Structure of the 2,4'-dihydroxyacetophenone dioxygenase from Alcaligenes sp. 4HAP.

The enzyme 2,4'-dihydroxyacetophenone dioxygenase (DAD) catalyses the conversion of 2,4'-dihydroxyacetophenone to 4-hydroxybenzoic acid and formic acid with the incorporation of molecular oxygen. Whilst the vast majority of dioxygenases cleave within the aromatic ring of the substrate, DAD is very unusual in that it is involved in C-C bond cleavage in a substituent of the aromatic ring. There is evidence that the enzyme is a homotetramer of 20.3 kDa subunits, each containing nonhaem iron, and its sequence suggests that it belongs to the cupin family of dioxygenases. In this paper, the first X-ray structure of a DAD enzyme from the Gram-negative bacterium Alcaligenes sp. 4HAP is reported, at a resolution of 2.2 Å. The structure establishes that the enzyme adopts a cupin fold, forming dimers with a pronounced hydrophobic interface between the monomers. The catalytic iron is coordinated by three histidine residues (76, 78 and 114) within a buried active-site cavity. The iron also appears to be tightly coordinated by an additional ligand which was putatively assigned as a carbonate dianion since this fits the electron density optimally, although it might also be the product formate. The modelled carbonate is located in a position which is highly likely to be occupied by the α-hydroxyketone group of the bound substrate during catalysis. Modelling of a substrate molecule in this position indicates that it will interact with many conserved amino acids in the predominantly hydrophobic active-site pocket where it undergoes peroxide radical-mediated heterolysis

Experimental measurement of specific impulse distribution and transient deformation of plates subjected to near-field explosive blasts

The shock wave generated from a high explosive detonation can cause significant damage to any objects that it encounters, particularly those objects located close to the source of the explosion. Understanding blast wave development and accurately quantifying its effect on structural systems remains a considerable challenge to the scientific community. This paper presents a comprehensive experimental study into the loading acting on, and subsequent deformation of, targets subjected to near-field explosive detonations. Two experimental test series were conducted at the University of Sheffield (UoS), UK, and the University of Cape Town (UCT), South Africa, where blast load distributions using Hopkinson pressure bars and dynamic target deflections using digital image correlation were measured respectively. It is shown through conservation of momentum and Hopkinson-Cranz scaling that initial plate velocity profiles are directly proportional to the imparted impulse distribution, and that spatial variations in loading as a result of surface instabilities in the expanding detonation product cloud are significant enough to influence the transient displacement profile of a blast loaded plate

Reflected near-field blast pressure measurements using high speed video

Background: The design and analysis of protective systems requires a detailed understanding of, and the ability to accurately predict, the distribution of pressure loads acting on an obstacle following an explosive detonation. In particular, there is a pressing need for accurate characterisation of blast loads in the region very close to a detonation, where even small improvised devices can produce serious structural or material damage. Objective: Accurate experimental measurement of these near-field blast events, using intrusive methods, is demanding owing to the high magnitudes (> 100 MPa) and short durations (< 1 ms) of loading. The objective of this article is to develop a non-intrusive method for measuring reflected blast pressure distributions using image analysis. Methods: This article presents results from high speed video analysis of near-field spherical PE4 explosive blasts. The Canny edge detection algorithm is used to track the outer surface of the explosive fireball, with the results used to derive a velocity-radius relationship. Reflected pressure distributions are calculated using this velocity-radius relationship in conjunction with the Rankine-Hugoniot jump conditions. Results: The indirectly measured pressure distributions from high speed video are compared with directly measured pressure distributions and are shown to be in good qualitative agreement with respect to distribution of reflected pressures, and in good quantitative agreement with peak reflected pressures (within 10% of the maximum recorded value). Conclusions: The results indicate that it is possible to accurately measure blast loads in the order of 100s MPa using techniques which do not require sensitive recording equipment to be located close to the source of the explosion

