Discrepancies in Determinations of the Ginzburg-Landau Parameter

Long-standing discrepancies within determinations of the Ginzburg-Landau parameter $\kappa$ from supercritical field measurements on superconducting microspheres are reexamined. The discrepancy in tin is shown to result from differing methods of analyses, whereas the discrepancy in indium is a consequence of significantly differing experimental results. The reanalyses however confirms the lower $\kappa$ determinations to within experimental uncertainties.Comment: submitted to Phys. Rev.

The properties of the three-nucleon system with the dressed-bag model for nn interaction. I: New scalar three-body force

A multi-component formalism is developed to describe three-body systems with nonstatic pairwise interactions and non-nucleonic degrees of freedom. The dressed-bag model for $NN$ interaction based on the formation of an intermediate six-quark bag dressed by a $\sigma$-field is applied to the $3N$ system, where it results in a new three-body force between the six-quark bag and a third nucleon. Concise variational calculations of $3N$ bound states are carried out in the dressed-bag model including the new three-body force. It is shown that this three-body force gives at least half the $3N$ total binding energy, while the weight of non-nucleonic components in the $^3$H and $^3$He wavefunctions can exceed 10%. The new force model provides a very good description of $3N$ bound states with a reasonable magnitude of the $\sigma NN$ coupling constant. The model can serve as a natural bridge between dynamical description of few-nucleon systems and the very successful Walecka approach to heavy nuclei and nuclear matter.Comment: 26 pages, Latex, 7 figure

Reconstruction of Northern Hemisphere 1950–2010 atmospheric non-methane hydrocarbons

The short-chain non-methane hydrocarbons (NMHC) are mostly emitted into the atmosphere by anthropogenic processes. Recent studies have pointed out a tight linkage between the atmospheric mole fractions of the NMHC ethane and the atmospheric growth rate of methane. Consequently, atmospheric NMHC are valuable indicators for tracking changes in anthropogenic emissions, photochemical ozone production, and greenhouse gases. This study investigates the 1950–2010 Northern Hemisphere atmospheric C₂–C₅ NMHC ethane, propane, <i>i</i>-butane, <i>n</i>-butane, <i>i</i>-pentane, and <i>n</i>-pentane by (a) reconstructing atmospheric mole fractions of these trace gases using firn air extracted from three boreholes in 2008 and 2009 at the North Greenland Eemian Ice Drilling (NEEM) site and applying state-of-the-art models of trace gas transport in firn, and by (b) considering eight years of ambient NMHC monitoring data from five Arctic sites within the NOAA Global Monitoring Division (GMD) Cooperative Air Sampling Network. Results indicate that these NMHC increased by ~40–120% after 1950, peaked around 1980 (with the exception of ethane, which peaked approximately 10 yr earlier), and have since dramatically decreased to be now back close to 1950 levels. The earlier peak time of ethane vs. the C₃–C₅ NMHC suggests that different processes and emissions mitigation measures contributed to the decline in these NMHC. The 60 yr record also illustrates notable increases in the ratios of the isomeric <i>iso-/n</i>-butane and <i>iso-/n</i>-pentane ratios. Comparison of the reconstructed NMHC histories with 1950–2000 volatile organic compounds (VOC) emissions data and with other recently published ethane trend analyses from ambient air Pacific transect data showed (a) better agreement with North America and Western Europe emissions than with total Northern Hemisphere emissions data, and (b) better agreement with other Greenland firn air data NMHC history reconstructions than with the Pacific region trends. These analyses emphasize that for NMHC, having atmospheric lifetimes on the order of < 2 months, the Greenland firn air records are primarily a representation of Western Europe and North America emission histories

Rheumatoid synovial fluid interleukin-17-producing CD4 T cells have abundant tumor necrosis factor-alpha co-expression, but little interleukin-22 and interleukin-23R expression

Introduction\ud Th17 cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to systematically analyse the phenotype, cytokine profile and frequency of interleukin-17 (IL-17) producing CD4-positive T cells in mononuclear cells isolated from peripheral blood, synovial fluid and synovial tissue of RA patients with established disease, and to correlate cell frequencies with disease activity. \ud \ud Methods\ud Flow cytometry was used to analyse the phenotype and cytokine production of mononuclear cells isolated from peripheral blood (PBMC) (n = 44), synovial fluid (SFMC) (n = 14) and synovium (SVMC) (n = 10) of RA patients and PBMC of healthy controls (n = 13). \ud \ud Results\ud The frequency of IL-17-producing CD4 T cells was elevated in RA SFMC compared with RA PBMC (P = 0.04). However, the frequency of this population in RA SVMC was comparable to that in paired RA PBMC. The percentage of IL-17-producing CD4 T cells coexpressing tumor necrosis factor alpha (TNFα) was significantly increased in SFMC (P = 0.0068). The frequency of IFNγ-producing CD4 T cells was also significantly higher in SFMC than paired PBMC (P = 0.042). The majority of IL-17-producing CD4 T cells coexpressed IFNγ. IL-17-producing CD4 T cells in RA PBMC and SFMC exhibited very little IL-22 or IL-23R coexpression. \ud \ud Conclusions\ud These findings demonstrate a modest enrichment of IL-17-producing CD4 T cells in RA SFMC compared to PBMC. Th17 cells in SFMC produce more TNFα than their PBMC counterparts, but are not a significant source of IL-22 and do not express IL-23R. However, the percentage of CD4 T cells which produce IL-17 in the rheumatoid joint is low, suggesting that other cells may be alternative sources of IL-17 within the joints of RA patients. \ud \u

Glucocorticoids, master modulators of the thymic catecholaminergic system?

