Multi-Community Risk Assessment Framework for Drinking Water

PresentationDrinking water supply involves a complex network of natural and man-made infrastructure necessary to capture, store, convey, treat, and discharge this necessary resource. Each component in this “cloud to tap” supply chain faces a host of threats such as systemic decay, population change, natural disaster, cyber and physical attacks, and/or contamination incidents. Evaluating and quantifying the near- and long-term implications of these stressors on the risk and resilience of the current water infrastructure system has historically been implemented at the local utility level. The Drinking Water Resilience Project (DWRP), a collaboration between the Department of Homeland Security, Oak Ridge National Laboratory (ORNL), Sandia National Laboratories, the University of Colorado, Colorado Springs (UCCS), and the University of Tennessee (UT) is aimed at providing a more comprehensive view of water utility risk and resilience. Specifically, Sandia’s effort will develop an infrastructure risk assessment tool to support self-assessment by the asset owner/operator using an interactive, data-rich, web-based application that guides the user through the analysis. The associated analysis is intended to be simple, consistent and comparable. This facilitates the sharing of results, in a secure environment, across multiple levels of government as the need requires. This sharing helps place individual utility results in the broader context of risk borne by similar utilities across the U.S. Shared analysis also helps identify and address issues with assets and resources shared across multiple utilities. Most importantly, risks and mitigating measures can be prioritized across different geographic scales to aid funding decisions made at levels beyond the capacity of a single utility. A demonstration of the framework will be given along with demonstration results from several public utilities

Loss of MECP2 Leads to Activation of P53 and Neuronal Senescence.

To determine the role for mutations of MECP2 in Rett syndrome, we generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal-specific gene expression changes, including induction of a senescence-associated secretory phenotype (SASP) program. Patient-derived neurons made without MECP2 showed signs of stress, including induction of P53, and senescence. The induction of P53 appeared to affect dendritic branching in Rett neurons, as P53 inhibition restored dendritic complexity. The induction of P53 targets was also detectable in analyses of human Rett patient brain, suggesting that this disease-in-a-dish model can provide relevant insights into the human disorder

Against Whitewashing

This article is an account of recent activity in the U.K. archives sector against white supremacy which is written by a number of people active in the work. Through our work, we are aware of previous initiatives in this area, but written sources about the history of this work are patchy at best. This account offers a description of recent activity so that it is “on record”. We recognise that a historical account of previous efforts would be valuable, but that is not our objective here. This article offers a statement of the problem of white supremacy in the U.K.’s archives sector. It then provides an overview of the work of organisations such as the Black Cultural Archives (BCA), The National Archives (TNA), and the Archives and Records Association (ARA). This is background for more grassroots activities and networks, which are described in the article. The article discusses the events at the ARA 2019 conference, which was a flashpoint for resistance to white supremacy in the profession, before discussing a number of subsequent activities that sought to define a vision for the profession in which white supremacy and other violent power structures are abolished. The article concludes by offering some thoughts about the future of this work

Against Whitewashing: The Recent History of Anti-Racist Action in the British Archives Sector

This article is an account of recent activity in the U.K. archives sector against white supremacy which is written by a number of people active in the work. Through our work, we are aware of previous initiatives in this area, but written sources about the history of this work are patchy at best. This account offers a description of recent activity so that it is on record . We recognise that a historical account of previous efforts would be valuable, but that is not our objective here. This article offers a statement of the problem of white supremacy in the U.K.’s archives sector. It then provides an overview of the work of organisations such as the Black Cultural Archives (BCA), The National Archives (TNA), and the Archives and Records Association (ARA). This is background for more grassroots activities and networks, which are described in the article. The article discusses the events at the ARA 2019 conference, which was a flashpoint for resistance to white supremacy in the profession, before discussing a number of subsequent activities that sought to define a vision for the profession in which white supremacy and other violent power structures are abolished. The article concludes by offering some thoughts about the future of this work

“All roads lead to Rome”, but “Rome wasn’t built in a day". Advice on QSEP navigation from the ‘Roman Gods’ of assessment!

This article aims to explore assessors’ observations and experiences of QSEP in relation to trainee competence development and demonstration, and help QSEP trainees and supervisors to identify some of the potholes in the road and consider ways to avoid them. Specifically, assessors have written a short review of their QSEP observations and commentary about what they want to see more of in the future. Their views are forthright, but given in good faith in the spirit of providing advice to candidates, and guidance to supervisors, about the nature and scope of QSEP submissions

Antibody targeting of Cathepsin S induces antibody-dependent cellular cytotoxicity

<p>Abstract</p> <p>Background</p> <p>Proteolytic enzymes have been implicated in driving tumor progression by means of their cancer cell microenvironment activity where they promote proliferation, differentiation, apoptosis, migration, and invasion. Therapeutic strategies have focused on attenuating their activity using small molecule inhibitors, but the association of proteases with the cell surface during cancer progression opens up the possibility of targeting these using antibody dependent cellular cytotoxicity (ADCC). Cathepsin S is a lysosomal cysteine protease that promotes the growth and invasion of tumour and endothelial cells during cancer progression. Our analysis of colorectal cancer patient biopsies shows that cathepsin S associates with the cell membrane indicating a potential for ADCC targeting.</p> <p>Results</p> <p>Here we report the cell surface characterization of cathepsin S and the development of a humanized antibody (Fsn0503h) with immune effector function and a stable <it>in vivo </it>half-life of 274 hours. Cathepsin S is expressed on the surface of tumor cells representative of colorectal and pancreatic cancer (23%-79% positive expression). Furthermore the binding of Fsn0503h to surface associated cathepsin S results in natural killer (NK) cell targeted tumor killing. In a colorectal cancer model Fsn0503h elicits a 22% cytotoxic effect.</p> <p>Conclusions</p> <p>This data highlights the potential to target cell surface associated enzymes, such as cathepsin S, as therapeutic targets using antibodies capable of elicitingADCC in tumor cells.</p

Madagascar’s extraordinary biodiversity: Evolution, distribution, and use

Madagascar's biota is hyperdiverse and includes exceptional levels of endemicity. We review the current state of knowledge on Madagascar's past and current terrestrial and freshwater biodiversity by compiling and presenting comprehensive data on species diversity, endemism, and rates of species description and human uses, in addition to presenting an updated and simplified map of vegetation types. We report a substantial increase of records and species new to science in recent years; however, the diversity and evolution of many groups remain practically unknown (e.g., fungi and most invertebrates). Digitization efforts are increasing the resolution of species richness patterns and we highlight the crucial role of field- and collections-based research for advancing biodiversity knowledge and identifying gaps in our understanding, particularly as species richness corresponds closely to collection effort. Phylogenetic diversity patterns mirror that of species richness and endemism in most of the analyzed groups. We highlight humid forests as centers of diversity and endemism because of their role as refugia and centers of recent and rapid radiations. However, the distinct endemism of other areas, such as the grassland-woodland mosaic of the Central Highlands and the spiny forest of the southwest, is also biologically important despite lower species richness. The documented uses of Malagasy biodiversity are manifold, with much potential for the uncovering of new useful traits for food, medicine, and climate mitigation. The data presented here showcase Madagascar as a unique living laboratory for our understanding of evolution and the complex interactions between people and nature. The gathering and analysis of biodiversity data must continue and accelerate if we are to fully understand and safeguard this unique subset of Earth's biodiversity

Madagascar’s extraordinary biodiversity: Threats and opportunities

Madagascar's unique biota is heavily affected by human activity and is under intense threat. Here, we review the current state of knowledge on the conservation status of Madagascar's terrestrial and freshwater biodiversity by presenting data and analyses on documented and predicted species-level conservation statuses, the most prevalent and relevant threats, ex situ collections and programs, and the coverage and comprehensiveness of protected areas. The existing terrestrial protected area network in Madagascar covers 10.4% of its land area and includes at least part of the range of the majority of described native species of vertebrates with known distributions (97.1% of freshwater fishes, amphibians, reptiles, birds, and mammals combined) and plants (67.7%). The overall figures are higher for threatened species (97.7% of threatened vertebrates and 79.6% of threatened plants occurring within at least one protected area). International Union for Conservation of Nature (IUCN) Red List assessments and Bayesian neural network analyses for plants identify overexploitation of biological resources and unsustainable agriculture as themost prominent threats to biodiversity. We highlight five opportunities for action at multiple levels to ensure that conservation and ecological restoration objectives, programs, and activities take account of complex underlying and interacting factors and produce tangible benefits for the biodiversity and people of Madagascar

Wnt signalling and cancer stem cells

[Abstract] Intracellular signalling mediated by secreted Wnt proteins is essential for the establishment of cell fates and proper tissue patterning during embryo development and for the regulation of tissue homeostasis and stem cell function in adult tissues. Aberrant activation of Wnt signalling pathways has been directly linked to the genesis of different tumours. Here, the components and molecular mechanisms implicated in the transduction of Wnt signal, along with important results supporting a central role for this signalling pathway in stem cell function regulation and carcinogenesis will be briefly reviewed.Ministerio de Ciencia e Innovación; SAF2008-0060