gebhart/patrepeval huggingface dataset:
A protein phosphatase related to the vaccinia virus VH1 is encoded in the genomes of several orthopoxviruses and a baculovirus. (1993)

The vaccinia virus VH1 gene product is a dual specificity protein phosphatase with activity against both phosphoserine- and phosphotyrosine-containing substrates. We investigated the potential presence of VH1 analogs in other viruses. Hybridization and sequence data indicated that a phosphatase related to the VH1 phosphatase is highly conserved in the genomes of smallpox variola virus and other orthopoxviruses. The open reading frames from the raccoonpox virus and the smallpox variola virus Bangladesh major strain genomes encoding the VH1 analogs were sequenced and found to be highly conserved with the vaccinia virus VH1. An open reading frame from the baculovirus Autographa californica has sequence similarity to the VH1 phosphatase. The viral proteins appear to be structurally related to the cell cycle control protein p80cdc25. A recombinant phosphatase expressed from the baculovirus gene was found to share with the VH1 phosphatase the ability to hydrolyze substrates that contained both phosphoserine and phosphotyrosine.
Proteolytic processing of a plasma membrane-bound precursor to human macrophage colony-stimulating factor (CSF-1) is accelerated by phorbol ester. (1991)

A transmembrane precursor to human macrophage colony-stimulating factor (M-CSF, CSF-1) is stably expressed at the cell surface where it is slowly and inefficiently cleaved to yield a soluble form of the growth factor. Incubation in the presence of phorbol ester resulted in rapid cleavage of the plasma membrane-bound precursor and release of soluble CSF-1. Within 60 min after phorbol treatment the quantity of growth factor recovered in the medium was more than 30-fold greater than that observed in the absence of the agent. The growth factor released in the presence of phorbol was biologically active and exhibited the same electrophoretic mobility as that obtained in the absence of the drug. Phorbol ester-accelerated processing of the cell surface CSF-1 precursor was abrogated by long-term exposure to phorbol, but was not inhibited by pretreatment with cycloheximide or incubation in serum-free medium. These results suggest that the enhanced post-translational processing of the CSF-1 precursor resulted from activation of a pre-existing cellular protease via a mechanism involving phorbol ester-mediated stimulation of protein kinase C.
Arabidopsis MET1 Cytosine Methyltransferase Mutants (2003)

We describe the isolation and characterization of two missense mutations in the cytosine-DNA-methyltransferase gene, MET1, from the flowering plant Arabidopsis thaliana. Both missense mutations, which affect the catalytic domain of the protein, led to a global reduction of cytosine methylation throughout the genome. Surprisingly, the met1-2 allele, with the weaker DNA hypomethylation phenotype, alters a well-conserved residue in methyltransferase signature motif I. The stronger met1-1 allele caused late flowering and a heterochronic delay in the juvenile-to-adult rosette leaf transition. The distribution of late-flowering phenotypes in a mapping population segregating met1-1 indicates that the flowering-time phenotype is caused by the accumulation of inherited defects at loci unlinked to the met1 mutation. The delay in flowering time is due in part to the formation and inheritance of hypomethylated fwa epialleles, but inherited defects at other loci are likely to contribute as well. Centromeric repeat arrays hypomethylated in met1-1 mutants are partially remethylated when introduced into a wild-type background, in contrast to genomic sequences hypomethylated in ddm1 mutants. ddm1 met1 double mutants were constructed to further our understanding of the mechanism of DDM1 action and the interaction between two major genetic loci affecting global cytosine methylation levels in Arabidopsis.
Δ-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway (2000)

