First results for a superconducting imaging-surface sensor array for magnetoencephalography

Magnetoencephalography (MEG) follows from the initial fundamental work of Cohen in 1968 and development by several groups, most notably at MIT and at NYU, based on the development of the Superconducting QUantum Interference Device (SQUID) using the Josephson effect. The SQUID`s incredible sensitivity to magnetic fields permits the measurement of the very weak magnetic fields emitted from the human brain due to intracellular neuronal currents. Current growth in MEG is dominated by multiple sensor arrays covering much of the head. These new large devices have primarily been developed and made commercially available by several companies including BTI in the US, CTF in Canada, and Neuromag in Finland. Large projects are also in place in Japan. These systems contain more than 100 sensors spaced at various intervals over the head using various configurations of magnetometers and gradiometers. The different designs available on the market are driven by factors such as detection efficiency, cost, and application. They now present a completely novel whole-head SQUID array system using a superconducting imaging-surface gradiometer concept derived at Los Alamos. Preliminary tests have demonstrated higher performance, lower noise, and additional shielding of background fields while using simpler fabrication techniques than existing whole-head MEG systems, which should reduce production costs

Is the Sun Embedded in a Typical Interstellar Cloud?

The physical properties and kinematics of the partially ionized interstellar material near the Sun are typical of warm diffuse clouds in the solar vicinity. The interstellar magnetic field at the heliosphere and the kinematics of nearby clouds are naturally explained in terms of the S1 superbubble shell. The interstellar radiation field at the Sun appears to be harder than the field ionizing ambient diffuse gas, which may be a consequence of the low opacity of the tiny cloud surrounding the heliosphere. The spatial context of the Local Bubble is consistent with our location in the Orion spur.Comment: "From the Outer Heliosphere to the Local Bubble", held at International Space Sciences Institute, October 200

uPA is upregulated by high dose celecoxib in women at increased risk of developing breast cancer

<p>Abstract</p> <p>Background</p> <p>While increased urokinase-type plasminogen activator (uPA) expression in breast cancer tissue is directly associated with poor prognosis, recent evidence suggests that uPA overexpression may suppress tumor growth and prolong survival. Celecoxib has been shown to have antiangiogenic and antiproliferative properties. We sought to determine if uPA, PA inhibitor (PAI)-1 and prostaglandin (PG)E₂expression in nipple aspirate fluid (NAF) and uPA and PGE₂expression in plasma were altered by celecoxib dose and concentration in women at increased breast cancer risk.</p> <p>Methods</p> <p>NAF and plasma samples were collected in women at increased breast cancer risk before and 2 weeks after taking celecoxib 200 or 400 mg twice daily (bid). uPA, PAI-1 and PGE₂were measured before and after intervention.</p> <p>Results</p> <p>Celecoxib concentrations trended higher in women taking 400 mg (median 1025.0 ng/mL) compared to 200 mg bid (median 227.3 ng/mL), and in post- (534.6 ng/mL) compared to premenopausal (227.3 ng/mL) women. In postmenopausal women treated with the higher (400 mg bid) celecoxib dose, uPA concentrations increased, while PAI-1 and PGE₂decreased. In women taking the higher dose, both PAI-1 (r = -.97, p = .0048) and PGE₂(r = -.69, p = .019) in NAF and uPA in plasma (r = .45, p = .023) were correlated with celecoxib concentrations.</p> <p>Conclusion</p> <p>Celecoxib concentrations after treatment correlate inversely with the change in PAI-1 and PGE₂in the breast and directly with the change in uPA in the circulation. uPA upregulation, in concert with PAI-1 and PGE₂downregulation, may have a cancer preventive effect.</p

Weak Decays Beyond Leading Logarithms

We review the present status of QCD corrections to weak decays beyond the leading logarithmic approximation including particle-antiparticle mixing and rare and CP violating decays. After presenting the basic formalism for these calculations we discuss in detail the effective hamiltonians for all decays for which the next-to-leading corrections are known. Subsequently, we present the phenomenological implications of these calculations. In particular we update the values of various parameters and we incorporate new information on m_t in view of the recent top quark discovery. One of the central issues in our review are the theoretical uncertainties related to renormalization scale ambiguities which are substantially reduced by including next-to-leading order corrections. The impact of this theoretical improvement on the determination of the Cabibbo-Kobayashi-Maskawa matrix is then illustrated in various cases.Comment: 229 pages, 32 PostScript figures (included); uses RevTeX, epsf.sty, rotate.sty, rmpbib.sty (included), times.sty (included; requires LaTeX 2e); complete PostScript version available at ftp://feynman.t30.physik.tu-muenchen.de/pub/preprints/tum-100-95.ps.gz or ftp://feynman.t30.physik.tu-muenchen.de/pub/preprints/tum-100-95.ps2.gz (scaled down and rotated version to print two pages on one sheet of paper

