45 resultados para Walton, Izaak, 1593-1683.
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Neutron diffraction has been used to investigate the structure of liquid mixtures of 1,3-dimethylimidazolium hexafluorophosphate with benzene. Two concentrations of benzene were investigated, namely, 33 mol % and 67 mol %, and show similar structures in each case. The presence of benzene significantly alters the ionic liquid structure, in particular, in the cation-cation interactions, in agreement with the single-crystal structure described recently (Holbrey, J. D.; Reichert, W. M.; Nieuwenhuyzen, M.; Sheppard, O.; Hardacre, C.; Rogers, R. D. Chem. Commun. 2003, 476). In each case, the data was analyzed using an empirical potential structure refinement process.
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Background BRCA1-mutant breast tumors are typically estrogen receptor alpha (ER alpha) negative, whereas most sporadic tumors express wild-type BRCA1 and are ER alpha positive. We examined a possible mechanism for the observed ER alpha-negative phenotype of BRCA1-mutant tumors.
Methods We used a breast cancer disease-specific microarray to identify transcripts that were differentially expressed between paraffin-embedded samples of 17 BRCA1-mutant and 14 sporadic breast tumors. We measured the mRNA levels of estrogen receptor 1 (ESR1) ( the gene encoding ER alpha), which was differentially expressed in the tumor samples, by quantitative polymerase chain reaction. Regulation of ESR1 mRNA and ER alpha protein expression was assessed in human breast cancer HCC1937 cells that were stably reconstituted with wild-type BRCA1 expression construct and in human breast cancer T47D and MCF-7 cells transiently transfected with BRCA1-specific short-interfering RNA ( siRNA). Chromatin immunoprecipitation assays were performed to determine if BRCA1 binds the ESR1 promoter and to identify other interacting proteins. Sensitivity to the antiestrogen drug fulvestrant was examined in T47D and MCF-7 cells transfected with BRCA1-specific siRNA. All statistical tests were two-sided.
Results Mean ESR1 gene expression was 5.4-fold lower in BRCA1-mutant tumors than in sporadic tumors ( 95% confidence interval [CI]=2.6-fold to 40.1-fold, P =.0019). The transcription factor Oct-1 recruited BRCA1 to the ESR1 promoter, and both BRCA1 and Oct-1 were required for ER alpha expression. BRCA1-depleted breast cancer cells expressing exogenous ER alpha were more sensitive to fulvestrant than BRCA1-depleted cells transfected with empty vector ( T47D cells, the mean concentration of fulvestrant that inhibited the growth of 40% of the cells [IC40] for empty vector versus ER alpha: > 10(-5) versus 8.0 x 10(-9) M [ 95% CI=3.1x10(-10) to 3.2 x 10(-6) M]; MCF-7 cells, mean IC40 for empty vector versus ER alpha : > 10(-5) versus 4.9 x 10(-8) M [ 95% CI=2.0 x 10(-9) to 3.9 x 10(-6) M]).
Conclusions BRCA1 alters the response of breast cancer cells to antiestrogen therapy by directly modulating ER alpha expression.
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Changes of the electron dynamics during the mode transition (E- to H-mode) in a hydrogen radio-frequency (rf) inductively coupled plasma are investigated using space and phase resolved optical emission spectroscopy. The E- mode is characterized through relatively weak optical emission which is strongly modulated on a nanosecond time scale during the rf-cycle, with one pronounced maximum per cycle. The modulation in H-mode, with twice the rf-frequency, is significantly weaker while the emission intensities are about two orders of magnitude higher. In particular the transition between these two modes is studied under variations of rf-power input and gas pressure. Characteristic spatio-temporal structures are observed and can be understood in the frame of a simple model combining both coupling mechanisms in the transition regime.
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Major sporting events such as the Olympics are usually assessed in terms of economic impacts. Recently, policy makers have begun to place greater emphasis on possible intangible effects (such as civic pride, legacy of sporting facilities) associated with such events. To date, little work has been carried out on quantifying these effects in a meaningful way. This study uses contingent valuation methodology to assess the value of the proposed 2012 London Olympic Games. The survey is carried out on the provincial city of Bath, approximately 2 hours west of London. Conducting the survey outside of London is justified on the basis that the organizers of London 2012 have emphasized the value of the event to the United Kingdom as a whole. The results suggest that positive intangible effects are associated with the event and residents outside of London are willing to pay toward funding.
