226 research outputs found

    Threshold FlipThem:when the winner does not need to take all

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    We examine a FlipIt game in which there are multiple resources which a monolithic attacker is trying to compromise. This extension to FlipIt was considered in a paper in GameSec 2014, and was there called FlipThem. Our analysis of such a situation is focused on the situation where the attacker’s goal is to compromise a threshold of the resources. We use our game theoretic model to enable a defender to choose the correct configuration of resources (number of resources and the threshold) so as to ensure that it makes no sense for a rational adversary to try to attack the system. This selection is made on the basis of the relative costs of the attacker and the defender

    Self-reported competence, attitude and approach of physicians towards patients with dementia in ambulatory care: Results of a postal survey

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    <p>Abstract</p> <p>Background</p> <p>Caring for patients with dementia is a demanding task. Little is known as to whether physicians feel competent enough to perform this task or whether a lack of self-perceived competence influences attitudes and professional approach. Even less is known with respect to potential differences between general practitioners (GPs) and specialists. The purpose of this study was to investigate the interrelationship between the self-perceived competence, attitude and professional approach of physicians in ambulatory care in Germany. A further aim was to compare GPs and specialists with regard to differences in these areas.</p> <p>Methods</p> <p>A standardised postal survey was sent to 389 GPs and 239 neurologists and psychiatrists in six metropolitan areas in Germany. The 49-item questionnaire consisted of attitudinal statements to be rated on a Likert-type scale. Return rates were 54 percent for GPs and 40 percent for specialists. Statistical methods used to analyze data included correlation analysis, cluster analysis and ordinal regression analysis.</p> <p>Results</p> <p>No differences were found between GPs and specialists with regard to their general attitude towards caring for patients with dementia. Approximately 15 percent of both disciplines showed a clearly negative attitude. Self-reported competence was strongly associated with general attitude. In particular among GPs, and less so among specialists, a strong positive association was found between self-reported competence, general attitude and professional approach (e.g. early detection, active case finding and cooperation with caregivers). Differences between GPs and specialists were smaller than expected and appear to predominantly reflect task differences within the German health care system.</p> <p>Conclusion</p> <p>Training opportunities which enable in particular GPs to enhance not only their competence but also their general attitude towards dementia care would appear to be beneficial and might carry positive consequences for patients and their caregivers.</p

    The Evolution of a High Copy Gene Array in Arabidopsis

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    Local gene duplication is a prominent mechanism of gene copy number expansion. Elucidating the mechanisms by which local duplicates arise is necessary in understanding the evolution of genomes and their host organisms. Chromosome one of Arabidopsis thaliana contains an 81-gene array subdivided into 27 triplet units (t-units), with each t-unit containing three pre-transfer RNA genes. We utilized phylogenetic tree reconstructions and comparative genomics to order the events leading to the array’s formation, and propose a model using unequal crossing-over as the primary mechanism of array formation. The model is supported by additional phylogenetic information from intergenic spacer sequences separating each t-unit, comparative analysis to an orthologous array of 12 t-units in the sister taxa Arabidopsis lyrata, and additional modeling using a stochastic simulation of orthologous array divergence. Lastly, comparative phylogenetic analysis demonstrates that the two orthologous t-unit arrays undergo concerted evolution within each taxa and are likely fluctuating in copy number under neutral evolutionary drift. These findings hold larger implications for future research concerning gene and genome evolution

    Revision 1 Size and position of the healthy meniscus, and its Correlation with sex, height, weight, and bone area- a cross-sectional study

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    <p>Abstract</p> <p>Background</p> <p>Meniscus extrusion or hypertrophy may occur in knee osteoarthritis (OA). However, currently no data are available on the position and size of the meniscus in asymptomatic men and women with normal meniscus integrity.</p> <p>Methods</p> <p>Three-dimensional coronal DESSwe MRIs were used to segment and quantitatively measure the size and position of the medial and lateral menisci, and their correlation with sex, height, weight, and tibial plateau area. 102 knees (40 male and 62 female) were drawn from the Osteoarthritis Initiative "non-exposed" reference cohort, including subjects without symptoms, radiographic signs, or risk factors for knee OA. Knees with MRI signs of meniscus lesions were excluded.</p> <p>Results</p> <p>The tibial plateau area was significantly larger (p < 0.001) in male knees than in female ones (+23% medially; +28% laterally), as was total meniscus surface area (p < 0.001, +20% medially; +26% laterally). Ipsi-compartimental tibial plateau area was more strongly correlated with total meniscus surface area in men (r = .72 medially; r = .62 laterally) and women (r = .67; r = .75) than contra-compartimental or total tibial plateau area, body height or weight. The ratio of meniscus versus tibial plateau area was similar between men and women (p = 0.22 medially; p = 0.72 laterally). Tibial coverage by the meniscus was similar between men and women (50% medially; 58% laterally), but "physiological" medial meniscal extrusion was greater in women (1.83 ± 1.06mm) than in men (1.24mm ± 1.18mm; p = 0.011).</p> <p>Conclusions</p> <p>These data suggest that meniscus surface area strongly scales with (ipsilateral) tibial plateau area across both sexes, and that tibial coverage by the meniscus is similar between men and women.</p

