Hepatitis C viral evolution in genotype 1 treatment-naïve and treatment-experienced patients receiving telaprevir-based therapy in clinical trials

Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR. Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment. Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients. Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment

Impact of climate change on maize grown in the brazilian cerrado.

Crops are subject to instabilities of climatic conditions that affect yield. Maize is very sensitive to factors like temperature, solar radiation and rainfall. The objective of this work was to evaluate, using crop growth models, the effects of climate change on maize grain yield produced under rainfed conditions. Two global circulation models, HadGEM2-ES and MIROC5, coupled to the regional model Eta, were used to generate projections of changes in maximum and minimum air temperature, solar radiation and rainfall for conditions in southeastern Brazil. The CSM-CERES-Maize model was then used to evaluate the effect of climate changes on rainfed maize grain yield. For each combination of global and regional circulation models, two greenhouse gas concentration scenarios were used: RCP4.5 and RCP8.5. The combined use of global circulation and crop growth models allowed us to estimate the expected average grain yield of corn as affected by future climate. The simulated results indicated that, even at best sowing dates, considerable reduction in maize grain yield may occur. Our simulated results also indicated that the largest grain yield reductions may occur for future climate scenarios from 2071 to the end of the 21st century

Materials and corrosion characterization using the confocal resonator

Improved characterization and process control is important to many Sandia and DOE programs related to manufacturing. Many processes/structures are currently under-characterized including thin film growth, corrosion and semiconductor structures, such as implant profiles. A sensitive tool is required that is able to provide lateral and vertical imaging of the electromagnetic properties of a sample. The confocal resonator is able to characterize the surface and near-surface impedance of materials. This device may be applied to a broad range of applications including in situ evaluation of thin film processes, physical defect detection/characterization, the characterization of semiconductor devices and corrosion studies. In all of these cases, the technology should work as a real-time process diagnostic or as a feedback mechanism regarding the quality of a manufacturing process. This report summarizes the development and exploration of several diagnostic applications

Complex and unexpected dynamics in simple genetic regulatory networks

Peer reviewedPublisher PD

Measuring quality and outcomes of research collaborations: An integrative review

Introduction: Although the science of team science is no longer a new field, the measurement of team science and its standardization remain in relatively early stages of development. To describe the current state of team science assessment, we conducted an integrative review of measures of research collaboration quality and outcomes. Methods: Collaboration measures were identified using both a literature review based on specific keywords and an environmental scan. Raters abstracted details about the measures using a standard tool. Measures related to collaborations with clinical care, education, and program delivery were excluded from this review. Results: We identified 44 measures of research collaboration quality, which included 35 measures with reliability and some form of statistical validity reported. Most scales focused on group dynamics. We identified 89 measures of research collaboration outcomes; 16 had reliability and 15 had a validity statistic. Outcome measures often only included simple counts of products; publications rarely defined how counts were delimited, obtained, or assessed for reliability. Most measures were tested in only one venue. Conclusions: Although models of collaboration have been developed, in general, strong, reliable, and valid measurements of such collaborations have not been conducted or accepted into practice. This limitation makes it difficult to compare the characteristics and impacts of research teams across studies or to identify the most important areas for intervention. To advance the science of team science, we provide recommendations regarding the development and psychometric testing of measures of collaboration quality and outcomes that can be replicated and broadly applied across studies

Development, characterization, and applications of high temperature superconductor nanobridge Josephson junctions

A well-controlled, high-yield Josephson junction process in high temperature superconductors (HTS) is necessary for the demonstration of ultra-high-speed devices and circuits which exceed the capabilities of conventional electronics. The authors developed nanobridge Josephson junctions in high quality thin-film YBaCuO with dimensions below 100 nm fabricated using electron-beam nanolithography. They characterized this Josephson junction technology for process yield, junction parameter uniformity, and overall applicability for use in high-performance circuits. To facilitate the determination of junction parameters, they developed a measurement technique based on spectral analysis in the range of 90--160 GHz of phase-locked, oscillating arrays of up to 2,450 Josephson junctions. Because of the excellent yield and uniformity of the nanobridge junctions, they successfully applied the junction technology to a wide variety of circuits. These circuits included transmission-line pulse formers and 32 and 64-bit shift registers. The 32-bit shift register was shown to operate at clock speeds near 100 GHz and is believed to be one of the faster and more complex digital circuit demonstrated to date using high temperature superconductor technology