There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P lt 0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P lt 0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P lt 0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis

Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, phase II proof-of-concept trial

Objective: To evaluate the efficacy and safety of secukinumab, a fully human, anti-interleukin (IL)-17A monoclonal antibody, in patients with psoriatic arthritis (PsA). Methods: 42 patients with active PsA fulfilling ClASsification for Psoriatic ARthritis (CASPAR) criteria were randomly assigned (2:1) to receive two intravenous secukinumab doses (10 mg/kg; n=28) or placebo (n=14) 3 weeks apart. The primary endpoint was the proportion of American College of Rheumatology (ACR) 20 responses at week 6 for secukinumab versus placebo (one-sided p<0.1). Results: Primary endpoint: ACR20 responses at week 6 were 39% (9/23) for secukinumab versus 23% (3/13) for placebo (p=0.27). ACR20 responses were greater with secukinumab versus placebo at week 12 (39% (9/23) vs 15% (2/13), p=0.13) and week 24 (43% (10/23) vs 18% (2/11), p= 0.14). At week 6, ‘good’ European League Against Rheumatism response was seen in 21.7% (5/23) secukinumab versus 9.1% (1/11) placebo patients. Compared with placebo at week 6, significant reductions were observed among secukinumab recipients for C reactive protein (p=0.039), erythrocyte sedimentation rate (p=0.038), Health Assessment Questionnaire Disability Index (p=0.002) and Short Form Health Survey (SF-36; p=0.030) scores. The overall adverse event (AE) frequency was comparable between secukinumab (26 (93%)) and placebo (11 (79%)) recipients. Six serious AEs (SAEs) were reported in four secukinumab patients and one SAE in one placebo patient. Conclusions: Although the primary endpoint was not met, clinical responses, acute-phase reactant and quality of life improvements were greater with secukinumab versus placebo, suggesting some clinical benefit. Secukinumab exhibited satisfactory safety. Larger clinical trials of secukinumab in PsA are warranted

MGIS: managing banana (Musa spp.) genetic resources information and high-throughput genotyping data

Unraveling the genetic diversity held in genebanks on a large scale is underway, due to advances in Next-generation sequence (NGS) based technologies that produce high-density genetic markers for a large number of samples at low cost. Genebank users should be in a position to identify and select germplasm from the global genepool based on a combination of passport, genotypic and phenotypic data. To facilitate this, a new generation of information systems is being designed to efficiently handle data and link it with other external resources such as genome or breeding databases. The Musa Germplasm Information System (MGIS), the database for global ex situ-held banana genetic resources, has been developed to address those needs in a user-friendly way. In developing MGIS, we selected a generic database schema (Chado), the robust content management system Drupal for the user interface, and Tripal, a set of Drupal modules which links the Chado schema to Drupal. MGIS allows germplasm collection examination, accession browsing, advanced search functions, and germplasm orders. Additionally, we developed unique graphical interfaces to compare accessions and to explore them based on their taxonomic information. Accession-based data has been enriched with publications, genotyping studies and associated genotyping datasets reporting on germplasm use. Finally, an interoperability layer has been implemented to facilitate the link with complementary databases like the Banana Genome Hub and the MusaBase breeding database. Database URL:https://www.crop-diversity.org/mgis

Directed Neural Differentiation of Mouse Embryonic Stem Cells Is a Sensitive System for the Identification of Novel Hox Gene Effectors

The evolutionarily conserved Hox family of homeodomain transcription factors plays fundamental roles in regulating cell specification along the anterior posterior axis during development of all bilaterian animals by controlling cell fate choices in a highly localized, extracellular signal and cell context dependent manner. Some studies have established downstream target genes in specific systems but their identification is insufficient to explain either the ability of Hox genes to direct homeotic transformations or the breadth of their patterning potential. To begin delineating Hox gene function in neural development we used a mouse ES cell based system that combines efficient neural differentiation with inducible Hoxb1 expression. Gene expression profiling suggested that Hoxb1 acted as both activator and repressor in the short term but predominantly as a repressor in the long run. Activated and repressed genes segregated in distinct processes suggesting that, in the context examined, Hoxb1 blocked differentiation while activating genes related to early developmental processes, wnt and cell surface receptor linked signal transduction and cell-to-cell communication. To further elucidate aspects of Hoxb1 function we used loss and gain of function approaches in the mouse and chick embryos. We show that Hoxb1 acts as an activator to establish the full expression domain of CRABPI and II in rhombomere 4 and as a repressor to restrict expression of Lhx5 and Lhx9. Thus the Hoxb1 patterning activity includes the regulation of the cellular response to retinoic acid and the delay of the expression of genes that commit cells to neural differentiation. The results of this study show that ES neural differentiation and inducible Hox gene expression can be used as a sensitive model system to systematically identify Hox novel target genes, delineate their interactions with signaling pathways in dictating cell fate and define the extent of functional overlap among different Hox genes