gebhart/patrepeval huggingface dataset:
A phase II trial of low-dose interleukin-2 (IL-2) and bevacizumab in patients with metastatic renal cell carcinoma (mRCC) (2007)

5103 Background: Interleukin-2 and bevacizumab, a VEGF ligand-binding antibody, have each demonstrated antitumor activity in mRCC. Increased VEGF levels can lead to immunosuppression and resistance to immunotherapy through inhibition of dendritic cell (DC) differentiation and increase in immunosuppressive regulatory T cells (Tregs). To further evaluate the clinical and immunomodulatory effect of low-dose IL-2 and bevacizumab in mRCC, a phase II trial was conducted. Methods: Previously untreated good and intermediate risk mRCC pts received 8-week cycles of IL-2 (250,000 U/kg/d SC D1–5 during week 1 and 125,000 U/kg/d SC D1–5 during weeks 2–6, followed by a 2 week break). Bevacizumab 10mg/kg was administered IV every 2 weeks starting on day -14. Eligibility included RECIST-defined measurable disease, clear cell histology, normal organ function, and prior nephrectomy. A Simon 2 stage phase II design was employed to test the hypothesis of a 40% improvement in the 3-month PFS vs. historical IL-2-treated controls. Overall response rate (ORR) and toxicity were recorded. Exploratory endpoints included activation of circulating DC’s, Tregs and VEGF levels. Results: To date 16 of a planned 35 pts are enrolled. Median age is 59 years (range, 44–67); Eight patients have >1 site of metastasis; median treatment duration is 8 weeks (8–32+). Among 11 pts evaluable for response, 1 PR and 3 SD lasting >3 months have been observed. All pts with SD have demonstrated some degree of tumor shrinkage. Seven pts have discontinued therapy (5 PD, 2 withdrew consent). Most common treatment-related toxicity included fatigue, nausea, diarrhea, and fever. When comparing immune correlates at day 56 of therapy vs. baseline, all pts had an increase in the number of Tregs (median increase 1.65, range; 0.76–10.4; p= 0.008). Similarly, all pts had a decline in VEGF levels (median decline 164.38 pg/ml, range; 2.20–393.04 pg/ml; p= 0.008). No differences in DC activation have been observed. Conclusions: The combination of LD IL-2 and bevacizumab produces antitumor activity and moderate toxicity. Preliminary correlative data demonstrates inhibition of VEGF and increase in Tregs without effect on DC activation. No significant financial relationships to disclose.
PCR amplification of species-specific DNA sequences can distinguish among Phytophthora species (1994)

We used PCR to differentiate species in the genus Phytophthora, which contains a group of devastating plant pathogenic fungi. We focused on Phytophthora parasitica, a species that can infect solanaceous plants such as tomato, and on Phytophthora citrophthora, which is primarily a citrus pathogen. Oligonucleotide primers were derived from sequences of a 1,300-bp P. parasitica-specific DNA segment and of an 800-bp P. citrophthora-specific segment. Under optimal conditions, the primers developed for P. parasitica specifically amplified a 1,000-bp sequence of DNA from isolates of P. parasitica. Primers for P. citrophthora similarly and specifically amplified a 650-bp sequence of DNA from isolates of P. citrophthora. Detectable amplification of these specific DNA sequences required picogram quantities of chromosomal DNA. Neither pair of primers amplified these sequences with DNAs from other species of Phytophthora or from the related genus Pythium. DNAs from P. parasitica and P. citrophthora growing in infected tomato stem tissue were amplified as distinctly as DNAs from axenic cultures of each fungal species. This is the first report on PCR-driven amplification with Phytophthora species-specific primers.
Molecular basis of the attenuated phenotype of human APOBEC3B DNA mutator enzyme (2015)

The human APOBEC3A and APOBEC3B genes (A3A and A3B) encode DNA mutator enzymes that deaminate cytidine and 5-methylcytidine residues in single-stranded DNA (ssDNA). They are important sources of mutations in many cancer genomes which show a preponderance of CG->TA transitions. Although both enzymes can hypermutate chromosomal DNA in an experimental setting, only A3A can induce double strand DNA breaks, even though the catalytic domains of A3B and A3A differ by only 9% at the protein level. Accordingly we sought the molecular basis underlying A3B attenuation through the generation of A3A-A3B chimeras and mutants. It transpires that the N-terminal domain facilitates A3B activity while a handful of substitutions in the catalytic C-terminal domain impacting ssDNA binding serve to attenuate A3B compared to A3A. Interestingly, functional attenuation is also observed for the rhesus monkey rhA3B enzyme compared to rhA3A indicating that this genotoxic dichotomy has been selected for and maintained for some 38 million years. Expression of all human ssDNA cytidine deaminase genes is absent in mature sperm indicating they contribute to somatic mutation and cancer but not human diversity.
Structure of d(GT)<i><sub>n</sub></i>·d(GA)<i><sub>n</sub></i> Sequences:  Formation of Parallel Stranded Duplex DNA (1998)

