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

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

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

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

Blood glucose levels in patients with metastatic renal cell carcinoma treated with sunitinib

Sunitinib, a multitargeted tyrosine-kinase inhibitor, extends survival of patients with metastatic renal cell carcinoma (mRCC) and gastrointestinal stromal tumours. Between October 2005 and March 2007, we retrospectively reviewed blood glucose level variations associated with sunitinib therapy in patients treated for mRCC. Nineteen of the patients had type II diabetes. All 19 patients had a decrease in blood glucose level (mean 1.77 mmol l−1) after 4 weeks of treatment. This was followed by re-elevation in the 2-week rest period. After two cycles of sunitinib administration, two patients had stopped blood glucose-lowering drugs whereas five other patients had normalised their blood glucose level. On the basis of pre-clinical data, we hypothesise that several mechanisms could be involved in this process, such as capillary regression of pancreatic islets, IGF-1 modulation through HIF1-α or NF-κB activation. In addition, a decrease of glucose uptake in the context of concomitant gastrointestinal toxicity cannot be excluded. Glycaemic control should be carefully evaluated in diabetic patients treated with sunitinib, and routine monitoring is warranted

Artificial intelligence in clinical and translational science: Successes, challenges and opportunities

Artificial intelligence (AI) is transforming many domains, including finance, agriculture, defense, and biomedicine. In this paper, we focus on the role of AI in clinical and translational research (CTR), including preclinical research (T1), clinical research (T2), clinical implementation (T3), and public (or population) health (T4). Given the rapid evolution of AI in CTR, we present three complementary perspectives: (1) scoping literature review, (2) survey, and (3) analysis of federally funded projects. For each CTR phase, we addressed challenges, successes, failures, and opportunities for AI. We surveyed Clinical and Translational Science Award (CTSA) hubs regarding AI projects at their institutions. Nineteen of 63 CTSA hubs (30%) responded to the survey. The most common funding source (48.5%) was the federal government. The most common translational phase was T2 (clinical research, 40.2%). Clinicians were the intended users in 44.6% of projects and researchers in 32.3% of projects. The most common computational approaches were supervised machine learning (38.6%) and deep learning (34.2%). The number of projects steadily increased from 2012 to 2020. Finally, we analyzed 2604 AI projects at CTSA hubs using the National Institutes of Health Research Portfolio Online Reporting Tools (RePORTER) database for 2011-2019. We mapped available abstracts to medical subject headings and found that nervous system (16.3%) and mental disorders (16.2) were the most common topics addressed. From a computational perspective, big data (32.3%) and deep learning (30.0%) were most common. This work represents a snapshot in time of the role of AI in the CTSA program