Graphene microwave transistors on sapphire substrates

We have developed metal-oxide graphene field-effect transistors (MOGFETs) on sapphire substrates working at microwave frequencies. For monolayers, we obtain a transit frequency up to ~ 80 GHz for a gate length of 200 nm, and a power gain maximum frequency of about ~ 3 GHz for this specific sample. Given the strongly reduced charge noise for nanostructures on sapphire, the high stability and high performance of this material at low temperature, our MOGFETs on sapphire are well suited for a cryogenic broadband low-noise amplifier

Functional consequence of the MET-T1010I polymorphism in breast cancer.

Major breast cancer predisposition genes, only account for approximately 30% of high-risk breast cancer families and only explain 15% of breast cancer familial relative risk. The HGF growth factor receptor MET is potentially functionally altered due to an uncommon germline single nucleotide polymorphism (SNP), MET-T1010I, in many cancer lineages including breast cancer where the MET-T1010I SNP is present in 2% of patients with metastatic breast cancer. Expression of MET-T1010I in the context of mammary epithelium increases colony formation, cell migration and invasion in-vitro and tumor growth and invasion in-vivo. A selective effect of MET-T1010I as compared to wild type MET on cell invasion both in-vitro and in-vivo suggests that the MET-T1010I SNP may alter tumor pathophysiology and should be considered as a potential biomarker when implementing MET targeted clinical trials

Quantum interference and Klein tunneling in graphene heterojunctions

The observation of quantum conductance oscillations in mesoscopic systems has traditionally required the confinement of the carriers to a phase space of reduced dimensionality. While electron optics such as lensing and focusing have been demonstrated experimentally, building a collimated electron interferometer in two unconfined dimensions has remained a challenge due to the difficulty of creating electrostatic barriers that are sharp on the order of the electron wavelength. Here, we report the observation of conductance oscillations in extremely narrow graphene heterostructures where a resonant cavity is formed between two electrostatically created bipolar junctions. Analysis of the oscillations confirms that p-n junctions have a collimating effect on ballistically transmitted carriers. The phase shift observed in the conductance fringes at low magnetic fields is a signature of the perfect transmission of carriers normally incident on the junctions and thus constitutes a direct experimental observation of ``Klein Tunneling.''Comment: 13 pages and 6 figures including supplementary information. The paper has been modified in light of new theoretical results available at arXiv:0808.048

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

SAR-Mode altimetry observations of internal solitary waves in the tropical ocean part 2: a method of detection

It is demonstrated that the synthetic aperture radar altimeter (SRAL) on board of the Sentinel-3A can detect short-period internal solitary waves (ISWs) with scales of the order of a kilometer. A variety of signatures owing to the surface manifestations of the ISWs are apparent in the SRAL Level-2 products over the ocean. These signatures are identified in several geophysical parameters, such as radar backscatter ( σ0 ) and sea level anomaly (SLA). Radar backscatter is the primary parameter in which ISWs can be identified owing to the measurable sea surface roughness perturbations in the along-track direction resulting from the sharpened SRAL footprint. The SRAL footprint is sufficiently small (300 m in the along-track direction) to capture radar power fluctuations over successive wave crests and troughs, which produce rough and slick surface patterns arrayed in parallel bands with scales of a few kilometers along-track. Furthermore, it was possible to calculate the mean square slope ( s2¯¯¯ ) for the dual-band (Ku and C bands) altimeter of Sentinel-3, which made the ISW signatures unambiguously identified because of the large s2¯¯¯ variations in exact synergy with ocean and land color instrument (OLCI) images. Hence, the detection method is validated in cloud-free sun glint OLCI images. It is shown that both σ0 and SLA yield realistic estimates for routine observation of ISWs with the SRAL. The detection method that is used relies on the parameter s2¯¯¯ which is calculated from σ0 . This is a significant improvement from previous observations recently reported for conventional pulse-limited altimeters (Jason-2). An algorithm is developed to be used in any ocean region. Wavelets were applied for a first analysis of the s2¯¯¯ variations because ISWs can be readily identified in high-frequency signals. Other geophysical parameters such as SLA were used to exclude phenomena that are unlikely to be ISWs

High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype

The current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior

Futibatinib, an irreversible FGFR1-4 inhibitor, in patients with advanced solid tumors harboring FGF/FGFR aberrations: a phase I dose-expansion study

Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy

Performance of Monolayer Graphene Nanomechanical Resonators with Electrical Readout

The enormous stiffness and low density of graphene make it an ideal material for nanoelectromechanical (NEMS) applications. We demonstrate fabrication and electrical readout of monolayer graphene resonators, and test their response to changes in mass and temperature. The devices show resonances in the MHz range. The strong dependence of the resonant frequency on applied gate voltage can be fit to a membrane model, which yields the mass density and built-in strain. Upon removal and addition of mass, we observe changes in both the density and the strain, indicating that adsorbates impart tension to the graphene. Upon cooling, the frequency increases; the shift rate can be used to measure the unusual negative thermal expansion coefficient of graphene. The quality factor increases with decreasing temperature, reaching ~10,000 at 5 K. By establishing many of the basic attributes of monolayer graphene resonators, these studies lay the groundwork for applications, including high-sensitivity mass detectors

Efficacy of futibatinib, an irreversible fibroblast growth factor receptor inhibitor, in FGFR-altered breast cancer.

Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib\u27s efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (\u3e 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib