The dynamical evolution of molecular clouds near the Galactic Centre - II. Spatial structure and kinematics of simulated clouds

The evolution of molecular clouds in galactic centres is thought to differ from that in galactic discs due to a significant influence of the external gravitational potential. We present a set of numerical simulations of molecular clouds orbiting on the 100-pc stream of the Central Molecular Zone (the central $\sim500$ pc of the Galaxy) and characterise their morphological and kinematic evolution in response to the background potential and eccentric orbital motion. We find that the clouds are shaped by strong shear and torques, by tidal and geometric deformation, and by their passage through the orbital pericentre. Within our simulations, these mechanisms control cloud sizes, aspect ratios, position angles, filamentary structure, column densities, velocity dispersions, line-of-sight velocity gradients, spin angular momenta, and kinematic complexity. By comparing these predictions to observations of clouds on the Galactic Centre 'dust ridge', we find that our simulations naturally reproduce a broad range of key observed morphological and kinematic features, which can be explained in terms of well-understood physical mechanisms. We argue that the accretion of gas clouds onto the central regions of galaxies, where the rotation curve turns over and the tidal field is fully compressive, is accompanied by transformative dynamical changes to the clouds, leading to collapse and star formation. This can generate an evolutionary progression of cloud collapse with a common starting point, which either marks the time of accretion onto the tidally-compressive region or of the most recent pericentre passage. Together, these processes may naturally produce the synchronised starbursts observed in numerous (extra)galactic nuclei

Dense gas in the Galactic central molecular zone is warm and heated by turbulence

The Galactic center is the closest region in which we can study star formation under extreme physical conditions like those in high-redshift galaxies. We measure the temperature of the dense gas in the central molecular zone (CMZ) and examine what drives it. We mapped the inner 300 pc of the CMZ in the temperature-sensitive J = 3-2 para-formaldehyde (p-H$_2$CO) transitions. We used the $3_{2,1} - 2_{2,0} / 3_{0,3} - 2_{0,2}$ line ratio to determine the gas temperature in $n \sim 10^4 - 10^5$cm$^{-3}$ gas. We have produced temperature maps and cubes with 30" and 1 km/s resolution and published all data in FITS form. Dense gas temperatures in the Galactic center range from ~60 K to > 100 K in selected regions. The highest gas temperatures T_G > 100 K are observed around the Sgr B2 cores, in the extended Sgr B2 cloud, the 20 km/s and 50 km/s clouds, and in "The Brick" (G0.253+0.016). We infer an upper limit on the cosmic ray ionization rate ${\zeta}_{CR} < 10^{-14}$ 1/s. The dense molecular gas temperature of the region around our Galactic center is similar to values found in the central regions of other galaxies, in particular starburst systems. The gas temperature is uniformly higher than the dust temperature, confirming that dust is a coolant in the dense gas. Turbulent heating can readily explain the observed temperatures given the observed line widths. Cosmic rays cannot explain the observed variation in gas temperatures, so CMZ dense gas temperatures are not dominated by cosmic ray heating. The gas temperatures previously observed to be high in the inner ~75 pc are confirmed to be high in the entire CMZ

Orbiting Astronomical Satellite for Investigating Stellar Systems (OASIS): following the water trail from the interstellar medium to oceans

Orbiting Astronomical Satellite for Investigating Stellar Systems (OASIS) is a space-based, MIDEX-class mission concept that employs a 17-meter diameter inflatable aperture with cryogenic heterodyne receivers, enabling high sensitivity and high spectral resolution (resolving power ≥106) observations at terahertz frequencies. OASIS science is targeting submillimeter and far-infrared transitions of H2O and its isotopologues, as well as deuterated molecular hydrogen (HD) and other molecular species from 660 to 80 μm, which are inaccessible to ground-based telescopes due to the opacity of Earth’s atmosphere. OASIS will have <20x the collecting area and ~5x the angular resolution of Herschel, and it complements the shorter wavelength capabilities of the James Webb Space Telescope. With its large collecting area and suite of terahertz heterodyne receivers, OASIS will have the sensitivity to follow the water trail from galaxies to oceans, as well as directly measure gas mass in a wide variety of astrophysical objects from observations of the ground-state HD line. OASIS will operate in a Sun-Earth L1 halo orbit that enables observations of large numbers of galaxies, protoplanetary systems, and solar system objects during the course of its 1-year baseline mission. OASIS embraces an overarching science theme of “following water from galaxies, through protostellar systems, to oceans.” This theme resonates with the NASA Astrophysics Roadmap and the 2010 Astrophysics Decadal Survey, and it is also highly complementary to the proposed Origins Space Telescope’s objectives

