gebhart/patrepeval huggingface dataset:
Asthma and Atopic Dermatitis: A Review of Targeted Inhibition of Interleukin-4 and Interleukin-13 As Therapy for Atopic Disease. (2016)

Type 2 helper T cell (Th2)-mediated inflammation plays a critical role in the pathogenesis of allergic asthma and atopic dermatitis (AD). Recent research focusing on the suppression of the Th2 axis with targeted inhibitors in atopic disease is showing promising early results. In particular, the simultaneous blockage of interleukin (IL)-4 and IL-13 has successfully mitigated symptoms of allergic asthma and AD in preliminary clinical trials. Given the current therapeutic challenges of treating these chronic and severe diseases, this review brings to light new data demonstrating that agents targeting IL-4 and IL-13 are relatively safe and effective medications in blocking the inflammatory cascade responsible for allergic asthma and atopic dermatitis.
La famille des récepteurs couplés aux protéines G et ses orphelins (1995)

G protein-coupled receptors are encoded by one of the mammalian largest gene families. These receptors share a common transmembrane organization, respond to a large variety of structurally different ligands, and regulate intracellular enzymes and channels through heterotrimeric G proteins. The first genes encoding receptors of this family were isolated following the purification of the protein and sequencing of peptides generated by proteolytic cleavage. Subsequently, a number of G protein-coupled receptor genes were cloned through expression screening procedures based either on the binding of a specific ligand, or on the functional coupling of the recombinant receptor to a transduction cascade. Most members in this gene family were however obtained by homology cloning, using cross-hybridization or low-stringency polymerase chain reaction. The result is the availability of more than 140 receptor types and subtypes (olfactory receptors excluded). With a few exceptions, all pharmacologically well-defined receptors have now been cloned. Molecular cloning confirmed the existence of poorly characterized subtypes and uncovered other unsuspected subtypes. Genes encoding uncharacterized receptors have also been made available, either related to identified subfamilies, or defining new subfamilies by themselves. These so-called orphan receptors are waiting for the identification of the corresponding ligands and of their biological function. The availability of cloned human receptors is expected to speed up the search for more specific drugs. Determination of the three dimensional structure of selected recombinant receptors, and computer modelling of receptor-ligand interaction and ligand-mediated receptor activation will probably allow in the long run die rational design of specific agonists and antagonists. The increasing number of reported orphan receptors will certainly be instrumental in the discovery of new regulatory pathways linking cells, with the potential of opening new avenues in pharmacology.
Software Sensor-Based STATCOM Control Under Unbalanced Conditions (2009)

A new control strategy for static compensators (STATCOMs) operating under unbalanced voltages and currents is presented in this paper. The proposed strategy adopts a state observer (software sensor) to estimate ac voltages at the STATCOM connection point. This way, physical voltage sensors are not needed and the hardware gets simplified, among other advantages. Using the superposition principle, a controller is designed to independently control both positive and negative sequence currents, eliminating the risk of overcurrents during unbalanced conditions and improving the power quality at the STATCOM connection bus. Two operating modes are proposed for the computation of the reference currents, depending on whether the objective is to compensate unbalanced load currents or regulate bus voltages. The proposed observer allows positive and negative sequences to be estimated in a fraction of the fundamental cycle, avoiding the delay often introduced by filter-based methods. Overall, the STATCOM performance is improved under unbalanced conditions, according to simulation results presented in the paper.
PIK3CA/PTEN Mutations and Akt Activation As Markers of Sensitivity to Allosteric mTOR Inhibitors (2012)

PIK3CA/PTEN genomic aberrations and high p-Akt levels are associated with rapamycin sensitivity in vitro. Rapamycin-mediated Akt activation is greater in RS cells, with a similar observation in patients with clinical responses on exploratory biomarker analysis; thus feedback loop activation of Akt is not a marker of resistance but rather may function as an indicator of rapamycin activity.
Impact of biofilm on the in vitro activity of vancomycin alone and in combination with tigecycline and rifampicin against Staphylococcus aureus (2008)

