gebhart/patrepeval huggingface dataset:
Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists (1988)

3-(Acylamino)-5-phenyl-2H-1,4-benzodiazepines, antagonists of the peptide hormone cholecystokinin (CCK), are described. Developed by reasoned modification of the known anxiolytic benzodiazepines, these compounds provide highly potent, orally effective ligands selective for peripheral (CCK-A) receptors, with binding affinities approaching or equaling that of the natural ligand CCK-8. The distinction between CCK-A receptors on the one hand and CNS (CCK-B), gastrin, and central benzodiazepine receptors on the other is demonstrated by using the structure-activity profiles of the new compounds. Details of the binding of these agents to CCK-A receptors are examined, and the method of development of these compounds is discussed in terms of its relevance to the general problem of drug discovery.
A double-blind randomized placebo-controlled phase III study of a Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients (2007)

Pseudomonas aeruginosa causes life-threatening lung infections in patients with cystic fibrosis. We hypothesized that vaccination may prevent P. aeruginosa lung infection. In a double-blind, placebo-controlled, multicenter trial, 483 European patients, 2-18 years of age without P. aeruginosa colonization were randomly assigned to receive four intramuscular injections of a bivalent P. aeruginosa flagella vaccine or placebo over a 14-month period. Patients were evaluated quarterly for P. aeruginosa-positive throat cultures and antipseudomonal serum antibody titers during the study period of 2 years. The vaccine was well tolerated, and the patients developed high and long-lasting serum antiflagella IgG titers. In the intention-to-treat group (all patients enrolled), 82 of 239 vaccinated patients had P. aeruginosa infection and/or antipseudomonal serum titers compared with 105 of 244 patients in the placebo group (P = 0.05; relative risk: 0.80; 95% CI: 0.64-1.00). Analysis of the 381 patients in the per-protocol group, who received all four vaccinations or placebo treatments, revealed 37 of 189 patients with infection episodes in the vaccine group compared with 59 of 192 patients with such episodes in the placebo group (P = 0.02; relative risk: 0.66; 95% CI: 0.46-0.93). P. aeruginosa strains, exhibiting flagella subtypes included in the vaccine, were significantly less frequently isolated from vaccinates than from placebo controls (P = 0.016, relative risk: 0.319; 95% CI: 0.12-0.86). Chronic P. aeruginosa infection was rare because of recent institution of early antibiotic eradication regimes. Active immunization of patients with cystic fibrosis lowers the risk for infection with P. aeruginosa and therefore may contribute to a longer survival of these patients.
Transforming Growth Factor-β and Notch Signaling Mediate Stem Cell Differentiation into Smooth Muscle Cells (2010)

The differentiation of stem cells into smooth muscle cells (SMCs) plays an important role in vascular development and remodeling. In addition, stem cells represent a potential source of SMCs for regenerative medicine applications such as constructing vascular grafts. Previous studies have suggested that various biochemical factors, including transforming growth factor-beta (TGF-beta) and the Notch pathway, may play important roles in vascular differentiation. However, the interactions of these two signaling pathways in the differentiation of bone marrow mesenchymal stem cells (MSCs) have not been clearly defined. In this study, we profiled the gene expression in MSCs in response to TGF-beta, and showed that TGF-beta induced Notch ligand Jagged 1 (JAG1) and SMC markers, including smooth muscle alpha-actin (ACTA2), calponin 1 (CNN1), and myocardin (MYOCD), which were dependent on the activation of SMAD3 and Rho kinase. In addition, knocking down JAG1 expression partially blocked ACTA2 and CNN1 expression and completely blocked MYOCD expression, suggesting that JAG1 plays an important role in TGF-beta-induced expression of SMC markers. On the other hand, the activation of Notch signaling induced the expression of SMC markers in MSCs and human embryonic stem cells (hESCs). Notch activation in hESCs also resulted in an increase of neural markers and a decrease of endothelial markers. These results suggest that Notch signaling mediates TGF-beta regulation of MSC differentiation and that Notch signaling induces the differentiation of MSCs and hESCs into SMCs, which represents a novel mechanism involved in stem cell differentiation.
Functional Characterization of Two Type III Secretion Systems of Vibrio parahaemolyticus (2004)

