NAIP/NLRC4 inflammasome activation in MRP8+ cells is sufficient to cause systemic inflammatory disease.

Inflammasomes are cytosolic multiprotein complexes that initiate protective immunity in response to infection, and can also drive auto-inflammatory diseases, but the cell types and signalling pathways that cause these diseases remain poorly understood. Inflammasomes are broadly expressed in haematopoietic and non-haematopoietic cells and can trigger numerous downstream responses including production of IL-1β, IL-18, eicosanoids and pyroptotic cell death. Here we show a mouse model with endogenous NLRC4 inflammasome activation in Lysozyme2 + cells (monocytes, macrophages and neutrophils) in vivo exhibits a severe systemic inflammatory disease, reminiscent of human patients that carry mutant auto-active NLRC4 alleles. Interestingly, specific NLRC4 activation in Mrp8 + cells (primarily neutrophil lineage) is sufficient to cause severe inflammatory disease. Disease is ameliorated on an Asc -/- background, and can be suppressed by injections of anti-IL-1 receptor antibody. Our results provide insight into the mechanisms by which NLRC4 inflammasome activation mediates auto-inflammatory disease in vivo

Laboratory procedures manual for the firefly luciferase assay for adenosine triphosphate (ATP)

A manual on the procedures and instruments developed for the adenosine triphosphate (ATP) luciferase assay is presented. Data cover, laboratory maintenance, maintenance of bacterial cultures, bacteria measurement, reagents, luciferase procedures, and determination of microbal susceptibility to antibiotics

Effect of baryon density on parton production, chemical equilibration and thermal photon emission from quark gluon plasma

The effect of baryon density on parton production processes of $gg\rightleftharpoons ggg$ and $gg\rightleftharpoons q{\bar q}$ is studied using full phase space distribution function and also with inclusion of quantum statistics i.e. Pauli blocking and Bose enhancement factors, in the case of both saturated and unsaturated quark gluon plasma. The rate for the process $gg \rightleftharpoons q{\bar q}$ is found to be much less as compared to the most commonly used factorized result obtained on the basis of classical approximation. This discrepancy, which is found both at zero as well as at finite baryon densities, however, is not due to the lack of quantum statistics in the classical approximation, rather due to the use of Fermi-Dirac and Bose-Einstein distribution functions for partons instead of Boltzmann distribution which is appropriate under such approximation. Interestingly, the rates of parton production are found to be insensitive to the baryo-chemical potential particularly when the plasma is unsaturated although the process of chemical equilibration strongly depends on it. The thermal photon yields, have been calculated specifically from unsaturated plasma at finite baryon density. The exact results obtained numerically are found to be in close agreement with the analytic expression derived using factorized distribution functions appropriate for unsaturated plasma. Further, it is shown that in the case of unsaturated plasma, the thermal photon production is enhanced with increasing baryon density both at fixed temperature and fixed energy density of the quark gluon plasma.Comment: Latex, 24 pages, 6 postscript figures. Submitted to Phys. Rev.

Domain Wall Bubbles in High Energy Heavy Ion Collisions

It has been recently shown that meta-stable domain walls exist in high-density QCD ($\mu\neq 0$) as well as in QCD with large number of colors ($N_c\to\infty$), with the lifetime being exponentially long in both cases. Such metastable domain walls may exist in our world as well, especially in hot hadronic matter with temperature close to critical. In this paper we discuss what happens if a bubble made of such wall is created in heavy ion collisions, in the mixed phase between QGP and hadronic matter. We show it will further be expanded to larger volume $\sim 20 fm^3$ by the pion pressure, before it disappears, either by puncture or contraction. Both scenarios leave distinctive experimental signatures of such events, negatively affecting the interference correlations between the outgoing pions.Comment: 6 pages, 1 fi

