SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses

<p>The incidence of allergy and asthma in developed countries is on the increase and this trend looks likely to continue. CD4(+) T helper 2 (Th2) cells are major drivers of these diseases and their commitment is controlled by cytokines such as interleukin 4, which are in turn regulated by the suppressor of cytokine signaling (SOCS) proteins. We report that SOCS2(-/-) CD4(+) T cells show markedly enhanced Th2 differentiation. SOCS2(-/-) mice, as well as RAG1(-/-) mice transferred with SOCS2(-/-) CD4(+) T cells, exhibit elevated type 2 responses after helminth antigen challenge. Moreover, in in vivo models of atopic dermatitis and allergen-induced airway inflammation, SOCS2(-/-) mice show significantly elevated IgE, eosinophilia, type 2 responses, and inflammatory pathology relative to wild-type mice. Finally, after T cell activation, markedly enhanced STAT6 and STAT5 phosphorylation is observed in SOCS2(-/-) T cells, whereas STAT3 phosphorylation is blunted. Thus, we provide the first evidence that SOCS2 plays an important role in regulating Th2 cell expansion and development of the type 2 allergic responses.</p>

Framework for Establishing Limits of Tabular Aerodynamic Models for Flight Dynamics Analysis

This paper describes the use of the Euler equations for the generation and testing of tabular aerodynamic models for flight dynamics analysis. Maneuvers for the AGARD Standard Dynamics Model sharp leading-edge wind-tunnel geometry are considered as a test case. Wind-tunnel data is first used to validate the prediction of static and dynamic coefficients at both low and high angles, featuring complex vortical flow, with good agreement obtained at low to moderate angles of attack. Then the generation of aerodynamic tables is described based on a data fusion approach. Time-optimal maneuvers are generated based on these tables, including level flight trim, pull-ups at constant and varying incidence, and level and 90 degrees turns. The maneuver definition includes the aircraft states and also the control deflections to achieve the motion. The main point of the paper is then to assess the validity of the aerodynamic tables which were used to define the maneuvers. This is done by replaying them, including the control surface motions, through the time accurate computational fluid dynamics code. The resulting forces and moments are compared with the tabular values to assess the presence of inadequately modeled dynamic or unsteady effects. The agreement between the tables and the replay is demonstrated for slow maneuvers. Increasing rate maneuvers show discrepancies which are ascribed to vortical flow hysteresis at the higher rate motions. The framework is suitable for application to more complex viscous flow models, and is powerful for the assessment of the validity of aerodynamics models of the type currently used for studies of flight dynamics.

Transonic aeroelastic simulation for instability searches and uncertainty analysis

In this paper the use of eigenvalue stability analysis of very large dimension aeroelastic numerical models arising from the exploitation of computational fluid dynamics is reviewed. A formulation based on a block reduction of the system Jacobian proves powerful to allow various numerical algorithms to be exploited, including frequency domain solvers, reconstruction of a term describing the fluid–structure interaction from the sparse data which incurs the main computational cost, and sampling to place the expensive samples where they are most needed. The stability formulation also allows non-deterministic analysis to be carried out very efficiently through the use of an approximate Newton solver. Finally, the system eigenvectors are exploited to produce nonlinear and parameterised reduced order models for computing limit cycle responses. The performance of the methods is illustrated with results from a number of academic and large dimension aircraft test cases.

Social Participation and Maintaining Recommended Waist Circumference: Prospective Evidence From the English Longitudinal Study of Aging

Objectives: To investigate whether older adults participating in social activities are more likely to maintain or achieve recommended waist circumference (WC) levels. Method: A total of 4,280 older adults who participated in Wave 2 (baseline) and Wave 4 (follow-up) of the English Longitudinal Study of Ageing. WC was measured by a nurse in both study waves. Results: Participation in education, arts, music groups, evening classes, and in charitable associations was associated with maintaining recommended WC only in those men whose WC was in the recommended range at baseline. Participation in social activities was not associated with achieving recommended WC in women or men with initially large waist. Discussion: Participation in cultural and charitable activities may help in maintaining a recommended level of WC in older men with WC originally in the recommended range.

