Race, power, history, and justice in America

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Political Science, 2009.Includes bibliographical references.This project sets out two broad aims. First, I seek to explain the persistence of racial inequality in an era of formal racial inequality. I offer a theory of power, historically evolved socially embedded power. The theory states that racial inequality is to be explained in the first instance by the way historical racial norms become embedded in practices and processes of path dependent institutions, shaping the way institutions value persons of color. Subsequently, this impacts the way broader society values persons of color, and the way they value themselves. This sets up the conclusion that the problem of racial inequality is fundamentally a problem of racial valuation rather than a problem of distributive justice. In articulating the theory of power, I depart from orthodox analytic political thought methodology by relying on a cross-section of empirical resources, such as history, sociology, and social psychology. Second, I conclude from the above that a theory of justice appropriate for the needs of racial inequality must center on a normative ideal as its primary aim to counteract this more fundamental dynamic. Given the above characterization of racial inequality, I argue that self-respect is the necessary ideal and the social bases of self-respect are the appropriate currency of justice. By self-respect I mean, one's disposition towards oneself such that plans and perceived purposes are reflectively developed in line with an autonomously articulated morally appropriate conception of the good life.(cont.) By the social bases of self-respect I mean, the public commitment and efforts made by major social institutions to embrace and affirm persons of color as substantive equals in a way that reckons with both the history and contemporary reality of racial injustice. I formulate justice as democratic partnership as the appropriate conception of racial justice. It states that justice obtains when institutions consistently provide the social bases of self-respect as per a defined set of institutional principles, and persons of color utilize this resource, as per a defined set of personal principles, by conceiving and pursuing the good of their lives just as the more socially and politically advantaged are able to.by Christopher J. Lebron.Ph.D

Marine nutrient subsidies promote biogeochemical hotspots in undisturbed, highly humic estuaries

The land-ocean dissolved organic carbon (DOC) flux represents a significant term within the global carbon budget, with peatland-dominated regions representing the most intense sources of terrestrial DOC export. As the interface between freshwater and marine systems, estuaries have the potential to act as a filter of the land-ocean carbon flux, removing terrestrially derived DOC, which is present at low concentrations in the oceans, via a combination of physicochemical and biological processes. However, the fate of peat-derived DOC within estuaries remains poorly quantified, partly due to the complicating influences of heterogeneous soils, land-use, point sources, and upstream modification of organic matter. To minimize these modifying factors, we studied DOC and inorganic nutrients in four small, peat-dominated, minimally disturbed, and oligotrophic Falkland Island estuaries. Contrary to expectations, we found limited evidence of physicochemical estuarine DOC removal, and instead observed apparent "hot zones" of biogeochemical activity, where terrestrially-derived silicate mixed with inorganic nitrogen and phosphorus entering the estuaries from the nutrient-rich marine ecosystem. In two estuaries, this coincided with apparent in situ DOC production. We suggest that the observed phenomena of marine nutrient subsidy of estuarine productivity, and flexible utilization of multiple nutrients within the oligotrophic system, may once have been widespread in temperate estuaries. However, this function has been lost in many ecosystems due to catchment eutrophication by agricultural and urban development. We conclude that the estuaries of the Falkland Islands provide a valuable pre-disturbance analogue for natural biogeochemical functioning in temperate estuaries receiving high organic matter inputs

Exposure to ambient particulate matter is associated with accelerated functional decline in idiopathic pulmonary fibrosis

BACKGROUND: Idiopathic pulmonary fibrosis (IPF), a progressive disease with an unknown pathogenesis, may be due in part to an abnormal response to injurious stimuli by alveolar epithelial cells. Air pollution and particulate inhalation of matter evoke a wide variety of pulmonary and systemic inflammatory diseases. We therefore hypothesized that increased average ambient particulate matter (PM) concentrations would be associated with an accelerated rate of decline in FVC in IPF. METHODS: We identified a cohort of subjects seen at a single university referral center from 2007 to 2013. Average concentrations of particulate matter < 10 and < 2.5 μg/m3 (PM10 and PM2.5, respectively) were assigned to each patient based on geocoded residential addresses. A linear multivariable mixed-effects model determined the association between the rate of decline in FVC and average PM concentration, controlling for baseline FVC at first measurement and other covariates. RESULTS: One hundred thirty-five subjects were included in the final analysis after exclusion of subjects missing repeated spirometry measurements and those for whom exposure data were not available. There was a significant association between PM10 levels and the rate of decline in FVC during the study period, with each μg/m3 increase in PM10 corresponding with an additional 46 cc/y decline in FVC (P = .008). CONCLUSIONS: Ambient air pollution, as measured by average PM10 concentration, is associated with an increase in the rate of decline of FVC in IPF, suggesting a potential mechanistic role for air pollution in the progression of disease

