Microarray analyses demonstrate the involvement of type i interferons in psoriasiform pathology development in D6-deficient mice

The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes

Novel Resilience Phenotypes from a Natural Disease Challenge Model for Wean-to-Finish Pigs

Novel phenotypes from a commercial testing system could add value to selection for resilience to disease and other stressors beyond simply collecting mortality. Day-to-day variability in feed intake (FI) and in duration at the feeder (DUR), quantified by root mean squared errors (RMSE), were investigated as novel measures of resilience using data from grow-finish pigs in a natural disease challenge facility. • RMSE of FI and DUR were moderately heritable • RMSE of FI and DUR showed moderate to strong genetic correlations with mortality and treatments These results show that day-to-day variation in FI and DUR in a challenge environment can be used as indicator traits to select for disease resilience

New improved Moser-Trudinger inequalities and singular Liouville equations on compact surfaces

We consider a singular Liouville equation on a compact surface, arising from the study of Chern-Simons vortices in a self dual regime. Using new improved versions of the Moser-Trudinger inequalities (whose main feature is to be scaling invariant) and a variational scheme, we prove new existence results.Comment: to appear in GAF

Damped Bloch oscillations of cold atoms in optical lattices

The paper studies Bloch oscillations of cold neutral atoms in the optical lattice. The effect of spontaneous emission on the dynamics of the system is analyzed both analytically and numerically. The spontaneous emission is shown to cause (i) the decay of Bloch oscillations with the decrement given by the rate of spontaneous emission and (ii) the diffusive spreading of the atoms with a diffusion coefficient depending on {\em both} the rate of spontaneous emission and the Bloch frequency.Comment: 10 pages, 8 figure

Microcraters in aluminum foils exposed by Stardust

We will present preliminary results on the nature and size frequency distribution of microcraters that formed in aluminum foils during the flyby of comet Wild 2 by the Stardust spacecraft

Genome-wide association study of disease resilience traits from a natural polymicrobial disease challenge model in pigs identifies the importance of the major histocompatibility complex region

Infectious diseases cause tremendous financial losses in the pork industry, emphasizing the importance of disease resilience, which is the ability of an animal to maintain performance under disease. Previously, a natural polymicrobial disease challenge model was established, in which pigs were challenged in the late nursery phase by multiple pathogens to maximize expression of genetic differences in disease resilience. Genetic analysis found that performance traits in this model, including growth rate, feed and water intake, and carcass traits, as well as clinical disease phenotypes, were heritable and could be selected for to increase disease resilience of pigs. The objectives of the current study were to identify genomic regions that are associated with disease resilience in this model, using genome-wide association studies and fine-mapping methods, and to use gene set enrichment analyses to determine whether genomic regions associated with disease resilience are enriched for previously published quantitative trait loci, functional pathways, and differentially expressed genes subject to physiological states. Multiple quantitative trait loci were detected for all recorded performance and clinical disease traits. The major histocompatibility complex region was found to explain substantial genetic variance for multiple traits, including for growth rate in the late nursery (12.8%) and finisher (2.7%), for several clinical disease traits (up to 2.7%), and for several feeding and drinking traits (up to 4%). Further fine mapping identified 4 quantitative trait loci in the major histocompatibility complex region for growth rate in the late nursery that spanned the subregions for class I, II, and III, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects, explaining 0.8–27.1% of genetic variance for growth rate and for multiple clinical disease traits. This singlenucleotide polymorphism was located in the enhancer of TRIM39 gene, which is involved in innate immune response. The major histocompatibility complex region was pleiotropic for growth rate in the late nursery and finisher, and for treatment and mortality rates. Growth rate in the late nursery showed strong negative genetic correlations in the major histocompatibility complex region with treatment or mortality rates (–0.62 to –0.85) and a strong positive genetic correlation with growth rate in the finisher (0.79). Gene set enrichment analyses found genomic regions associated with resilience phenotypes to be enriched for previously identified disease susceptibility and immune capacity quantitative trait loci, for genes that were differentially expressed following bacterial or virus infection and immune response, and for gene ontology terms related to immune and inflammatory response. In conclusion, the major histocompatibility complex and other quantitative trait loci that harbor immune-related genes were identified to be associated with disease resilience traits in a large-scale natural polymicrobial disease challenge. The major histocompatibility complex region was pleiotropic for growth rate under challenge and for clinical disease traits. Four quantitative trait loci were identified across the class I, II, and III subregions of the major histocompatibility complex for nursery growth rate under challenge, with 1 single-nucleotide polymorphism in the major histocompatibility complex class I subregion capturing the largest effects. The major histocompatibility complex and other quantitative trait loci identified play an important role in host response to infectious diseases and can be incorporated in selection to improve disease resilience, in particular the identified singlenucleotide polymorphism in the major histocompatibility complex class I subregion

Prioritization of HCV treatment in the direct-acting antiviral era: an economic evaluation

BACKGROUND & AIMS: We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). METHODS: A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. RESULTS: The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. CONCLUSIONS: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high

Chaos and flights in the atom-photon interaction in cavity QED

We study dynamics of the atom-photon interaction in cavity quantum electrodynamics (QED), considering a cold two-level atom in a single-mode high-finesse standing-wave cavity as a nonlinear Hamiltonian system with three coupled degrees of freedom: translational, internal atomic, and the field. The system proves to have different types of motion including L\'{e}vy flights and chaotic walkings of an atom in a cavity. It is shown that the translational motion, related to the atom recoils, is governed by an equation of a parametric nonlinear pendulum with a frequency modulated by the Rabi oscillations. This type of dynamics is chaotic with some width of the stochastic layer that is estimated analytically. The width is fairly small for realistic values of the control parameters, the normalized detuning $\delta$ and atomic recoil frequency $\alpha$. It is demonstrated how the atom-photon dynamics with a given value of $\alpha$ depends on the values of $\delta$ and initial conditions. Two types of L\'{e}vy flights, one corresponding to the ballistic motion of the atom and another one corresponding to small oscillations in a potential well, are found. These flights influence statistical properties of the atom-photon interaction such as distribution of Poincar\'{e} recurrences and moments of the atom position $x$. The simulation shows different regimes of motion, from slightly abnormal diffusion with $\sim\tau^{1.13}$ at $\delta =1.2$ to a superdiffusion with $\sim \tau^{2.2}$ at $\delta=1.92$ that corresponds to a superballistic motion of the atom with an acceleration. The obtained results can be used to find new ways to manipulate atoms, to cool and trap them by adjusting the detuning $\delta$.Comment: 16 pages, 7 figures. To be published in Phys. Rev.

Granular Solid Hydrodynamics

Granular elasticity, an elasticity theory useful for calculating static stress distribution in granular media, is generalized to the dynamic case by including the plastic contribution of the strain. A complete hydrodynamic theory is derived based on the hypothesis that granular medium turns transiently elastic when deformed. This theory includes both the true and the granular temperatures, and employs a free energy expression that encapsulates a full jamming phase diagram, in the space spanned by pressure, shear stress, density and granular temperature. For the special case of stationary granular temperatures, the derived hydrodynamic theory reduces to {\em hypoplasticity}, a state-of-the-art engineering model.Comment: 42 pages 3 fi

A New Upper Limit for the Tau-Neutrino Magnetic Moment

Using a prompt neutrino beam in which a nu_tau component was identified for the first time, the nu_tau magnetic moment was measured based on a search for an anomalous increase in the number of neutrino-electron interactions. One such event was observed when 2.3 were expected from background processes, giving an upper 90% confidence limit of 3.9x10^-7 Bohr magnetons.Comment: 9 pages; 1 figur