Realistic Earth escape strategies for solar sailing

With growing interest in solar sailing comes the requirement to provide a basis for future detailed planetary escape mission analysis by drawing together prior work, clarifying and explaining previously anomalies. Previously unexplained seasonal variations in sail escape times from Earth orbit are explained analytically and corroborated within a numerical trajectory model. Blended-sail control algorithms, explicitly independent of time, which providenear-optimal escape trajectories and maintain a safe minimum altitude and which are suitable as a potential autonomous onboard controller, are then presented. These algorithms are investigated from a range of initial conditions and are shown to maintain the optimality previously demonstrated by the use of a single-energy gain control law but without the risk of planetary collision. Finally, it is shown that the minimum sail characteristic acceleration required for escape from a polar orbit without traversing the Earth shadow cone increases exponentially as initial altitude is decreased

The two-iron ferredoxins in spinach, parsley, pig adrenal cortex, Azotobacter vinelandii, and Clostridium pasteurianum: Studies by magnetic field Mossbauer spectroscopy

The two-iron ferredoxins from spinach, parsley, Azotobacter vinelandii, Clostridium pasteurianum and the pig adrenal cortex were investigated by Mossbauer spectroscopy at temperatures from 4 to 256[deg]K and in magnetic fields up to 46 kGauss. Computational programs were devised to allow comparison of the experimental data with computer-simulated spectra in order to facilitate identification of the experimental spectral detail with specific Mossbauer spectroscopic parameters (quadrupole splittings, isomer shifts and nuclear hyperfine and nuclear Zeeman interactions). The results of the analysis permit the following properties of the active center to be established directly as the result of these experiments: 1. 1. In the oxidized forms of the proteins, each iron is in the high spin (S = 5/2) ferric state, spin-coupled to produce a resultant molecular diamagnetism for the protein at temperatures below 100[deg]K.2. 2. In the reduced state of the protein, the active center contains a single ferric site, retaining many properties of the ferric iron in the oxidized protein, but spincoupled to a high spin (S = 2) ferrous site, producing a molecular paramagnetism due to a net electron spin of one half at low temperatures (S = 1/2).3. 3. In spinach and parsley ferredoxins, the ligand symmetry around the ferrous site in the reduced form of the proteins is tetrahedral with measurable axial and rhombic distortions.4. 4. The iron sites in both the oxidized and reduced forms of all the proteins studied are similar, with the possible exception that the ligand symmetry at the ferrous site in the reduced form of the two-iron ferredoxins from C. pasteurianum, A. vinelandii (Azotobacter I and II), and pig adrenal cortex has not been characterized as being square planar or tetrahedral, although octahedral symmetry has been excluded.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33534/1/0000033.pd

"We're worth what we are paid": Unravelling the 'paradox of the contented female worker'

Pay satisfaction research has suggested that women are more satisfied with their pay than men, even though, in general, women earn less. This paper argues that this body of research has misconceptualised this phenomenon as an issue of women only. It also argues that previous explanations for this gender pay paradox have not adequately explained these patterns of satisfaction. A social constructionist approach to pay satisfaction is proposed which situates satisfaction within the context of structural inequality. This draws upon the scholarly work of feminist scholars and the conceptual ideas of Pierre Bourdieu. This theoretical approach is explored with data from qualitative interviews with support staff at universities in the United Kingdom. This evidence suggests that their pay satisfaction is influenced by beliefs about the ‘value’ of different occupations

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls. We directly implicate ten genes in general onset CD for the first time to our knowledge via association to coding variation, four of which lie within established CD GWAS loci. In nine instances, a single coding variant is significantly associated, and in the tenth, ATG4C, we see additionally a significantly increased burden of very rare coding variants in CD cases. In addition to reiterating the central role of innate and adaptive immune cells as well as autophagy in CD pathogenesis, these newly associated genes highlight the emerging role of mesenchymal cells in the development and maintenance of intestinal inflammation.Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn's disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility

peer reviewe

General Paralysis Treated by Intraventricular Injection of Arsphenamin: Report of the Necropsy Findings in a Case

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Effects of vedolizumab induction therapy for patients with Crohn's disease in whom tumor necrosis factor antagonist treatment failed