Vancomycin exposures at 15 mg/L may not be adequate in eradicating biofilm-producing S. aureus. Alternative treatments or combination therapy should be explored to optimize outcomes in biofilm-associated infections.
Retinal microenvironment controls resident and infiltrating macrophage function during uveoretinitis. (2002)

Resident retinal myeloid-derived cells are primed and are resistant to further cytokine stimulation, and, similar to macrophages derived during EAU recovery, behave operationally as though TGF-beta primed. During peak inflammation, infiltrating macrophages adapt to concurrent hierarchical Th1 T-cell response (IFN-gamma/TNF-alpha), generating NO. The results provide evidence of in vivo programming of macrophages within the retina.
Integration of a novel high-voltage Giga-Hertz DMOS transistor into a standard CMOS process (2002)

A new type of DMOS transistor aimed at high voltage power amplifications in the Giga-Hertz region is integrated into a standard CMOS process. By optimising the design for high voltage and high frequency, remarkable good electrical behaviour is obtained. The frequency performance was measured to f/sub T/=4.6 GHz and f/sub MAX/=10 GHz for a device with a channel length of 0.3 /spl mu/m and a breakdown voltage V/sub BR//spl ges/60 V. For a similar device fabricated on the same chip and using the same process flow, but designed to handle voltages above 300 V, f/sub T/=1.8 GHz and f/sub MAX/=3.2 GHz were measured.
Hepatitis B Virus Infection: Epidemiology and Vaccination (2006)

Worldwide, two billion people have been infected with hepatitis B virus (HBV), 360 million have chronic infection, and 600,000 die each year from HBV-related liver disease or hepatocellular carcinoma. This comprehensive review of hepatitis B epidemiology and vaccines focuses on definitive and influential studies and highlights current trends, policies, and directions. HBV can be transmitted vertically, through sexual or household contact, or by unsafe injections, but chronic infections acquired during infancy or childhood account for a disproportionately large share of worldwide morbidity and mortality. Vaccination against HBV infection can be started at birth and provides long-term protection against infection in more than 90% of healthy people. In the 1990s, many industrialized countries and a few less-developed countries implemented universal hepatitis B immunization and experienced measurable reductions in HBV-related disease. For example, in Taiwan, the prevalence of chronic infection in children declined by more than 90%. Many resource-poor nations have recently initiated universal hepatitis B immunization programs with assistance from the Global Alliance for Vaccines and Immunization. Further progress towards the elimination of HBV transmission will require sustainable vaccination programs with improved vaccination coverage, practical methods of measuring the impact of vaccination programs, and targeted vaccination efforts for communities at high risk of infection.
Nasally administered cholera toxin A-subunit acts as a mucosal adjuvant (2003)

It is well established that cholera toxin (CT) produced by Vibrio cholerae acts as a potent mucosal adjuvant; however, the native form of this molecule causes severe diarrhea. Furthermore, both native CT and its B-subunit derivative bind to monosialogangliosides (GM1) in membrane raft micro-domains on neural tissues and are thus unsuitable for use in humans. In this study, we evaluated the adjuvanticity of the CT A-subunit (CT-A) administered with ovalbumin (OVA) by the nasal route. We found that nasal administration of OVA plus CT-A elicited both mucosal and systemic antibody (Ab) responses. Immunization of mice with OVA plus CT-A resulted in the induction of OVA-specific IgA Abs in saliva and nasal secretions. Furthermore, significant OVA-specific serum immunoglobulin (Ig) G and IgA Ab responses were induced. Antibody-forming cell (AFC) analysis confirmed the Ab titer findings by revealing significant numbers of OVA-specific IgA AFCs in submandibular glands. In addition, splenic lymphocytes restimulated with OVA in vitro exhibited significant proliferative responses. Thus, CT-A might be a candidate for an effective adjuvant for inducing antigen (Ag)-specific Ab responses in human systemic and mucosal compartments, such as the oral cavity.
Thalamic Stimulation for Control of Movement Disorders (1983)

