207 research outputs found

    The Crowd in Requirements Engineering: The Landscape and Challenges

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    Crowd-based requirements engineering (CrowdRE) could significantly change RE. Performing RE activities such as elicitation with the crowd of stakeholders turns RE into a participatory effort, leads to more accurate requirements, and ultimately boosts software quality. Although any stakeholder in the crowd can contribute, CrowdRE emphasizes one stakeholder group whose role is often trivialized: users. CrowdRE empowers the management of requirements, such as their prioritization and segmentation, in a dynamic, evolved style through collecting and harnessing a continuous flow of user feedback and monitoring data on the usage context. To analyze the large amount of data obtained from the crowd, automated approaches are key. This article presents current research topics in CrowdRE; discusses the benefits, challenges, and lessons learned from projects and experiments; and assesses how to apply the methods and tools in industrial contexts. This article is part of a special issue on Crowdsourcing for Software Engineering

    Interaction of eukaryotic translation initiation factor 4G with the nuclear cap-binding complex provides a link between nuclear and cytoplasmic functions of the m7 guanosine cap

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    In eukaryotes the majority of mRNAs have an m7G cap that is added cotranscriptionally and that plays an important role in many aspects of mRNA metabolism. The nuclear cap-binding complex (CBC; consisting of CBP20 and CBP80) mediates the stimulatory functions of the cap in pre-mRNA splicing, 3' end formation, and U snRNA export. As little is known about how nuclear CBC mediates the effects of the cap in higher eukaryotes, we have characterized proteins that interact with CBC in HeLa cell nuclear extracts as potential mediators of its function. Using cross-linking and coimmunoprecipitation, we show that eukaryotic translation initiation factor 4G (eIF4G), in addition to its function in the cytoplasm, is a nuclear CBC-interacting protein. We demonstrate that eIF4G interacts with CBC in vitro and that, in addition to its cytoplasmic localization, there is a significant nuclear pool of eIF4G in mammalian cells in vivo. Immunoprecipitation experiments suggest that, in contrast to the cytoplasmic pool, much of the nuclear eIF4G is not associated with eIF4E (translation cap binding protein of eIF4F) but is associated with CBC. While eIF4G stably associates with spliceosomes in vitro and shows close association with spliceosomal snRNPs and splicing factors in vivo, depletion studies show that it does not participate directly in the splicing reaction. Taken together the data indicate that nuclear eIF4G may be recruited to pre-mRNAs via its interaction with CBC and accompanies the mRNA to the cytoplasm, facilitating the switching of CBC for eIF4F. This may provide a mechanism to couple nuclear and cytoplasmic functions of the mRNA cap structure

    Survival probability of mutually killing Brownian motions and the O'Connell process

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    Recently O'Connell introduced an interacting diffusive particle system in order to study a directed polymer model in 1+1 dimensions. The infinitesimal generator of the process is a harmonic transform of the quantum Toda-lattice Hamiltonian by the Whittaker function. As a physical interpretation of this construction, we show that the O'Connell process without drift is realized as a system of mutually killing Brownian motions conditioned that all particles survive forever. When the characteristic length of interaction killing other particles goes to zero, the process is reduced to the noncolliding Brownian motion (the Dyson model).Comment: v2: AMS-LaTeX, 20 pages, 2 figures, minor corrections made for publication in J. Stat. Phy

    Using the cre-lox recombination system to assess functional impairment caused by amino acid substitutions in yeast proteins

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    A method was developed to assess the functional significance of a sequence motif in yeast Upf3p, a protein required for nonsense-mediated mRNA decay (NMD). The motif lies at the edge of the Upf3p-Upf2p interaction domain, but at the same time resembles the canonical leucine-rich nuclear export sequence (NES) found in proteins that bind Crm1p exportin. To test the function of the putative NES, site-directed mutations that cause substitutions of conserved NES-A residues were first selected to identify hypermorphic alleles. Next, a portable Crm1p-binding NES from HIV-1 Rev protein that functions in yeast was fused en masse to the C-terminus of variant Upf3 proteins using loxP sites recognized by bacterial cre-recombinase. Finally, variant Upf3-Rev proteins that were functional in NMD were selected and examined for the types of amino acid substitutions present in NES-A. The mutational analysis revealed that amino acid substitutions in the Upf3 NES impair both nuclear export and the Upf2p-Upf3p interaction, both of which are required for Upf3p to function in NMD. The method described in this report could be modified for the genetic analysis of a variety of portable protein domains

    Nucleocytoplasmic transport: a thermodynamic mechanism

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    The nuclear pore supports molecular communication between cytoplasm and nucleus in eukaryotic cells. Selective transport of proteins is mediated by soluble receptors, whose regulation by the small GTPase Ran leads to cargo accumulation in, or depletion from the nucleus, i.e., nuclear import or nuclear export. We consider the operation of this transport system by a combined analytical and experimental approach. Provocative predictions of a simple model were tested using cell-free nuclei reconstituted in Xenopus egg extract, a system well suited to quantitative studies. We found that accumulation capacity is limited, so that introduction of one import cargo leads to egress of another. Clearly, the pore per se does not determine transport directionality. Moreover, different cargo reach a similar ratio of nuclear to cytoplasmic concentration in steady-state. The model shows that this ratio should in fact be independent of the receptor-cargo affinity, though kinetics may be strongly influenced. Numerical conservation of the system components highlights a conflict between the observations and the popular concept of transport cycles. We suggest that chemical partitioning provides a framework to understand the capacity to generate concentration gradients by equilibration of the receptor-cargo intermediary.Comment: in press at HFSP Journal, vol 3 16 text pages, 1 table, 4 figures, plus Supplementary Material include

