gebhart/patrepeval huggingface dataset:
Long-Term Treatment of Glucagon-Like Peptide-1 Analog Exendin-4 Ameliorates Diabetic Nephropathy through Improving Metabolic Anomalies in db/db Mice (2007)

Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone and is a new clinically available class of agents for improving of insulin resistance in both animals and humans with type 2 diabetes. These studies aimed to determine whether long-term treatment with a long-acting GLP-1 analog, exendin-4, delayed the progression of diabetes. Male db/db mice and db/m mice at 8 wk of age were treated with exendin-4 for 8 wk, whereas the control db/db mice received only vehicle. Urinary albumin excretion was significantly decreased in db/db mice that were treated with 1 nmol/kg exendin-4 compared with those in db/db mice that were treated with 0.5 nmol/kg exendin-4 and control db/db mice (P < 0.005). Intraperitoneal glucose tolerance test was improved in db/db mice that were treated with 1 nmol/kg exendin-4 compared with other groups (P < 0.05). Despite this, fasting blood glucose, glycated hemoglobin, and creatinine concentrations were not significantly different among db/db mice. Renal histology studies further demonstrated that glomerular hypertrophy, mesangial matrix expansion, TGF-beta1 expression, and type IV collagen accumulation and associated glomerular lipid accumulation were significantly decreased in db/db mice that were treated with 1 nmol/kg exendin-4. Furthermore, there were fewer infiltrating inflammatory cells and apoptotic cells in the glomeruli of db/db mice that were treated with 1 nmol/kg exendin-4 compared with those in the other groups accompanied by an increase in the renal immunoreactivity of peroxisome proliferator-activated receptor alpha and GLP-1 receptor-positive cells and a decrease in 24-h urinary 8-hydroxy-deoxyguanosine levels (P < 0.01, respectively) along with decreases in lipid content. Taken together, exendin-4 treatment seems to ameliorate diabetic nephropathy together with improvement of the metabolic anomalies. These results suggest that exendin-4 could provide a therapeutic role in diabetic nephropathy that results from type 2 diabetes.
Synthetic approaches to the quinolinequinone system of streptonigrin (1977)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthetic approaches to the quinolinequinone system of streptonigrinSatoshi Hibino and Steven M. WeinrebCite this: J. Org. Chem. 1977, 42, 2, 232–236Publication Date (Print):January 1, 1977Publication History Published online1 May 2002Published inissue 1 January 1977https://pubs.acs.org/doi/10.1021/jo00422a012https://doi.org/10.1021/jo00422a012research-articleACS PublicationsRequest reuse permissionsArticle Views305Altmetric-Citations29LEARN 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 Little Hulton Project: A Pilot Child Clinical Psychology Service for Pre‐School Children and their Families (2002)

A community‐based early intervention psychology service for pre‐school children with emotional and behavioural problems is described. The intervention included parent training groups, a weekly open clinic, and multi‐agency training, liaison and consultancy. The aims were to provide successful intervention to families, to maximise liaison with community staff and to provide a seamless service to and from the main hospital department. Evidence indicated improvements in parental coping and children's behavioural difficulties using standardised measures and gains were maintained at 6‐ and 12‐month follow‐up. This article outlines a framework for service delivery in a small community with high socio‐economic deprivation.
EFFECT OF PORCINE GROWTH HORMONE-RELEASING FACTOR (1-29)NH2 AND THYROTROPIN-RELEASING FACTOR ON PIG GROWTH PERFORMANCE (1990)