Physical constraints of cultural evolution of dialects in killer whales

Data collection was supported by a variety of organizations, including the Russian Fund for the Fundamental Research (Grant No. 15-04-05540), the Rufford Small Grants Fund, Whale and Dolphin Conservation, the Fundação para a Ciência e a Tecnologia (Grant No. SFRH/BD/30303/2006), Russell Trust Award of the University of St. Andrews, the Office of Naval Research, the Icelandic Research Fund (i. Rannsóknasjóður), the National Geographic Society Science and Exploration Europe (Grant No. GEFNE65-12), Vancouver Aquarium Marine Science Centre, the Canadian Ministry of Fisheries and Oceans, and the North Gulf Oceanic Society.Odontocete sounds are produced by two pairs of phonic lips situated in soft nares below the blowhole; the right pair is larger and is more likely to produce clicks, while the left pair is more likely to produce whistles. This has important implications for the cultural evolution of delphinid sounds: the greater the physical constraints, the greater the probability of random convergence. In this paper the authors examine the call structure of eight killer whale populations to identify structural constraints and to determine if they are consistent among all populations. Constraints were especially pronounced in two-voiced calls. In the calls of all eight populations, the lower component of two-voiced (biphonic) calls was typically centered below 4 kHz, while the upper component was typically above that value. The lower component of two-voiced calls had a narrower frequency range than single-voiced calls in all populations. This may be because some single-voiced calls are homologous to the lower component, while others are homologous to the higher component of two-voiced calls. Physical constraints on the call structure reduce the possible variation and increase the probability of random convergence, producing similar calls in different populations.PostprintPeer reviewe

Impact of stream impurities on compressor power requirements for CO2 pipeline transportation

The economic viability of Carbon Capture and Sequestration (CCS) as a means of mitigating CO2 emissions is significantly dependent on the minimisation of costs associated with the compression and transportation of the captured CO2. This paper describes the development and application of a rigorous thermodynamic model to compute and compare power requirements for various multistage compression strategies for CO2 streams containing typical impurities originating from various capture technologies associated with industrial and power emission sectors. The compression options examined include conventional multistage integrally geared centrifugal compressors, supersonic shockwave compressors and multistage compression combined with subcritical liquefaction and pumping. The study shows that for all the compression options examined, the compression power reduces with the increase in the purity of the CO2 stream, while the inter-stage cooling duty is predicted to be significantly higher than the compression power demand. For CO2 streams carrying less than 5% impurities, multistage compression combined with liquefaction and subsequent pumping from ca 62 bar pressure can offer higher efficiency than conventional gas-phase compression. In the case of a raw/dehumidified oxy-fuel CO2 stream of ca 85% purity, subcritical liquefaction at 62 bar pressure is shown to increase the cooling duty by ca 50% as compared to pure CO2

Gene expression model (in)validation by Fourier analysis

The determination of the right model structure describing a gene regulation network and the identification of its parameters are major goals in systems biology. The task is often hampered by the lack of relevant experimental data with sufficiently low noise level, but the subset of genes whose concentration levels exhibit an oscillatory behavior in time can readily be analyzed on the basis of their Fourier spectrum, known to turn complex signals into few relatively noise-free parameters. Such genes therefore offer opportunities of understanding gene regulation quantitatively.Journal ArticleResearch Support, Non-U.S. Gov'tValidation StudiesSCOPUS: ar.jinfo:eu-repo/semantics/publishe