3,137 research outputs found

    Electrochemical Characterization of Platinum Nanotubules Made via Template Wetting Nanofabrication

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    Standard oxidation-reduction reactions such as those of ferrocyanide and ferrocene have long been employed in evaluating and comparing new electrode structures with more traditional configurations. A variety of nanostructured carbon electrodes developed in recent years have been reported to exhibit faster electron transfer kinetics than more traditional carbon structures when studied with these redox reactions. This type of comparison has not been widely explored for nanostructured platinum electrodes that have become increasingly common. In this work, a platinum nanotubule array electrode was fabricated via a simple template-based process and evaluated using the standard ferrocyanide redox reaction. The nanotubule array electrodes were observed to more closely approach ideal reversible behavior than a typical Pt black/Nafion fuel cell electrode or a standard polished Pt disc electrode. The apparent heterogeneous electron transfer coefficient was determined using the Nicholson method and found to be one to two orders of magnitude greater for the nanotubule array electrodes, depending on the diameter of the nanotubules, in comparison with these same two more traditional electrode structures

    Intrinsic Disorder within an AKAP-protein Kinase A Complex Guides Local Substrate Phosphorylation

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    Anchoring proteins sequester kinases with their substrates to locally disseminate intracellular signals and avert indiscriminate transmission of these responses throughout the cell. Mechanistic understanding of this process is hampered by limited structural information on these macromolecular complexes. A-kinase anchoring proteins (AKAPs) spatially constrain phosphorylation by cAMP-dependent protein kinases (PKA). Electron microscopy and three-dimensional reconstructions of type-II PKA-AKAP18γ complexes reveal hetero-pentameric assemblies that adopt a range of flexible tripartite configurations. Intrinsically disordered regions within each PKA regulatory subunit impart the molecular plasticity that affords an ∟16 nanometer radius of motion to the associated catalytic subunits. Manipulating flexibility within the PKA holoenzyme augmented basal and cAMP responsive phosphorylation of AKAP-associated substrates. Cell-based analyses suggest that the catalytic subunit remains within type-II PKA-AKAP18γ complexes upon cAMP elevation. We propose that the dynamic movement of kinase sub-structures, in concert with the static AKAP-regulatory subunit interface, generates a solid-state signaling microenvironment for substrate phosphorylation

    Outbreak of Aeromonas hydrophila wound infections association with mud football

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    On 16 February 2002, a total of 26 people presented to the emergency department of the local hospital in the rural town of Collie in southwest Western Australia with many infected scratches and pustules distributed over their bodies. All of the patients had participated in a “mud football” competition the previous day, in which there had been 100 participants. One patient required removal of an infected thumbnail, and another required surgical debridement of an infected toe. Aeromonas hydrophila was isolated from all 3 patients from whom swab specimens were obtained. To prepare the mud football fields, a paddock was irrigated with water that was pumped from an adjacent river during the 1-month period before the competition. A. hydrophila was subsequently isolated from a water sample obtained from the river. This is the first published report of an outbreak of A. hydrophila wound infections associated with exposure to mud.Hassan Vally, Amanda Whittle, Scott Cameron, Gary K. Dowse and Tony Watso

    Thrombocytosis and abnormal liver enzymes:A trigger for investigation of underlying malignancy

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    BackgroundThrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy, guidelines for investigating thrombocytosis in the absence of red flag symptoms remain unclear. A novel automated system of laboratory analysis, intelligent Liver Function Testing (iLFT), launched in Tayside in 2018 and has identified a patient group with thrombocytosis and abnormal liver test (LFT) results. This study analysed the outcome of these patients and investigated the use of thrombocytosis combined with LFTs in predicting risk of cancer.Methods and findingsBetween August 2018 and August 2020, 6792 patients underwent iLFT, with 246 found to have both thrombocytosis and at least one abnormal LFT. A random case-matched control group of 492 iLFT patients with normal platelet count and at least one abnormal LFT was created. 7.7% (95% CI 4.7-11.8%) of patients with thrombocytosis had cancer compared to 2.0% (1.0-3.7%) of controls. Patients ConclusionsThese findings suggest a substantial increased risk of cancer in patients with thrombocytosis and raised ALP. This could be developed as an adjunct to current investigation algorithms, highlighting high-risk patients and prompting further investigation (such as computed tomography scans) where indicated

    The Spatiotemporal Regulation of cAMP Signaling in Blood Platelets—Old Friends and New Players

