gebhart/patrepeval huggingface dataset:
BMS-354825 Potently Inhibits the Kinase Activity of KIT Activation Loop Mutations Associated with Systemic Mastocytosis and Induces Apoptosis of Mastocytosis Cell Lines. (2004)

Abstract Activating mutations of the activation loop (AL) of KIT are reported in several human neoplasms including a subset of patients with AML or systemic mast cell disorders. The small molecule tyrosine kinase inhibitor, imatinib, is a potent inhibitor of wild type KIT and certain mutant KIT isoforms and has become the standard of care for treating patients with metastatic GI stromal tumors. However, KIT AL mutations such as D816V that are typically found in AML and systemic mast cell disease are insensitive to imatinib (IC50 &gt; 5–10 micromolar). In addition, acquired AL mutations are associated with imatinib resistance in GI stromal tumors. Experimental models of these diseases suggests that targeted inhibition of AL-mutant KIT in such cells would result in decreased proliferation and induction of apoptosis. BMS-354825 is a synthetic small-molecule ATP-competitive inhibitor of SRC and ABL tyrosine kinases with potency in the low nanomoloar range. In addition, BMS-354825 also inhibits many of the acquired BCR-ABL mutations associated with imatinib-resistant CML. Notably, BMS-354825 binds to the ATP-binding site in ABL regardless of the conformation of the AL and is therefore able to potently inhibit the kinase activity of AL-mutants of BCR-ABL. BMS-354825 is currently being tested in phase I studies for safety and efficacy in the treatment of imatinib-resistant CML as well as for various solid tumors. We investigated the inhibitory potential of BMS-354825 against KIT AL-mutants expressed by different mastocytosis/mast cell leukemia cell lines. We first examined the activity of BMS-354825 against the kinase activity of wild-type KIT kinase expressed by M07e cells. BMS-354825 potently inhibited the kinase activity of SLF-dependent M07E cells with an IC50 of 1–10 nM for autophosphorylation and cellular proliferation. In contrast, the IC50 for inhibition of GM-CSF-dependent proliferation was ~5 micromolar. BMS-354825 also potently inhibited the proliferation of the human mast cell leukemia cell line HMC-1 that expresses a juxtamembrane KIT V560G mutant kinase (IC50 1–10 nM). Notably, BMS-354825 inhibited autophosphorylation of KIT D816V with an IC50 of ~100 nM. Similar potency for inhibition of proliferation and induction of apoptosis (IC50 150–400 nM) was seen using three different cell lines expressing human D816V or the homologous murine D814Y KIT kinase. We conclude that BMS-354825 potently inhibits the kinase activity of wild-type KIT and imatinib-resistant KIT AL-mutant kinases associated with AML and systemic mast cell disorders. If BMS-354825 proves to be safe and tolerable in ongoing phase I trials, it should be further tested in clinical studies targeting patients with human malignancies associated with imatinib-resistant KIT AL-mutations.
Molecular regulation of tumor necrosis factor-alpha and lymphotoxin production in T cells. Inhibition by prostaglandin E2. (1992)

