Meta-analysis Reveals Genome-Wide Significance at 15q13 for Nonsyndromic Clefting of Both the Lip and the Palate, and Functional Analyses Implicate GREM1 As a Plausible Causative Gene

Nonsyndromic orofacial clefts are common birth defects with multifactorial etiology. The most common type is cleft lip, which occurs with or without cleft palate (nsCLP and nsCLO, respectively). Although genetic components play an important role in nsCLP, the genetic factors that predispose to palate involvement are largely unknown. In this study, we carried out a meta-analysis on genetic and clinical data from three large cohorts and identified strong association between a region on chromosome 15q13 and nsCLP (P = 8.13×10−14 for rs1258763; relative risk (RR): 1.46, 95% confidence interval (CI): 1.32–1.61)) but not nsCLO (P = 0.27; RR: 1.09 (0.94–1.27)). The 5 kb region of strongest association maps downstream of Gremlin-1 (GREM1), which encodes a secreted antagonist of the BMP4 pathway. We show during mouse embryogenesis, Grem1 is expressed in the developing lip and soft palate but not in the hard palate. This is consistent with genotype-phenotype correlations between rs1258763 and a specific nsCLP subphenotype, since a more than two-fold increase in risk was observed in patients displaying clefts of both the lip and soft palate but who had an intact hard palate (RR: 3.76, CI: 1.47–9.61, Pdiff<0.05). While we did not find lip or palate defects in Grem1-deficient mice, wild type embryonic palatal shelves developed divergent shapes when cultured in the presence of ectopic Grem1 protein (P = 0.0014). The present study identified a non-coding region at 15q13 as the second, genome-wide significant locus specific for nsCLP, after 13q31. Moreover, our data suggest that the closely located GREM1 gene contributes to a rare clinical nsCLP entity. This entity specifically involves abnormalities of the lip and soft palate, which develop at different time-points and in separate anatomical regions.Clefts of the lip and palate are common birth defects, and require long-term multidisciplinary management. Their etiology involves genetic factors and environmental influences and/or a combination of both, however, these interactions are poorly defined. Moreover, although clefts of the lip may or may not involve the palate, the determinants predisposing to specific subphenotypes are largely unknown. Here we demonstrate that variations in the non-coding region near the GREM1 gene show a highly significant association with a particular phenotype in which cleft lip and cleft palate co-occ

Investigating strangeness enhancement with multiplicity in pp collisions using angular correlations

A study of strange hadron production associated with hard scattering processes and with the underlying event is conducted to investigate the origin of the enhanced production of strange hadrons in small collision systems characterised by large charged-particle multiplicities. For this purpose, the production of the single-strange meson KS0 and the double-strange baryon Ξ± is measured, in each event, in the azimuthal direction of the highest-pT particle (“trigger” particle), related to hard scattering processes, and in the direction transverse to it in azimuth, associated with the underlying event, in pp collisions at s = 5.02 TeV and s = 13 TeV using the ALICE detector at the LHC. The per-trigger yields of KS0 and Ξ± are dominated by the transverse-to-leading production (i.e., in the direction transverse to the trigger particle), whose contribution relative to the toward-leading production is observed to increase with the event charged-particle multiplicity. The transverse-to-leading and the toward-leading Ξ±/KS0 yield ratios increase with the multiplicity of charged particles, suggesting that strangeness enhancement with multiplicity is associated with both hard scattering processes and the underlying event. The relative production of Ξ± with respect to KS0 is higher in transverse-to-leading processes over the whole multiplicity interval covered by the measurement. The KS0 and Ξ± per-trigger yields and yield ratios are compared with predictions of three different phenomenological models, namely Pythia8.2 with the Monash tune, Pythia8.2 with ropes and EPOS LHC. The comparison shows that none of them can quantitatively describe either the transverse-to-leading or the toward-leading yields of KS0 and Ξ±.publishedVersio

Multiplicity dependence of charged-particle intra-jet properties in pp collisions at √s = 13 TeV

