1,763 research outputs found

    Plate motions recorded in tectonostratigraphic terranes of the Franciscan Complex and evolution of the Mendocino triple junction, northwestern California

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    The Mendocino triple junction area of northern California is underlain by the Coastal belt of the Franciscan complex, flanked on the east by the Central and Eastern belts of the Franciscan Complex. The coastal belt is further divided into three tectonostratigraphic terranes. Upper Cretaceous through middle Miocene rocks included in these terranes were accreted to the North American plate margin partly during normal convergence with the Farallon plate between 49 and 25 Ma at poleward rates of 2 to 5cm /yr, and partly during translation with the Pacific plate between 14 and 2 Ma at poleward rates of 3 to 6cm/yr. The evolution of the triple junction is discussed. -from Author

    Short-term dietary supplementation with fructose accelerates gastric emptying of a fructose but not a glucose solution

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    Objective Short-term dietary glucose supplementation has been shown to accelerate the gastric emptying rate of both glucose and fructose solutions. The aim of this study was to examine gastric emptying rate responses to monosaccharide ingestion following short-term dietary fructose supplementation. Methods The gastric emptying rate of a fructose solution containing 36 g of fructose and an equicaloric glucose solution containing 39.6 g glucose monohydrate were measured in 10 healthy non-smoking men with and without prior fructose supplementation (water control) using a randomized crossover design. Gastric emptying rate was assessed for a period of 1 h using the [13C]breath test with sample collections at baseline and 10-min intervals following drink ingestion. Additionally, appetite ratings of hunger, fullness, and prospective food consumption were recorded at baseline and every 10 min using visual analog scales. Results Increased dietary fructose ingestion resulted in significantly accelerated half-emptying time of a fructose solution (mean = 48, SD = 6 versus 58, SD = 14 min control; P = 0.037), whereas the emptying of a glucose solution remained unchanged (mean = 85, SD = 31 versus 78, SD = 27 min control; P = 0.273). Time of maximal emptying rate of fructose was also significantly accelerated following increased dietary fructose intake (mean = 33, SD = 6 versus 38, SD = 9 min control; P = 0.042), while it remained unchanged for glucose (mean = 45, SD = 14 versus 44, SD = 14 min control; P = 0.757). No effects of supplementation were observed for appetite measures. Conclusion Three d of supplementation with 120 g/d of fructose resulted in an acceleration of gastric emptying rate of a fructose solution but not a glucose solution

    RNA-directed activation of cytoplasmic ayriein-1 in reconstituted transport RNPs

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    Polarised mRNA transport is a prevalent mechanism for spatial control of protein synthesis. However, the composition of transported ribonucleoprotein particles (RNPs) and the regulation of their movement are poorly understood. We have reconstituted microtubule minus end-directed transport of mRNAs using purified components. A Bicaudal-D (BicD) adaptor protein and the RNA-binding protein Egalitarian (Egl) are sufficient for long-distance mRNA transport by the dynein motor and its accessory complex dynactin, thus defining a minimal transport-competent RNP. Unexpectedly, the RNA is required for robust activation of dynein motility. We show that a cis-acting RNA localisation signal promotes the interaction of Egl with BicD, which licenses the latter protein to recruit dynein and dynactin. Our data support a model for BicD activation based on RNA-induced occupancy of two Egl-binding sites on the BicD dimer. Scaffolding of adaptor protein assemblies by cargoes is an attractive mechanism for regulating intracellular transport

    A new concept for the combination of optical interferometers and high-resolution spectrographs

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    The combination of high spatial and spectral resolution in optical astronomy enables new observational approaches to many open problems in stellar and circumstellar astrophysics. However, constructing a high-resolution spectrograph for an interferometer is a costly and time-intensive undertaking. Our aim is to show that, by coupling existing high-resolution spectrographs to existing interferometers, one could observe in the domain of high spectral and spatial resolution, and avoid the construction of a new complex and expensive instrument. We investigate in this article the different challenges which arise from combining an interferometer with a high-resolution spectrograph. The requirements for the different sub-systems are determined, with special attention given to the problems of fringe tracking and dispersion. A concept study for the combination of the VLTI (Very Large Telescope Interferometer) with UVES (UV-Visual Echelle Spectrograph) is carried out, and several other specific instrument pairings are discussed. We show that the proposed combination of an interferometer with a high-resolution spectrograph is indeed feasible with current technology, for a fraction of the cost of building a whole new spectrograph. The impact on the existing instruments and their ongoing programs would be minimal.Comment: 27 pages, 9 figures, Experimental Astronomy; v2: accepted versio

    On the Importance of Countergradients for the Development of Retinotopy: Insights from a Generalised Gierer Model

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    During the development of the topographic map from vertebrate retina to superior colliculus (SC), EphA receptors are expressed in a gradient along the nasotemporal retinal axis. Their ligands, ephrin-As, are expressed in a gradient along the rostrocaudal axis of the SC. Countergradients of ephrin-As in the retina and EphAs in the SC are also expressed. Disruption of any of these gradients leads to mapping errors. Gierer's (1981) model, which uses well-matched pairs of gradients and countergradients to establish the mapping, can account for the formation of wild type maps, but not the double maps found in EphA knock-in experiments. I show that these maps can be explained by models, such as Gierer's (1983), which have gradients and no countergradients, together with a powerful compensatory mechanism that helps to distribute connections evenly over the target region. However, this type of model cannot explain mapping errors found when the countergradients are knocked out partially. I examine the relative importance of countergradients as against compensatory mechanisms by generalising Gierer's (1983) model so that the strength of compensation is adjustable. Either matching gradients and countergradients alone or poorly matching gradients and countergradients together with a strong compensatory mechanism are sufficient to establish an ordered mapping. With a weaker compensatory mechanism, gradients without countergradients lead to a poorer map, but the addition of countergradients improves the mapping. This model produces the double maps in simulated EphA knock-in experiments and a map consistent with the Math5 knock-out phenotype. Simulations of a set of phenotypes from the literature substantiate the finding that countergradients and compensation can be traded off against each other to give similar maps. I conclude that a successful model of retinotopy should contain countergradients and some form of compensation mechanism, but not in the strong form put forward by Gierer

    Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

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    BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

    Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension

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    Background Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-naïve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants. Methods AMBITION was an event-driven, double-blind study in which participants were randomized 2:1:1 to once-daily initial combination therapy with ambrisentan 10 mg plus tadalafil 40 mg, ambrisentan 10 mg plus placebo, or tadalafil 40 mg plus placebo. In this pre-specified subgroup analysis, we compared the efficacy data between those with functional class (FC) II vs. FC III symptoms at baseline. Results This analysis included 500 participants in the previously defined primary analysis set (n = 155 FC II, n = 345 FC III). Comparing combination therapy to pooled monotherapy, the risk of clinical failure events was reduced by 79% (hazard ratio, 0.21 [95% confidence interval: 0.071, 0.63]) for FC II patients and 42% (hazard ratio, 0.58 [95% confidence interval: 0.39, 0.86]) for FC III patients. In a post-hoc analysis, the risk of first hospitalization for worsening PAH was also reduced by combination therapy, particularly for FC II patients (0 combination vs. 11 [14%] pooled monotherapy). Adverse events were frequent but comparable between the subgroups. Conclusions Treatment benefit from initial combination therapy appeared at least as great for FC II as for FC III participants. Hospitalizations for worsening PAH were not observed in FC II participants assigned to combination. The present data support an initial combination strategy for newly diagnosed patients even when symptoms are less severe
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