Chronic recurrent thalamic stimulation has been effective in alleviating a variety of movement disorders. In contrast to thalamic lesions, it is preferred for the treatment of intractable motor disorders in low-risk elderly patients and patients with diffuse brain lesions secondary to trauma. Abnormal diencephalic electrical discharges have been observed and thought to be associated, in some way, with either generating or sustaining the movement abnormalities. The beneficial effects are ascribed to an electrophysiologic functional ablation of the discharging systems. This interpretation is based on the observation that the diencephalic discharges are attenuated by the applied stimulation and that the beneficial effects are reversible even after several months of applied therapeutic stimulation.
Hypohydration impairs endurance exercise performance in temperate but not cold air (2005)

This study compared the effects of hypohydration (HYP) on endurance exercise performance in temperate and cold air environments. On four occasions, six men and two women (age = 24 +/- 6 yr, height = 170 +/- 6 cm, weight = 72.9 +/- 11.1 kg, peak O2 consumption = 48 +/- 9 ml.kg(-1).min(-1)) were exposed to 3 h of passive heat stress (45 degrees C) in the early morning with [euhydration (EUH)] or without (HYP; 3% body mass) fluid replacement. Later in the day, subjects sat in a cold (2 degrees C) or temperate (20 degrees C) environment with minimal clothing for 1 h before performing 30 min of cycle ergometry at 50% peak O2 consumption followed immediately by a 30-min performance time trial. Rectal and mean skin temperatures, heart rate, and ratings of perceived exertion measurements were made at regular intervals. Performance was assessed by the total amount of work (kJ) completed in the 30-min time trial. Skin temperature was significantly lower in the cold compared with the temperate trial, but there was no independent effect of hydration. Rectal temperature in both HYP trials was higher than EUH after 60 min of exercise, but the difference was only significant within the temperate trials (P < 0.05). Heart rate was significantly higher at 30 min within the temperate trial (HYP > EUH) and at 60 min within the cold trial (HYP > EUH) (P < 0.05). Ratings of perceived exertion increased over time with no differences among trials. Total work performed during the 30-min time trial was not influenced by environment but was less (P < 0.05) for HYP than EUH in the temperate trials. The corresponding change in performance (EUH-HYP) was greater for temperate (-8%) than for cold (-3%) (P < 0.05). These data demonstrate that 1) HYP impairs endurance exercise performance in temperate but not cold air but 2) cold stress per se does not.
Mechanistic and Structural Analysis of Aminoglycoside <i>N</i>-Acetyltransferase AAC(6′)-Ib and Its Bifunctional, Fluoroquinolone-Active AAC(6′)-Ib-cr Variant (2008)

Enzymatic modification of aminoglycoside antibiotics mediated by regioselective aminoglycoside N-acetyltransferases is the predominant cause of bacterial resistance to aminoglycosides. A recently discovered bifunctional aminoglycoside acetyltransferase (AAC(6')-Ib variant, AAC(6')-Ib-cr) has been shown to catalyze the acetylation of fluoroquinolones as well as aminoglycosides. We have expressed and purified AAC(6')-Ib-wt and its bifunctional variant AAC(6')-Ib-cr in Escherichia coli and characterized their kinetic and chemical mechanism. Initial velocity and dead-end inhibition studies support an ordered sequential mechanism for the enzyme(s). The three-dimensional structure of AAC(6')-Ib-wt was determined in various complexes with donor and acceptor ligands to resolutions greater than 2.2 A. Observation of the direct, and optimally positioned, interaction between the 6'-NH 2 and Asp115 suggests that Asp115 acts as a general base to accept a proton in the reaction. The structure of AAC(6')-Ib-wt permits the construction of a molecular model of the interactions of fluoroquinolones with the AAC(6')-Ib-cr variant. The model suggests that a major contribution to the fluoroquinolone acetylation activity comes from the Asp179Tyr mutation, where Tyr179 makes pi-stacking interactions with the quinolone ring facilitating quinolone binding. The model also suggests that fluoroquinolones and aminoglycosides have different binding modes. On the basis of kinetic properties, the pH dependence of the kinetic parameters, and structural information, we propose an acid/base-assisted reaction catalyzed by AAC(6')-Ib-wt and the AAC(6')-Ib-cr variant involving a ternary complex.
Electrophilic opioid ligands. Oxygen-tethered .alpha.-methylene-.gamma.-lactone, acrylate, isothiocyanate, and epoxide derivatives of 6.beta.-naltrexol (1992)

