Genome Resources for Climate‐Resilient Cowpea, an Essential Crop for Food Security

Cowpea (Vigna unguiculata L. Walp.) is a legume crop that is resilient to hot and drought‐prone climates, and a primary source of protein in sub‐Saharan Africa and other parts of the developing world. However, genome resources for cowpea have lagged behind most other major crops. Here we describe foundational genome resources and their application to the analysis of germplasm currently in use in West African breeding programs. Resources developed from the African cultivar IT97K‐499‐35 include a whole‐genome shotgun (WGS) assembly, a bacterial artificial chromosome (BAC) physical map, and assembled sequences from 4355 BACs. These resources and WGS sequences of an additional 36 diverse cowpea accessions supported the development of a genotyping assay for 51 128 SNPs, which was then applied to five bi‐parental RIL populations to produce a consensus genetic map containing 37 372 SNPs. This genetic map enabled the anchoring of 100 Mb of WGS and 420 Mb of BAC sequences, an exploration of genetic diversity along each linkage group, and clarification of macrosynteny between cowpea and common bean. The SNP assay enabled a diversity analysis of materials from West African breeding programs. Two major subpopulations exist within those materials, one of which has significant parentage from South and East Africa and more diversity. There are genomic regions of high differentiation between subpopulations, one of which coincides with a cluster of nodulin genes. The new resources and knowledge help to define goals and accelerate the breeding of improved varieties to address food security issues related to limited‐input small‐holder farming and climate stress

Identification of patients with ovarian cancer experiencing the highest benefit from bevacizumab in the first-line setting on the basis of their tumor-intrinsic chemosensitivity (KELIM): The GOG-0218 validation study

PURPOSE: In patients with high-grade ovarian cancer, predictors of bevacizumab efficacy in first-line setting are needed. In the ICON-7 trial, a poor tumor intrinsic chemosensitivity (defined by unfavorable modeled cancer antigen-125 [CA-125] ELIMination rate constant K [KELIM] score) was a predictive biomarker. Only the patients with high-risk disease (suboptimally resected stage III, or stage IV) exhibiting unfavorable KELIM score \u3c 1.0 had overall survival (OS) benefit from bevacizumab (median: 29.7 METHODS: In GOG-0218, 1,873 patients were treated with carboplatin-paclitaxel ± concurrent-maintenance bevacizumab/placebo. Patient KELIM values were calculated with CA-125 kinetics during the first 100 chemotherapy days by the Lyon University team. The association between KELIM score (favorable ≥ 1.0, or unfavorable \u3c 1.0) and bevacizumab benefit for progression-free survival (PFS)/OS was independently assessed by NGR-GOG using univariate/multivariate analyses. RESULTS: KELIM was assessable in 1,662 patients with ≥ 3 CA-125 available values. An unfavorable KELIM score was associated with bevacizumab benefit compared with placebo (PFS: HR, 0.70; 95% CI, 0.59 to 0.82; OS: HR, 0.87; 95% CI, 0.73 to 1.03), whereas a favorable KELIM was not (PFS: HR, 0.96; 95% CI, 0.79 to 1.17; OS: HR, 1.11; 95% CI, 0.89 to 1.39). The highest benefit was observed in patients with a high-risk disease exhibiting unfavorable KELIM, for PFS (median: 9.1 CONCLUSION: This GOG-0218 trial investigation validates ICON-7 findings about the association between poor tumor chemosensitivity and benefit from concurrent-maintenance bevacizumab, suggesting that bevacizumab may mainly be effective in patients with poorly chemosensitive disease. Bevacizumab may be prioritized in patients with a high-risk and poorly chemosensitive disease to improve their PFS/OS (patient KELIM score calculator available on the Biomarker Kinetics website)

The histone demethylase LSD1/KDM1A promotes the DNA damage response

Histone demethylation is known to regulate transcription, but its role in other processes is largely unknown. We report a role for the histone demethylase LSD1/KDM1A in the DNA damage response (DDR). We show that LSD1 is recruited directly to sites of DNA damage. H3K4 dimethylation, a major substrate for LSD1, is reduced at sites of DNA damage in an LSD1-dependent manner. The E3 ubiquitin ligase RNF168 physically interacts with LSD1 and we find this interaction to be important for LSD1 recruitment to DNA damage sites. Although loss of LSD1 did not affect the initial formation of pH2A.X foci, 53BP1 and BRCA1 complex recruitment were reduced upon LSD1 knockdown. Mechanistically, this was likely a result of compromised histone ubiquitylation preferentially in late S/G2. Consistent with a role in the DDR, knockdown of LSD1 resulted in moderate hypersensitivity to γ-irradiation and increased homologous recombination. Our findings uncover a direct role for LSD1 in the DDR and place LSD1 downstream of RNF168 in the DDR pathway

Surface-potential-based compact model for the gate current of p-GaN Gate HEMTs

The gate leakage current of p-GaN gate HEMTs is modeled based on surface potential calculations. The model accurately describes the bias and temperature dependence of the gate leakage. Thermionic emission is the main mechanism of the gate current in forward bias operation while hopping transport component is the main mechanism of gate current in reverse bias operation. This newly developed gate current model was implemented in Verilog-A. A good agreement between the simulations and experimental data demonstrates the accuracy of the model

Observation of dynamic V-TH of p-GaN Gate HEMTs by fast sweeping characterization

