2,678 research outputs found

    Structure and stereochemistry of the base excision repair glycosylase MutY reveal a mechanism similar to retaining glycosidases.

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    MutY adenine glycosylases prevent DNA mutations by excising adenine from promutagenic 8-oxo-7,8-dihydroguanine (OG):A mismatches. Here, we describe structural features of the MutY active site bound to an azaribose transition state analog which indicate a catalytic role for Tyr126 and approach of the water nucleophile on the same side as the departing adenine base. The idea that Tyr126 participates in catalysis, recently predicted by modeling calculations, is strongly supported by mutagenesis and by seeing close contact between the hydroxyl group of this residue and the azaribose moiety of the transition state analog. NMR analysis of MutY methanolysis products corroborates a mechanism for adenine removal with retention of stereochemistry. Based on these results, we propose a revised mechanism for MutY that involves two nucleophilic displacement steps akin to the mechanisms accepted for 'retaining' O-glycosidases. This new-for-MutY yet familiar mechanism may also be operative in related base excision repair glycosylases and provides a critical framework for analysis of human MutY (MUTYH) variants associated with inherited colorectal cancer

    Goodwill Going Green: How Green Branding Can Generate $1M in Revenue

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    Goodwill Industries is a nonprofit organization. Not only do they specialize in charity work, but they also have a chain of stores that focus on thrift shopping. Additionally, Goodwill provides other services, such as recycling clothing, electronics, and other goods. Recently, Goodwill of Akron, Ohio received a grant of five million dollars, where the money for the grant would have to be utilized in five years. The main objective of this project was to find a way for Goodwill to use grant money efficiently, to generate revenue for a new transportation initiative. Our team has recommended utilizing the most popular social media platforms a little more, along with improving the Goodwill app, and utilizing in-store marketing to increase awareness about green branding. Overall, Goodwill should focus on green branding when using their grant

    Retrospective Study of Midazolam Protocol for Prehospital Behavioral Emergencies

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    Introduction: Agitated patients in the prehospital setting pose challenges for both patient care and emergency medical services (EMS) provider safety. Midazolam is frequently used to control agitation in the emergency department setting; however, limited data exist in the prehospital setting. We describe our experience treating patients with midazolam for behavioral emergencies in a large urban EMS system. We hypothesized that using midazolam for acute agitation leads to improved clinical conditions without causing significant clinical deterioration.Methods: We performed a retrospective review of EMS patient care reports following implementation of a behavioral emergencies protocol in a large urban EMS system from February 2014–June 2016. For acute agitation, paramedics administered midazolam 1 milligram (mg) intravenous (IV), 5 mg intramuscular (IM), or 5 mg intranasal (IN). Results were analyzed using descriptive statistics, Levene’s test for assessing variance among study groups, and t-test to evaluate effectiveness based on route.Results: In total, midazolam was administered 294 times to 257 patients. Median age was 30 (interquartile range 24–42) years, and 66.5% were male. Doses administered were 1 mg (7.1%) and 5 mg (92.9%). Routes were IM (52.0%), IN (40.8%), and IV (7.1%). A second dose was administered to 37 patients. In the majority of administrations, midazolam improved the patient’s condition (73.5%) with infrequent adverse events (3.4%). There was no significant difference between the effectiveness of IM and IN midazolam (71.0% vs 75.4%; p = 0.24).Conclusion: A midazolam protocol for prehospital agitation was associated with reduced agitation and a low rate of adverse events

    Dual-Balance Electrodynamic Trap as a Microanalytical Tool for Identifying Gel Transitions and Viscous Properties of Levitated Aerosol Particles

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    The formation of gelatinous networks within an aerosol particle significantly alters the physicochemical properties of the aerosol material. Existing techniques for studying gel transitions rely on bulk rheometry, which is limited by contact with the sample, or microrheological techniques such as holographic optical tweezers, which rely on expensive equipment and high-powered lasers that can degrade light-absorbing aerosol. Here, we present a new technique to probe the microrheological characteristics of aerosol particles and explore gel formation under atmospheric conditions in a contactless environment without the need for high-power light sources. In a dual-balance quadrupole electrodynamic balance, levitated droplets of opposite polarity are trapped and equilibrated at fixed relative humidity (RH) and then subsequently merged, and the physical characteristics of the merged droplets are monitored as a function of time and RH using imaging techniques. By comparing the RH-dependent characteristics of MgSO4 (known to undergo a gel transition) to glucose and sucrose (known to remain as viscous Newtonian fluids) under fixed equilibration time scales, we demonstrate that gel phase transitions can be identified in aerosol particles, with MgSO4 abruptly transitioning to a rigid microgel at 30% RH. Further, we demonstrate this technique can be used to also measure aerosol viscosity and identify non-Newtonian fluid dynamics in model sea spray aerosol composed of NaCl, CaCl2, and sorbitol. Thus, using this experimental technique, it is possible to distinguish between aerosol compositions that form viscous Newtonian fluids and those that undergo a gel transition or form non-Newtonian fluids. This technique offers a simple and cost-effective analytical tool for probing gel transitions outside of bulk solubility limits, with relevant applications ranging from atmospheric science to microengineering of soft matter materials

