gebhart/patrepeval huggingface dataset:
Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. (1991)

Using an oligonucleotide hybridization assay, we studied the clinical implication of wild-type hepatitis B virus (HBV) and a HBV mutant that is unable to secrete hepatitis B e antigen (HBeAg) because of a translational defect due to a stop codon in the pre-C region in 106 hepatitis B surface antigen-positive patients with chronic hepatitis B. Wild-type HBV was detected in 31 of 42 (73.8%) HBeAg-positive patients, whereas a mixed viral population was present in 10 (23.8%). Significant differences in the severity and outcome of liver disease were not observed in the two groups of patients. However, the emergence of HBeAg-minus HBV in wild-type HBV carriers was associated with an exacerbation of liver disease and was followed by the presence of antibodies against HBeAg (anti-HBe) in serum in 50% of the cases. In 61 of 64 (95.3%) anti-HBe-positive patients, HBeAg-minus HBV was the predominant virus: HBeAg-minus HBV was detected in 42 patients (65.6%), whereas both wild-type and HBeAg-minus HBV were present in 19 (29.7%). HBeAg-minus HBV was associated with a course of hepatitis characterized by flare-ups of liver cell necrosis interspersed with periods of asymptomatic HBV carriage (P less than 0.01). These data support the hypothesis that genetic heterogeneity of HBV significantly influences the course and outcome of chronic hepatitis B. Wild-type HBV secreting HBeAg induces immunologic tolerance and causes chronic infection. HBeAg-minus HBV might be unable to induce chronic infection without the helper function of wild-type HBV, but it appears to be more pathogenic. Once chronic infection is established, HBeAg-minus HBV variants may prevail and displace wild-type virus.
Antidiabetic and antiobesity effects of a highly selective β3‐adrenoceptor agonist (CL 316,243) (1994)

Abstract A third β‐adrenoceptor subtype has been cloned form the rat, mouse, and human genomes. The presence of these receptors primarily on adipose tissue has raised the possibility that β 3 ‐adrenoceptor selective agonists may be useful antiobesity agents. CL 316,243 is a highly selective β 3 ‐agonist; it has a &lt;30,000 to 1 β 3 ‐to‐β 1 ‐adrenoceptor selectivity ratio and a 10,000 to 1 β 3 ‐to‐β 2 ‐adrenoceptor selectivity ratio in in vitro functional assays. In vivo, animals were treated with CL 314,698, a diester prodrug of CL 316,243, which is rapidly converted to CL 316,243. In obese (ob/ob) and diabetic (db/db) mice, treatment with CL 314,698 reduced their hyperglycemia to the euglycemia of their lean littermates, and decreased plasma insulin levels. In obese mice, the compound also caused decreased weight gain despite increased food consumption, and the decreased weight was due to loss of fat while lean body mass was spared. CL 314,698 treatment also improved both glucose and insulin tolerance in obese mice, suggesting that it decreased insulin resistance. CL 314,698 also prevented further weight gain, without affecting food consumption, in rats previously made obese by feeding a high fat diet. The compound reduced plasma insulin and triglyceride levels, and reduced fat pad weights, while having no effect on plasma glucose, cholesterol, thyroxine, or T 3 levels or on skeletal muscle weight. Decreased weight gain without decreased food consumption suggested that CL 316,243 stimulated thermogenesis. Treatment of obese mice for 3 weeks with CL 316,243 increased thermogenesis by 45% as measured by indirect calorimetry. Thus, CL 316,243 is a potent, β 3 ‐adrenoceptor selective agonist with thermogenic, antidiabetic, and antiobesity properties in several models of non‐insulin dependent diabetes and obesity.
CD137 agonist antibody prevents cancer recurrence: contribution of CD137 on both hematopoietic and nonhematopoietic cells (2010)