Cities as Organisms

Since the UN report by the Brundtland Committee, sustainability in the built environment has mainly been seen from a technical focus on single buildings or products. With the energy efficiency approaching 100%, fossil resources depleting and a considerable part of the world still in need of better prosperity, the playing field of a technical focus has become very limited. It will most probably not lead to the sustainable development needed to avoid irreversible effects on climate, energy provision and, not least, society.<br/>Cities are complex structures of independently functioning elements, all of which are nevertheless connected to different forms of infrastructure, which provide the necessary sources or solve the release of waste material. With the current ambitions regarding carbon- or energy-neutrality, retreating again to the scale of a building is likely to fail. Within an urban context a single building cannot become fully resource-independent, and need not, from our viewpoint. Cities should be considered as an organism that has the ability to intelligently exchange sources and waste flows. Especially in terms of energy, it can be made clear that the present situation in most cities are undesired: there is simultaneous demand for heat and cold, and in summer a lot of excess energy is lost, which needs to be produced again in winter. The solution for this is a system that intelligently exchanges and stores essential sources, e.g. energy, and that optimally utilises waste flows.<br/>This new approach will be discussed and exemplified. The Rotterdam Energy Approach and Planning (REAP) will be illustrated as a means for urban planning, whereas Swarm Planning will be introduced as another nature-based principle for swift changes towards sustainability

Restrospective genetic monitoring of the threatened Yellow marsh saxifrage (Saxifraga hirculus) reveals genetic erosion but provides valuable information for conservation strategies

Aim: Retrospective genetic monitoring, comparing genetic diversity of extant populations with historical samples, can provide valuable and often unique insights into evolutionary processes informing conservation strategies. The Yellow marsh saxifrage (Saxifraga hirculus) is listed as ‘critically endangered’ in Ireland with only two extant populations. We quantified genetic changes over time and identified genotypes in extant populations that could be used as founders for reintroductions to sites where the species is extinct.<br/><br/>Location: Ireland.<br/><br/>Methods: Samples were obtained from both locations where the species is currently found, including the most threatened site at the Garron Plateau, Co. Antrim, which held only 13 individuals during 2011. Herbarium samples covering the period from 1886 to 1957 were obtained including plants from the same area as the most threatened population, as well as three extinct populations. In total, 422 individuals (319 present-day and 103 historical) were genotyped at six microsatellite loci. Species distribution modelling was used to identify areas of potentially suitable habitat for reintroductions.<br/><br/>Results: Level of phenotypic diversity within the most threatened population was significantly lower in the present-day compared with historical samples but levels of observed heterozygosity and number of alleles, whilst reduced, did not differ significantly. However, Bayesian clustering analysis suggested gradual lineage replacement over time. All three measures of genetic diversity were generally lower at the most threatened population compared with the more substantial extant populations in Co. Mayo. Species distribution modelling suggested that habitat at one site where the species is extinct may be suitable for reintroduction.<br/><br/>Main conclusions: The dominant genetic lineage in the most threatened population is rare elsewhere; thus, care needs to be taken when formulating any potential reintroduction programme. Our findings highlight both the need for genetic monitoring of threatened populations, but also for its swift implementation before levels of diversity become critically low.

Precursors to aggression are evident by 6 months of age

We tested the hypothesis that developmental precursors to aggression are apparent in infancy. Up to three informants rated 301 firstborn infants for early signs of anger, hitting and biting; 279 (93%) were assessed again as toddlers. Informants' ratings were validated by direct observation at both ages. The precursor behaviours were significantly associated with known risk factors for high levels of aggressiveness. Individual differences were stable from early infancy to the third year and predicted broader conduct problems. These findings suggest that some individuals set forth on the trajectory to high levels of aggression by 6 months of age. The findings have implications for developmental studies of aggression, clinical prevention and intervention strategies, and theoretical considerations regarding the detection of precursors in different domains of development.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