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Nova V458 Vul erupted on 2007 August 8 and reached a visual magnitude of 8.1 a few days later. Ha images obtained 6 weeks before the outburst as part of the IPHAS Galactic plane survey reveal an 18th magnitude progenitor surrounded by an extended nebula. Subsequent images and spectroscopy of the nebula reveal an inner nebular knot increasing rapidly in brightness due to flash ionization by the nova event. We derive a distance of 13 kpc based on light travel time considerations, which is supported by two other distance estimation methods. The nebula has an ionized mass of 0.2 Msolar and a low expansion velocity: this rules it out as ejecta from a previous nova eruption, and is consistent with it being a ~14,000 year old planetary nebula, probably the product of a prior common envelope (CE) phase of evolution of the binary system. The large derived distance means that the mass of the erupting WD component of the binary is high. We identify two possible evolutionary scenarios, in at least one of which the system is massive enough to produce a Type Ia supernova upon merging.
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Colourless single crystals of [Hg(CF3)(2)(Pur)](4) and [Hg(CF3)(2)(Dat)](2) were obtained from aqueous and etheric solutions of the respective components Purine, (imidazo[4,5-d]pyrimidine, Pur), 3,5-dimethyl-4 '-amino-triazole (Dat) and bis(trifluoromethyl)mercury(II), Hg(CF3)(2). [Hg(CF3)(2)(Pur)](4) crystallizes with the tetragonal system (P-4, Z = 8, a = 1486.8(2), c = 1026.2(l) pm, R-all = 0.0657) with tetrameric molecules consisting of four purine molecules bridged by slightly bent Hg(CF3)2 molecules forming a cage with the CF3 ligands surrounding this cage. The two modifications of [Hg(Dat)(CF3)2]2 (1: 170 K, triclinic, P-1, Z = 2, a 814.9(2), b = 845.4(2), c = 968.4(3) pm, alpha = 106.55(2)degrees, beta= 103.41(2)degrees, gamma = 110.79(2)degrees, R-all = 0.1189; II: monoclinic, P2(1)/c, Z = 8, a = 879.8(2), b = 1731.0(3), c = 1593.9(3) pm, beta = 106.89(2)degrees, R-all = 0.1199) both contain dimeric molecules that are stacked parallel to one crystal axis to strands which are arranged in a parallel fashion in I and rotated against each other in 11 by 110 degrees. In both, the tetrameric [Hg(CF3)(2)(Pur)](4) and the dimeric [Hg(CF3)(2)(Dat)](2) the Hg(CF3)(2) molecules are slightly bent (around 167 and 170 degrees) and rather weakly attached to the N-donor ligands Pur and Dat with Hg-N distances around 272 pm, although in both cases the Hg atoms bridge between two ligand molecules.
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Richards, M., Hedges, R., Walton, I; Stoddart, S., Malone, C.,
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The coupled heat, air and moisture transfer between building envelopes and indoor air is complicated, and has a significant influence on the indoor environment and the energy performance of buildings. In the paper, a model for predicting coupled multi-zone hygrothermal-airflow transfer is presented. Both heat and moisture transfer in the building envelope and multi-zone indoor airflow are simultaneously considered; their interactions are modeled. The coupled system model is implemented into Matlab–Simulink, and is validated by using a series of testing tools and experiments. The new program is applied to investigate the moisture transfer effect on indoor air humidity and building energy consumption in different climates (hot-humid, temperate and hot-dry climates). The results show that not accounting for hygrothermal effects in modeling will result in overestimation of energy costs for hot and humid climate situations and possible over sizing of plant leading to inefficient operation.
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This study is concerned with men's talk about emotions and with how emotion discourses function in the construction and negotiation of masculine ways of doing emotions and of consonant masculine subject positions. A sample group of 16 men, who were recruited from two social contexts in England, participated in focus groups on 'men and emotions'. Group discussions were transcribed and analysed using discourse analysis. Participants drew upon a range of discursive resources in constructing masculine emotional behaviour and negotiating masculine subject positions. They constructed men as emotional beings, but only within specific, rule-governed contexts, and cited death, a football match and a nightclub scenario as prototypical contexts for the permissible/understandable expression of grief, joy and anger, respectively. However, in the nightclub scenario, the men distanced themselves from the expression of anger as violence, whilst maintaining a masculine subject position. These discursive practices are discussed in terms of the possibilities for effecting change in men's emotional lives.
