Design of a combinatorial DNA microarray for protein-DNA interaction studies

BACKGROUND: Discovery of precise specificity of transcription factors is an important step on the way to understanding the complex mechanisms of gene regulation in eukaryotes. Recently, double-stranded protein-binding microarrays were developed as a potentially scalable approach to tackle transcription factor binding site identification. RESULTS: Here we present an algorithmic approach to experimental design of a microarray that allows for testing full specificity of a transcription factor binding to all possible DNA binding sites of a given length, with optimally efficient use of the array. This design is universal, works for any factor that binds a sequence motif and is not species-specific. Furthermore, simulation results show that data produced with the designed arrays is easier to analyze and would result in more precise identification of binding sites. CONCLUSION: In this study, we present a design of a double stranded DNA microarray for protein-DNA interaction studies and show that our algorithm allows optimally efficient use of the arrays for this purpose. We believe such a design will prove useful for transcription factor binding site identification and other biological problems

SuperCLASS - III. Weak lensing from radio and optical observations in Data Release 1

We describe the first results on weak gravitational lensing from the SuperCLASS survey: the first survey specifically designed to measure the weak lensing effect in radio-wavelength data, both alone and in cross-correlation with optical data. We analyse 1.53deg2 of optical data from the Subaru telescope and 0.26deg2 of radio data from the e-MERLIN and VLA telescopes (the DR1 data set). Using standard methodologies on the optical data only we make a significant (10σ) detection of the weak lensing signal (a shear power spectrum) due to the massive supercluster of galaxies in the targeted region. For the radio data we develop a new method to measure the shapes of galaxies from the interferometric data, and we construct a simulation pipeline to validate this method. We then apply this analysis to our radio observations, treating the e-MERLIN and VLA data independently. We achieve source densities of 0.5 arcmin−2 in the VLA data and 0.06 arcmin−2 in the e-MERLIN data, numbers which prove too small to allow a detection of a weak lensing signal in either the radio data alone or in cross-correlation with the optical data. Finally, we show preliminary results from a visibility-plane combination of the data from e-MERLIN and VLA which will be used for the forthcoming full SuperCLASS data release. This approach to data combination is expected to enhance both the number density of weak lensing sources available, and the fidelity with which their shapes can be measured

On-line mass spectrometry: membrane inlet sampling

Significant insights into plant photosynthesis and respiration have been achieved using membrane inlet mass spectrometry (MIMS) for the analysis of stable isotope distribution of gases. The MIMS approach is based on using a gas permeable membrane to enable the entry of gas molecules into the mass spectrometer source. This is a simple yet durable approach for the analysis of volatile gases, particularly atmospheric gases. The MIMS technique strongly lends itself to the study of reaction flux where isotopic labeling is employed to differentiate two competing processes; i.e., O2 evolution versus O2 uptake reactions from PSII or terminal oxidase/rubisco reactions. Such investigations have been used for in vitro studies of whole leaves and isolated cells. The MIMS approach is also able to follow rates of isotopic exchange, which is useful for obtaining chemical exchange rates. These types of measurements have been employed for oxygen ligand exchange in PSII and to discern reaction rates of the carbonic anhydrase reactions. Recent developments have also engaged MIMS for online isotopic fractionation and for the study of reactions in inorganic systems that are capable of water splitting or H2 generation. The simplicity of the sampling approach coupled to the high sensitivity of modern instrumentation is a reason for the growing applicability of this technique for a range of problems in plant photosynthesis and respiration. This review offers some insights into the sampling approaches and the experiments that have been conducted with MIMS

SuperCLASS - I. The super cluster assisted shear survey: Project overview and data release 1

The SuperCLuster Assisted Shear Survey (SuperCLASS) is a legacy programme using the e-MERLIN interferometric array. The aim is to observe the sky at L-band (1.4 GHz) to a r.m.s. of 7μJybeam−1 over an area of ∼1deg2 centred on the Abell 981 supercluster. The main scientific objectives of the project are: (i) to detect the effects of weak lensing in the radio in preparation for similar measurements with the Square Kilometre Array (SKA); (ii) an extinction free census of star formation and AGN activity out to z ∼ 1. In this paper we give an overview of the project including the science goals and multiwavelength coverage before presenting the first data release. We have analysed around 400 h of e-MERLIN data allowing us to create a Data Release 1 (DR1) mosaic of ∼0.26deg2 to the full depth. These observations have been supplemented with complementary radio observations from the Karl G. Jansky Very Large Array (VLA) and optical/near infrared observations taken with the Subaru, Canada-France-Hawaii, and Spitzer Telescopes. The main data product is a catalogue of 887 sources detected by the VLA, of which 395 are detected by e-MERLIN and 197 of these are resolved. We have investigated the size, flux, and spectral index properties of these sources finding them compatible with previous studies. Preliminary photometric redshifts, and an assessment of galaxy shapes measured in the radio data, combined with a radio-optical cross-correlation technique probing cosmic shear in a supercluster environment, are presented in companion papers

