35 resultados para Ferdinand II, King of the Two Sicilies, 1810-1859.
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PURPOSE: poly(ADP ribose) polymerase inhibition has been shown to potentiate the cytotoxicity of DNA damaging agents. A phase I study of rucaparib and temozolomide showed that full-dose temozolomide could be given during PARP inhibition. We report the results of a phase II study of intravenous rucaparib 12 mg/m(2) and oral temozolomide 200 mg/m(2) on days 1-5 every 28 days in patients with advanced metastatic melanoma. METHODS: Patients with chemotherapy naïve measurable metastatic melanoma, performance status =2 and good end-organ function were recruited. Treatment was given until progression. A two stage phase II design was used, with response rate the primary endpoint. Population pharmacokinetics and pharmacodynamics were also explored. RESULTS: Forty-six patients were recruited with 37 patients receiving at least 2 cycles and 17 patients at least 6 cycles. Myelosuppression occurred with 25 patients (54 %) requiring a 25 % dose reduction in temozolomide. The response rate was 17.4 %, median time to progression 3.5 months, median overall survival 9.9 months, and 36 % of patients were progression-free at 6 months. CONCLUSIONS: This study showed that temozolomide (150-200 mg/m(2)/day) can safely be given with a PARP inhibitory dose of rucaparib, increasing progression-free survival over historical controls in metastatic melanoma patients.
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We present a set of Roche tomography reconstructions of the secondary stars in the cataclysmic variables AM Her, QQ Vul, IP Peg and HU Aqr. The image reconstructions show distinct asymmetries in the irradiation pattern for all four systems that can be attributed to shielding of the secondary star by the accretion stream/column in AM Her, QQ Vul and HU Aqr, and increased irradiation by the bright-spot in IP Peg. We use the entropy landscape technique to derive accurate system parameters (M-1, M-2, i and gamma) for the four binaries. In principle, this technique should provide the most reliable mass determinations available, since the intensity distribution across the secondary star is known. We also find that the intensity distribution can systematically affect the value of gamma derived from circular orbit fits to radial velocity variations.
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Background: Our previous laboratory and clinical data suggested that one mechanism underlying the development of platinum resistance in ovarian cancer is the acquisition of DNA methylation. We therefore tested the hypothesis that the DNA hypomethylating agent 5-aza-2'-deoxycytodine (decitabine) can reverse resistance to carboplatin in women with relapsed ovarian cancer.
Methods: Patients progressing 6-12 months after previous platinum therapy were randomised to decitabine on day 1 and carboplatin (AUC 6) on day 8, every 28 days or carboplatin alone. The primary objective was response rate in patients with methylated hMLH1 tumour DNA in plasma.
Results: After a pre-defined interim analysis, the study closed due to lack of efficacy and poor treatment deliverability in 15 patients treated with the combination. Responses by GCIG criteria were 9 out of 14 vs 3 out of 15 and by RECIST were 6 out of 13 vs 1 out of 12 for carboplatin and carboplatin/decitabine, respectively. Grade 3/4 neutropenia was more common with the combination (60% vs 15.4%) as was G2/3 carboplatin hypersensitivity (47% vs 21%).
Conclusions: With this schedule, the addition of decitabine appears to reduce rather than increase the efficacy of carboplatin in partially platinum-sensitive ovarian cancer and is difficult to deliver. Patient-selection strategies, different schedules and other demethylating agents should be considered in future combination studies.
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Density-functional theory calculations have been carried out to systematically study single surface oxygen vacancies on CeO2(111). It is surprisingly found that multiple structures with the two excess electrons localized at different positions can exist. We show that the origin of the multiconfigurations of 4f electrons is a result of geometric relaxation on the surface and strong localization characteristic of 4f electrons in ceria. The importance of 4f electron structures is also presented and discussed. These results may possess implications for our understanding of materials with f electrons.