In this work, fast sweeping characterization with an extremely short relaxation time was used to probe the V-TH instability of p-GaN gate HEMTs. As the I-D-V-G sweeping time deceases from 5 ms to 5 mu s, the V-TH dramatically degenerates from 3.13 V to 1.76 V, meanwhile the hysteresis deteriorates from 22.6mV to 1.37 V. Positive bias temperature instability (PBTI) measurement by fast sweeping shows the V-TH features a very fast shifting process but a slower recovering process. D-mode HEMTs counterpart without Mg contamination demonstrates a negligible V-TH shift and hysteresis, proving the V-TH instability is probably due to the ionization of acceptor-like traps in the p-GaN depletion region. Finally, the V-TH instability is verified by a GaN circuit under switching stress. The V-TH instability under different sweeping speed uncovers the fact that the high V-TH by conventionally slow DC measurements is probably artificial. The DC V-TH should be high enough to avoid HEMT faulty turn-on

Use of Bilayer gate insulator in GaN-on-Si Vertical Trench MOSFETs : impact on performance and reliability

We propose to use a bilayer insulator (2.5 nm Al2O3 + 35 nm SiO2) as an alternative to a conventional uni-layer Al2O3 (35 nm), for improving the performance and the reliability of GaN-on-Si semi vertical trench MOSFETs. This analysis has been performed on a test vehicle structure for module development, which has a limited OFF-state performance. We demonstrate that devices with the bilayer dielectric present superior reliability characteristics than those with the uni-layer, including: (i) gate leakage two-orders of magnitude lower; (ii) 11 V higher off-state drain breakdown voltage; and (iii) 18 V higher gate-source breakdown voltage. From Weibull slope extractions, the uni-layer shows an extrinsic failure, while the bilayer presents a wear-out mechanism. Extended reliability tests investigate the degradation process, and hot-spots are identified through electroluminescence microscopy. TCAD simulations, in good agreement with measurements, reflect electric field distribution near breakdown for gate and drain stresses, demonstrating a higher electric field during positive gate stress. Furthermore, DC capability of the bilayer and unilayer insulators are found to be comparable for same bias points. Finally, comparison of trapping processes through double pulsed and V-th transient methods confirms that the V-th shifts are similar, despite the additional interface present in the bilayer devices

Mathematical modeling of the early modeled CA-125 longitudinal kinetics (KELIM-PARP) as a pragmatic indicator of rucaparib efficacy in patients with recurrent ovarian carcinoma in ARIEL2 & STUDY 10

BackgroundPARP inhibitors (PARPi) have revolutionized the management of advanced ovarian carcinoma, and were investigated as forefront treatment in recurrent disease. The objective was to explore if mathematical modeling of the early longitudinal CA-125 kinetics could be used as a pragmatic indicator of the subsequent rucaparib efficacy, like it is for platinum-based chemotherapy. MethodsThe datasets of ARIEL2 and Study 10 involving recurrent HGOC patients treated with rucaparib were retrospectively investigated. The same strategy as those successfully developed for platinum chemotherapy, based on CA-125 ELIMination rate constant K (KELIM™), was implemented. Individual values of rucaparib-adjusted KELIM (KELIM-PARP) were estimated based on the longitudinal CA-125 kinetics during the first 100 treatment days, and then scored as favorable (KELIM-PARP ≥1.0) or unfavorable (KELIM-PARP &lt;1.0). The prognostic value of KELIM-PARP regarding treatment efficacy (radiological response, and progression-free survival (PFS)) was assessed using univariable/multivariable analyses, with respect to platinum-sensitivity and homologous recombination deficiency (HRD) status. FindingsThe data from 476 patients were assessed. The CA-125 longitudinal kinetics during the first 100-treatment days could be accurately assessed using the KELIM-PARP model. In patients with platinum-sensitive diseases, BRCA mutational status KELIM-PARP score and were associated with subsequent complete/partial radiological responses (KELIM-PARP: odds-ratio = 2.81, 95% CI 1.86–4.52), and PFS (KELIM-PARP: hazard-ratio = 0.67, 95% CI 0.50–0.91). The patients with BRCA-wild type cancer and favorable KELIM-PARP experienced long PFS with rucaparib regardless of HRD. In platinum-resistant disease patients, KELIM-PARP was associated with subsequent radiological response (odds-ratio = 2.80, 95% CI 1.82–4.72). InterpretationThis proof-of-concept study confirms the early CA-125 longitudinal kinetics during rucaparib in recurrent HGOC patients are assessable by mathematical modeling, to generate individual a KELIM-PARP score associated with the subsequent efficacy. This pragmatic strategy might be useful for selecting the patients for PARPi-based combination regimens, when identifying efficacy biomarker is challenging. Further assessment of this hypothesis is warranted. FundingThe present study was supported by Clovis Oncology with a grant to academic research association.</p

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

Modeling of gate capacitance of GaN-based trench-gate vertical metal-oxide-semiconductor devices

We propose a model for the gate capacitance of GaN-based trench-gate metal-oxide-semiconductor transistors, based on combined measurements, analytical calculations and TCAD simulations. The trench capacitance is found to be equivalent to four different capacitors, used to model the various regions with different doping and orientation of the semiconductor/dielectric interface. In addition, we demonstrate and explain the characteristic double-hump behavior of the G-D and G-DS capacitance of trench-MOSFETs. Lastly, a TCAD simulation results accurately reproduce the experimental data, thus confirming the interpretation on the double hump behavior, and providing insight on the electron density at the gate interface. (C) 2020 The Japan Society of Applied Physic