Vibrio parahaemolyticus, a gram-negative marine bacterium, is a worldwide cause of food-borne gastroenteritis. Recent genome sequencing of the clinical V. parahaemolyticus strain RIMD2210633 identified two sets of genes for the type III secretion system (TTSS), TTSS1 and TTSS2. Here, we constructed a series of mutant strains from RIMD2210633 to determine whether the two putative TTSS apparatus are functional. The cytotoxic activity of mutant strains having a deletion in one of the TTSS1 genes was significantly decreased compared with that of the parent and TTSS2-related mutant strains. In an enterotoxicity assay with the rabbit ileal loop test, intestinal fluid accumulation was diminished by deletion of the TTSS2-related genes while TTSS1-related mutants caused a level of fluid accumulation similar to that of the parent. VopD, a protein encoded in the proximity of the TTSS1 region and a homologue of the Yersinia YopD, was secreted in a TTSS1-dependent manner. In contrast, VopP, which is encoded by a pathogenicity island on chromosome 2 and is homologous to the Yersinia YopP, was secreted via the TTSS2 pathway. These results provide evidence that V. parahaemolyticus TTSSs function as secretion systems and may have a role in the pathogenicity of the organism. This is the first report of functional TTSSs in Vibrio species. The presence of TTSS apparatus gene homologues was demonstrated in other vibrios, such as Vibrio alginolyticus, Vibrio harveyi, and Vibrio tubiashii, suggesting that some other vibrios also contain TTSS and that the TTSS has a role in protein secretion in those organisms during interaction with eukaryotic cells.
Effective adenovirus-mediated gene expression in adult murine skeletal muscle (1999)

We established an efficient method for obtaining expression of a foreign marker gene transferred in vitro into myoblasts and in vivo into adult mouse skeletal muscles using adenovirus vector. After infection of the C2 myoblasts with the adenovirus vector containing the beta-actin promoter with cytomegalovirus (CMV) enhancer (CAG promoter) AxCALacZ, significantly greater number of cells express beta-galactosidase when compared with the adenovirus vector expressing the lacZ gene under the control of the SR alpha viral terminal repeat promoter (AxSRLacZL) or the myosin heavy chain (MHC) IIB promoter (AxMHCLacZ). We also injected AxCALacZ into the skeletal muscles of 5- to 6-week-old C57BL/10 mice and determined that more than 60% of their muscle fibers expressed the lacZ gene 7 days after injection. The CAG promoter may have application in the development of gene therapy for Duchenne muscular dystrophy (DMD) using adenovirus vector.
Comparing images using the Hausdorff distance (1993)

The Hausdorff distance measures the extent to which each point of a model set lies near some point of an image set and vice versa. Thus, this distance can be used to determine the degree of resemblance between two objects that are superimposed on one another. Efficient algorithms for computing the Hausdorff distance between all possible relative positions of a binary image and a model are presented. The focus is primarily on the case in which the model is only allowed to translate with respect to the image. The techniques are extended to rigid motion. The Hausdorff distance computation differs from many other shape comparison methods in that no correspondence between the model and the image is derived. The method is quite tolerant of small position errors such as those that occur with edge detectors and other feature extraction methods. It is shown that the method extends naturally to the problem of comparing a portion of a model against an image.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Competing Conceptions of Risk (1996)

Recent literature is said to reflect growing acknowledgment of multiple conceptions of risk but often to obscure an important distinction. Building on work of Kristin Shrader-Frechette, the authors explore the potential for debate over competing philosophical conceptions of risk.
Autophagy in lysosomal storage disorders (2012)

