Observation of an Exotic Insulator to Insulator Transition upon Electron Doping the Mott Insulator CeMnAsO

Acknowledgements This research was supported by EPSRC (Grant no. EP/L002493/1 (A.C.M.)), The Carnegie Trust for the Universities of Scotland (PhD scholarship for S.S. (S.S.)) and the ILL (PhD studentship for G.B.L. (A.C.M.)). By the membership of the UK's HEC Materials Chemistry Consortium, which is funded by EPSRC (EP/L000202 (A.W.)), this work used the ARCHER2 UK National Supercomputing Service (http://www.archer2.ac.uk). We also acknowledge STFC-GB for provision of beamtime at the ILL.Peer reviewe

A New 626 s Periodic X-ray Source in the Direction of the Galactic Center

Here we report the detection of a 626 s periodic modulation from the X-ray source 2XMM J174016.0-290337 located in the direction of the Galactic center. We present temporal and spectral analyses of archival XMM-Newton data and photometry of archived near-infrared data in order to investigate the nature of this source. We find that the X-ray light curve shows a strong modulation at 626 +/- 2 s with a confidence level > 99.9% and a pulsed fraction of 54%. Spectral fitting demonstrates that the spectrum is consistent with an absorbed power law. No significant spectral variability was observed over the 626 s period. We have investigated the possibility that the 626 s period is orbital in nature (either that of an ultra-compact X-ray binary or an AM CVn) or related to the spin of a compact object (either an accretion powered pulsar or an intermediate polar). The X-ray properties of the source and the photometry of the candidate near-infrared counterparts are consistent with an accreting neutron star X-ray binary on the near-side of the Galactic bulge, where the 626 s period is most likely indicative of the pulsar spin period. However, we cannot rule out an ultra-compact X-ray binary or an intermediate polar with the data at hand. In the former case, if the 626 s modulation is the orbital period of an X-ray binary, it would be the shortest period system known. In the latter case, the modulation would be the spin period of a magnetic white dwarf. However, we find no evidence for absorption dips over the 626 s period, a low temperature black body spectral component, or Fe Kalpha emission lines. These features are commonly observed in intermediate polars, making 2XMM J174016.0-290337 a rather unusual member of this class if confirmed. We instead suggest that 2XMM J174016.0-290337 could be a new addition to the emerging class of symbiotic X-ray binaries.Comment: 11 pages, 10 figures, submitted to A&A on 18th January 2010, accepted for publication 20th August 201

Effect of Midtreatment PET/CT-Adapted Radiation Therapy With Concurrent Chemotherapy in Patients With Locally Advanced Non–Small-Cell Lung Cancer

IMPORTANCE Our previous studies demonstrated that tumors significantly decrease in size and metabolic activity after delivery of 45 Gy of fractionated radiatiotherapy (RT), and that metabolic shrinkage is greater than anatomic shrinkage. This study aimed to determine whether 18F-fludeoxyglucose–positron emission tomography/computed tomography (FDG-PET/CT) acquired during the course of treatment provides an opportunity to deliver higher-dose radiation to the more aggressive areas of the tumor to improve local tumor control without increasing RT-induced lung toxicity (RILT), and possibly improve survival. OBJECTIVE To determine whether adaptive RT can target high-dose radiation to the FDG-avid tumor on midtreatment FDG-PET to improve local tumor control of locally advanced non–small-cell lung cancer (NSCLC). DESIGN, SETTING, AND PARTICIPANTS A phase 2 clinical trial conducted at 2 academic medical centers with 42 patients who had inoperable or unresectable stage II to stage III NSCLC enrolled from November 2008, to May 2012. Patients with poor performance, more than 10% weight loss, poor lung function, and/or oxygen dependence were included, providing that the patients could tolerate the procedures of PET scanning and RT. INTERVENTION Conformal RT was individualized to a fixed risk of RILT (grade >2) and adaptively escalated to the residual tumor defined on midtreatment FDG-PET up to a total dose of 86 Gy in 30 daily fractions. Medically fit patients received concurrent weekly carboplatin plus paclitaxel followed by 3 cycles of consolidation. MAIN OUTCOMES AND MEASURES The primary end point was local tumor control. The trial was designed to achieve a 20% improvement in 2-year control from 34% of our prior clinical trial experience with 63 to 69 Gy in a similar patient population. RESULTS The trial reached its accrual goal of 42 patients: median age, 63 years (range, 45–83 years); male, 28 (67%); smoker or former smoker, 39 (93%); stage III, 38 (90%). Median tumor dose delivered was 83 Gy (range, 63–86 Gy) in 30 daily fractions. Median follow-up for surviving patients was 47 months. The 2-year rates of infield and overall local regional tumor controls (ie, including isolated nodal failure) were 82% (95% CI, 62%–92%) and 62% (95% CI, 43%–77%), respectively. Median overall survival was 25 months (95% CI, 12–32 months). The 2-year and 5-year overall survival rates were 52% (95% CI, 36%–66%) and 30% (95% CI, 16%–45%), respectively. CONCLUSIONS AND RELEVANCE Adapting RT-escalated radiation dose to the FDG-avid tumor detected by midtreatment PET provided a favorable local-regional tumor control. The RTOG 1106 trial is an ongoing clinical trial to validate this finding in a randomized fashion. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT0119052

