725 research outputs found

    Major Element Composition of Sediments in Terms of Weathering and Provenance: Implications for Crustal Recycling

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    The elemental composition of a sediment is set by the composition of its protolithand modified by weathering, sorting, and diagenesis. An important problem is deconvolving these contributions to a sediment’s composition to arrive at information about processesthat operate on the Earth’s surface. We approach this problem by developing a predictive andinvertible model of sedimentary major-element composition. We compile a dataset of sedimentary rock, river sediment, soil, and igneous rock compositions. Principal componentanalysis of the dataset shows that most variation can be simplified to a small number of variables. We thus show that any sediment’s composition can be described with just two vectorsof igneous evolution and weathering. We hence define a model for sedimentary compositionas a combination of these processes. A 1:1 correspondence is observed between predictionsand independent data. The log-ratios ln(K 2 O/MgO) and ln(Al 2 O 3 /Na 2 O) are found to besimple proxies for respectively the model’s protolith and weathering indices. Significant deviations from the model can be explained by sodium-calcium exchange. Using this approach,we show that the major-element composition of the upper continental crust has been modified by weathering and we calculate the amount of each element that it must have lost tomodify it to its present composition. By extrapolating modern weathering rates over the ageof the crust we conclude that it has not retained a significant amount of the necessarily produced weathering restite. This restite has likely been subducted into the mantle, indicating acrust-to-mantle recycling rate of 1.33 ± 0.89 × 10 13 kg yr −1 .</p

    MicroRNA-34a promotes genomic instability by a broad suppression of genome maintenance mechanisms downstream of the oncogene KSHV-vGPCR

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    The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded chemokine receptor vGPCR acts as an oncogene in Kaposi's sarcomagenesis. Until now, the molecular mechanisms by which the vGPCR contributes to tumor development remain incompletely understood. Here, we show that the KSHV-vGPCR contributes to tumor progression through microRNA (miR)-34a-mediated induction of genomic instability. Large-scale analyses on the DNA, gene and protein level of cell lines derived from a mouse model of vGPCR-driven tumorigenesis revealed that a vGPCR-induced upregulation of miR-34a resulted in a broad suppression of genome maintenance genes. A knockdown of either the vGPCR or miR-34a largely restored the expression of these genes and confirmed miR-34a as a downstream effector of the KSHV-vGPCR that compromises genome maintenance mechanisms. This novel, protumorigenic role of miR-34a questions the use of miR-34a mimetics in cancer therapy as they could impair genome stability

    Salmeterol for the prevention of high-altitude pulmonary edema.

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    BACKGROUND: Pulmonary edema results from a persistent imbalance between forces that drive water into the air space and the physiologic mechanisms that remove it. Among the latter, the absorption of liquid driven by active alveolar transepithelial sodium transport has an important role; a defect of this mechanism may predispose patients to pulmonary edema. Beta-adrenergic agonists up-regulate the clearance of alveolar fluid and attenuate pulmonary edema in animal models. METHODS: In a double-blind, randomized, placebo-controlled study, we assessed the effects of prophylactic inhalation of the beta-adrenergic agonist salmeterol on the incidence of pulmonary edema during exposure to high altitudes (4559 m, reached in less than 22 hours) in 37 subjects who were susceptible to high-altitude pulmonary edema. We also measured the nasal transepithelial potential difference, a marker of the transepithelial sodium and water transport in the distal airways, in 33 mountaineers who were prone to high-altitude pulmonary edema and 33 mountaineers who were resistant to this condition. RESULTS: Prophylactic inhalation of salmeterol decreased the incidence of high-altitude pulmonary edema in susceptible subjects by more than 50 percent, from 74 percent with placebo to 33 percent (P=0.02). The nasal potential-difference value under low-altitude conditions was more than 30 percent lower in the subjects who were susceptible to high-altitude pulmonary edema than in those who were not susceptible (P&lt;0.001). CONCLUSIONS: Prophylactic inhalation of a beta-adrenergic agonist reduces the risk of high-altitude pulmonary edema. Sodium-dependent absorption of liquid from the airways may be defective in patients who are susceptible to high-altitude pulmonary edema. These findings support the concept that sodium-driven clearance of alveolar fluid may have a pathogenic role in pulmonary edema in humans and therefore represent an appropriate target for therapy

    Neural changes associated with appetite information processing in schizophrenic patients after 16 weeks of olanzapine treatment

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    There is evidence that some atypical antipsychotics, including olanzapine, can produce unwanted metabolic side effects, weight gain and diabetes. However, neuronal correlates of change related to food information processing have not been investigated with these medications. We studied the effect of a pharmacological manipulation with an antipsychotic known to cause weight gain on metabolites, cognitive tasks and neural correlates related to food regulation. We used functional magnetic resonance imaging in conjunction with a task requiring visual processing of appetitive stimuli in schizophrenic patients and healthy controls before and after 16 weeks of antipsychotic medication with olanzapine. In patients, the psychological and neuronal changes associated following the treatment correlated with appetite control measures and metabolite levels in fasting blood samples. After 16 weeks of olanzapine treatment, the patients gained weight, increased their waist circumference, had fewer positive schizophrenia symptoms, a reduced ghrelin plasma concentration and an increased concentration of triglycerides, insulin and leptin. In premotor area, somatosensory cortices as well as bilaterally in the fusiform gyri, the olanzapine treatment increased the neural activity related to appetitive information in schizophrenic patients to similar levels relative to healthy individuals. However, a higher increase in sensitivity to appetitive stimuli after the treatment was observed in insular cortices, amygdala and cerebellum in schizophrenic patients as compared with healthy controls. Furthermore, these changes in neuronal activity correlated with changes in some metabolites and cognitive measurements related to appetite regulation

    MicroWalk: A Framework for Finding Side Channels in Binaries

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    Microarchitectural side channels expose unprotected software to information leakage attacks where a software adversary is able to track runtime behavior of a benign process and steal secrets such as cryptographic keys. As suggested by incremental software patches for the RSA algorithm against variants of side-channel attacks within different versions of cryptographic libraries, protecting security-critical algorithms against side channels is an intricate task. Software protections avoid leakages by operating in constant time with a uniform resource usage pattern independent of the processed secret. In this respect, automated testing and verification of software binaries for leakage-free behavior is of importance, particularly when the source code is not available. In this work, we propose a novel technique based on Dynamic Binary Instrumentation and Mutual Information Analysis to efficiently locate and quantify memory based and control-flow based microarchitectural leakages. We develop a software framework named \tool~for side-channel analysis of binaries which can be extended to support new classes of leakage. For the first time, by utilizing \tool, we perform rigorous leakage analysis of two widely-used closed-source cryptographic libraries: \emph{Intel IPP} and \emph{Microsoft CNG}. We analyze 1515 different cryptographic implementations consisting of 112112 million instructions in about 105105 minutes of CPU time. By locating previously unknown leakages in hardened implementations, our results suggest that \tool~can efficiently find microarchitectural leakages in software binaries

    The composition and weathering of the continents over geologic time

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    The composition of continental crust records the balance between construction by tectonics and destruction by physical and chemical erosion. Quantitative constraints on how igneous addition and chemical weathering have modified the continents' bulk composition are essential for understanding the evolution of geodynamics and climate. Using novel data analytic techniques we have extracted temporal trends in sediments' protolith composition and weathering intensity from the largest available compilation of sedimentary major element compositions: ~15,000 samples from 4.0 Ga to the present. We find that the average Archean upper continental crust was silica-rich and had a similar compositional diversity to modern continents. This is consistent with an early Archean, or earlier, onset of plate tectonics. In the Archean, chemical weathering sequestered ~25 % more CO2 per mass eroded for the same weathering intensity than in subsequent time periods, consistent with carbon mass balance despite higher Archean outgassing rates and more limited continental exposure. Since 2.0 Ga, over long (>0.5 Gyr) timescales, crustal weathering intensity has remained relatively constant. Onshorter timescales over the Phanerozoic, weathering intensity is correlated to global climate state, consistent with a weathering feedback acting in response to changes in CO2 sources or sinks.AGL is funded by the Natural Environment Research Council Grantham Institute SSCP DTP (grant number NE/L002515/1). OS acknowledges support from NERC grants NE/T012455/1 and NE/T00696X/1. This work was supported by CAS

    The composition and weathering of the continents over geologic time

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    The composition of continental crust records the balance between construction by tectonics and destruction by physical and chemical erosion. Quantitative constraints on how igneous addition and chemical weathering have modified the continents’ bulk composition are essential for understanding the evolution of geodynamics and climate. Using novel data-analytic techniques we have extracted temporal trends in sediments’ protolith composition and weathering intensity from the largest available compilation of sedimentary major-element compositions: ∼ 15,000 samples from 4.0 Ga to the present. We find that the average Archean upper continental crust was silica rich and had a similar compositional diversity to modern continents. This is consistent with an early-Archean, or earlier, onset of plate tectonics. In the Archean, chemical weathering sequestered ∼ 25 % more CO2 per mass eroded for the same weathering intensity than in subsequent time periods, consistent with carbon mass-balance despite higher Archean outgassing rates and more limited continental exposure. Since 2.0 Ga, over long (> 0.5 Ga) timescales, crustal weathering intensity has remained relatively constant. On shorter timescales over the Phanerozoic, weathering intensity is correlated to global climate state, consistent with a weathering feedback acting in response to changes in CO2 sources or sinks
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