The effects of prostaglandin E2 (PGE2) and other eicosanoids were determined on tumor necrosis factor-alpha (TNF-alpha) and lymphotoxin (LT; TNF-beta) production by murine Th1, antigen-specific major histocompatibility complex class II-restricted T cell clones. T cells activated with immobilized anti-CD3 or with soluble concanavalin A (ConA) produced approximately 100-1,000 units/ml TNF-alpha/LT as determined by cytotoxicity against the WEHI-164 murine fibrosarcoma cell line. TNF-alpha/LT biological activity was induced rapidly with significant production evident approximately 4 h after stimulation with either anti-CD3 or ConA. PGE2 inhibited the anti-CD3- and ConA-induced production of TNF-alpha/LT bioactivity in a dose-dependent manner. Incubation with 1 x 10(-9) M PGE2 inhibited production of TNF-alpha/LT biological activity from anti-CD-activated F1.28, or 450A.1 T cell clones by approximately 50%. Incubation with 1 x 10(-7) M PGE2 resulted in 90% inhibition of biological activity. PGE2 also inhibited both TNF-alpha and LT mRNA accumulation by more than 90%. These results suggest that the reduced production of cytotoxic activity in the presence of PGE2 was caused by the inhibition of both TNF-alpha and LT. No inhibition of T cell TNF-alpha or LT production was observed when anti-CD3- or ConA-activated cells were incubated with PGD2, PGF2 alpha, 5-hydroxyeicosatetraenoic acid or leukotriene C4. Nuclear run-on experiments indicated that the PGE2-mediated decrease of TNF-alpha and LT mRNA accumulation was caused, in part, by an inhibitory effect on the transcription of these genes. This is the first report of PGE2-mediated inhibition of TNF-alpha in T cells and PGE2-mediated inhibition of LT production in any cell type.
The 100-genomes strains, an <i>S. cerevisiae</i> resource that illuminates its natural phenotypic and genotypic variation and emergence as an opportunistic pathogen (2015)

Saccharomyces cerevisiae, a well-established model for species as diverse as humans and pathogenic fungi, is more recently a model for population and quantitative genetics. S. cerevisiae is found in multiple environments-one of which is the human body-as an opportunistic pathogen. To aid in the understanding of the S. cerevisiae population and quantitative genetics, as well as its emergence as an opportunistic pathogen, we sequenced, de novo assembled, and extensively manually edited and annotated the genomes of 93 S. cerevisiae strains from multiple geographic and environmental origins, including many clinical origin strains. These 93 S. cerevisiae strains, the genomes of which are near-reference quality, together with seven previously sequenced strains, constitute a novel genetic resource, the "100-genomes" strains. Our sequencing coverage, high-quality assemblies, and annotation provide unprecedented opportunities for detailed interrogation of complex genomic loci, examples of which we demonstrate. We found most phenotypic variation to be quantitative and identified population, genotype, and phenotype associations. Importantly, we identified clinical origin associations. For example, we found that an introgressed PDR5 was present exclusively in clinical origin mosaic group strains; that the mosaic group was significantly enriched for clinical origin strains; and that clinical origin strains were much more copper resistant, suggesting that copper resistance contributes to fitness in the human host. The 100-genomes strains are a novel, multipurpose resource to advance the study of S. cerevisiae population genetics, quantitative genetics, and the emergence of an opportunistic pathogen.
Integrated Modeling of the European Trade and Transport Network (2013)

Trade and transport statistics are two sides of the same coin. Ideally we would like to have the data on the trade flow between two countries in combination with the information about the split of this flow between various (multi-modal) routes linking the pair of countries. In reality trade and transport statistics are quite difficult to match due to differences in methodology for data collection and the use of surveys. In particular transport statistics show us only the location of loading and unloading and does not say anything about origin and destination of the commodity flows. Trade data provides information on the origin and destination of the flows but may also include re-exports and transit flows. The unification and reconciliation of transport and trade statistics is of great value to both policy makers and the scientific community. The methodological approach presented in the present paper attempts to combine trade and transport data into a single consistent multi-commodity and multi-modal freight OD matrix for Europe. We apply logit shares for route choice in combination with a cross-entropy function in order to find the optimal trade-off between available trade and transport statistics. The result of this exercise is the identification of the transhipment flows and pure trade flows for the intra and extra-European trade. The methodology presented in this paper has been developed within the framework of the ETIS-Plus project for DG MOVE.
Using Hall Effect Sensors for 3D Space Text Entry on Smartwatches (2016)

The use of ultra-small smart devices, such as smartwatches, has become increasingly popular, particularly at the consumer level, in recent years. Smartwatch is a kind of interactive device that offers the ability to read text messages, email and notifications, once it is synchronized with a smartphone. But, performing efficient text input task on smartwatch is really difficult due to its small touch screen display. In this paper, we present hall effect sensors based text entry mechanism that effectively uses the 3D space around the smartwatch for entering alphanumeric characters. Our proposed text input technique (a) does not consume any screen space; (b) does not need any visual search to find a character and (c) does not suffer from fat finger problem.
Type 3 Secretion Translocators Spontaneously Assemble a Hexadecameric Transmembrane Complex (2016)

