gebhart/patrepeval huggingface dataset:
Data management in cloud environments: NoSQL and NewSQL data stores (2013)

Abstract Advances in Web technology and the proliferation of mobile devices and sensors connected to the Internet have resulted in immense processing and storage requirements. Cloud computing has emerged as a paradigm that promises to meet these requirements. This work focuses on the storage aspect of cloud computing, specifically on data management in cloud environments. Traditional relational databases were designed in a different hardware and software era and are facing challenges in meeting the performance and scale requirements of Big Data. NoSQL and NewSQL data stores present themselves as alternatives that can handle huge volume of data. Because of the large number and diversity of existing NoSQL and NewSQL solutions, it is difficult to comprehend the domain and even more challenging to choose an appropriate solution for a specific task. Therefore, this paper reviews NoSQL and NewSQL solutions with the objective of: (1) providing a perspective in the field, (2) providing guidance to practitioners and researchers to choose the appropriate data store, and (3) identifying challenges and opportunities in the field. Specifically, the most prominent solutions are compared focusing on data models, querying, scaling, and security related capabilities. Features driving the ability to scale read requests and write requests, or scaling data storage are investigated, in particular partitioning, replication, consistency, and concurrency control. Furthermore, use cases and scenarios in which NoSQL and NewSQL data stores have been used are discussed and the suitability of various solutions for different sets of applications is examined. Consequently, this study has identified challenges in the field, including the immense diversity and inconsistency of terminologies, limited documentation, sparse comparison and benchmarking criteria, and nonexistence of standardized query languages.
Identification of U2AF(35)-dependent exons by RNA-Seq reveals a link between 3′ splice-site organization and activity of U2AF-related proteins (2015)

The auxiliary factor of U2 small nuclear RNA (U2AF) is a heterodimer consisting of 65- and 35-kD proteins that bind the polypyrimidine tract (PPT) and AG dinucleotides at the 3' splice site (3'ss). The gene encoding U2AF35 (U2AF1) is alternatively spliced, giving rise to two isoforms U2AF35a and U2AF35b. Here, we knocked down U2AF35 and each isoform and characterized transcriptomes of HEK293 cells with varying U2AF35/U2AF65 and U2AF35a/b ratios. Depletion of both isoforms preferentially modified alternative RNA processing events without widespread failure to recognize 3'ss or constitutive exons. Over a third of differentially used exons were terminal, resulting largely from the use of known alternative polyadenylation (APA) sites. Intronic APA sites activated in depleted cultures were mostly proximal whereas tandem 3'UTR APA was biased toward distal sites. Exons upregulated in depleted cells were preceded by longer AG exclusion zones and PPTs than downregulated or control exons and were largely activated by PUF60 and repressed by CAPERα. The U2AF(35) repression and activation was associated with a significant interchange in the average probabilities to form single-stranded RNA in the optimal PPT and branch site locations and sequences further upstream. Although most differentially used exons were responsive to both U2AF subunits and their inclusion correlated with U2AF levels, a small number of transcripts exhibited distinct responses to U2AF35a and U2AF35b, supporting the existence of isoform-specific interactions. These results provide new insights into function of U2AF and U2AF35 in alternative RNA processing.
Identification of a Novel Transcription Factor Binding Element Involved in the Regulation by Differentiation of the Human Telomerase (hTERT) Promoter (2000)

Three different cell differentiation experimental model systems (human embryonic stem cells, mouse F9 cells, and human HL-60 promyelocytic cells) were used to determine the relationship between the reduction in telomerase activity after differentiation and the regulation of the promoter for the hTERT gene. Promoter constructs of three different lengths were subcloned into the PGL3-basic luciferase reporter vector. In all three experimental systems, all three promoter constructs drove high levels of reporter activity in the nondifferentiated state, with a marked and time-dependent reduction after the induction of differentiation. In all cases, the smallest core promoter construct (283 nt upstream of the ATG) gave the highest activity. Electrophoretic mobility shift assays revealed transcription factor binding to two E-box domains within the core promoter. There was also a marked time-dependent reduction in this binding with differentiation. In addition, a distinct and novel element was identified within the core promoter, which also underwent time-dependent reduction in transcription factor binding with differentiation. Site-directed mutagenesis of this novel element revealed a correlation between transcription factor binding and promoter activity. Taken together, the results indicate that regulation of overall telomerase activity with differentiation is mediated at least in part at the level of the TERT promoter and provides new information regarding details of the regulatory interactions that are involved in this process.
[PLAC1/CP1 gene expression and autologous humoral immunity in gastric cancer patients]. (2006)

