Top-Gated Chemical Vapor Deposited Mos2 Field-Effect Transistors On Si3N4 Substrates

We report the electrical characteristics of chemical vapor deposited (CVD) monolayer molybdenum disulfide (MoS2) top-gated field-effect transistors (FETs) on silicon nitride (Si3N4) substrates. We show that Si3N4 substrates offer comparable electrical performance to thermally grown SiO2 substrates for MoS2 FETs, offering an attractive passivating substrate for transition-metal dichalcogenides (TMD) with a smooth surface morphology. Single-crystal MoS2 grains are grown via vapor transport process using solid precursors directly on low pressure CVD Si3N4, eliminating the need for transfer processes which degrade electrical performance. Monolayer top-gated MoS2 FETs with Al2O3 gate dielectric on Si3N4 achieve a room temperature mobility of 24 cm(2)/V s with I-on/I-off current ratios exceeding 10(7). Using HfO2 as a gate dielectric, monolayer top-gated CVD MoS2 FETs on Si3N4 achieve current densities of 55 mu A/mu m and a transconductance of 6.12 mu S/mu m at V-tg of -5V and V-ds of 2V. We observe an increase in mobility at lower temperatures, indicating phonon scattering may dominate over charged impurity scattering in our devices. Our results show that Si3N4 is an attractive alternative to thermally grown SiO2 substrate for TMD FETs. (C) 2015 AIP Publishing LLC.STTR programNSF NASCENT ERCArmy Research Office under STTR W911NF-14-P-0030Microelectronics Research Cente

High-Resolution Genetics Identifies the Lipid Transfer Protein Sec14p as Target for Antifungal Ergolines.

Invasive infections by fungal pathogens cause more deaths than malaria worldwide. We found the ergoline compound NGx04 in an antifungal screen, with selectivity over mammalian cells. High-resolution chemogenomics identified the lipid transfer protein Sec14p as the target of NGx04 and compound-resistant mutations in Sec14p define compound-target interactions in the substrate binding pocket of the protein. Beyond its essential lipid transfer function in a variety of pathogenic fungi, Sec14p is also involved in secretion of virulence determinants essential for the pathogenicity of fungi such as Cryptococcus neoformans, making Sec14p an attractive antifungal target. Consistent with this dual function, we demonstrate that NGx04 inhibits the growth of two clinical isolates of C. neoformans and that NGx04-related compounds have equal and even higher potency against C. neoformans. Furthermore NGx04 analogues showed fungicidal activity against a fluconazole resistant C. neoformans strain. In summary, we present genetic evidence that NGx04 inhibits fungal Sec14p and initial data supporting NGx04 as a novel antifungal starting point

MHO1, an Evolutionarily Conserved Gene, Is Synthetic Lethal with PLC1; Mho1p Has a Role in Invasive Growth

The novel protein Memo (Mediator of ErbB2 driven cell motility) was identified in a screen for ErbB2 interacting proteins and found to have an essential function in cell motility. Memo is evolutionarily conserved with homologs found in all branches of life; the human and yeast proteins have a similarity of >50%. In the present study we used the model organism S. cerevisiae to characterize the Memo-homologue Mho1 (Yjr008wp) and to investigate its function in yeast. In a synthetic lethal screen we found MHO1 as a novel synthetic lethal partner of PLC1, which encodes the single phospholipase C in yeast. Double-deleted cells lacking MHO1 and PLC1, proliferate for up to ten generations. Introduction of human Memo into the memoΔplc1Δ strain rescued the synthetic lethal phenotype suggesting that yeast and human proteins have similar functions. Mho1 is present in the cytoplasm and the nucleus of yeast cells; the same distribution of Memo was found in mammalian cells. None of the Memo homologues have a characteristic nuclear localization sequence, however, a conserved nuclear export sequence is found in all. In mammalian cells, blocking nuclear export with Leptomycin B led to nuclear Memo accumulation, suggesting that it is actively exported from the nucleus. In yeast MHO1 expression is induced by stress conditions. Since invasive growth in S. cerevisiea is also stress-induced, we tested Mho1's role in this response. MHO1 deletion had no effect on invasion induced by nutrient deprivation, however, Mho1 overexpression blocked the invasive ability of yeast cells, suggesting that Mho1 might be acting in a dominant negative manner. Taken together, our results show that MHO1 is a novel synthetic lethal interactor with PLC1, and that both gene products are required for proliferation. Moreover, a role for Memo in cell motility/invasion appears to be conserved across species

The effect of graphene oxide (GO) nanoparticles on the processing of epoxy/glass fiber composites using resin infusion

In this paper, the effects of graphene oxide (GO) nanoparticles on glass fiber composite processing by incorporating them into epoxy resin were investigated. GO was synthesized from graphite powder and was mixed with epoxy resin. Three different GO contents of 0.05, 0.1, and 0.2 wt% were used. Epoxy/GO samples were tested for rheology and cure kinetics to evaluate the effects of GO content on important resin infusion processing parameters. The results show that adding GO to neat epoxy resin increased the viscosity and affected the resin cure reaction by reducing the resin gel time. After that, glass fiber composites were prepared using the resin infusion process. Samples with 0.2 wt% GO result in very slow resin infiltration time with premature resin gelation. A 30 % increase in flexural strength and a 21 % increase in flexural modulus are manifested by adding GO as the secondary reinforcement to glass fiber composites

Sorafenib for advanced and refractory desmoid tumors

BACKGROUND Desmoid tumors (also referred to as aggressive fibromatosis) are connective tissue neoplasms that can arise in any anatomical location and infiltrate the mesentery, neurovascular structures, and visceral organs. There is no standard of care. METHODS In this double-blind, phase 3 trial, we randomly assigned 87 patients with progressive, symptomatic, or recurrent desmoid tumors to receive either sorafenib (400- mg tablet once daily) or matching placebo. Crossover to the sorafenib group was permitted for patients in the placebo group who had disease progression. The primary end point was investigator-assessed progression-free survival; rates of objective response and adverse events were also evaluated. RESULTS With a median follow-up of 27.2 months, the 2-year progression-free survival rate was 81% (95% confidence interval [CI], 69 to 96) in the sorafenib group and 36% (95% CI, 22 to 57) in the placebo group (hazard ratio for progression or death, 0.13; 95% CI, 0.05 to 0.31; P<0.001). Before crossover, the objective response rate was 33% (95% CI, 20 to 48) in the sorafenib group and 20% (95% CI, 8 to 38) in the placebo group. The median time to an objective response among patients who had a response was 9.6 months (interquartile range, 6.6 to 16.7) in the sorafenib group and 13.3 months (interquartile range, 11.2 to 31.1) in the placebo group. The objective responses are ongoing. Among patients who received sorafenib, the most frequently reported adverse events were grade 1 or 2 events of rash (73%), fatigue (67%), hypertension (55%), and diarrhea (51%). CONCLUSIONS Among patients with progressive, refractory, or symptomatic desmoid tumors, sorafenib significantly prolonged progression-free survival and induced durable responses

Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.Peer reviewe