OXA1L mutations cause mitochondrial encephalopathy and a combined oxidative phosphorylation defect

OXA1, the mitochondrial member of the YidC/Alb3/Oxa1 membrane protein insertase family, is required for the assembly of oxidative phosphorylation complexes IV and V in yeast. However, depletion of human OXA1 (OXA1L) was previously reported to impair assembly of complexes I and V only. We report a patient presenting with severe encephalopathy, hypotonia and developmental delay who died at 5 years showing complex IV deficiency in skeletal muscle. Whole exome sequencing identified biallelic OXA1L variants (c.500507dup, p.(Ser170Glnfs*18) and c.620G>T, p.(Cys207Phe)) that segregated with disease. Patient muscle and fibroblasts showed decreased OXA1L and subunits of complexes IV and V. Crucially, expression of wild-type human OXA1L in patient fibroblasts rescued the complex IV and V defects. Targeted depletion of OXA1L in human cells or Drosophila melanogaster caused defects in the assembly of complexes I, IV and V, consistent with patient data. Immunoprecipitation of OXA1L revealed the enrichment of mtDNA-encoded subunits of complexes I, IV and V. Our data verify the pathogenicity of these OXA1L variants and demonstrate that OXA1L is required for the assembly of multiple respiratory chain complexes.Peer reviewe

Trends and variation in the management of oesophagogastric cancer patients: a population-based survey

<p>Abstract</p> <p>Background</p> <p>Previous evidence indicates potential variation in the quality of care of cancer patients. We aimed to examine whether recent changes in the treatment of oesophagogastric cancers have been distributed equally among different patient subgroups.</p> <p>Methods</p> <p>We analysed population-based cancer registry data about the treatment patterning of oesophagogastric cancer (other than oesophageal squamous cell carcinoma) during 1995-2006.</p> <p>Results</p> <p>There were 14,077 patients aged ≥40 years (69% men). There was only limited information on stage, and no information on co-morbidity status. During successive triennia, curative surgery use decreased from 28% to 20% (p < 0.001) whilst chemotherapy use increased from 9% to 30% (p < 0.001). Use of palliative surgery and of radiotherapy increased significantly but modestly (7% to 10%, and 9% to 11%, respectively). In multivariable logistic regression adjusting for age group, gender, diagnosis period and tumour type, curative surgery and chemotherapy were used less frequently in more deprived patients [per increasing deprivation group Odds Ratio (OR) = 0.96, 95% Confidence Interval (CI) 0.93-0.99, and OR = 0.90, 95%CI 0.87-0.93, respectively, p < 0.001 for both)]. Chemotherapy was also used less frequently in women (OR = 0.76, p < 0.001).</p> <p>Conclusions</p> <p>During the study period, curative surgery decreased by a third and chemotherapy use increased by more than three-fold, reflecting improvements in the appropriateness and quality of management, but chemotherapy use, in particular, was unequal, both by socioeconomic status and gender.</p

Genomic profiling distinguishes familial multiple and sporadic multiple meningiomas

<p>Abstract</p> <p>Background</p> <p>Meningiomas may occur either as familial tumors in two distinct disorders, familial multiple meningioma and neurofibromatosis 2 (NF2), or sporadically, as either single or multiple tumors in individuals with no family history. Meningiomas in NF2 and approximately 60% of sporadic meningiomas involve inactivation of the <it>NF2 </it>locus, encoding the tumor suppressor merlin on chromosome 22q. This study was undertaken to establish whether genomic profiling could distinguish familial multiple meningiomas from sporadic solitary and sporadic multiple meningiomas.</p> <p>Methods</p> <p>We compared 73 meningiomas presenting as sporadic solitary (64), sporadic multiple (5) and familial multiple (4) tumors using genomic profiling by array comparative genomic hybridization (array CGH).</p> <p>Results</p> <p>Sporadic solitary meningiomas revealed genomic rearrangements consistent with at least two mechanisms of tumor initiation, as unsupervised cluster analysis readily distinguished tumors with chromosome 22 deletion (associated with loss of the <it>NF2 </it>tumor suppressor) from those without chromosome 22 deletion. Whereas sporadic meningiomas without chromosome 22 loss exhibited fewer chromosomal imbalance events overall, tumors with chromosome 22 deletion further clustered into two major groups that largely, though not perfectly, matched with their benign (WHO Grade I) or advanced (WHO Grades II and III) histological grade, with the latter exhibiting a significantly greater degree of genomic imbalance (P < 0.001). Sporadic multiple meningiomas showed a frequency of genomic imbalance events comparable to the atypical grade solitary tumors. By contrast, familial multiple meningiomas displayed no imbalances, supporting a distinct mechanism for the origin for these tumors.</p> <p>Conclusion</p> <p>Genomic profiling can provide an unbiased adjunct to traditional meningioma classification and provides a basis for exploring the different genetic underpinnings of tumor initiation and progression. Most importantly, the striking difference observed between sporadic and familial multiple meningiomas indicates that genomic profiling can provide valuable information for differential diagnosis of subjects with multiple meningiomas and for considering the risk for tumor occurrence in their family members.</p

