3510-V 390-m Omega . cm(2) 4H-SiC Lateral JFET on a Semi-Insulating Substrate

The performance of high-voltage 4H-SiC lateral JFETs on a semi-insulating substrate is reported in this letter. The design of the voltage-supporting layers is based on the charge compensation of p- and n-type epilayers. The best measured breakdown voltage is 3510 V, which, to the authors\u27 knowledge, is the highest value ever reported for SiC lateral switching devices. The R-on of this device is 390 m Omega . cm(2), in which 61% is due to the drift-region resistance. The BV2/R-on is 32 MW/cm(2), which is typical among other reported SiC lateral devices

In vivo regeneration of rat laryngeal cartilage with mesenchymal stem cells derived from human induced pluripotent stem cells via neural crest cells

The laryngotracheal cartilage is a cardinal framework for the maintenance of the airway for breathing, which occasionally requires reconstruction. Because hyaline cartilage has a poor intrinsic regenerative ability, various regenerative approaches have been attempted to regenerate laryngotracheal cartilage. The use of autologous mesenchymal stem cells (MSCs) for cartilage regeneration has been widely investigated. However, long-term culture may limit proliferative capacity. Human-induced pluripotent stem cell-derived MSCs (iMSCs) can circumvent this problem due to their unlimited proliferative capacity. This study aimed to investigate the efficacy of iMSCs in the regeneration of thyroid cartilage in immunodeficient rats. Herein, we induced iMSCs through neural crest cell intermediates. For the relevance to prospective future clinical application, induction was conducted under xeno-free/serum-free conditions. Then, clumps fabricated from an iMSC/extracellular matrix complex (C-iMSC) were transplanted into thyroid cartilage defects in immunodeficient rats. Histological examinations revealed cartilage-like regenerated tissue and human nuclear antigen (HNA)-positive surviving transplanted cells in the regenerated lesion. HNA-positive cells co-expressed SOX9, and type II collagen was identified around HNA-positive cells. These results indicated that the transplanted C-iMSCs promoted thyroid cartilage regeneration and some of the iMSCs differentiated into chondrogenic lineage cells. Induced MSCs may be a promising candidate cell therapy for human laryngotracheal reconstruction

Waste processing facility location problem by stochastic programming: Models and solutions

The paper deals with the so-called waste processing facility location problem (FLP), which asks for establishing a set of operational waste processing units, optimal against the total expected cost. We minimize the waste management (WM) expenditure of the waste producers, which is derived from the related waste processing, transportation, and investment costs. We use a stochastic programming approach in recognition of the inherent uncertainties in this area. Two relevant models are presented and discussed in the paper. Initially, we extend the common transportation network flow model with on-and-off waste-processing capacities in selected nodes, representing the facility location. Subsequently, we model the randomly-varying production of waste by a scenario-based two-stage stochastic integer linear program. Finally, we employ selected pricing ideas from revenue management to model the behavior of the waste producers, who we assume to be environmentally friendly. The modeling ideas are illustrated on an example of limited size solved in GAMS. Computations on larger instances were realized with traditional and heuristic algorithms, implemented within MATLAB. © Springer Nature Switzerland AG 2019

Effect of suppressing the synthesis of different kafirin subclasses on grain endosperm texture, protein body structure and protein nutritional quality in improved sorghum lines

To improve sorghum grain protein nutritional quality, improved sorghum lines were transformed to suppress the synthesis of different kafirin sub-classes, or backcrossed into transgenic lines with improved protein quality. Co-suppression of the alpha-, gamma- and delta-kafirin sub-classes and removal of the tannin trait resulted in transgenic sorghum lines with high cooked protein digestibility ( 80%), improved Amino Acid Score (0.8) and Protein Digestibility Corrected Amino Acid Score (0.7) compared to the non-transgenic null controls ( 50%, 0.4 and 0.2, respectively). These high protein quality lines had a floury endosperm. They also had modified protein body structure, where the protein bodies were irregular shaped with few to numerous invaginations and were less densely packed, with a dense protein matrix visible around the protein bodies. When fewer sub-classes were suppressed, i.e. gamma 1 and delta 2, the endosperm was corneous with normal protein body structure but the improvement in cooked protein digestibility appeared to be less. Apparently, co-suppression of several kafirin sub-classes is required to obtain high protein nutritional quality sorghum lines, but this seems to result in floury-type grain endosperm texture.The Bill and Melinda Gates Grand Challenges 9, Africa Biofortified Sorghum (ABS) Project, the South African National Research Foundation, and the Faculty Research and Innovation Committee, Faculty of Science, Tshwane University of Technology.http://www.elsevier.com/locate/jc

