296 research outputs found

    Political Influence Efforts in the US Through Campaign Contributions and Lobbying Expenditures: An Index Approach

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    Efforts by private-sector entities, nongovernment organizations, and other interest groups to exert political influence are pervasive in American politics, as they are in Australia, Canada, France, the United Kingdom, and other high-income democracies. Such efforts are also found in more autocratic societies such as China and Russia. However, legalized forms of political influence such as campaign contributions and lobbying efforts are more widespread in well-established democracies such as the United States.Importantly, efforts to influence political and administrative decisions can be good or bad, but either way, understanding the extent to which individual sectors of the economy engage in efforts to affect policy and regulatory initiatives is of interest. In this report, using publicly available information on federal campaign contributions and lobbying expenditures associated with individual sectors of the economy, we construct a set of political influence effort indexes for 60 sectors of the United States economy.The indexes are estimated using publicly available data, compiled by OpenSecrets from public sources, on federal campaign contributions and expenditures on lobbying efforts, divided by each sector's gross value of output, for each year from 2003 to 2020. Thus, for each sector in each year, we obtain an estimate of the dollars spent on political influence efforts at the federal level per million dollars of sector gross output. Index values are obtained by dividing each sector's outlays by average outlays per million dollars of output among the entire 60 sectors (that is, total spending on campaign contributions and lobbying divided by total output for all 60 sectors). An index value of one for a given sector indicates that the sector's efforts to exert political influence through lobbying and campaign contributions are representative of economy-wide efforts. A value of two indicates that a sector is investing twice as much as the average amount among all industries; an index value of 0.5 indicates the sector's expenditures are half the average amoun

    Potent and Broad Inhibition of HIV-1 by a Peptide from the gp41 Heptad Repeat-2 Domain Conjugated to the CXCR4 Amino Terminus.

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    HIV-1 entry can be inhibited by soluble peptides from the gp41 heptad repeat-2 (HR2) domain that interfere with formation of the 6-helix bundle during fusion. Inhibition has also been seen when these peptides are conjugated to anchoring molecules and over-expressed on the cell surface. We hypothesized that potent anti-HIV activity could be achieved if a 34 amino acid peptide from HR2 (C34) were brought to the site of virus-cell interactions by conjugation to the amino termini of HIV-1 coreceptors CCR5 or CXCR4. C34-conjugated coreceptors were expressed on the surface of T cell lines and primary CD4 T cells, retained the ability to mediate chemotaxis in response to cognate chemokines, and were highly resistant to HIV-1 utilization for entry. Notably, C34-conjugated CCR5 and CXCR4 each exhibited potent and broad inhibition of HIV-1 isolates from diverse clades irrespective of tropism (i.e., each could inhibit R5, X4 and dual-tropic isolates). This inhibition was highly specific and dependent on positioning of the peptide, as HIV-1 infection was poorly inhibited when C34 was conjugated to the amino terminus of CD4. C34-conjugated coreceptors could also inhibit HIV-1 isolates that were resistant to the soluble HR2 peptide inhibitor, enfuvirtide. When introduced into primary cells, CD4 T cells expressing C34-conjugated coreceptors exhibited physiologic responses to T cell activation while inhibiting diverse HIV-1 isolates, and cells containing C34-conjugated CXCR4 expanded during HIV-1 infection in vitro and in a humanized mouse model. Notably, the C34-conjugated peptide exerted greater HIV-1 inhibition when conjugated to CXCR4 than to CCR5. Thus, antiviral effects of HR2 peptides can be specifically directed to the site of viral entry where they provide potent and broad inhibition of HIV-1. This approach to engineer HIV-1 resistance in functional CD4 T cells may provide a novel cell-based therapeutic for controlling HIV infection in humans

    Costs of Illness in the 1993 Waterborne Cryptosporidium Outbreak, Milwaukee, Wisconsin

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    To assess the total medical costs and productivity losses associated with the 1993 waterborne outbreak of cryptosporidiosis in Milwaukee, Wisconsin, including the average cost per person with mild, moderate, and severe illness, we conducted a retrospective cost-of-illness analysis using data from 11 hospitals in the greater Milwaukee area and epidemiologic data collected during the outbreak. The total cost of outbreak-associated illness was 96.2million:96.2 million: 31.7 million in medical costs and 64.6millioninproductivitylosses.Theaveragetotalcostsforpersonswithmild,moderate,andsevereillnesswere64.6 million in productivity losses. The average total costs for persons with mild, moderate, and severe illness were 116, 475,and475, and 7,808, respectively. The potentially high cost of waterborne disease outbreaks should be considered in economic decisions regarding the safety of public drinking water supplies

