364 research outputs found

    Advanced Electrodes for Solid Acid Fuel Cells by Platinum Deposition on CsH_(2)PO_4

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    We demonstrate cathodes for solid acid fuel cells fabricated by vapor deposition of platinum from the metalorganic precursor Pt(acac)_2 on the solid acid CsH_(2)PO_4 at 210 °C. A network of platinum nanoparticles with diameters of 2−4 nm serves as both the oxygen reduction catalyst and the electronic conductor in the electrode. Electrodes with a platinum content of 1.75 mg/cm^2 are more active for oxygen reduction than previously reported electrodes with a platinum content of 7.5 mg/cm^2. Electrodes containing <1.75 mg/cm^2 of platinum show significantly reduced catalytic activity and increased ohmic resistance indicative of a highly discontinuous catalytic-electronic platinum network

    Anti-phase synchronization of phase-reduced oscillators using open-loop control

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    In this letter, we present an elegant method to build and maintain an anti-phase configuration of two nonlinear oscillators with different natural frequencies and dynamics described by the sinusoidal phase-reduced model. The anti-phase synchronization is achieved using a common input that couples the oscillators and consists of a sequence of square pulses of appropriate amplitude and duration. This example provides a proof of principle that open-loop control can be used to create desired synchronization patterns for nonlinear oscillators, when feedback is expensive or impossible to obtain

    Medication review in preventing older adults\u27 fall-related injury: A systematic review & meta-analysis

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    Background: Medication review is essential in managing adverse drug reactions and improving drug safety in older adults. This systematic review evaluated medication review\u27s role as a single intervention or combined with other interventions in preventing fall-related injuries in older adults. Methods: Electronic databases search was conducted in PubMed, EMBASE, Scopus, and CINAHL. Two reviewers screened titles and abstracts, reviewed full texts, and performed data extraction and risk of bias assessment. Meta-analyses were conducted on studies with similar participants, interventions, outcomes or settings. Results: Fourteen randomized, controlled studies were included. The pooled results indicated that medication review as a standalone intervention was effective in preventing fall-related injuries in community-dwelling older adults (Risk Difference [RD] = -0.06, 95% CI: [-0.11, -0.00], I2 = 61%, p = .04). Medication review also had a positive impact on decreasing the risk of fall-related fractures (RD = -0.02, 95% CI: [-0.04, -0.01], I2 = 0%, p = .01). Discussion: This systematic review and meta-analysis has demonstrated that medication review is effective in preventing fall-related injuries in general, and fractures specifically, in communitydwelling older adults. Future investigations focusing on the process of performing medication review will further inform fall-related injury prevention for older adults

    Estrogens and genomic instability in human cancer cells-involvement of Src/Raf/Erk signaling in micronucleus formation by estrogenic chemicals

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    This article is available open access through the publisher’s website. Copyright @ 2008 The Authors.Reports of the ability of estrogenic agents such as 17β-estradiol (E2), estriol (E3) and bisphenol A (BPA) to induce micronuclei (MN) in MCF-7 breast cancer cells have prompted us to investigate whether these effects are linked to activation of the estrogen receptor (ER) α. Coadministration of tamoxifen and the pure ER antagonist ICI 182 780 to cells treated with E2 and E3 did not lead to significant reductions in micronucleus frequencies. Since these antiestrogens interfere with the transcriptional activity of the ER and block promotion of ER-dependent gene expression, it appears that this process is not involved in micronucleus formation. However, ER activation also triggers rapid signaling via the Src/Raf/extracellular signal-regulated kinase (Erk) pathway. When MCF-7 cells were exposed to E2 and BPA in combination with the specific kinase inhibitors pyrazolopyrimidine and 2′-amino-3′-methoxyflavone, reductions in micronucleus frequencies occurred. These findings suggest that the Src/Raf/Erk pathway plays a role in micronucleus formation by estrogenic agents. Enhanced activation of the Src/Raf/Erk cascade disturbs the localization of Aurora B kinase to kinetochores, leading to a defective spindle checkpoint with chromosome malsegregation. Using antikinetochore CREST antibody staining, a high proportion of micronucleus containing kinetochores was observed, indicating that such processes are relevant to the induction of MN by estrogens. Our results suggest that estrogens induce MN by causing improper chromosome segregation, possibly by interfering with kinase signaling that controls the spindle checkpoint, or by inducing centrosome amplification. Our findings may have some relevance in explaining the effects of estrogens in the later stages of breast carcinogenesis.European Commissio

