gebhart/patrepeval huggingface dataset:
Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers (2014)

Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types, into "high" and "low" AIM gene expression subsets in tumor expression data from both TCGA and GEO. Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers.
Characterizing the activity of abundant, diverse and active CRISPR-Cas systems in lactobacilli (2018)

CRISPR-Cas systems provide immunity against phages and plasmids in bacteria and archaea. Despite the popularity of CRISPR-Cas9 based genome editing, few endogenous systems have been characterized to date. Here, we sampled 1,262 publically available lactobacilli genomes found them to be enriched with CRISPR-Cas adaptive immunity. While CRISPR-Cas is ubiquitous in some Lactobacillus species, CRISPR-Cas content varies at the strain level in most Lactobacillus species. We identified that Type II is the most abundant type across the genus, with II-A being the most dominant sub-type. We found that many Type II-A systems are actively transcribed, and encode spacers that efficiently provide resistance against plasmid uptake. Analysis of various CRISPR transcripts revealed that guide sequences are highly diverse in terms of crRNA and tracrRNA length and structure. Interference assays revealed highly diverse target PAM sequences. Lastly, we show that these systems can be readily repurposed for self-targeting by expressing an engineered single guide RNA. Our results reveal that Type II-A systems in lactobacilli are naturally active in their native host in terms of expression and efficiently targeting invasive and genomic DNA. Together, these systems increase the possible Cas9 targeting space and provide multiplexing potential in native hosts and heterologous genome editing purpose.
Nrf2, a Cap'n'Collar Transcription Factor, Regulates Induction of the Heme Oxygenase-1 Gene (1999)

Stress response elements, which mediate induction of the mouse heme oxygenase-1 (HO-1) gene by several agents, resemble the binding site for the activator protein-1 (Jun/Fos), Maf, and Cap'n'Collar/basic leucine zipper (CNC-bZIP) families of proteins. In L929 fibroblasts, significant activation of an HO-1 enhancer-reporter fusion gene was observed only with the CNC-bZIP class of proteins with Nrf2 exhibiting the highest level of trans-activation, between 25- and 30-fold. To further examine the role of this factor in HO-1 gene regulation, a dominant-negative mutant, Nrf2M, was generated and conditionally expressed in L929 cells. The mutant protein was detected in cytoplasmic and nuclear fractions but did not affect cell growth. Under conditions of Nrf2M overexpression, HO-1 mRNA accumulation in response to heme, cadmium, zinc, arsenite, and tert-butylhydroquinone was inhibited by 85-95%. In contrast, overexpression of a dominant-negative mutant of c-Jun decreased L929 cell growth but did not inhibit HO-1 gene activation. Nrf2 does not homodimerize, but CNC-bZIP.small Maf protein heterodimers and Nrf2. Jun protein complexes are proposed to function as trans-activators. Co-expression of Jun proteins or p18, however, had no significant affect or inhibited Nrf2-mediated trans-activation. Taken together, these results implicate Nrf2 in the induction of the HO-1 gene but suggest that the Nrf2 partner in this function is a factor other than p18 or Jun proteins.
FSP27 Promotes Lipid Droplet Clustering and Then Fusion to Regulate Triglyceride Accumulation (2011)

Fat Specific Protein 27 (FSP27), a lipid droplet (LD) associated protein in adipocytes, regulates triglyceride (TG) storage. In the present study we demonstrate that FSP27 plays a key role in LD morphology to accumulate TGs. We show here that FSP27 promotes clustering of the LDs which is followed by their fusion into fewer and enlarged droplets. To map the domains of FSP27 responsible for these events, we generated GFP-fusion constructs of deletion mutants of FSP27. Microscopic analysis revealed that amino acids 173-220 of FSP27 are necessary and sufficient for both the targeting of FSP27 to LDs and the initial clustering of the droplets. Amino acids 120-140 are essential but not sufficient for LD enlargement, whereas amino acids 120-210 are necessary and sufficient for both clustering and fusion of LDs to form enlarged droplets. In addition, we found that FSP27-mediated enlargement of LDs, but not their clustering, is associated with triglyceride accumulation. These results suggest a model in which FSP27 facilitates LD clustering and then promotes their fusion to form enlarged droplets in two discrete, sequential steps, and a subsequent triglyceride accumulation.
Signs of Nephropathy May Occur Early in Young Adults With Diabetes Despite Modern Diabetes Management (2003)