In this study, we show that Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, suppresses host immune reactivity against lung cancer. In two different weakly immunogenic murine lung cancer models, intermittent administration of THC (5 mg/kg, four times/wk i.p. for 4 wk) led to accelerated growth of tumor implants compared with treatment with diluent alone. In contrast to our findings in immunocompetent mice, THC did not affect tumor growth in tumor-bearing SCID mice. The immune inhibitory cytokines, IL-10 and TGF-beta, were augmented, while IFN-gamma was down-regulated at both the tumor site and in the spleens of THC-treated mice. Administration of either anti-IL-10- or anti-TGF-beta-neutralizing Abs prevented the THC-induced enhancement in tumor growth. Both APC and T cells from THC-treated mice showed limited capacities to generate alloreactivity. Furthermore, lymphocytes from THC-treated mice transferred the effect to normal mice, resulting in accelerated tumor growth similar to that seen in the THC-treated mice. THC decreased tumor immunogenicity, as indicated by the limited capacity for tumor-immunized, THC-treated mice to withstand tumor rechallenge. In vivo administration of a specific antagonist of the CB2 cannabinoid receptor also blocked the effects of THC. Our findings suggest the THC promotes tumor growth by inhibiting antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway.
Topiramate in migraine prevention (2003)

Migraine is a common episodic headache disorder characterized by attacks that consist of various combinations of headache and neurologic, gastrointestinal and autonomic symptoms. Migraine with aura may be due to neuronal hyperexcitability, perhaps from cortical disinhibition. It is likely that headache results from the activation of meningeal and blood vessel nociceptors combined with a change in central pain modulation. Antiepileptic drugs are increasingly being recommended for migraine prevention since placebo-controlled, double-blind trials prove them to be effective. Topiramate is a structurally unique antiepileptic drug that was discovered by serendipity. It is a derivative of the naturally occurring monosaccharide D-fructose and contains sulfamate functionality. Topiramate may bind to membrane channel complexes at phosphorylation sites in the inner loop and, thereby, allosterically modulate ionic conductance through the channels. The topiramate MIGR-001, MIGR-002 and MIGR-003 trials represent the largest controlled trials of a migraine preventive agent ever performed. Treatment with 100 or 200 mg/day of topiramate was associated with significant reductions in migraine frequency, migraine days and the number of migraine attacks per month. Topiramate was also associated with a reduced use of acute medications. The most common adverse events were difficulty with concentration and attention, difficulty with memory, mood problems, anorexia and weight loss, paresthesias, hypoesthesia and language problems. Topiramate is a first-line migraine preventive drug and should be considered preferentially for all patients in whom weight gain is a concern, who are currently overweight or who have coexistent epilepsy or bipolar disease.
What did you do today? (2008)

&lt;p&gt;We present a framework built from two Hierarchical Bayesian topic models to discover human location-driven routines from mobile phones. The framework uses location-driven bag representations of people's daily activities obtained from celltower connections. Using 68 000+ hours of real-life human data from the Reality Mining dataset, we successfully discover various types of routines. The first studied model, Latent Dirichlet Allocation (LDA), automatically discovers characteristic routines for all individuals in the study, including "going to work at 10am", "leaving work at night", or "staying home for the entire evening". In contrast, the second methodology with the Author Topic model (ATM) finds routines characteristic of a selected groups of users, such as "being at home in the mornings and evenings while being out in the afternoon", and ranks users by their probability of conforming to certain daily routines.&lt;/p&gt;
Predictive frequency stability control based on wide-area phasor measurements (2003)

Wide-area phasor measurements provide a dynamic view of the power system in short-term intervals. The time synchronization and concentration of these measurements opens up a range for wide area applications for protection and control. For each kind of instability, related detection and action schemes can be defined to limit or prevent the system from severe disturbances or even collapses. This paper proposes a novel predictive method for emergency frequency control to be used on such occasions. The proposed method avoids the drawbacks of local underfrequency load shedding schemes, such as delayed response and overshedding, by basing control on synchronized phasor measurements. A single machine equivalent for each power system island including the frequency sensitivity of loads, is computed online using phasor measurements. Using this model the progression of frequency stability after a contingency is predicted and stabilizing load shedding is determined in a co-ordinated way for the supervised area of the power system.
Cytokine profiling of pulmonary aspergillosis (2006)

