GEN1 from a thermophilic fungus is functionally closely similar to non-eukaryotic junction-resolving enzymes

AbstractProcessing of Holliday junctions is essential in recombination. We have identified the gene for the junction-resolving enzyme GEN1 from the thermophilic fungus Chaetomium thermophilum and expressed the N-terminal 487-amino-acid section. The protein is a nuclease that is highly selective for four-way DNA junctions, cleaving 1nt 3′ to the point of strand exchange on two strands symmetrically disposed about a diagonal axis. CtGEN1 binds to DNA junctions as a discrete homodimer with nanomolar affinity. Analysis of the kinetics of cruciform cleavage shows that cleavage of the second strand occurs an order of magnitude faster than the first cleavage so as to generate a productive resolution event. All these properties are closely similar to those described for bacterial, phage and mitochondrial junction-resolving enzymes. CtGEN1 is also similar in properties to the human enzyme but lacks the problems with aggregation that currently prevent detailed analysis of the latter protein. CtGEN1 is thus an excellent enzyme with which to engage in biophysical and structural analysis of eukaryotic GEN1

A comprehensive methodology for determining the most informative mammographic features

This study aims to determine the most informative mammographic features for breast cancer diagnosis using mutual information (MI) analysis. Our Health Insurance Portability and Accountability Act-approved database consists of 44,397 consecutive structured mammography reports for 20,375 patients collected from 2005 to 2008. The reports include demographic risk factors (age, family and personal history of breast cancer, and use of hormone therapy) and mammographic features from the Breast Imaging Reporting and Data System lexicon. We calculated MI using Shannon's entropy measure for each feature with respect to the outcome (benign/malignant using a cancer registry match as reference standard). In order to evaluate the validity of the MI rankings of features, we trained and tested naïve Bayes classifiers on the feature with tenfold cross-validation, and measured the predictive ability using area under the ROC curve (AUC). We used a bootstrapping approach to assess the distributional properties of our estimates, and the DeLong method to compare AUC. Based on MI, we found that mass margins and mass shape were the most informative features for breast cancer diagnosis. Calcification morphology, mass density, and calcification distribution provided predictive information for distinguishing benign and malignant breast findings. Breast composition, associated findings, and special cases provided little information in this task. We also found that the rankings of mammographic features with MI and AUC were generally consistent. MI analysis provides a framework to determine the value of different mammographic features in the pursuit of optimal (i.e., accurate and efficient) breast cancer diagnosis. © 2013 Society for Imaging Informatics in Medicine

Astrophysical Uncertainties in the Cosmic Ray Electron and Positron Spectrum From Annihilating Dark Matter

In recent years, a number of experiments have been conducted with the goal of studying cosmic rays at GeV to TeV energies. This is a particularly interesting regime from the perspective of indirect dark matter detection. To draw reliable conclusions regarding dark matter from cosmic ray measurements, however, it is important to first understand the propagation of cosmic rays through the magnetic and radiation fields of the Milky Way. In this paper, we constrain the characteristics of the cosmic ray propagation model through comparison with observational inputs, including recent data from the CREAM experiment, and use these constraints to estimate the corresponding uncertainties in the spectrum of cosmic ray electrons and positrons from dark matter particles annihilating in the halo of the Milky Way.Comment: 21 pages, 9 figure

Scaling Tests of the Cross Section for Deeply Virtual Compton Scattering

We present the first measurements of the \vec{e}p->epg cross section in the deeply virtual Compton scattering (DVCS) regime and the valence quark region. The Q^2 dependence (from 1.5 to 2.3 GeV^2) of the helicity-dependent cross section indicates the twist-2 dominance of DVCS, proving that generalized parton distributions (GPDs) are accessible to experiment at moderate Q^2. The helicity-independent cross section is also measured at Q^2=2.3 GeV^2. We present the first model-independent measurement of linear combinations of GPDs and GPD integrals up to the twist-3 approximation.Comment: 5 pages, 4 figures, 2 tables. Text shortened for publication. References added. One figure remove

Pegasus IV: Discovery and Spectroscopic Confirmation of an Ultra-faint Dwarf Galaxy in the Constellation Pegasus