The Cyst Nematode SPRYSEC Protein RBP-1 Elicits Gpa2- and RanGAP2-Dependent Plant Cell Death

Plant NB-LRR proteins confer robust protection against microbes and metazoan parasites by recognizing pathogen-derived avirulence (Avr) proteins that are delivered to the host cytoplasm. Microbial Avr proteins usually function as virulence factors in compatible interactions; however, little is known about the types of metazoan proteins recognized by NB-LRR proteins and their relationship with virulence. In this report, we demonstrate that the secreted protein RBP-1 from the potato cyst nematode Globodera pallida elicits defense responses, including cell death typical of a hypersensitive response (HR), through the NB-LRR protein Gpa2. Gp-Rbp-1 variants from G. pallida populations both virulent and avirulent to Gpa2 demonstrated a high degree of polymorphism, with positive selection detected at numerous sites. All Gp-RBP-1 protein variants from an avirulent population were recognized by Gpa2, whereas virulent populations possessed Gp-RBP-1 protein variants both recognized and non-recognized by Gpa2. Recognition of Gp-RBP-1 by Gpa2 correlated to a single amino acid polymorphism at position 187 in the Gp-RBP-1 SPRY domain. Gp-RBP-1 expressed from Potato virus X elicited Gpa2-mediated defenses that required Ran GTPase-activating protein 2 (RanGAP2), a protein known to interact with the Gpa2 N terminus. Tethering RanGAP2 and Gp-RBP-1 variants via fusion proteins resulted in an enhancement of Gpa2-mediated responses. However, activation of Gpa2 was still dependent on the recognition specificity conferred by amino acid 187 and the Gpa2 LRR domain. These results suggest a two-tiered process wherein RanGAP2 mediates an initial interaction with pathogen-delivered Gp-RBP-1 proteins but where the Gpa2 LRR determines which of these interactions will be productive

Mainstreams of Horizontal Gene Exchange in Enterobacteria: Consideration of the Outbreak of Enterohemorrhagic E. coli O104:H4 in Germany in 2011

Escherichia coli O104:H4 caused a severe outbreak in Europe in 2011. The strain TY-2482 sequenced from this outbreak allowed the discovery of its closest relatives but failed to resolve ways in which it originated and evolved. On account of the previous statement, may we expect similar upcoming outbreaks to occur recurrently or spontaneously in the future? The inability to answer these questions shows limitations of the current comparative and evolutionary genomics methods.status: publishe

Prolonged diet-induced obesity in mice modifies the inflammatory response and leads to worse outcome after stroke

BACKGROUND: Obesity increases the risk for ischaemic stroke and is associated with worse outcome clinically and experimentally. Most experimental studies have used genetic models of obesity. Here, a more clinically relevant model, diet-induced obesity, was used to study the impact of obesity over time on the outcome and inflammatory response after stroke. METHODS: Male C57BL/6 mice were maintained on a high-fat (60% fat) or control (12% fat) diet for 2, 3, 4 and 6 months when experimental stroke was induced by transient occlusion of the middle cerebral artery (MCAo) for either 20 (6-month diet) or 30 min (2-, 3-, 4- and 6-month diet). Ischaemic damage, blood-brain barrier (BBB) integrity, neutrophil number and chemokine expression in the brain were assessed at 24 h. Plasma chemokine levels (at 4 and 24 h) and neutrophil number in the liver (at 24 h) were measured. Physiological parameters (body weight and blood glucose) were measured in naïve control- and high-fat-fed mice at all time points and blood pressure at 3 and 6 months. Blood cell counts were also assessed in naïve 6-month control- and high-fat-fed mice. RESULTS: Mice fed a high-fat diet for 6 months had greater body weight, blood glucose and white and red blood cell count but no change in systolic blood pressure. After 4 and 6 months of high-fat feeding, and in the latter group with a 30-min (but not 20-min) occlusion of the MCA, obese mice had greater ischaemic brain damage. An increase in blood-brain barrier permeability, chemokine expression (CXCL-1 and CCL3), neutrophil number and microglia/macrophage cells was observed in the brains of 6-month high-fat-fed mice after 30-min MCAo. In response to stroke, chemokine (CXCL-1) expression in the plasma and liver was significantly different in obese mice (6-month high-fat fed), and a greater number of neutrophils were detected in the liver of control but not obese mice. CONCLUSIONS: The detrimental effects of diet-induced obesity on stroke were therefore dependent on the severity of obesity and length of ischaemic challenge. The altered inflammatory response in obese mice may play a key role in its negative impact on stroke

Extrinsic Rewards and Intrinsic Motives: Standard and Behavioral Approaches to Agency and Labor Markets

Employers structure pay and employment relationships to mitigate agency problems. A large literature in economics documents how the resolution of these problems shapes personnel policies and labor markets. For the most part, the study of agency in employment relationships relies on highly stylized assumptions regarding human motivation, e.g., that employees seek to earn as much money as possible with minimal effort. In this essay, we explore the consequences of introducing behavioral complexity and realism into models of agency within organizations. Specifically, we assess the insights gained by allowing employees to be guided by such motivations as the desire to compare favorably to others, the aspiration to contribute to intrinsically worthwhile goals, and the inclination to reciprocate generosity or exact retribution for perceived wrongs. More provocatively, from the standpoint of standard economics, we also consider the possibility that people are driven, in ways that may be opaque even to themselves, by the desire to earn social esteem or to shape and reinforce identity

A genome-wide genetic map of NB-LRR disease resistance loci in potato

Like all plants, potato has evolved a surveillance system consisting of a large array of genes encoding for immune receptors that confer resistance to pathogens and pests. The majority of these so-called resistance or R proteins belong to the super-family that harbour a nucleotide binding and a leucine-rich-repeat domain (NB-LRR). Here, sequence information of the conserved NB domain was used to investigate the genome-wide genetic distribution of the NB-LRR resistance gene loci in potato. We analysed the sequences of 288 unique BAC clones selected using filter hybridisation screening of a BAC library of the diploid potato clone RH89-039-16 (S. tuberosum ssp. tuberosum) and a physical map of this BAC library. This resulted in the identification of 738 partial and full-length NB-LRR sequences. Based on homology of these sequences with known resistance genes, 280 and 448 sequences were classified as TIR-NB-LRR (TNL) and CC-NB-LRR (CNL) sequences, respectively. Genetic mapping revealed the presence of 15 TNL and 32 CNL loci. Thirty-six are novel, while three TNL loci and eight CNL loci are syntenic with previously identified functional resistance genes. The genetic map was complemented with 68 universal CAPS markers and 82 disease resistance trait loci described in literature, providing an excellent template for genetic studies and applied research in potato

Environmental and Molecular Mutagenesis Meeting Report Assessing Human Germ-Cell Mutagenesis in the Post-Genome Era: A Celebration of the Legacy of William Lawson (Bill) Russell

ABSTRACT Although numerous germ-cell mutagens have been identified in animal model systems, to date, no human germ-cell mutagens have been confirmed. Because the genomic integrity of our germ cells is essential for the continuation of the human species, a resolution of this enduring conundrum is needed. To facilitate such a resolution, we organized a workshop at The Jackson Laboratory in Bar Harbor, Maine on September [28][29][30] 2004. This interactive workshop brought together scientists from a wide range of disciplines to assess the applicability of emerging molecular methods for genomic analysis to the field of human germ-cell mutagenesis. Participants recommended that focused, coordinated human germ-cell mutation studies be conducted in relation to important societal exposures. Because cancer survivors represent a unique cohort with well-defined exposures, there was a consensus that studies should be designed to assess the mutational impact on children born to parents who had received certain types of mutagenic cancer chemotherapy prior to conceiving their children. Within this high-risk cohort, parents and children could be evaluated for inherited changes in (a) gene sequences and chromosomal structure, (b) repeat sequences and minisatellite regions, and (c) global gene expression and chromatin. Participants also recommended studies to examine trans-generational effects in humans involving mechanisms such as changes in imprinting and methylation patterns, expansion of nucleotide repeats, or induction of mitochondrial DNA mutations. Workshop participants advocated establishment of a bio-bank of human tissue samples that could be used to conduct a multiple-endpoint, comprehensive, and collaborative effort to detect exposure-induced heritable alterations in the human genome. Appropriate animal models of human germ-cell mutagenesis should be used in parallel with human studies to provide insights into the mechanisms of mammalian germ-cell mutagenesis. Finally, participants recommended that 4 scientific specialty groups be convened to address specific questions regarding the potential germ-cell mutagenicity of environmental, occupational, and lifestyle exposures. Strong support from relevant funding agencies and engagement of scientists outside the fields of genomics and germ-cell mutagenesis will be required to launch a full-scale assault on some of the most pressing and enduring questions in environmental mutagenesis: Do human germ-cell mutagens exist, what risk do they pose to future generations, and are some parents at higher risk than others for acquiring and transmitting germ-cell mutations?