Lysosomes are ubiquitous intracellular organelles that have an acidic internal pH, and play crucial roles in cellular clearance. Numerous functions depend on normal lysosomes, including the turnover of cellular constituents, cholesterol homeostasis, downregulation of surface receptors, inactivation of pathogenic organisms, repair of the plasma membrane and bone remodeling. Lysosomal storage disorders (LSDs) are characterized by progressive accumulation of undigested macromolecules within the cell due to lysosomal dysfunction. As a consequence, many tissues and organ systems are affected, including brain, viscera, bone and cartilage. The progressive nature of phenotype development is one of the hallmarks of LSDs. In recent years biochemical and cell biology studies of LSDs have revealed an ample spectrum of abnormalities in a variety of cellular functions. These include defects in signaling pathways, calcium homeostasis, lipid biosynthesis and degradation and intracellular trafficking. Lysosomes also play a fundamental role in the autophagic pathway by fusing with autophagosomes and digesting their content. Considering the highly integrated function of lysosomes and autophagosomes it was reasonable to expect that lysosomal storage in LSDs would have an impact upon autophagy. The goal of this review is to provide readers with an overview of recent findings that have been obtained through analysis of the autophagic pathway in several types of LSDs, supporting the idea that LSDs could be seen primarily as "autophagy disorders."
Periodate Oxidations of Oxazolines (1961)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPeriodate Oxidations of OxazolinesH. L. WEHRMEISTERCite this: J. Org. Chem. 1961, 26, 10, 3821–3824Publication Date (Print):October 1, 1961Publication History Published online1 May 2002Published inissue 1 October 1961https://pubs.acs.org/doi/10.1021/jo01068a047https://doi.org/10.1021/jo01068a047research-articleACS PublicationsRequest reuse permissionsArticle Views798Altmetric-Citations11LEARN 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
SQUASH: Simple QoS-Aware High-Performance Memory Scheduler for Heterogeneous Systems with Hardware Accelerators (2015)

Modern SoCs integrate multiple CPU cores and Hardware Accelerators (HWAs) that share the same main memory system, causing interference among memory requests from different agents. The result of this interference, if not controlled well, is missed deadlines for HWAs and low CPU performance. State-of-the-art mechanisms designed for CPU-GPU systems strive to meet a target frame rate for GPUs by prioritizing the GPU close to the time when it has to complete a frame. We observe two major problems when such an approach is adapted to a heterogeneous CPU-HWA system. First, HWAs miss deadlines because they are prioritized only close to their deadlines. Second, such an approach does not consider the diverse memory access characteristics of different applications running on CPUs and HWAs, leading to low performance for latency-sensitive CPU applications and deadline misses for some HWAs, including GPUs. In this paper, we propose a Simple Quality of service Aware memory Scheduler for Heterogeneous systems (SQUASH), that overcomes these problems using three key ideas, with the goal of meeting deadlines of HWAs while providing high CPU performance. First, SQUASH prioritizes a HWA when it is not on track to meet its deadline any time during a deadline period. Second, SQUASH prioritizes HWAs over memory-intensive CPU applications based on the observation that the performance of memory-intensive applications is not sensitive to memory latency. Third, SQUASH treats short-deadline HWAs differently as they are more likely to miss their deadlines and schedules their requests based on worst-case memory access time estimates. Extensive evaluations across a wide variety of different workloads and systems show that SQUASH achieves significantly better CPU performance than the best previous scheduler while always meeting the deadlines for all HWAs, including GPUs, thereby largely improving frame rates.
Covalent Sidewall Functionalization of Carbon Nanotubes (2001)

Progress of fluorination of single-wall carbon nanotubes is being reported. Covalent attachment of alkyl groups including methyl, n-butyl and n-hexyl groups to the sidewalls of single wall carbon nanotubes (SWNTs) has been achieved. Quantitative measurement of the alkylation was done by thermal gravimetric analysis. FTIR, Raman and UV-Vis-NIR were used to characterize these alkylated SWNTs. Application of these nanotubes are being investigated-fibers, composites, batteries, lubricants, etc.
Endocrine and antiprostatic effects of raloxifene (LY156758) in the male rat (1993)