Gene-Boosted Assembly of a Novel Bacterial Genome from Very Short Reads

Recent improvements in technology have made DNA sequencing dramatically faster and more efficient than ever before. The new technologies produce highly accurate sequences, but one drawback is that the most efficient technology produces the shortest read lengths. Short-read sequencing has been applied successfully to resequence the human genome and those of other species but not to whole-genome sequencing of novel organisms. Here we describe the sequencing and assembly of a novel clinical isolate of Pseudomonas aeruginosa, strain PAb1, using very short read technology. From 8,627,900 reads, each 33 nucleotides in length, we assembled the genome into one scaffold of 76 ordered contiguous sequences containing 6,290,005 nucleotides, including one contig spanning 512,638 nucleotides, plus an additional 436 unordered contigs containing 416,897 nucleotides. Our method includes a novel gene-boosting algorithm that uses amino acid sequences from predicted proteins to build a better assembly. This study demonstrates the feasibility of very short read sequencing for the sequencing of bacterial genomes, particularly those for which a related species has been sequenced previously, and expands the potential application of this new technology to most known prokaryotic species

Subclinical iron deficiency is a strong predictor of bacterial vaginosis in early pregnancy

BACKGROUND: Bacterial vaginosis (BV) is the single most common vaginal infection in women of childbearing age and associated with a sizeable infectious disease burden among both non-pregnant and pregnant women, including a significantly elevated risk of adverse pregnancy outcome. Overall, little progress has been made in identifying causal factors involved in BV acquisition and persistence. We sought to evaluate maternal iron status in early pregnancy as a putative risk factor for BV, considering that micronutrients, and iron deficiency in particular, affect the host response against bacterial colonization, even in the setting of mild micronutrient deficiencies. METHODS: In a nested case-control study, we compared maternal iron status at entry to prenatal care (mean gestational age 9.2 ± 2.6 weeks) between eighty women with healthy vaginal microflora and eighteen women with vaginosis-like microflora. Vaginal microflora status was assessed by assigning a modified Nugent score to a Gram-stained vaginal smear. Maternal iron status was assayed by an array of conventional erythrocyte and serum indicators for iron status assessment, but also by more sensitive and more specific indicators of iron deficiency, including soluble transferrin receptors (sTfR) as an accurate measure of cellular and tissue iron deficiency and the iron deficiency log(10)[sTfR/ferritin] index as the presently most accurate measure of body storage iron available. RESULTS: We found no statistically significant correlation between vaginal microflora status and routinely assessed iron parameters. In contrast, a highly significant difference between the healthy and vaginosis-like microflora groups of women was shown in mean values of sTfR concentrations (1.15 ± 0.30 mg/L versus 1.37 ± 0.38 mg/L, p = 0.008) and in mean iron deficiency log(10)[sTfR/ferritin] index values (1.57 ± 0.30 versus 1.08 ± 0.56, p = 0.003), indicating a strong association between iron deficiency and vaginosis-like microflora. An sTfR concentration >1.45 mg/L was associated with a 3-fold increased risk (95%CI: 1.4–6.7) of vaginosis-like microflora and after controlling for maternal age, gestational length, body mass, parity, and smoking habits with an adjusted odds ratio of 4.5 (95%CI: 1.4–14.2). CONCLUSION: We conclude that subclinical iron deficiency, presumably resulting from inadequate preconceptional iron supplies, is strongly and independently associated with vaginosis-like microflora during early pregnancy

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Evidence for the Higgs-boson Yukawa coupling to tau leptons with the ATLAS detector

Results of a search for H → τ τ decays are presented, based on the full set of proton-proton collision data recorded by the ATLAS experiment at the LHC during 2011 and 2012. The data correspond to integrated luminosities of 4.5 fb−1 and 20.3 fb−1 at centre-of-mass energies of √s = 7 TeV and √s = 8 TeV respectively. All combinations of leptonic (τ → `νν¯ with ` = e, µ) and hadronic (τ → hadrons ν) tau decays are considered. An excess of events over the expected background from other Standard Model processes is found with an observed (expected) significance of 4.5 (3.4) standard deviations. This excess provides evidence for the direct coupling of the recently discovered Higgs boson to fermions. The measured signal strength, normalised to the Standard Model expectation, of µ = 1.43 +0.43 −0.37 is consistent with the predicted Yukawa coupling strength in the Standard Model

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