A Self-Absorption Census of Cold HI Clouds in the Canadian Galactic Plane Survey

We present a 21cm line HI self-absorption (HISA) survey of cold atomic gas within Galactic longitudes 75 to 146 degrees and latitudes -3 to +5 degrees. We identify HISA as spatially and spectrally confined dark HI features and extract it from the surrounding HI emission in the arcminute-resolution Canadian Galactic Plane Survey (CGPS). We compile a catalog of the most significant features in our survey and compare our detections against those in the literature. Within the parameters of our search, we find nearly all previously detected features and identify many new ones. The CGPS shows HISA in much greater detail than any prior survey and allows both new and previously-discovered features to be placed into the larger context of Galactic structure. In space and radial velocity, faint HISA is detected virtually everywhere that the HI emission background is sufficiently bright. This ambient HISA population may arise from small turbulent fluctuations of temperature and velocity in the neutral interstellar medium. By contrast, stronger HISA is organized into discrete complexes, many of which follow a longitude-velocity distribution that suggests they have been made visible by the velocity reversal of the Perseus arm's spiral density wave. The cold HI revealed in this way may have recently passed through the spiral shock and be on its way to forming molecules and, eventually, new stars. This paper is the second in a series examining HISA at high angular resolution. A companion paper (Paper III) describes our HISA search and extraction algorithms in detail.Comment: 44 pages, including 13 figure pages; to appear in June 10 ApJ, volume 626; figure quality significantly reduced for astro-ph; for full resolution, please see http://www.ras.ucalgary.ca/~gibson/hisa/cgps1_survey

Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute PE, including both clinical data and consensus opinion to provide guidance for clinicians caring for these patients

Glastir Monitoring & Evaluation Programme. First year annual report

The Welsh Government has commissioned a comprehensive new ecosystem monitoring and evaluation programme to monitor the effects of Glastir, its new land management scheme, and to monitor progress towards a range of international biodiversity and environmental targets. A random sample of 1 km squares stratified by landcover types will be used both to monitor change at a national level in the wider countryside and to provide a backdrop against which intervention measures are assessed using a second sample of 1 km squares located in areas eligible for enhanced payments for advanced interventions. Modelling in the first year has forecast change based on current understanding, whilst a rolling national monitoring programme based on an ecosystem approach will provide an evidence-base for on-going, adaptive development of the scheme by Welsh Government. To our knowledge, this will constitute the largest and most in-depth ecosystem monitoring and evaluation programme of any member state of the European Union

Histone deacetylases suppress cgg repeat-induced neurodegeneration via transcriptional silencing in models of Fragile X Tremor Ataxia Syndrome

Fragile X Tremor Ataxia Syndrome (FXTAS) is a common inherited neurodegenerative disorder caused by expansion of a CGG trinucleotide repeat in the 59UTR of the fragile X syndrome (FXS) gene, FMR1. The expanded CGG repeat is thought to induce toxicity as RNA, and in FXTAS patients mRNA levels for FMR1 are markedly increased. Despite the critical role of FMR1 mRNA in disease pathogenesis, the basis for the increase in FMR1 mRNA expression is unknown. Here we show that overexpressing any of three histone deacetylases (HDACs 3, 6, or 11) suppresses CGG repeat-induced neurodegeneration in a Drosophila model of FXTAS. This suppression results from selective transcriptional repression of the CGG repeat-containing transgene. These findings led us to evaluate the acetylation state of histones at the human FMR1 locus. In patient-derived lymphoblasts and fibroblasts, we determined by chromatin immunoprecipitation that there is increased acetylation of histones at the FMR1 locus in pre-mutation carriers compared to control or FXS derived cell lines. These epigenetic changes correlate with elevated FMR1 mRNA expression in pre-mutation cell lines. Consistent with this finding, histone acetyltransferase (HAT) inhibitors repress FMR1 mRNA expression to control levels in pre-mutation carrier cell lines and extend lifespan in CGG repeat-expressing Drosophila. These findings support a disease model whereby the CGG repeat expansion in FXTAS promotes chromatin remodeling in cis, which in turn increases expression of the toxic FMR1 mRNA. Moreover, these results provide proof of principle that HAT inhibitors or HDAC activators might be used to selectively repress transcription at the FMR1 locus.open293