Alternating polypurine sequences exhibit remarkable polymorphism. In this study, we report that dGA.dGT sequences form parallel stranded duplex DNA at neutral pH. Using two model hairpins, 3'-d(GT)3-5'5'-T4(AG)3-3' (I) and 3'-d(GT)4-5'5'-T4(AG)4-3' (II), containing 5'5' linkages which direct parallel strand formation, we systematically explored the spectroscopic and thermodynamic properties of parallel stranded d(GA)n.d(GT)n. The parallel stranded hairpins are remarkably stable structures with TM's of 41.5 and 47.5 degreesC (in 0.4 M NaCl) for the shorter and longer hairpins, respectively. The van't Hoff enthalpies of 80.7 and 114 kJ mol-1 are relatively low but are comparable to a parallel stranded d(GA)n duplex. On the basis of the spectroscopic and electrophoretic characteristics, we conclude that parallel strand formation is not restricted to hairpin systems, but also readily occurs in unconstrained dimeric duplexes with the appropriate sequence homologies. Both melting curves and electrophoretic analyses of parallel stranded heteroduplexes in which the sequence enforces specific base pairing demonstrate that G-G and A-T base pairs are formed in d(GA)n.d(GT)n segments.
Growth Temperature and Electrochemical Performance in Vapor-Deposited Poly(3,4-ethylenedioxythiophene) Thin Films for High-Rate Electrochemical Energy Storage (2018)

Poly(ethylene 3,4-dioxythiophene (PEDOT) films synthesized by oxidative chemical vapor deposition (oCVD) display strong electrochemical activity in the region from 2 to 4.2 V vs Li/Li+. By contrast, the more commonly studied PEDOT:polystyrenesulfonate (PSS) films have negligible electrochemical activity in this region. For the oCVD films, its small dopant anions (Cl–) that can easily enter and exit the polymer structure allow exchange with the Li+ counterion in solution, while for PEDOT:PSS, the poly(styrenesulfonate) dopant is a large macromolecule having substantially lower mobility. Here, we seek to elucidate the relationship between the structural characteristics of oCVD PEDOT thin films and their electrochemical properties, particularly in Li-ion electrolyte systems. Specifically, we seek to rationally design the thin-film properties of oCVD PEDOT for high-rate performance and cycle life by varying the film growth temperature. We observe that the dominant effect of increasing growth temperature is an in situ reorganization to an edge-on film texture. In this case, the π–π stack is perpendicular to the substrate surface. The alternative dominant texture is face-on dominance, where the π–π stack is parallel to the substrate surface. For the first time, we show that edge-on dominant films provide higher specific capacities for a given charge/discharge rate. Furthermore, Raman spectroscopy demonstrates that edge-on dominant films are less susceptible to oxidative damage after long-term cycling. This also enables edge-on dominant films to maintain lower charge-transfer resistances compared to identically cycled face-on films. Edge-on oCVD PEDOT is paired with molybdenum disulfide to demonstrate thick, optimized oCVD PEDOT thin films in asymmetric devices for high-rate electrochemical energy storage.
Chemokine receptor CCR5 genotype influences the kinetics of human immunodeficiency virus type 1 infection in human PBL-SCID mice (1997)

Individuals homozygous for a 32-bp deletion (delta 32) in the CCR5 gene encoding the coreceptor for macrophage-tropic human immunodeficiency virus type 1 (HIV-1) are resistant to virus infection, and heterozygous individuals show some slowing of disease progression. The impact of the CCR5 genotype on HIV-1 infection was assessed in vitro and in the human PBL-SCID (hu-PBL-SCID) model. Cells and hu-PBL-SCID mice from CCR5 delta 32/delta 32 donors were resistant to infection with macrophage-tropic HIV-1 and showed slower replication of dual-tropic HIV-1. hu-PBL-SCID mice derived from CCR5 delta 32/+ heterozygotes showed delayed replication of macrophage-tropic HIV-1 despite a small and variable effect of heterozygosity on viral replication in vitro. The level of CCR5 expression appears to limit replication of macrophage-tropic and dual-tropic HIV-1 strains in vivo.
Mouse models of Huntington disease: variations on a theme (2009)

