Structure of Frequency-Interacting RNA Helicase from \u3ci\u3eNeurospora crassa\u3c/i\u3e Reveals High Flexibility in a Domain Critical for Circadian Rhythm and RNA Surveillance

The FRH (frequency-interacting RNA helicase) protein is the Neurospora crassa homolog of yeast Mtr4, an essential RNA helicase that plays a central role in RNA metabolism as an activator of the nuclear RNA exosome. FRH is also a required component of the circadian clock, mediating protein interactions that result in the rhythmic repression of gene expression. Here we show that FRH unwinds RNA substrates in vitro with a kinetic profile similar to Mtr4, indicating that while FRH has acquired additional functionality, its core helicase function remains intact. In contrast with the earlier FRH structures, a new crystal form of FRH results in an ATP binding site that is undisturbed by crystal contacts and adopts a conformation consistent with nucleotide binding and hydrolysis. Strikingly, this new FRH structure adopts an arch domain conformation that is dramatically altered from previous structures. Comparison of the existing FRH structures reveals conserved hinge points that appear to facilitate arch motion. Regions in the arch have been previously shown to mediate a variety of protein-protein interactions critical for RNA surveillance and circadian clock functions. The conformational changes highlighted in the FRH structures provide a platform for investigating the relationship between arch dynamics and Mtr4/FRH function

Attributable costs of enterococcal bloodstream infections in a nonsurgical hospital cohort

BACKGROUND: Vancomycin-resistant enterococcal (VRE) bloodstream infections (BSI) are associated with increased morbidity and mortality. OBJECTIVE: To determine the attributable costs of vancomycin-sensitive (VSE) and VRE BSI and the independent impact of vancomycin-resistance on hospital costs. METHODS: A retrospective cohort study was conducted of 21,154 non-surgical patients admitted to an academic medical center between 2002 and 2003. Using administrative data, attributable hospital costs (inflation adjusted to $2007) and length of stay were estimated with multivariate generalized least squares (GLS) models and propensity score matched-pairs. RESULTS: The cohort included 182 VSE and 94 VRE BSI cases. After adjustment for demographics, comorbidities, procedures, non-enterococcal BSI, and early mortality, the attributable costs of VSE BSI were$2,250 (95% confidence interval [CI], $1,758–$2,880) in the standard GLS model and $2,023 (95$1,588–$2,575) in the propensity-score weighted GLS model and the attributable costs of VRE BSI were$4,479 (95% CI, $3,500–$5,732) in the standard GLS model and $4,036 (95$3,170–$5,140) in the propensity-score weighted GLS model. The median of the difference in costs between matched-pairs was$5,282 ($2,042–$8,043) for VSE BSI and $9,949 (95$1,579–$24,693) for VRE BSI. The attributable costs of vancomycin-resistance were$1,713 (95% CI, $1,338–$2,192) in the standard GLS model and $1,546 (95$1,214–$1,968) in the propensity-score weighted GLS model. Attributable length of stay ranged from 1.1–2.2 days for VSE BSI and 2.2–3.5 days for VRE BSI cases. CONCLUSIONS: VSE and VRE BSI were independently associated with hospital costs and length of stay. Vancomycin-resistance was associated with increased costs

An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein

Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni

Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140217/1/sur.2013.9999.pd

Bichromatic beam splitter for three-level atoms

We investigate schemes for the clean splitting of beams of three-level atoms using two standing-wave laser fields within an optical cavity. The proposed beam splitter is shown to work for atoms in the Λ ladder, and ssV configurations. For appropriate values of Rabi frequencies and detunings, we obtain a triangular type of potential for the atomic states of interest. As well as modeling the coherent evolution of the systems, we have used quantum Monte Carlo wave-function methods to model the effects of spontaneous emission on the resulting diffraction pattern, finding significant differences between the three configurations. We also investigate the limits of the Raman-Nath approximation for our systems, using the symmetric split-operator technique to include the effects of the kinetic term in the Hamiltonian. We also present the results of calculations in which the split output beams are recombined, demonstrating the expected interference for differently prepared input beams. In comparison with two-level beam splitters using a single standing wave, we obtain a superior splitting, while, in comparison with magneto-optical beam splitters, our system possesses the worthwhile practical advantages of experimental simplicity

Measurement of the scintillation time spectra and pulse-shape discrimination of low-energy beta and nuclear recoils in liquid argon with DEAP-1

