15 research outputs found

    Tapped Out: Threats to the Human Right to Water in the Urban United States

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    In the United States today, the goal of universal water service is slipping out of reach. Water costs are rising across the country, forcing many individuals to forgo running water or sanitation, or to sacrifice other essential human rights. The fixed costs of water systems have increased in recent years, driven in part by underinvestment in infrastructure. In many cities, this has been exacerbated by population shifts and the economic downturn. In this era of increasing costs and limited financial resources, water providers struggle to balance the competing priorities of modernization and universal access. This report, researched and written by students of Georgetown Law’s Human Rights Institute in the winter of 2013, details the causes, effects, and solutions to the affordability crisis affecting water in the urban United States

    Orthogonal polynomials, reproducing kernels, and zeros of optimal approximants

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    We study connections between orthogonal polynomials, reproducing kernel functions, and polynomials P minimizing Dirichlet‐type norms ∄pf−1∄α for a given function f . For α ∈ [0,1] (which includes the Hardy and Dirichlet spaces of the disk) and general f , we show that such extremal polynomials are non‐vanishing in the closed unit disk. For negative α , the weighted Bergman space case, the extremal polynomials are non‐vanishing on a disk of strictly smaller radius, and zeros can move inside the unit disk. We also explain how dist Dα (1, f · Pn) , where Pn is the space of polynomials of degree at most n , can be expressed in terms of quantities associated with orthogonal polynomials and kernels, and we discuss methods for computing the quantities in question.This work was supported by NSF under the grant DMS1500675. DS was supported by ERC Grant 2011-ADG-20110209 from EU programme FP2007-2013 and MEC Projects MTM2014-51824-P and MTM2011-24606

    The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes

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    International audienceWith more than 80 members worldwide, the Orthobunyavirus genus in the Peribunyaviridae family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian host cells remains poorly characterized. Here, we investigated the entry mechanisms of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling of the virus with fluorescent dyes did not adversely affect its infectivity and allowed the monitoring of single particles in fixed and live cells. Using this approach, we found that endocytic internalization of bound viruses was asynchronous and occurred within 30 to 40 min. The virus entered Rab5a-positive (Rab5a(+)) early endosomes and, subsequently, late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did not require proteolytic cleavage, and endosomal acidification was sufficient and necessary for viral fusion. Acid-activated penetration began 15 to 25 min after initiation of virus internalization and relied on maturation of early endosomes to late endosomes. The optimal pH for viral membrane fusion was slightly below 6.0, and penetration was hampered when the potassium influx was abolished. Overall, our study provides real-time visualization of GERV entry into host cells and demonstrates the importance of late endosomal maturation in facilitating OBV penetration. IMPORTANCE Orthobunyaviruses (OBVs), which include La Crosse, Oropouche, and Schmallenberg viruses, represent a growing threat to humans and domestic animals worldwide. Ideally, preventing OBV spread requires approaches that target early stages of infection, i.e., virus entry. However, little is known about the molecular and cellular mechanisms by which OBVs enter and infect host cells. Here, we developed accurate, sensitive tools and assays to investigate the penetration process of GERV. Our data emphasize the central role of late endosomal maturation in GERV entry, providing a comprehensive overview of the early stages of an OBV infection. Our study also brings a complete toolbox of innovative methods to study each step of the OBV entry program in fixed and living cells, from virus binding and endocytosis to fusion and penetration. The information gained herein lays the foundation for the development of antiviral strategies aiming to block OBV entry.Orthobunyaviruses (OBVs), which include La Crosse, Oropouche, and Schmallenberg viruses, represent a growing threat to humans and domestic animals worldwide. Ideally, preventing OBV spread requires approaches that target early stages of infection, i.e., virus entry

    Millennium development health metrics: where do Africa's children and women of childbearing age live?

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    The Millennium Development Goals (MDGs) have prompted an expansion in approaches to deriving health metrics to measure progress toward their achievement. Accurate measurements should take into account the high degrees of spatial heterogeneity in health risks across countries, and this has prompted the development of sophisticated cartographic techniques for mapping and modeling risks. Conversion of these risks to relevant population-based metrics requires equally detailed information on the spatial distribution and attributes of the denominator populations. However, spatial information on age and sex composition over large areas is lacking, prompting many influential studies that have rigorously accounted for health risk heterogeneities to overlook the substantial demographic variations that exist subnationally and merely apply national-level adjustments.Here we outline the development of high resolution age- and sex-structured spatial population datasets for Africa in 2000-2015 built from over a million measurements from more than 20,000 subnational units, increasing input data detail from previous studies by over 400-fold. We analyze the large spatial variations seen within countries and across the continent for key MDG indicator groups, focusing on children under 5 and women of childbearing age, and find that substantial differences in health and development indicators can result through using only national level statistics, compared to accounting for subnational variation.Progress toward meeting the MDGs will be measured through national-level indicators that mask substantial inequalities and heterogeneities across nations. Cartographic approaches are providing opportunities for quantitative assessments of these inequalities and the targeting of interventions, but demographic spatial datasets to support such efforts remain reliant on coarse and outdated input data for accurately locating risk groups. We have shown here that sufficient data exist to map the distribution of key vulnerable groups, and that doing so has substantial impacts on derived metrics through accounting for spatial demographic heterogeneities that exist within nations across Africa.Journal Articleinfo:eu-repo/semantics/publishe
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