Studying trends of non-coding RNA function and evolution

RNA is a special type of molecule in the sense that it is an information carrier, and is also able to catalyze chemical reactions. It is consequently believed that RNA predated protein and DNA as a catalyst and information carrier in an \u22RNA World\u22. A greater understanding of evolutionary and functional features of non-coding RNA is not only fundamental to elucidating the evolutionary mechanisms that give rise to RNA function, perhaps giving insight into the origin of life in an RNA World, but is necessary for the advancement of RNA biotechnology and RNA based therapeutics. Recent advancements in high-throughput sequencing technologies have provided the ability to study the function of non-coding RNAs at an unprecedented depth, producing millions to billions of sequences from a single experiment. This poses new challenges to researchers, as traditional biochemical and computational techniques are unable to scale to the massive amounts of data each experiment produces. In this work, I present new computational tools, methods, and their applications in the study of non-coding RNA evolution. I have assembled a gold standard set of non- coding RNA alignments that have been manually curated and aligned to their known 3d structures. These manual alignments address the need for RNA alignments with structural annotation that current automated alignment algorithms do not provide. Next, I present an application of alignments to the study of tRNA evolution. tRNAs, an integral part of the modern translation machinery, are believed to be poor phylogenetic markers. Using UniFrac to cluster genomes based on the collection of tRNAs they contain, I show that these tRNA trees are similar to trees constructed from rRNA from the same organisms, congruent with universal phylogeny. Finally, I describe a technique developed to simultaneously measure the dissociation constant (KD) of a pool of thousands of amino acid binding RNA aptamers obtained by in vitro selection, improving over the traditional laborious process of determining KD one sequence at a time

Simple, recurring RNA binding sites for L-arginine

Seven new arginine binding motifs have been selected from a heterogeneous RNA pool containing 17, 25, and 50mer randomized tracts, yielding 131 independently derived binding sites that are multiply isolated. The shortest 17mer random region is sufficient to build varied arginine binding sites using five different conserved motifs (motifs 1a, 1b, 1c, 2, and 4). Dissociation constants are in the fractional millimolar to millimolar range. Binding sites are amino acid side-chain specific and discriminate moderately between L- and D-stereoisomers of arginine, suggesting a molecular focus on side-chain guanidinium. An arginine coding triplet (codon/anticodon) is highly conserved within the largest family of Arg sites (72% of all sequences), as has also been found in minimal, most prevalent RNA binding sites for Ile, His, and Trp

Multiplicity dependence of light (anti-)nuclei production in p–Pb collisions at sNN=5.02 TeV

The measurement of the deuteron and anti-deuteron production in the rapidity range −1 < y < 0 as a function of transverse momentum and event multiplicity in p–Pb collisions at √sNN = 5.02 TeV is presented. (Anti-)deuterons are identified via their specific energy loss dE/dx and via their time-of- flight. Their production in p–Pb collisions is compared to pp and Pb–Pb collisions and is discussed within the context of thermal and coalescence models. The ratio of integrated yields of deuterons to protons (d/p) shows a significant increase as a function of the charged-particle multiplicity of the event starting from values similar to those observed in pp collisions at low multiplicities and approaching those observed in Pb–Pb collisions at high multiplicities. The mean transverse particle momenta are extracted from the deuteron spectra and the values are similar to those obtained for p and particles. Thus, deuteron spectra do not follow mass ordering. This behaviour is in contrast to the trend observed for non-composite particles in p–Pb collisions. In addition, the production of the rare 3He and 3He nuclei has been studied. The spectrum corresponding to all non-single diffractive p-Pb collisions is obtained in the rapidity window −1 < y < 0 and the pT-integrated yield dN/dy is extracted. It is found that the yields of protons, deuterons, and 3He, normalised by the spin degeneracy factor, follow an exponential decrease with mass number

The importance of low-dose CT screening to identify emphysema in asymptomatic participants with and without a prior diagnosis of COPD

