gebhart/patrepeval huggingface dataset:
Platelet-derived Growth Factor-DD Targeting Arrests Pathological Angiogenesis by Modulating Glycogen Synthase Kinase-3β Phosphorylation (2010)

Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.
Genomewide Association Studies and Assessment of the Risk of Disease (2010)

Over the past 5 years, genomewide association studies have yielded a wealth of insight into genes and chromosomal loci that contribute to susceptibility to disease. This article, the second in the Genomic Medicine series, describes the design of these studies and considers the extent to which the data they provide are useful in predicting the risk of disease.
Transformation of Pneumococcal Types (1943)

These typewritten notes and discussion were prepared by McCarty and Avery for a presentation given by Avery to current (and several former) colleagues at the Rockefeller Institute during the weekly staff meeting held on 10 December 1943. McCarty later reported that the presentation was met with a long silence, then acclaim by those in attendance. The handwritten notes on the outline and discussion text are Avery's.
Requirement of NAD and SIR2 for Life-Span Extension by Calorie Restriction in Saccharomyces cerevisiae (2000)

Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.
Detecting Malicious Flux Service Networks through Passive Analysis of Recursive DNS Traces (2009)

In this paper we propose a novel, passive approach for detecting and tracking malicious flux service networks. Our detection system is based on passive analysis of recursive DNS (RDNS) traffic traces collected from multiple large networks. Contrary to previous work, our approach is not limited to the analysis of suspicious domain names extracted from spam emails or precompiled domain blacklists. Instead, our approach is able to detect malicious flux service networks in-the-wild, i.e., as they are accessed by users who fall victims of malicious content advertised through blog spam, instant messaging spam, social Website spam, etc., beside email spam. We experiment with the RDNS traffic passively collected at two large ISP networks. Overall, our sensors monitored more than 2.5 billion DNS queries per day from millions of distinct source IPs for a period of 45 days. Our experimental results show that the proposed approach is able to accurately detect malicious flux service networks. Furthermore, we show how our passive detection and tracking of malicious flux service networks may benefit spam filtering applications.
Aspergillus: biology and industrial applications. (1992)

Sexual and parasexual genetics of Aspergillus species early developmental events during asexual and sexual sporulation in Aspergillus nidulans control of gene expression in the catabolic pathways of Aspergillus nidulans protein synthesis in Aspergillus nidulans industrial acids and other small molecules new developments in fermented beverages and food with Aspergillus industrial enzymes from Aspergillus species expression of foreign proteins in the genus Aspergillus mycotoxins - molecular strategies for control mycoses and mycotoxicoses of animals caused by Aspergilli human pathogenesis United States government regulations affecting Aspergilli and their products patent protection for Aspergillus-related inventions culture collections sources and management of Aspergillus cultures for biotechnology ecology of the Aspergilli of soils and litter current taxonomic schemes of the genus Aspergillus and its teleomorphs. Appendices: molecular biology supplies selected media used for Aspergilli.
Phase I study of high-dose ifosfamide, carboplatin and etoposide with autologous hematopoietic stem cell support. (1995)

More effective high-dose combination regimens are needed which have broad cytotoxic activity, steep dose-response relations and non-overlapping non-hematologic toxicities (to allow administration of full doses of each agent). This study was designed to define the dose-limiting toxicities and maximum tolerated doses of ifosfamide, carboplatin and etoposide (ICE) with hematopoietic stem cell support. Ifosfamide and carboplatin were initially fixed at 75% and 80% of the single agent maximum tolerated doses, respectively, and etoposide added to the combination. After the dose-limiting toxicity of etoposide was reached, its dose was fixed and ifosfamide and carboplatin were individually dose escalated as tolerated. All agents were given by 96h continuous infusion (days -7 to -3). Autologous marrow, with or without peripheral blood progenitor cells, was reinfused on day 0. Forty eight adults with advanced malignancies were enrolled in cohorts of three to five patients. At the maximum tolerated doses of ifosfamide 16 g/m2, carboplatin 1.8 g/m2 and etoposide 1.2 g/m2, renal toxicity precluded further dose escalation. Two patients died of organ (renal, CNS) toxicity (4%). Renal toxicity was particularly prominent in patients with prior cisplatin exposure. An early chemotherapy-stopping rule was developed, supported by pharmacologic analysis, which resulted in immediate discontinuation of ifosfamide and carboplatin if the serum creatinine, monitored twice daily during chemotherapy, exceeded 1.5 mg/dl and was > 0.5 mg/dl above baseline. High-dose ICE is well tolerated if serum creatinines are carefully monitored during chemotherapy administration. The early chemotherapy-stopping rule may enhance safety of the regimen but requires validation by addition correlation with pharmacokinetic data for each of the chemotherapeutic agents.(ABSTRACT TRUNCATED AT 250 WORDS)
Inhibition of the function of the FcγRIIB by a monoclonal antibody to thymic shared antigen‐1, a Ly‐6 family antigen (2001)

