321 research outputs found

    Temperature and Performance Inhomogeneities in PEM Electrolysis Stacks with Industrial Scale Cells

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    In this work temperature inhomogeneities and their influence on PEMWE performance of industrial-scale stacks are investigated. Three temperature differences are examined: (i) between the inlet and outlet, (ii) in-between the cells of a stack, (iii) between the cell’s solid materials and the fluids. A validated stack model for temperature and performance is presented which is used to quantify the above-mentioned temperature fields and their influences on current density distribution and cell voltages. For a chosen scenario, with current densities of 2.0 A cm−2, fluid inlet temperatures of 60 °C and flow-rates of 0.15 kg s−1m−2, peak temperature differences amount to 8.2 K along-the-channel. This relates to inhomogeneities of current density of up to 10% inside a cell and deviations of cell voltage of 9 mV in-between cells in the center of the stack and outer cells. For higher current densities these differences increase further. More homogeneous temperatures allow operation at elevated average temperatures without exceeding temperature limitations and reduce the spread of degradation mechanisms. Hence, homogenous profiles lead to a more hole-some utilization of electrolysis stacks. Therefore, the ability to homogenize via alternative operation such as higher flow-rate, higher pressure and altered routing of fluid-flow is analyzed

    Review and Prospects of PEM Water Electrolysis at Elevated Temperature Operation

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    Polymer electrolyte membrane water electrolyzers (PEMWE) are currently restricted to an operating temperature range between 50 to 80 °C. This review shows that elevated temperature (ET) above 90 °C can be advantageous with respect to i) reduced cell voltages, ii) a reduction of catalyst loading or possibly the employment of less noble electrocatalysts, and iii) a greater potential for waste heat utilization when the electrolyzer is operated in exothermal mode (when the cell voltage is higher than the thermoneutral voltage). Together with presenting an overview of the materials and components utilized in elevated temperature PEMWE under liquid and steam operation, this article summarizes the experimental and modeling performances reported to date, highlights the challenges ahead, and suggests aspects, which will need to be considered to improve the performance at elevated temperature. Key points, which arise from this work are the extensive need of re-assessing the material selection both for the cell components and also at a system level, the effects and optimization of working with steam operation, and in the long run, the need for techno-economic analyses to ultimately assess whether efficiency gains will truly translate to a cost-effective technology alternative

    A Sequential Targeting Strategy Interrupts AKT-Driven Subclone-Mediated Progression in Glioblastoma

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    Purpose: Therapy resistance and fatal disease progression in glioblastoma are thought to result from the dynamics of intra-tumor heterogeneity. This study aimed at identifying and molecularly targeting tumor cells that can survive, adapt, and subclonally expand under primary therapy. Experimental design: To identify candidate markers and to experimentally access dynamics of subclonal progression in glioblastoma, we established a discovery cohort of paired vital cell samples obtained before and after primary therapy. We further used two independent validation cohorts of paired clinical tissues to test our findings. Follow-up preclinical treatment strategies were evaluated in patient-derived xenografts. Results: We describe, in clinical samples, an archetype of rare ALDH1A1+ tumor cells that enrich and acquire AKT-mediated drug resistance in response to standard-of-care temozolomide (TMZ). Importantly, we observe that drug resistance of ALDH1A1+ cells is not intrinsic, but rather an adaptive mechanism emerging exclusively after TMZ treatment. In patient cells and xenograft models of disease, we recapitulate the enrichment of ALDH1A1+ cells under the influence of TMZ. We demonstrate that their subclonal progression is AKT-driven and can be interfered with by well-timed sequential rather than simultaneous antitumor combination strategy. Conclusions: Drug-resistant ALDH1A1+/pAKT+ subclones accumulate in patient tissues upon adaptation to TMZ therapy. These subclones may therefore represent a dynamic target in glioblastoma. Our study proposes the combination of TMZ and AKT inhibitors in a sequential treatment schedule as a rationale for future clinical investigation

    The Effect of Repetitive Transcranial Magnetic Stimulation on Gamma Oscillatory Activity in Schizophrenia