Chronic Obstructive Pulmonary Disease (COPD) includes chronic bronchitis, small airways disease, and emphysema. Diagnosis of COPD requires spirometric evidence and may be normal even when small airways disease or emphysema is present. Emphysema increases the risk of exacerbations, and is associated with all-cause mortality and increased risk of lung cancer. We evaluated the prevalence of emphysema in participants with and without a prior history of COPD. We reviewed a prospective cohort of 52,726 subjects who underwent baseline low dose CT screening for lung cancer from 2003 to 2016 in the International Early Lung Cancer Action Program. Of 52,726 participants, 23.8%(12,542) had CT evidence of emphysema. Of these 12,542 participants with emphysema, 76.5%(9595/12,542) had no prior COPD diagnosis even though 23.6% (2258/9595) had moderate or severe emphysema. Among 12,542 participants, significant predictors of no prior COPD diagnosis were: male (OR = 1.47, p < 0.0001), younger age (ORage10 = 0.72, p < 0.0001), lower pack-years of smoking (OR10pack-years = 0.90, p < 0.0001), completed college or higher (OR = 1.54, p < 0.0001), no family history of lung cancer (OR = 1.12, p = 0.04), no self-reported cardiac disease (OR = 0.76, p = 0.0003) or hypertension (OR = 0.74, p < 0.0001). The severity of emphysema was significantly lower among the 9595 participants with no prior COPD diagnosis, the OR for moderate emphysema was ORmoderate = 0.58(p = 0.0007) and for severe emphysema, it was ORsevere = 0.23(p < 0.0001). Emphysema was identified in 23.8% participants undergoing LDCT and was unsuspected in 76.5%. LDCT provides an opportunity to identify emphysema, and recommend smoking cessation. •Emphysema was identified in 23.8% participants and was unsuspected in 76.5%.•23.6% of participants with unsuspected COPD had moderate or severe emphysema on LDCT.•COPD is underdiagnosed in patients undergoing LDCT.•LDCT provides an opportunity to identify emphysema, reduce morbidity and mortality

Measurement of electrons from semileptonic heavy-flavour hadron decays at midrapidity in pp and Pb–Pb collisions at √sNN = 5.02 TeV

The differential invariant yield as a function of transverse momentum (pT) of electrons from semileptonic heavy-flavour hadron decays was measured at midrapidity in central (0–10%), semi-central (30–50%) and peripheral (60–80%) lead–lead (Pb–Pb) collisions at √sNN = 5.02 TeV in the pT intervals 0.5–26 GeV/c (0–10% and 30–50%) and 0.5–10 GeV/c (60–80%). The production cross section in proton–proton (pp) collisions at √s = 5.02 TeV was measured as well in 0.5 < pT < 10 GeV/c and it lies close to the upper band of perturbative QCD calculation uncertainties up to pT = 5 GeV/c and close to the mean value for larger pT. The modification of the electron yield with respect to what is expected for an incoherent superposition of nucleon–nucleon collisions is evaluated by measuring the nuclear modification factor RAA. The measurement of the RAA in different centrality classes allows in-medium energy loss of charm and beauty quarks to be investigated. The RAA shows a suppression with respect to unity at intermediate pT, which increases while moving towards more central collisions. Moreover, the measured RAA is sensitive to the modification of the parton distribution functions (PDF) in nuclei, like nuclear shadowing, which causes a suppression of the heavy-quark production at low pT in heavy-ion collisions at LHC

Λ3H^3_\Lambda\mathrm{H} and Λˉ3H‾^3_{\bar{\Lambda}}\mathrm{\overline{H}} lifetime measurement in Pb-Pb collisions at sNN=\sqrt{s_{\mathrm{NN}}} = 5.02 TeV via two-body decay

International audienceAn improved value for the lifetime of the (anti-)hypertriton has been obtained using the data sample of Pb–Pb collisions at sNN=5.02 TeV collected by the ALICE experiment at the LHC. The (anti-)hypertriton has been reconstructed via its charged two-body mesonic decay channel and the lifetime has been determined from an exponential fit to the d N /d( ct ) spectrum. The measured value, τ=242−38+34 (stat.) ± 17 (syst.) ps, is compatible with representative theoretical predictions, thus contributing to the solution of the longstanding hypertriton lifetime puzzle