PLAC1/CP1 mRNA was expressed in high frequency and induced spontaneous antibody responses in gastric cancer patients. PLAC1/CP1 may be a valuable candidate antigen in gastric cancer immunotherapy.
Speed up of behavioral A.T.P.G. using a heuristic criterion (1993)

This paper presents an approach aiming at a significant acceleration of a Behavioral Test Pattern Generation process. Recently, new BTPG methods have been developed, based upon the application of a backtracking search procedure. The approach presented herein reduces the number of backtracks by firstly comparing search strategies and then by defining an improvement criteria.
Modeling, Molecular Dynamics Simulation, and Mutation Validation for Structure of Cannabinoid Receptor 2 Based on Known Crystal Structures of GPCRs (2014)

The cannabinoid receptor 2 (CB2) plays an important role in the immune system. Although a few of GPCRs crystallographic structures have been reported, it is still challenging to obtain functional transmembrane proteins and high resolution X-ray crystal structures, such as for the CB2 receptor. In the present work, we used 10 reported crystal structures of GPCRs which had high sequence identities with CB2 to construct homology-based comparative CB2 models. We applied these 10 models to perform a prescreen by using a training set consisting of 20 CB2 active compounds and 980 compounds randomly selected from the National Cancer Institute (NCI) database. We then utilized the known 170 cannabinoid receptor 1 (CB1) or CB2 selective compounds for further validation. Based on the docking results, we selected one CB2 model (constructed by β1AR) that was most consistent with the known experimental data, revealing that the defined binding pocket in our CB2 model was well-correlated with the training and testing data studies. Importantly, we identified a potential allosteric binding pocket adjacent to the orthosteric ligand-binding site, which is similar to the reported allosteric pocket for sodium ion Na(+) in the A2AAR and the δ-opioid receptor. Our studies in correlation of our data with others suggested that sodium may reduce the binding affinities of endogenous agonists or its analogs to CB2. We performed a series of docking studies to compare the important residues in the binding pockets of CB2 with CB1, including antagonist, agonist, and our CB2 neutral compound (neutral antagonist) XIE35-1001. Then, we carried out 50 ns molecular dynamics (MD) simulations for the CB2 docked with SR144528 and CP55940, respectively. We found that the conformational changes of CB2 upon antagonist/agonist binding were congruent with recent reports of those for other GPCRs. Based on these results, we further examined one known residue, Val113(3.32), and predicted two new residues, Phe183 in ECL2 and Phe281(7.35), that were important for SR144528 and CP55940 binding to CB2. We then performed site-directed mutation experimental study for these residues and validated the predictions by radiometric binding affinity assay.
Cancer therapies targeted to the epidermal growth factor receptor and its family members (2006)

This review will provide an overview of therapeutic strategies that are targeted to the epidermal growth factor receptor (EGFR) network of signal transduction, with a focus on EGFR itself and the closely related Her-2/neu/erbB2 (erbB2) receptor. EGFR is the founding member of the erbB family of receptor tyrosine kinases, type I membrane spanning proteins that bind a variety of peptide growth factor ligands and initiate signal transduction along multiple downstream pathways towards proliferation, survival and angiogenesis. EGFR and erbB2 are validated targets for anticancer therapy and several such targeted therapeutic agents are already approved for use in patients. These include monoclonal antibodies directed to the extracellular domains of one or more erbB receptor and small molecule inhibitors of their intracellular tyrosine kinase domains. The advantages and disadvantages of these agents, as well as new and emerging agents in this class of targeted therapeutics, will be discussed. Recent progress towards understanding the molecular and pharmacodynamic causes of treatment failure or success will also be addressed. Finally, the therapeutic potential of targeted combinations, those directed at multiple facets of erbB-family signalling and those targeted to erbB and non-erbB receptor systems, will be reviewed.
Effect of active smoking on the human bronchial epithelium transcriptome (2007)

Expression levels of some of the genes related to tobacco smoking return to levels similar to never smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation. These irreversible changes may account for the persistent lung cancer risk despite smoking cessation.
Novel Function of Rad27 (FEN-1) in Restricting Short-Sequence Recombination (2001)

Saccharomyces cerevisiae mutants lacking the structure-specific nuclease Rad27 display an enhancement in recombination that increases as sequence length decreases, suggesting that Rad27 preferentially restricts recombination between short sequences. Since wild-type alleles of both RAD27 and its human homologue FEN1 complement the elevated short-sequence recombination (SSR) phenotype of a rad27-null mutant, this function may be conserved from yeast to humans. Furthermore, mutant Rad27 and FEN-1 enzymes with partial flap endonuclease activity but without nick-specific exonuclease activity partially complement the SSR phenotype of the rad27-null mutant. This suggests that the endonuclease activity of Rad27 (FEN-1) plays a role in limiting recombination between short sequences in eukaryotic cells.
Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection (2015)