An accepted prerequisite for clinical trials of a compound in humans is the successful alleviation of the disease in animal models. For some diseases, however, successful translation of drug effects from mouse models to the bedside has been limited. One question is whether the current models accurately reproduce the human disease. Here, we examine the mouse models that are available for therapeutic testing in Huntington disease (HD), a late-onset neurodegenerative disorder for which there is no effective treatment. The current mouse models show different degrees of similarity to the human condition. Significant phenotypic differences are seen in mouse models that express either truncated or full-length human, or full-length mouse, mutant huntingtin (mHTT). These differences in phenotypic expression may be attributable to the influences of protein context, mouse strain and a difference in regulatory sequences between the mouse Htt and human HTT genes.
Interdisciplinary Environmental Education Program for Teachers (1973)

Environmental education offers a unique opportunity for innovative teaching because no one is around to say, "But, I always did it this way." Thus new environmental programs do not have to overcome the educational inertia of tradition which has stopped many new instructional movements dead in their tracks.
À propos des Bedik de Jacques Gomila : vers un renouveau de l'anthropologie (1972)

Thomas Louis-Vincent. À propos des Bedik de Jacques Gomila : vers un renouveau de l'anthropologie. In: Revue française d'histoire d'outre-mer, tome 59, n°217, 4e trimestre 1972. pp. 693-698.
Surface free energy characteristics of polyfluorinated silane films (1992)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSurface free energy characteristics of polyfluorinated silane filmsElek Lindner and Ernest AriasCite this: Langmuir 1992, 8, 4, 1195–1198Publication Date (Print):April 1, 1992Publication History Published online1 May 2002Published inissue 1 April 1992https://pubs.acs.org/doi/10.1021/la00040a029https://doi.org/10.1021/la00040a029research-articleACS PublicationsRequest reuse permissionsArticle Views451Altmetric-Citations35LEARN 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
Additive Manufacturing of Ceramics: Issues, Potentialities, and Opportunities (2015)

Additive manufacturing ( AM ) is a technology which has the potential not only to change the way of conventional industrial manufacturing processes, adding material instead of subtracting, but also to create entirely new production and business strategies. Since about three decades, AM technologies have been used to fabricate prototypes or models mostly from polymeric or metallic materials. Recently, products have been introduced into the market that cannot be produced in another way than additively. Ceramic materials are, however, not easy to process by AM technologies, as their processing requirements (in terms of feedstock and/or sintering) are very challenging. On the other hand, it can be expected that AM technologies, once successful, will have an extraordinary impact on the industrial production of ceramic components and, moreover, will open for ceramics new uses and new markets.
Reduction of oxides of nitrogen in vent gases (1958)

Abstract Oxides of nitrogen are present in the effluent gases from nitric acid and nylon intermediates plants and if released in sufficient quantity they could be objectionable owing to their intensive reddish‐brown color and to their corrosive and poisonous nature. A paper study showed that the oxides of nitrogen could be reduced by absorption in an alkaline solution. Based on pilot plant tests, a large fume abatement unit was designed, installed, and operated in a satisfactory manner to reduce the concentration of the oxides of nitrogen. In 1956, the color of the combined effluent gases was practically eliminated when a more economic waste ammonia‐caustic liquor replaced the dilute caustic scrubbing solution and finely dispersed ammonium salts were removed in a Venturi scrubber. The method may be used to eliminate the objectionable brownish‐red color of effluent gases leaving a nitric acid plant.
Small-Molecule RA-9 Inhibits Proteasome-Associated DUBs and Ovarian Cancer <i>In Vitro</i> and <i>In Vivo</i> via Exacerbating Unfolded Protein Responses (2014)

Our preclinical studies support further evaluation of RA-9 as an ovarian cancer therapeutic.
Targets of B lymphocyte antigen receptor signal transduction include the p21ras GTPase-activating protein (GAP) and two GAP-associated proteins (1993)

