The Clumpiness of Cold Dark Matter: Implications for the Annihilation Signal

We examine the expected signal from annihilation events in realistic cold dark matter halos. If the WIMP is a neutralino, with an annihilation cross-section predicted in minimal SUSY models for the lightest stable relic particle, the central cusps and dense substructure seen in simulated halos may produce a substantial flux of energetic gamma rays. We derive expressions for the relative flux from such events in simple halos with various density profiles, and use these to calculate the relative flux produced within a large volume as a function of redshift. This flux peaks when the first halos collapse, but then declines as small halos merge into larger systems of lower density. Simulations show that halos contain a substantial amount of dense substructure, left over from the incomplete disruption of smaller halos as they merge together. We calculate the contribution to the flux due to this substructure, and show that it can increase the annihilation signal substantially. Overall, the present-day flux from annihilation events may be an order of magnitude larger than predicted by previous calculations. We discuss the implications of these results for current and future gamma-ray experiments.Comment: 8 pages, 6 figures; submitted to MNRA

In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography

The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The 18F-radiolabeled polyamides were prepared by oxime ligation between 4-[18F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring β-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability. In vivo imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies

Bayesian optimization of massive material injection for disruption mitigation in tokamaks

A Bayesian optimization framework is used to investigate scenarios for disruptions mitigated with combined deuterium and neon injection in ITER. The optimization cost function takes into account limits on the maximum runaway current, the transported fraction of the heat loss and the current quench time. The aim is to explore the dependence of the cost function on injected densities, and provide insights into the behaviour of the disruption dynamics for representative scenarios. The simulations are conducted using the numerical framework Dream (Disruption Runaway Electron Analysis Model). We show that, irrespective of the quantities of the material deposition, multi-megaampere runaway currents will be produced in the deuterium-tritium phase of operations, even in the optimal scenarios. However, the severity of the outcome can be influenced by tailoring the radial profile of the injected material; in particular, if the injected neon is deposited at the edge region it leads to a significant reduction of both the final runaway current and the transported heat losses. The Bayesian approach allows us to map the parameter space efficiently, with more accuracy in favourable parameter regions, thereby providing us with information about the robustness of the optima

Artificial intelligence based automatic quantification of epicardial adipose tissue suitable for large scale population studies

To develop a fully automatic model capable of reliably quantifying epicardial adipose tissue (EAT) volumes and attenuation in large scale population studies to investigate their relation to markers of cardiometabolic risk. Non-contrast cardiac CT images from the SCAPIS study were used to train and test a convolutional neural network based model to quantify EAT by: segmenting the pericardium, suppressing noise-induced artifacts in the heart chambers, and, if image sets were incomplete, imputing missing EAT volumes. The model achieved a mean Dice coefficient of 0.90 when tested against expert manual segmentations on 25 image sets. Tested on 1400 image sets, the model successfully segmented 99.4% of the cases. Automatic imputation of missing EAT volumes had an error of less than 3.1% with up to 20% of the slices in image sets missing. The most important predictors of EAT volumes were weight and waist, while EAT attenuation was predicted mainly by EAT volume. A model with excellent performance, capable of fully automatic handling of the most common challenges in large scale EAT quantification has been developed. In studies of the importance of EAT in disease development, the strong co-variation with anthropometric measures needs to be carefully considered

The effect of annealing on the elastoplastic and viscoelastic responses of isotactic polypropylene

