Production of Cu/Diamond composites for first-wall heat sinks

Due to their suitable thermal conductivity and strength copper-based materials have been considered appropriate heat sinks for first wall panels in nuclear fusion devices. However, increased thermal conductivity and mechanical strength are demanded and the concept of property tailoring involved in the design of metal matrix composites advocates for the potential of nanodiamond dispersions in copper. Copper-nanodiamond composite materials can be produced by mechanical alloying followed by a consolidation operation. Yet, this powder metallurgy route poses several challenges: nanodiamond presents intrinsically difficult bonding with copper; contamination by milling media must be closely monitored; and full densification and microstructural homogeneity should be obtained with consolidation. The present line of work is aimed at an optimization of the processing conditions of Cu-nanodiamond composites. The challenges mentioned above have been addressed, respectively, by incorporating chromium in the matrix to form a stable carbide interlayer binding the two components; by assessing the contamination originating from the milling operation through particle-induced X-ray emission spectroscopy; and by comparing the densification obtained by spark plasma sintering with hot-extrusion data from previous studies

Blocking Zika virus vertical transmission.

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity

Fluência de Leitura, Reconhecimento de Palavras e Compreensão Leitora em Alunos do 4º ao 9º Ano do Ensino Fundamental: Revisão Sistemática

O processamento da leitura é resultado da interação de distintos processos cognitivos, como reconhecimento de palavras, compreensão oral e fluência. Há evidências sobre a importância da fluência para predizer a compreensão de leitura, mas ainda não é claro seu papel ao longo do desenvolvimento. Essa revisão sistemática analisou estudos nacionais e internacionais sobre a relação das habilidades de reconhecimento de palavras e fluência de leitura com a compreensão de leitura em alunos do 4º ao 9º ano. A revisão foi conduzida de acordo com a metodologia prisma e utilizou a base de dados PubMed, de 2000 a setembro de 2019. Foram incluídos artigos que respondiam à pergunta norteadora e atendiam à temática estabelecida pelos descritores e palavras-chave. Foram encontrados 992 artigos, dos quais 904 foram excluídos pelo título e resumo e 56 pela leitura do texto completo. Isto possibilitou a análise de 32 artigos. Os resultados sugerem que, diferentemente do reconhecimento de palavras, a habilidade de fluência de leitura tende a manter relação significativa com a compreensão de leitura no decorrer do segundo ciclo do Ensino Fundamental

Fluência de Leitura, Reconhecimento de Palavras e Compreensão Leitora em Alunos do 4º ao 9º Ano do Ensino Fundamental: Revisão Sistemática

Text processing results from the interaction of different cognitive processes, such as word recognition, listening comprehension, and fluency. There is evidence relating to the importance of fluency in predicting reading comprehension, but its role during the course of development is still uncertain. The present systematic review has analyzed national and international research on the relationship between word recognition skills and reading fluency with reading comprehension in students from the 4th to 9th grade. The review was conducted according to the PRISMA methodology and employed the PubMed database from 2000 to September 2019. The chosen papers answered the orienting question and corresponded to the topic established by the descriptors and keywords. We found 992 articles, of which 904 were excluded by reading the titles and abstracts and 56 by reading the full texts. It was possible to analyze 32 papers. The results suggest that, unlike word recognition, the ability to read fluently tends to uphold a significant relationship with reading comprehension during the second cycle of Elementary School.El procesamiento de la lectura es el resultado de la interacción de diferentes procesos cognitivos, como el reconocimiento de palabras, la comprensión oral y la fluidez. Existe evidencia sobre la importancia de la fluidez en la predicción de la comprensión lectora, pero a lo largo del desarrollo su papel no está claro. Esta revisión sistemática analizó estudios nacionales e internacionales sobre la relación entre las habilidades de reconocimiento de palabras y fluidez lectora con la comprensión lectora en estudiantes de 4° a 9° grado. La revisión se realizó de acuerdo con la metodología prisma y utilizó la base de datos  PubMed, desde el 2000 hasta septiembre de 2019. Fueron incluidos artículos que respondieron a la pregunta guía y cumplieron con la temática establecida por los descriptores y palabras clave. Se encontraron 992 artículos, de los cuales 904 fueron excluidos por título y resumen, y 56 por lectura de texto completo. Esto permitió el análisis de 32 artículos. Los resultados sugieren que, a diferencia del reconocimiento de palabras, la habilidad de fluidez lectora tiende a mantener una relación significativa con la comprensión lectora durante el segundo ciclo de la escuela primaria.O processamento da leitura é resultado da interação de distintos processos cognitivos, como reconhecimento de palavras, compreensão oral e fluência. Há evidências sobre a importância da fluência para predizer a compreensão de leitura, mas ainda não é claro seu papel ao longo do desenvolvimento. Essa revisão sistemática analisou estudos nacionais e internacionais sobre a relaçãodas habilidades de reconhecimento de palavrase fluência de leitura com a compreensão de leitura em alunos do 4º ao 9º ano. A revisão foi conduzida deacordo com a metodologia prisma e utilizou a basede dados PubMed, de 2000 a setembro de 2019. Foram incluídos artigos que respondiam à pergunta norteadora e atendiam à temática estabelecida pelos descritores e palavras-chave. Foram encontrados 992 artigos, dos quais 904 foram excluídos pelo título e resumo e 56 pela leitura do texto completo. Isto possibilitou a análise de 32 artigos. Os resultados sugerem que, diferentemente do reconhecimento de palavras, a habilidade de fluência de leitura tende a manter relação significativa com a compreensão de leitura no decorrer do segundo ciclo do Ensino Fundamental

The GOBLET training portal: a global repository of bioinformatics training materials, courses and trainers

