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

Spatial and temporal scales of variability in Tropical Atlantic sea surface salinity from the SMOS and Aquarius satellite missions

Taking advantage of the spatially dense, multi-year time series of global Sea Surface Salinity (SSS) from two concurrent satellite missions, the spatial and temporal decorrelation scales of SSS in the Tropical Atlantic 30°N–30°S are quantified for the first time from SMOS and Aquarius observations. Given the dominance of the seasonal cycle in SSS variability in the region, the length scales are calculated both for the mean and anomaly (i.e. seasonal cycle removed) SSS fields. Different 7–10 days composite SSS products from the two missions are examined to explore the possible effects of varying resolution, bias corrections and averaging characteristics. With the seasonal cycle retained, the SSS field is characterized by strongly anisotropic spatial variability. Homogeneous SSS variations in the Tropics have the longest zonal scales of over ~ 2000 km and long temporal scales of up to ~ 70–80 days, as shown by both SMOS and Aquarius. The longest meridional scales, reaching over ~ 1000 km, are seen in the South Atlantic between ~ 10°–25°S, most discernible in Aquarius data. The longest temporal scales of SSS variability are reported by both satellites to occur in the North-West Atlantic region 15°–30°N, at the Southern end of the Sargasso Sea, with SSS persisting for up to 150–200 days. The removal of the seasonal cycle results in a noticeable decrease in the spatio-temporal decorrelation scales over most of the basin. Overall, with the exception of the differences in the South Atlantic, there is general agreement between the spatial and temporal scales of SSS from the two satellites and different products, despite differences in individual product calibration and resolution characteristics. These new estimates of spatio-temporal decorrelation scales of SSS improve our knowledge of the processes and mechanisms controlling the Tropical Atlantic SSS variability, and provide valuable information for a wide range of oceanographic and modelling applications

Translational Research from an Informatics Perspective

Clinical and translational research (CTR) is an essential part of a sustainable global health system. Informatics is now recognized as an important en-abler of CTR and informaticians are increasingly called upon to help CTR efforts. The US National Institutes of Health mandated biomedical informatics activity as part of its new national CTR grant initiative, the Clinical and Translational Science Award (CTSA). Traditionally, translational re-search was defined as the translation of laboratory discoveries to patient care (bench to bedside). We argue, however, that there are many other kinds of translational research. Indeed, translational re-search requires the translation of knowledge dis-covered in one domain to another domain and is therefore an information-based activity. In this panel, we will expand upon this view of translational research and present three different examples of translation to illustrate the point: 1) bench to bedside, 2) Earth to space and 3) academia to community. We will conclude with a discussion of our local translational research efforts that draw on each of the three examples

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

BRAF V600E mutations in urine and plasma cell-free DNA from patients with Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare histiocytosis with a high prevalence of BRAF V600E mutation (&gt;50% of patients). Patients with BRAF-mutant ECD can respond to BRAF inhibitors. Unfortunately, the lack of adequate archival tissue often precludes BRAF testing. We hypothesized that cell-free DNA (cfDNA) from plasma or urine can offer an alternative source of biologic material for testing. We tested for BRAF V600E mutation in cfDNA from the plasma and urine of 6 ECD patients. In patients with available archival tissue, the result of BRAF mutation analysis was concordant with plasma and urine cfDNA results in all 3 patients (100% agreement, kappa 1.00). In all 6 patients, BRAF mutation analysis of plasma and urine cfDNA was concordant in 5 of 6 patients (83% agreement, kappa 0.67). Testing for BRAF V600E mutation in plasma and urine cfDNA should be further investigated as an alternative to archival tissue mutation analysis

Circadian signatures in rat liver: from gene expression to pathways

<p>Abstract</p> <p>Background</p> <p>Circadian rhythms are 24 hour oscillations in many behavioural, physiological, cellular and molecular processes that are controlled by an endogenous clock which is entrained to environmental factors including light, food and stress. Transcriptional analyses of circadian patterns demonstrate that genes showing circadian rhythms are part of a wide variety of biological pathways.</p> <p>Pathway activity method can identify the significant pattern of the gene expression levels within a pathway. In this method, the overall gene expression levels are translated to a reduced form, pathway activity levels, via singular value decomposition (SVD). A given pathway represented by pathway activity levels can then be as analyzed using the same approaches used for analyzing gene expression levels. We propose to use pathway activity method across time to identify underlying circadian pattern of pathways.</p> <p>Results</p> <p>We used synthetic data to demonstrate that pathway activity analysis can evaluate the underlying circadian pattern within a pathway even when circadian patterns cannot be captured by the individual gene expression levels. In addition, we illustrated that pathway activity formulation should be coupled with a significance analysis to distinguish biologically significant information from random deviations. Next, we performed pathway activity level analysis on a rich time series of transcriptional profiling in rat liver. The over-represented five specific patterns of pathway activity levels, which cannot be explained by random event, exhibited circadian rhythms. The identification of the circadian signatures at the pathway level identified 78 pathways related to energy metabolism, amino acid metabolism, lipid metabolism and DNA replication and protein synthesis, which are biologically relevant in rat liver. Further, we observed tight coordination between cholesterol biosynthesis and bile acid biosynthesis as well as between folate biosynthesis, one carbon pool by folate and purine-pyrimidine metabolism. These coupled pathways are parts of a sequential reaction series where the product of one pathway is the substrate of another pathway.</p> <p>Conclusions</p> <p>Rather than assessing the importance of a single gene beforehand and map these genes onto pathways, we instead examined the orchestrated change within a pathway. Pathway activity level analysis could reveal the underlying circadian dynamics in the microarray data with an unsupervised approach and biologically relevant results were obtained.</p