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PURPOSE: A phase I study to define toxicity and recommend a phase II dose of the HSP90 inhibitor alvespimycin (17-DMAG; 17-dimethylaminoethylamino-17-demethoxygeldanamycin). Secondary endpoints included evaluation of pharmacokinetic profile, tumor response, and definition of a biologically effective dose (BED). PATIENTS AND METHODS: Patients with advanced solid cancers were treated with weekly, intravenous (i.v.) 17-DMAG. An accelerated titration dose escalation design was used. The maximum tolerated dose (MTD) was the highest dose at which = 1/6 patients experienced dose limiting toxicity (DLT). Dose de-escalation from the MTD was planned with mandatory, sequential tumor biopsies to determine a BED. Pharmacokinetic and pharmacodynamic assays were validated prior to patient accrual. RESULTS: Twenty-five patients received 17-DMAG (range 2.5-106 mg/m(2)). At 106 mg/m(2) of 17-DMAG 2/4 patients experienced DLT, including one treatment-related death. No DLT occurred at 80 mg/m(2). Common adverse events were gastrointestinal, liver function changes, and ocular. Area under the curve and mean peak concentration increased proportionally with 17-DMAG doses 80 mg/m(2) or less. In peripheral blood mononuclear cells significant (P
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OBJECTIVE
To assess the relationship between glycemic control, pre-eclampsia, and gestational hypertension in women with type 1 diabetes.
RESEARCH DESIGN AND METHODS
Pregnancy outcome (pre-eclampsia or gestational hypertension) was assessed prospectively in 749 women from the randomized controlled Diabetes and Pre-eclampsia Intervention Trial (DAPIT). HbA1c (A1C) values were available up to 6 months before pregnancy (n = 542), at the first antenatal visit (median 9 weeks) (n = 721), at 26 weeks’ gestation (n = 592), and at 34 weeks’ gestation (n = 519) and were categorized as optimal (<6.1%: referent), good (6.1–6.9%), moderate (7.0–7.9%), and poor (=8.0%) glycemic control, respectively.
RESULTS
Pre-eclampsia and gestational hypertension developed in 17 and 11% of pregnancies, respectively. Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy compared with women who did not develop pre-eclampsia (P < 0.05, respectively). In early pregnancy, A1C =8.0% was associated with a significantly increased risk of pre-eclampsia (odds ratio 3.68 [95% CI 1.17–11.6]) compared with optimal control. At 26 weeks’ gestation, A1C values =6.1% (good: 2.09 [1.03–4.21]; moderate: 3.20 [1.47–7.00]; and poor: 3.81 [1.30–11.1]) and at 34 weeks’ gestation A1C values =7.0% (moderate: 3.27 [1.31–8.20] and poor: 8.01 [2.04–31.5]) significantly increased the risk of pre-eclampsia compared with optimal control. The adjusted odds ratios for pre-eclampsia for each 1% decrement in A1C before pregnancy, at the first antenatal visit, at 26 weeks’ gestation, and at 34 weeks’ gestation were 0.88 (0.75–1.03), 0.75 (0.64–0.88), 0.57 (0.42–0.78), and 0.47 (0.31–0.70), respectively. Glycemic control was not significantly associated with gestational hypertension.
CONCLUSIONS
Women who developed pre-eclampsia had significantly higher A1C values before and during pregnancy. These data suggest that optimal glycemic control both early and throughout pregnancy may reduce the risk of pre-eclampsia in women with type 1 diabetes.
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This article discusses the identification of nonlinear dynamic systems using multi-layer perceptrons (MLPs). It focuses on both structure uncertainty and parameter uncertainty, which have been widely explored in the literature of nonlinear system identification. The main contribution is that an integrated analytic framework is proposed for automated neural network structure selection, parameter identification and hysteresis network switching with guaranteed neural identification performance. First, an automated network structure selection procedure is proposed within a fixed time interval for a given network construction criterion. Then, the network parameter updating algorithm is proposed with guaranteed bounded identification error. To cope with structure uncertainty, a hysteresis strategy is proposed to enable neural identifier switching with guaranteed network performance along the switching process. Both theoretic analysis and a simulation example show the efficacy of the proposed method.