Sixty female pigs were divided into four treatment groups to evaluate the effect of chronic treatment with porcine growth hormone-releasing factor (pGRF), thyrotropin-releasing factor (TRF) and their combination on growth performance of Yorkshire-Landrace pigs. Animals were injected with either saline, pGRF(1-29)NH 2 at 15 μg kg −1 BW, TRF at 6 μg kg −1 BW, or pGRF plus TRF at doses previously mentioned, according to a 2 × 2 factorial design, using three pens of five pigs per treatment. Subcutaneous injections were made twice daily from 19.4 ± 0.8 to 95.2 ± 0.5 kg BW. Treatments did not affect (P &gt; 0.05) average daily weight gain, feed consumption, feed efficiency or age at slaughter. TRF had no effect (P &gt; 0.05) on carcass and blood variables except for reducing lung weight (P &lt; 0.05) and increasing blood-urea nitrogen after 4 wk of treatment. GRF reduced (P &lt; 0.01) backfat thickness at the level of the first thoracic rib, 13th thoracic rib, last lumbar vertebra and at 6.5 cm from the dorsal mid-line at the level of the 13th rib. Furthermore, pGRF increased carcass length, loin eye area at the 13th rib, lung weight and kidney weight. Blood glucose and free fatty acid concentrations were not affected (P &gt; 0.05) by treatments. No significant pGRF × TRF interaction was observed for any measured variables. At the doses injected, TRF and pGRF did not modify growth variables, while pGRF positively affected carcass characteristics by reducing lipid content and increasing carcass length as well as loin eye area. Key words: Growth hormone-releasing factor, thyrotropin-releasing factor, pig, growth performance, carcass characteristics
Remodeling of the Major Pig Xenoantigen by N-Acetylglucosaminyltransferase III in Transgenic Pig (2001)

We have been successful in generating several lines of transgenic mice and pigs that contain the human beta-d-mannoside beta-1,4-N-acetylglucosaminyltransferase III (GnT-III) gene. The overexpression of the GnT-III gene in mice and pigs reduced their antigenicity to human natural antibodies, especially the Galalpha1-3Galbeta1-4GlcNAc-R, as evidenced by immunohistochemical analysis. Endothelial cell studies from the GnT-III transgenic pigs also revealed a significant down-regulation in antigenicity, including Hanganutziu-Deicher antigen, and dramatic reductions in both the complement- and natural killer cell-mediated pig cell lyses. Changes in the enzymatic activities of other glycosyltransferases, such as alpha1,3-galactosyltransferase, GnT-IV, and GnT-V, did not support cross-talk between GnT-III and these enzymes in the transgenic animals. In addition, we demonstrated the effect of GnT-III in down-regulating the xenoantigen of pig heart grafts, using a pig to cynomolgus monkey transplantation model, suggesting that this approach may be useful in clinical xenotransplantation in the future.
Automatic Online Evaluation of Intelligent Assistants (2015)

Voice-activated intelligent assistants, such as Siri, Google Now, and Cortana, are prevalent on mobile devices. However, it is challenging to evaluate them due to the varied and evolving number of tasks supported, e.g., voice command, web search, and chat. Since each task may have its own procedure and a unique form of correct answers, it is expensive to evaluate each task individually. This paper is the first attempt to solve this challenge. We develop consistent and automatic approaches that can evaluate different tasks in voice-activated intelligent assistants. We use implicit feedback from users to predict whether users are satisfied with the intelligent assistant as well as its components, i.e., speech recognition and intent classification. Using this approach, we can potentially evaluate and compare different tasks within and across intelligent assistants ac-cording to the predicted user satisfaction rates. Our approach is characterized by an automatic scheme of categorizing user-system interaction into task-independent dialog actions, e.g., the user is commanding, selecting, or confirming an action. We use the action sequence in a session to predict user satisfaction and the quality of speech recognition and intent classification. We also incorporate other features to further improve our approach, including features derived from previous work on web search satisfaction prediction, and those utilizing acoustic characteristics of voice requests. We evaluate our approach using data collected from a user study. Results show our approach can accurately identify satisfactory and unsatisfactory sessions.
Genome-wide association study identifies novel loci predisposing to cutaneous melanoma† (2011)

We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
Diagnostic and therapeutic applications of antiplatelet monoclonal antibodies (1987)