Cross-linking membrane Ig (mIg) on B cells stimulates tyrosine phosphorylation of proteins involved in signal transduction including the mIg-associated proteins Ig-alpha and Ig-beta, the tyrosine kinases p53/p56lyn, p55blk, p59fyn, and PTK72, phosphatidylinositol 3-kinase, phospholipase C gamma 1 and gamma 2, and the mitogen-activated protein kinase. We now show that the p21ras GTPase-activating protein (GAP) is also a substrate for mIg-activated tyrosine kinases. p21ras is a key regulator of cell growth and GAP may act as both a regulator of p21ras activity and as a downstream effector of p21ras. We found that mIg cross-linking caused a rapid increase in tyrosine phosphorylation of GAP in the immature B cell line WEHI-231, the mature B cell lines BAL 17 and Daudi, and the IgG-bearing B cell line A20. In fibroblasts, tyrosine kinase activation causes GAP to associate with two other tyrosine-phosphorylated proteins, p62 and p190, which have homologies to an RNA-binding protein and a transcriptional repressor, respectively. Similarly, mlg cross-linking induced the association of GAP with a 62-kDa tyrosine-phosphorylated protein in BAL 17, WEHI-231, and Daudi cells. Anti-Ig treatment also increased the amount of a 190-kDa tyrosine-phosphorylated protein associated with GAP in WEHI-231 and Daudi cells. After separation by SDS-PAGE and transfer to nitrocellulose, the tyrosine-phosphorylated p62 and p190 present in anti-GAP immunoprecipitates from B cells were capable of binding radiolabeled recombinant GAP, as previously reported for the GAP-associated p62 and p190 from fibroblasts. The amount of p62 that could be detected in this way after immunoprecipitation with antiphosphotyrosine antibodies was much greater from anti-IgM-treated BAL 17 cells than from unstimulated BAL 17 cells. This probably reflects anti-Ig-induced tyrosine phosphorylation of p62. In any case, GAP, p62, and/or p190 may be involved in signal transduction by mIg in B cells.
The Tie-2 ligand Angiopoietin-2 destabilizes quiescent endothelium through an internal autocrine loop mechanism (2005)

The angiopoietins Ang-1 and Ang-2 have been identified as ligands of the endothelial receptor tyrosine kinase Tie-2, which controls vascular assembly and endothelial quiescence. The largely complementary phenotypes of Ang-1-deficient mice and Ang-2-overexpressing mice have led to an antagonistic model in which Ang-1 acts as Tie-2-activating agonist and Ang-2 acts as a Tie-2-inhibiting antagonist. To date, no mechanistic equivalent of the antagonistic Ang-1/Ang-2 model has been established and the mechanisms of Ang-2 function in particular remain mysterious. We have studied the effector functions of Ang-1 and Ang-2 on quiescent endothelial cells using a three-dimensional co-culture model of endothelial cells and smooth-muscle cells. Endothelial-cell monolayer integrity in this model is dependent on Tie-2 signaling, as evidenced by detaching endothelial cells following exposure to the small molecular weight Tie-2 inhibitor A-422885.66, which cannot be overcome by exogenous Ang-1. Accordingly, exogenous Ang-2 rapidly destabilizes the endothelial layer, which can be observed within 30-60 minutes and leads to prominent endothelial-cell detachment within 4 hours. Exogenous Ang-2-mediated endothelial-cell detachment can be rescued by Ang-1, soluble Tie-2 and vascular endothelial growth factor. Similar findings were obtained in an umbilical-vein explant model. Ang-2 is mainly produced by endothelial cells and therefore acts primarily in an autocrine manner. Thus, stimulated release of endogenous Ang-2 or overexpression of Ang-2 in endothelial cells perturbs co-culture spheroid integrity, which can be rescued by exogenous Ang-1 and vascular endothelial growth factor. However, autocrine Ang-2-mediated endothelial-cell detachment cannot be blocked by soluble Tie-2. Taken together, the data demonstrate for the first time the antagonistic Ang-1/Ang-2 concept in a defined cellular model and identify Ang-2 as a rapidly acting autocrine regulator of the endothelium that acts through an internal autocrine loop mechanism.
Power-dissipation driven FPGA place and route under timing constraints (1999)

In this paper we address the problem of field programmable gate arrays (FPGAs) place and route for low power dissipation with critical path delay constraints. The presence of a large number of unprogrammed antifuses in the routing architecture adds to the capacitive loading of each net. Hence, a considerable amount of power is dissipated in the routing architecture, due to signal transitions occurring at the output of logic modules. Based on primary input signal distributions, signal activities at the internal nodes of a circuit are estimated. Placement and routing are then carried out, based on the signal activity measure so as to achieve routability with low power dissipation and required timing. Results show that a more than 40% reduction in power dissipation due to routing capacitances can be achieved, compared to a layout based only on area and timing.
Comprehensive evaluation of potato germplasm with high starch content. (2010)

