466 research outputs found

    DPP6A Confers Redox Sensitivity to Kv4 Channel Inactivation

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    Hybrid tabu search – strawberry algorithm for multidimensional knapsack problem

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    Multidimensional Knapsack Problem (MKP) has been widely used to model real-life combinatorial problems. It is also used extensively in experiments to test the performances of metaheuristic algorithms and their hybrids. For example, Tabu Search (TS) has been successfully hybridized with other techniques, including particle swarm optimization (PSO) algorithm and the two-stage TS algorithm to solve MKP. In 2011, a new metaheuristic known as Strawberry algorithm (SBA) was initiated. Since then, it has been vastly applied to solve engineering problems. However, SBA has never been deployed to solve MKP. Therefore, a new hybrid of TS-SBA is proposed in this study to solve MKP with the objective of maximizing the total profit. The Greedy heuristics by ratio was employed to construct an initial solution. Next, the solution was enhanced by using the hybrid TS-SBA. The parameters setting to run the hybrid TS-SBA was determined by using a combination of Factorial Design of Experiments and Decision Tree Data Mining methods. Finally, the hybrid TS-SBA was evaluated using an MKP benchmark problem. It consisted of 270 test problems with different sizes of constraints and decision variables. The findings revealed that on average the hybrid TS-SBA was able to increase 1.97% profit of the initial solution. However, the best-known solution from past studies seemed to outperform the hybrid TS-SBA with an average difference of 3.69%. Notably, the novel hybrid TS-SBA proposed in this study may facilitate decisionmakers to solve real applications of MKP. It may also be applied to solve other variants of knapsack problems (KPs) with minor modifications

    Incorporation of DPP6a and DPP6K Variants in Ternary Kv4 Channel Complex Reconstitutes Properties of A-type K Current in Rat Cerebellar Granule Cells

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    Dipeptidyl peptidase-like protein 6 (DPP6) proteins co-assemble with Kv4 channel Ξ±-subunits and Kv channel-interacting proteins (KChIPs) to form channel protein complexes underlying neuronal somatodendritic A-type potassium current (ISA). DPP6 proteins are expressed as N-terminal variants (DPP6a, DPP6K, DPP6S, DPP6L) that result from alternative mRNA initiation and exhibit overlapping expression patterns. Here, we study the role DPP6 variants play in shaping the functional properties of ISA found in cerebellar granule (CG) cells using quantitative RT-PCR and voltage-clamp recordings of whole-cell currents from reconstituted channel complexes and native ISA channels. Differential expression of DPP6 variants was detected in rat CG cells, with DPP6K (41Β±3%)>DPP6a (33Β±3%)>>DPP6S (18Β±2%)>DPP6L (8Β±3%). To better understand how DPP6 variants shape native neuronal ISA, we focused on studying interactions between the two dominant variants, DPP6K and DPP6a. Although previous studies did not identify unique functional effects of DPP6K, we find that the unique N-terminus of DPP6K modulates the effects of KChIP proteins, slowing recovery and producing a negative shift in the steady-state inactivation curve. By contrast, DPP6a uses its distinct N-terminus to directly confer rapid N-type inactivation independently of KChIP3a. When DPP6a and DPP6K are co-expressed in ratios similar to those found in CG cells, their distinct effects compete in modulating channel function. The more rapid inactivation from DPP6a dominates during strong depolarization; however, DPP6K produces a negative shift in the steady-state inactivation curve and introduces a slow phase of recovery from inactivation. A direct comparison to the native CG cell ISA shows that these mixed effects are present in the native channels. Our results support the hypothesis that the precise expression and co-assembly of different auxiliary subunit variants are important factors in shaping the ISA functional properties in specific neuronal populations

    Modeling-independent elucidation of inactivation pathways in recombinant and native A-type Kv channels.