The interaction of platelets with natural and artificial surfaces is briefly reviewed, emphasizing the role of the platelet glycoprotein Ib and IIb/IIIa receptors. Studies utilizing monoclonal antibodies to these receptors for the diagnosis and therapy of hemorrhagic and thrombotic disorders are described, indicating the potential of such agents as platelet inhibitors.
Annotating the world wide web using natural language (1997)

This paper describes the START Information Server built at the MIT Artificial Intelligence Laboratory. Available on the World Wide Web since December 1993, the START Server provides users with access to multi-media information in response to questions formulated in English. Over the last 3 years, the START Server answered hundreds of thousands of questions from users all over the world
Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism (2006)

Accumulating evidence suggests that progenitor cells may decrease destructive inflammation and reduce tissue loss by antiapoptotic mechanisms. However, they remain poorly characterized, and many questions remain regarding the mechanisms by which they may positively affect wound healing, tissue remodeling, or tissue regeneration. It has been speculated that various growth factors are responsible, but what components of the wound milieu stimulate progenitor cell production of growth factors and by what mechanisms? We hypothesized that tumor necrosis factor-alpha (TNF-alpha) stimulated progenitor cell secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor I (IGF-I) by a p38 mitogen-activated protein kinase (MAPK)-dependent mechanism. Human mesenchymal stem cells (hMSCs) and human adipose progenitor cells (hAPCs) were divided into four groups: control, p38 MAPK inhibitor (p38MKI), TNF, and TNF + p38MKI. After 24 h of incubation, supernatants were harvested for ELISA of VEGF, HGF, and IGF-I. Cells were collected for Western blot analysis of p38 MAPK activation. Secretion of VEGF, HGF, and IGF-I in hMSCs and hAPCs was significantly increased by stimulation with TNF and was associated with increased activation of p38 MAPK. The p38 MAPK inhibitor decreased production of TNF-stimulated VEGF, HGF, and IGF-I in hMSCs and hAPCs. However, p38 MAPK inhibitor alone had no effect on production of growth factors. These data demonstrate that progenitor cells are potent sources of VEGF, HGF, and IGF-I. TNF, a prominent tissue cytokine, strongly stimulated production of growth factors by hMSCs and hAPCs via a p38 MAPK-dependent mechanism.
Site-Directed Mutagenesis by Double Polymerase Chain Reaction: Megaprimer Method (2003)

The "megaprimer" method (1) based on polymerase chain reaction (PCR) is one of the simplest and most versatile procedures of site-specific in vitro mutagenesis available to date. The method utilizes three oligonucleotide primers and two rounds of PCR performed on a DNA template containing the cloned gene that is to be mutated. The rationale of the method is shown schematically in Fig. 1 where A and B represent the "flanking" primers that can map either within the cloned gene or outside the gene (i.e., within the vector sequence) and M represents the internal "mutant" primer containing the desired base change. The first round of PCR is performed using the mutant primer (e.g., M1 in Fig. 1) and one of the flanking primers (e.g., A). The double-stranded product (A-M1) is purified and used as one of the primers (hence the name "megaprimer") in the second round of PCR along with the other flanking primer (B). The wild type cloned gene is used as template in both PCR reactions. The final PCR product (A-M1-B) containing the mutation can be used in a variety of standard applications, such as cloning in expression vectors and sequencing, or in more specialized applications, such as production of the gene message in vitro if primer A (or the template sequence downstream of primer A) also contains a transcriptional promoter (e.g., that of SP6 or T7 phage).
Antithrombin activity of surface‐bound heparin studied under flow conditions (1995)

