Uniform polynomial rates of convergence for a class of L\'evy-driven controlled SDEs arising in multiclass many-server queues

We study the ergodic properties of a class of controlled stochastic differential equations (SDEs) driven by $\alpha$-stable processes which arise as the limiting equations of multiclass queueing models in the Halfin-Whitt regime that have heavy-tailed arrival processes. When the safety staffing parameter is positive, we show that the SDEs are uniformly ergodic and enjoy a polynomial rate of convergence to the invariant probability measure in total variation, which is uniform over all stationary Markov controls resulting in a locally Lipschitz continuous drift. We also derive a matching lower bound on the rate of convergence (under no abandonment). On the other hand, when all abandonment rates are positive, we show that the SDEs are exponentially ergodic uniformly over the above-mentioned class of controls. Analogous results are obtained for L\'evy-driven SDEs arising from multiclass many-server queues under asymptotically negligible service interruptions. For these equations, we show that the aforementioned ergodic properties are uniform over all stationary Markov controls. We also extend a key functional central limit theorem concerning diffusion approximations so as to make it applicable to the models studied here

Synchronized turbo apoptosis induced by cold-shock

In our research on the role of apoptosis in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE), we aim to evaluate the effects of early and late apoptotic cells and blebs on antigen presenting cells. This requires the in vitro generation of sufficiently large and homogeneous populations of early and late apoptotic cells. Here, we present a quick method encountered by serendipity that results in highly reproducible synchronized homogeneous apoptotic cell populations. In brief, granulocytic 32Dcl3 cells are incubated on ice for 2 h and subsequently rewarmed at 37°C. After 30–90 min at 37°C more than 80–90% of the cells become early apoptotic (Annexin V positive/propidium iodide negative). After 24 h of rewarming at 37°C 98% of the cells were late apoptotic (secondary necrotic; Annexin V positive/propidium iodide positive). Cells already formed apoptotic blebs at their cell surface after approximately 20 min at 37°C. Inter-nucleosomal chromatin cleavage and caspase activation were other characteristics of this cold-shock-induced process of apoptosis. Consequently, apoptosis could be inhibited by a caspase inhibitor. Finally, SLE-derived anti-chromatin autoantibodies showed a high affinity for apoptotic blebs generated by cold-shock. Overall, cold-shock induced apoptosis is achieved without the addition of toxic compounds or antibodies, and quickly leads to synchronized homogeneous apoptotic cell populations, which can be applied for various research questions addressing apoptosis

Changes in Electronic Structure and Chemical Bonding upon Crystallization of the Phase Change Material GeSb₂Te₄

High-resolution photoelectron spectroscopy of in situ prepared films of GeSb₂Te₄ reveals significant differences in electronic and chemical structure between the amorphous and the crystalline phase. Evidence for two different chemical environments of Ge and Sb in the amorphous structure is found. This observation can explain the pronounced property contrast between both phases and provides new insight into the formation of the amorphous state

Extremes of Gaussian random fields with regularly varying dependence structure

Let be a centered Gaussian random field with variance function sigma (2)(ai...) that attains its maximum at the unique point , and let . For a compact subset of a"e, the current literature explains the asymptotic tail behaviour of under some regularity conditions including that 1 - sigma(t) has a polynomial decrease to 0 as t -> t (0). In this contribution we consider more general case that 1 - sigma(t) is regularly varying at t (0). We extend our analysis to Gaussian random fields defined on some compact set , deriving the exact tail asymptotics of for the class of Gaussian random fields with variance and correlation functions being regularly varying at t (0). A crucial novel element is the analysis of families of Gaussian random fields that do not possess locally additive dependence structures, which leads to qualitatively new types of asymptotics

Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP

Most human protein-encoding genes contain multiple exons that are spliced together, frequently in alternative arrangements, by the spliceosome. It is established that U1 snRNP is an essential component of the spliceosome, in human consisting of RNA and ten proteins, several of which are post- translationally modified and exist as multiple isoforms. Unresolved and challenging to investigate are the effects of these post translational modifications on the dynamics, interactions and stability of the particle. Using mass spectrometry we investigate the composition and dynamics of the native human U1 snRNP and compare native and recombinant complexes to isolate the effects of various subunits and isoforms on the overall stability. Our data reveal differential incorporation of four protein isoforms and dynamic interactions of subunits U1-A, U1-C and Sm-B/B’. Results also show that unstructured post- ranslationally modified C-terminal tails are responsible for the dynamics of Sm-B/B’ and U1-C and that their interactions with the Sm core are controlled by binding to different U1-70k isoforms and their phosphorylation status in vivo. These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function.This work was funded by: BBSRC (OVM), BBSRC and EPSRC (HH and NM), EU Prospects (HH), European Science Foundation (NM), the Royal Society (CVR), and fellowship from JSPS and HFSP (YM and DAPK respectively)

