Complex demodulation applied to Pi2 geomagnetic pulsations

The spectral technique of complex demodulation is applied to Pi2 pulsations recorded along a meridional profile. The technique provides instantaneous values of amplitude and phase and allows frequency dispersion to be taken into account. The variations of magnetospheric wave polarization parameters are observed as a function of both space and time. The results are directly compared with recent theories of the resonance of geomagnetic field lines and the effects of the ionosphere on ground based observations. The theoretical predictions are tested and the experimental results indicate that the night-time ionosphere is capable of a controlling influence on the source characteristics of these magnetospheric waves in the plasmapause region

A high resolution study of continuous pulsations in the European sector

Complex demodulation has been described in detail and applied to Pi2 pulsations in a previous paper by Beamish et al. (1979). The technique is now extended to demonstrate spatio­ temporal variations in the fundamental characteristics of Pc3 and Pc4 pulsations along a meridional profile extending from the U.K. to Iceland. With the exception of a high latitude Pc4 coupled resonance the results are consistent with a -90° Hughes rotation (introduced by the ionosphere) of magnetospheric toroidal line resonances. Furthermore, the ionosphere appears capable of smoothing away the polarisation reversal which would be expected across such amplitude maxima within the plasmasphere. However, a toroidal line resonance in the Pc3 period range about which a sense of polarisation reversal is clearly observed on the ground is suggested as occurring at the plasmapause. This is accounted for in terms of the width of the resonance structure

Cigarette smoking and adenocarcinomas of the esophagus and esophagogastric junction: a pooled analysis from the International BEACON Consortium

BackgroundPrevious studies that showed an association between smoking and adenocarcinomas of the esophagus and esophagogastric junction were limited in their ability to assess differences by tumor site, sex, dose–response, and duration of cigarette smoking cessation.MethodsWe used primary data from 10 population-based case–control studies and two cohort studies from the Barrett’s Esophagus and Esophageal Adenocarcinoma Consortium. Analyses were restricted to white non-Hispanic men and women. Patients were classified as having esophageal adenocarcinoma (n = 1540), esophagogastric junctional adenocarcinoma (n = 1450), or a combination of both (all adenocarcinoma; n = 2990). Control subjects (n = 9453) were population based. Associations between pack-years of cigarette smoking and risks of adenocarcinomas were assessed, as well as their potential modification by sex and duration of smoking cessation. Study-specific odds ratios (ORs) estimated using multivariable logistic regression models, adjusted for age, sex, body mass index, education, and gastroesophageal reflux, were pooled using a meta-analytic methodology to generate summary odds ratios. All statistical tests were two-sided.ResultsThe summary odds ratios demonstrated strong associations between cigarette smoking and esophageal adenocarcinoma (OR = 1.96, 95% confidence interval [CI] = 1.64 to 2.34), esophagogastric junctional adenocarcinoma (OR = 2.18, 95% CI = 1.84 to 2.58), and all adenocarcinoma (OR = 2.08, 95% CI = 1.83 to 2.37). In addition, there was a strong dose–response association between pack-years of cigarette smoking and each outcome ( P &lt; .001). Compared with current smokers, longer smoking cessation was associated with a decreased risk of all adenocarcinoma after adjusting for pack-years (&lt;10 years of smoking cessation: OR = 0.82, 95% CI = 0.60 to 1.13; and ≥10 years of smoking cessation: OR = 0.71, 95% CI = 0.56 to 0.89). Sex-specific summary odds ratios were similar.ConclusionsCigarette smoking is associated with increased risks of adenocarcinomas of the esophagus and esophagogastric junction in white men and women; compared with current smoking, smoking cessation was associated with reduced risks.<br/

Interleukin-6 and Associated Cytokine Responses to An Acute Bout of High-intensity Interval Exercise: the Effect of Exercise Intensity and Volume

Acute increases in interleukin (IL)-6 following prolonged exercise are associated with the induction of a transient anti-inflammatory state (e.g., increases in IL-10) that is partly responsible for the health benefits of regular exercise. The purposes of this study were to investigate the IL-6–related inflammatory response to high-intensity interval exercise (HIIE) and to determine the impact of exercise intensity and volume on this response. Ten participants (5 males and 5 females) completed 3 exercise bouts of contrasting intensity and volume (LOW, MOD, and HIGH). The HIGH protocol was based upon standard HIIE protocols, while the MOD and LOW protocols were designed to enable a comparison of exercise intensity and volume with a fixed duration. Inflammatory cytokine concentrations were measured in plasma (IL-6, IL-10) and also determined the level of gene expression (IL-6, IL-10, and IL-4R) in peripheral blood. The plasma IL-6 response to exercise (reported as fold changes) was significantly greater in HIGH (2.70 ± 1.51) than LOW (1.40 ± 0.32) (P = 0.04) and was also positively correlated to the mean exercise oxygen uptake (r = 0.54, P < 0.01). However, there was no change in anti-inflammatory IL-10 or IL-4R responses in plasma or at the level of gene expression. HIIE caused a significant increase in IL-6 and was greater than that seen in low-intensity exercise of the same duration. The increases in IL-6 were relatively small in magnitude, and appear to have been insufficient to induce the acute systemic anti-inflammatory effects, which are evident following longer duration exercise

