gebhart/patrepeval huggingface dataset:
Distinct Transcriptional Programs Mediated by the Ligand-Dependent Full-Length Androgen Receptor and Its Splice Variants in Castration-Resistant Prostate Cancer (2012)

Continued androgen receptor (AR) signaling is an established mechanism underlying castration-resistant prostate cancer (CRPC), and suppression of androgen receptor signaling remains a therapeutic goal of CRPC therapy. Constitutively active androgen receptor splice variants (AR-Vs) lack the androgen receptor ligand-binding domain (AR-LBD), the intended target of androgen deprivation therapies including CRPC therapies such as abiraterone and MDV3100. While the canonical full-length androgen receptor (AR-FL) and AR-Vs are both increased in CRPCs, their expression regulation, associated transcriptional programs, and functional relationships have not been dissected. In this study, we show that suppression of ligand-mediated AR-FL signaling by targeting AR-LBD leads to increased AR-V expression in two cell line models of CRPCs. Importantly, treatment-induced AR-Vs activated a distinct expression signature enriched for cell-cycle genes without requiring the presence of AR-FL. Conversely, activation of AR-FL signaling suppressed the AR-Vs signature and activated expression programs mainly associated with macromolecular synthesis, metabolism, and differentiation. In prostate cancer cells and CRPC xenografts treated with MDV3100 or abiraterone, increased expression of two constitutively active AR-Vs, AR-V7 and ARV567ES, but not AR-FL, paralleled increased expression of the androgen receptor-driven cell-cycle gene UBE2C. Expression of AR-V7, but not AR-FL, was positively correlated with UBE2C in clinical CRPC specimens. Together, our findings support an adaptive shift toward AR-V-mediated signaling in a subset of CRPC tumors as the AR-LBD is rendered inactive, suggesting an important mechanism contributing to drug resistance to CRPC therapy.
Biosynthesis of Defense-Related Proteins in Transformed Root Cultures of Trichosanthes kirilowii Maxim. var japonicum (Kitam.) (1994)

We have established transformed ("hairy") root cultures from Trichosanthes kirilowii Maxim. var japonicum Kitam. (Cucurbitaceae) and four related species to study the biosynthesis of the ribosome-inactivating protein trichosanthin (TCN) and other root-specific defense-related plant proteins. Stable, fast-growing root clones were obtained for each species by infecting in vitro grown plantlets with Agrobacterium rhizogenes American Type Culture Collection strain 15834. Each species accumulated reproducibly a discrete protein pattern in the culture medium. Analysis of the extracellular proteins from T. kirilowii var japonicum root cultures showed differential protein accumulation in the medium during the time course of growth in batch cultures. Maximum protein accumulation, approaching 20 micrograms/mL, was observed at mid-exponential phase, followed by a degradation of a specific protein subset that coincided with the onset of stationary phase. Two major extracellular proteins and one intracellular protein, purified by ion-exchange and reverse-phase high-performance liquid chromatography, were identified as class III chitinases (EC 3.2.1.14) based on N-terminal amino acid sequence and amino acid composition homologies with other class III chitinases. The Trichosanthes chitinases also showed reactivity with a cucumber class III chitinase antiserum and chitinolytic activity in a glycol chitin gel assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis of intracellular proteins showed that normal and transformed T. kirilowii var japonicum roots accumulated only low levels of TCN (approximately 0.5% total soluble protein). Storage roots from the plant displayed protein and antigen patterns different from root cultures and produced TCN as the dominant protein. Roots undergoing secondary growth and differentiation exhibited patterns similar to those of storage roots, including increased TCN levels, indicating that high production of TCN is associated with induction of secondary growth in roots.
Mature Cystic Fibrosis Airway Neutrophils Suppress T Cell Function: Evidence for a Role of Arginase 1 but Not Programmed Death-Ligand 1 (2015)