When the Transmission of Culture Is Child's Play

Background: Humans frequently engage in arbitrary, conventional behavior whose primary purpose is to identify with cultural in-groups. The propensity for doing so is established early in human ontogeny as children become progressively enmeshed in their own cultural milieu. This is exemplified by their habitual replication of causally redundant actions shown to them by adults. Yet children seemingly ignore such actions shown to them by peers. How then does culture get transmitted intra-generationally? Here we suggest the answer might be 'in play'. Principal Findings: Using a diffusion chain design preschoolers first watched an adult retrieve a toy from a novel apparatus using a series of actions, some of which were obviously redundant. These children could then show another child how to open the apparatus, who in turn could show a third child. When the adult modeled the actions in a playful manner they were retained down to the third child at higher rates than when the adult seeded them in a functionally oriented way. Conclusions: Our results draw attention to the possibility that play might serve a critical function in the transmission of human culture by providing a mechanism for arbitrary ideas to spread between children

IL-21 signaling is essential for optimal host resistance against Mycobacterium tuberculosis infection

IL-21 is produced predominantly by activated CD4(+) T cells and has pleiotropic effects on immunity via the IL-21 receptor (IL-21R), a member of the common gamma chain (gamma(c)) cytokine receptor family. We show that IL-21 signaling plays a crucial role in T cell responses during Mycobacterium tuberculosis infection by augmenting CD8(+) T cell priming, promoting T cell accumulation in the lungs, and enhancing T cell cytokine production. In the absence of IL-21 signaling, more CD4(+) and CD8(+) T cells in chronically infected mice express the T cell inhibitory molecules PD-1 and TIM-3. We correlate these immune alterations with increased susceptibility of IL-21R(-/-) mice, which have increased lung bacterial burden and earlier mortality compared to WT mice. Finally, to causally link the immune defects with host susceptibility, we use an adoptive transfer model to show that IL-21R(-/-) T cells transfer less protection than WT T cells. These results prove that IL-21 signaling has an intrinsic role in promoting the protective capacity of T cells. Thus, the net effect of IL-21 signaling is to enhance host resistance to M. tuberculosis. These data position IL-21 as a candidate biomarker of resistance to tuberculosis.This work was supported by National Institutes of Health Grants R21 AI100766, R01 AI106725, and P01 AI073748

Large Scale Comparison of Innate Responses to Viral and Bacterial Pathogens in Mouse and Macaque

Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens

The Treatment In Morning versus Evening (TIME) study:Analysis of recruitment, follow-up and retention rates post-recruitment

Abstract Background The use of information technology (IT) is now the preferred method of capturing and storing clinical research data. The Treatment In Morning versus Evening (TIME) study predominantly uses electronic data capture and IT to compare morning dosing of hypertensive medication against evening dosing. Registration, consent, participant demographics and follow-up data are all captured via the study website. The aim of this article is to assess the success of the TIME methodology compared with similar studies. Methods To assess the TIME study, published literature on similar clinical trials was reviewed and compared against TIME recruitment, follow-up and email interaction data. Results The TIME website registered 31,695 individuals, 21,116 of whom were randomised. Recruitment cost per randomised participant varied by strategy: £17.40 by GP practice, £3.08 by UK Biobank and £58.82 for GoShare. Twelve-month follow-up retention rates were 96%. A total of 1089 participants have withdrawn from their assigned time of dosing, 2% of whom have declined follow-up by record linkage or further contact. When the TIME data are compared with similar study data, study recruitment is very successful. However, TIME suffers difficulties with participant follow-up and withdrawal rates similar to those of conventional studies. Conclusions The TIME study has been successful in recruitment. Follow-up, retention rates and withdrawal rates are all acceptable, but ongoing work is required to ensure participants remain engaged with the study. Various recruitment strategies are necessary, and all viable options should be encouraged to maintain participant engagement throughout the life of studies using IT

Myogenin Regulates Exercise Capacity but Is Dispensable for Skeletal Muscle Regeneration in Adult mdx Mice

Duchenne muscular dystrophy (DMD) is the most prevalent inherited childhood muscle disorder in humans. mdx mice exhibit a similar pathophysiology to the human disorder allowing for an in-depth investigation of DMD. Myogenin, a myogenic regulatory factor, is best known for its role in embryonic myogenesis, but its role in adult muscle maintenance and regeneration is still poorly understood. Here, we generated an mdx:Myogflox/flox mouse harboring a tamoxifen-inducible Cre recombinase transgene, which was used to conditionally delete Myog during adult life. After tamoxifen treatment, three groups of mice were created to study the effects of Myog deletion: mdx:Myogflox/flox mice (mdx), Myogflox/flox mice (wild-type), and mdx:MyogfloxΔ/floxΔ:Cre-ER mice (mdx:Myog-deleted). mdx:Myog-deleted mice exhibited no adverse phenotype and behaved normally. When run to exhaustion, mdx:Myog-deleted mice demonstrated an enhanced capacity for exercise compared to mdx mice, running nearly as far as wild-type mice. Moreover, these mice showed the same signature characteristics of muscle regeneration as mdx mice. Unexpectedly, we found that myogenin was dispensable for muscle regeneration. Factors associated with muscle fatigue, metabolism, and proteolysis were significantly altered in mdx:Myog-deleted mice, and this might contribute to their increased exercise capacity. Our results reveal novel functions for myogenin in adult muscle and suggest that reducing Myog expression in other muscle disease models may partially restore muscle function