Ustekinumab for the treatment of psoriatic arthritis: an update.

Psoriatic arthritis occurs in 30% of psoriasis patients, and the treatment can be challenging in some patients. Recently, the US Food and Drug Administration approved ustekinumab, a fully human monoclonal antibody, for the management of psoriatic arthritis. In this article, we review large-scale randomized clinical trials addressing the efficacy and safety profile of ustekinumab for the treatment of psoriatic arthritis

The physical determinants of the DNA conformational landscape: an analysis of the potential energy surface of single-strand dinucleotides in the conformational space of duplex DNA

A multivariate analysis of the backbone and sugar torsion angles of dinucleotide fragments was used to construct a 3D principal conformational subspace (PCS) of DNA duplex crystal structures. The potential energy surface (PES) within the PCS was mapped for a single-strand dinucleotide model using an empirical energy function. The low energy regions of the surface encompass known DNA forms and also identify previously unclassified conformers. The physical determinants of the conformational landscape are found to be predominantly steric interactions within the dinucleotide backbone, with medium-dependent backbone-base electrostatic interactions serving to tune the relative stability of the different local energy minima. The fidelity of the PES to duplex DNA properties is validated through a correspondence to the conformational distribution of duplex DNA crystal structures and the reproduction of observed sequence specific propensities for the formation of A-form DNA. The utility of the PES is demonstrated through its succinct and accurate description of complex conformational processes in simulations of duplex DNA. The study suggests that stereochemical considerations of the nucleic acid backbone play a role in determining conformational preferences of DNA which is analogous to the role of local steric interactions in determining polypeptide secondary structure

Reducing dietary wild derived fishmeal inclusion levels in production diets for large yellowtail kingfish (Seriola lalandi)

Further research to understand the effect of dietary wild derived fishmeal (WD-FM) substitution with commercially relevant alternative ingredients for large yellowtail kingfish (Seriola lalandi; YTK) was investigated. This 36-week study was designed to replace dietary inclusions of WD-FM with alternative protein ingredients including poultry meal, soy protein concentrate and by-product fishmeal (PM, SPC and BP-FM) and measure the effect on the growth performance, feed utilisation, and health of large YTK (2.5 kg initial weight) at ambient water temperatures (average 16.6 °C). Six diets were formulated on a digestible basis to contain 39% digestible protein (∼45–46% crude protein), 23% digestible lipid (∼24–25% crude lipid), and a digestible energy level of 17 MJ kg−1 (∼19 MJ kg−1 gross energy level). Fish were fed to apparent satiation once daily at 10:00 h. Substitution of fish meal with alternative ingredients did not significantly impact fish growth, feed utilisation, gastrointestinal health, blood haematology or measured biochemistry indices. Results from the current study will allow reductions to the dietary WD-FM inclusion levels, with tangible sustainability benefits. The inclusion of the alternative protein sources resulted in improvements in the fish in-fish out ratios of up to 35.1%. This study suggests formulation criteria for large YTK should include a minimum of 10% WD-FM. Further to this, at least 30% of the diet should consist of a combination of poultry meal, soy protein concentrate and fishmeal (both wild and by-product). Our data further support the use of BP-FM up to ∼20% inclusion, while PM and SPC should be limited to ∼10% inclusion until further data is available on these raw materials in YTK feeds. These recommendations will facilitate formulation flexibility for large YTK feeds, enabling formulators to adapt to changes to extrinsic factors such as raw material availability, and sustainability while minimising cost and performance impacts

Ariel - Volume 3 Number 6

Editors Richard J. Bonanno Robin A. Edwards Associate Editors Steven Ager Tom Williams Lay-out Editor Eugenia Miller Contributing Editors Paul Bialas Robert Breckenridge Lynne Porter David Jacoby Mike LeWitt Terry Burt Mark Pearlman Michael Leo Editors Emeritus Delvyn C. Case, Jr. Paul M. Fernhof

AXTAR: Mission Design Concept

The Advanced X-ray Timing Array (AXTAR) is a mission concept for X-ray timing of compact objects that combines very large collecting area, broadband spectral coverage, high time resolution, highly flexible scheduling, and an ability to respond promptly to time-critical targets of opportunity. It is optimized for submillisecond timing of bright Galactic X-ray sources in order to study phenomena at the natural time scales of neutron star surfaces and black hole event horizons, thus probing the physics of ultradense matter, strongly curved spacetimes, and intense magnetic fields. AXTAR's main instrument, the Large Area Timing Array (LATA) is a collimated instrument with 2-50 keV coverage and over 3 square meters effective area. The LATA is made up of an array of supermodules that house 2-mm thick silicon pixel detectors. AXTAR will provide a significant improvement in effective area (a factor of 7 at 4 keV and a factor of 36 at 30 keV) over the RXTE PCA. AXTAR will also carry a sensitive Sky Monitor (SM) that acts as a trigger for pointed observations of X-ray transients in addition to providing high duty cycle monitoring of the X-ray sky. We review the science goals and technical concept for AXTAR and present results from a preliminary mission design study.Comment: 19 pages, 10 figures, to be published in Space Telescopes and Instrumentation 2010: Ultraviolet to Gamma Ray, Proceedings of SPIE Volume 773

