gebhart/patrepeval huggingface dataset:
Oncolytic Adenovirus Coding for Granulocyte Macrophage Colony-Stimulating Factor Induces Antitumoral Immunity in Cancer Patients (2010)

Granulocyte macrophage colony-stimulating factor (GMCSF) can mediate antitumor effects by recruiting natural killer cells and by induction of tumor-specific cytotoxic T-cells through antigen-presenting cells. Oncolytic tumor cell-killing can produce a potent costimulatory danger signal and release of tumor epitopes for antigen-presenting cell sampling. Therefore, an oncolytic adenovirus coding for GMCSF was engineered and shown to induce tumor-specific immunity in an immunocompetent syngeneic hamster model. Subsequently, 20 patients with advanced solid tumors refractory to standard therapies were treated with Ad5-D24-GMCSF. Of the 16 radiologically evaluable patients, 2 had complete responses, 1 had a minor response, and 5 had disease stabilization. Responses were frequently seen in injected and noninjected tumors. Treatment was well tolerated and resulted in the induction of both tumor-specific and virus-specific immunity as measured by ELISPOT and pentamer analysis. This is the first time that oncolytic virus-mediated antitumor immunity has been shown in humans. Ad5-D24-GMCSF is promising for further clinical testing.
Diagnosis and management of the metabolic syndrome: An American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Executive summary (2019)

"This Executive Summary is a synopsis of the full scientific statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI), which is intended to provide up to date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome has received increased attention in the past few years. It consists of multiple, interrelated risk factors of metabolic origin that appear to directly promote the develop- ment of atherosclerotic cardiovascular disease (ASCVD). This constellation of metabolic risk factors is strongly associated with type 2 diabetes mellitus or the risk for this condition. The metabolic risk factors consist of atherogenic dyslipidemia (elevated triglycerides and apolipoprotein B, small LDL particles, and low HDL cholesterol [HDL-C] concentrations), elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state. At present, it is not clear whether the metabolic syndrome has a single cause, and it appears that it can be precipitated by multiple underlying risk factors. The most important of these underlying risk factors are abdominal obesity and insulin resis- tance. Other associated conditions include physical inactivity, aging, hormonal imbalance, and genetic or ethnic predisposition. Prospective population studies show that the metabolic syndrome confers an [almost equal to]2-fold increase in relative risk for ASCVD events, and in individuals without established type 2 diabetes mellitus, an [almost equal to]5-fold increase in risk for developing diabetes as compared with people without the syndrome. This finding implies that the meta- bolic syndrome imparts a relatively high long-term risk for both ASCVD and diabetes. In the absence of diabetes, the absolute short-term (10-year) risk for major coronary heart disease (CHD) events is not necessarily high. In the Framingham Heart Study data, the 10-year risk for CHD depends on other risk factors in addition to the metabolic syndrome components contained in Framingham scoring (ie, blood pressure, HDL-C). These other risk factors are age, sex, serum total or LDL-C, and smoking status. For individuals with the metabolic syndrome who do not have established ASCVD or type 2 diabetes mellitus, the absolute 10-year risk is best assessed by Framingham risk scoring."
The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho (2002)

Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. The receptor for MAG or signals that elicit morphological changes in neurons remained to be established. Here we show that the neurotrophin receptor p75 (p75(NTR)) is the signal transducing element for MAG. Adult dorsal root ganglion neurons or postnatal cerebellar neurons from mice carrying a mutation in the p75(NTR) gene are insensitive to MAG with regard to neurite outgrowth. MAG activates small GTPase RhoA, leading to retarded outgrowth when p75(NTR)) is present. Colocalization of p75(NTR) and MAG binding is seen in neurons. Ganglioside GT1b, which is one of the binding partners of MAG, specifically associates with p75(NTR). Thus, p75(NTR) and GT1b may form a receptor complex for MAG to transmit the inhibitory signals in neurons.
Experiences in designing a capacity planning tool for intelligent networks (2002)

The intelligent network (IN) concept brings with it a series of new telecommunications challenges from service design and management through to performance and network planning. This paper outlines some of the challenges facing network engineers in the widescale deployment of INs and reports on prototype IN capacity planning tool development being undertaken at the Software Engineering Research Centre. We commence this paper with a description of the challenges that the IN concept brings in capacity planning and how these differ from the historical approach to network planning. These challenges provide the motivation behind our prototyping activity, locally known as the Planet7 project. We give a brief introduction to this work and a short demonstration of the prototype itself. We conclude with a summary of the work and some planned future directions.
Quantifying occupant comfort: are combined indices of the indoor environment practicable? (2005)

