The dependence of dijet production on photon virtuality in ep collisions at HERA

The dependence of dijet production on the virtuality of the exchanged photon, Q^2, has been studied by measuring dijet cross sections in the range 0 < Q^2 < 2000 GeV^2 with the ZEUS detector at HERA using an integrated luminosity of 38.6 pb^-1. Dijet cross sections were measured for jets with transverse energy E_T^jet > 7.5 and 6.5 GeV and pseudorapidities in the photon-proton centre-of-mass frame in the range -3 < eta^jet <0. The variable xg^obs, a measure of the photon momentum entering the hard process, was used to enhance the sensitivity of the measurement to the photon structure. The Q^2 dependence of the ratio of low- to high-xg^obs events was measured. Next-to-leading-order QCD predictions were found to generally underestimate the low-xg^obs contribution relative to that at high xg^obs. Monte Carlo models based on leading-logarithmic parton-showers, using a partonic structure for the photon which falls smoothly with increasing Q^2, provide a qualitative description of the data.Comment: 35 pages, 6 eps figures, submitted to Eur.Phys.J.

Beauty photoproduction measured using decays into muons in dijet events in ep collisions at s\sqrt{s}=318 GeV

The photoproduction of beauty quarks in events with two jets and a muon has been measured with the ZEUS detector at HERA using an integrated luminosity of 110 pb$^{- 1}$. The fraction of jets containing b quarks was extracted from the transverse momentum distribution of the muon relative to the closest jet. Differential cross sections for beauty production as a function of the transverse momentum and pseudorapidity of the muon, of the associated jet and of $x_{\gamma}^{jets}$, the fraction of the photon's momentum participating in the hard process, are compared with MC models and QCD predictions made at next-to-leading order. The latter give a good description of the data.Comment: 32 pages, 6 tables, 7 figures Table 6 and Figure 7 revised September 200

Analysis of the EIAV Rev-Responsive Element (RRE) Reveals a Conserved RNA Motif Required for High Affinity Rev Binding in Both HIV-1 and EIAV

A cis-acting RNA regulatory element, the Rev-responsive element (RRE), has essential roles in replication of lentiviruses, including human immunodeficiency virus (HIV-1) and equine infection anemia virus (EIAV). The RRE binds the viral trans-acting regulatory protein, Rev, to mediate nucleocytoplasmic transport of incompletely spliced mRNAs encoding viral structural genes and genomic RNA. Because of its potential as a clinical target, RRE-Rev interactions have been well studied in HIV-1; however, detailed molecular structures of Rev-RRE complexes in other lentiviruses are still lacking. In this study, we investigate the secondary structure of the EIAV RRE and interrogate regulatory protein-RNA interactions in EIAV Rev-RRE complexes. Computational prediction and detailed chemical probing and footprinting experiments were used to determine the RNA secondary structure of EIAV RRE-1, a 555 nt region that provides RRE function in vivo. Chemical probing experiments confirmed the presence of several predicted loop and stem-loop structures, which are conserved among 140 EIAV sequence variants. Footprinting experiments revealed that Rev binding induces significant structural rearrangement in two conserved domains characterized by stable stem-loop structures. Rev binding region-1 (RBR-1) corresponds to a genetically-defined Rev binding region that overlaps exon 1 of the EIAV rev gene and contains an exonic splicing enhancer (ESE). RBR-2, characterized for the first time in this study, is required for high affinity binding of EIAV Rev to the RRE. RBR-2 contains an RNA structural motif that is also found within the high affinity Rev binding site in HIV-1 (stem-loop IIB), and within or near mapped RRE regions of four additional lentiviruses. The powerful integration of computational and experimental approaches in this study has generated a validated RNA secondary structure for the EIAV RRE and provided provocative evidence that high affinity Rev binding sites of HIV-1 and EIAV share a conserved RNA structural motif. The presence of this motif in phylogenetically divergent lentiviruses suggests that it may play a role in highly conserved interactions that could be targeted in novel anti-lentiviral therapies

Search for Resonance Decays to Lepton+jet at DESY HERA and Limits on Leptoquarks

A search for narrow-width resonances that decay into electron+jet or neutrino+jet has been performed with the ZEUS detector at the DESY ep collider HERA operating at center-of-mass energies of 300 and 318 GeV. An integrated e+p luminosity of 114.8 pb-1 and e-p luminosity of 16.7 pb-1 were used. No evidence for any resonance was found. Limits were derived on the Yukawa coupling λ as a function of the mass of a hypothetical resonance that has arbitrary decay branching ratios into eq or vq. These limits also apply to squarks predicted by R-parity-violating supersymmetry. Limits for the production of leptoquarks described by the Buchmüller-Rückl-Wyler model were also derived for masses up to 400 GeV. For λ = 0.1, leptoquark masses up to 290 GeV are excluded

Can large scintillators be used for solar-axion searches to test the cosmological axion-photon oscillation proposal?

