2,618 research outputs found

    Age- and stress-associated C. elegans granulins impair lysosomal function and induce a compensatory HLH-30/TFEB transcriptional response.

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    The progressive failure of protein homeostasis is a hallmark of aging and a common feature in neurodegenerative disease. As the enzymes executing the final stages of autophagy, lysosomal proteases are key contributors to the maintenance of protein homeostasis with age. We previously reported that expression of granulin peptides, the cleavage products of the neurodegenerative disease protein progranulin, enhance the accumulation and toxicity of TAR DNA binding protein 43 (TDP-43) in Caenorhabditis elegans (C. elegans). In this study we show that C. elegans granulins are produced in an age- and stress-dependent manner. Granulins localize to the endolysosomal compartment where they impair lysosomal protease expression and activity. Consequently, protein homeostasis is disrupted, promoting the nuclear translocation of the lysosomal transcription factor HLH-30/TFEB, and prompting cells to activate a compensatory transcriptional program. The three C. elegans granulin peptides exhibited distinct but overlapping functional effects in our assays, which may be due to amino acid composition that results in distinct electrostatic and hydrophobicity profiles. Our results support a model in which granulin production modulates a critical transition between the normal, physiological regulation of protease activity and the impairment of lysosomal function that can occur with age and disease

    Survey of physics reasoning on uncertainty concepts in experiments: an assessment of measurement uncertainty for introductory physics labs

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    Measurement uncertainty is a critical feature of experimental research in the physical sciences, and the concepts and practices surrounding measurement uncertainty are important components of physics lab courses. However, there has not been a broadly applicable, research-based assessment tool that allows physics instructors to easily measure students' knowledge of measurement uncertainty concepts and practices. To address this need, we employed Evidence-Centered Design to create the Survey of Physics Reasoning on Uncertainty Concepts in Experiments (SPRUCE). SPRUCE is a pre-post assessment instrument intended for use in introductory (first- and second-year) physics lab courses to help instructors and researchers identify student strengths and challenges with measurement uncertainty. In this paper, we discuss the development of SPRUCE's assessment items guided by Evidence-Centered Design, focusing on how instructors' and researchers' assessment priorities were incorporated into the assessment items and how students' reasoning from pilot testing informed decisions around item answer options.Comment: 23 pages, 11 figures, submitted as part of the Physical Review Physics Education Research Focused Collection on Instructional Labs: Improving Traditions and New Direction

    Gallium gradients in chalcopyrite thin films: Depth profile analyses of films grown at different temperatures

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    The following article appeared in Journal of Applied Physics 110.9 (2011): 093509 and may be found at http://scitation.aip.org/content/aip/journal/jap/110/9/10.1063/1.3656986Cu(In,Ga)Se2 films are used as absorber layers in chalcopyrite thin film solar cells. As the gallium concentration in the absorber can be used to control the band gap, there have been many efforts to vary the gallium concentration in depth to gain an optimum balance of light absorption, carrier collection, and recombination at different depths of the absorber film, leading to improved quantum efficiency. In this study, we investigate the effect of the maximum substrate temperature during film growth on the depth dependent gallium concentration. For the in-depth gallium concentration analyses, we use two techniques, covering complementary depth ranges. Angle dependent soft x-ray emission spectroscopy provides access to information depths between 20 and 470 nm, which covers the depth range of the space charge region, where most of the photoexcited carriers are generated. Therefore, this depth range is of particular interest. To complement this investigation we use secondary neutral mass spectrometry, which destructively probes the whole thickness of the absorber (≈2 µm). The two methods show increasingly pronounced gallium and indium gradients with decreasing maximum substrate temperature. The probing of the complementary depth ranges of the absorbers gives a consistent picture of the in-depth gallium distribution, which provides a solid basis for a comprehensive discussion about the effect of a reduced substrate temperature on the formation of gallium gradients in Cu(In,Ga)Se2 and the device performance of the corresponding reference solar cells.The authors acknowledge the support of the European Commission in the framework of the ATHLET-project (Project No. 019670)

    Redox and Catalytic Properties of Promoted NiO Catalysts for the Oxidative Dehydrogenation of Ethane

