1,749 research outputs found

    Valley formation and methane precipitation rates on Titan

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    Branching valley networks near the landing site of the Huygens probe on Titan imply that fluid has eroded the surface. The fluid was most likely methane, which forms several percent of Titan's atmosphere and can exist as a liquid at the surface. The morphology of the valley networks and the nature of Titan's surface environment are inconsistent with a primary valley formation process involving thermal, chemical, or seepage erosion. The valleys were more likely eroded mechanically by surface runoff associated with methane precipitation. If mechanical erosion did occur, the flows must first have been able to mobilize any sediment accumulated in the valleys. We develop a model that links precipitation, open-channel flow, and sediment transport to calculate the minimum precipitation rate required to mobilize sediment and initiate erosion. Using data from two monitored watersheds in the Alps, we show that the model is able to predict precipitation rates in small drainage basins on Earth. The calculated precipitation rate is most sensitive to the sediment grain size. For a grain diameter of 1–10 cm, a range that brackets the median size observed at the Huygens landing site, the minimum precipitation rate required to mobilize sediment in the nearby branching networks is 0.5–15 mm hr^(−1). We show that this range is reasonable given the abundance of methane in Titan's atmosphere. These minimum precipitation rates can be compared with observations of tropospheric cloud activity and estimates of long-term methane precipitation rates to further test the hypothesis that runoff eroded the valleys

    Microfluidic and Nanofluidic Cavities for Quantum Fluids Experiments

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    The union of quantum fluids research with nanoscience is rich with opportunities for new physics. The relevant length scales in quantum fluids, 3He in particular, are comparable to those possible using microfluidic and nanofluidic devices. In this article, we will briefly review how the physics of quantum fluids depends strongly on confinement on the microscale and nanoscale. Then we present devices fabricated specifically for quantum fluids research, with cavity sizes ranging from 30 nm to 11 microns deep, and the characterization of these devices for low temperature quantum fluids experiments.Comment: 12 pages, 3 figures, Accepted to Journal of Low Temperature Physic

    A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes

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    Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect of sequence-specific RBPs on mRNA stability, we show that RBP-mediated stability programs are recurrently deregulated in cancerous tissues. Particularly, we uncovered several RBPs that contribute to the abnormal transcriptome of renal cell carcinoma (RCC), including PCBP2, ESRP2, and MBNL2. Modulation of these proteins in cancer cell lines alters the expression of pathways that are central to the disease and highlights RBPs as driving master regulators of RCC transcriptome. This study presents a framework for the screening of RBP activities based on computational modeling of mRNA stability programs in cancer and highlights the role of post-transcriptional gene dysregulation in RCC. Perron et al. develop a computational approach that models the functional activity of RBPs in individual cancer samples by monitoring their associated RNA stability programs. Applying this method to renal cell carcinoma transcriptomes, the authors identify RBPs that enhance cancer-associated pathways including hypoxia and cell cycle

    Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

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    Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

    Rhesus TRIM5α disrupts the HIV-1 capsid at the inter-hexamer interfaces

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    TRIM proteins play important roles in the innate immune defense against retroviral infection, including human immunodeficiency virus type-1 (HIV-1). Rhesus macaque TRIM5α (TRIM5αrh) targets the HIV-1 capsid and blocks infection at an early post-entry stage, prior to reverse transcription. Studies have shown that binding of TRIM5α to the assembled capsid is essential for restriction and requires the coiled-coil and B30.2/SPRY domains, but the molecular mechanism of restriction is not fully understood. In this study, we investigated, by cryoEM combined with mutagenesis and chemical cross-linking, the direct interactions between HIV-1 capsid protein (CA) assemblies and purified TRIM5αrh containing coiled-coil and SPRY domains (CC-SPRYrh). Concentration-dependent binding of CC-SPRYrh to CA assemblies was observed, while under equivalent conditions the human protein did not bind. Importantly, CC-SPRYrh, but not its human counterpart, disrupted CA tubes in a non-random fashion, releasing fragments of protofilaments consisting of CA hexamers without dissociation into monomers. Furthermore, such structural destruction was prevented by inter-hexamer crosslinking using P207C/T216C mutant CA with disulfide bonds at the CTD-CTD trimer interface of capsid assemblies, but not by intra-hexamer crosslinking via A14C/E45C at the NTD-NTD interface. The same disruption effect by TRIM5αrh on the inter-hexamer interfaces also occurred with purified intact HIV-1 cores. These results provide insights concerning how TRIM5α disrupts the virion core and demonstrate that structural damage of the viral capsid by TRIM5α is likely one of the important components of the mechanism of TRIM5α-mediated HIV-1 restriction. © 2011 Zhao et al

    First Test Results of the Trans-Impedance Amplifier Stage of the Ultra-fast HPSoC ASIC

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    We present the first results from the HPSoC ASIC designed for readout of Ultra-fast Silicon Detectors. The 4-channel ASIC manufactured in 65 nm CMOS by TSMC has been optimized for 50 um thick AC-LGAD. The evaluation of the analog front end with \b{eta}-particles impinging on 3x3 AC-LGAD arrays (500 um pitch, 200x200 um2 metal) confirms a fast output rise time of 600 ps and good timing performance with a jitter of 45 ps. Further calibration experiments and TCT laser studies indicate some gain limitations that are being investigated and are driving the design of the second-generation pre-amplification stages to reach a jitter of 15 ps.Comment: 7 pages, 6 figure

    The long-run behaviour of the terms of trade between primary commodities and manufactures : a panel data approach

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    This paper examines the Prebisch and Singer hypothesis using a panel of twenty-four commodity prices from 1900 to 2010. The modelling approach stems from the need to meet two key concerns: (i) the presence of cross-sectional dependence among commodity prices; and (ii) the identification of potential structural breaks. To address these concerns, the Hadri and Rao (Oxf Bull Econ Stat 70:245–269, 2008) test is employed. The findings suggest that all commodity prices exhibit a structural break whose location differs across series, and that support for the Prebisch and Singer hypothesis is mixed. Once the breaks are removed from the underlying series, the persistence of commodity price shocks is shorter than that obtained in other studies using alternative methodologies.info:eu-repo/semantics/publishedVersio

    Derivation of consistent hard rock (1000<Vs<3000 m/s) GMPEs from surface and down-hole recordings: Analysis of KiK-net data

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    A key component in seismic hazard assessment is the estimation of ground motion for hard rock sites, either for applications to installations built on this site category, or as an input motion for site response computation. Empirical ground motion prediction equations (GMPEs) are the traditional basis for estimating ground motion while VS30 is the basis to account for site conditions. As current GMPEs are poorly constrained for VS30 larger than 1000 m/s, the presently used approach for estimating hazard on hard rock sites consists of “host-to-target” adjustment techniques based on VS30 and Îș0 values. The present study investigates alternative methods on the basis of a KiK-net dataset corresponding to stiff and rocky sites with 500 < VS30 < 1350 m/s. The existence of sensor pairs (one at the surface and one in depth) and the availability of P- and S-wave velocity profiles allow deriving two “virtual” datasets associated to outcropping hard rock sites with VS in the range [1000, 3000] m/s with two independent corrections: 1/down-hole recordings modified from within motion to outcropping motion with a depth correction factor, 2/surface recordings deconvolved from their specific site response derived through 1D simulation. GMPEs with simple functional forms are then developed, including a VS30 site term. They lead to consistent and robust hard-rock motion estimates, which prove to be significantly lower than host-to-target adjustment predictions. The difference can reach a factor up to 3–4 beyond 5 Hz for very hard-rock, but decreases for decreasing frequency until vanishing below 2 Hz
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