591 research outputs found

    Executive computer program for linking independent computer programs: ODINEX

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    Program controls sequence of execution of network of program elements and maintains data base of common information which forms communication link among them. Approach is applicable to any multiple-program task

    Repository as a Service (RaaS)

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    In his oft-quoted seminal paper ‘Institutional Repositories: Essential Infrastructure For Scholarship In The Digital Age’ Clifford Lynch (2003) described the Institutional Repository as “a set of services that a university offers to the members of its community for the management and dissemination of digital materials created by the institution and its community members.” This paper seeks instead to define the repository service at a more primitive level, without the specialism of being an ‘Institutional Repository’, and looks at how it can viewed as providing a service within appropriate boundaries, and what that could mean for the future development of repositories, our expectations of what repositories should be, and how they could fit into the set of services required to deliver an Institutional Repository service as describe by Lynch

    Adenylyl Cyclase Isoform Specific Effects in Lipid Raft and Non-Lipid Raft Membrane Domains Regulate cAMP Compartmentation in Human Airway Smooth Muscle Cells

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    The formation of distinct macromolecular signaling complexes allows different G-protein coupled receptors to produce diverse functional responses, even while sharing a common second messenger such as cAMP. In human airway smooth muscle (HASM) cells, segregation of specific receptors into different membrane microdomains is thought to critically aid in generating compartmentalized cAMP responses. Whereas, E type prostaglandin receptors (EPRs) have been shown to be expressed in non-lipid raft domains of the plasma membrane, β-Adrenergic receptors (βARs) are predominantly expressed in caveolar lipid rafts. In the present study, we tested the hypothesis that adenylyl cyclase type 2 (AC2) preferentially couples to EPRs in a non-lipid raft domain, while adenylyl cyclase type 6 (AC6) selectively couples to βARs in lipid rafts. To do this, we examined the effect of overexpressing AC2 and AC6 on cAMP responses detected using genetically-encoded FRET-based biosensors targeted to lipid raft and non-lipid raft domains of the plasma membrane, as well as the bulk cytosolic compartment in HASM cells. This approach has the advantage of measuring the kinetics of cAMP production in living cells without the use of PDE inhibitors. Overexpression of AC2 enhanced the cAMP response to EPR activation associated with non-lipid raft domains, without significantly affecting responses detected elsewhere. AC2 overexpression also had no effect on cAMP responses to βAR activation detected in any subcellular location. These data confirm the hypothesis that AC2 couples exclusively with EPRs in a non-lipid raft membrane compartment. Overexpression of AC6, on the other hand, actually decreased the response to βAR stimulation associated with lipid rafts, without significantly affecting responses elsewhere. AC6 overexpression also had no effect on the responses to EPR activation detected anywhere in the cell. The ability of AC6 overexpression to inhibit βAR production of cAMP in lipid raft domains was reversed by inhibition of PDE4 activity with rolipram. It was also reversed by overexpression of Ht31 peptide, which disrupts the interaction of protein kinase A with A-kinase anchoring proteins (AKAPs). These results suggests that AC6 overexpression upregulates and/or recruits PKA and PDE4 activity, which then reduces βAR production of cAMP associated specifically with lipid raft domains

    Imaging and treatment of posttraumatic ankle and hindfoot osteoarthritis

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    Posttraumatic osteoarthritis of the ankle and hindfoot is a common and frequently debil-itating disorder. 70% to 90% of ankle osteoarthritis is related to prior trauma that encompasses a spectrum of disorders including fractures and ligamentous injuries that either disrupt the articular surface or result in instability of the joint. In addition to clinical evaluation, imaging plays a sub-stantial role in the treatment planning of posttraumatic ankle and hindfoot osteoarthritis. Imaging evaluation must be tailored to specific clinical scenarios and includes weight bearing radiography that utilizes standard and specialty views, computed tomography which can be performed with a standard or a weight bearing technique, magnetic resonance imaging, and ultrasound evaluation. This review article aims to familiarize the reader with treatment rationale, to provide a brief review of surgical techniques and to illustrate expected imaging appearances of common operative procedures performed in the setting of posttraumatic ankle and hindfoot osteoarthritis, such as joint‐preserving procedures, ankle fusion, subtalar fusion, tibiotalarcalcaneal fusion and ankle arthroplasty. Preoperative findings will be discussed along with the expected postoperative ap-pearance of various procedures in order to improve detection of their complications on imaging and to provide optimal patient care

    Direct Visualization of 3-Dimensional Force and Energy Map of a Single Molecular Switch

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    Mechanical properties of molecules adsorbed on materials surfaces are increasingly vital for the applications of molecular thin films. Here, we conduct a fundamental research to induce conformational change mechanically on a single molecule and quantify the driving force needed for such molecular shape switch via a low temperature (~ 5K) Scanning Tunneling Microscope (STM) and Qplus Atomic Force Microscope (Q+AFM). Our measurement maps a three-dimensional landscape for mechanical potential and force at single molecule level with high spatial resolution in all three dimensions of a few angstrom (10-10 m). Molecule TBrPP-Co (a cobalt porphyrin) deposited on an atomically clean gold substrate typically has two of its pentagon rings tilted upward and the other two downward. An atomically sharp tip of the STM/Q+AFM, which vibrates with a high frequency (~ 30kHz), is employed to scan the molecule at different heights with 0.1Å increment and meanwhile record tip-molecule interaction strength in the form of tip frequency change. When tip approaches to the threshold distance to the molecule, mechanical force become large enough and cause pentagon rings flip their direction. Due to the sensitive nature of tip-molecule interaction, the rings flipping can be directly visualized by STM, as rings tilting upward exhibit two bright protrusions in contrast to rings downward in image. By processing frequency change, we obtain a three-dimensional mechanical potential and force map for a single molecule with the resolution of angstrom level in all three dimensions. Our preliminary results indicate that an energy barrier of ~400meV needs to be overcome for rings flipping of TBrPP-Co.https://digitalcommons.odu.edu/gradposters2021_sciences/1015/thumbnail.jp

    Inhibition of sarcolemmal FAT/CD36 by sulfo-N-succinimidyl oleate rapidly corrects metabolism and restores function in the diabetic heart following hypoxia/reoxygenation.