Determinants of GBP Recruitment to Toxoplasma gondii Vacuoles and the Parasitic Factors That Control It

IFN-γ is a major cytokine that mediates resistance against the intracellular parasite Toxoplasma gondii. The p65 guanylate-binding proteins (GBPs) are strongly induced by IFN-γ. We studied the behavior of murine GBP1 (mGBP1) upon infection with T. gondii in vitro and confirmed that IFN-γ-dependent re-localization of mGBP1 to the parasitophorous vacuole (PV) correlates with the virulence type of the parasite. We identified three parasitic factors, ROP16, ROP18, and GRA15 that determine strain-specific accumulation of mGBP1 on the PV. These highly polymorphic proteins are held responsible for a large part of the strain-specific differences in virulence. Therefore, our data suggest that virulence of T. gondii in animals may rely in part on recognition by GBPs. However, phagosomes or vacuoles containing Trypanosoma cruzi did not recruit mGBP1. Co-immunoprecipitation revealed mGBP2, mGBP4, and mGBP5 as binding partners of mGBP1. Indeed, mGBP2 and mGBP5 co-localize with mGBP1 in T. gondii-infected cells. T. gondii thus elicits a cell-autonomous immune response in mice with GBPs involved. Three parasitic virulence factors and unknown IFN-γ-dependent host factors regulate this complex process. Depending on the virulence of the strains involved, numerous GBPs are brought to the PV as part of a large, multimeric structure to combat T. gondii.National Institutes of Health (U.S.)Massachusetts Life Sciences Center (New Investigator Award)National Institute of General Medical Sciences (U.S.) (Pre-Doctoral Grant in the Biological Sciences (5-T32-GM007287-33))Studienstiftung des deutschen VolkesCancer Research Institute (New York, N.Y.)Cleo and Paul Schimmel FoundationBayer HealthcareHuman Frontier Science Program (Strasbourg, France

Sleep and Wakefulness Are Controlled by Ventral Medial Midbrain/Pons GABAergic Neurons in Mice

Sleep–wake behavior is controlled by a wide range of neuronal populations in the mammalian brain. Although the ventral midbrain/pons (VMP) area is suggested to participate in sleep–wake regulation, the neuronal mechanisms have remained unclear. Here, we found that nonspecific cell ablation or selective ablation of GABAergic neurons by expressing diphtheria toxin fragment A in the VMP in male mice induced a large increase in wakefulness that lasted at least 4 weeks. In contrast, selective ablation of dopaminergic neurons in the VMP had little effect on wakefulness. Chemogenetic inhibition of VMP GABAergic neurons also markedly increased wakefulness. The wake-promoting effect of the VMP GABAergic neuron ablation or inhibition was attenuated to varying degrees by the administration of dopamine D1 or D2/3 receptor antagonists and abolished by the administration of both antagonists together. In contrast, chemogenetic activation of VMP GABAergic neurons very strongly increased slow-wave sleep and reduced wakefulness. These findings suggest that VMP GABAergic neurons regulate dopaminergic actions in the sleep–wake behavior of mice

Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection

The interferon-γ (IFN-γ)-inducible immunity-related GTPase (IRG), Irgm1, plays an essential role in restraining activation of the IRG pathogen resistance system. However, the loss of Irgm1 in mice also causes a dramatic but unexplained susceptibility phenotype upon infection with a variety of pathogens, including many not normally controlled by the IRG system. This phenotype is associated with lymphopenia, hemopoietic collapse, and death of the mouse.Deutscher Akademischer Austausch Dienst (DAAD); International Graduate School in Development Health and Disease (IGS-DHD); Deutsche For-schungsgemeinschaft (SFBs 635, 670, 680); Max-Planck-Gesellschaft (Max Planck Fellowship)

Shrinking a large dataset to identify variables associated with increased risk of Plasmodium falciparum infection in Western Kenya

Large datasets are often not amenable to analysis using traditional single-step approaches. Here, our general objective was to apply imputation techniques, principal component analysis (PCA), elastic net and generalized linear models to a large dataset in a systematic approach to extract the most meaningful predictors for a health outcome. We extracted predictors for Plasmodium falciparum infection, from a large covariate dataset while facing limited numbers of observations, using data from the People, Animals, and their Zoonoses (PAZ) project to demonstrate these techniques: data collected from 415 homesteads in western Kenya, contained over 1500 variables that describe the health, environment, and social factors of the humans, livestock, and the homesteads in which they reside. The wide, sparse dataset was simplified to 42 predictors of P. falciparum malaria infection and wealth rankings were produced for all homesteads. The 42 predictors make biological sense and are supported by previous studies. This systematic data-mining approach we used would make many large datasets more manageable and informative for decision-making processes and health policy prioritization