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    [EN] NiO and metal-promoted NiO catalysts (M-NiO, with a M/(M+Ni) atomic ratio of 0.08, with M = Nb, Sn, or La) have been prepared, tested in the oxidative dehydrogenation (ODH) of ethane, and characterized by means of XRD, TPR, HRTEM, Raman, XPS, and in situ XAS (using H-2/He, air or C2H6/He mixtures). The selectivity to ethylene during the ODH of ethane decreases according to the following trend: Nb NiO Sn NiO > La NiO > NiO, whereas the catalyst reducibility (determined by both TPR and XAS using H-2/He mixtures) shows the opposite trend. However, different reducibility and catalytic behavior in the absence of oxygen (ethane/He mixtures) have been observed, especially when comparing Nb- and Sn-promoted NiO samples. These differences can be ascribed mainly to a different phase distribution of the promoter. The results presented here are discussed in terms of the nature of active and selective sites for ODH of ethane in selective and unselective catalysts, but also the role of promoters and the importance of their phase distribution.The authors would like to acknowledge the DGICYT in Spain CTQ2012-37925-C03-2, CTQ2015-68951-C3-1-R, and CTQ2015-68951-C3-3-R. Authors thank European Synchrotron Radiation Facility, ESRF (Project CH-4512; BM25-SpLine Beamlime). Authors from ITQ also thank Project SEV-2016-0683 for financial support. D.D. thanks MINECO and Severo Ochoa Excellence Program for his fellowship (SVP-2014-068669). B.S. also thanks UV-INV-AE16-484416. Finally, the authors thank the Electron Microscopy Service of Universitat Politecnica de Valencia for their support.Delgado-Muñoz, D.; Solsona Espriu, BE.; Ykrelef, A.; Rodriguez-Gomez, A.; Caballero, A.; Rodríguez-Aguado, E.; Rodriguez-Castellón, E.... (2017). Redox and Catalytic Properties of Promoted NiO Catalysts for the Oxidative Dehydrogenation of Ethane. The Journal of Physical Chemistry C. 121(45):25132-25142. https://doi.org/10.1021/acs.jpcc.7b07066S25132251421214

    Novel public-private partnerships to address the double burden of malnutrition

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    Public–private partnerships are an effective way to address the global double burden of malnutrition. While public–private partnerships operate in multiple forms, their leadership usually falls to governments, public health agencies, or nongovernmental organizations, with the private sector taking a subordinate role. The rapid ascent of social media and mass communications worldwide has provided a disruptive technology for new nutrition intervention programs. A new model, provisionally called private–public engagement, takes advantage of social media, mass media, and integrated social marketing to reach parents, families, and communities directly. These new private–public engagement initiatives need to be managed in ways suggested for public–private partnerships by the World Health Organization, especially if the private sector is in the lead. Once the rationale for engagement is defined, there is a need to mobilize resources, establish in-country partnerships and codes of conduct, and provide a plan for monitoring, evaluation, and accountability. Provided here is an example consistent with the private–public engagement approach, ie, the United for Healthier Kids program, which has been aimed at families with children aged less than 12 years. Materials to inspire behavioral change and promote healthier diets and lifestyle were disseminated in a number of countries through both digital and physical channels, often in partnership with local or regional governments. A description of this program, along with strategies to promote transparency and communication among stakeholders, serves to provide guidance for the development of future effective private–public engagements

    Early Obesity Prevention: A Randomized Trial of a Practice-Based Intervention in 0–24-Month Infants

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    Objective. A pediatric office-based intervention was implemented following a randomized, controlled design, aimed at improving child feeding practices and growth patterns and ultimately reducing risk for overweight and obesity later in life. Methods. Four clinics (232 infants) were randomized to control or intervention (I), the latter delivered by health care provider at each of 7–9 well-baby visits over 2 years, using a previously developed program (Growing Leaps and Bounds) that included verbal, visual, and text advice and information for parents. Results. The I group offered significantly less soda p=0.006, sweetened tea p=0.01, punch p=0.02 and/or cow’s milk p=0.001 to infants and delayed the introduction of drink/food other than breast milk p<0.05. Parents in the I group had a higher perceived parental monitoring p=0.05 and restriction p=0.01 on infant feeding. While the I group exhibited at baseline more adverse socioeconomic indicators than the control group, growth trajectory or body size indices did not significantly differ between groups. Conclusions. Education provided by health care providers in addition to follow-up monthly phone calls may help modify parental behaviors related to child feeding and increase parental sense of responsibility toward child eating behaviors

    Bridging Physics and Biology Teaching through Modeling

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    As the frontiers of biology become increasingly interdisciplinary, the physics education community has engaged in ongoing efforts to make physics classes more relevant to life sciences majors. These efforts are complicated by the many apparent differences between these fields, including the types of systems that each studies, the behavior of those systems, the kinds of measurements that each makes, and the role of mathematics in each field. Nonetheless, physics and biology are both sciences that rely on observations and measurements to construct models of the natural world. In the present theoretical article, we propose that efforts to bridge the teaching of these two disciplines must emphasize shared scientific practices, particularly scientific modeling. We define modeling using language common to both disciplines and highlight how an understanding of the modeling process can help reconcile apparent differences between the teaching of physics and biology. We elaborate how models can be used for explanatory, predictive, and functional purposes and present common models from each discipline demonstrating key modeling principles. By framing interdisciplinary teaching in the context of modeling, we aim to bridge physics and biology teaching and to equip students with modeling competencies applicable across any scientific discipline.Comment: 10 pages, 2 figures, 3 table
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