77 research outputs found

    Perspectives of the Clean Water Rule and an Alternative Policy

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    In this paper, we will analyze the different approaches that the Obama administration and the Trump administration took when determining the costs and benefits of the Clean Water Rule (CWR). Our goal is to determine the priorities of each administration and the economic justifications behind those considerations. We will begin by outlining forecasted benefits from clarifying the definition of Waters of the United States (WOTUS) determined by the Army Corp of Engineers and Environmental Protection Agency (EPA). Next we will look at how the Obama administration used these findings to draft the rule, and the potential social benefits from the policy. We will conduct a similar review of the actions and priorities of the Trump administration, then compare the two analyses. Additionally, we will examine the Clean Water Rule from the perspective of the agricultural industry. This examination will include a detailed description of how this industry is impacted by the rule; we will specify what, if any, additional regulations or burdens are faced. From there, we will use a political analysis to offer an explanation for why farm lobby groups oppose the legislation. We will discuss the social costs and benefits of further regulation and present our own policy for regulation that we believe will adequately supplement or replace the Clean Water Rule and Clean Water Act (CWA). This policy will both protect the environment and preserve incentives to invest and produce. Finally, we will comment on the long-term feasibility of our policy alternative and further research that would be necessary to proceed with policy revisions

    A High Spectral Resolution Study of the Soft X-ray Background with the X-ray Quantum Calorimeter

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    We present here a combined analysis of four high spectral resolution observations of the Diffuse X-ray Background (DXRB), made using the University of Wisconsin-Madison/Goddard Space Flight Center X-ray Quantum Calorimeter (XQC) sounding rocket payload. The observed spectra support the existence of a 0.1 \sim0.1~keV Local Hot Bubble and a 0.2 \sim0.2~keV Hot Halo, with discrepancies between repeated observations compatible with expected contributions of time-variable emission from Solar Wind Charge Exchange (SWCX). An additional component of 0.9 \sim0.9~keV emission observed only at low galactic latitudes can be consistently explained by unresolved dM stars.Comment: 21 pages, 6 figures, accepted for publication in Ap

    Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer\u27s Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study

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    With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer’s disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology

    AAV-mediated gene transfer to colon-innervating primary afferent neurons

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    Investigation of neural circuits underlying visceral pain is hampered by the difficulty in achieving selective manipulations of individual circuit components. In this study, we adapted a dual AAV approach, used for projection-specific transgene expression in the CNS, to explore the potential for targeted delivery of transgenes to primary afferent neurons innervating visceral organs. Focusing on the extrinsic sensory innervation of the mouse colon, we first characterized the extent of dual transduction following intrathecal delivery of one AAV9 vector and intracolonic delivery of a second AAV9 vector. We found that if the two AAV9 vectors were delivered one week apart, dorsal root ganglion (DRG) neuron transduction by the second vector was greatly diminished. Following delivery of the two viruses on the same day, we observed colocalization of the transgenes in DRG neurons, indicating dual transduction. Next, we delivered intrathecally an AAV9 vector encoding the inhibitory chemogenetic actuator hM4D(Gi) in a Cre-recombinase dependent manner, and on the same day injected an AAV9 vector carrying Cre-recombinase in the colon. DRG expression of hM4D(Gi) was demonstrated at the mRNA and protein level. However, we were unable to demonstrate selective inhibition of visceral nociception following hM4D(Gi) activation. Taken together, these results establish a foundation for development of strategies for targeted transduction of primary afferent neurons for neuromodulation of peripheral neural circuits

    Diffractive Dijet Production at sqrt(s)=630 and 1800 GeV at the Fermilab Tevatron

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    We report a measurement of the diffractive structure function FjjDF_{jj}^D of the antiproton obtained from a study of dijet events produced in association with a leading antiproton in pˉp\bar pp collisions at s=630\sqrt s=630 GeV at the Fermilab Tevatron. The ratio of FjjDF_{jj}^D at s=630\sqrt s=630 GeV to FjjDF_{jj}^D obtained from a similar measurement at s=1800\sqrt s=1800 GeV is compared with expectations from QCD factorization and with theoretical predictions. We also report a measurement of the ξ\xi (xx-Pomeron) and β\beta (xx of parton in Pomeron) dependence of FjjDF_{jj}^D at s=1800\sqrt s=1800 GeV. In the region 0.035<ξ<0.0950.035<\xi<0.095, t<1|t|<1 GeV2^2 and β<0.5\beta<0.5, FjjD(β,ξ)F_{jj}^D(\beta,\xi) is found to be of the form β1.0±0.1ξ0.9±0.1\beta^{-1.0\pm 0.1} \xi^{-0.9\pm 0.1}, which obeys β\beta-ξ\xi factorization.Comment: LaTeX, 9 pages, Submitted to Phys. Rev. Letter

