A Simple Empirically Motivated Template for the Unresolved Thermal Sunyaev-Zeldovich Effect

We develop a model for the power spectrum of unresolved clusters of galaxies arising from the thermal Sunyaev-Zeldovich (tSZ) effect. The model is based on a'universal' gas pressure profile constrained by X-ray observations and includes a parameter to describe departures from self-similar evolution. The model is consistent with recent Planck observations of the tSZ effect for X-ray clusters with redshifts z<1 and reproduces the low amplitude for the tSZ inferred from recent ground based observations. By adjusting two free parameters, we are able to reproduce the tSZ power spectra from recent numerical simulations to an accuracy that is well within theoretical uncertainties. Our model provides a simple, empirically motivated tSZ template that may be useful for the analysis of new experiments such as Planck.Comment: 6 pages 4 figure

A Search for leptophilic Z_(l) boson at future linear colliders

We study the possible dynamics associated with leptonic charge in future linear colliders. Leptophilic massive vector boson, Z_(l), have been investigated through the process e^(+)e^(-) -> mu^(+)mu^(-). We have shown that ILC and CLIC will give opportunity to observe Z_(l) with masses up to the center of mass energy if the corresponding coupling constant g_(l) exceeds 10^(-3).Comment: 12 pages, 10 figure

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

Infall Signatures in a Prestellar Core embedded in the High-Mass 70 μμm Dark IRDC G331.372-00.116

Using Galactic Plane surveys, we have selected a massive (1200 M$_\odot$), cold (14 K) 3.6-70 $\mu$m dark IRDC G331.372-00.116. This IRDC has the potential to form high-mass stars and, given the absence of current star formation signatures, it seems to represent the earliest stages of high-mass star formation. We have mapped the whole IRDC with the Atacama Large Millimeter/submillimeter Array (ALMA) at 1.1 and 1.3 mm in dust continuum and line emission. The dust continuum reveals 22 cores distributed across the IRDC. In this work, we analyze the physical properties of the most massive core, ALMA1, which has no molecular outflows detected in the CO (2-1), SiO (5-4), and H$_2$CO (3-2) lines. This core is relatively massive ($M$ = 17.6 M$_\odot$), subvirialized (virial parameter $\alpha_{vir}=M_{vir}/M=0.14$), and is barely affected by turbulence (transonic Mach number of 1.2). Using the HCO$^+$ (3-2) line, we find the first detection of infall signatures in a relatively massive, prestellar core (ALMA1) with the potential to form a high-mass star. We estimate an infall speed of 1.54 km s$^{-1}$ and a high accretion rate of 1.96 $\times$ 10$^{-3}$ M$_\odot$ yr$^{-1}$. ALMA1 is rapidly collapsing, out of virial equilibrium, more consistent with competitive accretion scenarios rather than the turbulent core accretion model. On the other hand, ALMA1 has a mass $\sim$6 times larger than the clumps Jeans mass, being in an intermediate mass regime ($M_{J}=2.7<M\lesssim$ 30 M$_\odot$), contrary to what both the competitive accretion and turbulent core accretion theories predict

Dynamical R-parity Breaking at the LHC

In a class of extensions of the minimal supersymmetric standard model with (B-L)/left-right symmetry that explains the neutrino masses, breaking R-parity symmetry is an essential and dynamical requirement for successful gauge symmetry breaking. Two consequences of these models are: (i) a new kind of R-parity breaking interaction that protects proton stability but adds new contributions to neutrinoless double beta decay and (ii) an upper bound on the extra gauge and parity symmetry breaking scale which is within the large hadron collider (LHC) energy range. We point out that an important prediction of such theories is a potentially large mixing between the right-handed charged lepton ($e^c$) and the superpartner of the right-handed gauge boson ($\widetilde W_R^+$), which leads to a brand new class of R-parity violating interactions of type $\widetilde{\mu^c}^\dagger\nu_\mu^c e^c$ and \widetilde{d^c}^\dagger\u^c e^c. We analyze the relevant constraints on the sparticle mass spectrum and the LHC signatures for the case with smuon/stau NLSP and gravitino LSP. We note the "smoking gun" signals for such models to be lepton flavor/number violating processes: $pp\to \mu^\pm\mu^\pm e^+e^-jj$ (or $\tau^\pm\tau^\pm e^+e^-jj$) and $pp\to\mu^\pm e^\pm b \bar{b} jj$ (or $\tau^\pm e^\pm b \bar{b} jj$) without significant missing energy. The predicted multi-lepton final states and the flavor structure make the model be distinguishable even in the early running of the LHC.Comment: 30 pages, 13 figures, 6 tables, reference adde

