gebhart/patrepeval huggingface dataset:
Epitope Mapping Porcine Reproductive and Respiratory Syndrome Virus by Phage Display: the nsp2 Fragment of the Replicase Polyprotein Contains a Cluster of B-Cell Epitopes (2001)

We screened phage display libraries of porcine reproductive and respiratory syndrome virus (PRRSV) protein fragments with sera from experimentally infected pigs to identify linear B-cell epitopes that are commonly recognized during infection in vivo. We identified 10 linear epitope sites (ES) 11 to 53 amino acids in length. In the replicase polyprotein, a total of eight ES were identified, six of which localized to the Nsp2 replicase polyprotein processing end product. In the structural proteins, a total of two ES were identified, in the ORF3 and ORF4 minor envelope glycoproteins. The ORF4 ES was previously identified by monoclonal antibody mapping (J. J. M. Meulenberg, A. P. van Nieuwstadt, A. van Essen-Zandenbergen, and J. P. M. Langeveld, J. Virol. 71:6061-6067, 1997), but its immunogenicity had not been examined in pigs. We found that six experimentally PRRSV-infected pigs consistently had very high antibody titers against the ORF4 ES. In some animals, sera diluted 1:62,500 still gave weak positive enzyme immunoassay reactivity against the ORF4 ES. This hitherto unrecognized immunodominance likely caused phages displaying the ORF4 ES to outcompete phages displaying other ES during library screening with porcine sera and accounted for our failure to identify more than two ES in the structural genes of PRRSV. Genetic analysis showed that variable ES were also the most immunogenic in vivo. Serological analysis indicated differences in the immunoglobulin A responses between short-term and longer-term viremic pigs towards some ES. The implications of these findings for PRRSV diagnostics and immunopathogenesis are discussed.
A Highly Efficient Method for Porcine Cloning by Nuclear Transfer Using In Vitro -Matured Oocytes (2002)

To date, the efficiency of pig cloning by nuclear transfer of somatic cell nuclei has been extremely low, with less than 1% of transferred embryos surviving to term. Even the utilization of complex procedures such as two rounds of nuclear transfer has not resulted in greater overall efficiencies. As a result, the applicability of the technology for the generation of transgenic and cloned animals has not moved forward rapidly. We report here a simple nuclear transfer protocol, utilizing commercially available in vitro-matured oocytes, that results in greater than 5% overall cloning efficiency. Of five recipients receiving nuclear transfer embryos produced with a fetal fibroblast cell line as nuclear donor, all five established pregnancies by day 28 (100%), and 4/5 (80%) went to term. Efficiencies for each transfer were 7% (9 piglets/128 doublets transferred), 5% (5/100), 12% (7/59), and 6.6% (7/106). The overall efficiency in all recipients was 5.5% and in pregnant recipients 7.7%, with a total of 28 cloned piglets produced. With the average fusion rate being 58%, the percentage of fused doublets producing a live piglet approached 12%. The method described here can be undertaken by a single micromanipulator at a reasonable cost, and should facilitate the broad utilization of porcine cloning technology in transgenic and nontransgenic applications.
Predictors of Migraine Headache Recurrence: A Pooled Analysis From the Eletriptan Database (2007)

Female gender, age > or = 35 years, and severe baseline headache pain are significant predictors of headache recurrence during a migraine attack. Eletriptan is effective at reducing the incidence of headache recurrence in high-risk subgroups.
Pseudo-task Augmentation: From Deep Multitask Learning to Intratask Sharing---and Back (2018)

Deep multitask learning boosts performance by sharing learned structure across related tasks. This paper adapts ideas from deep multitask learning to the setting where only a single task is available. The method is formalized as pseudo-task augmentation, in which models are trained with multiple decoders for each task. Pseudo-tasks simulate the effect of training towards closely-related tasks drawn from the same universe. In a suite of experiments, pseudo-task augmentation is shown to improve performance on single-task learning problems. When combined with multitask learning, further improvements are achieved, including state-of-the-art performance on the CelebA dataset, showing that pseudo-task augmentation and multitask learning have complementary value. All in all, pseudo-task augmentation is a broadly applicable and efficient way to boost performance in deep learning systems.
Tissue specific promoters improve specificity of AAV9 mediated transgene expression following intra-vascular gene delivery in neonatal mice (2008)

