Extremes on the discounted aggregate claims in a time dependent risk model

This paper presents an extension of the classical compound Poisson risk model for which the inter-claim time and the forthcoming claim amount are no longer independent random variables (rv's). Asymptotic tail probabilities for the discounted aggregate claims are presented when the force of interest is constant and the claim amounts are heavy tail distributed rv's. Furthermore, we derive asymptotic finite time ruin probabilities, as well as asymptotic approximations for some common risk measures associated with the discounted aggregate claims. A simulation study is performed in order to validate the results obtained in the free interest risk model

Giant Right Intrathoracic Myxoid Fusocellular Lipoma

Intrathoracic lipomas are rare benign tumors; their behavior is not completely clear and their surgical removal may be challenging. We report a case of a giant right intrathoracic myxoid fusocellular lipoma compressing the lung, tracheobronchial tree, and esophagus which was removed through a posterolateral thoracotomy. Complete removal resulted in resolution of the chest pain and improvement of the dyspnea, with no recurrence at 4-year follow-up

Reducing Residual-Mass Effects for Domain-Wall Fermions

It has been suggested to project out a number of low-lying eigenvalues of the four-dimensional Wilson--Dirac operator that generates the transfer matrix of domain-wall fermions in order to improve simulations with domain-wall fermions. We investigate how this projection method reduces the residual chiral symmetry-breaking effects for a finite extent of the extra dimension. We use the standard Wilson as well as the renormalization--group--improved gauge action. In both cases we find a substantially reduced residual mass when the projection method is employed. In addition, the large fluctuations in this quantity disappear.Comment: 18 pages, 10 figures, references updated, comments adde

Simulation of Atmospheric Muon and Neutrino Fluxes with CORSIKA

The fluxes of atmospheric muons and neutrinos are calculated by a three dimensional Monte Carlo simulation with the air shower code CORSIKA using the hadronic interaction models DPMJET, VENUS, GHEISHA, and UrQMD. For the simulation of low energy primary particles the original CORSIKA has been extended by a parametrization of the solar modulation and a microscopic calculation of the directional dependence of the geomagnetic cut-off functions. An accurate description for the geography of the Earth has been included by a digital elevation model, tables for the local magnetic field in the atmosphere, and various atmospheric models for different geographic latitudes and annual seasons. CORSIKA is used to calculate atmospheric muon fluxes for different locations and the neutrino fluxes for Kamioka. The results of CORSIKA for the muon fluxes are verified by an extensive comparison with recent measurements. The obtained neutrino fluxes are compared with other calculations and the influence of the hadronic interaction model, the geomagnetic cut-off and the local magnetic field on the neutrino fluxes is investigated.Comment: revtex, 19 pages, 19 Postscript figures, submitted to Phys. Rev.

Structural basis for cell surface patterning through NetrinG-NGL interactions

Brain wiring depends on cells making highly localized and selective connections through surface protein-protein interactions, including those between NetrinGs and NetrinG ligands (NGLs). The NetrinGs are members of the structurally uncharacterized netrin family. We present a comprehensive crystallographic analysis comprising NetrinG1-NGL1 and NetrinG2-NGL2 complexes, unliganded NetrinG2 and NGL3. Cognate NetrinG-NGL interactions depend on three specificity-conferring NetrinG loops, clasped tightly by matching NGL surfaces. We engineered these NGL surfaces to implant custom-made affinities for NetrinG1 and NetrinG2. In a cellular patterning assay, we demonstrate that NetrinG-binding selectivity can direct the sorting of a mixed population of NGLs into discrete cell surface subdomains. These results provide a molecular model for selectivity-based patterning in a neuronal recognition system, dysregulation of which is associated with severe neuropsychological disorders

Lattice QCD Simulations in External Background Fields

We discuss recent results and future prospects regarding the investigation, by lattice simulations, of the non-perturbative properties of QCD and of its phase diagram in presence of magnetic or chromomagnetic background fields. After a brief introduction to the formulation of lattice QCD in presence of external fields, we focus on studies regarding the effects of external fields on chiral symmetry breaking, on its restoration at finite temperature and on deconfinement. We conclude with a few comments regarding the effects of electromagnetic background fields on gluodynamics.Comment: 31 pages, 10 figures, minor changes and references added. To appear in Lect. Notes Phys. "Strongly interacting matter in magnetic fields" (Springer), edited by D. Kharzeev, K. Landsteiner, A. Schmitt, H.-U. Ye

Sensitivity of simulated regional Arctic climate to the choice of coupled model domain