ATLASGAL - star forming efficiencies and the Galactic star formation rate

The ATLASGAL survey has characterized the properties of approximately 1000 embedded H ii regions and found an empirical relationship between the clump mass and bolometric luminosity that covers 3-4 orders of magnitude. Comparing this relation with simulated clusters drawn from an initial mass function and using different star formation efficiencies we find that a single value is unable to fit the observed luminosity to mass (L/M) relation. We have used a Monte Carlo simulation to generate 200 000 clusters using the L/M-ratio as a constraint to investigate how the star formation efficiency changes as a function of clump mass. This has revealed that the star formation efficiency decreases with increasing clump mass with a value of 0.2 for clumps with masses of a few hundred solar masses and dropping to 0.08 for clumps with masses of a few thousand solar masses. We find good agreement between our results and star formation efficiencies determined from counts of embedded objects in nearby molecular clouds. Using the star formation efficiency relationship and the infrared excess time for embedded star formation of 2 ± 1 Myr we estimate the Galactic star formation rate to be approximately 0.9 ± 0.45 M· yr-1, which is in good agreement with previously reported values. This model has the advantage of providing a direct means of determining the star formation rate and avoids the difficulties encountered in converting infrared luminosities to stellar mass that affect previous galactic and extragalactic studies

CHIMPS: Physical properties of molecular clumps across the inner Galaxy

The latest generation of high-angular-resolution unbiased Galactic plane surveys in molecular-gas tracers are enabling the interiors of molecular clouds to be studied across a range of environments. The CO Heterodyne Inner MilkyWay Plane Survey (CHIMPS) simultaneously mapped a sector of the inner Galactic plane, within 27:8 . 46:2 and jbj 0: 5, in 13CO (3-2) and C18O (3-2) at an angular resolution of 15 arcsec. The combination of the CHIMPS data with 12CO (3-2) data from the CO High Resolution Survey (COHRS) has enabled us to perform a voxel-by-voxel local-thermodynamic-equilibrium (LTE) analysis, determining the excitation temperature, optical depth, and column density of 13CO at each; b; v position. Distances to discrete sources identified by FELLWALKER in the 13CO (3-2) emission maps were determined, allowing the calculation of numerous physical properties of the sources, and we present the first source catalogues in this paper.We find that, in terms of size and density, the CHIMPS sources represent an intermediate population between large-scale molecular clouds identified by CO and dense clumps seen in thermal dust continuum emission, and therefore represent the bulk transition from the diffuse to the dense phase of molecular gas.We do not find any significant systematic variations in the masses, column densities, virial parameters, mean excitation temperature, or the turbulent pressure over the range of Galactocentric distance probed, but we do find a shallow increase in the mean volume density with increasing Galactocentric distance. We find that inter-arm clumps have significantly narrower linewidths, and lower virial parameters and excitation temperatures than clumps located in spiral arms. When considering the most reliable distance-limited subsamples, the largest variations occur on the clump-to-clump scale, echoing similar recent studies that suggest that the star-forming process is largely insensitive to the Galactic-scale environment, at least within the inner disc

An ALMA study of hub-filament systems – I. On the clump mass concentration within the most massive cores

The physical processes behind the transfer of mass from parsec-scale clumps to massive star-forming cores remain elusive. We investigate the relation between the clump morphology and the mass fraction that ends up in its most massive core (MMC) as a function of infrared brightness, i.e. a clump evolutionary tracer. Using Atacama Large Millimeter/submillimeter Array (ALMA) 12 m and Atacama Compact Array, we surveyed six infrared dark hubs in 2.9 mm continuum at ∼3 arcsec resolution. To put our sample into context, we also re-analysed published ALMA data from a sample of 29 high-mass surface density ATLASGAL sources. We characterize the size, mass, morphology, and infrared brightness of the clumps using Herschel and Spitzer data. Within the six newly observed hubs, we identify 67 cores, and find that the MMCs have masses between 15 and 911 M⊙ within a radius of 0.018–0.156 pc. The MMC of each hub contains 3–24 per cent of the clump mass (fMMC), becoming 5–36 per cent once core masses are normalized to the median core radius. Across the 35 clumps, we find no significant difference in the median fMMC values of hub and non-hub systems, likely the consequence of a sample bias. However, we find that fMMC is ∼7.9 times larger for infrared dark clumps compared to infrared bright ones. This factor increases up to ∼14.5 when comparing our sample of six infrared dark hubs to infrared bright clumps. We speculate that hub-filament systems efficiently concentrate mass within their MMC early on during its evolution. As clumps evolve, they grow in mass, but such growth does not lead to the formation of more massive MMCs