Modeling of Human Prokineticin Receptors: Interactions with Novel Small-Molecule Binders and Potential Off-Target Drugs

The Prokineticin receptor (PKR) 1 and 2 subtypes are novel members of family A GPCRs, which exhibit an unusually high degree of sequence similarity. Prokineticins (PKs), their cognate ligands, are small secreted proteins of ∼80 amino acids; however, non-peptidic low-molecular weight antagonists have also been identified. PKs and their receptors play important roles under various physiological conditions such as maintaining circadian rhythm and pain perception, as well as regulating angiogenesis and modulating immunity. Identifying binding sites for known antagonists and for additional potential binders will facilitate studying and regulating these novel receptors. Blocking PKRs may serve as a therapeutic tool for various diseases, including acute pain, inflammation and cancer.Ligand-based pharmacophore models were derived from known antagonists, and virtual screening performed on the DrugBank dataset identified potential human PKR (hPKR) ligands with novel scaffolds. Interestingly, these included several HIV protease inhibitors for which endothelial cell dysfunction is a documented side effect. Our results suggest that the side effects might be due to inhibition of the PKR signaling pathway. Docking of known binders to a 3D homology model of hPKR1 is in agreement with the well-established canonical TM-bundle binding site of family A GPCRs. Furthermore, the docking results highlight residues that may form specific contacts with the ligands. These contacts provide structural explanation for the importance of several chemical features that were obtained from the structure-activity analysis of known binders. With the exception of a single loop residue that might be perused in the future for obtaining subtype-specific regulation, the results suggest an identical TM-bundle binding site for hPKR1 and hPKR2. In addition, analysis of the intracellular regions highlights variable regions that may provide subtype specificity

Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient

In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick high-throughput assays. On the one hand, recent progress in microfluidics technologies is expected to strongly support the development of miniaturized analytical devices, which will speed up (bio)analytical assays. On the other hand, a higher throughput can be obtained by the simultaneous screening of one sample for multiple targets (multiplexing) by means of encoded particle-based assays. Multiplexing at the macro level is now common in research labs and is expected to become part of clinical diagnostics. This review aims to debate on the “added value” we can expect from (bio)analysis with particles in microfluidic devices. Technologies to (a) decode, (b) analyze, and (c) manipulate the particles are described. Special emphasis is placed on the challenges of integrating currently existing detection platforms for encoded microparticles into microdevices and on promising microtechnologies that could be used to down-scale the detection units in order to obtain compact miniaturized particle-based multiplexing platforms

Bovine Tuberculosis and Badger Culling in England: A Utilitarian Analysis of Policy Options

Bovine tuberculosis (bovine TB) is an important animal health policy issue in Britain, which impacts farmers, the public, domestic farmed cattle and the wild badger population. The Westminster government’s badger culling policy in England, which began in 2013, has caused considerable controversy. This is in part because the Independent Scientific Group advised against culling, based on the Randomised Badger Culling Trial. Those opposed to badger culling support more stringent cattle-based measures and the vaccination of badgers. This paper argues for ethical analysis of public policy options which impact sentient species. It provides a summary Animal Welfare Impact Assessment of (1) a do-nothing approach, (2) badger culling, and (3) badger vaccination. A utilitarian analysis is then applied to these policy options considering human wellbeing and animal welfare. The analysis compares a badger culling policy that achieves a 19% reduction in bovine TB incidence, a badger vaccination model achieving a 12.5% reduction, and a do-nothing approach. Policy options are assessed over 9 years and a longer timeframe, and uncertainty is considered. The analysis finds that non-culling approaches, particularly badger vaccination, result in greater total utility, compared to badger culling. Badger culling causes 30% reduction in the badger population in England as well as substantial harms due to the culling process. Culling is opposed by public opinion and is associated with considerable risks and uncertainty. In contrast, non-culling approaches, such as cattle-based measures and badger vaccination, are supported by public opinion and are not associated with such risks