Electrochemically Induced pH Change: Time-Resolved Confocal Fluorescence Microscopy Measurements and Comparison with Numerical Model

Confocal fluorescence microscopy is a proven technique, which can image near-electrode pH changes. For a complete understanding of electrode processes, time-resolved measurements are required, which have not yet been provided. Here we present the first measurements of time-resolved pH profiles with confocal fluorescence microscopy. The experimental results compare favorably with a one-dimensional reaction-diffusion model; this holds up to the point where the measurements reveal three-dimensionality in the pH distribution. Specific factors affecting the pH measurement such as attenuation of light and the role of dye migration are also discussed in detail. The method is further applied to reveal the buffer effects observed in sulfate-containing electrolytes. The work presented here is paving the way toward the use of confocal fluorescence microscopy in the measurement of 3D time-resolved pH changes in numerous electrochemical settings, for example in the vicinity of bubbles.Comment: 10 pages, 7 figures, Supplementary informatio

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer:A Phase II Multi-Cohort Study

PURPOSE: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). PATIENTS AND METHODS: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). RESULTS: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. CONCLUSIONS: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.</p

Olaparib plus Durvalumab, with or without Bevacizumab, as Treatment in PARP Inhibitor-Naïve Platinum-Sensitive Relapsed Ovarian Cancer:A Phase II Multi-Cohort Study

PURPOSE: Early results from the phase II MEDIOLA study (NCT02734004) in germline BRCA1- and/or BRCA2-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSROC) showed promising efficacy and safety with olaparib plus durvalumab. We report efficacy and safety of olaparib plus durvalumab in an expansion cohort of women with gBRCAm PSROC (gBRCAm expansion doublet cohort) and two cohorts with non-gBRCAm PSROC, one of which also received bevacizumab (non-gBRCAm doublet and triplet cohorts). PATIENTS AND METHODS: In this open-label, multicenter study, PARP inhibitor-naïve patients received olaparib plus durvalumab treatment until disease progression; the non-gBRCAm triplet cohort also received bevacizumab. Primary endpoints were objective response rate (ORR; gBRCAm expansion doublet cohort), disease control rate (DCR) at 24 weeks (non-gBRCAm cohorts), and safety (all cohorts). RESULTS: The full analysis and safety analysis sets comprised 51, 32, and 31 patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively. ORR was 92.2% [95% confidence interval (CI), 81.1-97.8] in the gBRCAm expansion doublet cohort (primary endpoint); DCR at 24 weeks was 28.1% (90% CI, 15.5-43.9) in the non-gBRCAm doublet cohort (primary endpoint) and 74.2% (90% CI, 58.2-86.5) in the non-gBRCAm triplet cohort (primary endpoint). Grade ≥ 3 adverse events were reported in 47.1%, 65.6%, and 61.3% of patients in the gBRCAm expansion doublet, non-gBRCAm doublet, and non-gBRCAm triplet cohorts, respectively, most commonly anemia. CONCLUSIONS: Olaparib plus durvalumab continued to show notable clinical activity in women with gBRCAm PSROC. Olaparib plus durvalumab with bevacizumab demonstrated encouraging clinical activity in women with non-gBRCAm PSROC. No new safety signals were identified.</p

Euclid preparation. XXIX. Water ice in spacecraft part I:The physics of ice formation and contamination

Molecular contamination is a well-known problem in space flight. Water is the most common contaminant and alters numerous properties of a cryogenic optical system. Too much ice means that Euclid's calibration requirements and science goals cannot be met. Euclid must then be thermally decontaminated, a long and risky process. We need to understand how iced optics affect the data and when a decontamination is required. This is essential to build adequate calibration and survey plans, yet a comprehensive analysis in the context of an astrophysical space survey has not been done before. In this paper we look at other spacecraft with well-documented outgassing records, and we review the formation of thin ice films. A mix of amorphous and crystalline ices is expected for Euclid. Their surface topography depends on the competing energetic needs of the substrate-water and the water-water interfaces, and is hard to predict with current theories. We illustrate that with scanning-tunnelling and atomic-force microscope images. Industrial tools exist to estimate contamination, and we must understand their uncertainties. We find considerable knowledge errors on the diffusion and sublimation coefficients, limiting the accuracy of these tools. We developed a water transport model to compute contamination rates in Euclid, and find general agreement with industry estimates. Tests of the Euclid flight hardware in space simulators did not pick up contamination signals; our in-flight calibrations observations will be much more sensitive. We must understand the link between the amount of ice on the optics and its effect on Euclid's data. Little research is available about this link, possibly because other spacecraft can decontaminate easily, quenching the need for a deeper understanding. In our second paper we quantify the various effects of iced optics on spectrophotometric data

Euclid preparation. XXIX. Water ice in spacecraft part I: The physics of ice formation and contamination

Molecular contamination is a well-known problem in space flight. Water is the most common contaminant and alters numerous properties of a cryogenic optical system. Too much ice means that Euclid's calibration requirements and science goals cannot be met. Euclid must then be thermally decontaminated, a long and risky process. We need to understand how iced optics affect the data and when a decontamination is required. This is essential to build adequate calibration and survey plans, yet a comprehensive analysis in the context of an astrophysical space survey has not been done before. In this paper we look at other spacecraft with well-documented outgassing records, and we review the formation of thin ice films. A mix of amorphous and crystalline ices is expected for Euclid. Their surface topography depends on the competing energetic needs of the substrate-water and the water-water interfaces, and is hard to predict with current theories. We illustrate that with scanning-tunnelling and atomic-force microscope images. Industrial tools exist to estimate contamination, and we must understand their uncertainties. We find considerable knowledge errors on the diffusion and sublimation coefficients, limiting the accuracy of these tools. We developed a water transport model to compute contamination rates in Euclid, and find general agreement with industry estimates. Tests of the Euclid flight hardware in space simulators did not pick up contamination signals; our in-flight calibrations observations will be much more sensitive. We must understand the link between the amount of ice on the optics and its effect on Euclid's data. Little research is available about this link, possibly because other spacecraft can decontaminate easily, quenching the need for a deeper understanding. In our second paper we quantify the various effects of iced optics on spectrophotometric data.Comment: 35 pages, 22 figures, A&A in press. Changes to previous version: language edits, added Z. Bolag as author in the arxiv PDF (was listed in the ASCII author list and in the journal PDF, but not in the arxiv PDF). This version is identical to the journal versio

Examining the generalizability of research findings from archival data

This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability—for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe