171 research outputs found

    Critical analysis of the T-history method: A fundamental approach

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    Energy storage is a key challenge to a sustainable energy supply. To design new storage systems accurateand representative thermal property measurements are essential. The T-history method is quick anduncomplicated, however numerous adaptations have been proposed over the years. In this study thesemethods have been classified and critically assessed based on their mathematical formulation and exper-imental configuration. They can be broadly categorized according to one of three assumptions regardingthe heat transfer coefficient for natural convection: it is constant either as a function of time or tem-perature, or it is negligible. This work proves in addition that the heat transfer coefficient for naturalconvection, varies both as a function of time and temperature. This is demonstrated both experimentallyand through rigorous simulation of the proposed configurations. Thus T-history methods which show themost promise for precise and unambiguous measurements eliminate convection by making conductionthe dominant thermal resistance in the system. These techniques can be tailored to different materialsand do not require a simultaneous reference due to the use of a rigorous fundamental model comparedto the lumped parameter approximation. The addition of heat flux sensors to quantify actual heat lossesis recommended for absolute measurement certainty.The research leading to these results has received funding from the European Commission Seventh Framework Programme (FP/2007-2013) and under Grant agreement N°PIRSES-GA-2013-610692 (INNOSTORAGE), and from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 657466 (INPATH-TES). The work is partially funded by the Spanish government (ENE2015-64117-C5-1-R (MINECO/FEDER)). Dr. Luisa F. Cabeza would like to thank the Catalan Government for the quality accreditation given to the research group GREA (2014 SGR 123)

    Multiple doses of trandolapril do not affect warfarin pharmacodynamics

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    Objective. The effects of multiple doses of trandolapril (a new angiotensin-converting enzyme inhibitor) on the pharmacodynamics of a single 25 mg dose of warfarin were investigated in 19 men.Design. A double-blind, placebo-controlled cross-over design was used. The study consisted of two periods of 13 days each, during which subjects received either trandolapril 2 mg or placebo once daily according to a randomisation plan. Warfarin was given on day 8 of each of these periods.Setting. The study was carried out at the Hoechst Research Centre for Clinical Pharmacology, Department of Pharmacology, University of the Orange Free State, Bloemfontein.Patients. Nineteen healthy white men aged between 18 and 28 years and weighing between 65 and 98 kg volunteered for the study.Outcome measures. Prothrombin time (PT) and coagulation factors II, VII, IX and X were measured before and sequentially up to 6 days after warfarin administration. Areas under the PT and coagulation factor time curves for warfarin + trandolapril were compared with the corresponding areas for warfarin + placebo. The two treatment combinations were also compared at each measuring time.Results. The point estimate for the ratio of the treatment means of warfarin + trandolapril relative to warfarin + placebo for PT was 97% (90% confidence interval: 90% 103%). The corresponding value for factor VII was 97% (90% confidence interval: 91 % - 102%).Conclusion. The concomitant administration of trandolapril did not affect the pharmacodynamic effects of warfarin

    ISWI Regulates Higher-Order Chromatin Structure and Histone H1 Assembly In Vivo

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    Imitation SWI (ISWI) and other ATP-dependent chromatin-remodeling factors play key roles in transcription and other processes by altering the structure and positioning of nucleosomes. Recent studies have also implicated ISWI in the regulation of higher-order chromatin structure, but its role in this process remains poorly understood. To clarify the role of ISWI in vivo, we examined defects in chromosome structure and gene expression resulting from the loss of Iswi function in Drosophila. Consistent with a broad role in transcriptional regulation, the expression of a large number of genes is altered in Iswi mutant larvae. The expression of a dominant-negative form of ISWI leads to dramatic alterations in higher-order chromatin structure, including the apparent decondensation of both mitotic and polytene chromosomes. The loss of ISWI function does not cause obvious defects in nucleosome assembly, but results in a significant reduction in the level of histone H1 associated with chromatin in vivo. These findings suggest that ISWI plays a global role in chromatin compaction in vivo by promoting the association of the linker histone H1 with chromatin

    A Novel Pzg-NURF Complex Regulates Notch Target Gene Activity

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    The Putzig (Pzg) protein is associated with the NURF nucleosome remodeling complex, thereby promoting Notch target gene expression. Our findings suggest a novel Pzg-NURF complex that is responsible for the epigenetic regulation of Notch target genes

    Occupational health and safety and the National Public Health Institute of South Africa : deliberations from a national consultative meeting

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    On 11 November 2015, the National Department of Health (NDoH) published the National Public Health Institute of South Africa (NAPHISA) Draft Bill 2015 for public comment. The aim of the Draft Bill is: '[t]o provide for the establishment of the National Public Health Institute of South Africa in order to conduct disease and injury surveillance and to provide specialised public health services, public health interventions, training and research directed towards the major health challenges affecting the population of the Republic.'http://www.samj.org.zaam2016School of Health Systems and Public Health (SHSPH

    Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

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    We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo

    Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans

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    The Southern African Human Genome Programme is a national initiative that aspires to unlock the unique genetic character of southern African populations for a better understanding of human genetic diversity. In this pilot study the Southern African Human Genome Programme characterizes the genomes of 24 individuals (8 Coloured and 16 black southeastern Bantu-speakers) using deep whole-genome sequencing. A total of ~16 million unique variants are identified. Despite the shallow time depth since divergence between the two main southeastern Bantu-speaking groups (Nguni and Sotho-Tswana), principal component analysis and structure analysis reveal significant (p < 10−6) differentiation, and FST analysis identifies regions with high divergence. The Coloured individuals show evidence of varying proportions of admixture with Khoesan, Bantu-speakers, Europeans, and populations from the Indian sub-continent. Whole-genome sequencing data reveal extensive genomic diversity, increasing our understanding of the complex and region-specific history of African populations and highlighting its potential impact on biomedical research and genetic susceptibility to disease

    A new strategy for isolating genes controlling dosage compensation in Drosophila using a simple epigenetic mosaic eye phenotype

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    <p>Abstract</p> <p>Background</p> <p>The <it>Drosophila </it>Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and non-coding <it>roX </it>RNA. It paints the male X at hundreds of bands where it acetylates histone H4 at lysine 16. This epigenetic mark increases expression from the single male X chromosome approximately twofold above what gene-specific factors produce from each female X chromosome. This equalises X-linked gene expression between the sexes. Previous screens for components of dosage compensation relied on a distinctive male-specific lethal phenotype.</p> <p>Results</p> <p>Here, we report a new strategy relying upon an unusual male-specific mosaic eye pigmentation phenotype produced when the MSL complex acts upon autosomal <it>roX1 </it>transgenes. Screening the second chromosome identified at least five loci, two of which are previously described components of the MSL complex. We focused our analysis on the modifier alleles of MSL1 and MLE (for 'maleless'). The MSL1 lesions are not simple nulls, but rather alter the PEHE domain that recruits the MSL3 chromodomain and MOF ('males absent on first') histone acetyltransferase subunits to the complex. These mutants are compromised in their ability to recruit MSL3 and MOF, dosage compensate the X, and support long distance spreading from <it>roX1 </it>transgenes. Yet, paradoxically, they were isolated because they somehow increase MSL complex activity immediately around <it>roX1 </it>transgenes in combination with wild-type MSL1 subunits.</p> <p>Conclusions</p> <p>We propose that these diverse phenotypes arise from perturbations in assembly of MSL subunits onto nascent <it>roX </it>transcripts. This strategy is a promising alternative route for identifying previously unknown components of the dosage compensation pathway and novel alleles of known MSL proteins.</p

    Psychological and social consequences among mothers suffering from perinatal loss: perspective from a low income country

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    <p>Abstract</p> <p>Background</p> <p>In developed countries, perinatal death is known to cause major emotional and social effects on mothers. However, little is known about these effects in low income countries which bear the brunt of perinatal mortality burden. This paper reports the impact of perinatal death on psychological status and social consequences among mothers in a rural area of Bangladesh.</p> <p>Methods</p> <p>A total of 476 women including 122 women with perinatal deaths were assessed with the Edinburgh Postnatal Depression Scale (EPDS-B) at 6 weeks and 6 months postpartum, and followed up for negative social consequences at 6 months postpartum. Trained female interviewers carried out structured interviews at women's home.</p> <p>Results</p> <p>Overall 43% (95% CI: 33.7-51.8%) of women with a perinatal loss at 6 weeks postpartum were depressed compared to 17% (95% CI: 13.7-21.9%) with healthy babies (p = < 0.001). Depression status were significantly associated with women reporting negative life changes such as worse relationships with their husband (adjusted OR = 3.89, 95% CI: 1.37-11.04) and feeling guilty (adjusted OR = 2.61, 95% CI: 1.22-5.63) following the results of their last pregnancy outcome after 6 months of childbirth.</p> <p>Conclusions</p> <p>This study highlights the greatly increased vulnerability of women with perinatal death to experience negative psychological and social consequences. There is an urgent need to develop appropriate mental health care services for mothers with perinatal deaths in Bangladesh, including interventions to develop positive family support.</p

    Stress-Induced PARP Activation Mediates Recruitment of Drosophila Mi-2 to Promote Heat Shock Gene Expression

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    Eukaryotic cells respond to genomic and environmental stresses, such as DNA damage and heat shock (HS), with the synthesis of poly-[ADP-ribose] (PAR) at specific chromatin regions, such as DNA breaks or HS genes, by PAR polymerases (PARP). Little is known about the role of this modification during cellular stress responses. We show here that the nucleosome remodeler dMi-2 is recruited to active HS genes in a PARP–dependent manner. dMi-2 binds PAR suggesting that this physical interaction is important for recruitment. Indeed, a dMi-2 mutant unable to bind PAR does not localise to active HS loci in vivo. We have identified several dMi-2 regions which bind PAR independently in vitro, including the chromodomains and regions near the N-terminus containing motifs rich in K and R residues. Moreover, upon HS gene activation, dMi-2 associates with nascent HS gene transcripts, and its catalytic activity is required for efficient transcription and co-transcriptional RNA processing. RNA and PAR compete for dMi-2 binding in vitro, suggesting a two step process for dMi-2 association with active HS genes: initial recruitment to the locus via PAR interaction, followed by binding to nascent RNA transcripts. We suggest that stress-induced chromatin PARylation serves to rapidly attract factors that are required for an efficient and timely transcriptional response
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