There is an increasing need for new treatments for patients with Crohn's disease (CD) in whom previous therapy with tumor necrosis factor (TNF) antagonists has failed. We performed a placebo-controlled, phase 3, double-blind trial to evaluate the efficacy and safety of vedolizumab, an antibody against the integrin α4β7, as induction therapy. Patients with moderately to severely active CD (CD activity index [CDAI] score, 220-400 points) were assigned randomly to groups given vedolizumab (300 mg) or placebo intravenously at weeks 0, 2, and 6. The primary analysis involved 315 patients with previous TNF antagonist failure (ie, an inadequate response to, loss of response to, or intolerance of ≥1 TNF antagonists); we determined the proportion of patients in clinical remission (CDAI, ≤150 points) at week 6. Secondary analyses evaluated outcomes at weeks 6 and 10 in this population and in the overall population (N = 416), which included patients naive to TNF antagonist therapy (n = 101). Among patients who had experienced previous TNF antagonist failure, 15.2% of those given vedolizumab and 12.1% of those given placebo were in remission at week 6 (P = .433). At week 10, a higher proportion of this population given vedolizumab was in remission (26.6%) than those given placebo (12.1%) (nominal P = .001; relative risk, 2.2; 95% confidence interval, 1.3-3.6). A higher proportion of patients with previous TNF antagonist failure given vedolizumab also had a CDAI-100 response (≥100-point decrease in CDAI score from baseline) at week 6 than those given placebo (39.2% vs 22.3%; nominal P = .001; relative risk, 1.8; 95% confidence interval, 1.2-2.5). Adverse event results were similar among all groups. Vedolizumab was not more effective than placebo in inducing clinical remission at week 6 among patients with CD in whom previous treatment with TNF antagonists had failed. The therapeutic benefits of vedolizumab in these patients were detectable at week 10. ClinicalTrials.gov number: NCT0122417

Vedolizumab as induction and maintenance therapy for Crohn's disease.

BACKGROUND: The efficacy of vedolizumab, an alpha4beta7 integrin antibody, in Crohn's disease is unknown. METHODS: In an integrated study with separate induction and maintenance trials, we assessed intravenous vedolizumab therapy (300 mg) in adults with active Crohn's disease. In the induction trial, 368 patients were randomly assigned to receive vedolizumab or placebo at weeks 0 and 2 (cohort 1), and 747 patients received open-label vedolizumab at weeks 0 and 2 (cohort 2); disease status was assessed at week 6. In the maintenance trial, 461 patients who had had a response to vedolizumab were randomly assigned to receive placebo or vedolizumab every 8 or 4 weeks until week 52. RESULTS: At week 6, a total of 14.5% of the patients in cohort 1 who received vedolizumab and 6.8% who received placebo were in clinical remission (i.e., had a score on the Crohn's Disease Activity Index [CDAI] of /=100-point decrease in the CDAI score) (P=0.23). Among patients in cohorts 1 and 2 who had a response to induction therapy, 39.0% and 36.4% of those assigned to vedolizumab every 8 weeks and every 4 weeks, respectively, were in clinical remission at week 52, as compared with 21.6% assigned to placebo (P<0.001 and P=0.004 for the two vedolizumab groups, respectively, vs. placebo). Antibodies against vedolizumab developed in 4.0% of the patients. Nasopharyngitis occurred more frequently, and headache and abdominal pain less frequently, in patients receiving vedolizumab than in patients receiving placebo. Vedolizumab, as compared with placebo, was associated with a higher rate of serious adverse events (24.4% vs. 15.3%), infections (44.1% vs. 40.2%), and serious infections (5.5% vs. 3.0%). CONCLUSIONS: Vedolizumab-treated patients with active Crohn's disease were more likely than patients receiving placebo to have a remission, but not a CDAI-100 response, at week 6; patients with a response to induction therapy who continued to receive vedolizumab (rather than switching to placebo) were more likely to be in remission at week 52. Adverse events were more common with vedolizumab. (Funded by Millennium Pharmaceuticals; GEMINI 2 ClinicalTrials.gov number, NCT00783692.)