The AAV9 capsid displays a high natural affinity for the heart following a single intravenous (IV) administration in both newborn and adult mice. It also results in substantial albeit relatively lower expression levels in many other tissues. To increase the overall safety of this gene delivery method we sought to identify which one of a group of promoters is able to confer the highest level of cardiac specific expression and concurrently, which is able to provide a broad biodistribution of expression across both cardiac and skeletal muscle. The in vivo behavior of five different promoters was compared: CMV, desmin (Des), alpha-myosin heavy chain (alpha-MHC), myosin light chain 2 (MLC-2) and cardiac troponin C (cTnC). Following IV administration to newborn mice, LacZ expression was measured by enzyme activity assays. Results showed that rAAV2/9-mediated gene delivery using the alpha-MHC promoter is effective for focal transgene expression in the heart and the Des promoter is highly suitable for achieving gene expression in cardiac and skeletal muscle following systemic vector administration. Importantly, these promoters provide an added layer of control over transgene activity following systemic gene delivery.
Human fecal flora: variation in bacterial composition within individuals and a possible effect of emotional stress (1976)

Data are presented on the distribution of 101 bacterial species and subspecies among 1,442 isolates from 25 fecal specimens from three men on: (i) their normal diet and normal living conditions, (ii) normal living conditions but eating the controlled metabolic diet designed for use in the Skylab simulation and missions, and (iii) the Skylab diet in simulated Skylab (isolation) conditions. These bacteria represent the most numerous kinds in the fecal flora. Analyses of the kinds of bacteria from each astronaut during the 5-month period showed more variation in the composition of the flora among the individual astronauts than among the eight or nine samples from each person. This observation indicates that the variations in fecal flora reported previously, but based on the study of only one specimen from each person, more certainly reflect real differences (and not daily variation) in the types of bacteria maintained by individual people. The proportions of the predominant fecal species in the astronauts were similar to those reported earlier from a Japanese-Hawaiian population and were generally insensitive to changes from the normal North American diet to the Skylab diet; only two of the most common species were affected by changes in diet. However, one of the predominant species (Bacteroides fragilis subsp. thetaiotaomicron) appeared to be affected during confinement of the men in the Skylab test chamber. Evidence is presented suggesting that an anger stress situation may have been responsible for the increase of this species simultaneously in all of the subjects studied. Phenotypic characteristics of some of the less common isolates are given. The statistical analyses used in interpretation of the results are discussed.
Functional variation in the 3′ untranslated region of the serotonin transporter in human and rhesus macaque (2008)

The serotonin system underlies a wide variety of behavioral traits and its dysregulation is the cause of numerous neuropsychiatric disorders. Among genes involved in the system, the serotonin transporter (SERT) is integral and has been repeatedly shown to be associated with disease as well as being a primary drug target. In addition to promoter region variation, we identify here variation in a regulatory region in the 3' untranslated region (UTR) of the SERT gene in both humans and rhesus macaques. We comprehensively survey the 3' UTR of SLC6A4 in Indian-origin rhesus macaques to identify three single nucleotide polymorphisms (SNPs) creating two haplotypes, both derived from an ancestral sequence, that represent the vast majority of the alleles in the population. Through the use of a luciferase reporter gene assay, we are able to show that not only do these alleles have differential effects on gene expression, modulated through changes in messenger RNA stability, but that different commonly occurring SNPs in the human 3' UTR also have similar effects. This finding not only offers additional insight into the regulation, and thus dysregulation, of SERT expression, but also suggests the role of natural selection in maintaining both high and low SERT expression levels broadly across populations of multiple primate species.
Mechanism for Cyclization Reaction by Clavaminic Acid Synthase. Insights from Modeling Studies (2007)