    Percutaneous Heel Cord Release for Clubfoot: A Retrospective, Multicentre Cost Analysis

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    Purpose The Ponseti method of treatment is the standard of care for idiopathic clubfoot. Following serial casting, percutaneous tendo-Achilles tenotomy (TAT) is performed to correct residual equinus. This procedure can be performed in either the outpatient clinic or the operating room. The purpose of this study was to evaluate the expense of this procedure by examining hospital charges in both settings. Methods We retrospectively reviewed charts of 382 idiopathic clubfoot patients with a mean age of 2.4 months (0.6 to 26.6) treated with the Ponseti method at three institutions. Patients were divided into three groups depending on the setting for the TAT procedure: 140 patients in the outpatient clinic (CL), 219 in the operating room with discharge following the procedure (OR) and 23 in the operating room with admission to hospital for observation (OR+). Medical records were reviewed to analyze age, deformity, perioperative complications and specific time spent in each setting. Hospital charges for all three groups were standardized to one institution\u27s charge structure. Results Charges among the three groups undergoing TAT (CL, OR, OR+) were found to be significantly different (3840.60versus3840.60 versus 7962.30 versus $9110.00, respectively; p ≤ 0.001), and remained significant when separating unilateral and bilateral deformities (p \u3c 0.001). There were nine total perioperative complications (six returns to the ER and three unexpected admissions to the hospital): five (2.3%) in the OR group, four (17.4%) in the OR+ group and none in the CL group. The OR+ group statistically had a higher rate of complications compared with the other two groups (p = 0.006). The total event time of the CL group was significantly shorter compared with the OR and OR+ groups (129.1, 171.7 and 1571.6 minutes respectively; p \u3c 0.001). Conclusion Hospital charges and total event time were significantly less when percutaneous TAT was performed in the outpatient clinic compared with the operating room. In addition, performing the procedure in clinic was associated with the lowest rate of complications. Level of Evidence Therapeutic, Level II

    Movements of Spawning and Non-Spawning Shovelnose Sturgeon in the Missouri River Above Fort Peck Reservoir

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    During the last 40 yrs there has been a lack of pallid sturgeon (Scaphirhynchus albus) recruitment in the upper Missouri River (UMR). However, shovelnose sturgeon (Scaphirhynchus platorynchus) continue to exhibit recruitment in the UMR. Understanding the recruitment dichotomy between species is receiving much attention throughout their range. The objectives of this study were to identify the effects of varying discharge on spawning locations and spawning movements for pallid and shovelnose sturgeon. Two female pallid sturgeon, 32 gravid female shovelnose sturgeon, and 32 non-reproductively active female shovelnose sturgeon were radio tagged at three locations and tracked from 1 May to 5 July 2009. Unfortunately, no data are available for spawning pallid sturgeon movements because fish were not reproductively active. Upstream movement by gravid shovelnose sturgeon varied from 20 percent of the fish tagged at Judith Landing to 56 percent of the fish tagged at Coal Banks Recreation Area (CBRA). Mean maximum upstream movement of gravid shovelnose sturgeon varied from 35.7 km at CBRA to 87.9 km at Fred Robinson Bridge (FRB), mean maximum downstream movement varied from 24.9 km at FRB to 80.3 km at CBRA. Reproductively inactive shovelnose sturgeon exhibited lower mean maximum movements than reproductively active fish (mean maximum distance 5.7 km). Shovelnose sturgeon in the UMR exhibit both upstream and downstream movements prior to spawning and are using several spawning areas. Thus, maintaining spawning habitat throughout a regulated river is important with regard to shovelnose sturgeon conservation

    Ion-Molecule Interactions Enable Unexpected Phase Transitions in Organic-Inorganic Aerosol