Solar-axion interaction rates in NaI, CsI and Xe scintillators via the axio-electric effect were calculated. A table is presented with photoelectric and axioelectric cross sections, solar-axion fluxes, and the interaction rates from 2.0 to 10.0 keV. The results imply that annual-modulation data of large NaI and CsI arrays, and large Xe scintillation chambers, might be made sensitive enough to probe coupling to photons at levels required to explain axion-photon oscillation phenomena proposed to explain the survival of high-energy photons traveling cosmological distances. The DAMAA/LIBRA data are used to demonstrate the power of the model-independent annual modulation due to the seasonal variation in the earth sun distance.Comment: 7 pages and no figure

Measurement of Proton-dissociative Diffractive Photoproduction of Vector Mesons at Large Momentum Transfer at HERA: The ZEUS Collaboration

Diffractive photoproduction of vector mesons, γp → VY, where Y is a proton-dissociative system, has been measured in e+p interactions with the ZEUS detector at HERA using an integrated luminosity of 25 pb-1. The differential cross section, dσ/dt, is presented for 1.2 \u3c -t \u3c 12 GeV2, where t is the square of the four-momentum transferred to the vector meson. The data span the range in photon-proton centre-of-mass energy, W, from 80 GeV to 120 GeV. The t distributions are well fit by a power law, dσ/dt ∝ (-t)-n. The slope of the effective Pomeron trajectory, measured from the W dependence of the ρ0 and φ cross sections in bins of t, is consistent with zero. The ratios dσγp→φY/dt to dσγp→ρ0Y/dt and dσγp→J/ψY/dt to dσγp→ρ0Y/dt increase with increasing -t. Decay-angle analyses for ρ0, φ and J/ψ mesons have been carried out. For the ρ0 and φ mesons, contributions from single and double helicity flip are observed. The results are compared to expectations of theoretical models

Discovery and Functional Implications of a Novel Mir-29b/Mir-29a Polymorphism in Acute Myeloid Leukemia.