Despite modern treatment and self-monitoring of blood glucose, young adult patients with diabetes may still develop renal involvement during the first 10 years of diabetes duration. Inadequate HbA(1c), high blood pressure, and type 2 diabetes appear to be risk markers for early occurrence of diabetic nephropathy.
Destructive Adsorption of Chlorinated Benzenes on Ultrafine (Nanoscale) Particles of Magnesium Oxide and Calcium Oxide (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDestructive Adsorption of Chlorinated Benzenes on Ultrafine (Nanoscale) Particles of Magnesium Oxide and Calcium OxideYong-Xi. Li, Hui. Li, and Kenneth J. KlabundeCite this: Environ. Sci. Technol. 1994, 28, 7, 1248–1253Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://pubs.acs.org/doi/10.1021/es00056a011https://doi.org/10.1021/es00056a011research-articleACS PublicationsRequest reuse permissionsArticle Views329Altmetric-Citations34LEARN 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 Get e-Alerts
The flaA locus of Bacillus subtilis is part of a large operon coding for flagellar structures, motility functions, and an ATPase-like polypeptide (1991)

We cloned and sequenced 8.3 kb of Bacillus subtilis DNA corresponding to the flaA locus involved in flagellar biosynthesis, motility, and chemotaxis. The DNA sequence revealed the presence of 10 complete and 2 incomplete open reading frames. Comparison of the deduced amino acid sequences to data banks showed similarities of nine of the deduced products to a number of proteins of Escherichia coli and Salmonella typhimurium for which a role in flagellar functioning has been directly demonstrated. In particular, the sequence data suggest that the flaA operon codes for the M-ring protein, components of the motor switch, and the distal part of the basal-body rod. The gene order is remarkably similar to that described for region III of the enterobacterial flagellar regulon. One of the open reading frames was translated into a protein with 48% amino acid identity to S. typhimurium FliI and 29% identity to the beta subunit of E. coli ATP synthase.
Semantic-Driven Model Composition for Accurate Anomaly Diagnosis (2008)

In this paper, we introduce a semantic-driven approach to system modeling for improving the accuracy of anomaly diagnosis. Our framework composes heterogeneous families of models, including generic statistical models, and resource-specific models into a belief network, i.e., Bayesian network. Given a set of models which sense the behavior of various system components, the key idea is to incorporate expert knowledge about the system structure and dependencies within this structure, as meta-correlations across components and models. Our approach is flexible, easily extensible and does not put undue burden on the system administrator. Expert beliefs about the system hierarchy, relationships and known problems can guide learning, but do not need to be fully specified. The system dynamically evolves its beliefs about anomalies over time. We evaluate our prototype implementation on a dynamic content site running the TPC-W industry-standard e- commerce benchmark. We sketch a system structure and train our belief network using automatic fault injection. We demonstrate that our technique provides accurate problem diagnosis in cases of single and multiple faults. We also show that our semantic-driven modeling approach effectively finds the component containing the root cause of injected anomalies, and avoids false alarms for normal changes in environment or workload.
Up-regulation of Glucosylceramide Synthesis upon Stimulation of Axonal Growth by Basic Fibroblast Growth Factor (2000)

We have previously shown that ongoing glucosylceramide (GlcCer) synthesis is required for basic fibroblast growth factor (bFGF) and laminin to stimulate axonal growth in cultured hippocampal neurons (Boldin, S., and Futerman, A. H. (1997) J. Neurochem. 68, 882-885). We now demonstrate that stimulation of axonal growth by bFGF leads to an increase in the rate of GlcCer synthesis. Within minutes of incubation with bFGF, a significant increase in the rate of metabolism of [(14)C]hexanoyl ceramide to [(14)C]hexanoyl GlcCer is detected, but there are no changes in the rate of [(14)C]hexanoyl sphingomyelin synthesis. In vitro analysis of GlcCer synthase activity revealed an approximately 2-fold increase in the rate of [(14)C]hexanoyl GlcCer synthesis upon incubation with either bFGF or laminin; other growth factors, which did not effect the rate of axon growth, had no effect on the rate of [(14)C]hexanoyl GlcCer synthesis. The increased rate of [(14)C]hexanoyl GlcCer synthesis was not affected by preincubation with either cycloheximide or actinomycin, and no elevation of GlcCer synthase mRNA levels was detected, suggesting that GlcCer synthase is up-regulated by a post-translational mechanism. The relevance of these results for understanding the regulation of axonal growth is discussed.
Learning to Find Good Correspondences (2018)

