymide), and IP3-mediated calcium release (xestospongin C), but was not prevented by an activator of G(s) (cholera toxin) or an inhibitor of protein kinase A (H89). Facilitation of NMDA-triggered calcium flux by Tat was reversed by inhibitors of tyrosine kinase (genestein and herbimycin A) and by an inhibitor of NMDA receptor function (zinc). Tat increased 32P incorporation into NMDA receptor subunits NR2A and NR2B and this effect was blocked by genestein. Subtoxic concentrations of Tat combined with subtoxic concentrations of glutamate or staurosporine increased neuronal cell death significantly. Together, these findings suggest that NMDA receptors play an important role in Tat neurotoxicity and the mechanisms identified may provide additional therapeutic targets for the treatment of HIV-1 associated dementia.
Using the Amazon Mechanical Turk for transcription of spoken language (2010)

We investigate whether Amazon's Mechanical Turk (MTurk) service can be used as a reliable method for transcription of spoken language data. Utterances with varying speaker demographics (native and non-native English, male and female) were posted on the MTurk marketplace together with standard transcription guidelines. Transcriptions were compared against transcriptions carefully prepared in-house through conventional (manual) means. We found that transcriptions from MTurk workers were generally quite accurate. Further, when transcripts for the same utterance produced by multiple workers were combined using the ROVER voting scheme, the accuracy of the combined transcript rivaled that observed for conventional transcription methods. We also found that accuracy is not particularly sensitive to payment amount, implying that high quality results can be obtained at a fraction of the cost and turnaround time of conventional methods.
Angiogenesis and obesity (2007)

Development of obesity is associated with substantial modulation of adipose tissue structure, involving adipogenesis, angiogenesis, and extracellular matrix remodelling. These processes require proteolytic activity, provided mainly by the fibrinolytic (plasminogen/plasmin), matrix metalloproteinase, and ADAM/ADAMTS systems. In early-stage development of adipose tissue, adipogenesis is tightly associated with angiogenesis. Thus, adipose tissue explants trigger blood vessel formation, and in turn adipose tissue endothelial cells promote pre-adipocyte differentiation. Modulation of angiogenesis and of proteolytic systems may have the potential to impair adipose tissue development.
Dose Scheduling – Herceptin<sup>®</sup> (2001)

Preclinical and phase I/II studies of Herceptin demonstrated a dose-related, non-linear pharmacokinetic profile. The results of a dose-finding study supported a regimen comprising an initial intravenous (i.v.) dose of 4 mg/kg with subsequent weekly doses of 2 mg/kg. However, pharmacokinetic and safety data suggested that increased dose and reduced frequency of Herceptin administration are feasible. In addition, evidence shows that Herceptin plus paclitaxel has additive antitumor efficacy in vitro, and this regimen produces significant clinical benefits. These observations form the rationale for conducting a phase I/II trial of Herceptin (8 mg/kg initial dose, 6 mg/kg maintenance dose) plus paclitaxel, both given 3-weekly. Preliminary results are promising, with serum trough Herceptin concentrations being similar and AUC being greater than those observed with weekly Herceptin plus 3-weekly paclitaxel. Two further trials are proposed: 3-weekly Herceptin as first-line monotherapy of metastatic breast cancer; and 3-weekly Herceptin with the oral 5-fluorouracil derivative, Xeloda (capecitabine). Subcutaneous (s.c.) administration of Herceptin would further simplify administration and studies are also underway to clinically evaluate s.c. administration of Herceptin in combination with paclitaxel. With the recent development of oral taxanes, it is predicted that combinations including an oral taxane, Xeloda and either 3-weekly or possibly s.c. Herceptin may become future therapies for breast cancer patients.