Downscaling extremes: A comparison of extreme value distributions in point-source and gridded precipitation data

There is substantial empirical and climatological evidence that precipitation extremes have become more extreme during the twentieth century, and that this trend is likely to continue as global warming becomes more intense. However, understanding these issues is limited by a fundamental issue of spatial scaling: most evidence of past trends comes from rain gauge data, whereas trends into the future are produced by climate models, which rely on gridded aggregates. To study this further, we fit the Generalized Extreme Value (GEV) distribution to the right tail of the distribution of both rain gauge and gridded events. The results of this modeling exercise confirm that return values computed from rain gauge data are typically higher than those computed from gridded data; however, the size of the difference is somewhat surprising, with the rain gauge data exhibiting return values sometimes two or three times that of the gridded data. The main contribution of this paper is the development of a family of regression relationships between the two sets of return values that also take spatial variations into account. Based on these results, we now believe it is possible to project future changes in precipitation extremes at the point-location level based on results from climate models.Comment: Published in at http://dx.doi.org/10.1214/09-AOAS287 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Predicting the coherence resonance curve using a semi-analytical treatment

Emergence of noise induced regularity or Coherence Resonance in nonlinear excitable systems is well known. We explain theoretically why the normalized variance ($V_{N}$) of inter spike time intervals, which is a measure of regularity in such systems, has a unimodal profile. Our semi-analytic treatment of the associated spiking process produces a general yet simple formula for $V_{N}$, which we show is in very good agreement with numerics in two test cases, namely the FitzHugh-Nagumo model and the Chemical Oscillator model.Comment: 5 pages, 5 figure

Local Bone Marrow Renin-Angiotensin System and Atherosclerosis

Local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) affects the growth, production, proliferation differentiation, and function of hematopoietic cells. Angiotensin II (Ang II), the dominant effector peptide of the RAS, regulates cellular growth in a wide variety of tissues in pathobiological states. RAS, especially Ang II and Ang II type 1 receptor (AT1R), has considerable proinflammatory and proatherogenic effects on the vessel wall, causing progression of atherosclerosis. Recent investigations, by analyzing several BM chimeric mice whose BM cells were positive or negative for AT1R, disclosed that AT1R in BM cells participates in the pathogenesis of atherosclerosis. Therefore, AT1R blocking not only in vascular cells but also in the BM could be an important therapeutic approach to prevent atherosclerosis. The aim of this paper is to review the function of local BM RAS in the pathogenesis of atherosclerosis

Stuttering Min oscillations within E. coli bacteria: A stochastic polymerization model

We have developed a 3D off-lattice stochastic polymerization model to study subcellular oscillation of Min proteins in the bacteria Escherichia coli, and used it to investigate the experimental phenomenon of Min oscillation stuttering. Stuttering was affected by the rate of immediate rebinding of MinE released from depolymerizing filament tips (processivity), protection of depolymerizing filament tips from MinD binding, and fragmentation of MinD filaments due to MinE. Each of processivity, protection, and fragmentation reduces stuttering, speeds oscillations, and reduces MinD filament lengths. Neither processivity or tip-protection were, on their own, sufficient to produce fast stutter-free oscillations. While filament fragmentation could, on its own, lead to fast oscillations with infrequent stuttering; high levels of fragmentation degraded oscillations. The infrequent stuttering observed in standard Min oscillations are consistent with short filaments of MinD, while we expect that mutants that exhibit higher stuttering frequencies will exhibit longer MinD filaments. Increased stuttering rate may be a useful diagnostic to find observable MinD polymerization in experimental conditions.Comment: 21 pages, 7 figures, missing unit for k_f inserte

Block of death-receptor apoptosis protects mouse cytomegalovirus from macrophages and is a determinant of virulence in immunodeficient hosts.

The inhibition of death-receptor apoptosis is a conserved viral function. The murine cytomegalovirus (MCMV) gene M36 is a sequence and functional homologue of the human cytomegalovirus gene UL36, and it encodes an inhibitor of apoptosis that binds to caspase-8, blocks downstream signaling and thus contributes to viral fitness in macrophages and in vivo. Here we show a direct link between the inability of mutants lacking the M36 gene (ΔM36) to inhibit apoptosis, poor viral growth in macrophage cell cultures and viral in vivo fitness and virulence. ΔM36 grew poorly in RAG1 knockout mice and in RAG/IL-2-receptor common gamma chain double knockout mice (RAGγC(-/-)), but the depletion of macrophages in either mouse strain rescued the growth of ΔM36 to almost wild-type levels. This was consistent with the observation that activated macrophages were sufficient to impair ΔM36 growth in vitro. Namely, spiking fibroblast cell cultures with activated macrophages had a suppressive effect on ΔM36 growth, which could be reverted by z-VAD-fmk, a chemical apoptosis inhibitor. TNFα from activated macrophages synergized with IFNγ in target cells to inhibit ΔM36 growth. Hence, our data show that poor ΔM36 growth in macrophages does not reflect a defect in tropism, but rather a defect in the suppression of antiviral mediators secreted by macrophages. To the best of our knowledge, this shows for the first time an immune evasion mechanism that protects MCMV selectively from the antiviral activity of macrophages, and thus critically contributes to viral pathogenicity in the immunocompromised host devoid of the adaptive immune system