Growth charts for children with Ellis–van Creveld syndrome

Ellis–van Creveld (EvC) syndrome is a congenital malformation syndrome with marked growth retardation. In this study, specific growth charts for EvC patients were derived to allow better follow-up of growth and earlier detection of growth patterns unusual for EvC. With the use of 235 observations of 101 EvC patients (49 males, 52 females), growth charts for males and females from 0 to 20 years of age were derived. Longitudinal and cross-sectional data were collected from an earlier review of growth data in EvC, a database of EvC patients, and from recent literature. To model the growth charts, the GAMLSS package for the R statistical program was used. Height of EvC patients was compared to healthy children using Dutch growth charts. Data are presented both on a scale for age and on a scale for the square root of age. Compared to healthy Dutch children, mean height standard deviation score values for male and female EvC patients were −3.1 and −3.0, respectively. The present growth charts should be useful in the follow-up of EvC patients. Most importantly, early detection of growth hormone deficiency, known to occur in EvC, will be facilitated

Calcitriol modulates the CD46 pathway in T cells

The complement regulator CD46 is a costimulatory molecule for human T cells that induces a regulatory Tr1 phenotype, characterized by large amounts of IL-10 secretion. Secretion of IL-10 upon CD46 costimulation is largely impaired in T cells from patients with multiple sclerosis (MS). Vitamin D can exert a direct effect on T cells, and may be beneficial in several pathologies, including MS. In this pilot study, we examined whether active vitamin D (1,25(OH)2D3 or calcitriol) could modulate the CD46 pathway and restore IL-10 production by CD46-costimulated CD4+ T cells from patients with MS. In healthy T cells, calcitriol profoundly affects the phenotype of CD46-costimulated CD4+ T cells, by increasing the expression of CD28, CD25, CTLA-4 and Foxp3 while it concomitantly decreased CD46 expression. Similar trends were observed in MS CD4+ T cells except for CD25 for which a striking opposite effect was observed: while CD25 was normally induced on MS T cells by CD46 costimulation, addition of calcitriol consistently inhibited its induction. Despite the aberrant effect on CD25 expression, calcitriol increased the IL-10:IFNc ratio, characteristic of the CD46-induced Tr1 phenotype, in both T cells from healthy donors and patients with MS. Hence, we show that calcitriol affects the CD46 pathway, and that it promotes anti-inflammatory responses mediated by CD46. Moreover, it might be beneficial for T cell responses in MS

Characteristic scale of star formation - I. Clump formation efficiency on local scales

We have used the ratio of column densities derived independently from the 850-μm continuum James Clerk Maxwell Telescope Plane Survey and the 13CO/C18O (J = 3 → 2) Heterodyne Inner Milky Way Plane Survey to produce maps of the dense-gas mass fraction (DGMF) in two slices of the Galactic plane centred at ℓ = 30° and 40°. The observed DGMF is a metric for the instantaneous clump formation efficiency (CFE) in the molecular gas. We split the two fields into velocity components corresponding to the spiral arms that cross them, and a two-dimensional power-spectrum analysis of the spiral-arm DGMF maps reveals a break in slope at the approximate size scale of molecular clouds. We interpret this as the characteristic scale of the amplitude of variations in the CFE and a constraint on the dominant mechanism regulating the CFE and, hence, the star formation efficiency in CO-traced clouds