What are the various ways in which evaluation of the several aspects of the indoor environment might combine to form an occupant's overall assessment of that environment? Data from an environmental survey of 26 offices in Europe (the Smart Controls and Thermal Comfort, or SCATs, project) are used. These show that dissatisfaction with one or more aspects of the indoor environment does not necessarily produce dissatisfaction with the environment overall. Conversely, satisfaction with one or more environmental aspect does not necessarily produce satisfaction with the total environment. Building occupants balance the good features against the bad to reach their overall assessment. Not all aspects are equally important in this subjective averaging process. Satisfaction with warmth and air quality is more important than satisfaction with the level of lighting or humidity. The relative importance of the various aspects differed from country to country, making it impossible to develop an internationally valid index to rate office environments by means of a single number. The best linear index constructed from the data failed to rank the indoor environments of the buildings in the correct order, as defined by the occupants' overall assessments. It is therefore wise to assess each of the several aspects separately rather than rely only on a combined index.
Neuronal muscarinic receptors attenuate vagally‐induced contraction of feline bronchial smooth muscle (1985)

In anaesthetized cats, stimulation of the vagus nerves produced bradycardia and a bronchoconstriction which was measured as an increase in lung resistance (RL) and a fall in dynamic lung compliance (Cdyn); these effects were abolished by atropine. Gallamine potentiated vagally-mediated changes in RL and Cdyn at doses that blocked muscarinic receptors in the heart and inhibited neuromuscular transmission. (+)-Tubocurarine and suxamethonium did not affect the response of the lung or the heart to vagal stimulation. Bronchoconstriction induced by intravenous acetylcholine was not potentiated by gallamine, indicating that postsynaptic muscarinic receptors in the lung and changes in muscle tone were not involved. Potentiation of vagally-induced bronchoconstriction appears to be due to blockade of inhibitory muscarinic receptors located in the pulmonary parasympathetic nerves innervating both central and peripheral airways. Pilocarpine was an agonist for these neuronal receptors as it inhibited vagally-induced bronchoconstriction at low doses (10 ng to 1 microgram kg-1). The results demonstrate that gallamine is an antagonist and pilocarpine an agonist at neuronal muscarinic receptors which attenuate parasympathetic nerve activity in feline lung.
Akkermansia Muciniphila Protects Against Atherosclerosis by Preventing Metabolic Endotoxemia-Induced Inflammation in Apoe −/− Mice (2016)

A muciniphila attenuates atherosclerotic lesions by ameliorating metabolic endotoxemia-induced inflammation through restoration of the gut barrier.
A New Methodology for the Synthesis of Fluorinated exo‐Glycals and Their Time‐Dependent Inhibition of UDP‐Galactopyranose Mutase (2006)

Fluorinated carbohydrates constitute a very important class of mechanistic probes for glycosyl-processing enzymes. In this study, we describe the first synthesis of fluorinated and phosphonylated exo-glycals and their corresponding nucleotide sugars in the galactofuranose series. The synthetic protocol that we have developed is a Selectfluor-mediated fluorination/elimination sequence on phosphonylated exo-glycals, and it offers a new entry into fluorinated carbohydrate chemistry. The challenging E/Z stereochemical assignment of the resulting tetrasubstituted alkenes, which bear an alkoxy, an alkyl, a fluoro, and a phosphonyl group, has been achieved through NMR experiments. The corresponding (E)- and (Z)-nucleotide fluorosugars have been prepared and tested as inhibitors of UDP-galactopyranose mutase (UGM). UGM is a flavoenzyme that catalyzes the isomerization of uridine diphosphate(UDP)-galactopyranose into UDP-galactofuranose, a key step of the biosynthesis of important mycobacterial cell-wall glycoconjugates. The two diastereomeric molecules were found to display time-dependent inactivation of UGM, as expected from preliminary results using non-fluorinated exo-glycal nucleotides. The inhibitory properties of the two fluorinated molecules led us to suggest that the inactivation mechanism proceeds through two-electron processes, despite the presence of the flavin cofactor within the UGM catalytic site.
Clinical Efficacy and Safety of Pimobendan in Treatment of Heart Failure &ndash; Experience in Japan (1997)

