Overcoming the critical slowing down of flat-histogram Monte Carlo simulations: Cluster updates and optimized broad-histogram ensembles

We study the performance of Monte Carlo simulations that sample a broad histogram in energy by determining the mean first-passage time to span the entire energy space of d-dimensional ferromagnetic Ising/Potts models. We first show that flat-histogram Monte Carlo methods with single-spin flip updates such as the Wang-Landau algorithm or the multicanonical method perform sub-optimally in comparison to an unbiased Markovian random walk in energy space. For the d=1,2,3 Ising model, the mean first-passage time \tau scales with the number of spins N=L^d as \tau \propto N^2L^z. The critical exponent z is found to decrease as the dimensionality d is increased. In the mean-field limit of infinite dimensions we find that z vanishes up to logarithmic corrections. We then demonstrate how the slowdown characterized by z>0 for finite d can be overcome by two complementary approaches - cluster dynamics in connection with Wang-Landau sampling and the recently developed ensemble optimization technique. Both approaches are found to improve the random walk in energy space so that \tau \propto N^2 up to logarithmic corrections for the d=1 and d=2 Ising model

Mechanisms of immunosenescence

On April 7,8, 2009 a Symposium entitled "Pathophysiology of Successful and Unsuccessful Ageing" took place in Palermo, Italy. Here, the lectures of G. Pawelec, D. Dunn-Walters and. G. Colonna-Romano on T and B immunosenescence are summarized. In the elderly, many alterations of both innate and acquired immunity have been described. Alterations to the immune system in the older person are generally viewed as a deterioration of immunity, leading to the use of the catch-all term immunosenescence. Indeed, many immunological parameters are often markedly different in elderly compared to young people, and some, mostly circumstantial, evidence suggests that retained function of both innate and acquired immunity in the elderly is correlated with health status. What is often not clear from studies is how far immune dysfunction is a cause or an effect. A better understanding of immunosenescence and mechanisms responsible for proven deleterious changes is needed to maintain a healthy state in later life and to design possible therapeutic interventions

Overcoming the slowing down of flat-histogram Monte Carlo simulations: Cluster updates and optimized broad-histogram ensembles

We study the performance of Monte Carlo simulations that sample a broad histogram in energy by determining the mean first-passage time to span the entire energy space of d-dimensional ferromagnetic Ising/Potts models. We first show that flat-histogram Monte Carlo methods with single-spin flip updates such as the Wang-Landau algorithm or the multicanonical method perform suboptimally in comparison to an unbiased Markovian random walk in energy space. For the d=1, 2, 3 Ising model, the mean first-passage time τ scales with the number of spins N=Ld as τ∝N2Lz. The exponent z is found to decrease as the dimensionality d is increased. In the mean-field limit of infinite dimensions we find that z vanishes up to logarithmic corrections. We then demonstrate how the slowdown characterized by z\u3e0 for finite d can be overcome by two complementary approaches—cluster dynamics in connection with Wang-Landau sampling and the recently developed ensemble optimization technique. Both approaches are found to improve the random walk in energy space so that τ∝N2 up to logarithmic corrections for the d=1, 2 Ising model

A double-negative (IgD CD27 ) B cell population is increased in the peripheral blood of elderly people

The T cell branch of the immune system has been extensively studied in the elderly and it is known that the elderly have impaired immune function, mainly due to the chronic antigenic load that ultimately causes shrinkage of the T cell repertoire and filling of the immunologic space with memory T cells. In the present paper,we describe the IgD CD27 double-negative B cell population which (aswe have recently described) is higher in the elderly. Most of these cells were IgG+. Evaluation of the telomere length and expression of the ABCB1 transporter and anti-apoptotic molecule, Bcl2, shows that they have the markers of memory B cells. We also show that these cells do not act as antigen presenting cells, as indicated by the low levels of CD80 and DR, nor do they express significant levels of the CD40 molecule necessary to interact with T lymphocytes through the ligand, CD154. Hence, we hypothesize that these expanded cells are late memory or exhausted cells that have down-modulated the expression of CD27 and filled the immunologic space in the elderly. These cells might be the age-related manifestation of time-enduring stimulation or dysregulation of the immune system

B cell immunosenescence: different features of naive and memory B cells in elderly

Elderly people show a reduced protection against new infections and a decreased response to vaccines as a consequence of impairment of both cellular and humoral immunity. In this paper we have studied memory/na\uefve B cells in the elderly, evaluating surface immunoglobulin expression, production of the pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-\u3b1 and interleukin (IL)-10, and presence of somatic hypermutation, focusing on the IgG(+)IgD(-)CD27(-) double negative (DN) B cells that are expanded in the elderly. Our results show that na\uefve B cells from young donors need a sufficiently strong stimulus to be activated "in vitro", while na\uefve B cells from old subjects are able to produce IL-10 and TNF-\u3b1 when stimulated "physiologically" (\u3b1-CD40/IL-4), suggesting that these cells might play a role in the control of the immuno-inflammatory environment in the elderly. In addition, in the elderly there is an accumulation of DN B cells with a reduced rate of somatic hypermutation. Thus, DN B lymphocytes may be exhausted cells that are expanded and accumulate as a by-product of persistent stimulation or impaired germinal center formatio