Aspergillus fumigatus is ubiquitous and yet causes invasive, chronic and allergic disease of the lung. Chronic cavitary pulmonary aspergillosis (CCPA) is a slowly destructive form of pulmonary aspergillosis, without immunocompromise. We hypothesized that CCPA cytokine gene polymorphisms would differ from patients with allergic bronchopulmonary aspergillosis (ABPA) and uninfected controls. We have profiled functional cytokine gene polymorphisms for interleukin (IL)-10, IL-15, transforming growth factors (TGF)-beta1, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in patients with CCPA (n = 24) who were compared with other forms of aspergillosis (mostly ABPA) (n = 15) and with ethnically matched controls (n = 65-330). Results are described with reference to the high-producing genotype in each case. Susceptibility to aspergillosis (all patients compared with normal controls) was associated with higher frequency of the IL-15 +13689*A allele (OR = 2.37, P = 0.0028) and A/A genotype (chi(2) = 10.31, P < 0.001), with a lower frequency of the TNF-alpha-308*A/A genotype (chi(2) = 11.05, P < 0.01). Within the aspergillosis patients, CCPA is associated with lower frequency of the IL-10 -1082*G allele (OR = 0.38, P = 0.0006) and G/G genotype (chi(2) = 22.45, P < 0.001) and with a lower frequency of the TGF-beta1 +869 *T allele (OR +0.42, P < 0.0029) and T/T genotype (chi(2) = 17.82, P < 0.001) compared with non-CCPA patients and normal controls. Patients infected with Aspergillus appear to be higher producers of IL-15, a Th2-promoting cytokine, and lower producers of TNF-alpha, a cytokine central in protective responses. CCPA occurs in patients who are genetically lower producers of both IL-10 and TGF-beta1. As these cytokines are regulatory and anti-inflammatory, CCPA may be a consequence of poor inflammatory response control in the lung.
Increased expression of adenylylcyclase type VI proportionately increases β-adrenergic receptor-stimulated production of cAMP in neonatal rat cardiac myocytes (1998)

Cellular content of cAMP generated by activation of adenylylcyclase (AC; EC 4.6.1.1) is a key determinant of functional responsiveness in the heart and other tissues. We have tested two hypotheses regarding the relationship between AC content and beta-adrenergic receptor (betaAR)-mediated signal transduction in cardiac myocytes. First, that AC content limits adrenergic signal transduction, and, second, that increased AC, independent of (betaAR) number and G-protein content, yields a proportional increase in betaAR-mediated transmembrane signaling. We used recombinant adenovirus to increase AC isoform VI (ACVI) expression in neonatal cardiac myocytes. Cells that overexpressed ACVI responded to agonist stimulation with marked increases in cAMP production in proportion to protein expressed. In parallel experiments performed on cells transfected with lacZ (control) or ACVI, [3H]forskolin binding, used to assess AC protein expression, was amplified 6-fold, while betaAR-stimulated cAMP production from these cells was increased 7-fold. No changes in betaAR number, or in the heterotrimeric GTP-binding proteins, Galphas or Galphai2, were observed. Previous studies indicate that increased cardiac expression of betaAR or Galphas does not yield proportional increases in transmembrane adrenergic signaling. In contrast, the current data demonstrate that increased ACVI expression provides a proportional increase in beta-adrenergic signal transduction. Our results show that the amount of AC sets a limit on transmembrane beta-adrenergic signaling. We speculate that similar functional responses are possible in other cell types in which AC plays an important physiological role.
Ambient Sampling/Ionization Mass Spectrometry: Applications and Current Trends (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTAmbient Sampling/Ionization Mass Spectrometry: Applications and Current TrendsGlenn A. Harris, Asiri S. Galhena, and Facundo M. Fernández*View Author Information School of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta Georgia 30332, United StatesE-mail: [email protected]. Phone: 404 385 4432. Fax: 404 385 3399.Cite this: Anal. Chem. 2011, 83, 12, 4508–4538Publication Date (Web):April 15, 2011Publication History Published online6 May 2011Published inissue 15 June 2011https://pubs.acs.org/doi/10.1021/ac200918uhttps://doi.org/10.1021/ac200918ureview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views9962Altmetric-Citations465LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Desorption,Ionization,Ions,Liquids,Molecules Get e-Alerts
Clinical and Demographic Characteristics of Patients With Chronic Pain After Major Thoracotomy (2008)