Inactivation of PNKP by mutant ATXN3 triggers apoptosis by activating the DNA damage-response pathway in SCA3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an untreatable autosomal dominant neurodegenerative disease, and the most common such inherited ataxia worldwide. The mutation in SCA3 is the expansion of a polymorphic CAG tri-nucleotide repeat sequence in the C-terminal coding region of the ATXN3 gene at chromosomal locus 14q32.1. The mutant ATXN3 protein encoding expanded glutamine (polyQ) sequences interacts with multiple proteins in vivo, and is deposited as aggregates in the SCA3 brain. A large body of literature suggests that the loss of function of the native ATNX3-interacting proteins that are deposited in the polyQ aggregates contributes to cellular toxicity, systemic neurodegeneration and the pathogenic mechanism in SCA3. Nonetheless, a significant understanding of the disease etiology of SCA3, the molecular mechanism by which the polyQ expansions in the mutant ATXN3 induce neurodegeneration in SCA3 has remained elusive. In the present study, we show that the essential DNA strand break repair enzyme PNKP (polynucleotide kinase 3'-phosphatase) interacts with, and is inactivated by, the mutant ATXN3, resulting in inefficient DNA repair, persistent accumulation of DNA damage/strand breaks, and subsequent chronic activation of the DNA damage-response ataxia telangiectasia-mutated (ATM) signaling pathway in SCA3. We report that persistent accumulation of DNA damage/strand breaks and chronic activation of the serine/threonine kinase ATM and the downstream p53 and protein kinase C-d pro-apoptotic pathways trigger neuronal dysfunction and eventually neuronal death in SCA3. Either PNKP overexpression or pharmacological inhibition of ATM dramatically blocked mutant ATXN3-mediated cell death. Discovery of the mechanism by which mutant ATXN3 induces DNA damage and amplifies the pro-death signaling pathways provides a molecular basis for neurodegeneration due to PNKP inactivation in SCA3, and for the first time offers a possible approach to treatment.This study was funded by NIH grant NS073976 to TKH and a John Sealy Grant to PSS

Allele-Specific Knockdown of ALS-Associated Mutant TDP-43 in Neural Stem Cells Derived from Induced Pluripotent Stem Cells

TDP-43 is found in cytoplasmic inclusions in 95% of amyotrophic lateral sclerosis (ALS) and 60% of frontotemporal lobar degeneration (FTLD). Approximately 4% of familial ALS is caused by mutations in TDP-43. The majority of these mutations are found in the glycine-rich domain, including the variant M337V, which is one of the most common mutations in TDP-43. In order to investigate the use of allele-specific RNA interference (RNAi) as a potential therapeutic tool, we designed and screened a set of siRNAs that specifically target TDP-43(M337V) mutation. Two siRNA specifically silenced the M337V mutation in HEK293T cells transfected with GFP-TDP-43(wt) or GFP-TDP-43(M337V) or TDP-43 C-terminal fragments counterparts. C-terminal TDP-43 transfected cells show an increase of cytosolic inclusions, which are decreased after allele-specific siRNA in M337V cells. We then investigated the effects of one of these allele-specific siRNAs in induced pluripotent stem cells (iPSCs) derived from an ALS patient carrying the M337V mutation. These lines showed a two-fold increase in cytosolic TDP-43 compared to the control. Following transfection with the allele-specific siRNA, cytosolic TDP-43 was reduced by 30% compared to cells transfected with a scrambled siRNA. We conclude that RNA interference can be used to selectively target the TDP-43(M337V) allele in mammalian and patient cells, thus demonstrating the potential for using RNA interference as a therapeutic tool for ALS

The handbook for standardized field and laboratory measurements in terrestrial climate change experiments and observational studies (ClimEx)

1. Climate change is a world‐wide threat to biodiversity and ecosystem structure, functioning and services. To understand the underlying drivers and mechanisms, and to predict the consequences for nature and people, we urgently need better understanding of the direction and magnitude of climate change impacts across the soil–plant–atmosphere continuum. An increasing number of climate change studies are creating new opportunities for meaningful and high‐quality generalizations and improved process understanding. However, significant challenges exist related to data availability and/or compatibility across studies, compromising opportunities for data re‐use, synthesis and upscaling. Many of these challenges relate to a lack of an established ‘best practice’ for measuring key impacts and responses. This restrains our current understanding of complex processes and mechanisms in terrestrial ecosystems related to climate change. 2. To overcome these challenges, we collected best‐practice methods emerging from major ecological research networks and experiments, as synthesized by 115 experts from across a wide range of scientific disciplines. Our handbook contains guidance on the selection of response variables for different purposes, protocols for standardized measurements of 66 such response variables and advice on data management. Specifically, we recommend a minimum subset of variables that should be collected in all climate change studies to allow data re‐use and synthesis, and give guidance on additional variables critical for different types of synthesis and upscaling. The goal of this community effort is to facilitate awareness of the importance and broader application of standardized methods to promote data re‐use, availability, compatibility and transparency. We envision improved research practices that will increase returns on investments in individual research projects, facilitate second‐order research outputs and create opportunities for collaboration across scientific communities. Ultimately, this should significantly improve the quality and impact of the science, which is required to fulfil society's needs in a changing world