Clinical alcohol guidelines are welcome—but upstream action is paramount

Letter to the edito

Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3

INTRODUCTION: Involution of the mammary gland is a complex process of controlled apoptosis and tissue remodelling. The aim of the project was to identify genes that are specifically involved in this process. METHODS: We used Affymetrix oligonucleotide microarrays to perform a detailed transcript analysis on the mechanism of controlled involution after withdrawal of the pups at day seven of lactation. Some of the results were confirmed by semi-quantitative reverse transcriptase polymerase chain reaction, Western blotting or immunohistochemistry. RESULTS: We identified 145 genes that were specifically upregulated during the first 4 days of involution; of these, 49 encoded immunoglobulin genes. A further 12 genes, including those encoding the signal transducer and activator of transcription 3 (STAT3), the lipopolysaccharide receptor (CD14) and lipopolysaccharide-binding protein (LBP), were involved in the acute-phase response, demonstrating that the expression of acute-phase response genes can occur in the mammary gland itself and not only in the liver. Expression of LBP and CD14 was upregulated, at both the RNA and protein level, immediately after pup withdrawal; CD14 was strongly expressed in the luminal epithelial cells. Other genes identified suggested neutrophil activation early in involution, followed by macrophage activation late in the process. Immunohistochemistry and histological staining confirmed the infiltration of the involuting mammary tissue with neutrophils, plasma cells, macrophages and eosinophils. CONCLUSION: Oligonucleotide microarrays are a useful tool for identifying genes that are involved in the complex developmental process of mammary gland involution. The genes identified are consistent with an immune cascade, with an early acute-phase response that occurs in the mammary gland itself and resembles a wound healing process

Cluster of Dipolar Coupled Spins as a Quantum Memory Storage

Spin dynamics of a cluster of coupled spins 1/2 can be manipulated to store and process a large amount of information. A new type of dynamic response makes it possible to excite coherent long-living signals, which can be used for exchanging information with a mesoscopic quantum system. An experimental demonstration is given for a system of 19 proton spins of a liquid crystal molecule.Comment: 5 pages, 1 figur

Evolving Lorentzian Wormholes

Evolving Lorentzian wormholes with the required matter satisfying the Energy conditions are discussed. Several different scale factors are used and the corresponding consequences derived. The effect of extra, decaying (in time) compact dimensions present in the wormhole metric is also explored and certain interesting conclusions are derived for the cases of exponential and Kaluza--Klein inflation.Comment: 10 pages( RevTex, Twocolumn format), Two figures available on request from the first author. transmission errors corrected

On the exact gravitational lens equation in spherically symmetric and static spacetimes

Lensing in a spherically symmetric and static spacetime is considered, based on the lightlike geodesic equation without approximations. After fixing two radius values r_O and r_S, lensing for an observation event somewhere at r_O and static light sources distributed at r_S is coded in a lens equation that is explicitly given in terms of integrals over the metric coefficients. The lens equation relates two angle variables and can be easily plotted if the metric coefficients have been specified; this allows to visualize in a convenient way all relevant lensing properties, giving image positions, apparent brightnesses, image distortions, etc. Two examples are treated: Lensing by a Barriola-Vilenkin monopole and lensing by an Ellis wormhole.Comment: REVTEX, 11 pages, 12 eps-figures, figures partly improved, minor revision

Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci

Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10(-3)), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10(-4)). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10(-4)) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other

Tisa: A Language Design and Modular Verification Technique for Temporal Policies in Web Services

Web services are distributed software components, that are decoupled from each other using interfaces with specified functional behaviors. However, such behavioral specifications are insufficient to demonstrate compliance with certain temporal non-functional policies. An example is demonstrating that a patient’s health-related query sent to a health care service is answered only by a doctor (and not by a secretary). Demonstrating compliance with such policies is important for satisfying governmental privacy regulations. It is often necessary to expose the internals of the web service implementation for demonstrating such compliance, which may compromise modularity. In this work, we provide a language design that enables such demonstrations, while hiding majority of the service’s source code. The key idea is to use greybox specifications to allow service providers to selectively hide and expose parts of their implementation. The overall problem of showing compliance is then reduced to two subproblems: whether the desired properties are satisfied by the service’s greybox specification, and whether this greybox specification is satisfied by the service’s implementation. We specify policies using LTL and solve the first problem by model checking. We solve the second problem by refinement techniques

