gebhart/patrepeval huggingface dataset:
NBI 30775 (R121919), an orally active antagonist of the corticotropin‐releasing factor (CRF) type‐1 receptor for the treatment of anxiety and depression (2005)

Abstract Since the discovery of corticotropin‐releasing factor (CRF), extensive research has attempted to provide novel treatment strategies for diseases related to the malfunctions of the hypothalamic–pituitary–adrenocortical (HPA) system. In depression, cerebrospinal fluid levels of CRF are higher than that in normal individuals. Specifically, increased CRF signaling via the CRF 1 receptor is thought to be an important factor in the pathogenesis of major depression and anxiety disorders. Consequently, a number of compounds have been in various stages of development targeting the postulated overactivity of CRF/CRF 1 ‐receptor signaling. NBI 30775, also known as R121919, is a potent, selective, and functional antagonist of the human CRF 1 receptor that was being developed as a potentially novel treatment for anxiety and depression. In pharmacological assays in vitro, NBI 30775 was shown to be a potent functional antagonist at the CRF 1 receptor, while having little affinity at the CRF 2 receptor subtype. In animal studies, this translated into central CRF 1 receptor inhibition determined by ex vivo binding studies. NBI 30775 was able to reduce stress‐induced elevations of plasma ACTH. It also exhibited behavioral effects in several animal models measuring both anxiety and depression, which included elevate plus maze, defense withdrawal, and tail suspension tests. Finally, in an open‐label dose‐escalation Phase 2a clinical study in patients with major depressive disorder, NBI 30775 was able to reduce the scores on self‐rated or physician‐administered depression scales in the patients. Although there were no untoward effects seen in the Phase 2a study, the clinical development of this compound was discontinued because of a reversible elevation of liver enzyme activity in two healthy volunteers in a parallel Phase I dose‐escalation study. This first clinical experience has certainly had a positive impact in the efforts to find a safe CRF 1 receptor antagonist as a novel therapeutic for depression‐ and anxiety‐related disorders. Drug Dev. Res. 65:216–226, 2005. © 2005 Wiley‐Liss, Inc.
Divergent cytokine production profile in Behçet's disease. Altered Th1/Th2 cell cytokine pattern. (1998)

The immune system in BD may be characterized by a divergent cytokine production profile of mixed Th1/Th2 (Th0) cell type; IFN-gamma is critical in modulating the IL-4, IL-10, and IL-12 cytokine network pathway in this disease.
Current concept of the role of monocytes/macrophages in inflammatory bowel disease--balance of proinflammatory and immunosuppressive mediators. (1998)

Macrophages are important in providing the first line of intestinal defence against microorganisms or toxins that break the epithelial barrier, by presenting antigen to sensitised T cells and releasing a variety of cytokines and inflammatory mediators. During active states in inflammatory bowel disease, large numbers of monocytes leave the bloodstream and migrate into the inflamed mucosa and submucosa. Phenotypic studies have previously shown the presence of much more marked macrophage heterogeneity in inflammatory bowel disease mucosa than in normal mucosa. In both Crohn's disease and in ulcerative colitis, distinct macrophage populations have been found, being prominent in active disease, but absent from normal mucosa. Studies in our institution have shown that the Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 (27E10 epitope) are expressed in the majority of granulocytes and macrophages in active but not inactive inflammatory bowel disease. Furthermore, a strong complex MRP8/14 immunoreactivity was present in epithelial cells of the terminal ileum adjacent to ulcerative and fissuring lesions, while epithelial cells of large bowel tissues were consistently negative. In vitro studies revealed that interleukin-13, interleukin-10 and interleukin-4 strongly suppress secretion of different monocytic proteins. A combination of TH2-cytokines even at suboptimal concentrations significantly suppressed protein secretion, much more than using interleukin-13, interleukin-10 or interleukin-4 at a double concentration alone. Our morphological findings demonstrate the presence of MRP8/14 (27E10 antigen) both in monocytes/macrophages and in epithelial cells in active inflammatory bowel disease. Systemic or topical application of combined cytokine treatment might be a new effective therapeutic approach for chronic inflammatory bowel disease especially in those cases in which monocytes/macrophages lose their ability to respond, to some degree, to anti-inflammatory cytokines.
HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice (2013)

Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1-infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, lowering the initial viral load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn. Similarly, a single injection of adeno-associated virus directing expression of one bNAb produced durable viremic control after ART was terminated. We conclude that immunotherapy reduces plasma viral load and cell-associated HIV-1 DNA and that decreasing the initial viral load enables single bNAbs to control viremia in hu-mice.
Dedicated Breast CT: Initial Clinical Experience (2008)