Three hundred and eighty two potato germplasm collected both at home and abroad were screened for high content of crude starch.Forty germplasm selected with high content of starch were evaluated further for disease resistance and storage ability.Through comprehensive evaluation,5 germplasm including Colmo,Spunta,Gasore,NS51-5 and Kexin 15 with high resistance to potato late blight(LB),good storage ability,high starch content and shallow eyes were identified.
Silicon nanopillar anodes for lithium-ion batteries using nanoimprint lithography with flexible molds (2014)

The lithium ion battery, a preferred energy storage technology, is limited by its volumetric and gravimetric energy densities, as well as its capacity retention with prolonged cycling. In this work, the authors exploited the extremely high lithium storage capacity of Si as an anode material and tackled the issue of lithium-induced volume expansion by patterning the Si into a nanopillar array using nanoimprint lithography and reactive-ion etching. Arrays of 200 nm-pitch Si pillars of 50–70 nm diameter and 200–500 nm height were fabricated on stainless steel substrates, assembled into coin cells, and tested against lithium counter electrodes. Initial charge capacities in excess of 3000 mAh/g, and a low rate-dependence, were obtained with these Si pillar anodes. This represents an improvement over previously reported nanoimprint-patterned Si anodes. Though this initial capacity is roughly equivalent to previously reported values for bulk Si anodes, our nanopillar anodes exhibit far superior capacity retention with subsequent charge–discharge cycles.
QUANTIFYING MUTANT HUNTINGTIN IN HUNTINGTON'S DISEASE CSF (2014)

Huntington9s disease (HD) is a fatal, autosomal dominant neurodegenerative disease. No disease-modifying treatments exist, but oligonucleotide-based ‘gene silencing’ approaches that aim to reduce expression of the causative mutant huntingtin (mHTT) protein are in advanced development. Low-abundance mHTT has never been quantified in the patient CNS, limiting our understanding of its role in the neuropathobiology of HD in vivo, and precluding the demonstration of target engagement by HTT-lowering drugs. We developed a novel ultra-sensitive mHTT immunoassay using single-molecule counting technology. Using cerebrospinal fluid (CSF) collected from 9 HD mutation carriers and 3 controls, under strictly standardised conditions, mHTT was successfully quantified and its levels completely distinguished controls, premanifest mutation carriers and manifest HD patients. mHTT level was significantly associated with disease burden score, a measure of lifetime exposure to mHTT, suggesting that soluble mHTT species increase in concentration with disease progression. An independent association with CSF neurofilament light chain level suggests the mHTT detected is neuronal in origin. Quantifying mHTT in CSF may provide a means of monitoring disease progression in HD. Our novel assay will be refined using larger CSF collections, and used to better understand the neuropathobiology of HD and to support clinical trials of disease-modifying HD therapeutics.
Electrospinning and the Formation of Nanofibers (2001)

No AccessStructure Formation in Polymeric FibersApr 2001Electrospinning and the Formation of NanofibersDavid R. Salem, Hao Fong, Darrell H. RenekerDavid R. Salem, Hao Fong, Darrell H. Renekerhttps://doi.org/10.3139/9783446456808.006SectionsAboutPDF ToolsAdd to FavoritesDownload CitationTrack CitationsCopy LTI LinkPDF key 'share (en)' returned an object instead of string.FacebookTwitterEmailLinkedIn previous chapternext chapter FiguresReferencesRelatedDetails 2001Pages: 225-246Print ISBN: 978-3-446-18203-5eISBN: 978-3-446-45680-8 Copyright & Permissions© 2001 Carl Hanser Verlag GmbH & Co. KGPDF downloadLoading ...
Potential Antimalarials. XXI. Mannich Base Derivatives of 4-[7-Chloro(and 7-trifluoromethyl)quinolin-4-ylamino]phenols (1994)

Syntheses are reported for 4-(7-chloroquinolin-4-ylamino)-2,6-bis(piperidin-1-ylmethyl)phenol (2) and its 3-fluoro and 3-piperidinyl derivatives. Some mono-Mannich analogues with 2-fluoro, 2-t-butyl and 3-trifluoromethyl substituents have also been prepared. In tests for antimalarial activity against the FC-27 and K-1 isolates of Plasmodium falciparum in vitro, compound (2) proved to be the most active (IC50 6.3-12.5 nM).