Physical Conditions in Shocked Interstellar Gas Interacting with the Supernova Remnant IC 443

We present the results of a detailed investigation into the physical conditions in interstellar material interacting with the supernova remnant IC 443. Our analysis is based on a comprehensive examination of high-resolution far-ultraviolet spectra obtained with the Space Telescope Imaging Spectrograph onboard the Hubble Space Telescope of two stars behind IC 443. One of our targets (HD 43582) probes gas along the entire line of sight through the supernova remnant, while the other (HD 254755) samples material located ahead of the primary supernova shock front. We identify low velocity quiescent gas in both directions and find that the densities and temperatures in these components are typical of diffuse atomic and molecular clouds. Numerous high velocity components are observed in the absorption profiles of neutral and singly-ionized atomic species toward HD 43582. These components exhibit a combination of greatly enhanced thermal pressures and significantly reduced dust-grain depletions. We interpret this material as cooling gas in a recombination zone far downstream from shocks driven into neutral gas clumps. The pressures derived for a group of ionized gas components at high positive velocity toward HD 43582 are lower than those of the other shocked components, pointing to pressure inhomogeneities across the remnant. A strong very high velocity component near -620 km/s is seen in the absorption profiles of highly-ionized species toward HD 43582. The velocity of this material is consistent with the range of shock velocities implied by observations of soft thermal X-ray emission from IC 443. Moderately high-velocity gas toward HD 254755 may represent shocked material from a separate foreground supernova remnant.Comment: 88 pages, 27 figures, accepted for publication in Ap

Nuclear safety policy working group recommendations on nuclear propulsion safety for the space exploration initiative

An interagency Nuclear Safety Working Group (NSPWG) was chartered to recommend nuclear safety policy, requirements, and guidelines for the Space Exploration Initiative (SEI) nuclear propulsion program. These recommendations, which are contained in this report, should facilitate the implementation of mission planning and conceptual design studies. The NSPWG has recommended a top-level policy to provide the guiding principles for the development and implementation of the SEI nuclear propulsion safety program. In addition, the NSPWG has reviewed safety issues for nuclear propulsion and recommended top-level safety requirements and guidelines to address these issues. These recommendations should be useful for the development of the program's top-level requirements for safety functions (referred to as Safety Functional Requirements). The safety requirements and guidelines address the following topics: reactor start-up, inadvertent criticality, radiological release and exposure, disposal, entry, safeguards, risk/reliability, operational safety, ground testing, and other considerations

ARL3 mutations cause Joubert syndrome by disrupting ciliary protein composition

Joubert syndrome (JBTS) is a genetically heterogeneous autosomal recessive neurodevelopmental ciliopathy. We investigated further the underlying genetic etiology of Joubert syndrome by studying two unrelated families in whom JBTS was not associated with pathogenic variants in known JBTSrelated genes. Combined autozygosity mapping of both families highlighted a candidate locus on chromosome 10 (chr10: 101569997-109106128 (hg 19)), and exome sequencing revealed two missense variants in ARL3 within the candidate locus. The encoded protein, ADP Ribosylation Factor-Like GTPase 3, ARL3, is a small GTP-binding protein that is involved in directing lipid-modified proteins into the cilium in a GTP-dependent manner. Both missense variants replace the highly conserved Arg149 residue, which we show to be necessary for the interaction with its guanine nucleotide exchange factor ARL13B, such that the mutant protein is associated with reduced INPP5E and NPHP3 localisation in cilia. We propose that ARL3 provides a potential hub in the network of encoded ciliopathy genes, whereby perturbation of ARL3 results in the mislocalisation of multiple ciliary proteins due to abnormal displacement of lipidated protein cargo

The medical student

The Medical Student was published from 1888-1921 by the students of Boston University School of Medicine