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    Atmospheric aerosol particles are commonly complex, aqueous organic-inorganic mixtures, and accurately predicting the properties of these particles is essential for air quality and climate projections. The prevailing assumption is that aqueous organic-inorganic aerosols exist predominately with liquid properties and that the hygroscopic inorganic fraction lowers aerosol viscosity relative to the organic fraction alone. Here, in contrast to those assumptions, we demonstrate that increasing inorganic fraction can increase aerosol viscosity (relative to predictions) and enable a humidity-dependent gel phase transition through cooperative ion-molecule interactions that give rise to long-range networks of atmospherically relevant low-mass oxygenated organic molecules (180 to 310 Da) and divalent inorganic ions. This supramolecular, ion-molecule effect can drastically influence the phase and physical properties of organic-inorganic aerosol and suggests that aerosol may be (semi)solid under more conditions than currently predicted. These observations, thus, have implications for air quality and climate that are not fully represented in atmospheric models

    A Spectroscopic Survey of Faint Quasars in the SDSS Deep Stripe: I. Preliminary Results from the Co-added Catalog

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    In this paper we present the first results of a deep spectroscopic survey of faint quasars in the Sloan Digital Sky Survey (SDSS) Southern Survey, a deep survey carried out by repeatedly imaging a 270 deg^2 area. Quasar candidates were selected from the deep data with good completeness over 0<z<5, and 2 to 3 magnitudes fainter than the SDSS main survey. Spectroscopic follow-up was carried out on the 6.5m MMT with Hectospec. The preliminary sample of this SDSS faint quasar survey (hereafter SFQS) covers ~ 3.9 deg^2, contains 414 quasars, and reaches g=22.5. The overall selection efficiency is ~ 66% (~ 80% at g<21.5); the efficiency in the most difficult redshift range (2<z<3) is better than 40%. We use the 1/V_{a} method to derive a binned estimate of the quasar luminosity function (QLF) and model the QLF using maximum likelihood analysis. The best model fits confirm previous results showing that the QLF has steep slopes at the bright end and much flatter slopes (-1.25 at z<2.0 and -1.55 at z>2.0) at the faint end, indicating a break in the QLF slope. Using a luminosity-dependent density evolution model, we find that the quasar density at M_{g}<-22.5 peaks at z~2, which is later in cosmic time than the peak of z~2.5 found from surveys of more luminous objects. The SFQS QLF is consistent with the results of the 2dF QSO Redshift Survey, the SDSS, and the 2dF-SDSS LRG and QSO Survey, but probes fainter quasars. We plan to obtain more quasars from future observations and establish a complete faint quasar sample with more than 1000 objects over 10 deg^2.Comment: 25 pages, 13 figures, accepted for publication in A

    SDSS J115517.35+634622.0: A Newly Discovered Gravitationally Lensed Quasar

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    We report the discovery of SDSSJ115517.35+634622.0, a previously unknown gravitationally lensed quasar. The lens system exhibits two images of a z=2.89z = 2.89 quasar, with an image separation of 1{\farcs}832 \pm 0.007 . Near-IR imaging of the system reveals the presence of the lensing galaxy between the two quasar images. Based on absorption features seen in the Sloan Digital Sky Survey (SDSS) spectrum, we determine a lens galaxy redshift of z=0.1756z = 0.1756. The lens is rather unusual in that one of the quasar images is only 0{\farcs}22\pm0{\farcs}07 (∼0.1Reff\sim 0.1 R_{\rm eff}) from the center of the lens galaxy and photometric modeling indicates that this image is significantly brighter than predicted by a SIS model. This system was discovered in the course of an ongoing search for strongly lensed quasars in the dataset from the SDSS.Comment: 18 pages, 6 figures. Accepted for publication in A

    Combined analysis of the integrated Sachs-Wolfe effect and cosmological implications

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    We present a global measurement of the integrated Sachs-Wolfe (ISW) effect obtained by cross-correlating all relevant large scale galaxy data sets with the cosmic microwave background radiation map provided by the Wilkinson Microwave Anisotropy Probe. With these measurements, the overall ISW signal is detected at the ~ 4.5 sigma level. We also examine the cosmological implications of these measurements, particularly the dark energy equation of state w, its sound speed, and the overall curvature of the Universe. The flat LCDM model is a good fit to the data and, assuming this model, we find that the ISW data constrain Omega_m = 0.20 +0.19 -0.11 at the 95% confidence level. When we combine our ISW results with the latest baryon oscillation and supernovae measurements, we find that the result is still consistent with a flat LCDM model with w = -1 out to redshifts z > 1.Comment: 24 pages, 15 figures. Version accepted by PRD. Improved quasar data, revised parameter constraint
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