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    Gamma (γ) oscillations (30-50 Hz) have been shown to be excessive in patients with schizophrenia (SCZ) during working memory (WM). WM is a cognitive process that involves the online maintenance and manipulation of information that is mediated largely by the dorsolateral prefrontal cortex (DLPFC). Repetitive transcranial magnetic stimulation (rTMS) represents a non-invasive method to stimulate the cortex that has been shown to enhance cognition and γ oscillatory activity during WM.We examined the effect of 20 Hz rTMS over the DLPFC on γ oscillatory activity elicited during the N-back task in 24 patients with SCZ compared to 22 healthy subjects. Prior to rTMS, patients with SCZ elicited excessive γ oscillatory activity compared to healthy subjects across WM load. Active rTMS resulted in the reduction of frontal γ oscillatory activity in patients with SCZ, while potentiating activity in healthy subjects in the 3-back, the most difficult condition. Further, these effects on γ oscillatory activity were found to be specific to the frontal brain region and were absent in the parieto-occipital brain region.We suggest that this opposing effect of rTMS on γ oscillatory activity in patients with SCZ versus healthy subjects may be related to homeostatic plasticity leading to differential effects of rTMS on γ oscillatory activity depending on baseline differences. These findings provide important insights into the neurophysiological mechanisms underlying WM deficits in SCZ and demonstrated that rTMS can modulate γ oscillatory activity that may be a possible avenue for cognitive potentiation in this disorder

    Neuroarchitecture of Aminergic Systems in the Larval Ventral Ganglion of Drosophila melanogaster

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    Biogenic amines are important signaling molecules in the central nervous system of both vertebrates and invertebrates. In the fruit fly Drosophila melanogaster, biogenic amines take part in the regulation of various vital physiological processes such as feeding, learning/memory, locomotion, sexual behavior, and sleep/arousal. Consequently, several morphological studies have analyzed the distribution of aminergic neurons in the CNS. Previous descriptions, however, did not determine the exact spatial location of aminergic neurite arborizations within the neuropil. The release sites and pre-/postsynaptic compartments of aminergic neurons also remained largely unidentified. We here used gal4-driven marker gene expression and immunocytochemistry to map presumed serotonergic (5-HT), dopaminergic, and tyraminergic/octopaminergic neurons in the thoracic and abdominal neuromeres of the Drosophila larval ventral ganglion relying on Fasciclin2-immunoreactive tracts as three-dimensional landmarks. With tyrosine hydroxylase- (TH) or tyrosine decarboxylase 2 (TDC2)-specific gal4-drivers, we also analyzed the distribution of ectopically expressed neuronal compartment markers in presumptive dopaminergic TH and tyraminergic/octopaminergic TDC2 neurons, respectively. Our results suggest that thoracic and abdominal 5-HT and TH neurons are exclusively interneurons whereas most TDC2 neurons are efferent. 5-HT and TH neurons are ideally positioned to integrate sensory information and to modulate neuronal transmission within the ventral ganglion, while most TDC2 neurons appear to act peripherally. In contrast to 5-HT neurons, TH and TDC2 neurons each comprise morphologically different neuron subsets with separated in- and output compartments in specific neuropil regions. The three-dimensional mapping of aminergic neurons now facilitates the identification of neuronal network contacts and co-localized signaling molecules, as exemplified for DOPA decarboxylase-synthesizing neurons that co-express crustacean cardioactive peptide and myoinhibiting peptides

    Structural variants exhibit widespread allelic heterogeneity and shape variation in complex traits

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    This work is licensed under a Creative Commons Attribution 4.0 International License.It has been hypothesized that individually-rare hidden structural variants (SVs) could account for a significant fraction of variation in complex traits. Here we identified more than 20,000 euchromatic SVs from 14 Drosophila melanogaster genome assemblies, of which ~40% are invisible to high specificity short-read genotyping approaches. SVs are common, with 31.5% of diploid individuals harboring a SV in genes larger than 5kb, and 24% harboring multiple SVs in genes larger than 10kb. SV minor allele frequencies are rarer than amino acid polymorphisms, suggesting that SVs are more deleterious. We show that a number of functionally important genes harbor previously hidden structural variants likely to affect complex phenotypes. Furthermore, SVs are overrepresented in candidate genes associated with quantitative trait loci mapped using the Drosophila Synthetic Population Resource. We conclude that SVs are ubiquitous, frequently constitute a heterogeneous allelic series, and can act as rare alleles of large effect