TLR3-mediated apoptosis and activation of phosphorylated Akt in the salivary gland epithelial cells of primary Sjögren’s syndrome patients

This study aimed at ascertain whether innate immunity is involved in the apoptosis of primary cultured salivary gland epithelial cells (SGECs) in primary Sjögren\u27s syndrome (pSS). Induction of apoptosis of SGECs was performed using a TLR3 ligand, poly (I:C). Activation of phosphorylated-Akt (pAkt) and cleaved-caspase 3 was determined by Western blotting or immunofluorescence. Expression of TLR2 and TLR3 with pAkt was observed in cultured SGECs after 24-h stimulation with each ligand. Compared with stimulation with the peptidoglycan or lipopolysaccharide, that with poly (I:C) induced significant nuclear fragmentation, as determined by Hoechst staining (p = 0.0098). Apoptosis was confirmed by terminal deoxynucleotidyltransferase-mediated dUTP nick end-labeling (TUNEL) staining of SGECs from pSS patients and a normal subject. A significant increase in TUNEL-positive cells was observed by the addition of a PI3K inhibitor, LY294002. Poly (I:C) phosphorylated stress-activated protein kinase/Jun-terminal kinase and p44/42 MAP kinase as well as Akt. Furthermore, poly (I:C)-induced caspase 3 cleavage in SGECs was also inhibited by LY294002. Similar results were obtained using SGECs obtained from a normal subject. The results demonstrated for the first time that TLR3 induces the apoptotic cell death of SGECs via the PI3K-Akt signaling pathway

Effective knowledge management in translational medicine

<p>Abstract</p> <p>Background</p> <p>The growing consensus that most valuable data source for biomedical discoveries is derived from human samples is clearly reflected in the growing number of translational medicine and translational sciences departments across pharma as well as academic and government supported initiatives such as Clinical and Translational Science Awards (CTSA) in the US and the Seventh Framework Programme (FP7) of EU with emphasis on translating research for human health.</p> <p>Methods</p> <p>The pharmaceutical companies of Johnson and Johnson have established translational and biomarker departments and implemented an effective knowledge management framework including building a data warehouse and the associated data mining applications. The implemented resource is built from open source systems such as i2b2 and GenePattern.</p> <p>Results</p> <p>The system has been deployed across multiple therapeutic areas within the pharmaceutical companies of Johnson and Johnsons and being used actively to integrate and mine internal and public data to support drug discovery and development decisions such as indication selection and trial design in a translational medicine setting. Our results show that the established system allows scientist to quickly re-validate hypotheses or generate new ones with the use of an intuitive graphical interface.</p> <p>Conclusions</p> <p>The implemented resource can serve as the basis of precompetitive sharing and mining of studies involving samples from human subjects thus enhancing our understanding of human biology and pathophysiology and ultimately leading to more effective treatment of diseases which represent unmet medical needs.</p

Age-related changes in global motion coherence: conflicting haemodynamic and perceptual responses

Our aim was to use both behavioural and neuroimaging data to identify indicators of perceptual decline in motion processing. We employed a global motion coherence task and functional Near Infrared Spectroscopy (fNIRS). Healthy adults (n = 72, 18-85) were recruited into the following groups: young (n = 28, mean age = 28), middle-aged (n = 22, mean age = 50), and older adults (n = 23, mean age = 70). Participants were assessed on their motion coherence thresholds at 3 different speeds using a psychophysical design. As expected, we report age group differences in motion processing as demonstrated by higher motion coherence thresholds in older adults. Crucially, we add correlational data showing that global motion perception declines linearly as a function of age. The associated fNIRS recordings provide a clear physiological correlate of global motion perception. The crux of this study lies in the robust linear correlation between age and haemodynamic response for both measures of oxygenation. We hypothesise that there is an increase in neural recruitment, necessitating an increase in metabolic need and blood flow, which presents as a higher oxygenated haemoglobin response. We report age-related changes in motion perception with poorer behavioural performance (high motion coherence thresholds) associated with an increased haemodynamic response