Incremental testing of the Community Multiscale Air Quality (CMAQ) modeling system version 4.7

This paper describes the scientific and structural updates to the latest release of the Community Multiscale Air Quality (CMAQ) modeling system version 4.7 (v4.7) and points the reader to additional resources for further details. The model updates were evaluated relative to observations and results from previous model versions in a series of simulations conducted to incrementally assess the effect of each change. The focus of this paper is on five major scientific upgrades: (a) updates to the heterogeneous N<sub>2</sub>O<sub>5</sub> parameterization, (b) improvement in the treatment of secondary organic aerosol (SOA), (c) inclusion of dynamic mass transfer for coarse-mode aerosol, (d) revisions to the cloud model, and (e) new options for the calculation of photolysis rates. Incremental test simulations over the eastern United States during January and August 2006 are evaluated to assess the model response to each scientific improvement, providing explanations of differences in results between v4.7 and previously released CMAQ model versions. Particulate sulfate predictions are improved across all monitoring networks during both seasons due to cloud module updates. Numerous updates to the SOA module improve the simulation of seasonal variability and decrease the bias in organic carbon predictions at urban sites in the winter. Bias in the total mass of fine particulate matter (PM<sub>2.5</sub>) is dominated by overpredictions of unspeciated PM<sub>2.5</sub> (PM<sub>other</sub>) in the winter and by underpredictions of carbon in the summer. The CMAQv4.7 model results show slightly worse performance for ozone predictions. However, changes to the meteorological inputs are found to have a much greater impact on ozone predictions compared to changes to the CMAQ modules described here. Model updates had little effect on existing biases in wet deposition predictions

IRB perspectives on the return of individual results from genomic research

Return of individual research results from genomic studies is a hotly debated ethical issue in genomic research. However, the perspective of key stakeholders—Institutional Review Board (IRB) reviewers—has been missing from this dialogue. This study explores the positions and experiences of IRB members and staff regarding this issue

Simone Weil: The Ethics of Affliction and the Aesthetics of Attention

For Simone Weil the invocation of ‘rights’ to address extreme human suffering–what she calls ‘affliction’–is ‘ludicrously inadequate’. Rights, Weil argues, invite a response, whereas what the afflicted require is not dialogue but simply to be heard. For Weil, hearing the ‘cry’ of the afflicted is the basis of all justice. The task of such a hearing is given over to Weil’s concept of attention, which demands an ethics of creative silence. This paper will argue that central to Weil’s ethics of attention, and thus the way she thinks we should show compassion and act justly, is the Kantian aesthetic concept of disinterestedness. I will argue that whilst Weil is influenced by Kant in multiple ways, it is his aesthetics, rather than his normative moral theory, that is most at play in her own ethical theory of attention

In Vivo Electroporation Enhances the Immunogenicity of an HIV-1 DNA Vaccine Candidate in Healthy Volunteers

DNA-based vaccines have been safe but weakly immunogenic in humans to date.We sought to determine the safety, tolerability, and immunogenicity of ADVAX, a multigenic HIV-1 DNA vaccine candidate, injected intramuscularly by in vivo electroporation (EP) in a Phase-1, double-blind, randomized placebo-controlled trial in healthy volunteers. Eight volunteers each received 0.2 mg, 1 mg, or 4 mg ADVAX or saline placebo via EP, or 4 mg ADVAX via standard intramuscular injection at weeks 0 and 8. A third vaccination was administered to eleven volunteers at week 36. EP was safe, well-tolerated and considered acceptable for a prophylactic vaccine. EP delivery of ADVAX increased the magnitude of HIV-1-specific cell mediated immunity by up to 70-fold over IM injection, as measured by gamma interferon ELISpot. The number of antigens to which the response was detected improved with EP and increasing dosage. Intracellular cytokine staining analysis of ELISpot responders revealed both CD4+ and CD8+ T cell responses, with co-secretion of multiple cytokines.This is the first demonstration in healthy volunteers that EP is safe, tolerable, and effective in improving the magnitude, breadth and durability of cellular immune responses to a DNA vaccine candidate.ClinicalTrials.gov NCT00545987

Does agri-environmental management enhance biodiversity and multiple ecosystem services?: A farm-scale experiment