O6-Ether derivatives of 6 beta-naltrexol in which the ether substituent includes various electrophilic groups have been synthesized in an effort to examine structure-activity requirements at the 6 beta-substituent for receptor affinity and irreversibility of binding in opioid receptor preparations. A series of tethered 6 beta-ethers having terminal epoxides, alpha-methylene-gamma-lactones, and an isothiocyanate group were prepared. The stereochemistry of the alpha-methylene-gamma-lactones was established by convergent synthesis of their reduction products from epoxides of known absolute stereochemistry. In general, the tested compounds showed comparable affinity and selectivity for the receptor subtypes. All were found with high affinity for mu-sites. The terminal epoxide ether diastereomers 8 and 9 were not bound irreversibly in the assay for total opioid receptors. The alpha-methylene-gamma-lactone diastereomers 10 and 11, and their O14-acetyl precursors 20 and 21, respectively, varied in their irreversible effects, but where noted these effects were mu-site selective. Methacrylate ether 7 and isothiocyanate ether 12 were bound irreversibly at both mu- and delta-sites.
A gyroscopic data based pedometer algorithm (2013)

Accuracy of step counting is one of the main problems that exist in current Pedometers, especially when walking slowly on flat lands and performing different activities, such as climbing up and down stairs and walking on inclined planes. Although accelerometer based pedometers provide a reasonable accuracy when walking at higher speeds, the accuracy of them are not sufficient at slow walking speeds and performing different activities. This paper proposes a novel algorithm to detect steps using single-point gyroscopic sensors embedded in mobile devices. Preliminary analysis of data collected in different environments with the involvement of male and female volunteers indicated that gyroscope alone provides sufficient information necessary for accurate step detection. Algorithm was developed based on the gyroscopic data in conjunction with zero crossing and threshold detection techniques. The results proved that gyroscope based step detection algorithm provide a high accuracy when performing different activities and at slow paced walking.
Diabetes, obesity and gut microbiota (2013)

The gut microbiota composition has been associated with several hallmarks of metabolic syndrome (e.g., obesity, type 2 diabetes, cardiovascular diseases, and non-alcoholic steatohepatitis). Growing evidence suggests that gut microbes contribute to the onset of the low-grade inflammation characterising these metabolic disorders via mechanisms associated with gut barrier dysfunctions. Recently, enteroendocrine cells and the endocannabinoid system have been shown to control gut permeability and metabolic endotoxaemia. Moreover, targeted nutritional interventions using non-digestible carbohydrates with prebiotic properties have shown promising results in pre-clinical studies in this context, although human intervention studies warrant further investigations. Thus, in this review, we discuss putative mechanisms linking gut microbiota and type 2 diabetes. These data underline the advantage of investigating and changing the gut microbiota as a therapeutic target in the context of obesity and type 2 diabetes.
A Survey of Cloud Database Systems (2013)

This survey of 15 popular cloud databases provides an overview of each system and its storage platform, license type, and programming language used for writing the source code of the NoSQLs. It also considers important features such as data handling techniques and billing practices.
IDO and Clinical Conditions Associated with Depressive Symptoms (2007)