'Education, education, education' : legal, moral and clinical

This article brings together Professor Donald Nicolson's intellectual interest in professional legal ethics and his long-standing involvement with law clinics both as an advisor at the University of Cape Town and Director of the University of Bristol Law Clinic and the University of Strathclyde Law Clinic. In this article he looks at how legal education may help start this process of character development, arguing that the best means is through student involvement in voluntary law clinics. And here he builds upon his recent article which argues for voluntary, community service oriented law clinics over those which emphasise the education of students

Studying Millisecond Pulsars in X-rays

Millisecond pulsars represent an evolutionarily distinct group among rotation-powered pulsars. Outside the radio band, the soft X-ray range ($\sim 0.1$--10 keV) is most suitable for studying radiative mechanisms operating in these fascinating objects. X-ray observations revealed diverse properties of emission from millisecond pulsars. For the most of them, the bulk of radiation is of a thermal origin, emitted from small spots (polar caps) on the neutron star surface heated by relativistic particles produced in pulsar acceleration zones. On the other hand, a few other very fast rotating pulsars exhibit almost pure nonthermal emission generated, most probably, in pulsar magnetospheres. There are also examples of nonthermal emission detected from X-ray nebulae powered by millisecond pulsars, as well as from pulsar winds shocked in binary systems with millisecond pulsars as companions. These and other most important results obtained from X-ray observations of millisecond pulsars are reviewed in this paper, as well as results from the search for millisecond pulsations in X-ray flux of the radio-quite neutron star RX J1856.5-3754

Mutational analysis of human CEACAM1: the potential of receptor polymorphism in increasing host susceptibility to bacterial infection

A common overlapping site on the N-terminal IgV-like domain of human carcinoembryonic antigen (CEA)-related cell adhesion molecules (CEACAMs) is targeted by several important human respiratory pathogens. These include Neisseria meningitidis (Nm) and Haemophilus influenzae (Hi) that can cause disseminated or persistent localized infections. To define the precise structural features that determine the binding of distinct pathogens with CEACAMs, we have undertaken molecular modelling and mutation of the receptor molecules at previously implicated key target residues required for bacterial binding. These include Ser-32, Tyr-34, Val-39, Gln-44 and Gln-89, in addition to Ile-91, the primary docking site for the pathogens. Most, but not all, of these residues located adjacent to each other in a previous N-domain model of human CEACAM1, which was based on REI, CD2 and CD4. In the current studies, we have refined this model based on the mouse CEACAM1 crystal structure, and observe that all of the above residues form an exposed continuous binding region on the N-domain. Examination of the model also suggested that substitution of two of these residues 34 and 89 could affect the accessibility of Ile-91 for ligand binding. By introducing selected mutations at the positions 91, 34 and 89, we confirmed the primary importance of Ile-91 in all bacterial binding to CEACAM1 despite the inter- and intraspecies structural differences between the bacterial CEACAM-binding ligands. The studies further indicated that the efficiency of binding was significantly enhanced for specific strains by mutations such as Y34F and Q89N, which also altered the hierarchy of Nm versus Hi strain binding. These studies imply that distinct polymorphisms in human epithelial CEACAMs have the potential to decrease or increase the risk of infection by the receptor-targeting pathogens

Near-intrinsic energy resolution for 30-662 keV gamma rays in a high pressure xenon electroluminescent TPC

We present the design, data and results from the NEXT prototype for Double Beta and Dark Matter (NEXT-DBDM) detector, a high-pressure gaseous natural xenon electroluminescent time projection chamber (TPC) that was built at the Lawrence Berkeley National Laboratory. It is a prototype of the planned NEXT-100 136Xe neutrino-less double beta decay (0νββ) experiment with the main objectives of demonstrating near-intrinsic energy resolution at energies up to 662 keV and of optimizing the NEXT-100 detector design and operating parameters. Energy resolutions of ∼1% FWHM for 662 keV gamma rays were obtained at 10 and 15 atm and ∼5% FWHM for 30 keV fluorescence xenon X-rays. These results demonstrate that 0.5% FWHM resolutions for the 2,459 keV hypothetical neutrino-less double beta decay peak are realizable. This energy resolution is a factor 7 to 20 better than that of the current leading 0νββ experiments using liquid xenon and thus represents a significant advancement. We present also first results from a track imaging system consisting of 64 silicon photo-multipliers recently installed in NEXT-DBDM that, along with the excellent energy resolution, demonstrates the key functionalities required for the NEXT-100 0νββ search

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk