931 resultados para Preliminary Injunctions
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The article is devoted to analysis of various countercultures aspects. The Author hypothesizes that the forms of contemporary politics are the result of two fundamentally interrelated strategic vectors. First is built upon a politics of ressentiment, setting “ordinary” folks against the socio‐cultural elite which constututed to the “new right” movement. Second vector is originated of counterculture of the 1960s. The author states that counterculture exists without a singular identity. It is a space of hybridity and heterogenity. On the other hand counterculture is related to the concept of contemporary ambivalence as well it transforms of affective experience of everyday life. Another feature of counterculture is connected with the conviction that counterculture stands against of dominant culture. Also the author puts counterculture movements against various aspects of new american modernity including reconstruction of the practice of the hegemony, as well as through popular culture and reconstruction of the „left” and „right” idelogy and practice.
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We consider the problems of typability[1] and type checking[2] in the Girard/Reynolds second-order polymorphic typed λ-calculus, for which we use the short name "System F" and which we use in the "Curry style" where types are assigned to pure λ -terms. These problems have been considered and proven to be decidable or undecidable for various restrictions and extensions of System F and other related systems, and lower-bound complexity results for System F have been achieved, but they have remained "embarrassing open problems"[3] for System F itself. We first prove that type checking in System F is undecidable by a reduction from semi-unification. We then prove typability in System F is undecidable by a reduction from type checking. Since the reverse reduction is already known, this implies the two problems are equivalent. The second reduction uses a novel method of constructing λ-terms such that in all type derivations, specific bound variables must always be assigned a specific type. Using this technique, we can require that specific subterms must be typable using a specific, fixed type assignment in order for the entire term to be typable at all. Any desired type assignment may be simulated. We develop this method, which we call "constants for free", for both the λK and λI calculi.
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The purpose of this preliminary study is to identify signs of fatigue in specific muscle groups that in turn directly influence accuracy in professional darts. Electromyography (EMG) sensors are employed to monitor the electrical activity produced by skeletal muscles of the trunk and upper limb during throw. It is noted that the Flexor Pollicis Brevis muscle which controls the critical release action during throw shows signs of fatigue. This is accompanied by an inherent increase in mean integral EMG amplitude for a number of other throw related muscles indicating an attempt to maintain constant applied throwing force. A strong correlation is shown to exist between average score and decrease in mean integral ECG amplitude for the Flexor Pollicis Brevis.
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info:eu-repo/semantics/published
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info:eu-repo/semantics/nonPublished
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G protein-coupled receptor kinase 2 (GRK2) phosphorylates activated G protein-coupled receptors (GPCRs), which ultimately leads to their desensitization and/or downregulation. The enzyme is recruited to the plasma membrane via the interaction of its carboxyl-terminal pleckstrin-homology (PH) domain with the beta and gamma subunits of heterotrimeric G proteins (Gbetagamma). An improved purification scheme for GRK2 has been developed, conditions under which GRK2 forms a complex with Gbeta(1)gamma(2) have been determined and the complex has been crystallized in CHAPS detergent micelles. Crystals of the GRK2-Gbetagamma complex belong to space group C2 and have unit-cell parameters a = 187.0, b = 72.1, c = 122.0 A, beta = 115.2 degrees. A complete data set has been collected to 3.2 A resolution with Cu Kalpha radiation.
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Chemotherapy and radiotherapy induce premature ovarian failure in many patients treated for oncological or benign diseases. The present paper reviews the risk of developing premature ovarian failure according to the type of treatment and the different options to preserve fertility, focusing on the cryopreservation of ovarian tissue. This technique constitutes a promising approach to preserve the fertility of young patients and offers the advantage of storing a large number of follicles that could be subsequently transplanted or cultured in vitro to obtain mature oocytes. Based on 34 requests, from which 19 were performed, the feasibility of the ovarian cryopreservation procedure is evaluated. The medical and ethical approaches of this protocol are also discussed. Cryopreservation of ovarian tissue constitutes new hope for many patients, but must still be kept for selected cases, with a significant risk of premature ovarian failure after treatments such as bone marrow transplantation.
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BACKGROUND: Anticoagulation can reduce quality of life, and different models of anticoagulation management might have different impacts on satisfaction with this component of medical care. Yet, to our knowledge, there are no scales measuring quality of life and satisfaction with anticoagulation that can be generalized across different models of anticoagulation management. We describe the development and preliminary validation of such an instrument - the Duke Anticoagulation Satisfaction Scale (DASS). METHODS: The DASS is a 25-item scale addressing the (a) negative impacts of anticoagulation (limitations, hassles and burdens); and (b) positive impacts of anticoagulation (confidence, reassurance, satisfaction). Each item has 7 possible responses. The DASS was administered to 262 patients currently receiving oral anticoagulation. Scales measuring generic quality of life, satisfaction with medical care, and tendency to provide socially desirable responses were also administered. Statistical analysis included assessment of item variability, internal consistency (Cronbach's alpha), scale structure (factor analysis), and correlations between the DASS and demographic variables, clinical characteristics, and scores on the above scales. A follow-up study of 105 additional patients assessed test-retest reliability. RESULTS: 220 subjects answered all items. Ceiling and floor effects were modest, and 25 of the 27 proposed items grouped into 2 factors (positive impacts, negative impacts, this latter factor being potentially subdivided into limitations versus hassles and burdens). Each factor had a high degree of internal consistency (Cronbach's alpha 0.78-0.91). The limitations and hassles factors consistently correlated with the SF-36 scales measuring generic quality of life, while the positive psychological impact scale correlated with age and time on anticoagulation. The intra-class correlation coefficient for test-retest reliability was 0.80. CONCLUSIONS: The DASS has demonstrated reasonable psychometric properties to date. Further validation is ongoing. To the degree that dissatisfaction with anticoagulation leads to decreased adherence, poorer INR control, and poor clinical outcomes, the DASS has the potential to help identify reasons for dissatisfaction (and positive satisfaction), and thus help to develop interventions to break this cycle. As an instrument designed to be applicable across multiple models of anticoagulation management, the DASS could be crucial in the scientific comparison between those models of care.