    Human Occupancy as a Source of Indoor Airborne Bacteria

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    Exposure to specific airborne bacteria indoors is linked to infectious and noninfectious adverse health outcomes. However, the sources and origins of bacteria suspended in indoor air are not well understood. This study presents evidence for elevated concentrations of indoor airborne bacteria due to human occupancy, and investigates the sources of these bacteria. Samples were collected in a university classroom while occupied and when vacant. The total particle mass concentration, bacterial genome concentration, and bacterial phylogenetic populations were characterized in indoor, outdoor, and ventilation duct supply air, as well as in the dust of ventilation system filters and in floor dust. Occupancy increased the total aerosol mass and bacterial genome concentration in indoor air PM10 and PM2.5 size fractions, with an increase of nearly two orders of magnitude in airborne bacterial genome concentration in PM10. On a per mass basis, floor dust was enriched in bacterial genomes compared to airborne particles. Quantitative comparisons between bacterial populations in indoor air and potential sources suggest that resuspended floor dust is an important contributor to bacterial aerosol populations during occupancy. Experiments that controlled for resuspension from the floor implies that direct human shedding may also significantly impact the concentration of indoor airborne particles. The high content of bacteria specific to the skin, nostrils, and hair of humans found in indoor air and in floor dust indicates that floors are an important reservoir of human-associated bacteria, and that the direct particle shedding of desquamated skin cells and their subsequent resuspension strongly influenced the airborne bacteria population structure in this human-occupied environment. Inhalation exposure to microbes shed by other current or previous human occupants may occur in communal indoor environments

    Neuronal Assembly Detection and Cell Membership Specification by Principal Component Analysis

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    In 1949, Donald Hebb postulated that assemblies of synchronously activated neurons are the elementary units of information processing in the brain. Despite being one of the most influential theories in neuroscience, Hebb's cell assembly hypothesis only started to become testable in the past two decades due to technological advances. However, while the technology for the simultaneous recording of large neuronal populations undergoes fast development, there is still a paucity of analytical methods that can properly detect and track the activity of cell assemblies. Here we describe a principal component-based method that is able to (1) identify all cell assemblies present in the neuronal population investigated, (2) determine the number of neurons involved in ensemble activity, (3) specify the precise identity of the neurons pertaining to each cell assembly, and (4) unravel the time course of the individual activity of multiple assemblies. Application of the method to multielectrode recordings of awake and behaving rats revealed that assemblies detected in the cerebral cortex and hippocampus typically contain overlapping neurons. The results indicate that the PCA method presented here is able to properly detect, track and specify neuronal assemblies, irrespective of overlapping membership

    Design Novel Dual Agonists for Treating Type-2 Diabetes by Targeting Peroxisome Proliferator-Activated Receptors with Core Hopping Approach

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    Owing to their unique functions in regulating glucose, lipid and cholesterol metabolism, PPARs (peroxisome proliferator-activated receptors) have drawn special attention for developing drugs to treat type-2 diabetes. By combining the lipid benefit of PPAR-alpha agonists (such as fibrates) with the glycemic advantages of the PPAR-gamma agonists (such as thiazolidinediones), the dual PPAR agonists approach can both improve the metabolic effects and minimize the side effects caused by either agent alone, and hence has become a promising strategy for designing effective drugs against type-2 diabetes. In this study, by means of the powerful “core hopping” and “glide docking” techniques, a novel class of PPAR dual agonists was discovered based on the compound GW409544, a well-known dual agonist for both PPAR-alpha and PPAR-gamma modified from the farglitazar structure. It was observed by molecular dynamics simulations that these novel agonists not only possessed the same function as GW409544 did in activating PPAR-alpha and PPAR-gamma, but also had more favorable conformation for binding to the two receptors. It was further validated by the outcomes of their ADME (absorption, distribution, metabolism, and excretion) predictions that the new agonists hold high potential to become drug candidates. Or at the very least, the findings reported here may stimulate new strategy or provide useful insights for discovering more effective dual agonists for treating type-2 diabetes. Since the “core hopping” technique allows for rapidly screening novel cores to help overcome unwanted properties by generating new lead compounds with improved core properties, it has not escaped our notice that the current strategy along with the corresponding computational procedures can also be utilized to find novel and more effective drugs for treating other illnesses

    Run-Off Replication of Host-Adaptability Genes Is Associated with Gene Transfer Agents in the Genome of Mouse-Infecting Bartonella grahamii

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    The genus Bartonella comprises facultative intracellular bacteria adapted to mammals, including previously recognized and emerging human pathogens. We report the 2,341,328 bp genome sequence of Bartonella grahamii, one of the most prevalent Bartonella species in wild rodents. Comparative genomics revealed that rodent-associated Bartonella species have higher copy numbers of genes for putative host-adaptability factors than the related human-specific pathogens. Many of these gene clusters are located in a highly dynamic region of 461 kb. Using hybridization to a microarray designed for the B. grahamii genome, we observed a massive, putatively phage-derived run-off replication of this region. We also identified a novel gene transfer agent, which packages the bacterial genome, with an over-representation of the amplified DNA, in 14 kb pieces. This is the first observation associating the products of run-off replication with a gene transfer agent. Because of the high concentration of gene clusters for host-adaptation proteins in the amplified region, and since the genes encoding the gene transfer agent and the phage origin are well conserved in Bartonella, we hypothesize that these systems are driven by selection. We propose that the coupling of run-off replication with gene transfer agents promotes diversification and rapid spread of host-adaptability factors, facilitating host shifts in Bartonella
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