A type 3 secretion system is used by many bacterial pathogens to inject proteins into eukaryotic cells. Pathogens insert a translocon complex into the target eukaryotic membrane by secreting two proteins known as translocators. How these translocators form a translocon in the lipid bilayer and why both proteins are required remains elusive. Pseudomonas aeruginosa translocators PopB and PopD insert pores into membranes forming homo- or hetero-complexes of undetermined stoichiometry. Single-molecule fluorescence photobleaching experiments revealed that PopD formed mostly hexameric structures in membranes, whereas PopB displayed a bi-modal distribution with 6 and 12 subunits peaks. However, individually the proteins are not functional for effector translocation. We have found that when added together, the translocators formed distinct hetero-complexes containing 8 PopB and 8 PopD molecules. Thus, the interaction between PopB and PopD guide the assembly of a unique hetero-oligomer in membranes.
Hypothalamic deep brain stimulation in the treatment of chronic cluster headache (2010)

Cluster headache (CH) is a short-lasting unilateral headache associated with ipsilateral craniofacial autonomic manifestations. A positron emission tomography (PET) study has shown that the posterior hypothalamus is activated during CH attacks, suggesting that hypothalamic hyperactivity plays a key role in CH pathophysiology. On this basis, stimulation of the ipsilateral posterior hypothalamus was hypothesized to counteract such hyperactivity to prevent intractable CH. Ten years after its introduction, hypothalamic stimulation has been proved to successfully prevent attacks in more than 60% of 58 hypothalamic implanted drug-resistant chronic CH patients. The implantation procedure has generally been proved to be safe, although it carries a small risk of brain haemorrhage. Long-term stimulation is safe, and nonsymptomatic impairment of orthostatic adaptation is the only noteworthy change. Microrecording studies will make it possible to better identify the target site. Neuroimaging investigations have shown that hypothalamic stimulation activates ipsilateral trigeminal complex, but with no immediate perceived sensation within the trigeminal distribution. Other studies on the pain threshold in chronically stimulated patients showed increased threshold for cold pain in the distribution of the first trigeminal branch ipsilateral to stimulation. These studies suggest that activation of the hypothalamus and of the trigeminal system are both necessary, but not sufficient to generate CH attacks. In addition to the hypothalamus, other unknown brain areas are likely to play a role in the pathophysiology of this illness. Hypothalamus implantation is associated with a small risk of intracerebral haemorrhage and must be performed by an expert neurosurgical team, in selected patients.
Simultaneous heat and moisture transport in building components. One- and two-dimensional calculation using simple parameters (2022)

Performance and service life of building components are to a large extent determined by their hygrothermal behaviour. Since experimental examinations, apart from being expensive, can cover only small aspects of the real phenomena, the demand for computational tools has increased in recent years. In contrast to previous moisture calculations depending on sophisticated material parameters which were difficult and sometimes impossible to measure, new investigations have led to rather simple yet very accurate models requiring mostly standard material properties. Numerous applications have already proven the validity of the described calculations, which are based on physically plausible formulations.
Trends in the phase stability and thermochemical oxygen exchange of ceria doped with potentially tetravalent metals (2017)

Screening of tetravalent dopants correlates dopant radius and oxygen exchange capacity for ceria optimization in solar thermochemical CO<sub>2</sub>reduction.
Monolithically integrated InP-based front-end photoreceivers (1991)