Polyacrylamide-grafted polyetherurethane sheets were modified by end-point and multipoint attachment of heparin. The surface-bound heparin was firmly attached. No release of heparin activity could be detected when the surface was rinsed at a wall shear rate of 2000 s-1. Uptake of antithrombin and thrombin inactivation were investigated under well-defined flow conditions by the use of a spinning device with an attached disk-shaped heparinized surface. It is demonstrated that the rate of thrombin inactivation at the antithrombin-heparin surface equals the maximal rate of transport of thrombin toward the surface when the surface coverage of antithrombin exceeds 10 pmol/cm2. This result indicates that a higher intrinsic catalytic efficiency of a surface does not necessarily result in a higher antithrombin activity. We varied the heparin content of the surfaces between 0 and 35 micrograms/cm2 by increasing the number of functional groups to which heparin could be covalently attached. The uptake of antithrombin increased with the heparin content of the surface, but the stoichiometry decreased from 2 to 0.5 pmol antithrombin/micrograms heparin. Apparently, antithrombin could not bind to heparins buried in the poly(acrylamide) layer. The rate of thrombin inactivation at surfaces with low heparin content (2 micrograms/cm2) fells below the transport limit of thrombin and became proportional with the heparin content of the surface. Although the contribution of surface-bound heparin to the neutralization of fluid-phase thrombin was found to be negligible compared with the effect of fluid-phase antithrombin at physiologic relevant concentrations, these heparinized surfaces markedly delayed the onset of thrombin generation in platelet-rich plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of cyclin-dependent kinase activity triggers neuronal differentiation of mouse neuroblastoma cells. (1995)

Studies on the molecular mechanisms underlying neuronal differentiation are frequently performed using cell lines established from neuroblastomas. In this study we have used mouse N1E-115 neuroblastoma cells that undergo neuronal differentiation in response to DMSO. During differentiation, cyclin-dependent kinase (cdk) activities decline and phosphorylation of the retinoblastoma gene product (pRb) is lost, leading to the appearance of a pRb-containing E2F DNA-binding complex. The loss of cdk2 activity is due to a decrease in cdk2 abundance whereas loss of cdk4 activity is caused by strong association with the cdk inhibitor (CKI) p27KIP1 and concurrent loss of cdk4 phosphorylation. Moreover, neuronal differentiation can be induced by overexpression of p27KIP1 or pRb, suggesting that inhibition of cdk activity leading to loss of pRb phosphorylation, is the major determinant for neuronal differentiation.
Tumor suppressor protein (p)53, is a regulator of NF-κB repression by the glucocorticoid receptor (2011)

Glucocorticoids can inhibit inflammation by abrogating the activity of NF-κB, a family of transcription factors that regulates the production of proinflammatory cytokines. To understand the molecular mechanism of repression of NF-κB activity by glucocorticoids, we performed a high-throughput siRNA oligo screen to identify novel genes involved in this process. Here, we report that loss of p53, a tumor suppressor protein, impaired repression of NF-κB target gene transcription by glucocorticoids. Additionally, loss of p53 also impaired transcription of glucocorticoid receptor (GR) target genes, whereas upstream NF-κB and glucocorticoid receptor signaling cascades remained intact. We further demonstrate that p53 loss severely impaired glucocorticoid rescue of death in a mouse model of LPS shock. Our findings unveil a new role for p53 in the repression of NF-κB by glucocorticoids and suggest important implications for treatment of the proinflammatory microenvironments found in tumors with aberrant p53 activity.
Effects of Methylthiodeoxyadenosine and Its Analogs on in vitro Invasion of Rat Ascites Hepatoma Cells and Methylation of Their Phospholipids (1991)