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    AIMS: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress. METHODS AND RESULTS: Hearts from type 2 diabetic and control male Wistar rats were perfused in normoxia, hypoxia and reoxygenation, with the FAT/CD36 inhibitor sulfo-N-succinimidyl oleate (SSO) infused 4 min before hypoxia. SSO infusion into diabetic hearts decreased the fatty acid oxidation rate by 29% and myocardial triglyceride concentration by 48% compared with untreated diabetic hearts, restoring fatty acid metabolism to control levels following hypoxia-reoxygenation. SSO infusion increased the glycolytic rate by 46% in diabetic hearts during hypoxia, increased pyruvate dehydrogenase activity by 53% and decreased lactate efflux rate by 56% compared with untreated diabetic hearts during reoxygenation. In addition, SSO treatment of diabetic hearts increased intermediates within the second span of the Krebs cycle, namely fumarate, oxaloacetate, and the FAD total pool. The cardiac dysfunction in diabetic hearts following decreased oxygen availability was prevented by SSO-infusion prior to the hypoxic stress. Infusing SSO into diabetic hearts increased rate pressure product by 60% during hypoxia and by 32% following reoxygenation, restoring function to control levels. CONCLUSIONS: Diabetic hearts have limited metabolic flexibility and cardiac dysfunction when stressed, which can be rapidly rectified by reducing fatty acid uptake with the FAT/CD36 inhibitor, SSO. This novel therapeutic approach not only reduces fat oxidation but also lipotoxicity, by targeting the primary step in the fatty acid metabolism pathway

    Swabian MOSES 2021: An interdisciplinary field campaign for investigating convective storms and their event chains

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    The Neckar Valley and the Swabian Jura in southwest Germany comprise a hotspot for severe convective storms, causing tens of millions of euros in damage each year. Possible reasons for the high frequency of thunderstorms and the associated event chain across compartments were investigated in detail during the hydro-meteorological field campaign Swabian MOSES carried out between May and September 2021. Researchers from various disciplines established more than 25 temporary ground-based stations equipped with state-of-the-art in situ and remote sensing observation systems, such as lidars, dual-polarization X- and C-band Doppler weather radars, radiosondes including stratospheric balloons, an aerosol cloud chamber, masts to measure vertical fluxes, autosamplers for water probes in rivers, and networks of disdrometers, soil moisture, and hail sensors. These fixed-site observations were supplemented by mobile observation systems, such as a research aircraft with scanning Doppler lidar, a cosmic ray neutron sensing rover, and a storm chasing team launching swarmsondes in the vicinity of hailstorms. Seven Intensive Observation Periods (IOPs) were conducted on a total of 21 operating days. An exceptionally high number of convective events, including both unorganized and organized thunderstorms such as multicells or supercells, occurred during the study period. This paper gives an overview of the Swabian MOSES (Modular Observation Solutions for Earth Systems) field campaign, briefly describes the observation strategy, and presents observational highlights for two IOPs

    Increased oxidative metabolism following hypoxia in the type 2 diabetic heart, despite normal hypoxia signalling and metabolic adaptation

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    Hypoxia activates the hypoxia-inducible factor (HIF), promoting glycolysis and suppressing mitochondrial respiration. In the type 2 diabetic heart, glycolysis is suppressed whereas fatty acid metabolism is promoted. The diabetic heart experiences chronic hypoxia as a consequence of increased obstructive sleep apnoea and cardiovascular disease. Given the opposing metabolic effects of hypoxia and diabetes, we questioned whether diabetes affects cardiac metabolic adaptation to hypoxia. Control and type 2 diabetic rats were housed for 3 weeks in normoxia or 11% oxygen. Metabolism and function were measured in the isolated perfused heart using radiolabelled substrates. Following chronic hypoxia, both control and diabetic hearts upregulated glycolysis, lactate efflux and glycogen content and decreased fatty acid oxidation rates, with similar activation of HIF signalling pathways. However, hypoxia-induced changes were superimposed on diabetic hearts that were metabolically abnormal in normoxia, resulting in glycolytic rates 30% lower, and fatty acid oxidation 36% higher, in hypoxic diabetic hearts than hypoxic controls. Peroxisome proliferator-activated receptor Îą target proteins were suppressed by hypoxia, but activated by diabetes. Mitochondrial respiration in diabetic hearts was divergently activated following hypoxia compared with controls. These differences in metabolism were associated with decreased contractile recovery of the hypoxic diabetic heart following an acute hypoxic insult. In conclusion, type 2 diabetic hearts retain metabolic flexibility to adapt to hypoxia, with normal HIF signalling pathways. However, they are more dependent on oxidative metabolism following hypoxia due to abnormal normoxic metabolism, which was associated with a functional deficit in response to stress
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