Ectopic expression of the AtCDF1 transcription factor in potato enhances tuber starch and amino acid contents and yield under open field conditions

Introduction Cycling Dof transcription factors (CDFs) have been involved in different aspects of plant growth and development. In Arabidopsis and tomato, one member of this family (CDF1) has recently been associated with the regulation of primary metabolism and abiotic stress responses, but their roles in crop production under open field conditions remain unknown. Methods In this study, we compared the growth, and tuber yield and composition of plants ectopically expressing the CDF1 gene from Arabidopsis under the control of the 35S promoter with wild-type (WT) potato plants cultured in growth chamber and open field conditions. Results In growth chambers, the 35S::AtCDF1 plants showed a greater tuber yield than the WT by increasing the biomass partition for tuber development. Under field conditions, the ectopic expression of CDF1 also promoted the sink strength of the tubers, since 35S::AtCDF1 plants exhibited significant increases in tuber size and weight resulting in higher tuber yield. A metabolomic analysis revealed that tubers of 35S::AtCDF1 plants cultured under open field conditions accumulated higher levels of glucose, starch and amino acids than WT tubers. A comparative proteomic analysis of tubers of 35S::AtCDF1 and WT plants cultured under open field conditions revealed that these changes can be accounted for changes in the expression of proteins involved in energy production and different aspects of C and N metabolism. Discussion The results from this study advance our collective understanding of the role of CDFs and are of great interest for the purposes of improving the yield and breeding of crop plants

Particle-yield modification in jet-like azimuthal di-hadron correlations in Pb-Pb collisions at sNN\sqrt{s_{\rm NN}} = 2.76 TeV

The yield of charged particles associated with high-$p_{\rm T}$ trigger particles ($8 < p_{\rm T} < 15$ GeV/$c$) is measured with the ALICE detector in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV relative to proton-proton collisions at the same energy. The conditional per-trigger yields are extracted from the narrow jet-like correlation peaks in azimuthal di-hadron correlations. In the 5% most central collisions, we observe that the yield of associated charged particles with transverse momenta $p_{\rm T}> 3$ GeV/$c$ on the away-side drops to about 60% of that observed in pp collisions, while on the near-side a moderate enhancement of 20-30% is found.Comment: 15 pages, 2 captioned figures, 1 table, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/350

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication

Background: The phase III CLinical Evaluation Of Pertuzumab And TRAstuzumab (CLEOPATRA) trial established the combination of pertuzumab, trastuzumab and docetaxel as standard first-line therapy for human epidermal growth factor receptor 2 (HER2)-positive locally recurrent/metastatic breast cancer (LR/mBC). The multicentre single-arm PERtUzumab global SafEty (PERUSE) study assessed the safety and efficacy of pertuzumab and trastuzumab combined with investigator-selected taxane in this setting. Patients and methods: Eligible patients with inoperable HER2-positive LR/mBC and no prior systemic therapy for LR/mBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab and pertuzumab until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). Prespecified subgroup analyses included subgroups according to taxane, hormone receptor (HR) status and prior trastuzumab. Exploratory univariable analyses identified potential prognostic factors; those that remained significant in multivariable analysis were used to analyse PFS and OS in subgroups with all, some or none of these factors. Results: Of 1436 treated patients, 588 (41%) initially received paclitaxel and 918 (64%) had HR-positive disease. The most common grade 653 adverse events were neutropenia (10%, mainly with docetaxel) and diarrhoea (8%). At the final analysis (median follow-up: 5.7 years), median PFS was 20.7 [95% confidence interval (CI) 18.9-23.1] months overall and was similar irrespective of HR status or taxane. Median OS was 65.3 (95% CI 60.9-70.9) months overall. OS was similar regardless of taxane backbone but was more favourable in patients with HR-positive than HR-negative LR/mBC. In exploratory analyses, trastuzumab-pretreated patients with visceral disease had the shortest median PFS (13.1 months) and OS (46.3 months). Conclusions: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design

The ALICE Transition Radiation Detector: Construction, operation, and performance

The Transition Radiation Detector (TRD) was designed and built to enhance the capabilities of the ALICE detector at the Large Hadron Collider (LHC). While aimed at providing electron identification and triggering, the TRD also contributes significantly to the track reconstruction and calibration in the central barrel of ALICE. In this paper the design, construction, operation, and performance of this detector are discussed. A pion rejection factor of up to 410 is achieved at a momentum of 1 GeV/c in p-Pb collisions and the resolution at high transverse momentum improves by about 40% when including the TRD information in track reconstruction. The triggering capability is demonstrated both for jet, light nuclei, and electron selection. (c) 2017 CERN for the benefit of the Authors. Published by Elsevier B.V

Inclusive and multiplicity dependent production of electrons from heavy-flavour hadron decays in pp and p-Pb collisions