Some technical challenges remain, but breast CT is promising and may have potential clinical applications.
Taste and flavour: their importance in food choice and acceptance (1998)

An abstract is not available for this content so a preview has been provided. As you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Vitamin D and gastrointestinal diseases: inflammatory bowel disease and colorectal cancer (2010)

Over the past 5 years, there has been a rapid resurgence of interest in vitamin D outside of its traditional role in metabolic bone disease. Some nontraditional roles ascribed to vitamin D include anti-inflammatory and immune-modulating effects. These effects have led to possible implications in the pathophysiology of immune-mediated diseases including multiple sclerosis and inflammatory bowel disease (IBD). In addition, vitamin D insufficiency has been linked to higher rates of cancers including colon, prostate and breast cancers. Given these diverse associations of vitamin D and disease states, this review describes recent advances with regard to vitamin D and gastrointestinal diseases, in particular IBD and colorectal cancer.
Permissive role of thrombopoietin and granulocyte colony-stimulating factor receptors in hematopoietic cell fate decisions in vivo (1999)

The question of whether extracellular signals influence hematopoiesis by instructing stem cells to commit to a specific hematopoietic lineage (instructive model) or solely by permitting the survival and proliferation of predetermined progenitors (permissive model) has been controversial since the discovery of lineage-dominant hematopoietic cytokines. To study the potential role of cytokines and their receptors in hematopoietic cell fate decisions, we used homologous recombination to replace the thrombopoietin receptor gene (mpl) with a chimeric construct encoding the extracellular domain of mpl and the cytoplasmic domain of the granulocyte colony-stimulating factor receptor (G-CSFR). This chimeric receptor binds thrombopoietin but signals through the G-CSFR intracellular domain. We found that, despite the absence of a functional mpl signaling domain, homozygous knock-in mice had a normal platelet count, indicating that in vivo the cytoplasmic domain of G-CSFR can functionally replace mpl signaling to support normal megakaryopoiesis and platelet formation. This finding is compatible with the permissive model, according to which cytokine receptors provide a nonspecific survival or proliferation signal, and argues against an instructive role of mpl or G-CSFR in hematopoietic cell fate decisions.
Opportunities and challenges of III-V nanoelectronics for future high-speed, low-power logic applications (2005)

This paper highlights the opportunities and challenges of III-V nanoelectronics for future high-speed, low- power digital logic applications. III-V materials in general have significantly higher electron mobility than Si and can potentially play a major role along with Si in future high-speed, low-power computing. The major potential advantage of using a III-V quantum-well field-effect transistor as a logic transistor is that it can be operated under very low supply voltage (e.g., 0.5 V), and hence, lower power dissipation while still achieving very high speed. Compared to other emerging high-mobility materials, such as, carbon nanotubes and semiconductor nanowires, which require "bottom-up" chemical synthesis for formation and suffer from the fundamental placement problem, III-V materials are far more practical in terms of patterning. However, many significant challenges remain to be overcome before III-V materials become applicable for future high-speed, low-power logic applications. These include: (i) finding a compatible high-K gate dielectric on III-Vs, (ii) demonstrating gate length scalability below 35 nm with acceptable I/sub ON//I/sub OFF/ ratio, (iii) improving the hole mobility in III-Vs or finding the right p-channel FET for the complementary metal-oxide-semiconductor (CMOS) configuration, and (iv) integrating III-V materials onto the Si substrate.
KRAS mutation testing for predicting response to anti-EGFR therapy for colorectal carcinoma: proposal for an European quality assurance program (2008)

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with colorectal carcinoma. However, these therapies are effective only in a subset of patients. Activating mutations in the KRAS gene are found in 30-40% of colorectal tumors and are associated with poor response to anti-EGFR therapies. Thus, KRAS mutation status can predict which patient may or may not benefit from anti-EGFR therapy. Although many diagnostic tools have been developed for KRAS mutation analysis, validated methods and standardized testing procedures are lacking. This poses a challenge for the optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Here we review the molecular basis of EGFR-targeted therapies and the resistance to treatment conferred by KRAS mutations. We also present guideline recommendations and a proposal for a European quality assurance program to help ensure accuracy and proficiency in KRAS mutation testing across the European Union.
The application of pattern recognition technology in the diagnosis and analysis on the heart disease: Current status and future (2012)

Electrocardiography (ECG) is an important tool for the doctor to analyze the basic function and pathology of the heart. Consequently, it is significant to perform the pattern recognition oriented feature extraction and waveform classification on the ECG signal. In this paper, we first present the world-wide risk of the heart disease and the motivation of introducing pattern recognition technology into the ECG data analysis. Next, we state in detail the current status of researches on the ECG pattern recognition technology as well as compare the commonly used methods of detection, analysis and classification. In the final, we discuss the prospect and the future issues on the ECG pattern recognition technology according to the advantage and disadvantage of the current methods for ECG data analysis.
Towards a framework for software measurement validation (1995)