New genetic loci link adipose and insulin biology to body fat distribution

<p>Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P &lt; 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.</p>

Genetic studies of body mass index yield new insights for obesity biology

<p>Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P &lt; 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for &gt;20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p>

Optical and near-infrared observations of SN 2011dh - The first 100 days

We present optical and near-infrared (NIR) photometry and spectroscopy of the Type IIb supernova (SN) 2011dh for the first 100 days. We complement our extensive dataset with Swift ultra-violet (UV) and Spitzer mid-infrared (MIR) data to build a UV to MIR bolometric lightcurve using both photometric and spectroscopic data. Hydrodynamical modelling of the SN based on this bolometric lightcurve have been presented in Bersten et al. (2012, ApJ, 757, 31). We find that the absorption minimum for the hydrogen lines is never seen below ~11 000 km s-1 but approaches this value as the lines get weaker. This suggests that the interface between the helium core and hydrogen rich envelope is located near this velocity in agreement with the Bersten et al. (2012) He4R270 ejecta model. Spectral modelling of the hydrogen lines using this ejecta model supports the conclusion and we find a hydrogen mass of 0.01-0.04 M⊙ to be consistent with the observed spectral evolution. We estimate that the photosphere reaches the helium core at 5-7 days whereas the helium lines appear between ~10 and ~15 days, close to the photosphere and then move outward in velocity until ~40 days. This suggests that increasing non-thermal excitation due to decreasing optical depth for the γ-rays is driving the early evolution of these lines. The Spitzer 4.5 μm band shows a significant flux excess, which we attribute to CO fundamental band emission or a thermal dust echo although further work using late time data is needed. Thedistance and in particular the extinction, where we use spectral modelling to put further constraints, is discussed in some detail as well as the sensitivity of the hydrodynamical modelling to errors in these quantities. We also provide and discuss pre- and post-explosion observations of the SN site which shows a reduction by ~75 percent in flux at the position of the yellow supergiant coincident with SN 2011dh. The B, V and r band decline rates of 0.0073, 0.0090 and 0.0053 mag day-1 respectively are consistent with the remaining flux being emitted by the SN. Hence we find that the star was indeed the progenitor of SN 2011dh as previously suggested by Maund et al. (2011, ApJ, 739, L37) and which is also consistent with the results from the hydrodynamical modelling. Figures 2, 3, Tables 3-10, and Appendices are available in electronic form at http://www.aanda.orgThe photometric tables are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/562/A17

Massive stars exploding in a He-rich circumstellar medium - IV. Transitional Type Ibn supernovae

<p>We present ultraviolet, optical and near-infrared data of the Type Ibn supernovae (SNe) 2010al and 2011hw. SN 2010al reaches an absolute magnitude at peak of M-R = -18.86 +/- 0.21. Its early light curve shows similarities with normal SNe Ib, with a rise to maximum slower than most SNe Ibn. The spectra are dominated by a blue continuum at early stages, with narrow P-Cygni He I lines indicating the presence of a slow-moving, He-rich circumstellar medium. At later epochs, the spectra well match those of the prototypical SN Ibn 2006jc, although the broader lines suggest that a significant amount of He was still present in the stellar envelope at the time of the explosion. SN 2011hw is somewhat different. It was discovered after the first maximum, but the light curve shows a double peak. The absolute magnitude at discovery is similar to that of the second peak (M-R = -18.59 +/- 0.25), and slightly fainter than the average of SNe Ibn. Though the spectra of SN 2011hw are similar to those of SN 2006jc, coronal lines and narrow Balmer lines are clearly detected. This indicates substantial interaction of the SN ejecta with He-rich, but not H-free, circumstellar material. The spectra of SN 2011hw suggest that it is a transitional SN Ibn/IIn event similar to SN 2005la. While for SN 2010al the spectrophotometric evolution favours a H-deprived Wolf-Rayet progenitor (of WN-type), we agree with the conclusion of Smith et al. that the precursor of SN 2011hw was likely in transition from a luminous blue variable to an early Wolf-Rayet (Ofpe/WN9) stage.</p>