1,380 research outputs found

    A Computational Comparison of Optimization Methods for the Golomb Ruler Problem

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    The Golomb ruler problem is defined as follows: Given a positive integer n, locate n marks on a ruler such that the distance between any two distinct pair of marks are different from each other and the total length of the ruler is minimized. The Golomb ruler problem has applications in information theory, astronomy and communications, and it can be seen as a challenge for combinatorial optimization algorithms. Although constructing high quality rulers is well-studied, proving optimality is a far more challenging task. In this paper, we provide a computational comparison of different optimization paradigms, each using a different model (linear integer, constraint programming and quadratic integer) to certify that a given Golomb ruler is optimal. We propose several enhancements to improve the computational performance of each method by exploring bound tightening, valid inequalities, cutting planes and branching strategies. We conclude that a certain quadratic integer programming model solved through a Benders decomposition and strengthened by two types of valid inequalities performs the best in terms of solution time for small-sized Golomb ruler problem instances. On the other hand, a constraint programming model improved by range reduction and a particular branching strategy could have more potential to solve larger size instances due to its promising parallelization features

    Pruning the regulatory tree

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62897/1/457534a.pd

    Exoplanets and SETI

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    The discovery of exoplanets has both focused and expanded the search for extraterrestrial intelligence. The consideration of Earth as an exoplanet, the knowledge of the orbital parameters of individual exoplanets, and our new understanding of the prevalence of exoplanets throughout the galaxy have all altered the search strategies of communication SETI efforts, by inspiring new "Schelling points" (i.e. optimal search strategies for beacons). Future efforts to characterize individual planets photometrically and spectroscopically, with imaging and via transit, will also allow for searches for a variety of technosignatures on their surfaces, in their atmospheres, and in orbit around them. In the near-term, searches for new planetary systems might even turn up free-floating megastructures.Comment: 9 page invited review. v2 adds some references and v3 has other minor additions and modification

    Setting priorities in health care organizations: criteria, processes, and parameters of success

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    BACKGROUND: Hospitals and regional health authorities must set priorities in the face of resource constraints. Decision-makers seek practical ways to set priorities fairly in strategic planning, but find limited guidance from the literature. Very little has been reported from the perspective of Board members and senior managers about what criteria, processes and parameters of success they would use to set priorities fairly. DISCUSSION: We facilitated workshops for board members and senior leadership at three health care organizations to assist them in developing a strategy for fair priority setting. Workshop participants identified 8 priority setting criteria, 10 key priority setting process elements, and 6 parameters of success that they would use to set priorities in their organizations. Decision-makers in other organizations can draw lessons from these findings to enhance the fairness of their priority setting decision-making. SUMMARY: Lessons learned in three workshops fill an important gap in the literature about what criteria, processes, and parameters of success Board members and senior managers would use to set priorities fairly

    Anaerobic Carbon Monoxide Dehydrogenase Diversity in the Homoacetogenic Hindgut Microbial Communities of Lower Termites and the Wood Roach

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    Anaerobic carbon monoxide dehydrogenase (CODH) is a key enzyme in the Wood-Ljungdahl (acetyl-CoA) pathway for acetogenesis performed by homoacetogenic bacteria. Acetate generated by gut bacteria via the acetyl-CoA pathway provides considerable nutrition to wood-feeding dictyopteran insects making CODH important to the obligate mutualism occurring between termites and their hindgut microbiota. To investigate CODH diversity in insect gut communities, we developed the first degenerate primers designed to amplify cooS genes, which encode the catalytic (β) subunit of anaerobic CODH enzyme complexes. These primers target over 68 million combinations of potential forward and reverse cooS primer-binding sequences. We used the primers to identify cooS genes in bacterial isolates from the hindgut of a phylogenetically lower termite and to sample cooS diversity present in a variety of insect hindgut microbial communities including those of three phylogenetically-lower termites, Zootermopsis nevadensis, Reticulitermes hesperus, and Incisitermes minor, a wood-feeding cockroach, Cryptocercus punctulatus, and an omnivorous cockroach, Periplaneta americana. In total, we sequenced and analyzed 151 different cooS genes. These genes encode proteins that group within one of three highly divergent CODH phylogenetic clades. Each insect gut community contained CODH variants from all three of these clades. The patterns of CODH diversity in these communities likely reflect differences in enzyme or physiological function, and suggest that a diversity of microbial species participate in homoacetogenesis in these communities

    Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

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    Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

    Using simulation to interpret a discrete time survival model in a complex biological system: fertility and lameness in dairy cows

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    The ever-growing volume of data routinely collected and stored in everyday life presents researchers with a number of opportunities to gain insight and make predictions. This study aimed to demonstrate the usefulness in a specific clinical context of a simulation-based technique called probabilistic sensitivity analysis (PSA) in interpreting the results of a discrete time survival model based on a large dataset of routinely collected dairy herd management data. Data from 12,515 dairy cows (from 39 herds) were used to construct a multilevel discrete time survival model in which the outcome was the probability of a cow becoming pregnant during a given two day period of risk, and presence or absence of a recorded lameness event during various time frames relative to the risk period amongst the potential explanatory variables. A separate simulation model was then constructed to evaluate the wider clinical implications of the model results (i.e. the potential for a herd’s incidence rate of lameness to influence its overall reproductive performance) using PSA. Although the discrete time survival analysis revealed some relatively large associations between lameness events and risk of pregnancy (for example, occurrence of a lameness case within 14 days of a risk period was associated with a 25% reduction in the risk of the cow becoming pregnant during that risk period), PSA revealed that, when viewed in the context of a realistic clinical situation, a herd’s lameness incidence rate is highly unlikely to influence its overall reproductive performance to a meaningful extent in the vast majority of situations. Construction of a simulation model within a PSA framework proved to be a very useful additional step to aid contextualisation of the results from a discrete time survival model, especially where the research is designed to guide on-farm management decisions at population (i.e. herd) rather than individual level

    Is the qualitative research interview an acceptable medium for research with palliative care patients and carers?

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    <p>Abstract</p> <p>Background</p> <p>Contradictory evidence exists about the emotional burden of participating in qualitative research for palliative care patients and carers and this raises questions about whether this type of research is ethically justified in a vulnerable population. This study aimed to investigate palliative care patients' and carers' perceptions of the benefits and problems associated with open interviews and to understand what causes distress and what is helpful about participation in a research interview.</p> <p>Methods</p> <p>A descriptive qualitative study. The data were collected in the context of two studies exploring the experiences of care of palliative care patients and carers. The interviews ended with questions about patients' and carers' thoughts on participating in the studies and whether this had been a distressing or helpful event. We used a qualitative descriptive analysis strategy generated from the interviews and the observational and interactional data obtained in the course of the study.</p> <p>Results</p> <p>The interviews were considered helpful: sharing problems was therapeutic and being able to contribute to research was empowering. However, thinking about the future was reported to be the most challenging. Consent forms were sometimes read with apprehension and being physically unable to sign was experienced as upsetting. Interviewing patients and carers separately was sometimes difficult and not always possible.</p> <p>Conclusion</p> <p>The open interview enables the perspectives of patients and carers to be heard, unfettered from the structure of closed questions. It also enables those patients or carers to take part who would be unable to participate in other study designs. The context is at least as important as the format of the research interview taking into account the relational circumstances with carers and appropriate ways of obtaining informed consent. Retrospective consent could be a solution to enhancing participants control over the interview.</p
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