Antigen-specific memory T cells (Tms) are essential in the immune surveillance of residual and metastatic tumors. Activation of Tms requires designing vaccines based on tumor rejection antigens, which are often not available to cancer patients. Therefore, it is desirable to have a general applicable approach to activate Tms without extensive knowledge of tumor antigens. Here, we report that activation of antigen-specific Tms could be achieved by the administration of agonistic anti-CD137 monoclonal antibody without additional tumor vaccination, leading to the prevention of recurrence and metastases after surgical resection of primary tumors in mouse models. By reconstitution with CD137-deficient Tms, we demonstrate that expression of CD137 on antigen-specific Tms is only partially required for the effect of anti-CD137 antibody. Other host cells, including those from hematopoietic and nonhematopoietic origins, are also important because ablation of CD137 from these cells partially but significantly eliminates antitumor effect of anti-CD137 antibody. Our findings implicate a potential new approach to prevent recurrence and metastases in cancer patients.
Antineoplastic Agents. 291. Isolation and Synthesis of Combretastatins A-4, A-5, and A-6. [Erratum to document cited in CA122:290568] (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleAntineoplastic Agents. 291. Isolation and Synthesis of Combretastatins A-4, A-5, and A-6. [Erratum to document cited in CA122:290568]George R. Pettit, Sheo Bux Singh, Michael R. Boyd, Ernest Hamel, Robin K. Pettit, Jean M. Schmidt, and Fiona HoganCite this: J. Med. Chem. 1995, 38, 15, 2994Publication Date (Print):July 1, 1995Publication History Published online1 May 2002Published inissue 1 July 1995https://pubs.acs.org/doi/10.1021/jm00015a024https://doi.org/10.1021/jm00015a024research-articleACS PublicationsRequest reuse permissionsArticle Views168Altmetric-Citations3LEARN 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
Frataxin Deficiency Leads to Defects in Expression of Antioxidants and Nrf2 Expression in Dorsal Root Ganglia of the Friedreich's Ataxia YG8R Mouse Model (2013)

These results support a mechanistic hypothesis in which frataxin deficiency decreases Nrf2 expression in vivo, causing the sensitivity to oxidative stress in target tissues the DRG and the cerebella, which contributes to the process of neurodegeneration.
Anticytokine Therapy in Autoimmune Diseases. (1999)

Autoimmune reaction and inflammation observed in autoimmune diseases may be caused by the deregulated production of cytokines. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities such as support of hematopoiesis, regulation of acute phase reactions, and generation of immune responses. Uncontrolled hyperproduction of IL-6 causes plasmacytosis, hyper-gamma-globulinemia, thrombocytosis, mesangial cell proliferation of the kidney as well as inflammatory symptoms which are frequently observed in autoimmune diseases. Thus, interference with IL-6 signal transduction may be useful for autoimmune disease therapy. The pathogenic significance of IL-6 in autoimmune disorders and new therapeutic approaches involving blocking of IL-6 signal transduction are discussed.
Turbidimetric measurement of haze in canola oil by acetone precipitation (1996)

Abstract Formation of turbidity in canola oil was facilitated with addition of acetone, and a method to measure the sediment content based on the oil turbidity has been developed. Canola oil was mixed with acetone at the ratio of 60:40, and the turbid solution developed in an ice bath for 20 min. The turbidity of the oil solution was determined by a turbidimeter. The relation between turbidity of the oil solution and sediment content was nonlinear and could be correlated by a second‐order polynomial. There was no difficulty in the development of turbidity in canola oil solutions in the presence of added lecithin (2%, w/w). However, with added lecithin, turbidity was 23% higher at the same sediment content.
Growth inhibitory response to activin A and B by human prostate tumour cell lines, LNCaP and DU145 (1997)