Evidence for less marked potential signs of T-cell immunosenescence in centenarian offspring than in the general age-matched population

People may reach the upper limits of the human life span at least partly because they have maintained more appropriate immune function, avoiding changes to immunity termed "immunosenescence." Exceptionally long-lived people may be enriched for genes that contribute to their longevity, some of which may bear on immune function. Centenarian offspring would be expected to inherit some of these, which might be reflected in their resistance to immunosenescence, and contribute to their potential longevity. We have tested this hypothesis by comparing centenarian offspring with age-matched controls. We report differences in the numbers and proportions of both CD4(+) and CD8(+) early- and late-differentiated T cells, as well as potentially senescent CD8(+) T cells, suggesting that the adaptive T-cell arm of the immune system is more "youthful" in centenarian offspring than controls. This might reflect a superior ability to mount effective responses against newly encountered antigens and thus contribute to better protection against infection and to greater longevity

Solving the large discrepancy between inclusive and exclusive measurements of the 8Li+4He→11B+n{}^8{\rm Li}+{}^4{\rm He}\to{}^{11}{\rm B}+n reaction cross section at astrophysical energies

A solution of the large discrepancy existing between inclusive and exclusive measurements of the ${}^8{\rm Li}+{}^4{\rm He}\to{}^{11}{\rm B}+n$ reaction cross section at $E_{cm} <3$ MeV is evaluated. This problem has profound astrophysical relevance for this reaction is of great interest in Big-Bang and r-process nucleosynthesis. By means of a novel technique, a comprehensive study of all existing ${}^8{\rm Li}+{}^4{\rm He}\to{}^{11}{\rm B}+n$ cross section data is carried out, setting up a consistent picture in which all the inclusive measurements provide the reliable value of the cross section. New unambiguous signatures of the strong branch pattern non-uniformities, near the threshold of higher ${}^{11}{\rm B}$ excited levels, are presented and their possible origin, in terms of the cluster structure of the involved excited states of ${}^{11}{\rm B}$ and ${}^{12}{\rm B}$ nuclei, is discussed.Comment: 5 pages, 4 figures, 1 tabl

Inflammation, genetic background and longevity

Ageing is an inexorable intrinsic process that affects all cells, tissues, organs and individuals. Due to a diminished homeostasis and increased organism frailty, ageing causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death. Actually, it is characterized by a state of reduced ability to maintain health and general homeodynamics of the organism.Alarge part of the ageing phenotype is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status of ageing, ‘‘inflamm-ageing’’. It is strictly linked to immunosenescence, and on the whole they are the major contributory factors to the increased frequency of morbidity and mortality among elderly. Inflammageing is compatible with longevity; even if centenarians have an increased level of inflammatory mediators in comparison to old subjects and they are very frail, they also have high level of anti-inflammatory cytokines together with protective genotypes. Actually, data on case control studies performed in Italian centenarians suggest that a pro-inflammatory genotype is unfavourable to reach extreme longevity in good health and likely favours the onset of age-related diseases such as cardiovascular diseases and Alzheimer’s disease, the leading causes of mortality and disability in the elderly. However, many associations between gene variants and longevity have been found only in Italian population. This should not be unexpected, since ageing and longevity are complex traits resulting not only and not exclusively from genetics, but rather from the interactions between genetics, environment and chance

The CMS RPC gas gain monitoring system: an overview and preliminary results

The status of the CMS RPC Gas Gain Monitoring (GGM) system developed at the Frascati Laboratory of INFN (Istituto Nazionale di Fisica Nucleare) is reported on. The GGM system is a cosmic ray telescope based on small RPC detectors operated with the same gas mixture used by the CMS RPC system. The GGM gain and efficiency are continuously monitored on-line, thus providing a fast and accurate determination of any shift in working point conditions. The construction details and the first result of GGM commissioning are described.Comment: 8 pages, 9 figures, uses lnfprepCMS.sty, presented by L. Benussi at RPC07, Mumbai, INDIA 200

Gas Analysis and Monitoring Systems for the RPC Detector of CMS at LHC

The Resistive Plate Chambers (RPC) detector of the CMS experiment at the LHC proton collider (CERN, Switzerland) will employ an online gas analysis and monitoring system of the freon-based gas mixture used. We give an overview of the CMS RPC gas system, describe the project parameters and first results on gas-chromatograph analysis. Finally, we report on preliminary results for a set of monitor RPC.Comment: 9 pages, 8 figures. Presented by Stefano Bianco (Laboratori Nazionali di Frascati dell'INFN) at the IEEE NSS, San Diego (USA), October 200