584 research outputs found

    Hybrid nanofabrication processes utilizing diblock copolymer nanotemplate prepared by self-assembled monolayer based surface neutralization

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    Nanostructures including nanohole and metal dot arrays were fabricated by hybrid processes combing self-assembled diblock copolymer and conventional semiconductor processes. The interfacial energy between polystyrene-b-polymethylmetacrylate (PS-b-PMMA) diblock copolymer and substrate surface was controlled by employing a self-assembled monolayer (SAM), resulting in a polymer template with well-ordered cylindrical nanohole array. The nanohole sizes were controlled within 10 to 22 nm in diameter using block copolymers with different molecular weights. The PS nanotemplates were fabricated on various substrates, including oxides, nitrides, and poly-Si. Nanohole pattern was transferred by dry etching process, producing inorganic nanohole templates. Also, gold nanodot arrays with diameter smaller than 10 nm were fabricated through lift off process. (c) 2008 American Vacuum Society.open112020sciescopu

    How Chromatin Is Remodelled during DNA Repair of UV-Induced DNA Damage in Saccharomyces cerevisiae

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    Global genome nucleotide excision repair removes DNA damage from transcriptionally silent regions of the genome. Relatively little is known about the molecular events that initiate and regulate this process in the context of chromatin. We've shown that, in response to UV radiation–induced DNA damage, increased histone H3 acetylation at lysine 9 and 14 correlates with changes in chromatin structure, and these alterations are associated with efficient global genome nucleotide excision repair in yeast. These changes depend on the presence of the Rad16 protein. Remarkably, constitutive hyperacetylation of histone H3 can suppress the requirement for Rad7 and Rad16, two components of a global genome repair complex, during repair. This reveals the connection between histone H3 acetylation and DNA repair. Here, we investigate how chromatin structure is modified following UV irradiation to facilitate DNA repair in yeast. Using a combination of chromatin immunoprecipitation to measure histone acetylation levels, histone acetylase occupancy in chromatin, MNase digestion, or restriction enzyme endonuclease accessibility assays to analyse chromatin structure, and finally nucleotide excision repair assays to examine DNA repair, we demonstrate that global genome nucleotide excision repair drives UV-induced chromatin remodelling by controlling histone H3 acetylation levels in chromatin. The concerted action of the ATPase and C3HC4 RING domains of Rad16 combine to regulate the occupancy of the histone acetyl transferase Gcn5 on chromatin in response to UV damage. We conclude that the global genome repair complex in yeast regulates UV-induced histone H3 acetylation by controlling the accessibility of the histone acetyl transferase Gcn5 in chromatin. The resultant changes in histone H3 acetylation promote chromatin remodelling necessary for efficient repair of DNA damage. Recent evidence suggests that GCN5 plays a role in NER in human cells. Our work provides important insight into how GG-NER operates in chromatin

    Factors affecting recruitment and retention of community health workers in a newborn care intervention in Bangladesh

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    <p>Abstract</p> <p>Background</p> <p>Well-trained and highly motivated community health workers (CHWs) are critical for delivery of many community-based newborn care interventions. High rates of CHW attrition undermine programme effectiveness and potential for implementation at scale. We investigated reasons for high rates of CHW attrition in Sylhet District in north-eastern Bangladesh.</p> <p>Methods</p> <p>Sixty-nine semi-structured questionnaires were administered to CHWs currently working with the project, as well as to those who had left. Process documentation was also carried out to identify project strengths and weaknesses, which included in-depth interviews, focus group discussions, review of project records (i.e. recruitment and resignation), and informal discussion with key project personnel.</p> <p>Results</p> <p>Motivation for becoming a CHW appeared to stem primarily from the desire for self-development, to improve community health, and for utilization of free time. The most common factors cited for continuing as a CHW were financial incentive, feeling needed by the community, and the value of the CHW position in securing future career advancement. Factors contributing to attrition included heavy workload, night visits, working outside of one's home area, familial opposition and dissatisfaction with pay.</p> <p>Conclusions</p> <p>The framework presented illustrates the decision making process women go through when deciding to become, or continue as, a CHW. Factors such as job satisfaction, community valuation of CHW work, and fulfilment of pre-hire expectations all need to be addressed systematically by programs to reduce rates of CHW attrition.</p

    Increased Phosphorylation of Vimentin in Noninfiltrative Meningiomas

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    International audienceBACKGROUND: Tissue invasion or tissue infiltration are clinical behaviors of a poor-prognosis subset of meningiomas. We carried out proteomic analyses of tissue extracts to discover new markers to accurately distinguish between infiltrative and noninfiltrative meningiomas. METHODOLOGY/PRINCIPAL FINDINGS: Protein lysates of 64 different tissue samples (including two brain-invasive and 32 infiltrative tumors) were submitted to SELDI-TOF mass spectrometric analysis. Mass profiles were used to build up both unsupervised and supervised hierarchical clustering. One marker was found at high levels in noninvasive and noninfiltrative tumors and appeared to be a discriminative marker for clustering infiltrative and/or invasive meningiomas versus noninvasive meningiomas in two distinct subsets. Sensitivity and specificity were 86.7% and 100%, respectively. This marker was purified and identified as a multiphosphorylated form of vimentin, a cytoskeletal protein expressed in meningiomas. CONCLUSIONS/SIGNIFICANCE: Specific forms of vimentin can be surrogate molecular indicators of the invasive/infiltrative phenotype in tumors