Activins are growth and differentiation factors which have been shown to have proliferative and antiproliferative actions in many tissues. In addition, they have been implicated in tumourigenesis in reproductive tissues. Although activin and inhibin are present in rat ventral prostate, inhibin beta, but not alpha, subunit proteins have been detected in the human prostate epithelial tumour cell lines LNCaP, DU145 and PC3. With this absence of capacity to produce inhibins, the aims of this study were to determine the effect of activin A and B and follistatin on DNA synthesis by these human prostate tumour cell lines. The results demonstrate a differential response to exogenously added activin A and B on DNA synthesis in vitro by the tumour cell lines. The inhibitory effects were observed on LNCaP cells in the absence or presence of stimulation with 1 nM 5 alpha-dihydrotestosterone and on the androgen-independent DU145 cells, but not the PC3 cells. Activin A caused a dose-dependent inhibition of DNA synthesis and proliferation by LNCaP and androgen-independent DU145 cells which was maximal at 8 ng/ml. The effect of exogenously added activin A was completely reversed by follistatin, but not by inhibin A. The addition of human recombinant FS 288 alone (400 ng/ml) did not have any effect on DNA synthesis, whereas inhibin A alone (400 ng/ml) caused a significant inhibition of DNA synthesis. The capacity of all three cell lines to produce activins and follistatins was demonstrated by the expression of the mRNAs and confirmed by the localisation of immunoreactivity for these ligands to the cytoplasm of the tumour cells. The growth inhibitory response to activins A and B by LNCaP and DU145 cells, and the ability of follistatin to block these effects, suggest that the autocrine interactions between activins and follistatins have a role in the regulation of LNCaP and DU145 prostate tumour cell growth.
A Nanoparticle System Specifically Designed to Deliver Short Interfering RNA Inhibits Tumor Growth In vivo (2009)

Use of short interfering RNA (siRNA) is a promising new approach thought to have a strong potential to lead to rapid development of gene-oriented therapies. Here, we describe a newly developed, systemically injectable siRNA vehicle, the "wrapsome" (WS), which contains siRNA and a cationic lipofection complex in a core that is fully enveloped by a neutral lipid bilayer and hydrophilic polymers. WS protected siRNA from enzymatic digestion, providing a long half-life in the systemic circulation. Moreover, siRNA/WS leaked from blood vessels within tumors into the tumor tissue, where it accumulated and was subsequently transfected into the tumor cells. Because the transcription factor KLF5 is known to play a role in tumor angiogenesis, we designed KLF5-siRNA to test the antitumor activity of siRNA/WS. KLF5-siRNA/WS exhibited significant antitumor activity, although neither WS containing control scrambled-siRNA nor saline containing KLF5-siRNA affected tumor growth. KLF5-siRNA/WS inhibited Klf5 expression within tumors at both mRNA and protein levels, significantly reducing angiogenesis, and we detected no significant acute or long-term toxicity. Our findings support the idea that siRNA/WS can be used to knock down specific genes within tumors and thereby exert therapeutic effects against cancers.
A connectionist parser with recursive sentence structure and lexical disambiguation (1992)

In order to be taken seriously, connectionist natural language processing systems must be able to parse syntactically complex sentences. Current connectionist parsers either ignore structure or impose prior restrictions on the structural complexity of the sentences they can process --- either number of phrases or the #depth&amp;quot; of the sentence structure. XERIC networks, presented here, are distributed representation connectionist parsers which can analyze and represent syntactically varied sentences, including ones with recursive phrase structure constructs. No a priori limits are placed on the depth or length of sentences by the architecture. XERIC networks use recurrent networks to read words one at a time. RAAMstyle reduced descriptions and X-Bar grammar are used to make an economical syntactic representation scheme. This is combined with a training technique which allows XERIC to use multiple, virtual copies of its RAAM decoder network to learn to parse and represent sentence structure using gradient-descent methods. XERIC networks also perform number-person disambiguation and lexical disambiguation. Results show that the networks train to a few percent error for sentences up to a phrase-nesting depth of ten or more and that this performance generalizes well.
The functional nitrite reductase activity of the heme-globins (2008)

Hemoglobin and myoglobin are among the most extensively studied proteins, and nitrite is one of the most studied small molecules. Recently, multiple physiologic studies have surprisingly revealed that nitrite represents a biologic reservoir of NO that can regulate hypoxic vasodilation, cellular respiration, and signaling. These studies suggest a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction. Biophysical and chemical analysis of the nitrite-deoxyhemoglobin reaction has revealed unexpected chemistries between nitrite and deoxyhemoglobin that may contribute to and facilitate hypoxic NO generation and signaling. The first is that hemoglobin is an allosterically regulated nitrite reductase, such that oxygen binding increases the rate of nitrite conversion to NO, a process termed R-state catalysis. The second chemical property is oxidative denitrosylation, a process by which the NO formed in the deoxyhemoglobin-nitrite reaction that binds to other deoxyhemes can be released due to heme oxidation, releasing free NO. Third, the reaction undergoes a nitrite reductase/anhydrase redox cycle that catalyzes the anaerobic conversion of 2 molecules of nitrite into dinitrogen trioxide (N(2)O(3)), an uncharged molecule that may be exported from the erythrocyte. We will review these reactions in the biologic framework of hypoxic signaling in blood and the heart.
Optimized contact configuration for the study of transport phenomena in ropes of single-wall carbon nanotubes (2001)