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Researchers have proposed 1-factor, 2-factor, and bifactor solutions to the 12-item Consideration of Future Consequences Scale (CFCS-12). In order to overcome some measurement problems and to create a robust and conceptually useful two-factor scale the CFCS-12 was recently modified to include two new items and to become the CFCS-14. Using a University sample, we tested four competing models for the CFCS-14: (a) a 12-item unidimensional model, (b) a model fitted for two uncorrelated factors (CFC-Immediate and CFC-Future), (c) a model fitted for two correlated factors (CFC-I and CFC-F), and (d) a bifactor model. Results suggested that the addition of the two new items has strengthened the viability of a two factor solution of the CFCS-14. Results of linear regression models suggest that the CFC-F factor is redundant. Further studies using alcohol and mental health indicators are required to test this redundancy.
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An analysis of high-resolution VLT/UVES spectra of two B-type main sequence stars, NGC 346-11 and AV 304, in the Small Magellanic Cloud (SMC), has been undertaken, using the non-LTE tlusty model atmospheres to derive the stellar parameters and chemical compositions of each star. The chemical compositions of the two stars are in reasonable agreement. Moreover, our stellar analysis agrees well with earlier analyses of H II regions. The results derived here should be representative of the current base-line chemical composition of the SMC interstellar medium as derived from B-type stars.
Towards an understanding of the causes and effects of software requirements change: two case studies
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Changes to software requirements not only pose a risk to the successful delivery of software applications but also provide opportunity for improved usability and value. Increased understanding of the causes and consequences of change can support requirements management and also make progress towards the goal of change anticipation. This paper presents the results of two case studies that address objectives arising from that ultimate goal. The first case study evaluated the potential of a change source taxonomy containing the elements ‘market’, ‘organisation’, ‘vision’, ‘specification’, and ‘solution’ to provide a meaningful basis for change classification and measurement. The second case study investigated whether the requirements attributes of novelty, complexity, and dependency correlated with requirements volatility. While insufficiency of data in the first case study precluded an investigation of changes arising due to the change source of ‘market’, for the remainder of the change sources, results indicate a significant difference in cost, value to the customer and management considerations. Findings show that higher cost and value changes arose more often from ‘organisation’ and ‘vision’ sources; these changes also generally involved the co-operation of more stakeholder groups and were considered to be less controllable than changes arising from the ‘specification’ or ‘solution’ sources. Results from the second case study indicate that only ‘requirements dependency’ is consistently correlated with volatility and that changes coming from each change source affect different groups of requirements. We conclude that the taxonomy can provide a meaningful means of change classification, but that a single requirement attribute is insufficient for change prediction. A theoretical causal account of requirements change is drawn from the implications of the combined results of the two case studies.
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The radical cations He-2(+) (H2O)(2)(+), and (NH3)(2)(+) with two-center three-electron A-A bonds are investigated at the configuration interaction (CI), accurate Kohn-Sham (KS), generalized gradient approximation (GGA), and meta-GGA levels. Assessment of seven different GGA and six meta-GGA methods shows that the A(2)(+) systems remain a difficult case for density functional theory (DFT). All methods tested consistently overestimate the stability of A(2)(+): the corresponding D-e errors decrease for more diffuse valence densities in the series He-2(+) > (H2O)(2)(+) > (NH3)(2)(+). Upon comparison to the energy terms of the accurate Kohn-Sham solutions, the approximate exchange functionals are found to be responsible for the errors of GGA-type methods, which characteristically overestimate the exchange in A(2)(+). These so-called exchange functionals implicitly use localized holes. Such localized holes do occur if there is left-right correlation, i.e., the exchange functionals then also describe nondynamical correlation. However, in the hemibonded A(2)(+) systems the typical molecular (left-right, nondynamical) correlation of the two-electron pair bond is absent. The nondynamical correlation built into the exchange functionals is then spurious and yields too low energies.
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Temporal overlapping of ultra-short and focussed laser pulses is a particularly challenging task, as this timescale lies orders of magnitude below the typical range of fast electronic devices. Here we present an optical technique that allows for the measurement of the temporal delay between two focussed and ultra-short laser pulses. This method is virtually applicable to any focussing geometry and relative intensity of the two lasers. Experimental implementation of this technique provides excellent quantitative agreement with theoretical expectations. The proposed technique will prove highly beneficial for high-power multiple-beam laser experiments.