The mechanism of the oxidative cyclization reaction catalyzed by clavaminic acid synthase (CAS) was studied in silico. First, a classical molecular dynamics (MD) simulation was performed to obtain a realistic structure of the CAS-Fe(IV)=O-succinate-substrate complex; then potential of mean force (PMF) was calculated to assess the feasibility of the beta-lactam ring, more specifically its C4' corner, approaching the oxo atom. Based on the MD structure, a relatively large model of the active site region was selected and used in the B3LYP investigation of the reaction mechanism. The computational results suggest that once the oxoferryl species is formed, the oxidative cyclization catalyzed by CAS most likely involves either a mechanism involving C4'(S)-H bond cleavage of the monocyclic beta-lactam ring, or a biosynthetically unprecedented mechanism comprising (1) oxidation of the hydroxyl group of PCA to an O-radical, (2) retro-aldol-like decomposition of the O-radical to an aldehyde and a C-centered radical, which is stabilized by the captodative effect, (3) abstraction of a hydrogen atom from the C4'(S) position of the C-centered radical by the Fe(III)-OH species yielding an azomethine ylide, and (4) 1,3-dipolar cycloaddition to the ylide with aldehyde acting as a dipolarophile. Precedent for the new proposed mechanism comes from the reported synthesis of oxapenams via 1,3-dipolar cycloaddition reactions of aldehydes and ketones.
Hypoxia promotes dissemination of multiple myeloma through acquisition of epithelial to mesenchymal transition-like features (2012)

The spread of multiple myeloma (MM) involves (re)circulation into the peripheral blood and (re)entrance or homing of MM cells into new sites of the BM. Hypoxia in solid tumors was shown to promote metastasis through activation of proteins involved in the epithelial-mesenchymal transition (EMT) process. We hypothesized that MM-associated hypoxic conditions activate EMT-related proteins and promote metastasis of MM cells. In the present study, we have shown that hypoxia activates EMT-related machinery in MM cells, decreases the expression of E-cadherin, and, consequently, decreases the adhesion of MM cells to the BM and enhances egress of MM cells to the circulation. In parallel, hypoxia increased the expression of CXCR4, consequently increasing the migration and homing of circulating MM cells to new BM niches. Further studies to manipulate hypoxia to regulate tumor dissemination as a therapeutic strategy are warranted.
Beneficial effects of n‐acetylcysteine on ischaemic brain injury (2000)

1. Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly (ADP-ribole) synthetase have been implicated as mediators of neuronal damage following focal ischaemia. Here we have investigated the effects of n-acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral ischaemia. 2. Treatment of gerbils with NAC (20 mg kg(-1) 30 min before reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post-ischaemic brain oedema, evaluated by water content. 3. NAC also attenuated the increase in the brain levels of malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia. 4. Positive staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian gerbils subjected to cerebral ischaemia also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received NAC. 5. NAC treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischaemia and reperfusion. 6. Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received NAC. 7. These results show that NAC improves brain injury induced by transient cerebral ischaemia.
Synthetic Serine Elastase Inhibitor Reduces Cigarette Smoke–induced Emphysema in Guinea Pigs (2002)

To test whether a serine elastase inhibitor could prevent or reduce emphysema, we exposed guinea pigs to cigarette smoke acutely, or daily for 6 months, and treated some animals with the neutrophil elastase inhibitor ZD0892. Acute smoke exposure increased lavage neutrophils and increased desmosine and hydroxyproline, measures of elastin and collagen breakdown; all these measures were reduced by ZD0892. Long-term smoke exposure produced emphysema and increases in lavage neutrophils, desmosine, hydroxyproline, and plasma tumor necrosis factor alpha (TNF-alpha). ZD0892 treatment returned lavage neutrophils, desmosine, and hydroxyproline levels to control values, and decreased airspace enlargement by 45% and TNF-alpha by 30%. Animals exposed to smoke for 4 months and then to smoke plus ZD0892 for 2 months were not protected against emphysema. Mice exposed to smoke showed increases in gene expression of neutrophil chemoattractant macrophage inflammatory protein-2, macrophage chemoattractant protein-1, and TNF-alpha at 2 hours along with increased plasma TNF-alpha; ZD0892 prevented the increases in macrophage inflammatory protein-2 and macrophage chemoattractant protein-1 expression and reduced plasma TNF-alpha levels to baseline. These data demonstrate that a serine elastase inhibitor ameliorates the inflammatory and destructive effects of cigarette smoke, and that these effects are mediated in part by neutrophils and by smoke-driven TNF-alpha production.
Oncogenic Function of a Novel WD-Domain Protein, STRAP, in Human Carcinogenesis (2006)

