5,037 research outputs found

    Exploiting Polyhedral Symmetries in Social Choice

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    A large amount of literature in social choice theory deals with quantifying the probability of certain election outcomes. One way of computing the probability of a specific voting situation under the Impartial Anonymous Culture assumption is via counting integral points in polyhedra. Here, Ehrhart theory can help, but unfortunately the dimension and complexity of the involved polyhedra grows rapidly with the number of candidates. However, if we exploit available polyhedral symmetries, some computations become possible that previously were infeasible. We show this in three well known examples: Condorcet's paradox, Condorcet efficiency of plurality voting and in Plurality voting vs Plurality Runoff.Comment: 14 pages; with minor improvements; to be published in Social Choice and Welfar

    Applying blockchain to improve the integrity of the software development process

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    Software development is a complex endeavor that encompasses application and implementation layers with functional (refers to what is done) and non-functional (how is done) aspects. The efforts to scale agile software development practices are not wholly able to address issues such as integrity, which is a crucial non-functional aspect of the software development process. However, if we consider most software failures are Byzantine failures (i.e., where components may fail and there is imperfect information on which a component has failed.) that might impair the operation but do not completely disable the production line. In this paper, we assume software practitioners who cause defects as Byzantine participants and claim that most software failures can be mitigated by viewing software development as the Byzantine Generals Problem. Consequently, we propose a test-driven incentive mechanism based on a blockchain concept to orchestrate the software development process where production is controlled by a similar infrastructure based on the working principles of blockchain. We discuss the model that integrates blockchain with the software development process, and provide some recommendations for future work to address the issues while orchestrating software productio

    A mathematical model for breath gas analysis of volatile organic compounds with special emphasis on acetone

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    Recommended standardized procedures for determining exhaled lower respiratory nitric oxide and nasal nitric oxide have been developed by task forces of the European Respiratory Society and the American Thoracic Society. These recommendations have paved the way for the measurement of nitric oxide to become a diagnostic tool for specific clinical applications. It would be desirable to develop similar guidelines for the sampling of other trace gases in exhaled breath, especially volatile organic compounds (VOCs) which reflect ongoing metabolism. The concentrations of water-soluble, blood-borne substances in exhaled breath are influenced by: (i) breathing patterns affecting gas exchange in the conducting airways; (ii) the concentrations in the tracheo-bronchial lining fluid; (iii) the alveolar and systemic concentrations of the compound. The classical Farhi equation takes only the alveolar concentrations into account. Real-time measurements of acetone in end-tidal breath under an ergometer challenge show characteristics which cannot be explained within the Farhi setting. Here we develop a compartment model that reliably captures these profiles and is capable of relating breath to the systemic concentrations of acetone. By comparison with experimental data it is inferred that the major part of variability in breath acetone concentrations (e.g., in response to moderate exercise or altered breathing patterns) can be attributed to airway gas exchange, with minimal changes of the underlying blood and tissue concentrations. Moreover, it is deduced that measured end-tidal breath concentrations of acetone determined during resting conditions and free breathing will be rather poor indicators for endogenous levels. Particularly, the current formulation includes the classical Farhi and the Scheid series inhomogeneity model as special limiting cases.Comment: 38 page

    A functional methylome map of ulcerative colitis

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    The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation

    Identification of Giardia lamblia DHHC Proteins and the Role of Protein S-palmitoylation in the Encystation Process

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    Protein S-palmitoylation, a hydrophobic post-translational modification, is performed by protein acyltransferases that have a common DHHC Cys-rich domain (DHHC proteins), and provides a regulatory switch for protein membrane association. In this work, we analyzed the presence of DHHC proteins in the protozoa parasite Giardia lamblia and the function of the reversible S-palmitoylation of proteins during parasite differentiation into cyst. Two specific events were observed: encysting cells displayed a larger amount of palmitoylated proteins, and parasites treated with palmitoylation inhibitors produced a reduced number of mature cysts. With bioinformatics tools, we found nine DHHC proteins, potential protein acyltransferases, in the Giardia proteome. These proteins displayed a conserved structure when compared to different organisms and are distributed in different monophyletic clades. Although all Giardia DHHC proteins were found to be present in trophozoites and encysting cells, these proteins showed a different intracellular localization in trophozoites and seemed to be differently involved in the encystation process when they were overexpressed. dhhc transgenic parasites showed a different pattern of cyst wall protein expression and yielded different amounts of mature cysts when they were induced to encyst. Our findings disclosed some important issues regarding the role of DHHC proteins and palmitoylation during Giardia encystation.Fil: Merino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Zamponi, Nahuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Vranych, Cecilia Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Touz, Maria Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Ropolo, Andrea Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

    Spinal involvement in mucopolysaccharidosis IVA (Morquio-Brailsford or Morquio A syndrome): presentation, diagnosis and management.