Agri-environmental management has been promoted as an approach to enhance delivery of multiple ecosystem services. Most agri-environment agreements include several actions that the farmer agrees to put in place. But, most studies have only considered how individual agri-environmental actions affect particular ecosystem services. Thus, there is little understanding of how the range of agri-environmental actions available to a farmer might be deployed on any individual farm to enhance multiple services. To address this knowledge gap, we carried out an experimental study in which we deployed a set of agri-environmental actions on a commercial farm in southern England. Agri-environmental actions comprised wildflower margins and fallow areas in arable fields, creating and enhancing grassland with wildflowers, and digging ponds. Alongside biodiversity responses, we measured effects on a number of ecosystem services: pollination, pest control, crop and forage yield, water quality, climate regulation and cultural services. Wildflower margins enhanced invertebrates, pest control and crop yield, and aesthetic appeal. A greater number of pollinators was linked to enhanced oilseed rape yield. But these margins and the fallows did not prevent run-off of nutrients and sediment into waterways, and showed limited carbon sequestration or reduction of greenhouse gas emissions. Newly-dug ponds captured large amounts of sediment and provided aesthetic appeal. Grasslands had higher soil carbon content and microbial biomass, lower N20 emissions, and net sequestration of carbon compared to arable land. Enhancement of grassland plant diversity increased forage quality and aesthetic appeal. Visitors and residents valued a range of agri-environmental features and biodiversity across the farm. Our findings suggest one cannot necessarily expect any particular agri-environmental action will enhance all of a hoped-for set of ecosystem services in any particular setting. A bet-hedging strategy would be for farmers to apply a suite of options to deliver a range of ecosystem service benefits, rather than assuming that one or two options will work as catch-all solutions

Dedifferentiation and Proliferation of Mammalian Cardiomyocytes

It has long been thought that mammalian cardiomyocytes are terminally-differentiated and unable to proliferate. However, myocytes in more primitive animals such as zebrafish are able to dedifferentiate and proliferate to regenerate amputated cardiac muscle.Here we test the hypothesis that mature mammalian cardiomyocytes retain substantial cellular plasticity, including the ability to dedifferentiate, proliferate, and acquire progenitor cell phenotypes. Two complementary methods were used: 1) cardiomyocyte purification from rat hearts, and 2) genetic fate mapping in cardiac explants from bi-transgenic mice. Cardiomyocytes isolated from rodent hearts were purified by multiple centrifugation and Percoll gradient separation steps, and the purity verified by immunostaining and RT-PCR. Within days in culture, purified cardiomyocytes lost their characteristic electrophysiological properties and striations, flattened and began to divide, as confirmed by proliferation markers and BrdU incorporation. Many dedifferentiated cardiomyocytes went on to express the stem cell antigen c-kit, and the early cardiac transcription factors GATA4 and Nkx2.5. Underlying these changes, inhibitory cell cycle molecules were suppressed in myocyte-derived cells (MDCs), while microRNAs known to orchestrate proliferation and pluripotency increased dramatically. Some, but not all, MDCs self-organized into spheres and re-differentiated into myocytes and endothelial cells in vitro. Cell fate tracking of cardiomyocytes from 4-OH-Tamoxifen-treated double-transgenic MerCreMer/ZEG mouse hearts revealed that green fluorescent protein (GFP) continues to be expressed in dedifferentiated cardiomyocytes, two-thirds of which were also c-kit(+).Contradicting the prevailing view that they are terminally-differentiated, postnatal mammalian cardiomyocytes are instead capable of substantial plasticity. Dedifferentiation of myocytes facilitates proliferation and confers a degree of stemness, including the expression of c-kit and the capacity for multipotency

The status of the world's land and marine mammals: diversity, threat, and knowledge

Knowledge of mammalian diversity is still surprisingly disparate, both regionally and taxonomically. Here, we present a comprehensive assessment of the conservation status and distribution of the world's mammals. Data, compiled by 1700+ experts, cover all 5487 species, including marine mammals. Global macroecological patterns are very different for land and marine species but suggest common mechanisms driving diversity and endemism across systems. Compared with land species, threat levels are higher among marine mammals, driven by different processes (accidental mortality and pollution, rather than habitat loss), and are spatially distinct (peaking in northern oceans, rather than in Southeast Asia). Marine mammals are also disproportionately poorly known. These data are made freely available to support further scientific developments and conservation action

Bodies Under Empire: The Territory of American Feminism

Exploring American feminist cultural productions as a space wherein the socially marked female body is used to expose and critique the oppressive rhetoric of culturally enforced female femininity, this dissertation examines art and poetry that critically and strategically uses women's corporeal bodies as violent or gruesome sites of resistance. In this kind of feminist art and literature, the physical body is sacrificed in the service of drawing attention to the violence of the rhetoric of female femininity and its connection to colonialism and notions of empire. Establishing a historical precedent for feminist cultural productions using the body as a site of resistance, this study links such projects to similar cultural phenomena in the colonial period of the Americas, analyzing each work in the context of the culturally relevant ideologies in which it was created. Thus it analyzes gender rhetoric as it relates to the colonial project during the Protestant Reformation and Catholic Counter-Reformation, as well as examining contemporary ideologies of gender, including appetites and hunger, sexuality and sexual accessibility, domesticity, and beauty in both the colonial era and post-1900. Based on Foucault's notion of the heterotopia as an "other space" that exists outside of the cultural milieu with the purpose of reflecting and troubling social norms, I develop the term "rhetoritopia," implicating the body as a physical, political, and rhetorical "other space," a location used to communicate what systematic language and social conventions cannot: that rigid gender conventions are intrinsically linked to the violence of imperialism