Based on these results, a daily dose range up to 200 mg has been selected for phase IIB dose-finding studies in patients with rheumatoid arthritis.
Heat Preconditioning Attenuates Renal Injury in Ischemic ARF in Rats (2006)

Although heat preconditioning has been known to be protective in various types of injury, the precise molecular mechanism for this is unclear. Recent observations that indicate that previous heat shock has an anti-inflammatory, antiapoptotic effect led to this investigation of the in vivo effect of heat preconditioning on NF-kappaB activation and inflammation and also on tubular cell injury in ischemic acute renal failure (ARF). Heat preconditioning provided marked functional protection and also reduced histologic evidence of tubular necrosis. Ischemia/reperfusion-induced NF-kappaB activation was suppressed by heat preconditioning with a subsequent decrease in monocyte chemoattractant protein-1 expression and inflammatory cell infiltration. Heat preconditioning also suppressed the accumulation of phosphorylated inhibitory kappaBalpha (IkappaBalpha) with a resultant depletion of cytoplasmic IkappaBalpha, indicating that heat preconditioning blocked the activation of the IkappaB kinase complex. Tubular cell apoptosis, determined by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, also was decreased by heat preconditioning, and this was accompanied by decreased caspase 3 activation. Among several heat-shock proteins (HSP), HSP-70 was induced primarily by heat preconditioning. Inhibition of HSP-70 by quercetin almost completely reversed the functional protection that was provided by heat preconditioning. These data provide evidence that HSP-70 affords protection via inhibition of NF-kappaB-mediated inflammation and also inhibition of the cell death pathway in ischemic ARF. Further elucidation of the cytoprotective mechanism of stress proteins could facilitate new target or drug development in the treatment of ARF.
Macrophage deactivation by interleukin 10. (1991)

Recombinant mouse interleukin 10 (IL-10) was exceedingly potent at suppressing the ability of mouse peritoneal macrophages (m phi) to release tumor necrosis factor alpha (TNF-alpha). The IC50 of IL-10 for the suppression of TNF-alpha release induced by 0.5 microgram/ml lipopolysaccharide was 0.04 +/- 0.03 U/ml, with as little as 1 U/ml suppressing TNF-alpha production by a factor of 21.4 +/- 2.5. At 10 U/ml, IL-10 markedly suppressed m phi release of reactive oxygen intermediates (ROI) (IC50 3.7 +/- 1.8 U/ml), but only weakly inhibited m phi release of reactive nitrogen intermediates (RNI). Since TNF-alpha is a T cell growth and differentiation factor, whereas ROI and RNI are known to inhibit lymphocyte function, it is possible that m phi exposed to low concentrations of IL-10 suppress lymphocytes. m phi deactivated by higher concentrations of IL-10 might be permissive for the growth of microbial pathogens and tumor cells, as TNF-alpha, ROI, and RNI are major antimicrobial and tumoricidal products of m phi. IL-10's effects on m phi overlap with but are distinct from the effects of the two previously described cytokines that suppress the function of mouse m phi, transforming growth factor beta and macrophage deactivation factor. Based on results with neutralizing antibodies, all three m phi suppressor factors appear to act independently.
Designed Multiple Ligands. An Emerging Drug Discovery Paradigm (2005)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTDesigned Multiple Ligands. An Emerging Drug Discovery ParadigmRichard Morphy and Zoran RankovicView Author Information Medicinal Chemistry Department, Organon Laboratories, Newhouse, Lanarkshire, ML1 5SH, U.K. Cite this: J. Med. Chem. 2005, 48, 21, 6523–6543Publication Date (Web):September 24, 2005Publication History Received3 May 2005Published online24 September 2005Published inissue 1 October 2005https://pubs.acs.org/doi/10.1021/jm058225dhttps://doi.org/10.1021/jm058225dreview-articleACS PublicationsCopyright © 2005 American Chemical SocietyRequest reuse permissionsArticle Views8941Altmetric-Citations982LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Antagonists,Inhibitors,Ligands,Peptides and proteins,Receptors Get e-Alerts
Effects of an Antibody to Interleukin-5 in a Monkey Model of Asthma (1995)