We develop a deep architecture to learn to find good correspondences for wide-baseline stereo. Given a set of putative sparse matches and the camera intrinsics, we train our network in an end-to-end fashion to label the correspondences as inliers or outliers, while simultaneously using them to recover the relative pose, as encoded by the essential matrix. Our architecture is based on a multi-layer perceptron operating on pixel coordinates rather than directly on the image, and is thus simple and small. We introduce a novel normalization technique, called Context Normalization, which allows us to process each data point separately while embedding global information in it, and also makes the network invariant to the order of the correspondences. Our experiments on multiple challenging datasets demonstrate that our method is able to drastically improve the state of the art with little training data.
Targeting cancer with phosphodiesterase inhibitors (2009)

Impaired cAMP and/or cGMP generation upon overexpression of PDE isoforms has been described in various cancer pathologies. Inhibition of selective PDE isoforms, which raises the levels of intracellular cAMP and/or cGMP, induces apoptosis and cell cycle arrest in a broad spectrum of tumour cells and regulates the tumour microenvironment. Therefore, the development and clinical application of inhibitors specific for individual PDE isoenzymes may selectively restore normal intracellular signalling, providing antitumour therapy with reduced adverse effects.
Chemistry with [18F]Fluoride Ion (2008)

Abstract The success of molecular imaging with positron‐emission tomography (PET) depends on the availability of selective molecular probes labeled with positron‐emitters, such asfluorine‐18 ( t 1/2 = 109.7 min). No‐carrier‐added (NCA) [ 18 F]fluoride ion ( 18 F – ) is the primary reagent for the preparation of 18 F‐labeled tracers in high specific activity. In this microreview, we survey current and advancing radiochemical methods and technologies for the use of NCA [ 18 F]fluoride ion in the preparation of 18 F‐labeled radiotracers for applications with PET. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)
Preemptive Pharmacologic Intervention in Radiation-Induced Salivary Dysfunction (1999)

Xerostomia (“dry mouth”) is a symptom of several diseases. It also occurs as a side effect of certain therapeutic interventions, most frequently pharmacotherapy. The most severe and irreversible forms of salivary dysfunction result from damage to or loss of salivary acinar cells. One of the severest forms of iatrogenic salivary gland destruction results from the therapeutic doses of irradiation given to treat head and neck cancer or to purge the bone marrow before transplantation. Xerostomia encompasses a wide range of involvement, from an inconvenience when mild, to a debilitating condition when severe. Reports of the symptom of dry mouth by patients do not always correlate with the degree of diminished salivary flow. However, a significant loss of stimulated flow makes it difficult to process solid food into a bolus that can be swallowed. If sustained, nutritional deficiencies may result. Saliva also facilitates formation of speech patterns. Its loss hinders speaking and communicating, possibly causing the patient to withdraw from social interaction. Together these conditions can impair the physiological and psychological well-being of the patient Thousands of individuals undergo radiation therapy for head and neck cancer in the United States each year. Increasing numbers are receiving total body radiation before transplantation of bone marrow. Although the salivary gland is not one of the more actively dividing organs in the body, nevertheless it ranks as one of the most radiosensitive. The mechanism of this sensitivity is not understood. This article reviews human and animal pathophysiology of radiation-induced salivary damage. We also discuss animal studies that have employed various strategies to modify and clarify this process. Finally, we describe encouraging results from early clinical trials suggesting that protection of salivary glands during therapeutic irradiation may be possible.
Unexpected Abundance of HLA Class II Presented Peptides in Primary Renal Cell Carcinomas (2006)

Thus, our direct approach will rapidly expand the limited number of T-helper epitopes from TAAs for their use in clinical vaccination protocols.
Bone-Specific Expression of the Alpha Chain of the Nascent Polypeptide-Associated Complex, a Coactivator Potentiating c-Jun-Mediated Transcription (1998)

The alpha chain of the nascent polypeptide-associated complex (alpha-NAC) coactivator was shown to potentiate the activity of the homodimeric c-Jun activator, while transcription mediated by the c-Fos/c-Jun heterodimer was unaffected. The use of deletion mutants in pull-down assays revealed that alpha-NAC interacted with amino acids 1 to 89 of the c-Jun protein and that the coactivator could interact with both the unphosphorylated and the serine 73-phosphorylated form of c-Jun. N-terminal-deleted c-Jun protein failed to interact with alpha-NAC in mammalian two-hybrid assays, while mutant c-Jun proteins lacking the leucine zipper or the basic domain retained interaction with alpha-NAC in vivo. Kinetics studies with purified c-Jun homodimer and recombinant alpha-NAC proteins allowed determination of the mechanism of coactivation by alpha-NAC: the coactivator stabilized the AP-1 complex formed by the c-Jun homodimer on its DNA recognition sequence through an eightfold reduction in the dissociation constant (kd) of the complex. This effect of alpha-NAC was specific, because alpha-NAC could not stabilize the interactions of JunB or Sp1 with their cognate binding sites. Interestingly, the expression of alpha-NAC was first detected at 14.5 to 15 days postconception, concomitantly with the onset of ossification during embryogenesis. The alpha-NAC protein was specifically expressed in differentiated osteoblasts at the centers of ossification. Thus, the alpha-NAC gene product exhibits the properties of a developmentally regulated, bone-specific transcriptional coactivator.
Stereochemistry of viminol, a novel central analgesic. (1978)

