2,102 research outputs found

    Exploring C++

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    This book is intended for use by C programmers who want to learn C++ . . . fast. It may also be helpful for Java programmers learning C++ . It assumes that the reader knows basic programming including types, control structures, functions, arrays, pointers, and simple data structures. The material should help you develop a deep understanding of clean program design and the features that make C++ a powerful and flexible language.https://digitalcommons.newhaven.edu/electricalcomputerengineering-books/1001/thumbnail.jp

    An Empirical Comparison of Widely Adopted Hash Functions in Digital Forensics: Does the Programming Language and Operating System Make a Difference?

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    Hash functions are widespread in computer sciences and have a wide range of applications such as ensuring integrity in cryptographic protocols, structuring database entries (hash tables) or identifying known files in forensic investigations. Besides their cryptographic requirements, a fundamental property of hash functions is efficient and easy computation which is especially important in digital forensics due to the large amount of data that needs to be processed when working on cases. In this paper, we correlate the runtime efficiency of common hashing algorithms (MD5, SHA-family) and their implementation. Our empirical comparison focuses on C-OpenSSL, Python, Ruby, Java on Windows and Linux and C and WinCrypto API on Windows. The purpose of this paper is to recommend appropriate programming languages and libraries for coding tools that include intensive hashing processes. In each programming language, we compute the MD5, SHA-1, SHA-256 and SHA-512 digest on datasets from 2MB to 1 GB. For each language, algorithm and data, we perform multiple runs and compute the average elapsed time. In our experiment, we observed that OpenSSL and languages utilizing OpenSSL (Python and Ruby) perform better across all the hashing algorithms and data sizes on Windows and Linux. However, on Windows, performance of Java (Oracle JDK) and C WinCrypto is comparable to OpenSSL and better for SHA-512

    Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

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    Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

    The Complete Genome Sequence of the Emerging Pathogen Mycobacterium haemophilum Explains Its Unique Culture Requirements

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    Mycobacterium haemophilum is an emerging pathogen associated with a variety of clinical syndromes, most commonly skin infections in immunocompromised individuals. M. haemophilum exhibits a unique requirement for iron supplementation to support its growth in culture, but the basis for this property and how it may shape pathogenesis is unclear. Using a combination of Illumina, PacBio, and Sanger sequencing, the complete genome sequence of M. haemophilum was determined. Guided by this sequence, experiments were performed to define the basis for the unique growth requirements of M. haemophilum. We found that M. haemophilum, unlike many other mycobacteria, is unable to synthesize iron-binding siderophores known as mycobactins or to utilize ferri-mycobactins to support growth. These differences correlate with the absence of genes associated with mycobactin synthesis, secretion, and uptake. In agreement with the ability of heme to promote growth, we identified genes encoding heme uptake machinery. Consistent with its propensity to infect the skin, we show at the whole-genome level the genetic closeness of M. haemophilumwith Mycobacterium leprae, an organism which cannot be cultivated in vitro, and we identify genes uniquely shared by these organisms. Finally, we identify means to express foreign genes in M. haemophilum. These data explain the unique culture requirements for this important pathogen, provide a foundation upon which the genome sequence can be exploited to improve diagnostics and therapeutics, and suggest use of M. haemophilum as a tool to elucidate functions of genes shared with M. leprae. IMPORTANCE Mycobacterium haemophilum is an emerging pathogen with an unknown natural reservoir that exhibits unique requirements for iron supplementation to grow in vitro. Understanding the basis for this iron requirement is important because it is fundamental to isolation of the organism from clinical samples and environmental sources. Defining the molecular basis for M. haemophilium\u27s growth requirements will also shed new light on mycobacterial strategies to acquire iron and can be exploited to define how differences in such strategies influence pathogenesis. Here, through a combination of sequencing and experimental approaches, we explain the basis for the iron requirement. We further demonstrate the genetic closeness of M. haemophilum and Mycobacterium leprae, the causative agent of leprosy which cannot be cultured in vitro, and we demonstrate methods to genetically manipulate M. haemophilum. These findings pave the way for the use of M. haemophilum as a model to elucidate functions of genes shared with M. leprae

    Measurement of χ c1 and χ c2 production with s√ = 7 TeV pp collisions at ATLAS

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    The prompt and non-prompt production cross-sections for the χ c1 and χ c2 charmonium states are measured in pp collisions at s√ = 7 TeV with the ATLAS detector at the LHC using 4.5 fb−1 of integrated luminosity. The χ c states are reconstructed through the radiative decay χ c → J/ψγ (with J/ψ → μ + μ −) where photons are reconstructed from γ → e + e − conversions. The production rate of the χ c2 state relative to the χ c1 state is measured for prompt and non-prompt χ c as a function of J/ψ transverse momentum. The prompt χ c cross-sections are combined with existing measurements of prompt J/ψ production to derive the fraction of prompt J/ψ produced in feed-down from χ c decays. The fractions of χ c1 and χ c2 produced in b-hadron decays are also measured

    The selection landscape and genetic legacy of ancient Eurasians

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    The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans

    A genome-wide association study of early menopause and the combined impact of identified variants

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    Early menopause (EM) affects up to 10% of the female population, reducing reproductive lifespan considerably. Currently, it constitutes the leading cause of infertility in the western world, affecting mainly those women who postpone their first pregnancy beyond the age of 30 years. The genetic aetiology of EM is largely unknown in the majority of cases. We have undertaken a meta-analysis of genome-wide association studies (GWASs) in 3493 EM cases and 13 598 controls from 10 independent studies. No novel genetic variants were discovered, but the 17 variants previously associated with normal age at natural menopause as a quantitative trait (QT) were also associated with EM and primary ovarian insufficiency (POI). Thus, EM has a genetic aetiology which overlaps variation in normal age at menopause and is at least partly explained by the additive effects of the same polygenic variants. The combined effect of the common variants captured by the single nucleotide polymorphism arrays was estimated to account for ∼30% of the variance in EM. The association between the combined 17 variants and the risk of EM was greater than the best validated non-genetic risk factor, smokin

    Low-Spin Heme b3 in the Catalytic Center of Nitric Oxide Reductase from Pseudomonas nautica

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    Biochemistry, 2011, 50 (20), pp 4251–4262 DOI: 10.1021/bi101605pRespiratory nitric oxide reductase (NOR) was purified from membrane extract of Pseudomonas (Ps.) nautica cells to homogeneity as judged by polyacrylamide gel electrophoresis. The purified protein is a heterodimer with subunits of molecular masses of 54 and 18 kDa. The gene encoding both subunits was cloned and sequenced. The amino acid sequence shows strong homology with enzymes of the cNOR class. Iron/heme determinations show that one heme c is present in the small subunit (NORC) and that approximately two heme b and one non-heme iron are associated with the large subunit (NORB), in agreement with the available data for enzymes of the cNOR class. Mössbauer characterization of the as-purified, ascorbate-reduced, and dithionite-reduced enzyme confirms the presence of three heme groups (the catalytic heme b(3) and the electron transfer heme b and heme c) and one redox-active non-heme Fe (Fe(B)). Consistent with results obtained for other cNORs, heme c and heme b in Ps. nautica cNOR were found to be low-spin while Fe(B) was found to be high-spin. Unexpectedly, as opposed to the presumed high-spin state for heme b(3), the Mössbauer data demonstrate unambiguously that heme b(3) is, in fact, low-spin in both ferric and ferrous states, suggesting that heme b(3) is six-coordinated regardless of its oxidation state. EPR spectroscopic measurements of the as-purified enzyme show resonances at the g ∼ 6 and g ∼ 2-3 regions very similar to those reported previously for other cNORs. The signals at g = 3.60, 2.99, 2.26, and 1.43 are attributed to the two charge-transfer low-spin ferric heme c and heme b. Previously, resonances at the g ∼ 6 region were assigned to a small quantity of uncoupled high-spin Fe(III) heme b(3). This assignment is now questionable because heme b(3) is low-spin. On the basis of our spectroscopic data, we argue that the g = 6.34 signal is likely arising from a spin-spin coupled binuclear center comprising the low-spin Fe(III) heme b(3) and the high-spin Fe(B)(III). Activity assays performed under various reducing conditions indicate that heme b(3) has to be reduced for the enzyme to be active. But, from an energetic point of view, the formation of a ferrous heme-NO as an initial reaction intermediate for NO reduction is disfavored because heme [FeNO](7) is a stable product. We suspect that the presence of a sixth ligand in the Fe(II)-heme b(3) may weaken its affinity for NO and thus promotes, in the first catalytic step, binding of NO at the Fe(B)(II) site. The function of heme b(3) would then be to orient the Fe(B)-bound NO molecules for the formation of the N-N bond and to provide reducing equivalents for NO reduction

    The Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A): a study with recently and non-recently divorced adults

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    Past research has demonstrated that divorced adults show more health problems and psychological distress than married adults. Considering the high prevalence rates of divorce among Western countries, new and robust measures should be developed to measure psychological distress after this specific transition in adulthood. The aim of this study was to adapt and validate a Portuguese version of the Psychological Adjustment to Separation Test-Part A (PAST-A; Sweeper and Halford in J Family Psychol 20(4):632–640, 2006). PAST-A is a self-report measure that assesses two key dimensions of separation adjustment problems: lonely-negativity and former partner attachment. Psychometric properties of the Portuguese version of PAST-A were assessed in terms of factor structure, internal consistency, and convergent and divergent validity, in an online convenience sample with divorced adults (N = 460). The PAST-A two-factor structure was confirmed by exploratory and confirmatory factor analyses, with each factor demonstrating very satisfactory internal consistency and good convergence. In terms of discriminant validity, the Portuguese PAST-A reveals a distinct factor from psychological growth after divorce. The results provided support for the use of the Portuguese PAST-A with divorced adults and also suggested that the explicative factors of the psychological adjustment to divorce may be cross-cultural stable. The non-existence of validated divorce-related well-being measures and its implications for divorce research are also discussed
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