The benzothiophene anti-estrogen, raloxifene [LY156758; (6-hydroxy-2-(4-hydroxyphenyl) benzo(b)thien-3-yl)(4-(2-1-piperidinyl)ethoxy)phenyl methanone hydrochloride] has selective estrogen pharmacological antagonist activity in female rats. The present studies were done in the male rat to assess activity of raloxifene related to inhibition of prostatic growth and effects on the hypothalamic-pituitary-gonadal axis. Raloxifene did not compete for binding of the androgen, [3H]-methyltrienolone (R1881) in cytosolic extracts of ventral prostate. Similarly, the compound did not inhibit prostatic 5 alpha-reductase or testicular 17 alpha-hydroxy/C17,20-lyase activities. Raloxifene had no effect on the ventral prostatic uptake of [3H]-R1881 in vivo. Administration of estradiol to castrated male rats stimulated fourfold increases of in vitro ventral prostatic binding of [3H]-R1881. Raloxifene was devoid of agonist activity in castrated animals, because the compound had no stimulatory effect on prostatic androgen receptor binding activity. When raloxifene was coadministered with estradiol, the compound markedly antagonized the estrogen-induced increase of prostatic [3H]-R1881 binding, confirming its antiestrogenic properties in male rats. Serum prolactin was also elevated significantly (P < 0.05) with a single injection of raloxifene (20.0 mg/kg). In these same animals, serum FSH was significantly (P < 0.05) decreased by one dose (10.0 mg/kg) of the compound. Luteinizing hormone levels in castrated male rats were unaffected by raloxifene administration. Raloxifene treatment of castrated males significantly (P < 0.05) antagonized the stimulatory response of the ventral prostate (VP) to exogenous androgens in a dose-dependent manner. Raloxifene treatment of intact male rats for 14 and 28 days produced significant (P < 0.05) dose-dependent regression of the VP and seminal vesicles (SV). The VP regressive responses to raloxifene were associated with a decline in serum testosterone levels. Histological analysis of the VPs in raloxifene-treated rats was consistent with an androgen-deprived state. These findings support the contention that raloxifene is a pure estrogen antagonist and a physiological antagonist of androgen action in male rats. These pharmacological properties provide support for further structure-activity and mechanistic investigations with benzothiophenes in the medical management of prostatic neoplasia.
Contralateral conjugate eye deviation during deep brain stimulation of the subthalamic nucleus (2007)

Given that stimulation of frontal eye field cortical regions produces similar contralateral conjugate eye deviation, these results are best explained by electrical current spread to nearby frontal eye field axons coursing lateral to the STN within the internal capsule. Thus, placement of the implanted electrode in a more medial, posterior, and inferior position may bring resolution of these symptoms by reducing the amount of current spread to internal capsule ax-
Biosynthesis of ketocarotenoids in transgenic cyanobacteria expressing the algal gene for β‐C‐4‐oxygenase,crtO (1997)

© 1997 Federation of European Biochemical Societies.
Soluble Polythiophenes with Pendant Fullerene Groups as Double Cable Materials for Photodiodes (2001)

A novel “double cable” material for photodiodes, containing both electron- and hole-transporting functional groups, is obtained by co-polymerization of thiophenes that bear a covalently linker-bound fullerene (see Figure). Even at 14 % of fullerene substitution, the order of the main polythiophene chain is not seriously disturbed.
A DNA polymerase stop assay for G-quadruplex-interactive compounds (1999)

We have developed and characterized an assay for G-quadruplex-interactive compounds that makes use of the fact that G-rich DNA templates present obstacles to DNA synthesis by DNA polymerases. Using Taq DNA polymerase and the G-quadruplex binding 2, 6-diamidoanthraquinone BSU-1051, we find that BSU-1051 leads to enhanced arrest of DNA synthesis in the presence of K+by stabilizing an intramolecular G-quadruplex structure formed by four repeats of either TTGGGG or TTAGGG in the template strand. The data provide additional evidence that BSU-1051 modulates telomerase activity by stabilization of telomeric G-quadruplex DNA and point to a polymerase arrest assay as a sensitive method for screening for G-quadruplex-interactive agents with potential clinical utility.
Cellular Function of Phosphoinositide 3-Kinases: Implications for Development, Immunity, Homeostasis, and Cancer (2001)