Bacteria colonize cystic fibrosis (CF) airways, and although T cells with appropriate Ag specificity are present in draining lymph nodes, they are conspicuously absent from the lumen. To account for this absence, we hypothesized that polymorphonuclear neutrophils (PMNs), recruited massively into the CF airway lumen and actively exocytosing primary granules, also suppress T cell function therein. Programmed death-ligand 1 (PD-L1), which exerts T cell suppression at a late step, was expressed bimodally on CF airway PMNs, delineating PD-L1(hi) and PD-L1(lo) subsets, whereas healthy control (HC) airway PMNs were uniformly PD-L1(hi). Blood PMNs incubated in CF airway fluid lost PD-L1 over time; in coculture, Ab blockade of PD-L1 failed to inhibit the suppression of T cell proliferation by CF airway PMNs. In contrast with PD-L1, arginase 1 (Arg1), which exerts T cell suppression at an early step, was uniformly high on CF and HC airway PMNs. However, arginase activity was high in CF airway fluid and minimal in HC airway fluid, consistent with the fact that Arg1 activation requires primary granule exocytosis, which occurs in CF, but not HC, airway PMNs. In addition, Arg1 expression on CF airway PMNs correlated negatively with lung function and positively with arginase activity in CF airway fluid. Finally, combined treatment with arginase inhibitor and arginine rescued the suppression of T cell proliferation by CF airway fluid. Thus, Arg1 and PD-L1 are dynamically modulated upon PMN migration into human airways, and, Arg1, but not PD-L1, contributes to early PMN-driven T cell suppression in CF, likely hampering resolution of infection and inflammation.
Mining the Web for Synonyms: PMI-IR versus LSA on TOEFL (2002)

This paper presents a simple unsupervised learning algorithm for recognizing synonyms, based on statistical data acquired by querying a Web search engine. The algorithm, called PMI-IR, uses Pointwise Mutual Information (PMI) and Information Retrieval (IR) to measure the similarity of pairs of words. PMI-IR is empirically evaluated using 80 synonym test questions from the Test of English as a Foreign Language (TOEFL) and 50 synonym test questions from a collection of tests for students of English as a Second Language (ESL). On both tests, the algorithm obtains a score of 74%. PMI-IR is contrasted with Latent Semantic Analysis (LSA), which achieves a score of 64% on the same 80 TOEFL questions. The paper discusses potential applications of the new unsupervised learning algorithm and some implications of the results for LSA and LSI (Latent Semantic Indexing).
Extremely sensitive, background-free gene detection using binary probes and beta replicase. (1996)

We have developed a specific and sensitive nucleic acid amplification assay that is suitable for routine gene detection. The assay is based on a novel molecular genetic strategy in which two different RNA probes are hybridized to adjacent positions on a target nucleic acid and then ligated to form an amplifiable reporter RNA. The reporter RNA is then replicated up to a hundred billion-fold in a 30-min isothermal reaction that signals the presence of the target. The assay can detect fewer than 100 nucleic acid molecules; it provides quantitative results over a wide range of target concentrations and it employs a universal format that can detect any infectious agent.
Surface‐Tension‐Confined Microfluidics and Their Applications (2013)

This article is a brief overview of the emerging microfluidic systems called surface-tension-confined microfluidic (STCM) devices. STCM devices utilize surface energy that can control the movement of fluid droplets. Unlike conventional poly(dimethylsiloxane)-based microfluidics which confine the movement of fluids by three-dimensional (3D) microchannels, STCM systems provide two-dimensional (2D) platforms for microfluidics. A variety of STCM devices have been prepared by various micro-/nanofabrication strategies. Advantages of STCM devices over conventional microfluidics are significant reduction of energy consumption during device operation, facile introduction of fluids onto 2D microchannels without the use of a micropump, increased flow rate in a special type of STCM device, among others. Thus, STCM devices can be excellent alternatives for certain areas in microfluidics. In this Minireview, fabrication methods, operating modes, and applications of STCM devices are introduced.
Handbook Of Batteries (2001)

Part 1 Principles of operation: basic concepts electrochemical principles and reactions factors affecting battery performance standardization of batteries battery design selection and application of batteries. Part 2 Primary batteries: zinc-carbon (Leclanche) cells magnesium and aluminium cells alkaline-manganese dioxide cells mercuric oxide cells silver oxide cells zinc/air cells lithium cells solid electrolyte batteries. Part 3 Reserve batteries: magnesium water-activated batteries spin-dependent reserve batteries liquid ammonia systems lithium anode reserve batteries thermal batteries. Part 4 Secondary batteries: lead acid batteries industrial nickel-cadmium batteries vented nickel-cadmium batteries sealed nickel-cadmium batteries nickel-zinc batteries iron electrode batteries silver-oxide batteries nickel-hydrogen batteries nickel-metal hydride batteries rechargeable alkaline-manganese dioxide batteries. Part 5 Advanced battery systems: ambient temperature lithium batteries zinc/bromine batteries metal/air batteries lithium/iron sulphide batteries sodium beta batteries.
Megalomycin C, a macrolide antibiotic that blocks protein glycosylation and shows antiviral activity (1988)