Measurements of the production of electrons from heavy-flavour hadron decays in pp collisions at root s = 13 TeV at midrapidity with the ALICE detector are presented down to a transverse momentum (p(T)) of 0.2 GeV/c and up to p(T) = 35 GeV/c, which is the largest momentum range probed for inclusive electron measurements in ALICE. In p-Pb collisions, the production cross section and the nuclear modification factor of electrons from heavy-flavour hadron decays are measured in the p(T) range 0.5 < p(T) < 26 GeV/c at root s(NN) = 8.16 TeV. The nuclear modification factor is found to be consistent with unity within the statistical and systematic uncertainties. In both collision systems, first measurements of the yields of electrons from heavy-flavour hadron decays in different multiplicity intervals normalised to the multiplicity-integrated yield (self-normalised yield) at midrapidity are reported as a function of the self-normalised charged-particle multiplicity estimated at midrapidity. The self-normalised yields in pp and p-Pb collisions grow faster than linear with the self-normalised multiplicity. A strong p(T) dependence is observed in pp collisions, where the yield of high-p(T) electrons increases faster as a function of multiplicity than the one of low-p(T) electrons. The measurement in p-Pb collisions shows no p(T) dependence within uncertainties. The self-normalised yields in pp and p-Pb collisions are compared with measurements of other heavy-flavour, light-flavour, and strange particles, and with Monte Carlo simulations

Hypertriton Production in p-Pb Collisions at √sNN = 5.02 TeV

The study of nuclei and antinuclei production has proven to be a powerful tool to investigate the formation mechanism of loosely bound states in high-energy hadronic collisions. The first measurement of the production of ${\rm ^{3}_{\Lambda}\rm H}$ in p-Pb collisions at $\sqrt{s_{\rm{NN}}}$ = 5.02 TeV is presented in this Letter. Its production yield measured in the rapidity interval -1 < y < 0 for the 40% highest multiplicity p-Pb collisions is ${\rm d} N /{\rm d} y =[\mathrm{6.3 \pm 1.8 (stat.) \pm 1.2 (syst.) ] \times 10^{-7}}$. The measurement is compared with the expectations of statistical hadronisation and coalescence models, which describe the nucleosynthesis in hadronic collisions. These two models predict very different yields of the hypertriton in small collision systems such as p-Pb and therefore the measurement of ${\rm d} N /{\rm d} y$ is crucial to distinguish between them. The precision of this measurement leads to the exclusion with a significance larger than 6$\sigma$ of some configurations of the statistical hadronisation, thus constraining the production mechanism of loosely bound states

Measurement of the non-prompt D-meson fraction as a function of multiplicity in proton-proton collisions at s \sqrt{s} = 13 TeV

The fractions of non-prompt (i.e. originating from beauty-hadron decays) D0 and D+ mesons with respect to the inclusive yield are measured as a function of the charged-particle multiplicity in proton-proton collisions at a centre-of-mass energy of √s = 13 TeV with the ALICE detector at the LHC. The results are reported in intervals of transverse momentum (pT) and integrated in the range 1 < pT < 24 GeV/c. The fraction of non-prompt D0 and D+ mesons is found to increase slightly as a function of pT in all the measured multiplicity intervals, while no significant dependence on the charged- particle multiplicity is observed. In order to investigate the production and hadronisation mechanisms of charm and beauty quarks, the results are compared to PYTHIA 8 as well as EPOS 3 and EPOS 4 Monte Carlo simulations, and to calculations based on the colour glass condensate including three-pomeron fusion

Characterizing the initial conditions of heavy-ion collisions at the LHC with mean transverse momentum and anisotropic flow correlations

Correlations between mean transverse momentum and anisotropic flow coefficients or are measured as a function of centrality in Pb–Pb and Xe–Xe collisions at sqrt(sNN) = 5.02 TeV and 5.44 TeV, respectively, with ALICE. In addition, the recently proposed higher-order correlation between [pt], v2, and v3 is measured for the first time, which shows an anticorrelation for the presented centrality ranges. These measurements are compared with hydrodynamic calculations using IP-Glasma and TRENTO initial-state shapes, the former based on the Color Glass Condensate effective theory with gluon saturation, and the latter a parameterized model with nucleons as the relevant degrees of freedom. The data are better described by the IP-Glasma rather than the TRENTO based calculations. In particular, Trajectum and JETSCAPE predictions, both based on the TRENTO initial state model but with different parameter settings, fail to describe the measurements. As the correlations between [pt] and vn are mainly driven by the correlations of the size and the shape of the system in the initial state, these new studies pave a novel way to characterize the initial state and help pin down the uncertainty of the extracted properties of the quark–gluon plasma recreated in relativistic heavy-ion collisions