    Diversity of Cortical Interneurons in Primates: The Role of the Dorsal Proliferative Niche

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    Summary Evolutionary elaboration of tissues starts with changes in the genome and location of the stem cells. For example, GABAergic interneurons of the mammalian neocortex are generated in the ventral telencephalon and migrate tangentially to the neocortex, in contrast to the projection neurons originating in the ventricular/subventricular zone (VZ/SVZ) of the dorsal telencephalon. In human and nonhuman primates, evidence suggests that an additional subset of neocortical GABAergic interneurons is generated in the cortical VZ and a proliferative niche, the outer SVZ. The origin, magnitude, and significance of this species-specific difference are not known. We use a battery of assays applicable to the human, monkey, and mouse organotypic cultures and supravital tissue to identify neuronal progenitors in the cortical VZ/SVZ niche that produce a subset of GABAergic interneurons. Our findings suggest that these progenitors constitute an evolutionary novelty contributing to the elaboration of higher cognitive functions in primates

    Spatial proteomics finds CD155 and Endophilin-A1 as mediators of growth and invasion in medulloblastoma

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    The composition of the plasma membrane (PM)-associated proteome of tumor cells determines cell-cell and cell-matrix interactions and the response to environmental cues. Whether the PM-associated proteome impacts the phenotype of Medulloblastoma (MB) tumor cells and how it adapts in response to growth factor cues is poorly understood. Using a spatial proteomics approach, we observed that hepatocyte growth factor (HGF)-induced activation of the receptor tyrosine kinase c-MET in MB cells changes the abundance of transmembrane and membrane-associated proteins. The depletion of MAP4K4, a pro-migratory effector kinase downstream of c-MET, leads to a specific decrease of the adhesion and immunomodulatory receptor CD155 and of components of the fast-endophilin-mediated endocytosis (FEME) machinery in the PM-associated proteome of HGF-activated MB cells. The decreased surface expression of CD155 or of the fast-endophilin-mediated endocytosis effector endophilin-A1 reduces growth and invasiveness of MB tumor cells in the tissue context. These data thus describe a novel function of MAP4K4 in the control of the PM-associated proteome of tumor cells and identified two downstream effector mechanisms controlling proliferation and invasiveness of MB cells

    Use of Community Support and Health Services in an Age-Friendly City: The Lived Experiences of the Oldest-Old

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    Increases in population ageing and urbanization have led to the development of age-friendly cities (AFC). While much has been done to integrate the needs of younger, healthier older adults, little research has examined the needs of the oldest-old. This phenomenological study explored the lived experience of 10 community-dwelling individuals, aged 80 years and older, using community support and health services. Three central themes emerged: individual circumstances, personal compensatory mechanisms and community design and structure. Numerous implications for AFC development were highlighted: (1) functional ability rather than chronological age should be considered in AFC planning, (2) informal social community supports are very important for those in advanced age; AFC planners must consider individuals in advanced age who are on the edge of losing their independence, and whose loss of independence may be hastened or delayed based on informal social supports available, (3) community design that recognizes and integrates structures to support the needs of frailer older adults may provide a protective buffer to enable these individuals to remain in their homes longer, and (4) socially isolated frail older adults are difficult to reach; innovative strategies are required to ensure their unique needs are discovered and incorporated in community planning

    PAK1 phosphorylation of MEK1 regulates fibronectin-stimulated MAPK activation

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    Activation of the Ras–MAPK signal transduction pathway is necessary for biological responses both to growth factors and ECM. Here, we provide evidence that phosphorylation of S298 of MAPK kinase 1 (MEK1) by p21-activated kinase (PAK) is a site of convergence for integrin and growth factor signaling. We find that adhesion to fibronectin induces PAK1-dependent phosphorylation of MEK1 on S298 and that this phosphorylation is necessary for efficient activation of MEK1 and subsequent MAPK activation. The rapid and efficient activation of MEK and phosphorylation on S298 induced by cell adhesion to fibronectin is influenced by FAK and Src signaling and is paralleled by localization of phospho-S298 MEK1 and phospho-MAPK staining in peripheral membrane–proximal adhesion structures. We propose that FAK/Src-dependent, PAK1-mediated phosphorylation of MEK1 on S298 is central to the organization and localization of active Raf–MEK1–MAPK signaling complexes, and that formation of such complexes contributes to the adhesion dependence of growth factor signaling to MAPK
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