Postoperative pain that persists but eventually dissipates was a common finding whose intensity was associated with immediate preoperative and postoperative pain levels. In contrast, pain later on during hospitalization, its impact, and perceived analgesic effectiveness best identified those who would continue to report pain almost 1 year after surgery.
Epigenetic dysregulation of the Wnt signalling pathway in chronic lymphocytic leukaemia (2008)

Wnt signalling is constitutively activated in CLL B lymphocytes in association with methylation of multiple soluble Wnt antagonist genes. Methylation of these soluble Wnt antagonist genes, occasionally multiple genes, in primary CLL marrow samples suggests an important role in CLL pathogenesis. Moreover, this study underscored the importance of studying methylation of a panel of, but not individual, genes regulating a cellular pathway.
Expression of a Dominant Negative Heat Shock Factor-1 Construct Inhibits Aneuploidy in Prostate Carcinoma Cells* (2004)

Recent studies have implicated heat shock proteins (HSP) and heat shock transcription factor 1 (HSF1) in tumor progression. We have examined the role of HSF1 in the malignant phenotype of PC-3 prostate carcinoma cells. We have developed a dominant negative construct of HSF1 that antagonizes transcription from HSP promoters and results in the depletion of intracellular HSP 70. Our studies indicate that expression of DN-HSF1 dramatically alters the DNA content of PC-3 cells (derived from p53 null prostatic carcinoma) and inhibits aneuploidy in these cells. This effect is due to prolonged expression of DN-HSF1, and transient expression of the dominant negative factor from an inducible promoter failed to cause the effect. Inhibition of aneuploidy in p53 null PC-3 cells by DN-HSF1 expression was recapitulated by expression within the cells of wild type p53. Furthermore, cells expressing DN-HSF1 showed a profound inhibition in the development of aneuploidy when exposed to chemical agents that disrupt the mitotic spindle and prevent progression through metaphase. Inhibition of aneuploidy in PC-3 cells expressing DN-HSF1 was associated with delayed breakdown of cyclin B1 compared with controls, consistent with a role for wild type HSF1 in the regulation of cyclin B1 degradation, a key step in the control of mitosis. Our experiments therefore demonstrate that HSF1 plays a functional role in cancer cells under nonstress conditions and influences cell cycle behavior and progression through mitosis and promotes the development of the aneuploid state.
« Un acteur, ou il est total ou il n’est pas » : Rencontre avec Ariane Mnouchkine et Pol Pelletier (1994)

The solubility of nickel powder was studied to estimate the inertness of the nickel metal in contact with deionized distilled water, saline solution, a chelating agent, ethylenediamine tetraacetate, and human serum. The human serum dissolved more than two times as much nickel as the saline solution and almost six times as much nickel as the EDTA solution in the first 24 h of the experiment. The resultant solubility curve can be an indication of the level of toxicity of an individual nickel compound or alloy. The degree of solubility may also be important in further studies on the mechanisms of nickel carcinogenesis.
Analyses of Variant Acid β-Glucosidases (2005)