Megalomycin C, a natural macrolide antibiotic showed a potent antiherpetic activity. At concentrations that efficiently prevented HSV-1 multiplication, the compound had no cytotoxic or antiproliferative effects. Viral DNA and protein synthesis took place at normal levels in the presence of the antibiotic, suggesting that neither the translation of viral mRNA, nor the synthesis of viral nucleic acids was affected. The incorporation of mannose and galactosamine into viral proteins was blocked and precursor, but not mature, HSV-1 glycoproteins were detected in the presence of megalomycin C. Non-infectious HSV-1 viral particles were formed when the compound was present, but their glycoproteins were not properly glycosylated.
Influence of Local Fibrin Deposition on Granulation Tissue Formation (1983)

A recently developed method for occlusion of fistulas with a fibrin clot initiated studies of the effects of deposited fibrin on granulation tissue formation. Perforated Teflon cylinders, empty or fibrin-filled, were implanted subcutaneously in rats for 2, 3 and 4 weeks and the composition of the ingrowing granulation tissue was followed by sequential biochemical analysis. The concentration of fat and water and the cellularity, measured as DNA concentration, were the same throughout the period studied in the granulation tissue from cylinders implanted empty and fibrin filled. After 2 weeks of implantation, the collagen concentration was higher in fibrin-filled cylinders than in cylinders implanted empty. The higher collagen concentration was explained by a higher proportion of mature collagen-synthesising cells. After 3 and 4 weeks of implantation there was no difference in the collagen concentration between cylinders implanted empty and fibrin filled.
Glucose-induced degradation of the MDH2 isozyme of malate dehydrogenase in yeast. (1992)

MDH2, the nonmitochondrial isozyme of malate dehydrogenase in Saccharomyces cerevisiae, was determined to be a target of glucose-induced proteolytic degradation. Shifting a yeast culture growing with acetate to medium containing glucose as a carbon source resulted in a 25-fold increase in turnover of MDH2. A truncated form of MDH2 lacking amino acid residues 1-12 was constructed by mutagenesis of the MDH2 gene and expressed in a haploid yeast strain containing a deletion disruption of the corresponding chromosomal gene. Measurements of malate dehydrogenase specific activity and determination of growth rates with diagnostic carbon sources indicated that the truncated form of MDH2 was expressed at authentic MDH2 levels and was fully active. However, the truncated enzyme proved to be less susceptible to glucose-induced proteolysis, exhibiting a 3.75-fold reduction in turnover rate following a shift to glucose medium. Rates of loss of activity for other cellular enzymes known to be subject to glucose inactivation were similarly reduced. An extended lag in attaining wild type rates of growth on glucose measured for strains expressing the truncated MDH2 enzyme represents the first evidence of a selective advantage for the phenomenon of glucose-induced proteolysis in yeast.
Effects of humidity on Young's modulus in poly(methyl methacrylate) (2002)

Abstract Tensile tests on poly (methyl methacrylate) (PMMA) were conducted to clarify the effects of humidity and strain rate on tensile properties, particularly Young's modulus. Prior to the tensile tests, specimens were kept under various humidity conditions at 293 K, which were the same as the test conditions, for a few months to adjust the sorbed water content in the specimens. The tensile tests were performed under each humidity condition at three different strain rates (approximately 1.4 × 10 −3 , 1.4 × 10 −4 , and 1.4 × 10 −5 s −1 ). Stress‐strain curves changed with humidity and strain rate. Young's moduli were also measured at small applied stresses (below 6.7 MPa) under various humidity conditions at 293 K. Young's modulus decreases linearly with increasing humidity and a decreasing logarithm of strain rate. These results suggest that Young's modulus of PMMA can be expressed as a function of two independent parameters that are humidity and strain rate. A constitutive equation for Young's modulus of PMMA was proposed. © 2002 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 40: 460–465, 2002; DOI 10.1002/polb.10107
Zero-Mode Waveguides for Single-Molecule Analysis at High Concentrations (2003)

