Motif Discovery through Predictive Modeling of Gene Regulation

We present MEDUSA, an integrative method for learning motif models of transcription factor binding sites by incorporating promoter sequence and gene expression data. We use a modern large-margin machine learning approach, based on boosting, to enable feature selection from the high-dimensional search space of candidate binding sequences while avoiding overfitting. At each iteration of the algorithm, MEDUSA builds a motif model whose presence in the promoter region of a gene, coupled with activity of a regulator in an experiment, is predictive of differential expression. In this way, we learn motifs that are functional and predictive of regulatory response rather than motifs that are simply overrepresented in promoter sequences. Moreover, MEDUSA produces a model of the transcriptional control logic that can predict the expression of any gene in the organism, given the sequence of the promoter region of the target gene and the expression state of a set of known or putative transcription factors and signaling molecules. Each motif model is either a $k$-length sequence, a dimer, or a PSSM that is built by agglomerative probabilistic clustering of sequences with similar boosting loss. By applying MEDUSA to a set of environmental stress response expression data in yeast, we learn motifs whose ability to predict differential expression of target genes outperforms motifs from the TRANSFAC dataset and from a previously published candidate set of PSSMs. We also show that MEDUSA retrieves many experimentally confirmed binding sites associated with environmental stress response from the literature.Comment: RECOMB 200

New developments in CLAMP: Calibration using global gridded meteorological data

Climate Leaf Analysis Multivariate Program (CLAMP) is a versatile technique for obtaining quantitative estimates for multiple terrestrial palaeoclimate variables from woody dicot leaf assemblages. To date it has been most widely applied to the Late Cretaceous and Tertiary of the mid- to high latitudes because of concerns over the relative dearth of calibration sites in modern low-latitude warm climates, and the loss of information associated with the lack of marginal teeth on leaves in paratropical to tropical vegetation. This limits CLAMP's ability to quantify reliably climates at low latitudes in greenhouse worlds of the past. One of the reasons for the lack of CLAMP calibration samples from warm environments is the paucity of climate stations close to potential calibration vegetation sites at low latitudes. Agriculture and urban development have destroyed most lowland sites and natural vegetation is now largely confined to mountainous areas where climate stations are few and climatic spatial variation is high due to topographic complexity. To attempt to overcome this we have utilised a 0.5° × 0.5° grid of global interpolated climate data based on the data set of New et al. (1999) supplemented by the ERA40 re-analysis data for atmospheric temperature at upper levels. For each location, the 3-D climatology of temperature from the ECMWF re-analysis project was used to calculate the mean lower tropospheric lapse rate for each month of the year. The gridded data were then corrected to the altitude of the plant site using the monthly lapse rates. Corrections for humidity were also made. From this the commonly returned CLAMP climate variables were calculated. A bi-linear interpolation scheme was then used to calculate the climate parameters at the exact lat/long of the site. When CLAMP analyses using the PHYSG3BR physiognomic data calibrated with the climate station based MET3BR were compared to analyses using the gridded data at the same locations (GRIDMET3BR), the results were indistinguishable in that they fell within the range of statistical uncertainty determined for each analysis. This opens the way to including natural vegetation anywhere in the world irrespective of the proximity of a meteorological station

Can filesharers be triggered by economic incentives? Results of an experiment

Illegal filesharing on the internet leads to considerable financial losses for artists and copyright owners as well as producers and sellers of music. Thus far, measures to contain this phenomenon have been rather restrictive. However, there are still a considerable number of illegal systems, and users are able to decide quite freely between legal and illegal downloads because the latter are still difficult to sanction. Recent economic approaches account for the improved bargaining position of users. They are based on the idea of revenue-splitting between professional sellers and peers. In order to test such an innovative business model, the study reported in this article carried out an experiment with 100 undergraduate students, forming five small peer-to-peer networks.The networks were confronted with different economic conditions.The results indicate that even experienced filesharers hold favourable attitudes towards revenue-splitting.They seem to be willing to adjust their behaviour to different economic conditions

Association of antenatal diet and physical activity-based interventions with gestational weight gain and pregnancy outcomes: a systematic review and meta-analysis