In this paper we propose a framework for validating software measurement. We start by defining a measurement structure model that identifies the elementary component of measures and the measurement process, and then consider five other models involved in measurement: unit definition models, instrumentation models, attribute relationship models, measurement protocols and entity population models. We consider a number of measures from the viewpoint of our measurement validation framework and identify a number of shortcomings; in particular we identify a number of problems with the construction of function points. We also compare our view of measurement validation with ideas presented by other researchers and identify a number of areas of disagreement. Finally, we suggest several rules that practitioners and researchers can use to avoid measurement problems, including the use of measurement vectors rather than artificially contrived scalars.
The role of asenapine in the treatment of manic or mixed states associated with bipolar I disorder (2011)

Research indicates that asenapine is generally well-tolerated, and that asenapine is efficacious and not inferior to olanzapine in the treatment of mixed or manic episodes associated with BD type 1 in the short-term and long-term.
Isolation and Characterization of a Regulatory Mutant of an Aminoacyl-Transfer Ribonucleic Acid Synthetase in Escherichia coli K-12 (1973)

From Escherichia coli strain K28, which is temperature sensitive for growth because of a mutation in its seryl-transfer ribonucleic acid (tRNA) synthetase gene (serS), temperature-resistant mutants were selected which were found to have a fivefold higher level of seryl-tRNA synthetase than the parent strain. The "high-level" character was found to be genetically stable and is due to a mutation in a locus denoted serO. This locus was found to be very closely linked to serS on the genetic map, and the relative gene order was concluded to be serS-serO-serC. In a serO(-) strain, the normal dependence of seryl-tRNA synthetase (SerRS) activity on changes of exogenous serine concentration was not observed. In a stable heterozygous merodiploid, the serO(-) mutation is still expressed, i.e., it is cis dominant. These results strongly suggest that serO is an operator site involved in the control of the serS gene.
Formal Chemoselective Synthesis of Leucascandrolide A (2007)

A chemoselective synthesis of the macrocyclic core of leucascandrolide A has been achieved, utilizing highly enantioselective allylmetalations, an enantioselective Noyori reduction of a propargylic ketone and olefin metatheses as the key steps.
Alemtuzumab vs. Interferon Beta-1a in Early Multiple Sclerosis (2008)

In patients with early, relapsing-remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura. The study was not powered to identify uncommon adverse events. (ClinicalTrials.gov number, NCT00050778.)
Fan Handbook: Selection, Application, and Design (1997)

Basics of Staionary and Moving Air. Airfoils and Single-Thickness Sheet Metal Profiles. Types of Fans, Terminology, and MechanicalConstruction. Axial-Flow Fans. Fan Laws. System Resistance. Contrifugal Fans. Fan Selection, Specific Speed, Examples. Axial-Centrifugal Fans. Roof Ventilators. Ventilation Requirements and Duct Systems. Agriculatural Ventilation Requirements. Cross-Flow Blowers. Flow Coefficient and Pressure Coefficient. Vortex Blowers. Various Methods to Drive a Fan. Fanless Air Movers. Performance Testing of Fans. Vacuum Cleaners. Fan Perforamnce as Shown in Catalogs. Air Curtains. Ceiling Fans. AMCA Standards. Mechanical Strength. Trouble Shooting and Problem Solving. Installation, Safety, and Maintenance.
Isolation of varicella-zoster virus from pharyngeal and nasal swabs in varicella patients. (1984)

Thirteen children aged 5 months to 4 years were observed during a varicella epidemic in an Infants' Hospital; except for two normal individuals, the children had various forms of congenital defects. Eleven of the children developed varicella. During the first 3 days of exanthem, a total of 17 VZ virus strains were isolated: 12 from vesicular fluid, 3 from 23 nasal and 2 from 22 pharyngeal swabs. No strain was isolated during the incubation period despite 57 and 56 swabs having been collected from the throat and nose, respectively; nor was VZ virus isolated from 6 pharyngeal and 7 nasal swabs taken on the first day of exanthem. Isolation attempts performed from vesicular fluid to control quality of the isolation conditions gave a positivity rate of 100%. Under these optimal isolation conditions VZ virus was found in the nose or throat alongside skin vesicles in four of the 11 ill children. Besides VZ virus, the pharyngeal and nasal swabs yielded, respectively, four and four cytomegalovirus strains. The cytomegalovirus infections were inapparent.
Liver-Targeted Prodrugs of 2‘-C-Methyladenosine for Therapy of Hepatitis C Virus Infection (2007)