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    Mucopolysaccharidosis IVA (MPS IVA), also known as Morquio-Brailsford or Morquio A syndrome, is a lysosomal storage disorder caused by a deficiency of the enzyme N-acetyl-galactosamine-6-sulphate sulphatase (GALNS). MPS IVA is multisystemic but manifests primarily as a progressive skeletal dysplasia. Spinal involvement is a major cause of morbidity and mortality in MPS IVA. Early diagnosis and timely treatment of problems involving the spine are critical in preventing or arresting neurological deterioration and loss of function. This review details the spinal manifestations of MPS IVA and describes the tools used to diagnose and monitor spinal involvement. The relative utility of radiography, computed tomography (CT) and magnetic resonance imaging (MRI) for the evaluation of cervical spine instability, stenosis, and cord compression is discussed. Surgical interventions, anaesthetic considerations, and the use of neurophysiological monitoring during procedures performed under general anaesthesia are reviewed. Recommendations for regular radiological imaging and neurologic assessments are presented, and the need for a more standardized approach for evaluating and managing spinal involvement in MPS IVA is addressed

    Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

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    Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

    De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development

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    Bosma arhinia microphthalmia syndrome (BAMS) is an extremely rare and striking condition characterized by complete absence of the nose with or without ocular defects. We report here that missense mutations in the epigenetic regulator SMCHD1 mapping to the extended ATPase domain of the encoded protein cause BAMS in all 14 cases studied. All mutations were de novo where parental DNA was available. Biochemical tests and in vivo assays in Xenopus laevis embryos suggest that these mutations may behave as gain-of-function alleles. This finding is in contrast to the loss-of-function mutations in SMCHD1 that have been associated with facioscapulohumeral muscular dystrophy (FSHD) type 2. Our results establish SMCHD1 as a key player in nasal development and provide biochemical insight into its enzymatic function that may be exploited for development of therapeutics for FSHD

    nIFTy galaxy cluster simulations – V. Investigation of the cluster infall region

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    We examine the properties of the galaxies and dark matter haloes residing in the cluster infall region surrounding the simulated Λ\Lambda cold dark matter galaxy cluster studied by Elahi et al. at zz = 0. The 1.1 × 1015^{15} h1h^{−1} M_\odot galaxy cluster has been simulated with eight different hydrodynamical codes containing a variety of hydrodynamic solvers and sub-grid schemes. All models completed a dark-matter-only, non-radiative and full-physics run from the same initial conditions. The simulations contain dark matter and gas with mass resolution mDMm_\text{DM} = 9.01 × 108^8 h1h^{−1} M_\odot and mgasm_\text{gas} = 1.9 × 108^8 h1h^{−1} M_\odot, respectively. We find that the synthetic cluster is surrounded by clear filamentary structures that contain ~60 per cent of haloes in the infall region with mass ~1012.5^{12.5}–1014^{14} h1h^{−1} M_\odot, including 2–3 group-sized haloes (>1013^{13} h1h^{−1} M_\odot). However, we find that only ~10 per cent of objects in the infall region are sub-haloes residing in haloes, which may suggest that there is not much ongoing pre-processing occurring in the infall region at zz = 0. By examining the baryonic content contained within the haloes, we also show that the code-to-code scatter in stellar fraction across all halo masses is typically ~2 orders of magnitude between the two most extreme cases, and this is predominantly due to the differences in sub-grid schemes and calibration procedures that each model uses. Models that do not include active galactic nucleus feedback typically produce too high stellar fractions compared to observations by at least ~1 order of magnitude.The authors would like the acknowledge the Centre for High Performance Computing in Rosebank, Cape Town, for financial support and for hosting the ‘Comparison Cape Town’ workshop in 2016, July. The authors would further like to acknowledge the support of the International Centre for Radio Astronomy Research (ICRAR) node at the University of Western Australia (UWA) in hosting the precursor workshop ‘Perth Simulated Cluster Comparison’ in 2015, March; the financial support of the UWA Research Collaboration Award 2014 and 2015 schemes; the financial support of the ARC Centre of Excellence for All Sky Astrophysics (CAASTRO) CE110001020 and ARC Discovery Projects DP130100117 and DP140100198. We would also like to thank the Instituto de Fisica Teorica (IFT-UAM/CSIC in Madrid) for its support, via the Centro de Excelencia Severo Ochoa Program under Grant No. SEV- 2012-0249, during the three-week workshop ‘nIFTy Cosmology’ in 2014, where the foundation for the whole comparison project was established. JA acknowledges support from a post-graduate award from STFC. PJE is supported by the SSimPL programme and the Sydney Institute for Astronomy (SIfA) and Australian Research Council (ARC) grants DP130100117 and DP140100198. AK is supported by the Ministerio de Econom´ıa y Competitividad (MINECO) in Spain through grant AYA2012-31101 as well as the ConsoliderIngenio 2010 Programme of the Spanish Ministerio de Ciencia e Innovacion (MICINN) under grant MultiDark CSD2009-00064. ´ He also acknowledges support from the ARC grant DP140100198. He further thanks Noonday Underground for surface noise. STK acknowledges support from STFC through grant ST/L000768/1. CP acknowledges the support of the ARC through Future Fellowship FT130100041 and Discovery Project DP140100198. WC and CP acknowledge the support of ARC DP130100117. GY and FS acknowledge support from MINECO (Spain) through the grant AYA 2012-31101. GY thanks also the Red Espanola de Supercomputa- ˜ cion for granting the computing time in the Marenostrum Supercomputer at BSC, where all the MUSIC simulations have been performed. AMB is supported by the DFG Research Unit 1254 ‘Magnetisation of interstellar and intergalactic media’ and by the DFG Cluster of Excellence ‘Universe’. GM acknowledge support from the PRIN-MIUR 2012 Grant ‘The Evolution of Cosmic Baryons’ funded by the Italian Minister of University and Research, by the PRIN-INAF 2012 Grant ‘Multi-scale Simulations of Cosmic Structures’, by the INFN INDARK Grant and by the ‘Consorzio per la Fisica di Trieste’. IGM acknowledges support from an STFC Advanced Fellowship. EP acknowledges support by the ERC grant ‘The Emergence of Structure During the Epoch of Reionization’

    Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems

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    A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re-distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand
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