English in Wartime: A Symposium by College Teachers

After the declaration of war upon us by the Axis nations, it seemed the editors of College English that the members of the College should, as soon as possible, co-operate in determining how best to fulfil our special responsibility throughout World War II. As a first step, we invited twenty-five teachers of English in colleges and universities to suggest how we should meet this professional emergency. The Planning Commission of the N.C.T.E., at their meeting in Chicago during the Christmas holidays, and the College Section, at their meeting in Indianapolis with the M.L.A., considered general and basic wartime policies for the National Council. The result of these deliberations will be presented in the March College English. To assemble a preliminary survey of opinion on the teaching of English in World War II, we had to act quickly in order to meet the deadline for the February issue. Nine letters from college men and women came back in time to be included in the symposium. The weakness of the small number, however, is overcome by the strength of the unified and obviously representative character of the responses. Teachers of English believe in the permanent value of the work they are doing. In peace or in war the discipline of the humanities is a way to decency in human relations. Those who have written for the symposium agree that our time of emergency requires of us, as teachers of English, a more vigorous concentration than ever upon clear expression and broad, permanently vital reading. We will need to make curriculum changes, and individually we will perform special wartime duties; but the initial message from outstanding college teachers is that we must do the job for which we are trained: help others to realize the power which emanates from great literature to live humanely in the midst of conflict

Need-based resource allocation: different need indicators, different results?

<p>Abstract</p> <p>Background</p> <p>A key policy objective in most publicly financed health care systems is to allocate resources according to need. Many jurisdictions implement this policy objective through need-based allocation models. To date, no gold standard exists for selecting need indicators. In the absence of a gold standard, sensitivity of the choice of need indicators is of concern. The primary objective of this study was to assess the consistency and plausibility of estimates of per capita relative need for health services across Canadian provinces based on different need indicators.</p> <p>Methods</p> <p>Using the 2000/2001 Canadian Community Health Survey, we estimated relative per capita need for general practitioner, specialist, and hospital services by province using two approaches that incorporated a different set of need indicators: (1) demographics (age and sex), and (2) demographics, socioeconomic status, and health status. For both approaches, we first fitted regression models to estimate standard utilization of each of three types of health services by indicators of need. We defined the standard as average levels of utilization by needs indicators in the national sample. Subsequently, we estimated expected per capita utilization of each type of health services in each province. We compared these estimates of per capita relative need with premature mortality in each province to check their face validity.</p> <p>Results</p> <p>Both approaches suggested that expected relative per capita need for three services vary across provinces. Different approaches, however, yielded different and inconsistent results. Moreover, provincial per capita relative need for the three health services did not always indicate the same direction of need suggested by premature mortality in each province. In particular, the two approaches suggested Newfoundland had less need than the Canadian average for all three services, but it had the highest premature mortality in Canada.</p> <p>Conclusion</p> <p>Substantial differences in need for health care may exist across Canadian provinces, but the direction and magnitude of differences depend on the need indicators used. Allocations from models using survey data lacked face validity for some provinces. These results call for the need to better understand the biases that may result from the use of survey data for resource allocation.</p

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al

A novel sialylation site on Neisseria gonorrhoeae lipooligosaccharide links heptose II lactose expression with pathogenicity [preprint]

Sialylation of lacto-N-neotetraose (LNnT) extending from heptose I (HepI) of gonococcal lipooligosaccharide (LOS) contributes to pathogenesis. Previously, gonococcal LOS sialyltransterase (Lst) was shown to sialylate LOS in Triton X-100 extracts of strain 15253, which expresses lactose from both HepI and HepII, the minimal structure required for mAb 2C7 binding. Ongoing work has shown that growth of 15253 in cytidine monophospho-N-acetylneuraminic acid (CMP-Neu5Ac)-containing media enables binding to CD33/Siglec-3, a cell surface receptor that binds sialic acid, suggesting that lactose termini on LOS of intact gonococci can be sialylated. Neu5Ac was detected on LOSs of strains 15253 and a MS11 mutant with only lactose from HepI and HepII by mass spectrometry; deleting HepII lactose rendered Neu5Ac undetectable. Resistance of HepII lactose Neu5Ac to desialylation by α2-3-specific neuraminidase suggested an α2-6-linkage. Although not associated with increased factor H binding, HepII lactose sialylation inhibited complement C3 deposition on gonococci. 15253 mutants that lacked Lst or HepII lactose were significantly attenuated in mice, confirming the importance of HepII Neu5Ac in virulence. All 75 minimally passaged clinical isolates from Nanjing, China, expressed HepII lactose, evidenced by reactivity with mAb 2C7; mAb 2C7 was bactericidal against the first 62 (of 75) isolates that had been collected sequentially and were sialylated before testing. mAb 2C7 effectively attenuated 15253 vaginal colonization in mice. In conclusion, this novel sialylation site could explain the ubiquity of gonococcal HepII lactose in vivo. Our findings reiterate the candidacy of the 2C7 epitope as a vaccine antigen and mAb 2C7 as an immunotherapeutic antibody