The climate over the Arctic has undergone changes in recent decades. In order to evaluate the coupled response of the Arctic system to external and internal forcing, our study focuses on the estimation of regional climate variability and its dependence on large-scale atmospheric and regional ocean circulations. A global ocean–sea ice model with regionally high horizontal resolution is coupled to an atmospheric regional model and global terrestrial hydrology model. This way of coupling divides the global ocean model setup into two different domains: one coupled, where the ocean and the atmosphere are interacting, and one uncoupled, where the ocean model is driven by prescribed atmospheric forcing and runs in a so-called stand-alone mode. Therefore, selecting a specific area for the regional atmosphere implies that the ocean–atmosphere system can develop ‘freely’ in that area, whereas for the rest of the global ocean, the circulation is driven by prescribed atmospheric forcing without any feedbacks. Five different coupled setups are chosen for ensemble simulations. The choice of the coupled domains was done to estimate the influences of the Subtropical Atlantic, Eurasian and North Pacific regions on northern North Atlantic and Arctic climate. Our simulations show that the regional coupled ocean–atmosphere model is sensitive to the choice of the modelled area. The different model configurations reproduce differently both the mean climate and its variability. Only two out of five model setups were able to reproduce the Arctic climate as observed under recent climate conditions (ERA-40 Reanalysis). Evidence is found that the main source of uncertainty for Arctic climate variability and its predictability is the North Pacific. The prescription of North Pacific conditions in the regional model leads to significant correlation with observations, even if the whole North Atlantic is within the coupled model domain. However, the inclusion of the North Pacific area into the coupled system drastically changes the Arctic climate variability to a point where the Arctic Oscillation becomes an ‘internal mode’ of variability and correlations of year-to-year variability with observational data vanish. In line with previous studies, our simulations provide evidence that Arctic sea ice export is mainly due to ‘internal variability’ within the Arctic region. We conclude that the choice of model domains should be based on physical knowledge of the atmospheric and oceanic processes and not on ‘geographic’ reasons. This is particularly the case for areas like the Arctic, which has very complex feedbacks between components of the regional climate system

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to in-clude antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of an-tivirals in use or development for any disease bears testament to the challenges of antiviral de-velopment. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic / endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate in-fections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus

SMC complexes differentially compact mitotic chromosomes according to genomic context

Structural maintenance of chromosomes (SMC) protein complexes are key determinants of chromosome conformation. Using Hi-C and polymer modelling, we study how cohesin and condensin, two deeply conserved SMC complexes, organize chromosomes in the budding yeast Saccharomyces cerevisiae. The canonical role of cohesin is to co-align sister chromatids, while condensin generally compacts mitotic chromosomes. We find strikingly different roles for the two complexes in budding yeast mitosis. First, cohesin is responsible for compacting mitotic chromosome arms, independently of sister chromatid cohesion. Polymer simulations demonstrate that this role can be fully accounted for through cis-looping of chromatin. Second, condensin is generally dispensable for compaction along chromosome arms. Instead, it plays a targeted role compacting the rDNA proximal regions and promoting resolution of peri-centromeric regions. Our results argue that the conserved mechanism of SMC complexes is to form chromatin loops and that distinct SMC-dependent looping activities are selectively deployed to appropriately compact chromosomes

Proteome changes in platelets activated by arachidonic acid, collagen, and thrombin

<p>Abstract</p> <p>Background</p> <p>Platelets are small anucleated blood particles that play a key role in the control of bleeding. Platelets need to be activated to perform their functions and participate in hemostasis. The process of activation is accompanied by vast protein reorganization and posttranslational modifications. The goal of this study was to identify changes in proteins in platelets activated by different agonists. Platelets were activated by three different agonists - arachidonic acid, collagen, and thrombin. 2D SDS-PAGE (pI 4-7) was used to separate platelet proteins. Proteomes of activated and resting platelets were compared with each other by Progenesis SameSpots statistical software; and proteins were identified by nanoLC-MS/MS.</p> <p>Results</p> <p>190 spots were found to be significantly different. Of these, 180 spots were successfully identified and correspond to 144 different proteins. Five proteins were found that had not previously been identified in platelets: protein CDV3 homolog, protein ETHE1, protein LZIC, FGFR1 oncogene partner 2, and guanine nucleotide-binding protein subunit beta-5. Using spot expression profile analysis, we found two proteins (WD repeat-containing protein 1 and mitochondrial glycerol-3-phosphate dehydrogenase) that may be part of thrombin specific activation or signal transduction pathway(s).</p> <p>Conclusions</p> <p>Our results, characterizing the differences within proteins in both activated (by various agonists) and resting platelets, can thus contribute to the basic knowledge of platelets and to the understanding of the function and development of new antiplatelet drugs.</p