    Mesothelioma incidence surveillance systems and claims for workers’ compensation. Epidemiological evidence and prospects for an integrated framework

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    <p>Abstract</p> <p>Background</p> <p>Malignant mesothelioma is an aggressive and lethal tumour strongly associated with exposure to asbestos (mainly occupational). In Italy a large proportion of workers are protected from occupational diseases by public insurance and an epidemiological surveillance system for incident mesothelioma cases.</p> <p>Methods</p> <p>We set up an individual linkage between the Italian national mesothelioma register (ReNaM) and the Italian workers’ compensation authority (INAIL) archives. Logistic regression models were used to identify and test explanatory variables.</p> <p>Results</p> <p>We extracted 3270 mesothelioma cases with occupational origins from the ReNaM, matching them with 1625 subjects in INAIL (49.7%); 91.2% (1,482) of the claims received compensation. The risk of not seeking compensation is significantly higher for women and the elderly. Claims have increased significantly in recent years and there is a clear geographical gradient (northern and more developed regions having higher claims rates). The highest rates of compensation claims were after work known to involve asbestos.</p> <p>Conclusions</p> <p>Our data illustrate the importance of documentation and dissemination of all asbestos exposure modalities. Strategies focused on structural and systematic interaction between epidemiological surveillance and insurance systems are needed.</p

    Acceptability of evidence-based neonatal care practices in rural Uganda – implications for programming

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    <p>Abstract</p> <p>Background</p> <p>Although evidence-based interventions to reach the Millennium Development Goals for Maternal and Neonatal mortality reduction exist, they have not yet been operationalised and scaled up in Sub-Saharan African cultural and health systems. A key concern is whether these internationally recommended practices are acceptable and will be demanded by the target community. We explored the acceptability of these interventions in two rural districts of Uganda.</p> <p>Methods</p> <p>We conducted 10 focus group discussions consisting of mothers, fathers, grand parents and child minders (older children who take care of other children). We also did 10 key informant interviews with health workers and traditional birth attendants.</p> <p>Results</p> <p>Most maternal and newborn recommended practices are acceptable to both the community and to health service providers. However, health system and community barriers were prevalent and will need to be overcome for better neonatal outcomes. Pregnant women did not comprehend the importance of attending antenatal care early or more than once unless they felt ill. Women prefer to deliver in health facilities but most do not do so because they cannot afford the cost of drugs and supplies which are demanded in a situation of poverty and limited male support. Postnatal care is non-existent. For the newborn, delayed bathing and putting nothing on the umbilical cord were neither acceptable to parents nor to health providers, requiring negotiation of alternative practices.</p> <p>Conclusion</p> <p>The recommended maternal-newborn practices are generally acceptable to the community and health service providers, but often are not practiced due to health systems and community barriers. Communities associate the need for antenatal care attendance with feeling ill, and postnatal care is non-existent in this region. Health promotion programs to improve newborn care must prioritize postnatal care, and take into account the local socio-cultural situation and health systems barriers including the financial burden. Male involvement and promotion of waiting shelters at selected health units should be considered in order to increase access to supervised deliveries. Scale-up of the evidence based practices for maternal-neonatal health in Sub-Saharan Africa should follow rapid appraisal and adaptation of intervention packages to address the local health system and socio-cultural situation.</p

    Discovery of New Molecular Subtypes in Oesophageal Adenocarcinoma

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    A large number of patients suffering from oesophageal adenocarcinomas do not respond to conventional chemotherapy; therefore, it is necessary to identify new predictive biomarkers and patient signatures to improve patient outcomes and therapy selections. We analysed 87 formalin-fixed and paraffin-embedded (FFPE) oesophageal adenocarcinoma tissue samples with a reverse phase protein array (RPPA) to examine the expression of 17 cancer-related signalling molecules. Protein expression levels were analysed by unsupervised hierarchical clustering and correlated with clinicopathological parameters and overall patient survival. Proteomic analyses revealed a new, very promising molecular subtype of oesophageal adenocarcinoma patients characterised by low levels of the HSP27 family proteins and high expression of those of the HER family with positive lymph nodes, distant metastases and short overall survival. After confirmation in other independent studies, our results could be the foundation for the development of a Her2-targeted treatment option for this new patient subgroup of oesophageal adenocarcinoma
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