Abstract Abstract 1975 Poster Board I-998 Background: MicroRNAs (miRNAs) are associated with cytogenetics and molecular subtypes of acute myelogeneous leukemia (AML). We have previously shown that miR-29 expression is down-regulated in cytogenetically normal AML (CN-AML) with wild type NPM1 and in t(11q23) primary blasts. Functionally, restoration of miR-29b in AML cell lines and primary samples induces apoptosis and dramatically reduces tumorigenicity in a xenograft leukemia model (Garzon et al, EHA 2008). Despite, these studies supporting a tumor suppressor role of miR-29b in AML, little is known about how miR-29 expression is down-regulated in AML. Since, miRNAs could be target for mutation, here we propose to screen mutations that could affect miR-29 expression and function. Methods: The miR-29 family is comprised of three isoforms arranged in 2 clusters; miR-29b-1 and -a located on chromosome 7q32 and miR-29b-2 and -c located on chromosome 1q23. To screen for mutations, the entire genomic region from blasts of 100 primary AML samples corresponding to the miR-29b-1 and -a cluster, including 200 bp at the 5' and 3' ends was amplified and sequenced using the Applied Biosystems DNA sequencing system. When a deviation from the normal sequence was found, a panel of DNA from the blood of 50 control subjects was screened to identify polymorphisms. Patient characteristics include: CN-AML: 62 (FLT3-ITD 10/43, NPM1 mutated (34/62); inv16: 10; t(8;21): 2; t11q23: 2; complex karyotype (CK): 10; monosomy 7(-7): 7; other cytogenetics: 7. miR-29 expression we performed by miRNA Taqman assays as per manufacturer recommendations. Results: We identified a thymidine (T) base deletion within the miR-29b-1 and -a cluster precursor miRNAs (at -264 bp from the 5' position of miR-29a in chromosome 7q32) in 17/100 patients. The (T) base deletion was observed in 4/10 inv16 and 6/62 CN-AML patients, while the other 7 cases were distributed among CK (2/10), -7 (3/7), 11q23 (1/2) and other cytogenetics (1/7). In 2 patients, normal cells from the buccal mucosa were heterozygous for this abnormality. The frequency of this germline abnormality in the normal population was 16% (8/50 cases). Next, we investigated the miR-29b and -a expression in 35/100 primary AML samples, where RNA was also available. Although miR-29a and -b levels were not significantly different in polymorphism (n=10) versus wild type (WT) (n=35) samples, we observed that the miR-29a/miR-29b ratios were significantly lower in the polymorphism than WT (43.5 vs. 24.9 respectively, P-value=0.007, t-test). To characterize further this abnormality, we cloned the polymorphism harboring miR-29b and -a cluster from 1 patient into p-Retro Super plasmid and transfected into K562 cells (lack miR-29 expression) along with WT and empty vector constructs. Northern blotting after 24-48 hours revealed an accumulation of the precursor miR-29a while the mature miR-29a level was decreased by 2 fold. The level of the mature miR-29b was unchanged. To asses whether this polymorphism affects miR-29 targeting efficiency, we co-transfected a reporter luciferase construct containing the 3' untranslated region of the known miR-29 target, MCL-1 with the WT, empty vector and polymorphism harboring miR-29b and -a cluster and performed luciferase assays. Interestingly, relative normalized luciferase activities were less inhibited with the polymorphism cluster than the WT construct (relative reduction WT:80%, Polym:63%. Likewise, MCL-1 protein down-regulation elicited by the ectopic WT cluster overexpression was stronger than the one observed for the polymorphism harboring cluster (b-actin/MCL-1 rations 0.35 vs 0.48, respectively). Conclusions: Our results identify a novel germline polymorphism within the miR-29b and —a cluster in AML. The frequency of this polymorphism in AML is similar to the normal population. However, the increased frequency observed in the inv16 subgroup (4/10) warrant further confirmation in a large cohort of patients. Functionally, this polymorphism affects the expression ratio of miR-29b and —a by dampening the processing of miR-29a and impacts negatively in the ability of this cluster to target the oncogene MCL-1. Disclosures: No relevant conflicts of interest to declare. </jats:sec

Circulating leukocyte telomere length and risk of overall and aggressive prostate cancer

BACKGROUND: Recent large-scale prospective studies suggest that long telomeres are associated with an increase cancer risk, counter to conventional wisdom. METHODS: To further clarify the association between leukocyte telomere length (LTL) and prostate cancer, and assess genetic variability in relation to both LTL and prostate cancer, we performed a nested case-control study (922 cases and 935 controls). The participants provided blood in 1993-1995 and were followed through August 2004 (prostate cancer incidence) or until 28 February 2013 (lethal or fatal prostate cancer). Relative LTL was measured by quantitative PCR and was calculated as the ratio of telomere repeat copy number to a single gene (36B4) copy number (T/S). Genotyping was performed using the TaqMan OpenArray SNP Genotyping Platform. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of all prostate cancer and subtypes defined by Gleason grade, stage and lethality (metastasis or death). RESULTS: We observed a positive association between each s.d. increase in LTL and all (multivariable-adjusted OR 1.11, 95% CI: 1.01-1.22), low-grade (OR 1.13, 95% CI:1.01-1.27), and localised (OR 1.12, 95% CI:1.01-1.24) prostate cancer. Associations for other subtypes were similar, but did not reach statistical significance. In subgroup analyses, associations for high grade and advanced stage (OR=2.04, 95% CI 1.00-4.17; Pinteraction=0.06) or lethal disease (OR=2.37, 95% CI 1.19-4.72; Pinteraction=0.01) were stronger in men with a family history of the disease compared with those without. The minor allele of SNP, rs7726159, which has previously been shown to be positively associated with LTL, showed an inverse association with all prostate cancer risk after correction for multiple testing (P=0.0005). CONCLUSION: In this prospective study, longer LTL was modestly associated with higher risk of prostate cancer. A stronger association for more aggressive cancer in men with a family history of the disease needs to be confirmed in larger studies