The DIRAC experiment at CERN

The DIRAC experiment at CERN aims to measure the lifetime of the pionium atom ($A_{2\pi}$), a $\pi^+\pi^-$ bound state with an accuracy of 10%. The experimental setup consists of a high precision magnetic double arm spectrometer, located at the high intensity proton beam of the CERN Proton Synchrotron. This measurement will provide - in a model independent way - the S-wave pion scattering length difference $|a_0 - a_2|$ with 5% precision.Comment: Talk presented at the XXXVIIIth Rencontres de Moriond session devoted to QCD and High Energy Hadronic Interactions. We give a status report of the DIRAC experiment and present new analysis result

The role of copeptin as a diagnostic and prognostic biomarker for risk stratification in the emergency department

The hypothalamic-pituitary-adrenal axis is activated in response to stress. One of the activated hypothalamic hormones is arginine vasopressin, a hormone involved in hemodynamics and osmoregulation. Copeptin, the C-terminal part of the arginine vasopressin precursor peptide, is a sensitive and stable surrogate marker for arginine vasopressin release. Measurement of copeptin levels has been shown to be useful in a variety of clinical scenarios, particularly as a prognostic marker in patients with acute diseases such as lower respiratory tract infection, heart disease and stroke. The measurement of copeptin levels may provide crucial information for risk stratification in a variety of clinical situations. As such, the emergency department appears to be the ideal setting for its potential use. This review summarizes the recent progress towards determining the prognostic and diagnostic value of copeptin in the emergency department

Detection of π+π−\pi^+\pi^-atoms with the DIRAC spectrometer at CERN

The goal of the DIRAC experiment at CERN is to measure with high precision the lifetime of the $\pi^+\pi^-$ atom ($A_{2\pi}$), which is of order $3\times10^{-15}$ s, and thus to determine the s-wave $\pi\pi$-scattering lengths difference $|a_{0}-a_{2}|$. $A_{2\pi}$ atoms are detected through the characteristic features of $\pi^+\pi^-$ pairs from the atom break-up (ionization) in the target. We report on a first high statistics atomic data sample obtained from p Ni interactions at 24 GeV/$c$ proton momentum and present the methods to separate the signal from the background.Comment: 19 pages, 12 figures, 1 tabl

Discriminating lymphomas and reactive lymphadenopathy in lymph node biopsies by gene expression profiling

<p>Abstract</p> <p>Background</p> <p>Diagnostic accuracy of lymphoma, a heterogeneous cancer, is essential for patient management. Several ancillary tests including immunophenotyping, and sometimes cytogenetics and PCR are required to aid histological diagnosis. In this proof of principle study, gene expression microarray was evaluated as a single platform test in the differential diagnosis of common lymphoma subtypes and reactive lymphadenopathy (RL) in lymph node biopsies.</p> <p>Methods</p> <p>116 lymph node biopsies diagnosed as RL, classical Hodgkin lymphoma (cHL), diffuse large B cell lymphoma (DLBCL) or follicular lymphoma (FL) were assayed by mRNA microarray. Three supervised classification strategies (global multi-class, local binary-class and global binary-class classifications) using diagonal linear discriminant analysis was performed on training sets of array data and the classification error rates calculated by leave one out cross-validation. The independent error rate was then evaluated by testing the identified gene classifiers on an independent (test) set of array data.</p> <p>Results</p> <p>The binary classifications provided prediction accuracies, between a subtype of interest and the remaining samples, of 88.5%, 82.8%, 82.8% and 80.0% for FL, cHL, DLBCL, and RL respectively. Identified gene classifiers include LIM domain only-2 (<it>LMO2</it>), Chemokine (C-C motif) ligand 22 (<it>CCL22</it>) and Cyclin-dependent kinase inhibitor-3 (<it>CDK3</it>) specifically for FL, cHL and DLBCL subtypes respectively.</p> <p>Conclusions</p> <p>This study highlights the ability of gene expression profiling to distinguish lymphoma from reactive conditions and classify the major subtypes of lymphoma in a diagnostic setting. A cost-effective single platform "mini-chip" assay could, in principle, be developed to aid the quick diagnosis of lymph node biopsies with the potential to incorporate other pathological entities into such an assay.</p