Exploration of jet substructure using iterative declustering in pp and Pb–Pb collisions at LHC energies

The ALICE collaboration at the CERN LHC reports novel measurements of jet substructure in pp collisions at $\sqrt{s}$= 7 TeV and central Pb-Pb collisions at $\sqrt{s_{\rm{NN}}}$ = 2.76 TeV. Jet substructure of track-based jets is explored via iterative declustering and grooming techniques. We present the measurement of the momentum sharing of two-prong substructure exposed via grooming, the $z_{\rm{g}}$, and its dependence on the opening angle, in both pp and Pb-Pb collisions. We also present the first measurement of the distribution of the number of branches obtained in the iterative declustering of the jet, which is interpreted as the number of its hard splittings. In Pb-Pb collisions, we observe a suppression of symmetric splittings at large opening angles and an enhancement of splittings at small opening angles relative to pp collisions, with no significant modification of the number of splittings. The results are compared to predictions from various Monte Carlo event generators to test the role of important concepts in the evolution of the jet in the medium such as color coherence

Measurement of charged jet cross section in pp collisions at √s = 5.02 TeV

The cross section of jets reconstructed from charged particles is measured in the transverse momentum range of 5<pT<100 GeV/c in pp collisions at the center-of-mass energy of s√=5.02 TeV with the ALICE detector. The jets are reconstructed using the anti-kT algorithm with resolution parameters R=0.2, 0.3, 0.4, and 0.6 in the pseudorapidity range |η|<0.9−R. The charged jet cross sections are compared with the leading order (LO) and to next-to-leading order (NLO) perturbative Quantum ChromoDynamics (pQCD) calculations. It was found that the NLO calculations agree better with the measurements. The cross section ratios for different resolution parameters were also measured. These ratios increase from low pT to high pT and saturate at high pT, indicating that jet collimation is larger at high pT than at low pT. These results provide a precision test of pQCD predictions and serve as a baseline for the measurement in Pb−Pb collisions at the same energy to quantify the effects of the hot and dense medium created in heavy-ion collisions at the LHC

Coherent J/ψ\psi photoproduction at forward rapidity in ultra-peripheral Pb-Pb collisions at sNN=5.02\sqrt{s_{\rm{NN}}}=5.02 TeV

The ALICE collaboration performed the first rapidity-differential measurement of coherent J/ψ photoproduction in ultra-peripheral Pb–Pb collisions at a center-of-mass energy $\sqrt{s_{\rm NN}}$ = 5.02 TeV. The J/ψ is detected via its dimuon decay in the forward rapidity region (−4.0 < y <−2.5 ) for events where the hadronic activity is required to be minimal. The analysis is based on an event sample corresponding to an integrated luminosity of about 750 $\mu$b$^{-1}$ . The cross section for coherent J/ψ production is presented in six rapidity bins. The results are compared with theoretical models for coherent J/ψ photoproduction. These comparisons indicate that gluon shadowing effects play a role in the photoproduction process. The ratio of ψ′ to J/ψ coherent photoproduction cross sections was measured and found to be consistent with that measured for photoproduction off protons

Measurement of charged jet cross section in pppp collisions at s=5.02{\sqrt{s}=5.02} TeV

International audienceThe cross section of jets reconstructed from charged particles is measured in the transverse momentum range of 5<pT<100  GeV/c in pp collisions at the center-of-mass energy of s=5.02  TeV with the ALICE detector. The jets are reconstructed using the anti-kT algorithm with resolution parameters R=0.2, 0.3, 0.4, and 0.6 in the pseudorapidity range |η|<0.9-R. The charged jet cross sections are compared with the leading-order (LO) and to next-to-leading-order (NLO) perturbative quantum chromodynamics (pQCD) calculations. It is found that the NLO calculations agree better with the measurements. The cross section ratios for different resolution parameters are also measured. These ratios increase from low pT to high pT and saturate at high pT, indicating that jet collimation is larger at high pT than at low pT. These results provide a precision test of pQCD predictions and serve as a baseline for the measurement in Pb-Pb collisions at the same energy to quantify the effects of the hot and dense medium created in heavy-ion collisions at the LHC