Apoptosis-induced histone H3 methylation is targeted by autoantibodies in systemic lupus erythematosus

Objectives: In systemic lupus erythematosus (SLE) apoptotic chromatin is present extracellularly, which is most likely the result of disturbed apoptosis and/or insufficient removal. Released chromatin, modified during apoptosis, activates the immune system resulting in the formation of autoantibodies. A study was undertaken to identify apoptosis-induced histone modifications that play a role in SLE. Methods: The lupus-derived monoclonal antibody BT164, recently established by selection using apoptotic nucleosomes, was analysed by ELISA, western blot analysis and immunofluorescence staining using chromatin, cells, plasma and renal sections. Random peptide phage display and peptide inhibition ELISA were used to identify precisely the epitope of BT164. The reactivity of plasma samples from lupus mice and patients with SLE with the epitope of BT164 was investigated by peptide ELISA. Results: The epitope of BT164 was mapped in the N-terminal tail of histone H3 (27-KSAPAT-32) and included the apoptosis-induced trimethylation of K27. siRNA-mediated silencing of histone demethylases in cultured cells resulted in hypermethylation of H3K27 and increased nuclear reactivity of BT164. This apoptosis-induced H3K27me3 is a target for autoantibodies in patients and mice with SLE and is present in plasma and in glomerular deposits. Conclusion: In addition to previously identified acetylation of histone H4, H2A and H2B, this study shows that trimethylation of histone H3 on lysine 27 is induced by apoptosis and associated with autoimmunity in SLE. This finding is important for understanding the autoimmune response in SLE and for the development of translational strategies

New insights into colloidal gold flakes: structural investigation, micro-ellipsometry and thinning procedure towards ultrathin monocrystalline layers

High-quality fabrication of plasmonic devices often relies on wet-chemically grown ultraflat, presumably single-crystalline gold flakes due to their superior materials properties. However, important details about their intrinsic structure and their optical properties are not well understood yet. In this study, we present a synthesis routine for large flakes with diameters of up to 70 μm and an in-depth investigation of their structural and optical properties. The flakes are precisely analyzed by transmission electron microscopy, electron backscatter diffraction and micro-ellipsometry. We found new evidence for the existence of twins extending parallel to the Au flake {111} surfaces which have been found to not interfere with the presented nanopatterning. Micro-Ellipsometry was carried out to determine the complex dielectric function and to compare it to previous measurements of bulk single crystalline gold. Finally, we used focused ion beam milling to prepare smooth crystalline layers and high-quality nanostructures with desired thickness down to 10 nm to demonstrate the outstanding properties of the flakes. Our findings support the plasmonics and nano optics community with a better understanding of this material which is ideally suited for superior plasmonic nanostructures

Activation of interferon regulatory factor-3 via toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA

U1-snRNA is an integral part of the U1 ribonucleoprotein pivotal for pre-mRNA splicing. Toll-like receptor (TLR) signaling has recently been associated with immunoregulatory capacities of U1-snRNA. Using lung A549 epithelial/carcinoma cells, we report for the first time on interferon regulatory factor (IRF)-3 activation initiated by endosomally delivered U1-snRNA. This was associated with expression of the IRF3-inducible genes interferon-β (IFN-β), CXCL10/IP-10 and indoleamine 2,3-dioxygenase. Mutational analysis of the U1-snRNA-activated IFN-β promoter confirmed the crucial role of the PRDIII element, previously proven pivotal for promoter activation by IRF3. Notably, expression of these parameters was suppressed by bafilomycin A1, an inhibitor of endosomal acidification, implicating endosomal TLR activation. Since resiquimod, an agonist of TLR7/8, failed to stimulate A549 cells, data suggest TLR3 to be of prime relevance for cellular activation. To assess the overall regulatory potential of U1-snRNA-activated epithelial cells on cytokine production, co-cultivation with peripheral blood mononuclear cells (PBMC) was performed. Interestingly, A549 cells activated by U1-snRNA reinforced phytohemagglutinin-induced interleukin-10 release by PBMC but suppressed that of tumor necrosis factor-α, indicating an anti-inflammatory potential of U1-snRNA. Since U1-snRNA is enriched in apoptotic bodies and epithelial cells are capable of performing efferocytosis, the present data in particular connect to immunobiological aspects of apoptosis at host/environment interfaces