Joint profiling of DNA methylation and chromatin architecture in single cells.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues

Vector boson pair production at the LHC

We present phenomenological results for vector boson pair production at the LHC, obtained using the parton-level next-to-leading order program MCFM. We include the implementation of a new process in the code, pp -> \gamma\gamma, and important updates to existing processes. We incorporate fragmentation contributions in order to allow for the experimental isolation of photons in \gamma\gamma, W\gamma, and Z\gamma production and also account for gluon-gluon initial state contributions for all relevant processes. We present results for a variety of phenomenological scenarios, at the current operating energy of \sqrt{s} = 7 TeV and for the ultimate machine goal, \sqrt{s} = 14 TeV. We investigate the impact of our predictions on several important distributions that enter into searches for new physics at the LHC.Comment: 35 pages, 14 figure

Extremely high He isotope ratios in MORB-source mantle from the proto-Iceland plume

The high <sup>3</sup>He/<sup>4</sup>He ratio of volcanic rocks thought to be derived from mantle plumes is taken as evidence for the existence of a mantle reservoir that has remained largely undegassed since the Earth's accretion. The helium isotope composition of this reservoir places constraints on the origin of volatiles within the Earth and on the evolution and structure of the Earth's mantle. Here we show that olivine phenocrysts in picritic basalts presumably derived from the proto-Iceland plume at Baffin Island, Canada, have the highest magmatic <sup>3</sup>He/<sup>4</sup>He ratios yet recorded. A strong correlation between <sup>3</sup>He/<sup>4</sup>He and <sup>87</sup>Sr/<sup>86</sup>Sr, <sup>143</sup>Nd/<sup>144</sup>Nd and trace element ratios demonstrate that the <sup>3</sup>He-rich end-member is present in basalts that are derived from large-volume melts of depleted upper-mantle rocks. This reservoir is consistent with the recharging of depleted upper-mantle rocks by small volumes of primordial volatile-rich lower-mantle material at a thermal boundary layer between convectively isolated reservoirs. The highest <sup>3</sup>He/<sup>4</sup>He basalts from Hawaii and Iceland plot on the observed mixing trend. This indicates that a <sup>3</sup>He-recharged depleted mantle (HRDM) reservoir may be the principal source of high <sup>3</sup>He/<sup>4</sup>He in mantle plumes, and may explain why the helium concentration of the 'plume' component in ocean island basalts is lower than that predicted for a two-layer, steady-state model of mantle structure

Enantioselective construction of the ABCDE pentacyclic core of the Strychnos alkaloids

An efficient enantioselective 12-step synthesis of the ABCDE pentacyclic core of the Strychnos alkaloids is described. A key feature of this approach is an organocatalyzed enantioselective desymmetrization to generate the morphan core in high ee and dr. After palladium-catalyzed installation of the indole moiety, a subsequent 5-exo-trig dearomatizing atom transfer radical cyclization was developed to construct the C-ring. Following a series of functional group interconversions, the pentacyclic amine core was obtained with all the relevant architecture including five stereocenters pertaining to the Strychnos alkaloids

Automation of one-loop QCD corrections

We present the complete automation of the computation of one-loop QCD corrections, including UV renormalization, to an arbitrary scattering process in the Standard Model. This is achieved by embedding the OPP integrand reduction technique, as implemented in CutTools, into the MadGraph framework. By interfacing the tool so constructed, which we dub MadLoop, with MadFKS, the fully automatic computation of any infrared-safe observable at the next-to-leading order in QCD is attained. We demonstrate the flexibility and the reach of our method by calculating the production rates for a variety of processes at the 7 TeV LHC.Comment: 64 pages, 12 figures. Corrected the value of m_Z in table 1. In table 2, corrected the values of cross sections in a.4 and a.5 (previously computed with mu=mtop/2 rather than mu=mtop/4). In table 2, corrected the values of NLO cross sections in b.3, b.6, c.3, and e.7 (the symmetry factor for a few virtual channels was incorrect). In sect. A.4.3, the labeling of the four-momenta was incorrec