    Absolute properties of the spotted eclipsing binary star CV Bootis

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    We present new V-band differential brightness measurements as well as new radial-velocity measurements of the detached, circular, 0.84-day period, double-lined eclipsing binary system CV Boo. These data along with other observations from the literature are combined to derive improved absolute dimensions of the stars for the purpose of testing various aspects of theoretical modeling. Despite complications from intrinsic variability we detect in the system, and despite the rapid rotation of the components, we are able to determine the absolute masses and radii to better than 1.3% and 2%, respectively. We obtain M(A) = 1.032 +/- 0.013 M(Sun) and R(B) = 1.262 +/- 0.023 R(Sun) for the hotter, larger, and more massive primary (star A), and M(B) = 0.968 +/- 0.012 M(Sun) and R(B) = 1.173 +/- 0.023 R(Sun) for the secondary. The estimated effective temperatures are 5760 +/- 150 K and 5670 +/- 150 K. The intrinsic variability with a period about 1% shorter than the orbital period is interpreted as being due to modulation by spots on one or both components. This implies that the spotted star(s) must be rotating faster than the synchronous rate, which disagrees with predictions from current tidal evolution models according to which both stars should be synchronized. We also find that the radius of the secondary is larger than expected from stellar evolution calculations by about 10%, a discrepancy also seen in other (mostly lower-mass and active) eclipsing binaries. We estimate the age of the system to be approximately 9 Gyr. Both components are near the end of their main-sequence phase, and the primary may have started the shell hydrogen-burning stage.Comment: 17 pages in emulateapj format, including figures and tables. To appear in The Astronomical Journa

    The Lower Main Sequence and the Orbital Period Distribution of Cataclysmic Variable Stars

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    The color-magnitude diagram of the lower main sequence, as measured from a volume-limited sample of nearby stars, shows an abrupt downward jump between Mv = 12 and 13. This jump indicates that the observed mass-radius relationship steepens between 0.3 and 0.2 solar masses, but theoretical models show no such effect. It is difficult to isolate the source of this disagreement: the observational mass-radius relationship relies upon transformations that may not be sufficiently accurate, while the theoretical relationship relies upon stellar models that may not be sufficiently complete, particularly in their treatment of the complex physics governing the interior equation-of-state. If the features in the observationally derived mass-radius relationship are real, their existence provides a natural explanation for the well-known gap in the orbital period distribution of cataclysmic variables. This explanation relies only upon the observed mass-radius relationship of low-mass stars, and does not require ad hoc changes in magnetic braking or in the structure of cataclysmic variable secondaries. If correct, it will allow broader application of cataclysmic variable observations to problems of basic stellar physics.Comment: 27 pages, 10 postscript figures, AASTeX (aaspp4), accepted by Ap

    Antigenic conservation and immunogenicity of the HIV coreceptor binding site

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    Immunogenic, broadly reactive epitopes of the HIV-1 envelope glycoprotein could serve as important targets of the adaptive humoral immune response in natural infection and, potentially, as components of an acquired immune deficiency syndrome vaccine. However, variability in exposed epitopes and a combination of highly effective envelope-cloaking strategies have made the identification of such epitopes problematic. Here, we show that the chemokine coreceptor binding site of HIV-1 from clade A, B, C, D, F, G, and H and circulating recombinant form (CRF)01, CRF02, and CRF11, elicits high titers of CD4-induced (CD4i) antibody during natural human infection and that these antibodies bind and neutralize viruses as divergent as HIV-2 in the presence of soluble CD4 (sCD4). 178 out of 189 (94%) HIV-1–infected patients had CD4i antibodies that neutralized sCD4-pretreated HIV-2 in titers (50% inhibitory concentration) as high as 1:143,000. CD4i monoclonal antibodies elicited by HIV-1 infection also neutralized HIV-2 pretreated with sCD4, and polyclonal antibodies from HIV-1–infected humans competed specifically with such monoclonal antibodies for binding. In vivo, variants of HIV-1 with spontaneously exposed coreceptor binding surfaces were detected in human plasma; these viruses were neutralized directly by CD4i antibodies. Despite remarkable evolutionary diversity among primate lentiviruses, functional constraints on receptor binding create opportunities for broad humoral immune recognition, which in turn serves to constrain the viral quasispecies

    Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells

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    The functional properties of circulating CD8+ T cells have been associated with immune control of HIV. However, viral replication occurs predominantly in secondary lymphoid tissues, such as lymph nodes (LNs). We used an integrated single-cell approach to characterize effective HIV-specific CD8+ T cell responses in the LNs of elite controllers (ECs), defined as individuals who suppress viral replication in the absence of antiretroviral therapy (ART). Higher frequencies of total memory and follicle-homing HIV-specific CD8+ T cells were detected in the LNs of ECs compared with the LNs of chronic progressors (CPs) who were not receiving ART. Moreover, HIV-specific CD8+ T cells potently suppressed viral replication without demonstrable cytolytic activity in the LNs of ECs, which harbored substantially lower amounts of CD4+ T cell–associated HIV DNA and RNA compared with the LNs of CPs. Single-cell RNA sequencing analyses further revealed a distinct transcriptional signature among HIV-specific CD8+ T cells from the LNs of ECs, typified by the down-regulation of inhibitory receptors and cytolytic molecules and the up-regulation of multiple cytokines, predicted secreted factors, and components of the protein translation machinery. Collectively, these results provide a mechanistic framework to expedite the identification of novel antiviral factors, highlighting a potential role for the localized deployment of noncytolytic functions as a determinant of immune efficacy against HIV

    A cellular trafficking signal in the SIV envelope protein cytoplasmic domain is strongly selected for in pathogenic infection

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    The HIV/SIV envelope glycoprotein (Env) cytoplasmic domain contains a highly conserved Tyr-based trafficking signal that mediates both clathrin-dependent endocytosis and polarized sorting. Despite extensive analysis, the role of these functions in viral infection and pathogenesis is unclear. An SIV molecular clone (SIVmac239) in which this signal is inactivated by deletion of Gly-720 and Tyr-721 (SIVmac239ΔGY), replicates acutely to high levels in pigtail macaques (PTM) but is rapidly controlled. However, we previously reported that rhesus macaques and PTM can progress to AIDS following SIVmac239ΔGY infection in association with novel amino acid changes in the Env cytoplasmic domain. These included an R722G flanking the ΔGY deletion and a nine nucleotide deletion encoding amino acids 734–736 (ΔQTH) that overlaps the rev and tat open reading frames. We show that molecular clones containing these mutations reconstitute signals for both endocytosis and polarized sorting. In one PTM, a novel genotype was selected that generated a new signal for polarized sorting but not endocytosis. This genotype, together with the ΔGY mutation, was conserved in association with high viral loads for several months when introduced into naïve PTMs. For the first time, our findings reveal strong selection pressure for Env endocytosis and particularly for polarized sorting during pathogenic SIV infection in vivo

    Accurate masses and radii of normal stars: modern results and applications

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    This paper presents and discusses a critical compilation of accurate, fundamental determinations of stellar masses and radii. We have identified 95 detached binary systems containing 190 stars (94 eclipsing systems, and alpha Centauri) that satisfy our criterion that the mass and radius of both stars be known to 3% or better. To these we add interstellar reddening, effective temperature, metal abundance, rotational velocity and apsidal motion determinations when available, and we compute a number of other physical parameters, notably luminosity and distance. We discuss the use of this information for testing models of stellar evolution. The amount and quality of the data also allow us to analyse the tidal evolution of the systems in considerable depth, testing prescriptions of rotational synchronisation and orbital circularisation in greater detail than possible before. The new data also enable us to derive empirical calibrations of M and R for single (post-) main-sequence stars above 0.6 M(Sun). Simple, polynomial functions of T(eff), log g and [Fe/H] yield M and R with errors of 6% and 3%, respectively. Excellent agreement is found with independent determinations for host stars of transiting extrasolar planets, and good agreement with determinations of M and R from stellar models as constrained by trigonometric parallaxes and spectroscopic values of T(eff) and [Fe/H]. Finally, we list a set of 23 interferometric binaries with masses known to better than 3%, but without fundamental radius determinations (except alpha Aur). We discuss the prospects for improving these and other stellar parameters in the near future.Comment: 56 pages including figures and tables. To appear in The Astronomy and Astrophysics Review. Ascii versions of the tables will appear in the online version of the articl
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