Free potential functions

We show that the derivative of a noncommutative free analytic map must be free-curl free -- an analog of having zero curl. Moreover, under the assumption that the free domain is connected, this necessary condition is sufficient. Specifically, if $T$ is analytic free demilinear (linear in half its variables) map defined on a connected free domain then $DT(X,H)[K,0] = DT(X,K)[H,0]$ if and only if there exists an analytic free map $f$ such that $Df(X)[H] = T(X,H)$.Comment: 13 page

Graphene field-effect transistors based on boron nitride gate dielectrics

Graphene field-effect transistors are fabricated utilizing single-crystal hexagonal boron nitride (h-BN), an insulating isomorph of graphene, as the gate dielectric. The devices exhibit mobility values exceeding 10,000 cm2/V-sec and current saturation down to 500 nm channel lengths with intrinsic transconductance values above 400 mS/mm. The work demonstrates the favorable properties of using h-BN as a gate dielectric for graphene FETs.Comment: 4 pages, 8 figure

Electronic compressibility of layer polarized bilayer graphene

We report on a capacitance study of dual gated bilayer graphene. The measured capacitance allows us to probe the electronic compressibility as a function of carrier density, temperature, and applied perpendicular electrical displacement D. As a band gap is induced with increasing D, the compressibility minimum at charge neutrality becomes deeper but remains finite, suggesting the presence of localized states within the energy gap. Temperature dependent capacitance measurements show that compressibility is sensitive to the intrinsic band gap. For large displacements, an additional peak appears in the compressibility as a function of density, corresponding to the presence of a 1-dimensional van Hove singularity (vHs) at the band edge arising from the quartic bilayer graphene band structure. For D > 0, the additional peak is observed only for electrons, while D < 0 the peak appears only for holes. This asymmetry that can be understood in terms of the finite interlayer separation and may be useful as a direct probe of the layer polarization

Phase Ib/II Study of the Safety and Efficacy of Combination Therapy with Multikinase VEGF Inhibitor Pazopanib and MEK Inhibitor Trametinib In Advanced Soft Tissue Sarcoma.

Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1–3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS. Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles. The primary endpoint was 4-month progression-free survival (PFS). Secondary endpoints were overall survival, response rate, and disease control rate. Results: Twenty-five patients were enrolled. The median age was 49 years (range, 22–77 years) and 52% were male. Median PFS was 2.27 months [95% confidence interval (CI), 1.9–3.9], and the 4-month PFS rate was 21.1% (95% CI, 9.7–45.9), which was not an improvement over the hypothesized null 4-month PFS rate of 28.3% (P ¼ 0.79). Median overall survival was 9.0 months (95% CI, 5.7–17.7). A partial response occurred in 2 (8%) of the evaluable patients (95% CI, 1.0–26.0), one with PIK3CA E542K-mutant embryonal rhabdomyosarcoma and another with spindle cell sarcoma. The disease control rate was 14/25 (56%; 95% CI, 34.9–75.6). The most common adverse events were diarrhea (84%), nausea (64%), and fatigue (56%). Conclusions: The combination of pazopanib and trametinib was tolerable without indication of added activity of the combination in STS. Further study may be warranted in RAS/RAF aberrant sarcomas. ©2017 AACR

NCI-MATCH Arms N & P: Phase II study of PI3K beta inhibitor GSK2636771 in patients (pts) with cancers (ca) with PTEN mutation/deletion (mut/del) or PTEN protein loss

