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

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

HLAProfiler utilizes k-mer profiles to improve HLA calling accuracy for rare and common alleles in RNA-seq data

BACKGROUND: The human leukocyte antigen (HLA) system is a genomic region involved in regulating the human immune system by encoding cell membrane major histocompatibility complex (MHC) proteins that are responsible for self-recognition. Understanding the variation in this region provides important insights into autoimmune disorders, disease susceptibility, oncological immunotherapy, regenerative medicine, transplant rejection, and toxicogenomics. Traditional approaches to HLA typing are low throughput, target only a few genes, are labor intensive and costly, or require specialized protocols. RNA sequencing promises a relatively inexpensive, high-throughput solution for HLA calling across all genes, with the bonus of complete transcriptome information and widespread availability of historical data. Existing tools have been limited in their ability to accurately and comprehensively call HLA genes from RNA-seq data. RESULTS: We created HLAProfiler ( https://github.com/ExpressionAnalysis/HLAProfiler ), a k-mer profile-based method for HLA calling in RNA-seq data which can identify rare and common HLA alleles with > 99% accuracy at two-field precision in both biological and simulated data. For 68% of novel alleles not present in the reference database, HLAProfiler can correctly identify the two-field precision or exact coding sequence, a significant advance over existing algorithms. CONCLUSIONS: HLAProfiler allows for accurate HLA calls in RNA-seq data, reliably expanding the utility of these data in HLA-related research and enabling advances across a broad range of disciplines. Additionally, by using the observed data to identify potential novel alleles and update partial alleles, HLAProfiler will facilitate further improvements to the existing database of reference HLA alleles. HLAProfiler is available at https://expressionanalysis.github.io/HLAProfiler/

Genomic Analysis of Immune Cell Infiltrates Across 11 Tumor Types

Background: Immune infiltration of the tumor microenvironment has been associated with improved survival for some patients with solid tumors. The precise makeup and prognostic relevance of immune infiltrates across a broad spectrum of tumors remain unclear

The LCMV gp33-specific memory T cell repertoire narrows with age

Abstract Background The memory response to LCMV in mice persists for months to years with only a small decrease in the number of epitope specific CD8 T cells. This long persistence is associated with resistance to lethal LCMV disease. In contrast to studies focused on the number and surface phenotype of the memory cells, relatively little attention has been paid to the diversity of TCR usage in these cells. CD8+ T cell responses with only a few clones of identical specificity are believed to be relatively ineffective, presumably due to the relative ease of virus escape. Thus, a broad polyclonal response is associated with an effective anti-viral CD8+ T cell response. Results In this paper we show that the primary CD8+ T cell response to the LCMV gp33-41 epitope is extremely diverse. Over time while the response remains robust in terms of the number of gp33-tetramer+ T cells, the diversity of the response becomes less so. Strikingly, by 26 months after infection the response is dominated by a small number TCRβ sequences. In addition, it is of note the gp33 specific CD8+ T cells sorted by high and low tetramer binding populations 15 and 22 months after infection. High and low tetramer binding cells had equivalent diversity and were dominated by a small number of clones regardless of the time tested. A similar restricted distribution was seen in NP396 specific CD8+ T cells 26 months after infection. The identical TCRVβ sequences were found in both the tetramerhi and tetramerlo binding populations. Finally, we saw no evidence of public clones in the gp33-specific response. No CDR3 sequences were found in more than one mouse. Conclusions These data show that following LCMV infection the CD8+ gp33-specific CD8 T cell response becomes highly restricted with enormous narrowing of the diversity. This narrowing of the repertoire could contribute to the progressively ineffective immune response seen in aging

Do Global Diversity Patterns of Vertebrates Reflect Those of Monocots?

Few studies of global diversity gradients in plants exist, largely because the data are not available for all species involved. Instead, most global studies have focussed on vertebrates, as these taxa have historically been associated with the most complete data. Here, we address this shortfall by first investigating global diversity gradients in monocots, a morphologically and functionally diverse clade representing a quarter of flowering plant diversity, and then assessing congruence between monocot and vertebrate diversity patterns. To do this, we create a new dataset that merges biome-level associations for all monocot genera with country-level associations for almost all ∼70,000 species. We then assess the evidence for direct versus indirect effects of this plant diversity on vertebrate diversity using a combination of linear regression and structural equation modelling (SEM). Finally, we also calculate overlap of diversity hotspots for monocots and each vertebrate taxon. Monocots follow a latitudinal gradient although with pockets of extra-tropical diversity, mirroring patterns in vertebrates. Monocot diversity is positively associated with vertebrate diversity, but the strength of correlation varies depending on the clades being compared. Monocot diversity explains marginal amounts of variance (<10%) after environmental factors have been accounted for. However, correlations remain among model residuals, and SEMs apparently reveal some direct effects of monocot richness. Our results suggest that collinear responses to environmental gradients are behind much of the congruence observed, but that there is some evidence for direct effects of producer diversity on consumer diversity. Much remains to be done before broad-scale diversity gradients among taxa are fully explained. Our dataset of monocot distributions will aid in this endeavour

The 2019 Philippine UHC Act, Pandemic Management and Implementation Implications in a Post-COVID-19 World: A Content Analysis