The study of the intrinsic transport properties of carbon nanotubes suffers from the difficulties in fabricating noninvasive contacts. Here, we present a scheme for the investigation of transport phenomena in metallic single-wall carbon nanotubes by means of a special four-terminal measurement configuration. To suppress the impact of the contacts on the measured conductance in a tube, we found a combination of top and bottom contacts to the rope of single-wall nanotubes to be most appropriate. Our experimental findings demonstrate that a linear decrease of the sample resistance can be observed under these circumstances without the common increase of resistance for decreasing temperatures.
A 5 kv, 250 ka rep-rated pulser using parallel ignitrons (2005)

A modulator system consisting of a 20 kW, 3 kV power supply, a resonant command charging circuit, and a low inductance capacitive discharge circuit was designed, built and tested at rep-rates up to 10 Hz. This pulsed power system, described in this paper, was used to power a developmental intense UV source. The dc power supply charged a 1.4 mF filter capacitor to 3 kV which was discharge with an SCR command charging switch through a 20 mH inductor to resonantly charge three paralleled 50 /spl mu/F capacitors to 5 kV The 50 /spl mu/F capacitors provided the energy storage section for three low inductance discharge circuits. Each discharge circuit consisted of the 50 /spl mu/F capacitor, an ignitron and low inductance buswork. The outputs of the circuits were connected in parallel to form a stripline 2ft. in width. The total effective inductance of the modulator was 90 nH. Simultaneity and jitter measurements, conducted using a 0.04 /spl Omega/ resistive load, showed that the average ignitron firing time was within 200 ns.
Fraud and misconduct in clinical research (1997)

Contributors Preface SECTION 1: SETTING THE SCENE 1. The concept of scientific dishonesty: Ethics, value systems, and research - Povl Riis 2. Ethical issues in the publication process - Richard Smith 3. What is research misconduct? - Drummond Rennie and C Kristina Gunsalus SECTION 2: THE HISTORICAL ASPECTS OF RESEARCH MISCONDUCT 4. An interpretive history of research misconduct policy in the USA and Canada - Nicholas H Steneck 5. Historical aspects of research misconduct: Europe - Frank Wells SECTION 3: THE PREVENTION OF RESEARCH MISCONDUCT 6. The promotion of good publication practice - Elizabeth Wager 7. Monitoring medical research: Better to prevent than to cure? - Helena van den Dungen 8. The role of research ethics committees - John Saunders SECTION 4: APPROACHES TO THE DETECTION OF RESEARCH MISCONDUCT 9. The role of the whistleblower - Sabine Kleinert 10. The role of the peer review process - Ana Marusic 11. Can statistical analysis reveal research misconduct? - Stephen Evans 12. The role of electronic tracking in monitoring data output in clinical trials - Erick Gaussens, Pierre-Henri Bertoye, and Jean-Marc Husson 13. The role of monitoring of research for compliance and detecting misconduct - Michael R Hamrell 14. The role of routine enhanced audit - Nicky Dodsworth SECTION 5: INVESTIGATION OF RESEARCH MISCONDUCT 15. Handling whistleblowers: Bane and boon - C Kristina Gunsalus and Drummond Rennie 16. Conduct of an inquiry into alleged misconduct - Jane Barrett SECTION 6: THE WAY FORWARD 17. The role of national advisory bodies - Michael Farthing Index
Shared genetic architecture in autoimmune disease - preliminary analysis (2015)

