Transgenic Drosophila for Investigating DUX4 and FRG1, Two Genes Associated with Facioscapulohumeral Muscular Dystrophy (FSHD)

Facioscapulohumeral muscular dystrophy (FSHD) is typically an adult onset dominant myopathy. Epigenetic changes in the chromosome 4q35 region linked to both forms of FSHD lead to a relaxation of repression and increased somatic expression of DUX4-fl (DUX4-full length), the pathogenic alternative splicing isoform of the DUX4 gene. DUX4-fl encodes a transcription factor expressed in healthy testis and pluripotent stem cells; however, in FSHD, increased levels of DUX4-fl in myogenic cells lead to aberrant regulation of target genes. DUX4-fl has proven difficult to study in vivo; thus, little is known about its normal and pathogenic roles. The endogenous expression of DUX4-fl in FSHD-derived human muscle and myogenic cells is extremely low, exogenous expression of DUX4-fl in somatic cells rapidly induces cytotoxicity, and, due in part to the lack of conservation beyond primate lineages, viable animal models based on DUX4-fl have been difficult to generate. By contrast, the FRG1 (FSHD region gene 1), which is linked to FSHD, is evolutionarily conserved from invertebrates to humans, and has been studied in several model organisms. FRG1 expression is critical for the development of musculature and vasculature, and overexpression of FRG1 produces a myopathic phenotype, yet the normal and pathological functions of FRG1 are not well understood. Interestingly, DUX4 and FRG1 were recently linked when the latter was identified as a direct transcriptional target of DUX4-FL. To better understand the pathways affected in FSHD by DUX4-fl and FRG1, we generated transgenic lines of Drosophila expressing either gene under control of the UAS/GAL4 binary system. Utilizing these lines, we generated screenable phenotypes recapitulating certain known consequences of DUX4-fl or FRG1 overexpression. These transgenic Drosophila lines provide resources to dissect the pathways affected by DUX4-fl or FRG1 in a genetically tractable organism and may provide insight into both muscle development and pathogenic mechanisms in FSHD

Building Environmentally Sustainable Communities: A Framework for Inclusivity

Reviews literature on past inequitable and unsustainable urban development and visions for linking sustainability, opportunity, and inclusion. Analyzes possible metrics for measuring sustainability and access as well as next steps for policy

Evaluation of Hydrogen Storage in Metal Organic Frameworks by Bridged Hydrogen Spillover

Hydrogen has the potential to be the next energy carrier. The ability to use hydrogen in fuel cell technologies depends largely on the ability to store hydrogen efficiently. Metal-Organic Frameworks (MOFs) belong to an interesting set of materials that consists of porous channels and have been shown to carry potential for hydrogen storage when added to metal catalysts. MOFs alone show no potential to store hydrogen, but when added to metal catalyst they can exhibit a spillover effect to increase hydrogen storage capacity. The key critical issues with MOFs are to validate the promises that MOFs can provide with spillover, since spillover intricately linked to more standard H2 storage mechanisms. The current project focuses on the synthesis of Isoreticular Metal Organic Framework-8 (IRMOF-8) added to platinum on Activated Carbon (AC) and bridged together with sucrose to enhance the spillover effect. In order to reach hydrogen storage goals, a method must be proven to have enough capacity for the adsorption/resorption (reversibility) at ambient and 120 bar reasonable pressures. With the tremendous interest in spillover materials for hydrogen storage, NREL and DOE have dedicated resources to synthesize specific materials and to develop, perform, and validate the requisite measurements

Building Successful Neighborhoods

Reviews the literature on direct interventions to revitalize distressed neighborhoods by improving housing, schools, and services in terms of basic policy and strategy, programmatic strategies, and building institutional infrastructure

Solution-Phase Synthesis of Heteroatom-Substituted Carbon Scaffolds for Hydrogen Storage

This paper reports a bottom-up solution-phase process for the preparation of pristine and heteroatom (boron, phosphorus, or nitrogen)-substituted carbon scaffolds that show good surface areas and enhanced hydrogen adsorption capacities and binding energies. The synthesis method involves heating chlorine-containing small organic molecules with metallic sodium at reflux in high-boiling solvents. For heteroatom incorporation, heteroatomic electrophiles are added to the reaction mixture. Under the reaction conditions, micrometer-sized graphitic sheets assembled by 3−5 nm-sized domains of graphene nanoflakes are formed, and when they are heteroatom-substituted, the heteroatoms are uniformly distributed. The substituted carbon scaffolds enriched with heteroatoms (boron ~7.3%, phosphorus ~8.1%, and nitrogen ~28.1%) had surface areas as high as 900 m^2 g^(−1) and enhanced reversible hydrogen physisorption capacities relative to pristine carbon scaffolds or common carbonaceous materials. In addition, the binding energies of the substituted carbon scaffolds, as measured by adsorption isotherms, were 8.6, 8.3, and 5.6 kJ mol^(−1) for the boron-, phosphorus-, and nitrogen-enriched carbon scaffolds, respectively