The 2019 Philippine Universal Health Care Act (Republic Act 11223) was set for implementation in January 2020 when disruptions brought on by the pandemic occurred. Will the provisions of the new UHC Act for an improved health system enable agile responses to forthcoming shocks, such as this COVID-19 pandemic? A content analysis of the 2019 Philippine UHC Act can identify neglected and leverage areas for systems’ improvement in a post-pandemic world. While content or document analysis is commonly undertaken as part of scoping or systematic reviews of a qualitative nature, quantitative analyses using a two-way mixed effects, consistency, multiple raters type of intraclass correlation coefficient (ICC) were applied to check for reliability and consistency of agreement among the study participants in the manual tagging of UHC components in the legislation. The intraclass correlation reflected the individuals’ consistency of agreement with significant reliability (0.939, p \u3c 0.001). The assessment highlighted a centralized approach to implementation, which can set aside the crucial collaborations and partnerships demonstrated and developed during the pandemic. The financing for local governments was strengthened with a new ruling that could alter UHC integration tendencies. A smarter allocation of tax-based financing sources, along with strengthened information and communications systems, can confront issues of trust and accountability, amidst the varying capacities of agents and systems

Male obesity associated gonadal dysfunction and the role of bariatric surgery

Obesity is an ever growing pandemic and a prevalent problem among men of reproductive age that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the precision and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and preclinical data support these findings. Clinical studies on the impact of medically induced weight loss on serum testosterone concentrations and spermatogenesis is promising but may show differential and unsustainable results. In contrast, literature has demonstrated that weight loss after bariatric surgery is correlated with an increase in serum testosterone concentrations that is superior than that obtained with only lifestyle modifications, supporting a further metabolic benefit from surgery that may be specific to the male reproductive system. The data on sperm and semen parameters is controversial to date. Emerging evidence in the burgeoning field of genetics and epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells. Understanding the impact of this reprogramming is critical to a comprehensive view of the impact of obesity on subsequent generations. Furthermore, conveying the potential impact of these lifestyle changes on future progeny can serve as a powerful tool for obese men to modify their behavior. Healthcare professionals treating male infertility and obesity need to adapt their practice to assimilate these new findings to better counsel men about the importance of paternal preconception health and the impact of novel non-medical therapeutic interventions. Herein, we summarize the pathophysiology of obesity on the male reproductive system and emerging evidence regarding the potential role of bariatric surgery as treatment of male obesity-associated gonadal dysfunction

CRI iAtlas: an interactive portal for immuno-oncology research.

The Cancer Research Institute (CRI) iAtlas is an interactive web platform for data exploration and discovery in the context of tumors and their interactions with the immune microenvironment. iAtlas allows researchers to study immune response characterizations and patterns for individual tumor types, tumor subtypes, and immune subtypes. iAtlas supports computation and visualization of correlations and statistics among features related to the tumor microenvironment, cell composition, immune expression signatures, tumor mutation burden, cancer driver mutations, adaptive cell clonality, patient survival, expression of key immunomodulators, and tumor infiltrating lymphocyte (TIL) spatial maps. iAtlas was launched to accompany the release of the TCGA PanCancer Atlas and has since been expanded to include new capabilities such as (1) user-defined loading of sample cohorts, (2) a tool for classifying expression data into immune subtypes, and (3) integration of TIL mapping from digital pathology images. We expect that the CRI iAtlas will accelerate discovery and improve patient outcomes by providing researchers access to standardized immunogenomics data to better understand the tumor immune microenvironment and its impact on patient responses to immunotherapy

Universal Vectorial and Ultrasensitive Nanomechanical Force Field Sensor

Miniaturization of force probes into nanomechanical oscillators enables ultrasensitive investigations of forces on dimensions smaller than their characteristic length scale. Meanwhile it also unravels the force field vectorial character and how its topology impacts the measurement. Here we expose an ultrasensitive method to image 2D vectorial force fields by optomechanically following the bidimensional Brownian motion of a singly clamped nanowire. This novel approach relies on angular and spectral tomography of its quasi frequency-degenerated transverse mechanical polarizations: immersing the nanoresonator in a vectorial force field does not only shift its eigenfrequencies but also rotate eigenmodes orientation as a nano-compass. This universal method is employed to map a tunable electrostatic force field whose spatial gradients can even take precedence over the intrinsic nanowire properties. Enabling vectorial force fields imaging with demonstrated sensitivities of attonewton variations over the nanoprobe Brownian trajectory will have strong impact on scientific exploration at the nanoscale

Deletion of naïve T cells recognizing the minor histocompatibility antigen HY with toxin-coupled peptide-MHC class I tetramers inhibits cognate CTL responses and alters immunodominance

Alloreactive T-cell responses directed against minor histocompatibility (H) antigens, which arise from diverse genetic disparities between donor and recipient outside the MHC, are an important cause of rejection of MHC-matched grafts. Because clinically significant responses appear to be directed at only a few antigens, the selective deletion of naïve T cells recognizing donor-specific, immunodominant minor H antigens in recipients before transplantation may be a useful tolerogenic strategy. We have previously demonstrated that peptide-MHC class I tetramers coupled to a toxin can efficiently eliminate specific TCR-transgenic T cells in vivo. Here, using the minor histocompatibility antigen HY as a model, we investigated whether toxic tetramers could inhibit the subsequent priming of the two H2-Db-restricted, immunodominant T-cell responses by deleting precursor CTL. Immunization of female mice with male bone marrow elicited robust CTL activity against the Uty and Smcy epitopes, with Uty constituting the major response. As hypothesized, toxic tetramer administration prior to immunization increased survival of cognate peptide-pulsed cells in an in vivo CTL assay, and reduced the frequency of corresponding T cells. However, tetramer-mediated decreases in either T-cell population magnified CTL responses against the non-targeted epitope, suggesting that Db-Uty+ and Db-Smcy+ T cells compete for a limited common resource during priming. Toxic tetramers conceivably could be used in combination to dissect or manipulate CD8+ T-cell immunodominance hierarchies, and to prevent the induction of donor-specific, minor H antigen CTL responses in allotransplantation