ZFIRE: The Evolution of the Stellar Mass Tully-Fisher Relation to Redshift 2.0 < Z < 2.5 with MOSFIRE

Using observations made with MOSFIRE on Keck I as part of the ZFIRE survey, we present the stellar mass Tully-Fisher relation at 2.0 < z < 2.5. The sample was drawn from a stellar mass limited, Ks-band selected catalog from ZFOURGE over the CANDELS area in the COSMOS field. We model the shear of the Halpha emission line to derive rotational velocities at 2.2X the scale radius of an exponential disk (V2.2). We correct for the blurring effect of a two-dimensional PSF and the fact that the MOSFIRE PSF is better approximated by a Moffat than a Gaussian, which is more typically assumed for natural seeing. We find for the Tully-Fisher relation at 2.0 < z < 2.5 that logV2.2 =(2.18 +/- 0.051)+(0.193 +/- 0.108)(logM/Msun - 10) and infer an evolution of the zeropoint of Delta M/Msun = -0.25 +/- 0.16 dex or Delta M/Msun = -0.39 +/- 0.21 dex compared to z = 0 when adopting a fixed slope of 0.29 or 1/4.5, respectively. We also derive the alternative kinematic estimator S0.5, with a best-fit relation logS0.5 =(2.06 +/- 0.032)+(0.211 +/- 0.086)(logM/Msun - 10), and infer an evolution of Delta M/Msun= -0.45 +/- 0.13 dex compared to z < 1.2 if we adopt a fixed slope. We investigate and review various systematics, ranging from PSF effects, projection effects, systematics related to stellar mass derivation, selection biases and slope. We find that discrepancies between the various literature values are reduced when taking these into account. Our observations correspond well with the gradual evolution predicted by semi-analytic models.Comment: 21 pages, 14 figures, 1 appendix. Accepted for publication by Apj, February 28, 201

Stigma as a fundamental hindrance to the United States opioid overdose crisis response.

Alexander Tsai and co-authors discuss the role of stigma in responses to the US opioid crisis

Recombination and its impact on the genome of the haplodiploid parasitoid wasp Nasonia

Homologous meiotic recombination occurs in most sexually reproducing organisms, yet its evolutionary advantages are elusive. Previous research explored recombination in the honeybee, a eusocial hymenopteran with an exceptionally high genome-wide recombination rate. A comparable study in a non-social member of the Hymenoptera that would disentangle the impact of sociality from Hymenoptera-specific features such as haplodiploidy on the evolution of the high genome-wide recombination rate in social Hymenoptera is missing. Utilizing single-nucleotide polymorphisms (SNPs) between two Nasonia parasitoid wasp genomes, we developed a SNP genotyping microarray to infer a high-density linkage map for Nasonia. The map comprises 1,255 markers with an average distance of 0.3 cM. The mapped markers enabled us to arrange 265 scaffolds of the Nasonia genome assembly 1.0 on the linkage map, representing 63.6% of the assembled N. vitripennis genome. We estimated a genome-wide recombination rate of 1.4-1.5 cM/Mb for Nasonia, which is less than one tenth of the rate reported for the honeybee. The local recombination rate in Nasonia is positively correlated with the distance to the center of the linkage groups, GC content, and the proportion of simple repeats. In contrast to the honeybee genome, gene density in the parasitoid wasp genome is positively associated with the recombination rate; regions of low recombination are characterized by fewer genes with larger introns and by a greater distance between genes. Finally, we found that genes in regions of the genome with a low recombination frequency tend to have a higher ratio of non-synonymous to synonymous substitutions, likely due to the accumulation of slightly deleterious non-synonymous substitutions. These findings are consistent with the hypothesis that recombination reduces interference between linked sites and thereby facilitates adaptive evolution and the purging of deleterious mutations. Our results imply that the genomes of haplodiploid and of diploid higher eukaryotes do not differ systematically in their recombination rates and associated parameters.Publisher PDFPeer reviewe

A magneto-optical trap with millimeter ball lenses

We present a magneto-optical trap (MOT) design based on millimeter ball lenses, contained within a metal cube of 0.75$^{\prime \prime}$ side length. We present evidence of trapping approximately $4.2\times 10^5$ of $^{85}$Rb atoms with a number density of $3.2\times 10^9$ atoms/cm$^{3}$ and a loading time of 1.3 s. Measurement and a kinetic laser-cooling model are used to characterize the atom trap design. The design provides several advantages over other types of MOTs: the laser power requirement is low, the small lens and cube sizes allow for miniaturization of MOT applications, and the lack of large-diameter optical beam pathways prevents external blackbody radiation from entering the trapping region.Comment: 8 pages, 4 figure

Smartphone scene generator for efficient characterization of visible imaging detectors

Full characterization of imaging detectors involves subjecting them to spatially and temporally varying illumination patterns over a large dynamic range. Here we present a scene generator that fulfills many of these functions. Based on a modern smartphone, it has a number of good features, including the ability to generate nearly arbitrary optical scenes, high spatial resolution (13 um), high dynamic range (~10^4), near-Poisson limited illumination stability over time periods from 100 ms to many days, and no background noise. The system does not require any moving parts and may be constructed at modest cost. We present the optical, mechanical, and software design, test data validating the performance, and application examples.Comment: 14 pages. This version includes code, available here: https://github.com/Leo-Nea