Thymic shared antigen-1 (TSA-1) is a member of the Ly-6 family of glycosyl-phosphatidylinositol (GPI)-linked proteins. While it has been proposed that TSA-1 may play a role in thymic development, a physiological ligand for this antigen has not been identified. Here we report that a monoclonal antibody (mAb) to TSA-1, generated by immunizing a hamster with CD40 ligand (CD40L)-activated B cells, interferes with the function of FcgammaRIIB on splenic B cells and the B-cell lymphoma cell line, M12, by binding to TSA on the same cells. The interaction of anti-TSA with FcgammaRIIB resulted in an inhibition of the ability of the FcgammaRIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-Cbeta T-cell receptor (TCR), leading to an inhibition of induction of expression of CD25 and CD69, interleukin (IL)-2 production and proliferation of naive T cells. Cross-blocking studies with mAbs strongly suggested that a physical association exists between TSA-1 and the FcgammaRIIB on the surface of activated B cells and favour the view that a functional intermolecular association exists between these two distinct membrane antigens.
BodyScope (2012)

Accurate activity recognition enables the development of a variety of ubiquitous computing applications, such as context-aware systems, lifelogging, and personal health systems. Wearable sensing technologies can be used to gather data for activity recognition without requiring sensors to be installed in the infrastructure. However, the user may need to wear multiple sensors for accurate recognition of a larger number of different activities. We developed a wearable acoustic sensor, called BodyScope, to record the sounds produced in the user's throat area and classify them into user activities, such as eating, drinking, speaking, laughing, and coughing. The F-measure of the Support Vector Machine classification of 12 activities using only our BodyScope sensor was 79.5%. We also conducted a small-scale in-the-wild study, and found that BodyScope was able to identify four activities (eating, drinking, speaking, and laughing) at 71.5% accuracy.
Derivatives of 1-methoxy-3-trimethylsilyloxy-1,3-butadiene for Diels-Alder reactions (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDerivatives of 1-methoxy-3-trimethylsilyloxy-1,3-butadiene for Diels-Alder reactionsSamuel Danishefsky, Cheng-Feng Yan, Rajendra K. Singh, Ronald B. Gammill, Patrick M. McCurry Jr., Nancy Fritsch, and Jon ClardyCite this: J. Am. Chem. Soc. 1979, 101, 23, 7001–7008Publication Date (Print):November 1, 1979Publication History Published online1 May 2002Published inissue 1 November 1979https://pubs.acs.org/doi/10.1021/ja00517a037https://doi.org/10.1021/ja00517a037research-articleACS PublicationsRequest reuse permissionsArticle Views1794Altmetric-Citations108LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Identification of the alpha subunit half-cystine specifically labeled by an affinity reagent for the acetylcholine receptor binding site. (1984)

Nicotinic acetylcholine receptors contain a readily reducible disulfide bond at the periphery of the acetylcholine binding site. Following reduction of this disulfide, the binding site is susceptible to affinity labeling by electrophilic reagents with quaternary ammonium moieties. We reduced purified receptor from Torpedo californica electric tissue and affinity alkylated it with 4-(N-maleimido)benzyltri[3H]methylammonium iodide. The label was incorporated solely into the alpha subunit of the receptor. Isolated, labeled alpha subunit was cleaved with CNBr, and the fragments were separated by reverse-phase high-performance liquid chromatography. A uniquely labeled CNBr fragment was isolated, and its partial sequence was determined by automated Edman degradation. This CNBr fragment was cleaved at tryptophan residues, the subfragments were separated, and the labeled subfragments were partially sequenced. From our protein sequence information, we identify the labeled CNBr fragment as residues 179 to 207 of the sequence of alpha predicted from the cDNA sequence (Noda, M., Takahashi, H., Tanabe, T., Toyosato, M., Furutani, Y., Hirose, T., Asai, M., Inayama, S., Miyata, T., and Numa, S. (1982) Nature (Lond.) 299, 793-797). From the cycle of the Edman degradation in which radioactive residues are released, we conclude that Cys 192 and, possibly in addition, Cys 193 are the residues specifically labeled by 4-(N-maleimido)benzyltri[3H]methylammonium iodide. They are, therefore, close to the acetylcholine binding site.
Recombinant Leishmania Antigens for Serodiagnosis of Visceral Leishmaniasis (2005)