Parametric Analyses In Randomized Clinical Trials

One salient feature of randomized clinical trials is that patients are randomly allocated to treatment groups, but not randomly sampled from any target population. Without random sampling parametric analyses are inexact, yet they are still often used in clinical trials. Given the availability of an exact test, it would still be conceivable to argue convincingly that for technical reasons (upon which we elaborate) a parametric test might be preferable in some situations. Having acknowledged this possibility, we point out that such an argument cannot be convincing without supporting facts concerning the specifics of the problem at hand. Moreover, we have never seen these arguments made in practice. We conclude that the frequent preference for parametric analyses over exact analyses is without merit. In this article we briefly present the scientific basis for preferring exact tests, and refer the interested reader to the vast literature backing up these claims. We also refute the assertions offered in some recent publications promoting parametric analyses as being superior in some general sense to exact analyses. In asking the reader to keep an open mind to our arguments, we are suggesting the possibility that numerous researchers have published incorrect advice, which has then been taught extensively in schools. We ask the reader to consider the relative merits of the arguments, but not the frequency with which each argument is made

NAIP proteins are required for cytosolic detection of specific bacterial ligands in vivo.

NLRs (nucleotide-binding domain [NBD] leucine-rich repeat [LRR]-containing proteins) exhibit diverse functions in innate and adaptive immunity. NAIPs (NLR family, apoptosis inhibitory proteins) are NLRs that appear to function as cytosolic immunoreceptors for specific bacterial proteins, including flagellin and the inner rod and needle proteins of bacterial type III secretion systems (T3SSs). Despite strong biochemical evidence implicating NAIPs in specific detection of bacterial ligands, genetic evidence has been lacking. Here we report the use of CRISPR/Cas9 to generate Naip1(-/-) and Naip2(-/-) mice, as well as Naip1-6(Δ/Δ) mice lacking all functional Naip genes. By challenging Naip1(-/-) or Naip2(-/-) mice with specific bacterial ligands in vivo, we demonstrate that Naip1 is uniquely required to detect T3SS needle protein and Naip2 is uniquely required to detect T3SS inner rod protein, but neither Naip1 nor Naip2 is required for detection of flagellin. Previously generated Naip5(-/-) mice retain some residual responsiveness to flagellin in vivo, whereas Naip1-6(Δ/Δ) mice fail to respond to cytosolic flagellin, consistent with previous biochemical data implicating NAIP6 in flagellin detection. Our results provide genetic evidence that specific NAIP proteins function to detect specific bacterial proteins in vivo

Controlled Irradiative Formation of Penitentes

Spike-shaped structures are produced by light-driven ablation in very different contexts. Penitentes 1-4 m high are common on Andean glaciers, where their formation changes glacier dynamics and hydrology. Laser ablation can produce cones 10-100 microns high with a variety of proposed applications in materials science. We report the first laboratory generation of centimeter-scale snow and ice penitentes. Systematically varying conditions allows identification of the essential parameters controlling the formation of ablation structures. We demonstrate that penitente initiation and coarsening requires cold temperatures, so that ablation leads to sublimation rather than melting. Once penitentes have formed, further growth of height can occur by melting. The penitentes intially appear as small structures (3 mm high) and grow by coarsening to 1-5 cm high. Our results are an important step towards understanding and controlling ablation morphologies.Comment: Accepted for publication in Physical Review Letter

Clocking hadronization in relativistic heavy ion collisions with balance functions

A novel state of matter has been hypothesized to exist during the early stage of relativistic heavy ion collisions, with normal hadrons not appearing until several fm/c after the start of the reaction. To test this hypothesis, correlations between charges and their associated anticharges are evaluated with the use of balance functions. It is shown that late-stage hadronization is characterized by tightly correlated charge/anticharge pairs when measured as a function of relative rapidity.Comment: 5 pages, 3 figure

Stability ordering of cycle expansions

We propose that cycle expansions be ordered with respect to stability rather than orbit length for many chaotic systems, particularly those exhibiting crises. This is illustrated with the strong field Lorentz gas, where we obtain significant improvements over traditional approaches.Comment: Revtex, 5 incorporated figures, total size 200