Observations are reported on isotactic polypropylene (i) in a series of tensile tests with a constant strain rate on specimens annealed for 24 h at various temperatures in the range from 110 to 150 C and (ii) in two series of creep tests in the sub-yield region of deformation on samples not subjected to thermal treatment and on specimens annealed at 140 C. A model is developed for the elastoplastic and nonlinear viscoelastic responses of semicrystalline polymers. A polymer is treated an equivalent transient network of macromolecules bridged by junctions (physical cross-links, entanglements and lamellar blocks). The network is assumed to be highly heterogeneous, and it is thought of as an ensemble of meso-regions with different activation energies for separation of strands from temporary nodes. The elastoplastic behavior is modelled as sliding of meso-domains with respect to each other driven by mechanical factors. The viscoelastic response is attributed to detachment of active strands from temporary junctions and attachment of dangling chains to the network. Constitutive equations for isothermal uniaxial deformation are derived by using the laws of thermodynamics. Adjustable parameters in the stress-strain relations are found by fitting the experimental data.Comment: 29 pages, 14 figure

Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden

Temporal dynamics of the gut microbiota potentially limit the identification of microbial features associated with health status. Here, we used whole-genome metagenomic and 16S rRNA gene sequencing to characterize the intra- and inter-individual variations of gut microbiota composition and functional potential of a disease-free Swedish population (n = 75) over one year. We found that 23% of the total compositional variance was explained by intra-individual variation. The degree of intra-individual compositional variability was negatively associated with the abundance of Faecalibacterium prausnitzii (a butyrate producer) and two Bifidobacterium species. By contrast, the abundance of facultative anaerobes and aerotolerant bacteria such as Escherichia coli and Lactobacillus acidophilus varied extensively, independent of compositional stability. The contribution of intra-individual variance to the total variance was greater for functional pathways than for microbial species. Thus, reliable quantification of microbial features requires repeated samples to address the issue of intra-individual variations of the gut microbiota

Prolonged Fasting Identifies Skeletal Muscle Mitochondrial Dysfunction as Consequence Rather Than Cause of Human Insulin Resistance

OBJECTIVE-Type 2 diabetes and insulin resistance have been associated with mitochondrial dysfunction, but it is debated whether this is a primary factor in the pathogenesis of the disease. To test the concept that mitochondrial dysfunction is secondary to the development of insulin resistance, we employed the unique model of prolonged fasting in humans. Prolonged fasting is a physiologic condition in which muscular insulin resistance develops in the presence of increased free fatty acid (FFA) levels, increased fat oxidation and low glucose and insulin levels. It is therefore anticipated that skeletal muscle mitochondrial function is maintained to accommodate increased fat oxidation unless factors secondary to insulin resistance exert negative effects on mitochondrial function. RESEARCH DESIGN AND METHODS-While in a respiration chamber, twelve healthy males were subjected to a 60 h fast and a 60 h normal fed condition in a randomized crossover design. Afterward, insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp, and mitochondrial function was quantified ex vivo in permeabilized muscle fibers using high-resolution respirometry. RESULTS-Indeed, FFA levels were increased approximately ninefold after 60 h of fasting in healthy male subjects, leading to elevated intramuscular lipid levels and decreased muscular insulin sensitivity. Despite an increase in whole-body fat oxidation, we observed an overall reduction in both coupled state 3 respiration and maximally uncoupled respiration in permeabilized skeletal muscle fibers, which could not be explained by changes in mitochondrial density. CONCLUSIONS-These findings confirm that the insulin-resistant State has secondary negative effects on mitochondrial function. Given the low insulin and glucose levels after prolonged fasting, hyperglycemia and insulin action per se can be excluded as underlying mechanisms, pointing toward elevated plasma FFA and/or intramuscular fat accumulation as possible causes for the observed reduction in mitochondrial capacity. Diabetes 59: 2117-2125, 201

Lower Intrinsic ADP-Stimulated Mitochondrial Respiration Underlies In Vivo Mitochondrial Dysfunction in Muscle of Male Type 2 Diabetic Patients

OBJECTIVE—A lower in vivo mitochondrial function has been reported in both type 2 diabetic patients and first-degree relatives of type 2 diabetic patients. The nature of this reduction is unknown. Here, we tested the hypothesis that a lower intrinsic mitochondrial respiratory capacity may underlie lower in vivo mitochondrial function observed in diabetic patients