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This article examines recent developments in the Cyprus negotiations and suggests a number of changes to the proposed electoral system. Specifically, cross-voting and other electoral methods that encourage coalition-building across ethnic communities might add significantly to the functionality of the Annan Plan. Combined with other innovative mechanisms already in the plan, cross-voting could force political parties to seriously take into account the interests and concerns of the two Cypriot communities, an element that is currently missing from both the Turkish Cypriot (TC) and Greek Cypriot (GC) political systems. Special conditions on the island, as well as the way most political parties operated in the critical pre-April 2004 referendum period, suggest the need for this amendment. Although this study respects the consociational logic of the Annan Plan, it supplements consociationalism with elements that foster integration and inter-dependence between the two communities and their voters. The article also reviews the postreferendum developments in Cyprus which might have worrisome future implications, not only for its two communities, but also for EU enlargement in general. Cyprus both holds one of the keys to Turkey's entrance into the EU and is a litmus test for the Euro-Atlantic nexus and its capacity to pacify and integrate ethnically divided societies in Europe and elsewhere.
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We present a model-atmosphere analysis for the bright (V similar to 13) star ZNG-1, in the globular cluster M10. From high-resolution (R similar to 40 000) optical spectra we confirm ZNG-1 to be a post-asymptotic giant branch (post-AGB) star. The derived atmospheric parameters are T-eff = 26 500 +/- 1000 K and log g = 3.6 +/- 0.2 dex. A differential abundance analysis reveals a chemical composition typical of hot post-AGB objects, with ZNG-1 being generally metal poor, although helium is approximately solar. The most interesting feature is the large carbon underabundance of more than 1.3 dex. This carbon deficiency, along with an observed nitrogen enhancement relative to other elements, may suggest that ZNG-1 evolved off the AGB before the third dredge-up occurred. Also, iron depletions observed in other similar stars suggest that gas- dust fractionation in the AGB progenitor could be responsible for the observed composition of these objects. However, we need not invoke either scenario since the chemical composition of ZNG-1 is in good agreement with abundances found for a Population II star of the same metallicity.
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A nonlinear equation of motion is found for the dimer comprising two charged H2O molecules. The THz dielectric response to nonharmonic vibration of a nonrigid dipole, forming the hydrogen bond (HB), is found in the direction transverse to this bond. An explicit expression is derived for the autocorrelator that governs the spectrum generated by transverse vibration (TV) of such a dipole. This expression is obtained by analytical solution of the truncated set of recurrence equations. The far infrared (FIR) spectra of ice at the temperature - 7 degrees C are calculated. The wideband, in the wavenumber (frequency) v range 0... 100.0 cm(-1), spectra are obtained for liquid water at room temperature and for supercooled water at -5.6 degrees C. All spectra are represented in terms of the complex permittivity epsilon(v) and the absorption coefficient alpha(v). The obtained analytical formula for epsilon comprises the term epsilon(perpendicular to) pertinent to the studied TV mechanism with three additional terms Delta epsilon(q), Delta epsilon(mu), and epsilon(or) arising, respectively, from: elastic harmonic vibration of charged molecules along the H-bond; elastic reorientation of HB permanent dipoles; and rather free libration of permanent dipoles in 'defects' of water/ice structure. The suggested TV-dielectric relaxation mechanism allows us: (a) to remove the THz 'deficit' of loss epsilon" inherent in previous theoretical studies; (b) to explain the THz loss and absorption spectra in supercooled (SC) water; and (c) to describe, in agreement with the experiment, the low- and high-frequency tails of the two bands of ice H2O located in the range 10...300 cm(-1). Specific THz dielectric properties of SC water are ascribed to association of water molecules, revealed in our study by transverse vibration of HB charged molecules. (C) 2006 Published by Elsevier B.V.