Optical approaches for observing the dynamics of single molecules have required pico- to nanomolar concentrations of fluorophore in order to isolate individual molecules. However, many biologically relevant processes occur at micromolar ligand concentrations, necessitating a reduction in the conventional observation volume by three orders of magnitude. We show that arrays of zero-mode waveguides consisting of subwavelength holes in a metal film provide a simple and highly parallel means for studying single-molecule dynamics at micromolar concentrations with microsecond temporal resolution. We present observations of DNA polymerase activity as an example of the effectiveness of zero-mode waveguides for performing single-molecule experiments at high concentrations.
Logic Gates and Computation from Assembled Nanowire Building Blocks (2001)

Miniaturization in electronics through improvements in established "top-down" fabrication techniques is approaching the point where fundamental issues are expected to limit the dramatic increases in computing seen over the past several decades. Here we report a "bottom-up" approach in which functional device elements and element arrays have been assembled from solution through the use of electronically well-defined semiconductor nanowire building blocks. We show that crossed nanowire p-n junctions and junction arrays can be assembled in over 95% yield with controllable electrical characteristics, and in addition, that these junctions can be used to create integrated nanoscale field-effect transistor arrays with nanowires as both the conducting channel and gate electrode. Nanowire junction arrays have been configured as key OR, AND, and NOR logic-gate structures with substantial gain and have been used to implement basic computation.
ChemInform Abstract: Reactivity of Heterocyclic Compounds. Part 6. 2,6‐Diaminopyrimidine‐5‐carbonitriles and 3,5‐Dicyanopyridones from 2‐Amino‐4H‐pyran‐3,5‐dicarbonitriles. (1986)

Abstract The reaction of the dicarbonitriles (Ia)‐(Ic) with guanidine (II) yields the carbonitriles (III), while ω‐cyanoacetophenone is eliminated.
Discovery of Potent Nonpeptide Vitronectin Receptor (αVβ3) Antagonists (1997)

ADVERTISEMENT RETURN TO ISSUELetterNEXTDiscovery of Potent Nonpeptide Vitronectin Receptor (αVβ3) AntagonistsRichard M. Keenan, William H. Miller, Chet Kwon, Fadia E. Ali, James F. Callahan, Raul R. Calvo, Shing-Mei Hwang, Kenneth D. Kopple, Catherine E. Peishoff, James M. Samanen, Angela S. Wong, Chuan-Kui Yuan, and William F. HuffmanView Author Information Departments of Medicinal Chemistry, Cellular Biochemistry, and Physical & Structural Chemistry, Research & Development Division, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, P. O. Box 1539, King of Prussia, Pennsylvania 19406-0939Cite this: J. Med. Chem. 1997, 40, 15, 2289–2292Publication Date (Web):July 18, 1997Publication History Received26 March 1997Published online18 July 1997Published inissue 1 July 1997https://doi.org/10.1021/jm970205rCopyright © 1997 American Chemical SocietyRIGHTS & PERMISSIONSArticle Views500Altmetric-Citations100LEARN 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 InReddit Read OnlinePDF (241 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Antagonists,Cells,Conformation,Monomers,Peptides and proteins Get e-Alerts
A primeira experiencia clinica do aluno: ansiedades e fantasias presentes no atendimento e na supervisao (2000)

Neste artigo apresentamos observacoes e reflexoes derivadas da experiencia de mais de dez anos supervisionando alunos de graduacao na sua primeira experiencia clinica, a qual consiste na realizacao de um processo psicodiagnostico. Mostramos atraves de exemplos clinicos que, numa linha de trabalho com abordagem psicanalitica, as ansiedades e fantasias do aluno em relacao ao atendimento e a supervisao desempenham um papel fundamental no aprendizado clinico. Palavras-chave : Supervisao; Ensino/Aprendizado Clinico; Formacao do Psicologo; Processo Psicodiagnostico; Estagio.
Abstract LB-140: Inhibition of cancer stemness sensitizes colorectal cancer to immune checkpoint inhibitors (2017)