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INTRODUCTION: Malignant gliomas frequently harbor mutations in the isocitrate dehydrogenase 1 (IDH1) gene. Studies suggest that IDH mutation contributes to tumor pathogenesis through mechanisms that are mediated by the neomorphic metabolite of the mutant IDH1 enzyme, 2-hydroxyglutarate (2-HG). The aim of this work was to synthesize and evaluate radiolabeled compounds that bind to the mutant IDH1 enzyme with the goal of enabling noninvasive imaging of mutant IDH1 expression in gliomas by positron emission tomography (PET). METHODS: A small library of nonradioactive analogs were designed and synthesized based on the chemical structure of reported butyl-phenyl sulfonamide inhibitors of mutant IDH1. Enzyme inhibition assays were conducted using purified mutant IDH1 enzyme, IDH1-R132H, to determine the IC50 and the maximal inhibitory efficiency of the synthesized compounds. Selected compounds, 1 and 4, were labeled with radioiodine ((125)I) and/or (18)F using bromo- and phenol precursors, respectively. In vivo behavior of the labeled inhibitors was studied by conducting tissue distribution studies with [(125)I]1 in normal mice. Cell uptake studies were conducted using an isogenic astrocytoma cell line that carried a native IDH1-R132H mutation to evaluate the potential uptake of the labeled inhibitors in IDH1-mutated tumor cells. RESULTS: Enzyme inhibition assays showed good inhibitory potency for compounds that have iodine or a fluoroethoxy substituent at the ortho position of the phenyl ring in compounds 1 and 4 with IC50 values of 1.7 μM and 2.3 μM, respectively. Compounds 1 and 4 inhibited mutant IDH1 activity and decreased the production of 2-HG in an IDH1-mutated astrocytoma cell line. Radiolabeling of 1 and 4 was achieved with an average radiochemical yield of 56.6 ± 20.1% for [(125)I]1 (n = 4) and 67.5 ± 6.6% for [(18)F]4 (n = 3). [(125)I]1 exhibited favorable biodistribution characteristics in normal mice, with rapid clearance from the blood and elimination via the hepatobiliary system by 4 h after injection. The uptake of [(125)I]1 in tumor cells positive for IDH1-R132H was significantly higher compared to isogenic WT-IDH1 controls, with a maximal uptake ratio of 1.67 at 3 h post injection. Co-incubation of the labeled inhibitors with the corresponding nonradioactive analogs, and decreasing the normal concentrations of FBS (10%) in the incubation media substantially increased the uptake of the labeled inhibitors in both the IDH1-mutant and WT-IDH1 tumor cell lines, suggesting significant non-specific binding of the synthesized labeled butyl-phenyl sulfonamide inhibitors. CONCLUSIONS: These data demonstrate the feasibility of developing radiolabeled probes for the mutant IDH1 enzyme based on enzyme inhibitors. Further optimization of the labeled inhibitors by modifying the chemical structure to decrease the lipophilicity and to increase potency may yield compounds with improved characteristics as probes for imaging mutant IDH1 expression in tumors.
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SCOPUS: ar.j
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p.25-36
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p.25-36
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This paper concerns a preliminary numerical simulation study of the evacuation of the World Trade Centre North Tower on 11 September 2001 using the buildingEXODUS evacuation simulation software. The analysis makes use of response time data derived from a study of survivor accounts appearing in the public domain. While exact geometric details of the building were not available for this study, the building geometry was approximated from descriptions available in the public domain. The study attempts to reproduce the events of 11 September 2001 and pursue several ‘what if’ questions concerning the evacuation. In particular, the study explores the likely outcome had a single staircase survived in tact from top to bottom.
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Traditionally, when designing a ship the driving issues are seen to be powering, stability, strength and seakeeping. Issues related to ship operations and evolutions are investigated later in the design process, within the constraint of a fixed layout. This can result in operational inefficiencies and limitations, excessive crew numbers and potentially hazardous situations. University College London and the University of Greenwich are in the final year of a three year EPSRC funded research project to integrate the simulation of personnel movement into early stage ship design. This allows the assessment of onboard operations while the design is still amenable to change. The project brings together the University of Greenwich developed maritimeEXODUS personnel movement simulation software and the SURFCON implementation of the Design Building Block approach to early stage ship design, which originated with the UCL Ship Design Research team. Central to the success of this project is the definition of a suitable series of Naval Combatant Human Performance Metrics which can be used to assess the performance of the design in different operational scenarios. The paper outlines the progress made on deriving the human performance metric from human factors criteria measured in simulations and their incorporation into a Behavioural Matrix for analysis. It describes the production of a series of SURFCON ship designs based on the RN Type 22 Batch 3 frigate, and their analysis using the PARAMARINE and maritimeEXODUS software. Conclusions to date will be presented on the integration of personnel movement simulation into the preliminary ship design process.