Imaging and Modeling of Myocardial Metabolism

Current imaging methods have focused on evaluation of myocardial anatomy and function. However, since myocardial metabolism and function are interrelated, metabolic myocardial imaging techniques, such as positron emission tomography, single photon emission tomography, and magnetic resonance spectroscopy present novel opportunities for probing myocardial pathology and developing new therapeutic approaches. Potential clinical applications of metabolic imaging include hypertensive and ischemic heart disease, heart failure, cardiac transplantation, as well as cardiomyopathies. Furthermore, response to therapeutic intervention can be monitored using metabolic imaging. Analysis of metabolic data in the past has been limited, focusing primarily on isolated metabolites. Models of myocardial metabolism, however, such as the oxygen transport and cellular energetics model and constraint-based metabolic network modeling, offer opportunities for evaluation interactions between greater numbers of metabolites in the heart. In this review, the roles of metabolic myocardial imaging and analysis of metabolic data using modeling methods for expanding our understanding of cardiac pathology are discussed

Genetic Knock-Down of HDAC7 Does Not Ameliorate Disease Pathogenesis in the R6/2 Mouse Model of Huntington's Disease

Huntington's disease (HD) is an inherited, progressive neurological disorder caused by a CAG/polyglutamine repeat expansion, for which there is no effective disease modifying therapy. In recent years, transcriptional dysregulation has emerged as a pathogenic process that appears early in disease progression. Administration of histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA) have consistently shown therapeutic potential in models of HD, at least partly through increasing the association of acetylated histones with down-regulated genes and by correcting mRNA abnormalities. The HDAC enzyme through which SAHA mediates its beneficial effects in the R6/2 mouse model of HD is not known. Therefore, we have embarked on a series of genetic studies to uncover the HDAC target that is relevant to therapeutic development for HD. HDAC7 is of interest in this context because SAHA has been shown to decrease HDAC7 expression in cell culture systems in addition to inhibiting enzyme activity. After confirming that expression levels of Hdac7 are decreased in the brains of wild type and R6/2 mice after SAHA administration, we performed a genetic cross to determine whether genetic reduction of Hdac7 would alleviate phenotypes in the R6/2 mice. We found no improvement in a number of physiological or behavioral phenotypes. Similarly, the dysregulated expression levels of a number of genes of interest were not improved suggesting that reduction in Hdac7 does not alleviate the R6/2 HD-related transcriptional dysregulation. Therefore, we conclude that the beneficial effects of HDAC inhibitors are not predominantly mediated through the inhibition of HDAC7

The impact of diabetes on the pathogenesis of sepsis

Diabetes is associated with an increased susceptibility to infection and sepsis. Conflicting data exist on whether the mortality of patients with sepsis is influenced by the presence of diabetes, fuelling the ongoing debate on the benefit of tight glucose regulation in patients with sepsis. The main reason for which diabetes predisposes to infection appears to be abnormalities of the host response, particularly in neutrophil chemotaxis, adhesion and intracellular killing, defects that have been attributed to the effect of hyperglycaemia. There is also evidence for defects in humoral immunity, and this may play a larger role than previously recognised. We review the literature on the immune response in diabetes and its potential contribution to the pathogenesis of sepsis. In addition, the effect of diabetes treatment on the immune response is discussed, with specific reference to insulin, metformin, sulphonylureas and thiazolidinediones

Spontaneous Reaction Silencing in Metabolic Optimization

Metabolic reactions of single-cell organisms are routinely observed to become dispensable or even incapable of carrying activity under certain circumstances. Yet, the mechanisms as well as the range of conditions and phenotypes associated with this behavior remain very poorly understood. Here we predict computationally and analytically that any organism evolving to maximize growth rate, ATP production, or any other linear function of metabolic fluxes tends to significantly reduce the number of active metabolic reactions compared to typical non-optimal states. The reduced number appears to be constant across the microbial species studied and just slightly larger than the minimum number required for the organism to grow at all. We show that this massive spontaneous reaction silencing is triggered by the irreversibility of a large fraction of the metabolic reactions and propagates through the network as a cascade of inactivity. Our results help explain existing experimental data on intracellular flux measurements and the usage of latent pathways, shedding new light on microbial evolution, robustness, and versatility for the execution of specific biochemical tasks. In particular, the identification of optimal reaction activity provides rigorous ground for an intriguing knockout-based method recently proposed for the synthetic recovery of metabolic function.Comment: 34 pages, 6 figure