Conditioned stochastic particle systems and integrable quantum spin systems

We consider from a microscopic perspective large deviation properties of several stochastic interacting particle systems, using their mapping to integrable quantum spin systems. A brief review of recent work is given and several new results are presented: (i) For the general disordered symmectric exclusion process (SEP) on some finite lattice conditioned on no jumps into some absorbing sublattice and with initial Bernoulli product measure with density $\rho$ we prove that the probability $S_\rho(t)$ of no absorption event up to microscopic time $t$ can be expressed in terms of the generating function for the particle number of a SEP with particle injection and empty initial lattice. Specifically, for the symmetric simple exclusion process on $\mathbb Z$ conditioned on no jumps into the origin we obtain the explicit first and second order expansion in $\rho$ of $S_\rho(t)$ and also to first order in $\rho$ the optimal microscopic density profile under this conditioning. For the disordered ASEP on the finite torus conditioned on a very large current we show that the effective dynamics that optimally realizes this rare event does not depend on the disorder, except for the time scale. For annihilating and coalescing random walkers we obtain the generating function of the number of annihilated particles up to time $t$, which turns out to exhibit some universal features.Comment: 25 page

Determining Atlantic Ocean province contrasts and variations

The Atlantic Meridional Transect (AMT) series of twenty-five cruises over the past twenty years has produced a rich depth-resolved biogeochemical in situ data resource consisting of a wealth of core variables. These multiple core datasets, key to the operation of AMT, such as temperature, salinity, oxygen and inorganic nutrients, are often only used as ancillary measurements for contextualising hypothesis-driven process studies. In this paper these core in situ variables, alongside data drawn from satellite Earth Observation (EO) and modelling, have been analysed to determine characteristic oceanic province variations encountered over the last twenty years on the AMT through the Atlantic Ocean. The EO and modelling analysis shows the variations of key environmental variables in each province, such as surface currents, the net heat flux and subsequent large scale biological responses, such as primary production. The in situ core dataset analysis allows the variation in features such as the tropical oxygen minimum zone to be quantified as well as showing clear contrasts between the provinces in nutrient stoichiometry. Such observations and relationships can be used within basin scale biogeochemical models to set realistic variation ranges

Recombination in Streptococcus pneumoniae Lineages Increase with Carriage Duration and Size of the Polysaccharide Capsule.

Streptococcus pneumoniae causes a high burden of invasive pneumococcal disease (IPD) globally, especially in children from resource-poor settings. Like many bacteria, the pneumococcus can import DNA from other strains or even species by transformation and homologous recombination, which has allowed the pneumococcus to evade clinical interventions such as antibiotics and pneumococcal conjugate vaccines (PCVs). Pneumococci are enclosed in a complex polysaccharide capsule that determines the serotype; the capsule varies in size and is associated with properties including carriage prevalence and virulence. We determined and quantified the association between capsule and recombination events using genomic data from a diverse collection of serotypes sampled in Malawi. We determined both the amount of variation introduced by recombination relative to mutation (the relative rate) and how many individual recombination events occur per isolate (the frequency). Using univariate analyses, we found an association between both recombination measures and multiple factors associated with the capsule, including duration and prevalence of carriage. Because many capsular factors are correlated, we used multivariate analysis to correct for collinearity. Capsule size and carriage duration remained positively associated with recombination, although with a reduced P value, and this effect may be mediated through some unassayed additional property associated with larger capsules. This work describes an important impact of serotype on recombination that has been previously overlooked. While the details of how this effect is achieved remain to be determined, it may have important consequences for the serotype-specific response to vaccines and other interventions. IMPORTANCE: The capsule determines >90 different pneumococcal serotypes, which vary in capsule size, virulence, duration, and prevalence of carriage. Current serotype-specific vaccines elicit anticapsule antibodies. Pneumococcus can take up exogenous DNA by transformation and insert it into its chromosome by homologous recombination. This mechanism has disseminated drug resistance and generated vaccine escape variants. It is hence crucial to pneumococcal evolutionary response to interventions, but there has been no systematic study quantifying whether serotypes vary in recombination and whether this is associated with serotype-specific properties such as capsule size or carriage duration. Larger capsules could physically inhibit DNA uptake, or given the longer carriage duration for larger capsules, this may promote recombination. We find that recombination varies among capsules and is associated with capsule size, carriage duration, and carriage prevalence and negatively associated with invasiveness. The consequence of this work is that serotypes with different capsules may respond differently to selective pressures like vaccines

Color & Weak triplet scalars, the dimuon asymmetry in BsB_s decay, the top forward-backward asymmetry, and the CDF dijet excess

The new physics required to explain the anomalies recently reported by the D0 and CDF collaborations, namely the top forward-backward asymmetry (FBA), the like-sign dimuon charge asymmetry in semileptonic b decay, and the CDF dijet excess, has to feature an amount of flavor symmetry in order to satisfy the severe constrains arising from flavor violation. In this paper we show that, once baryon number conservation is imposed, color & weak triplet scalars with hypercharge $Y=1/3$ can feature the required flavor structure as a consequence of standard model gauge invariance. The color & weak triplet model can simultaneously explain the top FBA and the dimuon charge asymmetry or the dimuon charge asymmetry and the CDF dijet excess. However, the CDF dijet excess appears to be incompatible with the top FBA in the minimal framework. Our model for the dimuon asymmetry predicts the observed pattern $h_d\ll h_s$ in the region of parameter space required to explain the top FBA, whereas our model for the CDF dijet anomaly is characterized by the absence of beyond the SM b-quark jets in the excess region. Compatibility of the color & weak triplet with the electroweak constraints is also discussed. We show that a Higgs boson mass exceeding the LEP bound is typically favored in this scenario, and that both Higgs production and decay can be significantly altered by the triplet. The most promising collider signature is found if the splitting among the components of the triplet is of weak scale magnitude.Comment: references added, published versio

Proteomic analysis of nipple aspirate fluid to detect biologic markers of breast cancer.

The early detection of breast cancer is the best means to minimise disease-related mortality. Current screening techniques have limited sensitivity and specificity. Breast nipple aspirate fluid can be obtained noninvasively and contains proteins secreted from ductal and lobular epithelia. Nipple aspirate fluid proteins are breast specific and generally more concentrated than corresponding blood levels. Proteomic analysis of 1 microl of diluted nipple aspirate fluid over a 5-40 kDa range from 20 subjects with breast cancer and 13 with nondiseased breasts identified five differentially expressed proteins. The most sensitive and specific proteins were 6500 and 15 940 Da, found in 75-84% of samples from women with cancer but in only 0-9% of samples from normal women. These findings suggest that (1) differential expression of nipple aspirate fluid proteins exists between women with normal and diseased breasts, and (2) analysis of these proteins may predict the presence of breast cancer

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT