97 research outputs found

    Elastic turbulence in two-dimensional Taylor-Couette flows

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    We report the onset of elastic turbulence in a two-dimensional Taylor-Couette geometry using numerical solutions of the Oldroyd-B model, also performed at high Weissenberg numbers with the program OpenFOAM. Beyond a critical Weissenberg number, an elastic instability causes a supercritical transition from the laminar Taylor-Couette to a turbulent flow. The order parameter, the time average of secondary-flow strength, follows the scaling law Φ(WiWic)γ\Phi \propto (\mathrm{Wi} -\mathrm{Wi}_c)^{\gamma} with Wic=10\mathrm{Wi}_c=10 and γ=0.45\gamma = 0.45. The power spectrum of the velocity fluctuations shows a power-law decay with a characteristic exponent, which strongly depends on the radial position. It is greater than two, which we relate to the dimension of the geometry

    Exploring Large Document Repositories with RDF Technology: The DOPE Project

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    This thesaurus-based search system uses automatic indexing, RDF-based querying, and concept-based visualization of results to support exploration of large online document repositories

    Mouse repeated electroconvulsive seizure (ECS) does not reverse social stress effects but does induce behavioral and hippocampal changes relevant to electroconvulsive therapy (ECT) side-effects in the treatment of depression

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    Electroconvulsive therapy (ECT) is an effective treatment for depression, but can have negative side effects including amnesia. The mechanisms of action underlying both the antidepressant and side effects of ECT are not well understood. An equivalent manipulation that is conducted in experimental animals is electroconvulsive seizure (ECS). Rodent studies have provided valuable insights into potential mechanisms underlying the antidepressant and side effects of ECT. However, relatively few studies have investigated the effects of ECS in animal models with a depression-relevant manipulation such as chronic stress. In the present study, mice were first exposed to chronic social stress (CSS) or a control procedure for 15 days followed by ECS or a sham procedure for 10 days. Behavioral effects were investigated using an auditory fear conditioning (learning) and expression (memory) test and a treadmill-running fatigue test. Thereafter, immunohistochemistry was conducted on brain material using the microglial marker Iba-1 and the cholinergic fibre marker ChAT. CSS did not increase fear learning and memory in the present experimental design; in both the control and CSS mice ECS reduced fear learning and fear memory expression. CSS induced the expected fatigue-like effect in the treadmill-running test; ECS induced increased fatigue in CSS and control mice. In CSS and control mice ECS induced inflammation in hippocampus in terms of increased expression of Iba-1 in radiatum of CA1 and CA3. CSS and ECS both reduced acetylcholine function in hippocampus as indicated by decreased expression of ChAT in several hippocampal sub-regions. Therefore, CSS increased fatigue and reduced hippocampal ChAT activity and, rather than reversing these effects, a repeated ECS regimen resulted in impaired fear learning-memory, increased fatigue, increased hippocampal Iba-1 expression, and decreased hippocampal ChAT expression. As such, the current model does not provide insights into the mechanism of ECT antidepressant function but does provide evidence for pathophysiological mechanisms that might contribute to important ECT side-effects.</p

    Structural changes in commercial agriculture

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    The basic idea of the conference on Structural Changes in Commercial Agriculture was planted in the spring of 1964 by Earl 0. Heady. He outlined for the North Central Farm Management Research Committee his concern about the kind and amount of response to both current and prospective structural changes in the commercial farm firm. Many changes represent adjustments to technological and other innovations originating in marketing, research, and educational agencies serving farmers.https://lib.dr.iastate.edu/card_reports/1025/thumbnail.jp

    Development and validation of a model gene therapy biodistribution assay for AVGN7 using digital droplet polymerase chain reaction

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    Biodistribution assays are integral to gene therapy commercialization and have traditionally used real-time qPCR. Droplet digital PCR (ddPCR), however, has distinct advantages including higher sensitivity and absolute quantification but is underused because of lacking regulatory guidance and meaningful examples in the literature. We report a fit-for-purpose model process to validate a good laboratory practice (GLP)-compliant ddPCR assay for AVGN7, a Smad7 gene therapeutic for muscle wasting. Duplexed primer/probe sets for Smad7 and mouse TATA-box binding protein were optimized using gBlock DNA over a dynamic range of 10–80,000 copies/reaction in 250 ng mouse gDNA. Linearized plasmid and mouse gDNA were used for validation, which determined precision, accuracy, ruggedness/robustness, selectivity, recovery, specificity, dilution linearity, and stability. Inter-run precision and accuracy met previously established criteria with bias between −5% and 15%, coefficient of variation (CV) less than 19%, and total error within 8%–35%. The limit of detection was 2.5 copies/reaction, linearity was confirmed at 40–80,000 copies/reaction, specificity was demonstrated by single droplet populations and assay stability was demonstrated for benchtop, refrigerated storage, and repeated freeze-thaw cycles. The procedural road map provided exceeds recently established standards. It is also relevant to many IND-enabling processes, as validated ddPCR assays can be used in biodistribution studies and with vector titering and manufacturing quality control

    Prolonged deprivation of arginine or leucine induces PI3K/ Akt-dependent reactivation of mTORC1

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    The mechanistic target of rapamycin complex 1 (mTORC1) is a serine/threonine kinase complex that promotes anabolic processes including protein, lipid, and nucleotide synthesis, while suppressing catabolic processes such as macroautophagy. mTORC1 activity is regulated by growth factors and amino acids, which signal through distinct but integrated molecular pathways: growth factors largely signal through the PI3K/Aktdependent pathway, whereas the availabilities of amino acids leucine and arginine are communicated to mTORC1 by the Rag-GTPase pathway. While it is relatively well described how acute changes in leucine and arginine levels affect mTORC1 signaling, the effects of prolonged amino acid deprivation remain less well understood. Here, we demonstrate that prolonged deprivation of arginine and/or leucine leads to reactivation of mTORC1 activity, which reaches activation levels similar to those observed in nutrient-rich conditions. Surprisingly, we find that this reactivation is independent of the regeneration of amino acids by canonical autophagy or proteasomal degradation but is dependent on PI3K/Akt signaling. Together, our data identify a novel crosstalk between the amino acid and PI3K/Akt signaling pathways upstream of mTORC1. These observations extend our understanding of the role of mTORC1 in growth-related diseases and indicate that dietary intervention by removal of leucine and/or arginine may be an ineffective therapeutic approach.Gwen R.Buel and Huy Q.Dang share first authorship</p
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