In the pathogenesis of depressive symptoms the neurotransmitter serotonin plays an important role--although the underlining mechanisms are still not clear. The synthesis of serotonin is dependent on the availability of tryptophan--an amino acid that is linked to the immune system by its catabolism via the enzyme indoleamine-2,3-dioxygenase (IDO). Based on this connection research approaches addressing different clinical conditions with depressive symptoms and immunological involvement have been considered. This review provides an overview on the latest research in the field.
Etched carbon-fiber electrodes as amperometric detectors of catecholamine secretion from isolated biological cells (1991)

Voltammetric electrodes with micrometer dimensions have been fabricated from carbon fibers etched to a conical shape and insulated with poly(oxyphenylene) following literature procedures. The resultant electrode has a tip radius in the micron range. The response of this electrode is compared to a carbon-fiber electrode prepared by sealing a carbon-fiber electrode in a glass pipet (electrode radius greater than 3.5 microns). While the etched electrodes did not follow electrochemical theory as well as the glass-encased electrode, the etched electrode was found to be suitable for the amperometric measurement of the secretion of catecholamines from isolated bovine adrenal cells. Comparable results are only obtained when the two different electrodes are placed 1 micron from the cell surface. When the etched electrode is placed further away, less secretion is observed, because of diffusion and accompanying dilution.
The Structure of Palau'amide, a Potent Cytotoxin from a Species of the Marine Cyanobacterium <i>Lyngbya</i> (2003)

Bioassay-guided fractionation of the extract of a species of Lyngbya from Palau has yielded Palau'amide (1), which had an IC(50) value of 13 nM against KB cells. The structure of 1 was elucidated by NMR analysis in a variety of solvents. In particular, a gradient-enhanced band-selective HMBC experiment allowed unambiguous assignment of HMBC correlations to carbon signals that were separated by 0.1 ppm. The relative stereochemistry and the absolute configurations of all but one (C-37) of the nine chiral centers were determined by NMR analysis of the alpha-methoxyphenylacetic acid (MPA) derivatives and chiral HPLC of the degradation products of 1. The assignment of S rather than R stereochemistry at C-37 is discussed in detail.
Optimal Use of Cryogenic Probe Technology in NMR Studies of Proteins (2000)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTOptimal Use of Cryogenic Probe Technology in NMR Studies of ProteinsPeter F. Flynn, Debra L. Mattiello, Howard D. W. Hill, and A. Joshua WandView Author Information The Johnson Research Foundation and Department of Biochemistry & Biophysics University of Pennsylvania School of Medicine Philadelphia, Pennsylvania 19104-6059 Varian Inc., 3120 Hansen Way Palo Alto, California 94304-1030 Cite this: J. Am. Chem. Soc. 2000, 122, 19, 4823–4824Publication Date (Web):April 27, 2000Publication History Received19 October 1999Revised31 March 2000Published online27 April 2000Published inissue 1 May 2000https://pubs.acs.org/doi/10.1021/ja993743xhttps://doi.org/10.1021/ja993743xrapid-communicationACS PublicationsCopyright © 2000 American Chemical SocietyRequest reuse permissionsArticle Views667Altmetric-Citations74LEARN 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 SUBJECTS:Encapsulation,Micelles,Nuclear magnetic resonance spectroscopy,Probes,Quality management Get e-Alerts
Green Engineering: Introduction (2000)

The field of engineering, especially chemical engineering, has led the development of environmental technology over the past two generations. The design and implementation of a wide range of treatment and control technologies ranging from smoke-stack scrubbers to water effluent treatment facilities has resulted in dramatic improvement in the quality of the air, water and land, especially in the past thirty years. As the approaches to environmental protection evolved to include pollution prevention, chemical engineering once again produced a wide range of technologies and process changes that allowed, not only the chemical industry, but all industrial sectors that use chemical processes to reduce pollution at the source. This again, resulted in large measurable reductions in releases of toxic substances to the environment. Today, as environmental protection is continuing to evolve, chemical engineering is once again responding with the innovation and ingenuity that has become a tradition in this field for addressing