Background: The NCI-MATCH trial is the largest national study (1173 sites) for ptswith relapsed/ refractory solid tumors, lymphomas and myeloma, which assigns tar-geted therapies based on individual tumor molecular alterations detected using theadapted Oncomine AmpliSeq panel (143 genes) and immunohistochemistry (IHC).We hypothesized that patients with PTEN-deficient cancers enrolled to Arms N and Pmay benefit from treatment with the PI3K beta-selective inhibitor GSK2636771. Methods: Eligibility: relapsed/refractory ca, good end-organ function, and ECOG PS ≤ 1. Pts were screened for molecular alterations by centralized testing on fresh tumor biopsy and had deleterious PTEN mut/del without loss of expression (Arm N) or complete loss of cytoplasmic and nuclear PTEN staining on IHC (Arm P), and no other aberrations activating the PI3K/MTOR and MAPK pathways (mut in PIK3CA, PIK3R1, BRAF, KRAS, AKT1, TSC1/2, mTOR, RHEB, NF2, NRAS, HRAS). Pts received GSK2636771 400mg/day (28-days cycles). RECIST 1.1 overall response rate (ORR) was the primary endpoint. Results: Of 59 enrolled pts, 56 were eligible and received treatment. Of 22 pts with PTEN mut/del (Arm N: 6 uterine, 2 breast, 2 prostate, 2 head/neck ca, 10 other), all are off treatment as of analysis (14 disease progression, 4 for adverse events [AEs], 4 other). One pt (4.5%) with prostate ca (PTEN deletion, MPRSS2-ERG fusion) attained a partial response (-42%). Of 7 (32%) pts with stable disease (SD), 2 had SD \u3e 6 months (uterine leiomyosarcoma; endometrial carcinoma). Of 34 pts with loss of PTEN protein by IHC (Arm P: 7 prostate, 6 breast, 3 squamous anal ca, 2 cholangiocarcinoma, 16 other), all are off treatment as of analysis (26 disease progression, 4 for AE, 4 other). Of 9 (37.5%) pts with SD, 3 had SD \u3e 6 months (prostate cancer; squamous bladder cancer, squamous anal cancer). Median progression-free survival was 1.8 months for both arms. Gr ≥ 3 treatment-related (tr) reversible toxicities were experienced by 30% (7) and 20% (7) of pts in arms N and P, respectively. No tr Gr 5 toxicities were observed in either arm. Conclusions: Single agent GSK2636771 has very modest activity in ca with PTEN gene mutation/deletion and/or PTEN protein loss

First assessment of geophysical sensitivities from spaceborne Galileo and BeiDou GNSS-Reflectometry data collected by the UK TechDemoSat-1 Mission

The UK’s TechDemoSat-1 (TDS-1), launched 2014, has demonstrated the use of global positioning system (GPS) signals for monitoring ocean winds and sea ice. Here it is shown, for the first time, that Galileo and BeiDou signals detected by TDS-1 show similar promise. TDS-1 made seven raw data collections, recovering returns from Galileo and BeiDou, between November 2015 and March 2019. The retrieved open ocean delay Doppler maps (DDMs) are similar to those from GPS. Over sea ice, the Galileo DDMs show a distinctive triple peak. Analysis, adapted from that for GPS DDMs, gives Galileo’s signal-to-noise ratio (SNR), which is found to be inversely sensitive to wind speed, as for GPS. A Galileo track transiting from open ocean to sea ice shows a strong instantaneous SNR response. These results demonstrate the potential of future spaceborne constellations of GNSS-R (global navigation satellite system–reflectometry) instruments for exploiting signals from multiple systems: GPS, Galileo, and BeiDou

MET nucleotide variations and amplification in advanced ovarian cancer: characteristics and outcomes with c-Met inhibitors.

PurposeMET alterations including amplifications and nucleotide variations have been associated with resistance to therapy and aggressive clinical behavior.Experimental designThe medical records of patients presenting to the University of Texas MD Anderson Cancer Center Phase I Clinic with relapsed or metastatic ovarian cancers and known MET nucleotide variation or amplification status were reviewed retrospectively (n=178). Categorical and continuous clinical and molecular characteristics were compared using Fisher's exact and Wilcoxon rank-sum tests, respectively. Univariate and multivariate survival were assessed via Kaplan-Meier and Cox regression analysis, respectively.ResultsMET amplification occurred in 4 (3.5%) of 113 patients, whereas nonsynonomous nucleotide variations were present in 9 (7.4%) of 122 patients. No patients exhibited concomitant amplification and variation. MET variations were observed only in white women with high-grade ovarian tumors, whereas amplifications were observed in both black and white women with high-grade serous ovarian primary tumors. No patients (n=4) exhibiting a MET alteration achieved an objective response when treated on a c-Met inhibitor phase I trial. In addition, ovarian cancer patients treated with a c-Met inhibitor with multikinase activity trended towards a longer time-to-failure compared with those treated with a c-Met-specific inhibitor (median: 1.5 vs. 4.5 months, p=0.07).ConclusionsMET alterations occur in a minority of patients with ovarian cancer. c-Met inhibitors with multikinase activity may exhibit less activity in ovarian cancer than c-Met specific drugs. These findings warrant further investigation