The development and progression of malignancies is a complex multistage process that involves the contribution of a number of genes giving growth advantage to cells when transformed. The role of transforming growth factor-beta (TGF-beta) in carcinogenesis is complex with tumor-suppressor or prooncogenic activities depending on the cell type and the stage of the disease. We have previously reported the identification of a novel WD-domain protein, STRAP, that associates with both TGF-beta receptors and that synergizes with the inhibitory Smad, Smad7, in the negative regulation of TGF-beta-induced transcription. Here, we show that STRAP is ubiquitously expressed and is localized in both cytoplasm and nucleus. STRAP is up-regulated in 60% colon and in 78% lung carcinomas. Stable expression of STRAP results in activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and in down-regulation of the cyclin-dependent kinase inhibitor p21(Cip1), which results in retinoblastoma protein hyperphosphorylation. In addition, we have observed that Smad2/3 phosphorylation, TGF-beta-mediated transcription, and growth inhibition are induced in STRAP-knockout mouse embryonic fibroblasts compared with wild-type cells. Ectopic expression of STRAP in A549 lung adenocarcinoma cell line inhibits TGF-beta-induced growth inhibition and enhances anchorage-independent growth of these cells. Moreover, overexpression of STRAP increases tumorigenicity in athymic nude mice. Knockdown of endogenous STRAP by small interfering RNA increases TGF-beta signaling, reduces ERK activity, increases p21(Cip1) expression, and decreases tumorigenicity. Taken together, these results suggest that up-regulation of STRAP in human cancers may provide growth advantage to tumor cells via TGF-beta-dependent and TGF-beta-independent mechanisms, thus demonstrating the oncogenic function of STRAP.
High levels of 5-hydroxymethylcytosine (5hmC) is an adverse predictor of biochemical recurrence after prostatectomy in ERG-negative prostate cancer (2015)

This is the first study to demonstrate a prognostic potential for 5hmC in PC. Our findings highlight the importance of ERG stratification in PC biomarker studies and suggest that epigenetic mechanisms involving 5hmC are important for the development and/or progression of ERG- PC.
Amplification in a Fiber Laser (1964)

Fiber lasers of neodymium-doped glass have been used on a pulsed basis to amplify 1.06-μ radiation. To prevent oscillation, the ends are polished at an angle such that reflected light is lost from the cavity. With the high inversion which can then be obtained, gains as large as 5 × 104 have been observed in a 1-m long fiber. The gain was measured as a function of pumping energy and as a function of time during the pumping pulse at which the amplification was determined.
Growth-promoting effect of recombinant interleukin 1 and tumor necrosis factor for a human astrocytoma cell line. (1987)

IL 1 can exhibit dichotomous effects in the sense that it is cytotoxic for certain cells, although growth promoting for other cells. Because IL 1 is growth promoting for astrocytes, but cytotoxic for melanoma cells, the current investigation evaluated the effect of IL 1 upon astrocytomas. The human astrocytoma U373 was found to incorporate [3H]thymidine after exposure to recombinant human IL 1 alpha and IL 1 beta and murine IL 1 alpha. Surprisingly, U373 also incorporated [3H]thymidine after exposure to recombinant TNF. The response of the U373 to IL 1 may be used as a simple and sensitive assay for IL 1.
Fatty acid monooxygenation by cytochrome P-450BM-3. (1990)