The relationship between tumor invasiveness in vitro and methylation of plasma membrane phospholipids was investigated. For this purpose, two hepatoma cell lines, C1-30 and LC-AH, were used which show specific penetration to below cultured monolayers of mesothelial cells from rat mesentery and endothelial cells from calf pulmonary artery, respectively. Methylthiodeoxyadenosine (MTA) and five of its analogs, difluoro-MTA, deoxyadenosine, sinefungin, phenylthiodeoxyadenosine and fluorophenylthiodeoxyadenosine, inhibited the invasion of the tumor cells without affecting their proliferation. This inhibition was associated with reduction in the incorporation of radioactivity of [methyl-3H]methionine into cellular phosphatidylethanolamine derivatives without changes in the labelings of RNA and DNA and carboxylmethylation of protein. These compounds also decreased the membrane fluidity of the tumor cells, measured by a steady-state fluorescence polarization method. Three other MTA analogs (fluorodideoxyadenosine, fluoroazidodideoxyadenosine and fluoroaminodideoxyuridine) did not affect the invasiveness of the tumor cells or alter their phospholipid methylation or membrane fluidity at concentrations that did not inhibit proliferation. These results suggest that the decrease in invasiveness of tumor cells by MTA and its analogs is due to alterations in the phospholipid composition and fluidity of the tumor cell membranes.
Genome Analysis Linking Recent European and African Influenza (H5N1) Viruses (2007)

To better understand the ecology and epidemiology of the highly pathogenic avian influenza virus in its transcontinental spread, we sequenced and analyzed the complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in Europe, northern Africa, and southeastern Asia. These sequences, among the first complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the lineages now infecting wild and domestic birds in Europe and Africa and show the relationships among these isolates and other strains affecting both birds and humans. The isolates fall into 3 distinct lineages, 1 of which contains all known non-Asian isolates. This new Euro-African lineage, which was the cause of several recent (2006) fatal human infections in Egypt and Iraq, has been introduced at least 3 times into the European-African region and has split into 3 distinct, independently evolving sublineages. One isolate provides evidence that 2 of these sublineages have recently reassorted.
A single mutation in uncoupling protein of rat brown adipose tissue mitochondria abolishes GDP sensitivity of H+ transport. (1994)

The uncoupling protein is one of a family of mitochondrial transport proteins involved in energy metabolism. It dissipates oxidative energy to generate heat, either by catalyzing proton transport directly or by catalyzing fatty acid anion transport, thus enabling fatty acids to act as cycling protonophores. This transport process is tightly regulated by purine nucleotides. We have expressed uncoupling protein in yeast and examined its proton transport activity after its reconstitution into proteoliposomes. A directed change of Arg276 to Leu or Gln completely abolished nucleotide inhibition of protonophoretic action of the reconstituted mutant uncoupling proteins without affecting the transport process. Arg276 is the first residue of functional importance to be identified in uncoupling protein. Mutation of the homologous residue in the yeast ADP/ATP translocator prevented the growth of yeast on a nonfermentable carbon source, presumably by interfering with nucleotide exchange (Nelson, D. R., Lawson, J. E., Klingenberg, M., and Douglas, M. G. (1993) J. Mol. Biol. 230, 1159-1170). Demonstration of the essential role of a single homologous residue in protein-nucleotide interaction within these two transporters is the first direct evidence that uncoupling protein and the ADP/ATP translocator belong to the same gene family.
Compression of Lumigraph with multiple reference frame (MRF) prediction and just-in-time rendering (2002)

In the form of a 2D image array, Lumigraph captures the complete appearance of an object or a scene, and is able to quickly render a novel view independent of the scene/object complexity. Since the data amount of Lumigraph is huge, efficient storage and access for Lumigraph are essential. In this paper, we propose a multiple reference frame (MRF) structure to compress the Lumigraph data. By predicting the Lumigraph view from multiple neighbor views, a higher compression ratio is achieved. We also implement the key functionality of just-in-time (JIT) Lumigraph rendering, in which only a small portion of the compressed bitstream necessary for rendering the current view is accessed and decoded. JIT rendering eliminates the need to predecode the entire Lumigraph data set, thus greatly reduces the memory requirement of Lumigraph rendering. A decoder cache has been implemented to speed up rendering by reusing the decoded data. The trade off between the computational speed and cache size of the decoder is discussed in the paper.