Diseases that have different underlying genetic risk component(s) may share similar phenotypes. Traditionally, disease classifications have focused on characterizing diseases based on sets of related phenotypes. As an example, type I diabetes and type II diabetes are both classified as a type of diabetes based on patients having high blood sugar over long periods of time. However, as our understanding of genetic contributions to disease susceptibility and progression evolves, we start noticing that diseases with similar symptoms may have completely different causes. For example, type II diabetes is due to insulin resistance while type I diabetes is caused by immune cells attacking insulin producing cells. As genetic data becomes more highly available, it becomes possible to classify diseases based on their genetic causative drivers instead of their phenotypes. In this study, we have (1) explored the relationship between 10 autoimmune diseases along with type II diabetes based on their genetic susceptibility information and compared such classifications to existing disease categorizations based on disease symptoms/phenotypes from Human Phenotype Ontology, NCI-thesaurus and the Disease Ontology, and (2) developed automated scripts to compute similarities and cluster diseases based on the specified criteria. Categorization based on genetic susceptibility can help identify diseases that share similar drug targets and benefit from similar diagnosis technologies. We hope to further develop our system to apply it to more disease categories.
Facet Formation In Selectively Overgrown Silicon By Reduced Pressure Chemical Vapor Deposition (1998)

Selective epitaxial growth (SEG) and epitaxial lateral overgrowth (ELO) of silicon have many applications in integrated circuit processing such as device isolation and self-aligned processes to enhance the integrated circuit performance as well as level of integration. However, in order for SEG to be applied for device fabrication, to the extent of production technology, reasonably high growth rate, high-quality epitaxial layers are prerequisite. Various facets were observed in the overgrown Si regions and it is known that the control of facet formation is important for subsequent device fabrication. (1 13) facets were primarily observed on (001) Si wafers, when SEG was made on Si window regions at high temperatures [1,2]. The mask patterns were along <110> direction. As SEG continued, some of SEG Si started to overgrow over the mask and (1 11) facets began to appear [2]. Recently, a (110) facet was reported in SEG silicon due to the stress induced at the overgrown silicon [3], however, the detailed mechanism for the (110) facet formation is not known.
Deeply-Learned Part-Aligned Representations for Person Re-Identification (2017)

In this paper, we address the problem of person re-identification, which refers to associating the persons captured from different cameras. We propose a simple yet effective human part-aligned representation for handling the body part misalignment problem. Our approach decomposes the human body into regions (parts) which are discriminative for person matching, accordingly computes the representations over the regions, and aggregates the similarities computed between the corresponding regions of a pair of probe and gallery images as the overall matching score. Our formulation, inspired by attention models, is a deep neural network modeling the three steps together, which is learnt through minimizing the triplet loss function without requiring body part labeling information. Unlike most existing deep learning algorithms that learn a global or spatial partition-based local representation, our approach performs human body partition, and thus is more robust to pose changes and various human spatial distributions in the person bounding box. Our approach shows state-of-the-art results over standard datasets, Market-$1501$, CUHK$03$, CUHK$01$ and VIPeR.
Identification of an α Helical Motif Sufficient for Association with Papillomavirus E6 (1998)

We recently identified a cellular protein named E6BP or ERC-55 that binds cancer-related papillomavirus E6 proteins (Chen, J. J., Reid, C. E., Band, V., and Androphy, E. J. (1995) Science 269, 529-531). By construction of a series of deletion mutants, the region of E6BP that is necessary and sufficient for complex formation with human papillomavirus type 16 E6 has been mapped to a 25-amino acid domain. The corresponding peptide was synthesized and found by nuclear magnetic resonance spectroscopy to bind calcium and fold into a classical helix-loop-helix EF-hand conformation. Additional deletion mutagenesis showed that 13 amino acids that form the second alpha helix mediated E6 association. Alanine replacement mutagenesis indicated that amino acids of this helix were most important for E6 binding. Alignment of this alpha helical E6 binding peptide with the 18-amino acid E6 binding region of E6AP (Huibregtse, J. M., Scheffner, M., and Howley, P. M. (1993) Mol. Cell. Biol. 13, 4918-4927) and the first LD repeat of another E6-binding protein, paxillin (Tong, X., and Howley, P. M. (1997) J. Biol. Chem. 272, 33373-33376), revealed substantial similarities among these E6 binding domains. The extent of homology and the mutational data define the peptide as an E6 binding motif.