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    A-type voltage-gated K(+) (Kv) channels self-regulate their activity by inactivating directly from the open state (open-state inactivation [OSI]) or by inactivating before they open (closed-state inactivation [CSI]). To determine the inactivation pathways, it is often necessary to apply several pulse protocols, pore blockers, single-channel recording, and kinetic modeling. However, intrinsic hurdles may preclude the standardized application of these methods. Here, we implemented a simple method inspired by earlier studies of Na(+) channels to analyze macroscopic inactivation and conclusively deduce the pathways of inactivation of recombinant and native A-type Kv channels. We investigated two distinct A-type Kv channels expressed heterologously (Kv3.4 and Kv4.2 with accessory subunits) and their native counterparts in dorsal root ganglion and cerebellar granule neurons. This approach applies two conventional pulse protocols to examine inactivation induced by (a) a simple step (single-pulse inactivation) and (b) a conditioning step (double-pulse inactivation). Consistent with OSI, the rate of Kv3.4 inactivation (i.e., the negative first derivative of double-pulse inactivation) precisely superimposes on the profile of the Kv3.4 current evoked by a single pulse because the channels must open to inactivate. In contrast, the rate of Kv4.2 inactivation is asynchronous, already changing at earlier times relative to the profile of the Kv4.2 current evoked by a single pulse. Thus, Kv4.2 inactivation occurs uncoupled from channel opening, indicating CSI. Furthermore, the inactivation time constant versus voltage relation of Kv3.4 decreases monotonically with depolarization and levels off, whereas that of Kv4.2 exhibits a J-shape profile. We also manipulated the inactivation phenotype by changing the subunit composition and show how CSI and CSI combined with OSI might affect spiking properties in a full computational model of the hippocampal CA1 neuron. This work unambiguously elucidates contrasting inactivation pathways in neuronal A-type Kv channels and demonstrates how distinct pathways might impact neurophysiological activity

    Graphitic carbon growth on crystalline and amorphous oxide substrates using molecular beam epitaxy

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    We report graphitic carbon growth on crystalline and amorphous oxide substrates by using carbon molecular beam epitaxy. The films are characterized by Raman spectroscopy and X-ray photoelectron spectroscopy. The formations of nanocrystalline graphite are observed on silicon dioxide and glass, while mainly sp2 amorphous carbons are formed on strontium titanate and yttria-stabilized zirconia. Interestingly, flat carbon layers with high degree of graphitization are formed even on amorphous oxides. Our results provide a progress toward direct graphene growth on oxide materials

    Timing of tracheostomy as a determinant of weaning success in critically ill patients: a retrospective study

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    INTRODUCTION: Tracheostomy is frequently performed in critically ill patients for prolonged intubation. However, the optimal timing of tracheostomy, and its impact on weaning from mechanical ventilation and outcomes in critically ill patients who require mechanical ventilation remain controversial. METHODS: The medical records of patients who underwent tracheostomy in the medical intensive care unit (ICU) of a tertiary medical centre from July 1998 to June 2001 were reviewed. Clinical characteristics, length of stay in the ICU, rates of post-tracheostomy pneumonia, weaning from mechanical ventilation and mortality rates were analyzed. RESULTS: A total of 163 patients (93 men and 70 women) were included; their mean age was 70 years. Patients were classified into two groups: successful weaning (n = 78) and failure to wean (n = 85). Shorter intubation periods (P = 0.02), length of ICU stay (P = 0.001) and post-tracheostomy ICU stay (P = 0.005) were noted in patients in the successful weaning group. Patients who underwent tracheostomy more than 3 weeks after intubation had higher ICU mortality rates and rates of weaning failure. The length of intubation correlated with the length of ICU stay in the successful weaning group (r = 0.70; P < 0.001). Multivariate analysis revealed that tracheostomy after 3 weeks of intubation, poor oxygenation before tracheostomy (arterial oxygen tension/fractional inspired oxygen ratio <250) and occurrence of nosocomial pneumonia after tracheostomy were independent predictors of weaning failure. CONCLUSION: The study suggests that tracheostomy after 21 days of intubation is associated with a higher rate of failure to wean from mechanical ventilation, longer ICU stay and higher ICU mortality

    Coordination tuning of cobalt phosphates towards efficient water oxidation catalyst

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    The development of efficient and stable water oxidation catalysts is necessary for the realization of practically viable water-splitting systems. Although extensive studies have focused on the metal-oxide catalysts, the effect of metal coordination on the catalytic ability remains still elusive. Here we select four cobalt-based phosphate catalysts with various cobalt-and phosphate-group coordination as a platform to better understand the catalytic activity of cobalt-based materials. Although they exhibit various catalytic activities and stabilities during water oxidation, Na2CoP2O7 with distorted cobalt tetrahedral geometry shows high activity comparable to that of amorphous cobalt phosphate under neutral conditions, along with high structural stability. First-principles calculations suggest that the surface reorganization by the pyrophosphate ligand induces a highly distorted tetrahedral geometry, where water molecules can favourably bind, resulting in a low overpotential (similar to 0.42 eV). Our findings emphasize the importance of local cobalt coordination in the catalysis and suggest the possible effect of polyanions on the water oxidation chemistry.
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