The performance characteristics of a monolithically integrated front-end photoreceiver, consisting of a photodiode and a MODFET amplifier, were analyzed and measured. A vertical scheme of integration was initially used to realize a photoreceiver circuit on InP consisting of an InGaAs p-i-n diode, an InGaAs/InAlAs pseudomorphic MODFET, and passive circuit elements. The device structures were grown by single-step molecular beam epitaxy with an isolating layer in between. The microwave performance of 1- mu m-gate MODFETs in the circuit is characterized by f/sub T/=9 GHz, although identical discrete devices have f/sub T/=30-35 GHz. The degradation is due to additional parasitic capacitances present in this integration scheme. In spite of this disadvantage the bandwidth of the circuit is 2.1 GHz. Integration of the p-i-n diode with 1.0- and 0.25- mu m-gate MODFETs has also been done in a planar scheme using regrowth, and receiver bandwidths of 6.5 GHz were measured. This value is comparable to that of hybrid circuits with InP-based devices.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Gas Transportation: Present and Future (2008)

Abstract Natural gas is a versatile form of non-polluting fuel. With just over a dozen nations accounting for 84% of the world-wide production, access to natural gas has become a significant factor in international economics and politics. The major difficulty in the use of natural gas is transportation and storage because of its low density. Despite this, natural gas production has seen tremendous growth over the years. This has been due to large amount of natural gas reserves, the wide variety of uses of natural gas and carbon dioxide emissions from natural gas energy generation are far less. In the past, the natural gas recovered in the course of producing petroleum could not be profitably sold, and was simply flared. This wasteful practice is now illegal in many countries. The most common method for transporting natural gas was high pressure in underground pipelines. Additionally, countries now recognize that value for the gas may be achieved with LNG, CNG, or other transportation methods to end-users in the future. In many cases the gas is now re-injected back into the formation for later recovery. Transportation is now a very important and key role in the supply chain for natural gas and the big challenge is to transport gas to markets at the lowest cost without too much environmental risks. Now re-gasification at the market is important when selecting the mode of transportation of natural gas. This paper reviews, analyzes and provide insight to present and future gas transportation methods. These options of transporting gas from oil and gas field to markets include pipelines, liquefied natural gas, compressed natural gas, gas to solids (hydrate), gas to liquids, gas to wire and other gas to commodity methods. The paper provides an overview of the challenges facing present transportation modes, and discussion on possibilities for improvement via new technology or new gas transport options. Another focus of the paper is to compare and highlight some critical factors affecting the different means of transportation of natural gas. These include economics, markets, gas concentrations, environmental risks and re-gasification issues.
Electrochemical Investigation of Glucose Sensor Fabricated at Copper-Plated Screen-Printed Carbon Electrodes (2002)

Copper-plated screen-printed carbon electrode (CuSPE) provides a suitable catalytic surface for the amperometric detection of hydrogen peroxide. Glucose oxidase (GOD) is immobilized on the top of the CuSPE to form a glucose sensor. The interaction of copper oxide with GOD was found to be an important factor in the glucose detection. Preliminary investigation under hydrodynamic conditions showed a linear calibration plot up to 26.7 mM glucose with a slope and regression coefficient of 4.5 μA/mM and 0.9902, respectively. The Michaelis-Menten kinetics by nonlinear curve fitting yielded a Km value close to that in solution indicating the ideality and suitability of the present system. Classical mixed potential mechanism is for the first time applied to the enzyme-coated CuSPE to further understand the system.
Addressing student problems in learning computer graphics (1996)

Our goal is to improve the performance of computer graphics students by including problem-solving activities and situating their knowledge of computer graphics in authentic problems. The framework for achieving this goal is based on the apprenticeship model of training and integrates four modules:&bull; An interactive notes module which includes note pages, in-depth pages and a variety of activities such as interactive visualizations and algorithm animations, aimed at enforcing the acquisition of conceptual and factual knowledge.&bull; A case library which consists of stories of projects in computer graphics and maps them to common problems encountered in these projects.&bull; A problem-solving module which presents problems to the learner in a real-world context and provides him/her with support to solve the problems.&bull; A collaborative tool to support the undertaking of complex projects by teams of students.
Current Trends in the Chemistry of Permanent Hair Dyeing (2011)

ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTCurrent Trends in the Chemistry of Permanent Hair DyeingOlivier J. X. Morel‡ and Robert M. Christie*§View Author Information‡ Xennia Technology Ltd., Monroe House, Works Road, Letchworth SG6 1LN, U.K.§ School of Textiles & Design, Heriot-Watt University, Scottish Borders Campus, Netherdale, Galashiels TD1 3HF, Scotland, U.K.*E-mail: [email protected]Cite this: Chem. Rev. 2011, 111, 4, 2537–2561Publication Date (Web):January 25, 2011Publication History Received14 January 2010Published online25 January 2011Published inissue 13 April 2011https://pubs.acs.org/doi/10.1021/cr1000145https://doi.org/10.1021/cr1000145review-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views13199Altmetric-Citations146LEARN 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:Color,Dyes and pigments,Fibers,Oxidation,Reaction products Get e-Alerts
Saliency-guided deep framework for image quality assessment (2015)

Image quality assessment (IQA) has thrived for decades, and researchers continue to explore how the human brain perceives visual stimuli. Psychological evidence shows that humans prefer qualitative descriptions when evaluating image quality, yet most researches still concentrate on numerical descriptions. Furthermore, handcrafting features are widely used in this community, which constrains the models' flexibility. A novel model is proposed with two major advantages: the saliency-guided feature learning can learn features unsupervisedly, and the deep framework recasts IQA as a classification problem, analogous to human qualitative evaluation. Experiments validate the proposed model's effectiveness.
Phage‐displayed Bet mim 1, a mimotope of the major birch pollen allergen Bet v 1, induces B cell responses to the natural antigen using bystander T cell help (2002)

Taking these results together, our data indicate that Bet mim 1 mimics a Bet v 1-epitope on the B cell but not on the T cell level. We suggest that the phage itself is responsible for the recruitment of T cells providing bystander help in the formation of a mimotope-specific humoral response.
[Comparative study on intravenous drip infusion of dibekacin once daily and twice daily in treatment of complicated urinary tract infections]. (1984)

Dibekacin (DKB) was administered to patients with complicated urinary tract infections without any indwelling catheter to evaluate objectively and comparatively the efficacy, safety and usefulness of intravenous drip infusion once daily and twice daily in a well-controlled study. A 50 mg dose of DKB was administered twice a day to group A, and a 100 mg dose was given once a day to group B. In both groups the drug was given by 1-hr i.v. infusion for 5 consecutive days. Drug efficacy was evaluated in 72 (group A: 36, group B: 36) of the 83 patients treated, and the safety was evaluated on 81 patients (group A: 41, group B: 40). There were no significant differences in the background characteristics between the two groups. The overall clinical efficacy judged by the Committee for Evaluation of Clinical Efficacy was "excellent" in 14% and "moderate" in 50% of group A, and "excellent" in 17% and "moderate" in 64% of group B, the efficacy being higher for group B than group A, but the difference was not statistically significant. The overall drug efficacy rate for each type of infection excluding group 2, was slightly higher in group B, but this difference was not significant either. The overall clinical efficacy for each site of infection, was higher for group B but the differences were not significant. The overall clinical efficacy as judged by the attending physicians was "excellent" in 17% and "moderate" in 58% of group A, and "excellent" in 25% and "moderate" in 61% of group B. The intergroup difference was thus smaller than that judged by the Committee. The elimination rates against bacteriuria were 58% for both groups A and B, and the decrease rates including "cleared" were 42% against pyuria for both groups A and B. Bacteriological evaluation, showed that there was no significant difference in the eradication rates, between group A (65%) and group B (70%). But the eradication rate for gram-positive bacteria was 40% in group A and 81% in group B, there being a significant difference (P less than 0.05) between them. The evaluation of usefulness gave 44% and 53% "satisfactory" rates, respectively, for groups A and B. The results for the "average score" were also the same in both groups. There were no side effects in any of the 81 patients examined. Abnormal laboratory test values attributed to the drug were seen only in 3 and 2 patients in groups A and B, respectively, there being no difference between the groups.(ABSTRACT TRUNCATED AT 400 WORDS)