The phosphoinositide 3-kinase (PI3K) family of enzymes is recruited upon growth factor receptor activation and produces 3' phosphoinositide lipids. The lipid products of PI3K act as second messengers by binding to and activating diverse cellular target proteins. These events constitute the start of a complex signaling cascade, which ultimately results in the mediation of cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. Therefore, PI3Ks play a central role in many cellular functions. The factors that determine which cellular function is mediated are complex and may be partly attributed to the diversity that exists at each level of the PI3K signaling cascade, such as the type of stimulus, the isoform of PI3K, or the nature of the second messenger lipids. Numerous studies have helped to elucidate some of the key factors that determine cell fate in the context of PI3K signaling. For example, the past two years has seen the publication of many transgenic and knockout mouse studies where either PI3K or its signaling components are deregulated. These models have helped to build a picture of the role of PI3K in physiology and indeed there have been a number of surprises. This review uses such models as a framework to build a profile of PI3K function within both the cell and the organism and focuses, in particular, on the role of PI3K in cell regulation, immunity, and development. The evidence for the role of deregulated PI3K signaling in diseases such as cancer and diabetes is reviewed.
The Future Is Now: Chimeric Antigen Receptors as New Targeted Therapies for Childhood Cancer (2012)

Improved outcomes for children with cancer hinge on the development of new targeted therapies with acceptable short-term and long-term toxicity. Progress in basic, preclinical, and clinical arenas spanning cellular immunology, gene therapy, and cell-processing technologies have paved the way for clinical applications of chimeric antigen receptor-based therapies. This is a new form of targeted immunotherapy that merges the exquisite targeting specificity of monoclonal antibodies with the potent cytotoxicity, potential for expansion, and long-term persistence provided by cytotoxic T cells. Although this field is still in its infancy, clinical trials have already shown clinically significant antitumor activity in neuroblastoma, chronic lymphocytic leukemia, and B-cell lymphoma, and trials targeting a variety of other adult and pediatric malignancies are under way. Ongoing work is focused on identifying optimal tumor targets and elucidating and manipulating both cell- and host-associated factors to support expansion and persistence of the genetically engineered cells in vivo. In pediatric oncology, CD19 and GD2 are compelling antigens that have already been identified for targeting pre-B acute lymphoblastic leukemia and neuroblastoma, respectively, with this approach, but it is likely that other antigens expressed in a variety of childhood cancers will also soon be targeted using this therapy. The potential to target essentially any tumor-associated cell-surface antigen for which a monoclonal antibody can be made opens up an entirely new arena for targeted therapy of childhood cancer.
Production of 16α-Hydroxydehydroepiandrosterone-3-succinate byStreptomyces roseochromogenes (1975)

Journal Article Production of 16α-Hydroxydehydroepiandrosterone-3-succinate by Streptomyces roseochromogenes Get access Haruo Yamashita, Haruo Yamashita Department of Chemistry, Research Laboratories, Teikoku Hormone Mfg. Co., Ltd., Kawasaki, Kanagawa Search for other works by this author on: Oxford Academic Google Scholar Yuichiro Kurosawa Yuichiro Kurosawa Department of Chemistry, Research Laboratories, Teikoku Hormone Mfg. Co., Ltd., Kawasaki, Kanagawa Search for other works by this author on: Oxford Academic Google Scholar Agricultural and Biological Chemistry, Volume 39, Issue 11, 1 November 1975, Pages 2243–2244, https://doi.org/10.1080/00021369.1975.10861940 Published: 01 November 1975 Article history Received: 29 May 1975 Published: 01 November 1975
Predominant expression of the long isoform of GP130-like (GPL) receptor is required for interleukin-31 signaling. (2005)

Gp130-like receptor (GPL) is a newly identified cytokine receptor. A recent study reported the involvement of GPL, together with OSMR, in the formation of the receptor complex for IL-31, a novel immune cytokine with a skin tropism. In the present work, we analyzed the signaling properties of IL-31 in glioblastoma and melanoma tumor cells. We demonstrate that in response to IL-31, its receptor complex recruits Jak1, Jak2, STAT1, -3, -5 signaling pathways, as well as the Pi3 kinase / AKT cascade. SHP-2 and Shc adapter molecules are also recruited and contribute to an increased activation of the MAP kinase pathway in response to IL-31. Different responses were observed depending on the expression of short or long GPL receptor isoform within the studied cell lines. We show that the short form of GPL receptor exerts a profound inhibitory effect on the signaling of IL-31 and behaves as a dominant negative receptor.