The results of Japanese studies on the clinical efficacy and safety of pimobendan in the treatment of heart failure are summarized in this paper. In patients with acute heart failure, a single oral 2.5 mg dose of pimobendan produced a significant increase in cardiac index (27.9%) and stroke volume index (24.4%), as well as a significant decrease in pulmonary capillary wedge pressure (-21.3%). A single oral 5.0 mg dose of pimobendan increased anaerobic threshold during exercise (7.3%). In a multicentre, placebo-controlled, double-blind trial, 8 weeks of treatment with pimobendan 2.5 mg b.i.d., which was suggested to be the optimal dose in a preceding dose-finding study, definitely improved symptoms and signs of heart failure in 52.6% of patients, and New York Heart Association function class in 64.1% of patients. This regimen was also associated with a significantly greater increase in physical activity than placebo. Furthermore, another double-blind, placebo-controlled study suggested that pimobendan 1.25 mg and 2.5 mg b.i.d. may have long-term beneficial effects on morbidity and quality of life in patients with chronic heart failure. Adverse reactions developed in 26 of 241 (10.8%) patients receiving multiple doses of pimobendan, but none of the reactions were serious. It is concluded that pimobendan may be useful in the treatment of patients with heart failure.
Optimization of the intensity gain of multiple-focus phased-array heating patterns (1991)

A new technique for enhancing the intensity gain at the focal points in multiple-focus patterns is introduced. The new technique is shown to be effective in reducing the interference typically associated with multiple-focus patterns. This reduction in interference patterns allows multiple-focus scanning to generate highly localized heating. Simulation results indicate that multiple-focus scanning not only provides an alternative to single-focus scanning, but also achieves better localization in the heating pattern. The maximization of intensity gain of multiple-focus heating patterns significantly reduces the pre-focal-depth high-temperature regions that can be caused by single-focus scanning. This is shown by computer simulation of a two-dimensional cylindrical-section array (CSA2D) as a heating applicator. Two series of simulations are presented in which different scan trajectories were used to therapeutically heat a small deep-seated target volume. In every case the heating pattern was generated using single-focus scanning and multiple-focus scanning (with and without intensity gain maximization). Multiple-focus scanning with gain maximization offers the best localization of heating to the target volume of the three methods.
Multiplexed Detection of Protein Cancer Markers with Biobarcoded Nanoparticle Probes (2006)

We have developed the chemistry for preparing a universal probe and the appropriate nano- and microparticle labels that can be used to do highly selective multiplexed detection of three protein cancer markers at low-femtomolar concentration in buffer and serum media. The approach relies on a new multiplexed version of the biobarcode amplification method and offers new opportunities for studying multiple protein markers in a single sample. This could lead to new forms of disease diagnosis and monitoring disease recurrence in a variety of settings.
Copper, Zinc, and the Metallobiology of Alzheimer Disease (2003)

From the Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Massachusetts General Hospital East, Charlestown, MA, U.S.A.; and Mental Health Research Institute of Victoria, and the Department of Pathology, University of Melbourne, Parkville, Victoria, Australia. Dr. Bush is a shareholder and has been a paid consultant and scientific board member of Prana Biotechnology Ltd. He is a board member and shareholder of Cogstate Pty Ltd. Reprints: Dr. Ashley I. Bush, Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Massachusetts General Hospital East, Bldg 114, 16th Street, Charlestown, MA 02129 (e-mail: [email protected]).
Targeted DNA Methylation Analysis by Next-generation Sequencing (2015)

The role of epigenetic processes in the control of gene expression has been known for a number of years. DNA methylation at cytosine residues is of particular interest for epigenetic studies as it has been demonstrated to be both a long lasting and a dynamic regulator of gene expression. Efforts to examine epigenetic changes in health and disease have been hindered by the lack of high-throughput, quantitatively accurate methods. With the advent and popularization of next-generation sequencing (NGS) technologies, these tools are now being applied to epigenomics in addition to existing genomic and transcriptomic methodologies. For epigenetic investigations of cytosine methylation where regions of interest, such as specific gene promoters or CpG islands, have been identified and there is a need to examine significant numbers of samples with high quantitative accuracy, we have developed a method called Bisulfite Amplicon Sequencing (BSAS). This method combines bisulfite conversion with targeted amplification of regions of interest, transposome-mediated library construction and benchtop NGS. BSAS offers a rapid and efficient method for analysis of up to 10 kb of targeted regions in up to 96 samples at a time that can be performed by most research groups with basic molecular biology skills. The results provide absolute quantitation of cytosine methylation with base specificity. BSAS can be applied to any genomic region from any DNA source. This method is useful for hypothesis testing studies of target regions of interest as well as confirmation of regions identified in genome-wide methylation analyses such as whole genome bisulfite sequencing, reduced representation bisulfite sequencing, and methylated DNA immunoprecipitation sequencing.
A retrospective cohort study of prognostic factors associated with outcome in pediatric severe sepsis: What is the role of steroids?* (2005)