    A Study of B0 -> J/psi K(*)0 pi+ pi- Decays with the Collider Detector at Fermilab

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    We report a study of the decays B0 -> J/psi K(*)0 pi+ pi-, which involve the creation of a u u-bar or d d-bar quark pair in addition to a b-bar -> c-bar(c s-bar) decay. The data sample consists of 110 1/pb of p p-bar collisions at sqrt{s} = 1.8 TeV collected by the CDF detector at the Fermilab Tevatron collider during 1992-1995. We measure the branching ratios to be BR(B0 -> J/psi K*0 pi+ pi-) = (8.0 +- 2.2 +- 1.5) * 10^{-4} and BR(B0 -> J/psi K0 pi+ pi-) = (1.1 +- 0.4 +- 0.2) * 10^{-3}. Contributions to these decays are seen from psi(2S) K(*)0, J/psi K0 rho0, J/psi K*+ pi-, and J/psi K1(1270)

    DNA methylation dynamics of the human preimplantation embryo

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    In mammals, cytosine methylation is predominantly restricted to CpG dinucleotides and stably distributed across the genome, with local, cell type-specific regulation directed by DNA binding factors1-3. This comparatively static landscape dramatically contrasts the events of fertilization, where the paternal genome is globally reprogrammed. Paternal genome demethylation includes the majority of CpGs, though methylation is maintained at several notable features4-7. While these dynamics have been extensively characterized in the mouse, only limited observations are available in other mammals, and direct measurements are required to understand the extent to which early embryonic landscapes are conserved8-10. We present genome-scale DNA methylation maps of human preimplantation development and embryonic stem cell (ESC) derivation, confirming a transient state of global hypomethylation that includes most CpGs, while sites of persistent maintenance are primarily restricted to gene bodies. While most features share similar dynamics to mouse, maternally contributed methylation is divergently targeted to species-specific sets of CpG island (CGI) promoters that extend beyond known Imprint Control Regions (ICRs). Retrotransposon regulation is also highly diverse and transitions from maternally to embryonically expressed, species-specific elements. Together, our data confirm that paternal genome demethylation is a general attribute of early mammalian development that is characterized by distinct modes of epigenetic regulation

    Withaferin a-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species

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    Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and MDA-MB-231 xenografts in vivo in association with apoptosis induction, but the mechanism of cell death is not fully understood. We now demonstrate, for the first time, that WA-induced apoptosis is mediated by reactive oxygen species (ROS) production due to inhibition of mitochondrial respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis. WA-mediated ROS production as well as apoptotic histone-associated DNA fragment release into the cytosol was significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7 cells were resistant to WA-induced ROS production, collapse of mitochondrial membrane potential, and apoptosis compared with respective wild-type cells. WA treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells, and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double knockout mouse were significantly more resistant to WA-induced apoptosis compared with fibroblasts derived from wild-type mouse. In conclusion, the present study provides novel insight into the molecular circuitry of WA-induced apoptosis involving ROS production and activation of Bax/Bak. © 2011 Hahm et al

    Existential Loneliness and end-of-life care: A Systematic Review

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    Contains fulltext : 88662.pdf (publisher's version ) (Closed access)Patients with a life-threatening illness can be confronted with various types of loneliness, one of which is existential loneliness (EL). Since the experience of EL is extremely disruptive, the issue of EL is relevant for the practice of end-of-life care. Still, the literature on EL has generated little discussion and empirical substantiation and has never been systematically reviewed. In order to systematically review the literature, we (1) identified the existential loneliness literature; (2) established an organising framework for the review; (3) conducted a conceptual analysis of existential loneliness; and (4) discussed its relevance for end-of-life care. We found that the EL concept is profoundly unclear. Distinguishing between three dimensions of EL-as a condition, as an experience, and as a process of inner growth-leads to some conceptual clarification. Analysis of these dimensions on the basis of their respective key notions-everpresent, feeling, defence; death, awareness, difficult communication; and inner growth, giving meaning, authenticity-further clarifies the concept. Although none of the key notions are unambiguous, they may function as a starting point for the development of care strategies on EL at the end of life.1 april 201
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