Summary: Rapid technological advances have led to an explosion of biomedical data in recent years. The pace of change has inspired new collaborative approaches for sharing materials and resources to help train life scientists both in the use of cutting-edge bioinformatics tools and databases and in how to analyse and interpret large datasets. A prototype platform for sharing such training resources was recently created by the Bioinformatics Training Network (BTN). Building on this work, we have created a centralized portal for sharing training materials and courses, including a catalogue of trainers and course organizers, and an announcement service for training events. For course organizers, the portal provides opportunities to promote their training events; for trainers, the portal offers an environment for sharing materials, for gaining visibility for their work and promoting their skills; for trainees, it offers a convenient one-stop shop for finding suitable training resources and identifying relevant training events and activities locally and worldwide. Availability and implementation: http://mygoblet.org/training-portal Contact: [email protected]

Divergent Biochemical Fractionation, Not Convergent Temperature, Explains Cellulose Oxygen Isotope Enrichment across Latitudes

Recent findings based on the oxygen isotope ratios of tree trunk cellulose indicate that the temperature of biomass production in biomes ranging from boreal to subtropical forests converge to an average leaf temperature of 21.4°C. The above conclusion has been drawn under the assumption that biochemically related isotopic fractionations during cellulose synthesis are not affected by temperature. Here we test the above assumption by heterotrophically generating cellulose at different temperatures and measuring the proportion of carbohydrate oxygen that exchange with water during cellulose synthesis and the average biochemical fractionation associated with this exchange. We observed no variation in the proportion of oxygen that exchange with different temperatures, which averaged 0.42 as it has been observed in other studies. On the other hand, the biochemical oxygen isotope fractionation during cellulose synthesis is affected by temperature and can be described by a 2nd order polynomial equation. The biochemical fractionation changes little between temperatures of 20 and 30°C averaging 26‰ but increases at lower temperatures to values of 31‰. This temperature sensitive biochemical fractionation explains the pattern of cellulose oxygen isotope ratios of aquatic plants encompassing several latitudes. The observed temperature sensitive biochemical fractionation also indicates that divergent biochemical fractionation and not convergent leaf temperature explains the increase in oxygen isotope enrichment of cellulose across several biomes

Author Correction: Blocking Zika virus vertical transmission.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

The role of the mammalian DNA end-processing enzyme polynucleotide kinase 3'-phosphatase in spinocerebellar ataxia Type 3 pathogenesis

DNA strand-breaks (SBs) with non-ligatable ends are generated by ionizing radiation, oxidative stress, various chemotherapeutic agents, and also as base excision repair (BER) intermediates. Several neurological diseases have already been identified as being due to a deficiency in DNA end-processing activities. Two common dirty ends, 3'-P and 5'-OH, are processed by mammalian polynucleotide kinase 3'-phosphatase (PNKP), a bifunctional enzyme with 3'-phosphatase and 5'-kinase activities. We have made the unexpected observation that PNKP stably associates with Ataxin-3 (ATXN3), a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph Disease (MJD). This disease is one of the most common dominantly inherited ataxias worldwide; the defect in SCA3 is due to CAG repeat expansion (from the normal 14-41 to 55-82 repeats) in the ATXN3 coding region. However, how the expanded form gains its toxic function is still not clearly understood. Here we report that purified wild-type (WT) ATXN3 stimulates, and by contrast the mutant form specifically inhibits, PNKP's 3' phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity. Furthermore, transgenic mice conditionally expressing the pathological form of human ATXN3 also showed decreased 3'-phosphatase activity of PNKP, mostly in the deep cerebellar nuclei, one of the most affected regions in MJD patients' brain. Finally, long amplicon quantitative PCR analysis of human MJD patients' brain samples showed a significant accumulation of DNA strand breaks. Our results thus indicate that the accumulation of DNA strand breaks due to functional deficiency of PNKP is etiologically linked to the pathogenesis of SCA3/MJD.This research was supported by USPHS grant NS073976 (TKH) and P30 ES 06676 that support the NIEHS Center Cell Biology Core and Molecular Genomics Core of UTMB’s NIEHS Center for DNA sequencing. TKP is supported by CA129537 and CA154320. This work was also supported by Fundação para a Ciência e Tecnologia through the project [PTDC/SAU-GMG/101572/2008] and through fellowships [SFRH/BPD/91562/2012 to ASF, SFRH/BD/51059/2010 to ANC]. IB is supported by NIEHS R01 ES018948 and NIAID/AI06288

An Atlas of the Thioredoxin Fold Class Reveals the Complexity of Function-Enabling Adaptations

The group of proteins that contain a thioredoxin (Trx) fold is huge and diverse. Assessment of the variation in catalytic machinery of Trx fold proteins is essential in providing a foundation for understanding their functional diversity and predicting the function of the many uncharacterized members of the class. The proteins of the Trx fold class retain common features—including variations on a dithiol CxxC active site motif—that lead to delivery of function. We use protein similarity networks to guide an analysis of how structural and sequence motifs track with catalytic function and taxonomic categories for 4,082 representative sequences spanning the known superfamilies of the Trx fold. Domain structure in the fold class is varied and modular, with 2.8% of sequences containing more than one Trx fold domain. Most member proteins are bacterial. The fold class exhibits many modifications to the CxxC active site motif—only 56.8% of proteins have both cysteines, and no functional groupings have absolute conservation of the expected catalytic motif. Only a small fraction of Trx fold sequences have been functionally characterized. This work provides a global view of the complex distribution of domains and catalytic machinery throughout the fold class, showing that each superfamily contains remnants of the CxxC active site. The unifying context provided by this work can guide the comparison of members of different Trx fold superfamilies to gain insight about their structure-function relationships, illustrated here with the thioredoxins and peroxiredoxins