We report the discovery of Pegasus IV, an ultra-faint dwarf galaxy found in archival data from the Dark Energy Camera processed by the DECam Local Volume Exploration Survey. Pegasus IV is a compact, ultra-faint stellar system (r1 2 = 41-+68 pc; MV = −4.25 ± 0.2 mag) located at a heliocentric distance of 90-+64 kpc. Based on spectra of seven nonvariable member stars observed with Magellan/IMACS, we confidently resolve Pegasus IV’s velocity dispersion, measuring sv = 3.3-+1.11.7 km s−1 (after excluding three velocity outliers); this implies a mass-to-light ratio of M1 2 LV,1 2 = 167-+99224M☉ L☉ for the system. From the five stars with the highest signal-to-noise spectra, we also measure a systemic metallicity of [Fe/H] =-2.63-+0.300.26 dex, making Pegasus IV one of the most metal-poor ultra-faint dwarfs. We tentatively resolve a nonzero metallicity dispersion for the system. These measurements provide strong evidence that Pegasus IV is a dark-matter-dominated dwarf galaxy, rather than a star cluster. We measure Pegasus IV’s proper motion using data from Gaia Early Data Release 3, finding (μα*, μδ) = (0.33 ± 0.07, −0.21 ± 0.08) mas yr−1. When combined with our measured systemic velocity, this proper motion suggests that Pegasus IV is on an elliptical, retrograde orbit, and is currently near its orbital apocenter. Lastly, we identify three potential RR Lyrae variable stars within Pegasus IV, including one candidate member located more than 10 half-light radii away from the system’s centroid. The discovery of yet another ultra-faint dwarf galaxy strongly suggests that the census of Milky Way satellites is still incomplete, even within 100 kpc

Exclusive Neutral Pion Electroproduction in the Deeply Virtual Regime

We present measurements of the ep->ep pi^0 cross section extracted at two values of four-momentum transfer Q^2=1.9 GeV^2 and Q^2=2.3 GeV^2 at Jefferson Lab Hall A. The kinematic range allows to study the evolution of the extracted hadronic tensor as a function of Q^2 and W. Results will be confronted with Regge inspired calculations and GPD predictions. An intepretation of our data within the framework of semi-inclusive deep inelastic scattering has also been attempted

Disposition kinetics and urinary excretion of ciprofloxacin in goats following single intravenous administration

We evaluated the pharmacokinetics of ciprofloxacin in serum (n = 6) and urine (n = 4) in goats following a single intravenous administration of 4 mg/kg body weight. The serum concentration-time curves of ciprofloxacin were best fitted by a two-compartment open model. The drug was detected in goat serum up to 12 h. The elimination rate constant (β) and elimination half-life (t1/2β) were 0.446 ± 0.04 h-1 and 1.630 ± 0.17 h, respectively. The apparent volume of distribution at steady state (Vdss) was 2.012 ± 0.37 l/kg and the total body clearance (ClB) was 16.27 ± 1.87 ml/min/kg. Urinary recovery of ciprofloxacin was 29.70% ± 10.34% of the administered dose within 36 h post administration. In vitro serum protein binding was 41% ± 13.10%. Thus, a single daily intravenous dose of 4 mg/kg is sufficient to maintain effective levels in serum and for 36 h in urine, allowing treatment of systemic, Gram-negative bacterial infections and urinary tract infections by most pathogens

Constraints on the Nucleon Strange Form Factors at Q^2 ~ 0.1 GeV^2

We report the most precise measurement to date of a parity-violating asymmetry in elastic electron-proton scattering. The measurement was carried out with a beam energy of 3.03 GeV and a scattering angle =6 degrees, with the result A_PV = -1.14 +/- 0.24 (stat) +/- 0.06 (syst) parts per million. From this we extract, at Q^2 = 0.099 GeV^2, the strange form factor combination G_E^s + 0.080 G_M^s = 0.030 +/- 0.025 (stat) +/- 0.006 (syst) +/- 0.012 (FF) where the first two errors are experimental and the last error is due to the uncertainty in the neutron electromagnetic form factor. This result significantly improves current knowledge of G_E^s and G_M^s at Q^2 ~0.1 GeV^2. A consistent picture emerges when several measurements at about the same Q^2 value are combined: G_E^s is consistent with zero while G_M^s prefers positive values though G_E^s=G_M^s=0 is compatible with the data at 95% C.L.Comment: minor wording changes for clarity, updated references, dropped one figure to improve focu

Flares, wind and nebulae: the 2015 December mini-outburst of V404 Cygni

After more than 26 years in quiescence, the black hole transient V404 Cyg went into a luminous outburst in June 2015, and additional activity was detected in late December of the same year. Here, we present an optical spectroscopic follow-up of the December mini-outburst, together with X-ray, optical and radio monitoring that spanned more than a month. Strong flares with gradually increasing intensity are detected in the three spectral ranges during the ∼ 10 days following the Swift trigger. Our optical spectra reveal the presence of a fast outflowing wind, as implied by the detection of a P-Cyg profile (He i–5876 ˚A) with a terminal velocity of ∼ 2500 kms−1 . Nebularlike spectra – with an H α equivalent width of ∼ 500 ˚A – are also observed. All these features are similar to those seen during the main June 2015 outburst. Thus, the fast optical wind simultaneous with the radio jet is most likely present in every V404 Cyg outburst. Finally, we report on the detection of a strong radio flare in late January 2016, when X-ray and optical monitoring had stopped due to Sun constraints

Colliders and Cosmology

Dark matter in variations of constrained minimal supersymmetric standard models will be discussed. Particular attention will be given to the comparison between accelerator and direct detection constraints.Comment: Submitted for the SUSY07 proceedings, 15 pages, LaTex, 26 eps figure