Cytochrome P-450BM-3 is a catalytically self-sufficient enzyme which monooxygenates saturated and unsaturated fatty acids, alcohols, and amides. The protein has two domains: one which contains heme and is P-450-like and the other which contains FAD and FMN and is P-450 reductase-like. Both domains are on a single polypeptide chain. Utilizing a plasmid containing the gene encoding P-450BM-3, we have transformed the Escherichia coli strain DH5 alpha. This clone overexpresses P-450BM-3 to make approximately 20% of the soluble protein of this organism under optimal conditions. P-450BM-3 can be purified to homogeneity from the soluble fraction of the protein of these cells with a recovery of 50% making this cell line an excellent source of this important enzyme. Purified preparations of P-450BM-3 hydroxylate palmitic acid at a rate of 1600 mol/min/mol of heme at 25 degrees C. The stoichiometry of NADPH to oxygen utilized was 1 for all conditions; however, the ratio of oxygen or NADPH utilized per molecule of fatty acid substrate metabolized was different for different homologs of saturated fatty acids, when low concentrations (less than 100 microM) of substrate were used. Lauric and myristic acids were metabolized to two hydroxylated products, irrespective of the initial concentration of fatty acid in the reaction mixture, and the ratio of oxygen consumed to fatty acid hydroxylated was 1. High concentrations of palmitic acid (greater than 200 microM) led to the formation of three polar metabolites and a stoichiometry of 1:1 was observed for oxygen and palmitic acid utilization. These results indicate that a single hydroxyl group was inserted into each of these molecules. Lower concentrations (less than 50 microM) of palmitic acid were metabolized to additional polar metabolites, and the ratio of oxygen consumed to fatty acid substrate consumed approximated 3:1. These results can be explained best by a hypothesis that the initial hydroxylated compounds, which accumulate during the oxidation of palmitic acid by P-450BM-3, can be further oxidized by this enzyme to polyhydroxy- or hydroxy-ketone products.
Poly(fluorenyleneethynylene)s by Alkyne Metathesis:  Optical Properties and Aggregation Behavior (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunication to the...Communication to the EditorNEXTPoly(fluorenyleneethynylene)s by Alkyne Metathesis: Optical Properties and Aggregation BehaviorNeil G. Pschirer and Uwe H. F. BunzView Author Information Department of Chemistry and Biochemistry, The University of South Carolina, Columbia, South Carolina 29208 Cite this: Macromolecules 2000, 33, 11, 3961–3963Publication Date (Web):May 9, 2000Publication History Received23 February 2000Revised13 April 2000Published online9 May 2000Published inissue 1 May 2000https://pubs.acs.org/doi/10.1021/ma0003250https://doi.org/10.1021/ma0003250rapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views719Altmetric-Citations102LEARN 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:Alcohols,Fluorescence,Hydrocarbons,Metathesis,Organic polymers Get e-Alerts
Animal models of asthma and chronic bronchitis (1999)

Human asthma is characterized by three critical phenotypic traits: intermittent reversible airway obstruction, airway hyperresponsiveness and airway inflammation. In animal models of asthma, airway hyperresponsiveness is an important feature. This trait is characterized by an exaggerated bronchoconstrictor response that would have little physiological consequence in an otherwise unaffected or normal individual. In this article we explore two distinct facets of airway responsiveness. The first is the genetic basis for variations in airway responsiveness that occur in mice in the absence of any specific environmental manipulation. We demonstrate that standard genetic approaches can be successfully applied to the identification of regions of the mouse genome linked to the expression of airway hyperresponsiveness. The second topic addressed in this review is the change in airway responsiveness induced in rats by repeated exposure to sulphur dioxide gas. With daily exposure to high concentrations of sulphur dioxide gas, there is chronic injury and repair of epithelial cells. Over time, rats develop mucous hypersecretion, airway inflammation, increased airway resistance and airway hyperresponsiveness. This model has provided useful information on the mechanisms underlying the pathophysiological events that typify the chronic bronchitis in humans.