    Cognitive effects of high-frequency repetitive transcranial magnetic stimulation: a systematic review

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    Transcranial magnetic stimulation (TMS) was introduced as a non-invasive tool for the investigation of the motor cortex. The repetitive application (rTMS), causing longer lasting effects, was used to study the influence on a variety of cerebral functions. High-frequency (>1 Hz) rTMS is known to depolarize neurons under the stimulating coil and to indirectly affect areas being connected and related to emotion and behavior. Researchers found selective cognitive improvement after high-frequency (HF) stimulation specifically over the left dorsolateral prefrontal cortex (DLPFC). This article provides a systematic review of HF-rTMS studies (1999–2009) stimulating over the prefrontal cortex of patients suffering from psychiatric/neurological diseases or healthy volunteers, where the effects on cognitive functions were measured. The cognitive effect was analyzed with regard to the impact of clinical status (patients/healthy volunteers) and stimulation type (verum/sham). RTMS at 10, 15 or 20 Hz, applied over the left DLPFC, within a range of 10–15 successive sessions and an individual motor threshold of 80–110%, is most likely to cause significant cognitive improvement. In comparison, patients tend to reach a greater improvement than healthy participants. Limitations concern the absence of healthy groups in clinical studies and partly the absence of sham groups. Thus, future investigations are needed to assess cognitive rTMS effects in different psychiatric disorders versus healthy subjects using an extended standardized neuropsychological test battery. Since the pathophysiological and neurobiological basis of cognitive improvement with rTMS remains unclear, additional studies including genetics, experimental neurophysiology and functional brain imaging are necessary to explore stimulation-related functional changes in the brain

    Governança e governamentalidade: relação e relevância de dois conceitos científico-sociais proeminentes na educação comparada

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    Contrapondo-se ao retrospecto da existência de uma relação volátil entre o Estado e "seu" sistema educacional, este trabalho enfoca dois conceitos que podem ser empregados como ferramentas de análise para estudar as transformações em curso. O termo "governança" está mais relacionado a aspectos técnicos: tratam-se de instrumentos e modos, procedimentos e atores, além de suas constelações e formas de cooperação. Ele concentra a pesquisa em questões como: quem oferece serviços educacionais, qual é a relação entre ensino público e privado etc. Ele também é extremamente útil na investigação da relação entre os diversos níveis de análise e provou-se particularmente importante para a compreensão teórica adequada do papel das organizações internacionais na formulação de políticas educacionais. A sociologia e a ciência política são duas disciplinas cuja associação se mostra mais notável na elaboração do conceito sob diversas perspectivas. "Governamentalidade", por sua vez, apesar de compartilhar muitas características com governança, é um termo foucautiano dedicado à geração de subjetividades distintas por meio de técnicas e modos de regulação e conduta em sentido lato. Assim, governamentalidade inclui investigações do nexo tipicamente foucautiano conhecimento/poder. Consideramos ambas as perspectivas em conjunto para discutir suas implicações para a educação comparada.Against the background of a changing relation between the state and "its" education system, the present contribution focuses on two concepts that can be used as analytical tools in order to analyze the current transformations. "Governance" is more concerned with technical issues: with instruments and modes, procedures and actors, with their constellations and forms of cooperation. It focuses research on questions such as: who provides educational services, what is the relation between public and private education etc. It is also very useful in investigating the relation between the various levels of analysis and has proven particularly useful for an adequate theoretical understanding of the role of international organizations in shaping educational policies. Sociology and political science are the two disciplines most prominently associated with elaborating the concept under various perspectives. Governmentality, on the other hand, although sharing many characteristics with governance, is a Foucauldian term concerned with the generation of different subjectivities through techniques and modes of ruling and guiding in an encompassing sense. Governmentality thus includes investigations of the typical Foucauldian knowledge/power nexus. Both perspectives are brought together to discuss the implications for comparative education
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