2'-C-Methyladenosine exhibits impressive inhibitory activity in the cell-based hepatitis C virus (HCV) subgenomic replicon assay, by virtue of intracellular conversion to the corresponding nucleoside triphosphate (NTP) and inhibition of NS5B RNA-dependent RNA polymerase (RdRp). However, rapid degradation by adenosine deaminase (ADA) limits its overall therapeutic potential. To reduce ADA-mediated deamination, we prepared cyclic 1-aryl-1,3-propanyl prodrugs of the corresponding nucleoside monophosphate (NMP), anticipating cytochrome P450 3A-mediated oxidative cleavage to the NMP in hepatocytes. Lead compounds identified in a primary rat hepatocyte screen were shown to result in liver levels of NTP predictive of efficacy after intravenous dosing to rats. The oral bioavailability of the initial lead was below 5%; therefore, additional analogues were synthesized and screened for liver NTP levels after oral administration to rats. Addition of a 2',3'-carbonate prodrug moiety proved to be a successful strategy, and the 1-(4-pyridyl)-1,3-propanyl prodrug containing a 2',3'-carbonate moiety displayed oral bioavailability of 39%.
Optimizing therapeutic efficacy of chemopreventive agents: A critical review of delivery strategies in oral cancer chemoprevention clinical trials (2011)

Due to its characterized progression from recognized premalignant oral epithelial changes (i.e., oral epithelial dysplasia) to invasive cancer, oral squamous cell carcinoma represents an optimal disease for chemopreventive intervention prior to malignant transformation. The primary goal of oral cancer chemoprevention is to reverse, suppress, or inhibit the progression of premalignant lesions to cancer. Over the last several decades, numerous oral cancer chemoprevention clinical trials have assessed the therapeutic efficacy of diverse chemopreventive agents. The standard of care for more advanced oral dysplastic lesions entails surgical excision and close clinical follow-up due to the potential (~33%) for local recurrence at a similar or more advanced histological stage. The purpose of this review was to identify prominent oral cancer chemoprevention clinical trials, assess their overall therapeutic efficacy, and delineate effects of local versus systemic drug administration. In addition, these compiled clinical trial data present concepts for consideration in the design and conduction of future clinical trials.
Differential antioxidative response of tolerant and sensitive maize (Zea mays L.) genotypes to drought stress at reproductive stage. (2013)

The role of oxidative stress management was evaluated in two maize (Zea mays L.) genotypes - Parkash (drought-resistant) and Paras (drought-sensitive), subjected to drought stress during reproductive stage. Alterations in their antioxidant pools - glutathione (GSH) and ascorbic acid (AsA) combined with activities of enzymes glutathione reductase (GR), ascorbate peroxidase (APX), peroxidase (POX) and catalase (CAT) involved in defense against oxidative stress and stress parameters, namely chlorophyll (Chl), hydrogen peroxide (H2O2) and malondialdehyde (MDA) were investigated in flag leaves from silk emergence till maturity. The drought caused transient increase in GR, APX, POX and CAT activities in drought-tolerant genotype (Parkash) which decreased at later stages with the extended period of drought stress. However, in Paras, drought stress caused decrease in activities of GR and CAT from initial period of stress till the end of experiment, except for POX which showed slight increase in activity. A significant increase in GSH content was observed in Parkash till 35 days after silking (DAS), whereas in Paras, GSH content remained lower than irrigated till maturity. Parkash which had higher AsA and Chl contents, also showed lower H2O2 and MDA levels than Paras under drought stress conditions. However, at the later stages, decline in antioxidant enzyme activities in Parkash due to severe drought stress led to enhanced membrane damage, as revealed by the accumulation of MDA. Our data indicated that significant activation of antioxidant system in Parkash might be responsible for its drought-tolerant behavior under drought stress and helped it to cope with the stress up to a definite period. Thus, the results indicate that antioxidant status and lipid peroxidation in flag leaves can be used as indices of drought tolerance in maize plants and also as potential biochemical targets for the crop improvement programmes to develop drought-tolerant cultivars.
Reduction of .DELTA.2-isoxazolines. 3. Raney nickel catalyzed formation of .beta.-hydroxy ketones (1983)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of .DELTA.2-isoxazolines. 3. Raney nickel catalyzed formation of .beta.-hydroxy ketonesDennis P. CurranCite this: J. Am. Chem. Soc. 1983, 105, 18, 5826–5833Publication Date (Print):September 1, 1983Publication History Published online1 May 2002Published inissue 1 September 1983https://pubs.acs.org/doi/10.1021/ja00356a021https://doi.org/10.1021/ja00356a021research-articleACS PublicationsRequest reuse permissionsArticle Views2397Altmetric-Citations259LEARN 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