El contrato de suministro de contenidos digitales y los contratos de desarrollo de software y creación web en el Derecho de consumidores. De la Propuesta CESL y la Directiva 2011/83/UE a la Propuesta de Directiva 634/2015, de 9 de diciembre

Tras la retirada de la Propuesta CESL por la Comisión europea en mayo de 2015 con intención de modificarla en aras de procurar un mayor avance en el Mercado Único Digital (tal como se expresa en la comunicación titulada “Una Estrategia para el Mercado Único Digital de Europa”) el pasado 9 de diciembre de 2015 se publicaron dos Propuestas de Directiva (634 y 635 /2015) y una Propuesta de Reglamento (627/2015) que inciden en dicha voluntad de avance en el Mercado Único Digital. A pesar de que estos textos se encuentran aún en fase de discusión, existe una firme voluntad por parte de la Comisión de sacarlos adelante en la presente legislatura. En este trabajo nos centraremos en el contrato para el suministro de contenidos digitales, regulado en la Propuesta 634/2015 sobre ciertos aspectos relativos a los contratos para el suministro de contenidos digitales (que varía en no pocos aspectos respecto de la establecida en la Propuesta CESL); en concreto, si el ámbito de aplicación de esta nueva figura puede referirse a dos contratos hasta ahora atípicos como son el contrato de desarrollo de software y el contrato de creación de página web, tanto si hablamos de webs o software específicos como si hablamos de software o webs estándar. Tendremos en cuenta, además de los textos señalados, la Directiva 2011/83/UE y la Ley 3/2014 de 27 de marzo, de modificación del TRLGDCU, que incorpora la mencionada Directiva al Ordenamiento español

The effect of extended strain fields on point defect scattering

Thermoelectric materials often require extensive tailoring of microstructure and composition to optimize their properties. Isoelectronic alloying is one of the most commonly applied techniques used to induce point defect scattering and reduce the lattice thermal conductivity. However, current approaches rely heavily on experiment and are not conducive to the high-throughput methods, which are becoming increasingly commonplace within the thermoelectric community. Herein, we present three computationally inexpensive approaches to the evaluation of point-defect scattering in thermoelectrics. These approaches also weave elements of structural chemistry associated with point defect scattering to provide a clear conceptual connection with classical phonon scattering. Computational results are further validated using bulk synthesis of SnSe and its alloys. Experimental transport measurements serve to assess model efficacy. Herein we develop and integrate three computational metrics with experimental data to find predictive metrics that can predict the relative strength of point defect scattering and associated reductions in the thermal conductivity. Ultimately, we find that all of the computational metrics are successful in predicting the relative strength of the various alloys, enabling computation to play a larger role in the screening and optimization of composition within thermoelectrics. Please click Additional Files below to see the full abstract

Planning the Housing Opportunity and Services Together Demonstration: Challenges and Lessons Learned

Offers insights from designing and implementing a project to address barriers to self-sufficiency among low-income parents, such as poor health and low education levels, while integrating services for children and youth in public and mixed-income housing

Cellulose crystallinity index: measurement techniques and their impact on interpreting cellulase performance

Although measurements of crystallinity index (CI) have a long history, it has been found that CI varies significantly depending on the choice of measurement method. In this study, four different techniques incorporating X-ray diffraction and solid-state 13C nuclear magnetic resonance (NMR) were compared using eight different cellulose preparations. We found that the simplest method, which is also the most widely used, and which involves measurement of just two heights in the X-ray diffractogram, produced significantly higher crystallinity values than did the other methods. Data in the literature for the cellulose preparation used (Avicel PH-101) support this observation. We believe that the alternative X-ray diffraction (XRD) and NMR methods presented here, which consider the contributions from amorphous and crystalline cellulose to the entire XRD and NMR spectra, provide a more accurate measure of the crystallinity of cellulose. Although celluloses having a high amorphous content are usually more easily digested by enzymes, it is unclear, based on studies published in the literature, whether CI actually provides a clear indication of the digestibility of a cellulose sample. Cellulose accessibility should be affected by crystallinity, but is also likely to be affected by several other parameters, such as lignin/hemicellulose contents and distribution, porosity, and particle size. Given the methodological dependency of cellulose CI values and the complex nature of cellulase interactions with amorphous and crystalline celluloses, we caution against trying to correlate relatively small changes in CI with changes in cellulose digestibility. In addition, the prediction of cellulase performance based on low levels of cellulose conversion may not include sufficient digestion of the crystalline component to be meaningful