Serological tests with crude or recombinant Leishmania antigens are important tools for the diagnosis of leishmania infection. However, these tests are not markers of active visceral leishmaniasis (VL), since antibodies to these markers are often observed in individuals with subclinical L. chagasi infection and they do not fall shortly after therapy. In this study, levels of immunoglobulin G (IgG) against three recombinant Leishmania antigens (rH2A, KMP11, and the "Q" protein) were evaluated in sera from individuals with subclinical L. chagasi infection and in patients with VL pre- and posttherapy. The sensitivity of the serological test for diagnosis of VL was 100% with all three antigens. The titers of IgG fell significantly after therapy. While most of the individuals with subclinical L. chagasi infection had antibodies to rH2A and the "Q" protein, only 1 out of 15 individuals had antibodies to KMP11. These data indicate that KMP11 may be used to discriminate L. chagasi infection from active VL and may serve as a marker of response to therapy.
Analogs and derivatives of tenoxicam. 1. Synthesis and antiinflammatory activities of analogs with different residues on the ring nitrogen and the amide nitrogen (1987)

The synthesis of tenoxicam, 4-hydroxy-2-methyl-N-2-pyridyl-2H-thieno[2,3-e]-1,2-thiazine-3-carboxami de 1,1-dioxide (1e), and of the analogues with various residues on the ring nitrogen and the amide nitrogen is described. This new class of "oxicams" has pronounced antiinflammatory and analgesic properties. The very specific structure-activity relationship of isomeric and isosteric groups at the amide nitrogen has been evaluated. The substituent in position 2 also has a great influence on the pharmacological properties. Tenoxicam is presently undergoing clinical trials.
α2 Adrenergic Modulation of NMDA Receptor Function as a Major Mechanism of RGC Protection in Experimental Glaucoma and Retinal Excitotoxicity (2008)

The results demonstrate alpha2 modulation of NMDA receptor function as an important mechanism for neuroprotection. These results suggest a new therapeutic approach based on neuromodulation, instead of direct inhibition, of the NMDA receptor for the treatment of glaucoma and other CNS disorders associated with NMDA receptor overactivation.
Short‐term treatment with ezetimibe, simvastatin or their combination does not alter circulating adiponectin, resistin or leptin levels in healthy men (2007)

Summary Objective Statin therapy decreases cardiovascular morbidity and mortality, and ezetimibe, a novel cholesterol absorption inhibitor has both lipid‐lowering and anti‐atherosclerotic effects in animal models. As several adipokines, that is, adiponectin, high molecular weight (HMW) adiponectin, leptin and/or possibly resistin are involved in the pathogenesis of insulin resistance (IR), dyslipidaemia and atherosclerosis, we investigated whether ezetimibe and/or statin treatment may modulate serum concentrations of these four major adipokines. Research design and methods One‐centre, randomized, parallel three‐group study in 72 healthy men [mean age 32 ± 9 years, mean body mass index (BMI) 25·7 ± 3·2 kg/m 2 ]. Patients Seventy‐two healthy men. Each group of 24 subjects received a 14‐day treatment with either ezetimibe (10 mg/day), simvastatin (40 mg/day) or their combination. Blood was drawn before and after the 14‐day treatment period. Measurements Lipid levels, IR indices, serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Results Neither ezetimibe nor simvastatin or their combination had any effect on serum leptin, adiponectin, HMW adiponectin and resistin concentrations. Baseline leptin levels correlated positively, while adiponectin and HMW adiponectin negatively, with BMI. Leptin concentrations correlated negatively while adiponectin and HMW adiponectin positively with plasma high‐density lipoprotein‐cholesterol concentrations. Resistin concentrations were not associated with BMI, lipid levels or indicators of IR. Conclusions Treatment with ezetimibe, simvastatin or their combination does not alter circulating levels of adiponectin, leptin or resistin in adult healthy men.
Identification of a soluble receptor for platelet-derived growth factor in cell-conditioned medium and human plasma (1993)

We have discovered a soluble form of the platelet-derived growth factor (PDGF) alpha receptor, designated sPDGF-R alpha, that is produced by and secreted into the conditioned medium of the human osteosarcoma cell line, MG-63. Additionally, sPDGF-R alpha activity has been detected in normal human blood plasma and serum. We have achieved partial purification of this protein by column chromatography using three different affinity matrices: anti-PDGF-R alpha monoclonal antibody (mAb) 292.15-Sepharose, PDGF-BB-Sepharose, and wheat germ agglutinin-agarose. All three matrices have been shown to purify a 90-kDa protein that is recognized by mAbs specific for the PDGF-R alpha extracellular domain. sPDGF-R alpha is capable of binding PDGF ligand in solution and can compete with cell-associated PDGF receptors for ligand binding. We provide three pieces of data suggesting that the sPDGF-R alpha is generated by proteolytic clipping of the full-length PDGF-R alpha protein. First, the conditioned medium of an expression cell line transfected with a cDNA construct designed to produce only full-length PDGF-R alpha exhibits sPDGF-R alpha activity. Second, a truncated intracellular fragment of the PDGF-R alpha, presumably representing the intracellular counterpart of the clipped sPDGF-R alpha, can be immunoprecipitated from the MG-63 osteosarcoma cell extracts using antiserum raised against an intracellular portion of PDGF-R alpha. Finally, we have been unable to detect alternative splicing in the PDGF-R alpha transcript using reverse transcription-polymerase chain reaction.
Polymers, Particles, and Surfaces with Hairy Coatings: Synthesis, Structure, Dynamics, and Resulting Properties (2003)