Very low latitude (L=1.08) whistlers and correlation with lightning activity

We present analysis of more than 2000 lightning-generated whistlers recorded at a low-latitude station, located at Allahabad (geographic latitude, 25.40°N; geographic longitude, 81.93°E; L = 1.081), India, during December 2010 to November 2011. The main focus of this work is on the correlation between observed low-latitude whistlers and lightning activity detected by the World-Wide Lightning Location Network near the conjugate point (geography 9.87°S, 83.59°E) of Allahabad. Whistler occurrence is higher in the postmidnight period as compared to the premidnight period. Whistlers were observed in the daytime only on 2 days that too before 8:30 LT (morning). Seasonally, occurrence is maximum during winter months, which is due to more lightning activity in the conjugate region and favorable ionospheric conditions. About 63% of whistlers were correlated with lightning strokes in the vicinity of the conjugate point within spatial extent of 1000 km (conjugate area). Most (about 53%) whistlers were found to be associated with lightning strokes that were offset to the southeast of the conjugate point. The results indicate that an energy range of 7.5–17.5 kJ of lightning strokes generate most of whistlers at this station. The L shell calculations show that propagation paths of the observed whistlers were embedded in the topside ionosphere. Based on these results we suggest a possibility of ducted mode of propagation even for such very low latitude whistlers

Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: effects of fat composition and gender

Background and Aims: We have reported that adverse effects on flow-mediated dilation of an acute elevation of non-esterified fatty acids rich in saturated fat (SFA) are reversed following addition of long-chain (LC) n-3 polyunsaturated fatty acids (PUFA), and hypothesised that these effects may be mediated through alterations in insulin signalling pathways. In a subgroup, we explored the effects of raised NEFA enriched with SFA, with or without LC n-3 PUFA, on whole body insulin sensitivity (SI) and responsiveness of the endothelium to insulin infusion. Methods and Results: Thirty adults (mean age 27.8 y, BMI 23.2 kg/m2) consumed oral fat loads on separate occasions with continuous heparin infusion to elevate NEFA between 60-390 min. For the final 150 min, a hyperinsulinaemic-euglycaemic clamp was performed, whilst FMD and circulating markers of endothelial function were measured at baseline, pre-clamp (240 min) and post-clamp (390 min). NEFA elevation during the SFA-rich drinks was associated with impaired FMD (P=0.027) whilst SFA+LC n-3 PUFA improved FMD at 240 min (P=0.003). In males, insulin infusion attenuated the increase in FMD with SFA+LC n-3 PUFA (P=0.049), with SI 10% greater with SFA+LC n-3 PUFA than SFA (P=0.041). Conclusion: This study provides evidence that NEFA composition during acute elevation influences both FMD and SI, with some indication of a difference by gender. However our findings are not consistent with the hypothesis that the effects of fatty acids on endothelial function and SI operate through a common pathway. Trial registered at clinicaltrials.gov, NCT01351324

Dynamics of fluctuations in a fluid below the onset of Rayleigh-B\'enard convection

We present experimental data and their theoretical interpretation for the decay rates of temperature fluctuations in a thin layer of a fluid heated from below and confined between parallel horizontal plates. The measurements were made with the mean temperature of the layer corresponding to the critical isochore of sulfur hexafluoride above but near the critical point where fluctuations are exceptionally strong. They cover a wide range of temperature gradients below the onset of Rayleigh-B\'enard convection, and span wave numbers on both sides of the critical value for this onset. The decay rates were determined from experimental shadowgraph images of the fluctuations at several camera exposure times. We present a theoretical expression for an exposure-time-dependent structure factor which is needed for the data analysis. As the onset of convection is approached, the data reveal the critical slowing-down associated with the bifurcation. Theoretical predictions for the decay rates as a function of the wave number and temperature gradient are presented and compared with the experimental data. Quantitative agreement is obtained if allowance is made for some uncertainty in the small spacing between the plates, and when an empirical estimate is employed for the influence of symmetric deviations from the Oberbeck-Boussinesq approximation which are to be expected in a fluid with its density at the mean temperature located on the critical isochore.Comment: 13 pages, 10 figures, 52 reference