The mQTL hotspot on linkage group 16 for phenolic compounds in apple fruits is probably the result of a leucoanthocyanidin reductase gene at that locus

BACKGROUND: Our previous study on ripe apples from a progeny of a cross between the apple cultivars 'Prima' and 'Fiesta' showed a hotspot of mQTLs for phenolic compounds at the top of LG16, both in peel and in flesh tissues. In order to find the underlying gene(s) of this mQTL hotspot, we investigated the expression profiles of structural and putative transcription factor genes of the phenylpropanoid and flavonoid pathways during different stages of fruit development in progeny genotypes. RESULTS: Only the structural gene leucoanthocyanidin reductase (MdLAR1) showed a significant correlation between transcript abundance and content of metabolites that mapped on the mQTL hotspot. This gene is located on LG16 in the mQTL hotspot. Progeny that had inherited one or two copies of the dominant MdLAR1 alleles (Mm, MM) showed a 4.4- and 11.8-fold higher expression level of MdLAR1 respectively, compared to the progeny that had inherited the recessive alleles (mm). This higher expression was associated with a four-fold increase of procyanidin dimer II as one representative metabolite that mapped in the mQTL hotspot. Although expression level of several structural genes were correlated with expression of other structural genes and with some MYB and bHLH transcription factor genes, only expression of MdLAR1 was correlated with metabolites that mapped at the mQTL hotspot.MdLAR1 is the only candidate gene that can explain the mQTL for procyanidins and flavan-3-ols. However, mQTLs for other phenylpropanoids such as phenolic esters, dihydrochalcones and flavonols, that appear to map at the same locus, have so far not been considered to be dependent on LAR, as their biosynthesis does not involve LAR activity. An explanation for this phenomenon is discussed. CONCLUSIONS: Transcript abundances and genomic positions indicate that the mQTL hotspot for phenolic compounds at the top of LG16 is controlled by the MdLAR1 gene. The dominant allele of the MdLAR1 gene, causing increased content of metabolites that are potentially health beneficial, could be used in marker assisted selection of current apple breeding programs and for cisgenesi

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Structure–activity relationships of low molecular weight alginate oligosaccharide therapy against Pseudomonas aeruginosa

Low molecular weight alginate oligosaccharides have been shown to exhibit anti-microbial activity against a range of multi-drug resistant bacteria, including Pseudomonas aeruginosa. Previous studies suggested that the disruption of calcium (Ca2+)–DNA binding within bacterial biofilms and dysregulation of quorum sensing (QS) were key factors in these observed effects. To further investigate the contribution of Ca2+ binding, G-block (OligoG) and M-block alginate oligosaccharides (OligoM) with comparable average size DPn 19 but contrasting Ca2+ binding properties were prepared. Fourier-transform infrared spectroscopy demonstrated prolonged binding of alginate oligosaccharides to the pseudomonal cell membrane even after hydrodynamic shear treatment. Molecular dynamics simulations and isothermal titration calorimetry revealed that OligoG exhibited stronger interactions with bacterial LPS than OligoM, although this difference was not mirrored by differential reductions in bacterial growth. While confocal laser scanning microscopy showed that both agents demonstrated similar dose-dependent reductions in biofilm formation, OligoG exhibited a stronger QS inhibitory effect and increased potentiation of the antibiotic azithromycin in minimum inhibitory concentration and biofilm assays. This study demonstrates that the anti-microbial effects of alginate oligosaccharides are not purely influenced by Ca2+-dependent processes but also by electrostatic interactions that are common to both G-block and M-block structures

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters

Wholesale pricing in a small open economy

This paper addresses the empirical analysis of wholesale profit margins using data of the Dutch wholesale sector, 1986. At the heart of the analysis is the typical nature of wholesale production: wholesalers do not produce a tangible product, but offer a service capacity. This has an immediate impact on the identification, interprelation and measurement of determinants of profit variations. A model is set up to explain variations in wholesale profit margins, which is inspired by two widely applied approaches to industry pricing: the behavioural mark-up model and the marginalist price-cost model

The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Worldwide, both the incidence and death rates of pancreatic cancer are increasing. Evaluation of pancreatic cancer burden and its global, regional, and national patterns is crucial to policy making and better resource allocation for controlling pancreatic cancer risk factors, developing early detection methods, and providing faster and more effective treatments. Methods: Vital registration, vital registration sample, and cancer registry data were used to generate mortality, incidence, and disability-adjusted life-years (DALYs) estimates. We used the comparative risk assessment framework to estimate the proportion of deaths attributable to risk factors for pancreatic cancer: smoking, high fasting plasma glucose, and high body-mass index. All of the estimates were reported as counts and age-standardised rates per 100 000 person-years. 95% uncertainty intervals (UIs) were reported for all estimates. Findings: In 2017, there were 448 000 (95% UI 439 000\u2013456 000) incident cases of pancreatic cancer globally, of which 232 000 (210 000\u2013221 000; 51\ub79%) were in males. The age-standardised incidence rate was 5\ub70 (4\ub79\u20135\ub71) per 100 000 person-years in 1990 and increased to 5\ub77 (5\ub76\u20135\ub78) per 100 000 person-years in 2017. There was a 2\ub73 times increase in number of deaths for both sexes from 196 000 (193 000\u2013200 000) in 1990 to 441 000 (433 000\u2013449 000) in 2017. There was a 2\ub71 times increase in DALYs due to pancreatic cancer, increasing from 4\ub74 million (4\ub73\u20134\ub75) in 1990 to 9\ub71 million (8\ub79\u20139\ub73) in 2017. The age-standardised death rate of pancreatic cancer was highest in the high-income super-region across all years from 1990 to 2017. In 2017, the highest age-standardised death rates were observed in Greenland (17\ub74 [15\ub78\u201319\ub70] per 100 000 person-years) and Uruguay (12\ub71 [10\ub79\u201313\ub75] per 100 000 person-years). These countries also had the highest age-standardised death rates in 1990. Bangladesh (1\ub79 [1\ub75\u20132\ub73] per 100 000 person-years) had the lowest rate in 2017, and S\ue3o Tom\ue9 and Pr\uedncipe (1\ub73 [1\ub71\u20131\ub75] per 100 000 person-years) had the lowest rate in 1990. The numbers of incident cases and deaths peaked at the ages of 65\u201369 years for males and at 75\u201379 years for females. Age-standardised pancreatic cancer deaths worldwide were primarily attributable to smoking (21\ub71% [18\ub78\u201323\ub77]), high fasting plasma glucose (8\ub79% [2\ub71\u201319\ub74]), and high body-mass index (6\ub72% [2\ub75\u201311\ub74]) in 2017. Interpretation: Globally, the number of deaths, incident cases, and DALYs caused by pancreatic cancer has more than doubled from 1990 to 2017. The increase in incidence of pancreatic cancer is likely to continue as the population ages. Prevention strategies should focus on modifiable risk factors. Development of screening programmes for early detection and more effective treatment strategies for pancreatic cancer are needed. Funding: Bill &amp; Melinda Gates Foundation