Summary: In this chapter, we discuss problems related to the synthesis, structure and dynamic behavior of macromolecular systems, in which many linear chains are anchored to other macromolecules, to nanoparticles or, in a general sense, to surfaces forming "hairy" coatings at these objects. Computer simulated and real systems are considered. In the preparation of such systems, both by means of adsorption and by means of synthesis, strongly competitive situations on the molecular level take place, which result in various, not necessary desired effects, such as high polydispersity of surface layers or backbone extension in molecular brushes. It is demonstrated how the considered molecular structures can influence the system dynamics and consequently the mechanical properties. Examples of new super soil materials based on a specific class of macromolecular architectures are presented.
Transmission-mode direct analysis in real time and desorption electrospray ionization mass spectrometry of insecticide-treated bednets for malaria control (2010)

Transmission-mode direct analysis in real time (TM-DART) is presented as an alternative sampling strategy to traditional methods of sample introduction for DART MS analysis. A custom-designed sample holder was fabricated to rapidly and reproducibly position insecticide-treated nets normal to the ionizing metastable gas stream, enabling transmission of desorbed analyte ions through the holder cavity and into the MS. Introduction of the sample at this fixed geometry eliminates the need for optimizing sample position and allows spectra based on factors such as metastable gas temperature and flow to be systematically evaluated. The results presented here, supported by computational fluid dynamic simulations, demonstrate the effects of these factors on the resulting mass spectra and the potential of this sampling strategy to be used for qualitative and quantitative analyses. Transmission-mode desorption electrospray ionization (TM-DESI) experiments on similar insecticide-treated nets were performed for comparison purposes.
Pharmacology of Leukotriene Receptor Antagonists (1998)

Preclinical pharmacological studies have demonstrated that cysLT, receptor antagonists, such as zafirlukast, montelukast, and pobilukast, are potent and selective antagonists of cysteinyl leukotriene (cysLT) activity. In vitro, these agents compete with [3H]LTD4 for binding to cysLT, receptors present on guinea pig and human lung cell membranes. Both zafirlukast and montelukast have affinities that are approximately two times greater than that of the natural ligand, LTD4. These agents block LTD4- and LTE4-induced contractions of isolated guinea pig trachea, but do not antagonize LTC4-induced contractions, which are putatively mediated by a different LT receptor, cysLT2. The cysLT2 receptor, however, has not yet been found in human airway smooth muscle. In animal models, these drugs inhibit LTD4-, LTE4-, and antigen-induced bronchoconstriction, reduce inflammatory markers in models of pulmonary inflammation, and inhibit antigen-induced late-phase bronchoconstriction. This preclinical profile suggests that cysLT, receptor antagonists may be useful in treating inflammatory conditions of the respiratory system, such as asthma and allergic rhinitis.
Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers (2016)

Approximately 70% of patients have breast cancers that are oestrogen receptor alpha positive (ER+) and are therefore candidates for endocrine treatment. Many of these patients relapse in the years during or following completion of adjuvant endocrine therapy. Thus, many ER+ cancers have primary resistance or develop resistance to endocrine therapy during treatment. Recent improvements in our understanding of how tumours evolve during treatment with endocrine agents have identified both changes in gene expression and mutational profiles, in the primary cancer as well as in circulating tumour cells. Analysing these changes has the potential to improve the prediction of which specific patients will respond to endocrine treatment. Serially profiled biopsies during treatment in the neoadjuvant setting offer promise for accurate and early prediction of response to both current and novel drugs and allow investigation of mechanisms of resistance. In addition, recent advances in monitoring tumour evolution through non-invasive (liquid) sampling of circulating tumour cells and cell-free tumour DNA may provide a method to detect resistant clones and allow implementation of personalized treatments for metastatic breast cancer patients. This review summarises current and future biomarkers and signatures for predicting response to endocrine treatment, and discusses the potential for using approved drugs and novel agents to improve outcomes. Increased prediction accuracy is likely to require sequential sampling, utilising preoperative or neoadjuvant treatment and/or liquid biopsies and an improved understanding of both the dynamics and heterogeneity of breast cancer.