Acid beta-glucosidase (GCase) is a 497-amino acid, membrane-associated lysosomal exo-beta-glucosidase whose defective activity leads to the Gaucher disease phenotypes. To move toward a structure/function map for disease mutations, 52 selected single amino acid substitutions were introduced into GCase, expressed in an insect cell system, purified, and characterized for basic kinetic, stability, and activator response properties. The variant GCases from Gaucher disease patients and selected variant GCases from the mouse had decreased relative k(cat) and differential effects on active site binding and/or attachment of mechanism-based covalent (conduritol B epoxide) or reversible (deoxynojirimycin derivatives) inhibitors. A defect in negatively charged phospholipid activation was present in the majority of variant GCases but was increased in two, N370S and V394L. Deficits in saposin C enhancement of k(cat) were present in variant GCases involving residues 48-122, whereas approximately 2-fold increases were obtained with the L264I GCase. About 50% of variant GCases each had wild-type or increased sensitivity to in vitro cathepsin D digestion. Mapping of these properties onto the crystal structures of GCase indicated wide dispersion of functional properties that can affect catalytic function and stability. Site-directed mutagenesis of cysteine residues showed that the disulfide bonds, Cys(4)-Cys(16) and Cys(18)-Cys(23), and a free Cys(342) were essential for activity; the free Cys(126) and Cys(248) were not. Relative k(cat) was highly sensitive to a His substitution at Arg(496) but not at Arg(495). These studies and high phylogenetic conservation indicate localized and general structural effects of Gaucher disease mutations that were not obvious from the nature of the amino acid substitution, including those predicted to be nondisruptive (e.g. Val --> Leu). These results provide initial studies for the engineering of variant GCases and, potentially, molecular chaperones for therapeutic use.
Tobacco Price Increase and Smoking Cessation in Japan, a Developed Country With Affordable Tobacco: A National Population-Based Observational Study (2015)

The tobacco price increase in Japan had a significant impact on smoking cessation in both sexes, especially among heavy smokers, with no clear difference in effect by socio-demographic status.
Amyloid β peptide load is correlated with increased β-secretase activity in sporadic Alzheimer's disease patients (2004)

Whether elevated beta-secretase (BACE) activity is related to plaque formation or amyloid beta peptide (Abeta) production in Alzheimer's disease (AD) brains remains inconclusive. Here, we report that we used sandwich enzyme-linked immunoabsorbent assay to quantitate various Abeta species in the frontal cortex of AD brains homogenized in 70% formic acid. We found that most of the Abeta species detected in rapidly autopsied brains (<3 h) with sporadic AD were Abeta(1-x) and Abeta(1-42), as well as Abeta(x-42). To establish a linkage between Abeta levels and BACE, we examined BACE protein, mRNA expression and enzymatic activity in the same brain region of AD brains. We found that both BACE mRNA and protein expression is elevated in vivo in the frontal cortex. The elevation of BACE enzymatic activity in AD is correlated with brain Abeta(1-x) and Abeta(1-42) production. To examine whether BACE elevation was due to mutations in the BACE-coding region, we sequenced the entire ORF region of the BACE gene in these same AD and nondemented patients and performed allelic association analysis. We found no mutations in the ORF of the BACE gene. Moreover, we found few changes of BACE protein and mRNA levels in Swedish mutated amyloid precursor protein-transfected cells. These findings demonstrate correlation between Abeta loads and BACE elevation and also suggest that as a consequence, BACE elevation may lead to increased Abeta production and enhanced deposition of amyloid plaques in sporadic AD patients.
Application of a single‐colony coculture technique to the isolation of hitherto unculturable gut bacteria (2014)

Molecular studies have led to postulation of a relationship between gut microbiota and certain diseases. However, because studies of hitherto uncultured species in vivo are essential for characterizing the biology and pathogenic properties of gut bacteria, techniques for culturing and isolating such bacteria must be developed. Here, a technique is described that partially overcomes the obstacles that prevent detection of interbacterial communication in vitro and are thus responsible for the failure to culture certain bacterial species. For this purpose, a ring with a membrane filter at the bottom was designed and a relatively simple nutrient medium was used instead of conventional media. Gut bacteria were cocultivated in soft agar separated by the membrane filter to simulate interbacterial communication in vitro. Use of this soft agar coculture technique led to the successful isolation of hitherto uncultured bacteria and the demonstration of multistage interbacterial communication among gut bacteria in vitro. Cultivation and isolation of single colonies of bacteria that require other bacteria for growth will enhance efforts to better understand the physiological and pathogenic roles of gut microbiota.