A T8.5 Brown Dwarf Member of the Xi Ursae Majoris System

The Wide-field Infrared Survey Explorer has revealed a T8.5 brown dwarf (WISE J111838.70+312537.9) that exhibits common proper motion with a solar-neighborhood (8 pc) quadruple star system - Xi Ursae Majoris. The angular separation is 8.5 arc-min, and the projected physical separation is about 4000 AU. The sub-solar metallicity and low chromospheric activity of Xi UMa A argue that the system has an age of at least 2 Gyr. The infrared luminosity and color of the brown dwarf suggests the mass of this companion ranges between 14 and 38 Jupiter masses for system ages of 2 and 8 Gyr respectively.Comment: AJ in press, 12 pages LaTeX with 6 figures. More astrometric data and a laser guide star adaptive optics image adde

Mutations in epigenetic regulators including SETD2 are gained during relapse in pediatric acute lymphoblastic leukemia

Relapsed pediatric acute lymphoblastic leukemia (ALL) has high rates of treatment failure. Epigenetic regulators have been proposed as modulators of chemoresistance, here we sequence genes encoding epigenetic regulators in matched diagnosis-remission-relapse ALL samples. We find significant enrichment of mutations in epigenetic regulators at relapse with recurrent somatic mutations in SETD2, CREBBP, MSH6, KDM6A and MLL2, mutations in signaling factors are not enriched. Somatic alterations in SETD2, including frameshift and nonsense mutations, are present at 12% in a large de novo ALL patient cohort. We conclude that the enrichment of mutations in epigenetic regulators at relapse is consistent with a role in mediating therapy resistance

Iron bioavailability in two commercial cultivars of wheat: a comparison between wholegrain and white flour and the effects of nicotianamine and 2'-deoxymugineic acid on iron uptake into Caco-2 cells

Iron bioavailability in unleavened white and wholegrain bread made from two commercial wheat varieties was assessed by measuring ferritin production in Caco-2 cells. The breads were subjected to simulated gastrointestinal digestion and the digests applied to the Caco-2 cells. Although Riband grain contained a lower iron concentration than Rialto, iron bioavailability was higher. No iron was taken up by the cells from white bread made from Rialto flour or from wholegrain bread from either variety, but Riband white bread produced a small ferritin response. The results probably relate to differences in phytate content of the breads, although iron in soluble monoferric phytate was demonstrated to be bioavailable in the cell model. Nicotianamine, an iron chelator in plants involved in iron transport, was a more potent enhancer of iron uptake into Caco-2 cells than ascorbic acid or 2'-deoxymugineic acid, another metal chelator present in plants

The behaviour of political parties and MPs in the parliaments of the Weimar Republic

Copyright @ 2012 The Authors. This is the author's accepted manuscript. The final published article is available from the link below.Analysing the roll-call votes of the MPs of the Weimar Republic we find: (1) that party competition in the Weimar parliaments can be structured along two dimensions: an economic left–right and a pro-/anti-democratic. Remarkably, this is stable throughout the entire lifespan of the Republic and not just in the later years and despite the varying content of votes across the lifespan of the Republic, and (2) that nearly all parties were troubled by intra-party divisions, though, in particular, the national socialists and communists became homogeneous in the final years of the Republic.Zukunftskolleg, University of Konstan

Science and Ideology in Economic, Political, and Social Thought

This paper has two sources: One is my own research in three broad areas: business cycles, economic measurement and social choice. In all of these fields I attempted to apply the basic precepts of the scientific method as it is understood in the natural sciences. I found that my effort at using natural science methods in economics was met with little understanding and often considerable hostility. I found economics to be driven less by common sense and empirical evidence, then by various ideologies that exhibited either a political or a methodological bias, or both. This brings me to the second source: Several books have appeared recently that describe in historical terms the ideological forces that have shaped either the direct areas in which I worked, or a broader background. These books taught me that the ideological forces in the social sciences are even stronger than I imagined on the basis of my own experiences. The scientific method is the antipode to ideology. I feel that the scientific work that I have done on specific, long standing and fundamental problems in economics and political science have given me additional insights into the destructive role of ideology beyond the history of thought orientation of the works I will be discussing

The On-Orbit Performance of the Galaxy Evolution Explorer

We report the first year on-orbit performance results for the Galaxy Evolution Explorer (GALEX), a NASA Small Explorer that is performing a survey of the sky in two ultraviolet bands. The instrument comprises a 50 cm diameter modified Ritchey-Chretien telescope with a 1.25 degree field of view, selectable imaging and objective grism spectroscopic modes, and an innovative optical system with a thin-film multilayer dichroic beam splitter that enables simultaneous imaging by a pair of photon counting, microchannel plate, delay line readout detectors. Initial measurements demonstrate that GALEX is performing well, meeting its requirements for resolution, efficiency, astrometry, bandpass definition and survey sensitivity.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issu