The synthesis of the stereoisomers of the centrally acting analgesic 1-[1-(2-chlorobenzyl)-pyrrol-2-yl]-2-di-sec.-butylamino-ethanol (viminol) is described. Their absolute configuration has been shown by comparing the circular dichroism (CD) curves with those of some phenyl analogs: for one of the viminol stereoisomers the postulated configurational assignment has been recently confirmed by an X-ray analysis. The pharmacological properties shared by the viminol stereoisomers are also described. The R,R configuration of the sec.-butyl groups and the S configuration of the hydroxy group appear to be essential for the agonistic effects: analgesia, tolerance and physical dependence in rodents. The S,R,R configurated viminol does not substitute, however, for morphine in monkeys, using the single dose suppression test. S,S or R,S(S,R) configurations of the sec.-butyl groups are associated with antagonistic properties. The binding capacity of the viminol stereoisomers to the opiate receptors and their influence on the acetylcholine release from the intestinal cholinergic terminals electrically stimulated are also described.
Modes of inhibition of cysteine proteases. (2004)

Cysteine proteases are involved in many physiological processes and their hyperactivity may lead to severe diseases. Nature has developed various strategies to protect cells and whole organisms against undesired proteolysis. One of them is the control of proteolytic activity by inhibition. This paper presents the mechanisms underlying the action of proteinaceous inhibitors of cysteine proteinases and covers propeptides binding backwards relative to the substrate or distorting the protease catalytic centre similarly to serpins, the p35 protein binding covalently to the enzyme, and cystatins that are exosite binding inhibitors. The paper also discusses tyropins and chagasins that, although unrelated to cystatins, inhibit cysteine proteinases by a similar mechanism, as well as inhibitors of the apoptosis protein family that bind in a direction opposite to that of the substrate, similarly to profragments. Special attention is given to staphostatins, a novel family of inhibitors acting in an unusual manner.
Identification of a conserved bacterial protein secretion system in Vibrio cholerae using the Dictyostelium host model system (2006)

The bacterium Vibrio cholerae, like other human pathogens that reside in environmental reservoirs, survives predation by unicellular eukaryotes. Strains of the O1 and O139 serogroups cause cholera, whereas non-O1/non-O139 strains cause human infections through poorly defined mechanisms. Using Dictyostelium discoideum as a model host, we have identified a virulence mechanism in a non-O1/non-O139 V. cholerae strain that involves extracellular translocation of proteins that lack N-terminal hydrophobic leader sequences. Accordingly, we have named these genes "VAS" genes for virulence-associated secretion, and we propose that these genes encode a prototypic "type VI" secretion system. We show that vas genes are required for cytotoxicity of V. cholerae cells toward Dictyostelium amoebae and mammalian J774 macrophages by a contact-dependent mechanism. A large number of Gram-negative bacterial pathogens carry genes homologous to vas genes and potential effector proteins secreted by this pathway (i.e., hemolysin-coregulated protein and VgrG). Mutations in vas homologs in other bacterial species have been reported to attenuate virulence in animals and cultured macrophages. Thus, the genes encoding the VAS-related, type VI secretion system likely play an important conserved function in microbial pathogenesis and represent an additional class of targets for vaccine and antimicrobial drug-based therapies.
High-voltage GaN pin vertical rectifierswith 2 µm thick i -Layer (2000)

Gallium nitride pin rectifiers have been fabricated and characterised. The device structures were grown by metalorganic chemical vapour deposition on c-plane sapphire substrates. The pin diode epitaxial structure consisted of an n+-GaN layer, followed by a 2 µm i-GaN layer and a p-type GaN layer on top. The mesa-structure pin diodes exhibited a blocking voltage as large as Vr ≃ –410 V at a reverse current density of Ir ≃ 10 A/cm2 and a forward voltage drop of only 8 V at a forward current density of ~100 A/cm2. These values indicate that GaN-based pin rectifiers can be useful in high-voltage circuits.