Published online December 20, 2021.Importance: Excessive gestational weight gain (GWG) is common and associated with adverse pregnancy outcomes. Antenatal lifestyle interventions limit GWG; yet benefits of different intervention types and specific maternal and neonatal outcomes are unclear. Objective: To evaluate the association of different types of diet and physical activity–based antenatal lifestyle interventions with GWG and maternal and neonatal outcomes. Data Sources: A 2-stage systematic literature search of MEDLINE, Embase, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, and Health Technology Assessment Database was conducted from February 1, 2017, to May 31, 2020. Search results from the present study were integrated with those from a previous systematic review from 1990 to February 2017. Study Selection: Randomized trials reporting GWG and maternal and neonatal outcomes. Data Extraction and Synthesis: Data were extracted for random-effects meta-analyses to calculate the summary effect estimates and 95% CIs. Main Outcomes and Measures: Outcomes were clinically prioritized, with mean GWG as the primary outcome. Secondary outcomes included gestational diabetes, hypertensive disorders of pregnancy, cesarean section, preterm delivery, large or small for gestational age neonates, neonatal intensive care unit admission, or fetal death. Results: A total of 117 randomized clinical trials of antenatal lifestyle interventions (involving 34 546 women) were included. Overall lifestyle intervention was associated with reduced GWG (−1.15 kg; 95% CI, −1.40 to −0.91), risk of gestational diabetes (odds ratio [OR], 0.79; 95% CI, 0.70-0.89), and total adverse maternal outcomes (OR, 0.89; 95% CI, 0.84-0.94) vs routine care. Compared with routine care, diet was associated with less GWG (−2.63 kg; 95% CI, −3.87 to −1.40) than physical activity (−1.04 kg; 95% CI, −1.33 to −0.74) or mixed interventions (eg, unstructured lifestyle support, written information with weight monitoring, or behavioral support alone) (−0.74 kg; 95% CI, −1.06 to −0.43). Diet was associated with reduced risk of gestational diabetes (OR, 0.61; 95% CI, 0.45-0.82), preterm delivery (OR, 0.43; 95% CI, 0.22-0.84), large for gestational age neonate (OR, 0.19; 95% CI, 0.08-0.47), neonatal intensive care admission (OR, 0.68; 95% CI, 0.48-0.95), and total adverse maternal (OR, 0.75; 95% CI, 0.61-0.92) and neonatal outcomes (OR, 0.44; 95% CI, 0.26-0.72). Physical activity was associated with reduced GWG and reduced risk of gestational diabetes (OR, 0.60; 95% CI, 0.47-0.75), hypertensive disorders (OR, 0.66; 95% CI, 0.48-0.90), cesarean section (OR, 0.85; 95% CI, 0.75-0.95), and total adverse maternal outcomes (OR, 0.78; 95% CI, 0.71-0.86). Diet with physical activity was associated with reduced GWG (−1.35 kg; 95% CI, −1.95 to −0.75) and reduced risk of gestational diabetes (OR, 0.72; 95% CI, 0.54-0.96) and total adverse maternal outcomes (OR, 0.81; 95% CI, 0.69-0.95). Mixed interventions were associated with reduced GWG only. Conclusions and Relevance: This systematic review and meta-analysis found level 1 evidence that antenatal structured diet and physical activity–based lifestyle interventions were associated with reduced GWG and lower risk of adverse maternal and neonatal outcomes. The findings support the implementation of such interventions in routine antenatal care and policy around the world.Helena J. Teede, Cate Bailey, Lisa J. Moran, Mahnaz Bahri Khomami, Joanne Enticott, Sanjeeva Ranasinha, Ewelina Rogozińska, Helen Skouteris, Jacqueline A. Boyle, Shakila Thangaratinam, Cheryce L. Harrison

Postnatal development of intestinal immune system in piglets: implications for the process of weaning

European-wide directives are in place to establish a sustainable production of pigs without using production enhancers and chemotherapeutics. Thus, an economically-viable pig production is now only possible when the physiological mechanisms of defense against pathogens and tolerance against nutrients and commensal bacteria in the intestinal immune system are taken into account. During the postnatal period the piglet is facing first the time large amounts of new antigens and at weaning a second wave of nutritional antigens is entering the intestinal tract. The appropriate development of humoral and cellular functions of the intestinal immune system is essential for optimum growth and performance of the piglets. The integrity of the intestinal surfaces is a prerequisite of intestinal immunity and tolerance. Secretory IgA serves to exclude harmful antigens from uptake. The induction of intestinal immune reactions starts with antigen presentation by professional antigen presenting cells of Peyer's patches and mesenteric lymph nodes. In addition, the intestinal lamina propria serves as a mucosal compartment for regulation of immune responses. Here especially T regulatory cells (CD4(+) CD25(+)) have their function for maintaining intestinal homeostasis. The network of mucosal T and B cells develops after birth in a programmed sequence; it is almost completed at week 7 after birth. Weaning is associated with changes in the regulation of the lymphoid cells in the mucosa. In small and large intestine increases in pro- and anti-inflammatory cytokines were observed after weaning in lymphocytes. Epithelial cells were studied both in intestinal samples and in vitro. Here the cytokine patterns provide evidence that weaning is inducing a transient inflammation of the mucosa. Piglets weaned under conventional conditions have a thicker mucosa than pigs weaned from isolators. Cells of isolator-reared pigs show slightly higher levels of activation markers - probably reflecting the interaction of the foreign protein derived from bovine milk. The results presented in this overview demonstrate that further effort is necessary to elucidate the function of the porcine intestinal immune system in the postnatal period and at the time of weaning to provide criteria for porcine intestinal health