Abstract Cancer stem cells (CSCs), a highly malignant tumor cell subpopulation capable of self-renewal, are considered to be fundamentally responsible for malignant growth and tumor recurrence. Emerging evidences indicate that CSCs and CSC pathways, such as STAT3, beta-Catenin, CD44 and Nanog pathway, are involved in the immune evasion in cancers. With the exception of a small percentage of colorectal cancers (CRC) patients that display microsatellite instability (MSI), the vast majority of CRC patients have been found to be resistant to immune checkpoint therapies. BBI-608 (napabucasin) is an orally-administered first-in-class cancer stemness inhibitor that works by targeting STAT3, which lead to inhibition of multiple cancer stemness pathways, including Stat3 and β-catenin pathways. In this study, we investigate the effect of cancer stemness inhibition on sensitizing CRC to immune checkpoint inhibitors in preclinical models. In the syngeneic tumor model, anti-PD-1 antibody monotherapy produced low level and temporary antitumor activity with rapid development of complete resistance to anti-PD1 in the MSS CT26 CRC model. The anti-PD-1 antibody treated CT26 tumors exhibited increased p-STAT3 activation and overexpression of a variety of stemness factors, including Nanog, CD44 and CD133, as well as enrichment of sphere-forming stemness-high cancer cells. BBI-608 was able to reduce basal as well as anti-PD1-induced STAT3 activation and other CSC features within CT26 tumors. Combination of stemness inhibitor BBI-608 with anti-PD-1 antibody to treat CT26 tumors led to tumor complete response (CR) virtually in all treated CT26 tumors with 40% of the mice remain tumor-free for 30 days following treatment termination. This combination also had a synergistic effect on the influx of tumor infiltrating CD8+ T cells, which likely contributed to the rapid tumor regression. Finally, mice CR-induced by BBI-608 and anti-PD-1 antibody were able to reject CT26 tumors upon rechallenge, but not the unrelated breast cancer 4T1 tumors. Our data suggests cancer stemness pathways contribute to immunotherapy resistance in MSS CRC and inhibition of cancer stemness by BBI-608 sensitizes colorectal cancer to immune checkpoint inhibition. This study provides compelling preclinical evidence to support the investigation of the combination of BBI608 with immune checkpoint inhibitors in CRC. Citation Format: Yuan Gao, Youzhi Li, Eric Hsu, Yuxin Wang, Janet Huang, Emily Brooks, Chiang J. Li. Inhibition of cancer stemness sensitizes colorectal cancer to immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-140. doi:10.1158/1538-7445.AM2017-LB-140
A Unique Galectin Signature in Human Prostate Cancer Progression Suggests Galectin-1 as a Key Target for Treatment of Advanced Disease (2012)

Galectins, a family of glycan-binding proteins, influence tumor progression by modulating interactions between tumor, endothelial, stromal, and immune cells. Despite considerable progress in identifying the roles of individual galectins in tumor biology, an integrated portrait of the galectin network in different tumor microenvironments is still missing. We undertook this study to analyze the "galectin signature" of the human prostate cancer microenvironment with the overarching goal of selecting novel-molecular targets for prognostic and therapeutic purposes. In examining androgen-responsive and castration-resistant prostate cancer cells and primary tumors representing different stages of the disease, we found that galectin-1 (Gal-1) was the most abundantly expressed galectin in prostate cancer tissue and was markedly upregulated during disease progression. In contrast, all other galectins were expressed at lower levels: Gal-3, -4, -9, and -12 were downregulated during disease evolution, whereas expression of Gal-8 was unchanged. Given the prominent regulation of Gal-1 during prostate cancer progression and its predominant localization at the tumor-vascular interface, we analyzed the potential role of this endogenous lectin in prostate cancer angiogenesis. In human prostate cancer tissue arrays, Gal-1 expression correlated with the presence of blood vessels, particularly in advanced stages of the disease. Silencing Gal-1 in prostate cancer cells reduced tumor vascularization without altering expression of other angiogenesis-related genes. Collectively, our findings identify a dynamically regulated "galectin-specific signature" that accompanies disease evolution in prostate cancer, and they highlight a major role for Gal-1 as a tractable target for antiangiogenic therapy in advanced stages of the disease.