204 research outputs found

    Design and fabrication of 3-D printed conductive polymer structures for THz polarization control

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    In this paper, we numerically and experimentally demonstrate the inverse polarization effect in three-dimensional (3-D) printed polarizers for the frequency range of 0.5 - 2.7 THz. The polarizers simply consist of 3-D printed strip lines of conductive polylactic acid (CPLA, Proto-Pasta) and do not require a substrate or any further metallic deposition. The experimental and numerical results show that the proposed structure acts as a broadband polarizer between the range of 0.3 THz to 2.7 THz, in which the inverse polarization effect is clearly seen for frequencies above 0.5 THz. In the inverse polarization effect, the transmission of the transverse electric (TE) component exceeds that of the TM component, in contrast to the behavior of a typical wire-grid polarizer. We show how the performance of the polarizers depends on the spacing and thickness of the CPLA structure; extinction ratios higher than 20 dB are achieved. This is the first report using CPLA to fabricate THz polarizers, demonstrating the potential of using conductive polymers to design THz components efficiently and robustly

    Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

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    Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

    Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

    Get PDF
    Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015–2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

    Accredited qualifications for capacity development in disaster risk reduction and climate change adaptation

    Get PDF
    Increasingly practitioners and policy makers working across the globe are recognising the importance of bringing together disaster risk reduction and climate change adaptation. From studies across 15 Pacific island nations, a key barrier to improving national resilience to disaster risks and climate change impacts has been identified as a lack of capacity and expertise resulting from the absence of sustainable accredited and quality assured formal training programmes in the disaster risk reduction and climate change adaptation sectors. In the 2016 UNISDR Science and Technology Conference on the Implementation of the Sendai Framework for Disaster Risk Reduction 2015-2030, it was raised that most of the training material available are not reviewed either through a peer-to-peer mechanism or by the scientific community and are, thus, not following quality assurance standards. In response to these identified barriers, this paper focuses on a call for accredited formal qualifications for capacity development identified in the 2015 United Nations landmark agreements in DRR and CCA and uses the Pacific Islands Region of where this is now being implemented with the launch of the Pacific Regional Federation of Resilience Professionals, for DRR and CCA. A key issue is providing an accreditation and quality assurance mechanism that is shared across boundaries. This paper argues that by using the United Nations landmark agreements of 2015, support for a regionally accredited capacity development that ensures all countries can produce, access and effectively use scientific information for disaster risk reduction and climate change adaptation. The newly launched Pacific Regional Federation of Resilience Professionals who work in disaster risk reduction and climate change adaptation may offer a model that can be used more widely

    Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium

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    AbstractBarrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype in adult mouse oesophageal epithelium and is present in the human condition. These data suggest that induction of HNF4α is a key early step in the formation of Barrett's metaplasia and are consistent with an origin of Barrett's metaplasia from the oesophageal epithelium

    Entrapment of Viral Capsids in Nuclear PML Cages Is an Intrinsic Antiviral Host Defense against Varicella-Zoster Virus

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    The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant proteins

    Human and mouse essentiality screens as a resource for disease gene discovery.

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    The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery

    Act now against new NHS competition regulations: an open letter to the BMA and the Academy of Medical Royal Colleges calls on them to make a joint public statement of opposition to the amended section 75 regulations.

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    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
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