Influenza A virus-derived defective interfering particles for antiviral treatment

Here, we report on genetically engineered, propagation-incompetent influenza A virus (IAV) particles, so-called defective interfering particles (DIPs) that have been suggested as a promising novel antiviral agent. Typically, IAV DIPs harbor a large internal deletion in one of their eight genomic viral RNA (vRNA) segments. Further, DIPs are capable of hijacking cellular and viral resources upon co-infection with fully infectious standard virus (STV), resulting in an antiviral effect. Besides this replication interference, DIP infection also stimulates innate immunity, adding to the antiviral efficacy. So far, DIPs were produced in embryonated chicken eggs. To improve scalability and flexibility of processes as well as to increase product quality, we established a cell culture-based DIP production system [1,2]. This includes the development of a genetically engineered virus-cell propagation system that allows production of DIPs without the need to add infectious STV to complement missing gene functions of DIPs. Specifically, the MDCK suspension cell line generated expresses the PB2 protein [2], encoded by segment 1 (S1) of IAV, which is not expressed by “DI244” - a prototypic, well-characterized DIP harboring a deletion in S1. Using this cell culture-based production process in batch [2,3] and perfusion mode [4] at laboratory scale, we show that we can achieve very high DI244 titers of up to 2.6E+11 DIPs/mL. Infections of mice demonstrated that intranasal administration of the produced DI244 material resulted in no apparent toxic effects and in a full rescue of mice co-treated with an otherwise lethal dose of IAV [2]. Please click Download on the upper right corner to see the full abstract

Turbulence and Multiscaling in the Randomly Forced Navier Stokes Equation

We present an extensive pseudospectral study of the randomly forced Navier-Stokes equation (RFNSE) stirred by a stochastic force with zero mean and a variance $\sim k^{4-d-y}$, where $k$ is the wavevector and the dimension $d = 3$. We present the first evidence for multiscaling of velocity structure functions in this model for $y \geq 4$. We extract the multiscaling exponent ratios $\zeta_p/\zeta_2$ by using extended self similarity (ESS), examine their dependence on $y$, and show that, if $y = 4$, they are in agreement with those obtained for the deterministically forced Navier-Stokes equation ($3d$NSE). We also show that well-defined vortex filaments, which appear clearly in studies of the $3d$NSE, are absent in the RFNSE.Comment: 4 pages (revtex), 6 figures (postscript

Cytotoxic polyfunctionality maturation of cytomegalovirus-pp65-specific CD4 + and CD8 + T-cell responses in older adults positively correlates with response size

Cytomegalovirus (CMV) infection is one of the most common persistent viral infections in humans worldwide and is epidemiologically associated with many adverse health consequences during aging. Previous studies yielded conflicting results regarding whether large, CMV-specific T-cell expansions maintain their function during human aging. In the current study, we examined the in vitro CMV-pp65-reactive T-cell response by comprehensively studying five effector functions (i.e., interleukin-2, tumor necrosis factor-α, interferon-γ, perforin, and CD107a expression) in 76 seropositive individuals aged 70 years or older. Two data-driven, polyfunctionality panels (IL-2-associated and cytotoxicity-associated) derived from effector function co-expression patterns were used to analyze the results. We found that, CMV-pp65-reactive CD8 + and CD4 + T cells contained similar polyfunctional subsets, and the level of polyfunctionality was related to the size of antigen-specific response. In both CD8 + and CD4 + cells, polyfunctional cells with high cytotoxic potential accounted for a larger proportion of the total response as the total response size increased. Notably, a higher serum CMV-IgG level was positively associated with a larger T-cell response size and a higher level of cytotoxic polyfunctionality. These findings indicate that CMV-pp65-specific CD4 + and CD8 + T cell undergo simultaneous cytotoxic polyfunctionality maturation during aging

Rotating Convection in an Anisotropic System

We study the stability of patterns arising in rotating convection in weakly anisotropic systems using a modified Swift-Hohenberg equation. The anisotropy, either an endogenous characteristic of the system or induced by external forcing, can stabilize periodic rolls in the K\"uppers-Lortz chaotic regime. For the particular case of rotating convection with time-modulated rotation where recently, in experiment, chiral patterns have been observed in otherwise K\"uppers-Lortz-unstable regimes, we show how the underlying base-flow breaks the isotropy, thereby affecting the linear growth-rate of convection rolls in such a way as to stabilize spirals and targets. Throughout we compare analytical results to numerical simulations of the Swift-Hohenberg equation