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Double-Spin Asymmetry in the Cross Section for Exclusive rho^0 Production in Lepton-Proton Scattering

Evidence for a positive longitudinal double-spin asymmetry = 0.24 +-0.11 (stat) +-0.02 (syst) in the cross section for exclusive diffractive rho^0(770) vector meson production in polarised lepton-proton scattering was observed by the HERMES experiment. The longitudinally polarised 27.56 GeV HERA positron beam was scattered off a longitudinally polarised pure hydrogen gas target. The average invariant mass of the photon-proton system has a value of = 4.9 GeV, while the average negative squared four-momentum of the virtual photon is = 1.7 GeV^2. The ratio of the present result to the corresponding spin asymmetry in inclusive deep-inelastic scattering is in agreement with an early theoretical prediction based on the generalised vector meson dominance model.Comment: 10 pages, 4 embedded figures, LaTe

Measurement of the partial widths of the Z into up- and down-type quarks

Using the entire OPAL LEP1 on-peak Z hadronic decay sample, Z -> qbarq gamma decays were selected by tagging hadronic final states with isolated photon candidates in the electromagnetic calorimeter. Combining the measured rates of Z -> qbarq gamma decays with the total rate of hadronic Z decays permits the simultaneous determination of the widths of the Z into up- and down-type quarks. The values obtained, with total errors, were Gamma u = 300 ^{+19}_{-18} MeV and Gamma d = 381 ^{+12}_{-12} MeV. The results are in good agreement with the Standard Model expectation.Comment: 22 pages, 5 figures, Submitted to Phys. Letts.

Search for R-Parity Violating Decays of Scalar Fermions at LEP

A search for pair-produced scalar fermions under the assumption that R-parity is not conserved has been performed using data collected with the OPAL detector at LEP. The data samples analysed correspond to an integrated luminosity of about 610 pb-1 collected at centre-of-mass energies of sqrt(s) 189-209 GeV. An important consequence of R-parity violation is that the lightest supersymmetric particle is expected to be unstable. Searches of R-parity violating decays of charged sleptons, sneutrinos and squarks have been performed under the assumptions that the lightest supersymmetric particle decays promptly and that only one of the R-parity violating couplings is dominant for each of the decay modes considered. Such processes would yield final states consisting of leptons, jets, or both with or without missing energy. No significant single-like excess of events has been observed with respect to the Standard Model expectations. Limits on the production cross- section of scalar fermions in R-parity violating scenarios are obtained. Constraints on the supersymmetric particle masses are also presented in an R-parity violating framework analogous to the Constrained Minimal Supersymmetric Standard Model.Comment: 51 pages, 24 figures, Submitted to Eur. Phys. J.

Measurement of the Strong Coupling alpha s from Four-Jet Observables in e+e- Annihilation

Data from e+e- annihilation into hadrons at centre-of-mass energies between 91 GeV and 209 GeV collected with the OPAL detector at LEP, are used to study the four-jet rate as a function of the Durham algorithm resolution parameter ycut. The four-jet rate is compared to next-to-leading order calculations that include the resummation of large logarithms. The strong coupling measured from the four-jet rate is alphas(Mz0)= 0.1182+-0.0003(stat.)+-0.0015(exp.)+-0.0011(had.)+-0.0012(scale)+-0.0013(mass) in agreement with the world average. Next-to-leading order fits to the D-parameter and thrust minor event-shape observables are also performed for the first time. We find consistent results, but with significantly larger theoretical uncertainties.Comment: 25 pages, 15 figures, Submitted to Euro. Phys. J.