To investigate the role of interleukin-5 (IL-5) on airway hyperreactivity and pulmonary inflammation in nonhuman primate airways, the effect of a neutralizing monoclonal antibody to murine IL-5 (TRFK-5) was investigated in a cynomolgus monkey model of allergic asthma. Anesthetized Ascaris-sensitive monkeys underwent bronchoalveolar lavage (BAL) to assess the granulocyte content of this fluid before and 24 h after aerosolized Ascaris suum extract inhalation. Airway reactivity was assessed by the concentration of inhaled histamine required to produce a 40% reduction in dynamic lung compliance (Cdyn40). Exposure to A. suum extract produced an increase in airway reactivity (Cdyn40 = 0.065 +/- 0.024% before Ascaris; Cdyn40 = 0.014 +/- 0.004% after Ascaris) and an inflammatory reaction in the airways characterized by an increase in BAL eosinophils (0.05 +/- 0.03 x 10(3) cells/ml before Ascaris; 176 +/- 76 x 10(3) cells/ml after Ascaris) and neutrophils (3 +/- 1 x 10(3) cells/ml before Ascaris; 406 +/- 211 x 10(3) cells/ml after Ascaris). In contrast, only small nonsignificant changes in airway reactivity and granulocyte influx into the BAL occurred after aerosolized saline as a sham challenge. When the monkeys were treated 1 h before Ascaris challenge with the TRFK-5 antibody (0.3 mg/kg, intravenously), there was no increase in airway reactivity after Ascaris challenge (Cdyn40 = 0.032 +/- 0.016% before Ascaris; Cdyn40 = 0.217 +/- 0.196% after Ascaris) and there were only small increases in the number of eosinophils and neutrophils in the BAL after Ascaris challenge. The inhibition of this pulmonary eosinophilia and bronchial hyperresponsiveness by TRFK-5 was seen for up to 3 mo after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Formation of hydroxyapatite in hydrogels from tetracalcium phosphate/dicalcium phosphate mixtures. (1989)

Apatitic calcium phosphate cements, formed by the ambient reaction of tetracalcium phosphate (TTCP) with dicalcium phosphates (DCP), have been recently reported. H2O or dilute aq. H3PO4 (0.2%) is used as the liquid vehicle for this reaction. The aim of this study was to ascertain if hydroxyapatite (HAp) can form in self-cured hydrogel composites containing TTCP/DCP mixes. The setting times (ST) and diametral tensile strengths (DTS) of these hydrogel composites were also determined. The hydrogels were of two types: (1) vinyl thermosets derived from the copolymerization of HEMA (2-hydroxyethyl methacrylate) and cross-linking monomers, and (2) polyelectrolyte-based hydrogels formed from aq. poly(alkenoic acids), e.g., poly(acrylic acid). Cylindrical specimens 6 mm D x 3 mm H were prepared and stored in H2O for up to 30 days. The HEMA composites were hardened in 7-15 min by free radical initiation (benzoyl peroxide/tertiary aromatic amine). The polyelectrolyte cements were hardened in 6-8 min. After various periods of storage in H2O at 37 degrees C, some of the specimens were examined by X-ray spectroscopy for HAp. HAp formation was not observed in the HEMA composites even after 30 days of H2O storage but was detected in the polyacid cements. The 24-h DTS values of the HEMA composites (14-26 MPa) were higher than those of the polyacid cements (7-12 MPa). Both the H2O content and pH may thus be factors controlling the rate and extent of HAp formation in hydrogel composites containing TTCP/DCP mixtures.
Flexible Readout and Integration Sensor (FRIS): New Class of Imaging Sensor Arrays Optimized for Air and Missile Defense (2010)

Biological sensory organs operate at performance levels set by fundamental physical limits, under severe constraints of size, weight, and energy resources-the same constraints that many sensor devices have to meet.
Mice thrive without Cdk4 and Cdk2 (2007)

Mammalian cell division is thought to be driven by sequential activation of several Cyclin-dependent kinases (Cdk), mainly Cdk4, Cdk6, Cdk2 and Cdk1. Since mice lacking Cdk4, Cdk6 or Cdk2 are viable, it has been proposed that they play compensatory roles. We report here that mice lacking Cdk4 and Cdk2 complete embryonic development to die shortly thereafter presumably due to heart failure. However, conditional ablation of Cdk2 in adult mice lacking Cdk4 does not result in obvious abnormalities. Moreover, these double mutant mice recover normally after partial hepatectomy. In culture, Cdk4(-/-);Cdk2(-/-) embryonic fibroblasts become immortal, display robust pRb phosphorylation and have normal S phase kinetics. These observations indicate that Cdk4 and Cdk2 are dispensable for the mammalian cell cycle and for adult homeostasis.
mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients (2001)

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-->GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17%-55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histological evidence of metastatic disease. Ninety-seven per cent of the patients with histologically involved nodes showed expression of mammaglobin mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicating the presence of metastases not detected by routine histological examination of one lymph node section. These results show that both mammaglobin RT-PCR and CEA RT-PCR are useful tools for the detection of breast cancer metastases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly one-third of cases.