From this administrative database analysis, there is no evidence that steroids are associated with improved outcome in critically ill infants and children with sepsis. Although steroids may be given preferentially to more severely ill children, their use was associated with increased mortality. Clinicians should maintain equipoise on this topic pending prospective randomized clinical trials.
Keyholes, correlations, and capacities of multielement transmit and receive antennas (2002)

Multielement system capacities are usually thought of as limited only by correlations between elements. It is shown here that degenerate channel phenomena called "keyholes" may arise under realistic assumptions which have zero correlation between the entries of the channel matrix H and yet only a single degree of freedom. Canonical physical examples of keyholes are presented. For outdoor environments, it is shown that roof edge diffraction is perceived as a "keyhole" by a vertical base array that may be avoided by employing instead a horizontal base array.
Estimation of the amount of internalized ricin that reaches the trans-Golgi network (1988)

We have used a protocol for internalization of ricin, a ligand binding to plasma membrane glycoproteins and glycolipids with terminal galactosyl residues, and infection with the vesicular stomatitis virus ts 045 mutant in BHK-21 cells to determine whether internalized plasma membrane molecules tagged by ricin reach distinct compartments of the biosynthetic-exocytic pathway. At 39.5 degrees C newly synthesized G protein of ts 045 was largely prevented from leaving the endoplasmic reticulum. At the same temperature ricin was endocytosed and reached, in addition to endosomes and lysosomes, elements of the Golgi complex. When the temperature was lowered to 19.5 degrees C, no more ricin was delivered to the Golgi complex, but now G protein accumulated in the Golgi stacks and the trans-Golgi network (TGN). Double-labeling immunogold cytochemistry on ultracryosections was used to detect G protein and ricin simultaneously. These data, combined with stereological and biochemical methods, showed that approximately 5% of the total amount of ricin within the cells, corresponding to 6-8 X 10(4) molecules per cell, colocalized with G protein in the Golgi complex after 60 min at 39.5 degrees C. Of this amount approximately 70-80% was present in the TGN. Since most of the ricin molecules remain bound to their binding sites at the low pH prevailing in compartments of the endocytic pathway, the results indicate that a fraction of the internalized plasma membrane molecules with terminal galactose are not recycled directly from endosomes or delivered to lysosomes, but are routed to the Golgi complex. Also, the results presented here, in combination with other recent studies on ricin internalization, suggest that translocation of the toxic ricin A-chain to the cytosol occurs in the TGN.
Degrees of confidence (2009)

This article explores how quality care has become a reality for older people in Lincoln and how continuing professional development (CPD) has made a real difference to patient care, and has supported the career development of two nurses working with older people at Lincoln County Hospital.
Solid phase synthesis of peptides containing the non-hydrolysable analog of (O)phosphotyrosine, p(CH2PO3H2)Phe. Application to the synthesis of 344-357 sequences of the beta 2 adrenergic receptor. (1992)

International audience
Stabilization of positive charge in SiO/sub 2//Si/sub 3/N/sub 4/ electrets (2006)

The stability of charge storage in electrets is a key parameter for their use in practical devices. For this purpose a new charging procedure for SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> /Si <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> N <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sub> thin film electret on a silicon carrier has been developed. It combines a heat-treatment at 450degC with a hexamethyldisilazane treatment before charging of the electret. The retention of a positive charge and the stability of its spatial trapping are investigated. The optimized technological parameters provide a lifetime of the charge on open air of about 200 years. No spatial charge retrapping has been observed after fabrication of the electret. A set of experiments has been carried out to characterize the properties of the charged electrets and to stabilize the charge retention using heat treatment at temperatures up to 450degC after charging, which is important for their packaging at elevated temperatures
Time-domain Fourier transform holography and possible applications in signal processing (1992)

The principles of holographic storage and the reconstruction of short light pulses based on spatial spectral decomposition of radiation are described. This method may be designated as time-domain Fourier transform holography or spectral holography. Also described are various transformations of optical time signals based on holographic spectral filtering and dynamic interaction of spectral decomposition waves in nonlinear media. A system of methods of time signal processing based on spectral holography is proposed. Among these methods are shaping optical pulses, space-time conversions of signals, matched filtering, and recognition oftime optical signals. In addition, the possibilities for realizing time-division multiplexing of data streams using dynamic spectral holography are shown.
Visible (660 nm) resonant cavity light-emitting diodes (1993)

The demonstration of the first visible resonant cavity light-emitting diodes (RCLEDs) is reported. The devices consist of an InAlGaP strained quantum well active region surrounded by AlAs/AlGaAs distributed Bragg reflectors. Linewidths from 0.9 nm (2.6 meV) to 45 nm (12.8 meV) were obtained by varying the cavity quality factor (Q).