DHODH modulates transcriptional elongation in the neural crest and melanoma

Melanoma is a tumour of transformed melanocytes, which are originally derived from the embryonic neural crest. It is unknown to what extent the programs that regulate neural crest development interact with mutations in the BRAF oncogene, which is the most commonly mutated gene in human melanoma1. We have used zebrafish embryos to identify the initiating transcriptional events that occur on activation of human BRAF(V600E) (which encodes an amino acid substitution mutant of BRAF) in the neural crest lineage. Zebrafish embryos that are transgenic for mitfa:BRAF(V600E) and lack p53 (also known as tp53) have a gene signature that is enriched for markers of multipotent neural crest cells, and neural crest progenitors from these embryos fail to terminally differentiate. To determine whether these early transcriptional events are important for melanoma pathogenesis, we performed a chemical genetic screen to identify small-molecule suppressors of the neural crest lineage, which were then tested for their effects on melanoma. One class of compound, inhibitors of dihydroorotate dehydrogenase (DHODH), for example leflunomide, led to an almost complete abrogation of neural crest development in zebrafish and to a reduction in the self-renewal of mammalian neural crest stem cells. Leflunomide exerts these effects by inhibiting the transcriptional elongation of genes that are required for neural crest development and melanoma growth. When used alone or in combination with a specific inhibitor of the BRAF(V600E) oncogene, DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies. Taken together, these studies highlight developmental pathways in neural crest cells that have a direct bearing on melanoma formation

Massive Stars In The W33 Giant Molecular Complex

Rich in H II regions, giant molecular clouds are natural laboratories to study massive stars and sequential star formation. The Galactic star-forming complex W33 is located at = ∼ ◦ l 12.8 and at a distance of 2.4 kpc and has a size of ≈10 pc and a total mass of ≈(0.8−8.0) × 105 M⊙. The integrated radio and IR luminosity of W33—when combined with the direct detection of methanol masers, the protostellar object W33A, and the protocluster embedded within the radio source W33 main—mark the region as a site of vigorous ongoing star formation. In order to assess the long-term star formation history, we performed an infrared spectroscopic search for massive stars, detecting for the first time 14 early-type stars, including one WN6 star and four O4–7 stars. The distribution of spectral types suggests that this population formed during the past ∼2–4 Myr, while the absence of red supergiants precludes extensive star formation at ages 6–30 Myr. This activity appears distributed throughout the region and does not appear to have yielded the dense stellar clusters that characterize other star-forming complexes such as Carina and G305. Instead, we anticipate that W33 will eventually evolve into a loose stellar aggregate, with Cyg OB2 serving as a useful, albeit richer and more massive, comparator. Given recent distance estimates, and despite a remarkably similar stellar population, the rich cluster Cl 1813–178 located on the northwest edge of W33 does not appear to be physically associated with W33

Acceptability of Carraguard Vaginal Microbicide Gel among HIV-Infected Women in Chiang Rai, Thailand

Background: Few studies of microbicide acceptability among HIV-infected women have been done. We assessed CarraguardH vaginal gel acceptability among participants in a randomized, controlled, crossover safety trial in HIV-infected women in Thailand. Methodology/Principal Findings: Participants used each of 3 treatments (Carraguard gel, methylcellulose placebo gel, and no product) for 7 days, were randomized to one of six treatment sequences, and were blinded to the type of gel they received in the two gel-use periods. After both gel-use periods, acceptability was assessed by face-to-face interview. Responses were compared to those of women participating in two previous Carraguard safety studies at the same study site. Sixty women enrolled with a median age of 34 years; 25 % were sexually active. Self-reported adherence (98%) and overall satisfaction rating of the gels (87% liked ‘‘somewhat’ ’ or ‘‘very much’’) were high, and most (77%) considered the volume of gel ‘‘just right.’ ’ For most characteristics, crossover trial participants evaluated the gels more favorably than women in the other two trials, but there were few differences in the desired characteristics of a hypothetical microbicide. Almost half (48%) of crossover trial participants noticed a difference between Carraguard and placebo gels; 33 % preferred Carraguard while 12 % preferred placebo (p=0.01). Conclusions/Significance: Daily Carraguard vaginal gel use was highly acceptable in this population of HIV-infecte