571 research outputs found
The Presampler for the Forward and Rear Calorimeter in the ZEUS Detector
The ZEUS detector at HERA has been supplemented with a presampler detector in
front of the forward and rear calorimeters. It consists of a segmented
scintillator array read out with wavelength-shifting fibers. We discuss its
desi gn, construction and performance. Test beam data obtained with a prototype
presampler and the ZEUS prototype calorimeter demonstrate the main function of
this detector, i.e. the correction for the energy lost by an electron
interacting in inactive material in front of the calorimeter.Comment: 20 pages including 16 figure
The quest for companions to post-common envelope binaries: I. Searching a sample of stars from the CSS and SDSS
As part of an ongoing collaboration between student groups at high schools
and professional astronomers, we have searched for the presence of
circum-binary planets in a bona-fide unbiased sample of twelve post-common
envelope binaries (PCEBs) from the Catalina Sky Survey (CSS) and the Sloan
Digital Sky Survey (SDSS). Although the present ephemerides are significantly
more accurate than previous ones, we find no clear evidence for orbital period
variations between 2005 and 2011 or during the 2011 observing season. The
sparse long-term coverage still permits O-C variations with a period of years
and an amplitude of tens of seconds, as found in other systems. Our
observations provide the basis for future inferences about the frequency with
which planet-sized or brown-dwarf companions have either formed in these
evolved systems or survived the common envelope (CE) phase.Comment: accepted by A&
KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia
High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P<0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone
Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease
BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks). RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO. CONCLUSIONS: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract
IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia
IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial deletions (53%). The latter included COBL-r, which were found in 12% of the IKZF1 ∆1-8 cohort. Patients with COBL-r are mostly classified as intermediate cytogenetic risk and frequently harbor ETV6, PAX5, CDKN2A/B deletions. Overall, 56% of breakpoints were located within COBL intron 5. Cryptic recombination signal sequence motifs were broadly distributed within the sequence of COBL, and no enrichment for the breakpoint cluster region was found. In summary, a diverse spectrum of alterations characterizes ΔIKZF1 and they also include deletion breakpoints within COBL. We confirmed that COBL is a hotspot associated with ΔIKZF1, but these rearrangements are not driven by RAG-mediated recombination
Top-down contingent feature-specific orienting with and without awareness of the visual input
In the present article, the role of endogenous feature-specific orienting for
conscious and unconscious vision is reviewed. We start with an overview of
orienting. We proceed with a review of masking research, and the definition of
the criteria of experimental protocols that demonstrate endogenous and exogenous
orienting, respectively. Against this background of criteria, we assess studies
of unconscious orienting and come to the conclusion that so far studies of
unconscious orienting demonstrated endogenous feature-specific orienting. The
review closes with a discussion of the role of unconscious orienting in action
control
Stimulus set size modulates the sex–emotion interaction in face categorization
Previous research has shown that invariant facial features—for example, sex—and variant facial features—for example, emotional expressions—interact during face categorization. The nature of this interaction is a matter of dispute, however, and has been reported as either asymmetrical, such that sex cues influence emotion perception but emotional expressions do not affect the perception of sex, or symmetrical, such that sex and emotion cues each reciprocally influence the categorization of the other. In the present research, we identified stimulus set size as the critical factor leading to this disparity. Using faces drawn from different databases, in two separate experiments we replicated the finding of a symmetrical interaction between face sex and emotional expression when larger sets of posers were used. Using a subset of four posers, in the same setups, however, did not provide evidence for a symmetrical interaction, which is also consistent with prior research. This pattern of results suggests that different strategies may be used to categorize aspects of faces that are encountered repeatedly
Measurement of Jet Shapes in Photoproduction at HERA
The shape of jets produced in quasi-real photon-proton collisions at
centre-of-mass energies in the range GeV has been measured using the
hadronic energy flow. The measurement was done with the ZEUS detector at HERA.
Jets are identified using a cone algorithm in the plane with a
cone radius of one unit. Measured jet shapes both in inclusive jet and dijet
production with transverse energies GeV are presented. The jet
shape broadens as the jet pseudorapidity () increases and narrows
as increases. In dijet photoproduction, the jet shapes have been
measured separately for samples dominated by resolved and by direct processes.
Leading-logarithm parton-shower Monte Carlo calculations of resolved and direct
processes describe well the measured jet shapes except for the inclusive
production of jets with high and low . The observed
broadening of the jet shape as increases is consistent with the
predicted increase in the fraction of final state gluon jets.Comment: 29 pages including 9 figure
- …