Predictions for Higgs production at the Tevatron and the associated uncertainties

We update the theoretical predictions for the production cross sections of the Standard Model Higgs boson at the Fermilab Tevatron collider, focusing on the two main search channels, the gluon-gluon fusion mechanism $gg \to H$ and the Higgs-strahlung processes $q \bar q \to VH$ with $V=W/Z$, including all relevant higher order QCD and electroweak corrections in perturbation theory. We then estimate the various uncertainties affecting these predictions: the scale uncertainties which are viewed as a measure of the unknown higher order effects, the uncertainties from the parton distribution functions and the related errors on the strong coupling constant, as well as the uncertainties due to the use of an effective theory approach in the determination of the radiative corrections in the $gg \to H$ process at next-to-next-to-leading order. We find that while the cross sections are well under control in the Higgs--strahlung processes, the theoretical uncertainties are rather large in the case of the gluon-gluon fusion channel, possibly shifting the central values of the next-to-next-to-leading order cross sections by more than $\approx 40$. These uncertainties are thus significantly larger than the $\approx 10$ error assumed by the CDF and D0 experiments in their recent analysis that has excluded the Higgs mass range $M_H=$162-166 GeV at the 95% confidence level. These exclusion limits should be, therefore, reconsidered in the light of these large theoretical uncertainties.Comment: 40 pages, 12 figures. A few typos are corrected and some updated numbers are provide

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

NLO Higgs boson production plus one and two jets using the POWHEG BOX, MadGraph4 and MCFM

We present a next-to-leading order calculation of Higgs boson production plus one and two jets via gluon fusion interfaced to shower Monte Carlo programs, implemented according to the POWHEG method. For this implementation we have used a new interface of the POWHEG BOX with MadGraph4, that generates the codes for generic Born and real processes automatically. The virtual corrections have been taken from the MCFM code. We carry out a simple phenomenological study of our generators, comparing them among each other and with fixed next-to-leading order results.Comment: 27 pages, 21 figure

Waiting time distribution in public health care: empirics and theory

Excessive waiting times for elective surgery have been a long-standing concern in many national healthcare systems in the OECD. How do the hospital admission patterns that generate waiting lists affect different patients? What are the hospitals characteristics that determine waiting times? By developing a model of healthcare provision and analysing empirically the entire waiting time distribution we attempt to shed some light on those issues. We first build a theoretical model that describes the optimal waiting time distribution for capacity constraint hospitals. Secondly, employing duration analysis, we obtain empirical representations of that distribution across hospitals in the UK from 1997–2005. We observe important differences on the ‘scale’ and on the ‘shape’ of admission rates. Scale refers to how quickly patients are treated and shape represents trade-offs across duration-treatment profiles. By fitting the theoretical to the empirical distributions we estimate the main structural parameters of the model and are able to closely identify the main drivers of these empirical differences. We find that the level of resources allocated to elective surgery (budget and physical capacity), which determines how constrained the hospital is, explains differences in scale. Changes in benefits and costs structures of healthcare provision, which relate, respectively, to the desire to prioritise patients by duration and the reduction in costs due to delayed treatment, determine the shape, affecting short and long duration patients differently

Enantioselective desymmetrization of prochiral cyclohexanones by organocatalytic intramolecular Michael additions to α,β-unsaturated esters

A new catalytic asymmetric desymmetrization reaction for the synthesis of enantioenriched derivatives of 2-azabicyclo[3.3.1]nonane, a key motif common to many alkaloids, has been developed. Employing a cyclohexanediamine-derived primary amine organocatalyst, a range of prochiral cyclohexanone derivatives possessing an α,β-unsaturated ester moiety linked to the 4-position afforded the bicyclic products, which possess three stereogenic centers, as single diastereoisomers in high enantioselectivity (83-99% ee) and in good yields (60-90%). Calculations revealed that stepwise C-C bond formation and proton transfer via a chair-shaped transition state dictate the exclusive endo selectivity and enabled the development of a highly enantioselective primary amine catalyst