The first measurement of the multiplicity dependence of intra-jet properties of leading charged-particle jets in proton–proton (pp) collisions is reported. Themean chargedparticle multiplicity and jet fragmentation distributions are measured in minimum-bias and high-multiplicity pp collisions at center-of-mass energy √s = 13 TeV using the ALICE detector. Jets are reconstructed from charged particles produced in the midrapidity region (|η| < 0.9) using the sequential recombination anti-kT algorithm with jet resolution parameters R = 0.2, 0.3, and 0.4 for the transverse momentum (pT) interval 5–110 GeV/c. The highmultiplicity events are selected by the forward V0 scintillator detectors. The mean charged-particle multiplicity inside the leading jet cone rises monotonically with increasing jet pT in qualitative agreement with previous measurements at lower energies. The distributions of jet fragmentation function variables zch and ξ ch are measured for different jet-pT intervals. Jet-pT independent fragmentation of leading jets is observed for wider jets except at high- and low-zch values. The observed “hump-backed plateau” structure in the ξ ch distribution indicates suppression of low-pT particles. In high-multiplicity events, an enhancement of the fragmentation probability of low-zch particles accompanied by a suppression of high-zch particles is observed compared to minimum-bias events. This behavior becomes more prominent for low-pT jets with larger jet radius. The results are compared with predictions of QCD-inspired event generators, PYTHIA8 with Monash 2013 tune and EPOS LHC. It is found that PYTHIA8 qualitatively reproduces the jet modification in high-multiplicity events except at high jet pT. These measurements provide important constraints to models of jet fragmentation.publishedVersio

Search for jet quenching effects in high-multiplicity pp collisions at √ s = 13 TeV via di-jet acoplanarity

The ALICE Collaboration reports a search for jet quenching effects in highmultiplicity (HM) proton-proton collisions at √ s = 13TeV, using the semi-inclusive azimuthaldifference distribution Δφ of charged-particle jets recoiling from a high transverse momentum (high-pT,trig) trigger hadron. Jet quenching may broaden the Δφ distribution measured in HM events compared to that in minimum bias (MB) events. The measurement employs a pT,trig-differential observable for data-driven suppression of the contribution of multiple partonic interactions, which is the dominant background. While azimuthal broadening is indeed observed in HM compared to MB events, similar broadening for HM events is observed for simulations based on the PYTHIA 8 Monte Carlo generator, which does not incorporate jet quenching. Detailed analysis of these data and simulations show that the azimuthal broadening is due to bias of the HM selection towards events with multiple jets in the final state. The identification of this bias has implications for all jet quenching searches where selection is made on the event activity.publishedVersio

First measurement of Ωc0 production in pp collisions at s=13 TeV

The inclusive production of the charm–strange baryon 0 c is measured for the first time via its hadronic √ decay into −π+ at midrapidity (|y| &lt;0.5) in proton–proton (pp) collisions at the centre-of-mass energy s =13 TeV with the ALICE detector at the LHC. The transverse momentum (pT) differential cross section multiplied by the branching ratio is presented in the interval 2 &lt; pT &lt; 12 GeV/c. The pT dependence of the 0 c-baryon production relative to the prompt D0-meson and to the prompt 0 c-baryon production is compared to various models that take different hadronisation mechanisms into consideration. In the measured pT interval, the ratio of the pT-integrated cross sections of 0 c and prompt + c baryons multiplied by the −π+ branching ratio is found to be larger by a factor of about 20 with a significance of about 4σ when compared to e+e− collisions

"Made in China" vs "Made in Italy"? Uno studio preliminare dei differenziali di prezzo nelle esportazioni di prodotti tradizionali

Questo breve contributo si inserisce nel dibattito sulla specializzazione industriale italiana e sulla capacità del nostro sistema produttivo di mantenere la propria capacità competitiva. In particolare, viene proposta una metodologia di confronto fra le esportazioni italiane e cinesi basata sui prezzi unitari volta ad evidenziare la presenza o l’assenza di sovrapposizione tra le esportazioni dei due paesi