The DEAP-1 low-background liquid argon detector was used to measure scintillation pulse shapes of electron and nuclear recoil events and to demonstrate the feasibility of pulse-shape discrimination (PSD) down to an electron-equivalent energy of 20 keV. In the surface dataset using a triple-coincidence tag we found the fraction of beta events that are misidentified as nuclear recoils to be $<1.4\times 10^{-7}$ (90% C.L.) for energies between 43-86 keVee and for a nuclear recoil acceptance of at least 90%, with 4% systematic uncertainty on the absolute energy scale. The discrimination measurement on surface was limited by nuclear recoils induced by cosmic-ray generated neutrons. This was improved by moving the detector to the SNOLAB underground laboratory, where the reduced background rate allowed the same measurement with only a double-coincidence tag. The combined data set contains $1.23\times10^8$ events. One of those, in the underground data set, is in the nuclear-recoil region of interest. Taking into account the expected background of 0.48 events coming from random pileup, the resulting upper limit on the electronic recoil contamination is $<2.7\times10^{-8}$ (90% C.L.) between 44-89 keVee and for a nuclear recoil acceptance of at least 90%, with 6% systematic uncertainty on the absolute energy scale. We developed a general mathematical framework to describe PSD parameter distributions and used it to build an analytical model of the distributions observed in DEAP-1. Using this model, we project a misidentification fraction of approx. $10^{-10}$ for an electron-equivalent energy threshold of 15 keV for a detector with 8 PE/keVee light yield. This reduction enables a search for spin-independent scattering of WIMPs from 1000 kg of liquid argon with a WIMP-nucleon cross-section sensitivity of $10^{-46}$ cm$^2$, assuming negligible contribution from nuclear recoil backgrounds.Comment: Accepted for publication in Astroparticle Physic

Nonlinear modeling of venous leg ulcer healing rates

<p>Abstract</p> <p>Background</p> <p>The purpose of this manuscript was to determine whether the change in wound surface area over time could be described through nonlinear mathematics.</p> <p>Methods</p> <p>We studied 3,588 serial wound tracings of 338 venous leg ulcers (VLUs) that had been followed during a controlled, prospective, randomized trial of two topical wound treatments.</p> <p>Results</p> <p>A majority (72%) of VLUs exhibited surface area reduction via an exponential decay model, particularly during the early stages of healing. These results were consistent with the mechanics of wound contraction and epithelial cell proliferation, supported by the higher frequency at which exponential surface area reduction associated with full wound closure (35% of wounds that fit the exponential model healed vs. 21% of wounds that did not fit the exponential model completely healed during the study period, p = 0.018). Goodness-of-fit statistics suggested that much of the individual variation in healing could be described as nonlinear variation from the exponential model.</p> <p>Conclusion</p> <p>We believe that parameter estimates from a mathematical model may provide a more accurate quantification of wound healing rates, and that similar models may someday reach routine use in comparing the efficacy of various treatments in routine practice and in product registration trials.</p

Emergence of contact injuries in invasion team sports : an ecological dynamics rationale

The incidence of contact injuries in team sports is considerable, and injury mechanisms need to be comprehensively understood to facilitate the adoption of preventive measures. In Association Football, evidence shows that the highest prevalence of contact injuries emerges in one-on-one interactions. However, previous studies have tended to operationally report injury mechanisms in isolation, failing to provide a theoretical rationale to explain how injuries might emerge from interactions between opposing players. In this position paper, we propose an ecological dynamics framework to enhance current understanding of behavioural processes leading to contact injuries in team sports. Based on previous research highlighting the dynamics of performer–environment interactions, contact injuries are proposed to emerge from symmetry-breaking processes during on-field interpersonal interactions among competing players and the ball. Central to this approach is consideration of candidate control parameters that may provide insights on the information sources used by players to reduce risk of contact injuries during performance. Clinically, an ecological dynamics analysis could allow sport practitioners to design training sessions based on selected parameter threshold values as primary and/or secondary preventing measures during training and rehabilitation sessions

The ACS Nearby Galaxy Survey Treasury II. Young Stars and their Relation to Halpha and UV Emission Timescales in the M81 Outer Disk

We have obtained resolved stellar photometry from Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) observations of a field in the outer disk of M81 as part of the ACS Nearby Galaxy Survey Treasury (ANGST). Motivated by the recent discovery of extended UV (XUV) disks around many nearby spiral galaxies, we use the observed stellar population to derive the recent star formation histories of five ~0.5 kpc-sized regions within this field. These regions were selected on the basis of their UV luminosity from GALEX and include two HII regions, two regions which are UV-bright but Halpha-faint, and one "control" region faint in both UV and Halpha. We estimate our effective SFR detection limit at ~2 x 10^-4 Msun/yr, which is lower than that of GALEX for regions of this size. As expected, the HII regions contain massive main sequence stars (in the mass range 18-27 Msun, based on our best extinction estimates), while similar massive main sequence stars are lacking in the UV-bright/Halpha-faint regions. The observations are consistent with stellar ages 16 Myr in the UV-bright/Halpha-faint regions. All regions but the control have formed ~10^4 Msun of stars over the past ~65 Myr. Thus, our results, for at least one small area in the outer disk of M81, are consistent with an age difference being sufficient to explain the observed discrepancy between star-forming regions detected in Halpha and those detected exclusively in UV. However, our data cannot conclusively rule out other explanations, such as a strongly truncated initial mass function (IMF).Comment: 18 pages, 12 figures, accepted for publication in ApJ, paper with full resolution figures available: http://www.nearbygalaxies.org/papers/M81_Halpha_uv.pd