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    Atherothrombosis, the pathology underlying numerous cardiovascular diseases, is a major cause of death globally. Hyperactive blood platelets play a key role in the atherothrombotic process through the release of inflammatory mediators and formation of thrombi. In healthy blood vessels, excessive platelet activation is restricted by endothelial-derived prostacyclin (PGI2) through cyclic adenosine-5′-monophosphate (cAMP) and protein kinase A (PKA)-dependent mechanisms. Elevation in intracellular cAMP is associated with the control of a number of distinct platelet functions including actin polymerisation, granule secretion, calcium mobilization and integrin activation. Unfortunately, in atherosclerotic disease the protective effects of cAMP are compromised, which may contribute to pathological thrombosis. The cAMP signaling network in platelets is highly complex with the presence of multiple isoforms of adenylyl cyclase (AC), PKA, and phosphodiesterases (PDEs). However, a precise understanding of the relationship between specific AC, PKA, and PDE isoforms, and how individual signaling substrates are targeted to control distinct platelet functions is still lacking. In other cells types, compartmentalisation of cAMP signaling has emerged as a key mechanism to allow precise control of specific cell functions. A-kinase anchoring proteins (AKAPs) play an important role in this spatiotemporal regulation of cAMP signaling networks. Evidence of AKAP-mediated compartmentalisation of cAMP signaling in blood platelets has begun to emerge and is providing new insights into the regulation of platelet function. Dissecting the mechanisms that allow cAMP to control excessive platelet activity without preventing effective haemostasis may unleash the possibility of therapeutic targeting of the pathway to control unwanted platelet activity

    Wigner Crystal in One Dimension

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    A one--dimensional gas of electrons interacting with long--range Coulomb forces (V(r)≈1/rV(r) \approx 1/r) is investigated. The excitation spectrum consists of separate collective charge and spin modes, with the charge excitation energies in agreement with RPA calculations. For arbitrarily weak Coulomb repulsion density correlations at wavevector 4kF4k_F decay extremely slowly and are best described as those of a one--dimensional Wigner crystal. Pinning of the Wigner crystal then leads to the nonlinear transport properties characteristic of CDW. The results allow a consistent interpretation of the plasmon and spin excitations observed in one--dimensional semiconductor structures, and suggest an interpretation of some of the observed features in terms of ``spinons''. A possible explanation for nonlinear transport phenomena is given.Comment: 10 pages, RevTe

    Estimates of unresolved point sources contribution to WMAP 5

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    We present an alternative estimate of the unresolved point source contribution to the WMAP temperature power spectrum based on current knowledge of sources from radio surveys in the 1.4-90 GHz range. We implement a stochastic extrapolation of radio point sources in the NRAO-VLA Sky Survey (NVSS) catalog, from the original 1.4 GHz to the ~ 100 GHz frequency range relevant for CMB experiments. With a bootstrap approach, we generate an ensemble of realizations that provides the probability distribution for the flux of each NVSS source at the final frequency. The predicted source counts agree with WMAP results for S > 1 Jy and the corresponding sky maps correlate with WMAP observed maps in Q-, V- and W- bands, for sources with flux S > 0.2 Jy. The low-frequency radio surveys found a steeper frequency dependence for sources just below the WMAP nominal threshold than the one estimated by the WMAP team. This feature is present in our simulations and translates into a shift of 0.3-0.4 \sigma in the estimated value of the tilt of the power spectrum of scalar perturbation, n_s, as well as \omega_c. This approach demonstrates the use of external point sources datasets for CMB data analysis.Comment: 12 pages, 8 figures, to be published on MNRA

    Advanced Imaging and Receipt of Guideline Concordant Care in Women with Early Stage Breast Cancer

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    Objective. It is unknown whether advanced imaging (AI) is associated with higher quality breast cancer (BC) care. Materials and Methods. Claims and Surveillance Epidemiology and End Results data were linked for women diagnosed with incident stage I-III BC between 2002 and 2008 in western Washington State. We examined receipt of preoperative breast magnetic resonance imaging (MRI) or AI (defined as computed tomography [CT]/positron emission tomography [PET]/PET/CT) versus mammogram and/or ultrasound (M-US) alone and receipt of guideline concordant care (GCC) using multivariable logistic regression. Results. Of 5247 women, 67% received M-US, 23% MRI, 8% CT, and 3% PET/PET-CT. In 2002, 5% received MRI and 5% AI compared to 45% and 12%, respectively, in 2008. 79% received GCC, but GCC declined over time and was associated with younger age, urban residence, less comorbidity, shorter time from diagnosis to surgery, and earlier year of diagnosis. Breast MRI was associated with GCC for lumpectomy plus radiation therapy (RT) (OR 1.55, 95% CI 1.08–2.26, and p=0.02) and AI was associated with GCC for adjuvant chemotherapy for estrogen-receptor positive (ER+) BC (OR 1.74, 95% CI 1.17–2.59, and p=0.01). Conclusion. GCC was associated with prior receipt of breast MRI and AI for lumpectomy plus RT and adjuvant chemotherapy for ER+ BC, respectively
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