    Are psychosocial interventions effective in reducing alcohol consumption during pregnancy and motherhood?:A systematic review and meta‐analysis

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    Background and Aims Alcohol use by pregnant and parenting women can have serious and long-lasting consequences for both the mother and offspring. We reviewed the evidence for psychosocial interventions to reduce maternal drinking. Design Literature searches of PsycINFO, PubMed and Scopus identified randomised controlled trials of interventions with an aim of reduced drinking or abstinence in mothers or pregnant women. Setting Interventions were delivered in healthcare settings and homes. Participants Pregnant women and mothers with dependent children. Interventions Psychosocial interventions were compared with usual care or no intervention. Measurements The revised Cochrane risk-of-bias tool for randomised trials was used for quality assessments. Narrative synthesis summarised the findings of the studies with a subset of trials eligible for random-effects meta-analysis. General and alcohol-specific behaviour change techniques (BCTs) were identified to investigate potential mechanism of change. Results Twenty-four studies were included (20 pregnancy, four motherhood). Because of quality of reporting, data from only six pregnancy and four motherhood studies could be pooled. A significant treatment effect was revealed by the meta-analyses of pregnancy studies regarding abstinence (OR = 2.31, 95% CI = 1.61, 3.32; P < 0.001) and motherhood studies regarding a reduction in drinking (standardised mean difference [SMD] = −0.20, 95% CI = −0.38, −0.02; P = 0.03). Narrative synthesis of the remaining trials yielded inconsistent results regarding intervention effectiveness. A wide range of BCTs were used, present in both effective and ineffective interventions. The most commonly used general and alcohol-specific BCTs included information about consequences, social support, goal setting and action planning. Conclusions In pregnant women identified as consuming alcohol, psychosocial interventions appear to increase abstinence rates compared with usual care or no intervention. Similarly, such interventions appear to lead to a reduction in alcohol consumption in mothers with dependent children. It is unclear that behaviour change techniques are contributing to these effects. Conclusions from randomised controlled trials are only meaningful if the behavioural outcome, population, setting, intervention and comparator are clearly reported. An important barrier when it comes to identifying effective behaviour change techniques is a widespread failure to provide enough information in study reports

    New insights into the Tyrolean Iceman's origin and phenotype as inferred by whole-genome sequencing

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    The Tyrolean Iceman, a 5,300-year-old Copper age individual, was discovered in 1991 on the Tisenjoch Pass in the Italian part of the Otztal Alps. Here we report the complete genome sequence of the Iceman and show 100% concordance between the previously reported mitochondrial genome sequence and the consensus sequence generated from our genomic data. We present indications for recent common ancestry between the Iceman and present-day inhabitants of the Tyrrhenian Sea, that the Iceman probably had brown eyes, belonged to blood group O and was lactose intolerant. His genetic predisposition shows an increased risk for coronary heart disease and may have contributed to the development of previously reported vascular calcifications. Sequences corresponding to similar to 60% of the genome of Borrelia burgdorferi are indicative of the earliest human case of infection with the pathogen for Lyme borreliosis

    Alcohol Use during Pregnancy: Considerations for Australian Policy

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    Although there is an extensive recorded history of concerns related to alcohol exposed pregnancies and possible outcomes of fetal alcohol spectrum disorder in recent scientific literature, Australia has only recently begun to accurately or systematically diagnose and record these conditions, or to provide comprehensive, coordinated, policy-guided funding, prevention, and treatment. This article discusses some considerations that can guide policy development within the Australian context including the social context and determinates of alcohol consumption during pregnancy and the need to consider the issue as one that goes beyond the decision making of individual women. The article also identifies the contribution of research to guide evidence-based policy development, including emerging evidence of epigenetics, and systematic reviews for prevention. Other policy considerations include costs, and the possibility of the prevention paradox applying to this field, with its associated impact on costs and focus of prevention

    Generalized Structural Description of Calcium–Sodium Aluminosilicate Hydrate Gels: The Cross-Linked Substituted Tobermorite Model

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    Structural models for the primary strength and durability-giving reaction product in modern cements, a calcium (alumino)silicate hydrate gel, have previously been based solely on non-cross-linked tobermorite structures. However, recent experimental studies of laboratory-synthesized and alkali-activated slag (AAS) binders have indicated that the calcium–sodium aluminosilicate hydrate [C-(N)-A-S-H] gel formed in these systems can be significantly cross-linked. Here, we propose a model that describes the C-(N)-A-S-H gel as a mixture of cross-linked and non-cross-linked tobermorite-based structures (the cross-linked substituted tobermorite model, CSTM), which can more appropriately describe the spectroscopic and density information available for this material. Analysis of the phase assemblage and Al coordination environments of AAS binders shows that it is not possible to fully account for the chemistry of AAS by use of the assumption that all of the tetrahedral Al is present in a tobermorite-type C-(N)-A-S-H gel, due to the structural constraints of the gel. Application of the CSTM can for the first time reconcile this information, indicating the presence of an additional activation product that contains highly connected four-coordinated silicate and aluminate species. The CSTM therefore provides a more advanced description of the chemistry and structure of calcium–sodium aluminosilicate gel structures than that previously established in the literature
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