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

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

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

Proton tracking in a high-granularity Digital Tracking Calorimeter for proton CT purposes

Radiation therapy with protons as of today utilizes information from x-ray CT in order to estimate the proton stopping power of the traversed tissue in a patient. The conversion from x-ray attenuation to proton stopping power in tissue introduces range uncertainties of the order of 2-3% of the range, uncertainties that are contributing to an increase of the necessary planning margins added to the target volume in a patient. Imaging methods and modalities, such as Dual Energy CT and proton CT, have come into consideration in the pursuit of obtaining an as good as possible estimate of the proton stopping power. In this study, a Digital Tracking Calorimeter is benchmarked for proof-of-concept for proton CT purposes. The Digital Tracking Calorimeteris applied for reconstruction of the tracks and energies of individual high energy protons. The presented prototype forms the basis for a proton CT system using a single technology for tracking and calorimetry. This advantage simplifies the setup and reduces the cost of a proton CT system assembly, and it is a unique feature of the Digital Tracking Calorimeter. Data from the AGORFIRM beamline at KVI-CART in Groningen in the Netherlands and Monte Carlo simulation results are used to in order to develop a tracking algorithm for the estimation of the residual ranges of a high number of concurrent proton tracks. The range of the individual protons can at present be estimated with a resolution of 4%. The readout system for this prototype is able to handle an effective proton frequency of 1 MHz by using 500 concurrent proton tracks in each readout frame, which is at the high end range of present similar prototypes. A future further optimized prototype will enable a high-speed and more accurate determination of the ranges of individual protons in a therapeutic beam.Comment: 21 pages, 8 figure

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

Retreatment with anti-EGFR based therapies in metastatic colorectal cancer: impact of intervening time interval and prior anti-EGFR response.

BackgroundThis retrospective study aims to investigate the activity of retreatment with anti-EGFR-based therapies in order to explore the concept of clonal evolution by evaluating the impact of prior activity and intervening time interval.MethodsEighty-nine KRAS exon 2-wild-type metastatic colorectal patients were retreated on phase I/II clinical trials containing anti-EGFR therapies after progressing on prior cetuximab or panitumumab. Response on prior anti-EGFR therapy was defined retrospectively per physician-records as response or stable disease ≥6 months. Multivariable statistical methods included a multiple logistic regression model for response, and Cox proportional hazards model for progression-free survival.ResultsRetreatment anti-EGFR agents were cetuximab (n = 76) or cetuximab plus erlotinib (n = 13). The median interval time between prior and retreatment regimens was 4.57 months (range: 0.46-58.7). Patients who responded to the prior cetuximab or panitumumab were more likely to obtain clinical benefit to the retreatment compared to the non-responders in both univariate (p = 0.007) and multivariate analyses (OR: 3.38, 95 % CI: 1.27, 9.31, p = 0.019). The clinical benefit rate on retreatment also showed a marginally significant association with interval time between the two anti-EGFR based therapies (p = 0.053). Median progression-free survival on retreatment was increased in prior responders (4.9 months, 95 % CI: 3.6, 6.2) compared to prior non-responders (2.5 months, 95 % CI, 1.58, 3.42) in univariate (p = 0.064) and multivariate analysis (HR: 0.70, 95 % CI: 0.43-1.15, p = 0.156).ConclusionOur data lends support to the concept of clonal evolution, though the clinical impact appears less robust than previously reported. Further work to determine which patients benefit from retreatment post progression is needed

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

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