Reduced ascending/descending pass bias in SMOS salinity data demonstrated by observing westward-propagating features in the South Indian Ocean

The European Space Agency (ESA) Soil Moisture and Ocean Salinity (SMOS) satellite has been providing data, including sea surface salinity (SSS) measurements, for more than five years. However, the operational ESA Level 2 SSS data are known to have significant spatially and temporally varying biases between measurements from ascending passes (SSSA) and measurements from descending passes (SSSD). This paper demonstrates how these biases are reduced through the use of SSS anomalies. Climatology products are constructed using SMOS Level 2 data to provide daily, one-degree by one-degree climatologies separately for ascending and descending passes using a moving window approach (in time and space). The daily, one-degree products can then be averaged to provide values of climatological SSS at different spatial and/or temporal resolutions. The averaged values of the SMOS climatology products are in good general agreement with data from the World Ocean Atlas 2013. However, there are significant differences at high latitudes, as well as in coastal and dynamic regions, as found by previous studies. Both the mean and standard deviation of the differences between data from ascending passes and data from descending passes for the anomalies are reduced compared with those obtained using the original salinity values. Geophysical signals are clearly visible in the anomaly products and an example is shown in the Southern Indian Ocean of westward-propagating signals that we conclude represent the surface expression of Rossby waves or large-scale non-linear eddies. The signals seen in salinity data agree (in speed) with those from sea surface temperature and sea surface height and are consistent with previous studies

Plankton patchiness investigated using simultaneous nitrate and chlorophyll observations

The complex patterns observed in marine phytoplankton distributions arise from the interplay of biological and physical processes, but the nature of the balance remains uncertain centuries after the first observations. Previous observations have shown a consistent trend of decreasing variability with decreasing length-scale. Influenced by similar scaling found for the properties of the water that the phytoplankton inhabit, ‘universal' theories have been proposed that simultaneously explain the variability seen from meters to hundreds of kilometers. However, data on the distribution of phytoplankton alone has proved insufficient to differentiate between the many causal mechanisms that have been suggested. Here we present novel observations from a cruise in the North Atlantic in which fluorescence (proxy for phytoplankton), nitrate and temperature were measured simultaneously at scales from 10 m to 100 km for the first time in the open ocean. These show a change in spectra between the small scale (10–100 m) and the mesoscale (10–100 km) which is different for the three tracers. We discuss these observations in relation to the current theories for phytoplankton patchiness

An observational assessment of the influence of mesoscale and submesoscale heterogeneity on ocean biogeochemical reactions

Numerous observations demonstrate that considerable spatial variability exists in components of the marine planktonic ecosystem at the mesoscale and submesoscale (100?km -1?km). The causes and consequences of physical processes at these scales (‘eddy advection’) influencing biogeochemistry have received much attention. Less studied, the non-linear nature of most ecological and biogeochemical interactions means that such spatial variability has consequences for regional estimates of processes including primary production and grazing, independent of the physical processes. This effect has been termed ‘eddy reactions’. Models remain our most powerful tools for extrapolating hypotheses for biogeochemistry to global scales and to permit future projections. The spatial resolution of most climate and global biogeochemical models means that processes at the mesoscale and submesoscale are poorly resolved. Modelling work has previously suggested that the neglected ‘eddy reactions’ may be almost as large as the mean field estimates in some cases. This study seeks to quantify the relative size of eddy and mean reactions observationally, using in situ and satellite data. For primary production, grazing and zooplankton mortality the eddy reactions are between 7% and 15% of the mean reactions. These should be regarded as preliminary estimates to encourage further observational estimates, and not taken as a justification for ignoring eddy reactions. Compared to modelling estimates, there are inconsistencies in the relative magnitude of eddy reactions and in correlations which are a major control on their magnitude. One possibility is that models exhibit much stronger spatial correlations than are found in reality, effectively amplifying the magnitude of eddy reactions