Common Mitochondrial DNA Mutations Generated through DNA-Mediated Charge Transport

Mutation sites that arise in human mitochondrial DNA as a result of oxidation by a rhodium photooxidant have been identified. HeLa cells were incubated with [Rh(phi)2bpy]Cl3 (phi is 9,10-phenanthrenequinone diimine), an intercalating photooxidant, to allow the complex to enter the cell and bind mitochondrial DNA. Photoexcitation of DNA-bound [Rh(phi)2bpy]3+ can promote the oxidation of guanine from a distance through DNA-mediated charge transport. After two rounds of photolysis and growth of cells incubated with the rhodium complex, DNA mutations in a portion of the mitochondrial genome were assessed via manual sequencing. The mutational pattern is consistent with dG to dT transversions in the repetitive guanine tracts. Significantly, the mutational pattern found overlaps oxidative damage hot spots seen previously. These mutations are found within conserved sequence block II, a critical regulatory element involved in DNA replication, and these have been identified as sites of low oxidation potential to which oxidative damage is funneled. On the basis of this mutational analysis and its correspondence to sites of long-range oxidative damage, we infer a critical role for DNA charge transport in generating these mutations and, thus, in regulating mitochondrial DNA replication under oxidative stress

Back-electron transfer suppresses the periodic length dependence of DNA-mediated charge transport across adenine tracts

DNA-mediated charge transport (CT) is exquisitely sensitive to the integrity of the bridging π-stack and is characterized by a shallow distance dependence. These properties are obscured by poor coupling between the donor/acceptor pair and the DNA bridge, or by convolution with other processes. Previously, we found a surprising periodic length dependence for the rate of DNA-mediated CT across adenine tracts monitored by 2-aminopurine fluorescence. Here we report a similar periodicity by monitoring N2-cyclopropylguanosine decomposition by rhodium and anthraquinone photooxidants. Furthermore, we find that this periodicity is attenuated by consequent back-electron transfer (BET), as observed by direct comparison between sequences that allow and suppress BET. Thus, the periodicity can be controlled by engineering the extent of BET across the bridge. The periodic length dependence is not consistent with a periodicity predicted by molecular wire theory but is consistent with a model where multiples of four to five base pairs form an ideal CT-active length of a bridging adenine domain

Defining boat wake impacts on shoreline stability toward management and policy solutions

Coastal economies are often supported by activities that rely on commercial or recreational vessels to move people or goods, such as shipping, transportation, cruising, and fishing. Unintentionally, frequent or intense vessel traffic can contribute to erosion of coastlines; this can be particularly evident in sheltered systems where shoreline erosion should be minimal in the absence of boat waves. We reviewed the state of the science of known effects of boat waves on shoreline stability, examined data on erosion, turbidity, and shoreline armoring patterns for evidence of a response to boat waves in Chesapeake Bay, and reviewed existing management and policy actions in Chesapeake Bay and nearby states to make recommendations for actions to minimize boat wake impacts. In the literature, as well as in our analyses, boat wake energy may be linked to elevated turbidity and shoreline erosion, particularly in narrow waterways. In Chesapeake Bay, three lines of evidence suggest boat waves are contributing to shoreline erosion and poor water clarity in some Bay creeks and tributaries: 1) nearshore turbidity was elevated in many waterways during periods of expected high boating activity, 2) armoring was placed along about a quarter of the low energy shorelines of three examined tidal creeks that are exposed to relatively high boating pressure, and 3) 15% of the shorelines we examined throughout the Bay (9000 km) are low energy shorelines that are experiencing high erosion (≥0.3 m/yr) that cannot be attributed to wind wave energy. Still, there remain significant data gaps that preclude the determination of the overall contribution of boat waves to shoreline erosion throughout the Bay, notably, shoreline erosion data in low energy waterways, recreational boating traffic patterns, and nearshore bathymetry. Interim protective measures can be (and have been) applied in high risk waterways, such as small, low energy waterways that have high recreational boating activity, to help reduce shoreline erosion. Policy options used in Bay states and elsewhere include setbacks from the shore, wake restrictions, and speed restrictions; other more restrictive policies may include prohibition on boats of a certain size or limiting the number of passages. Finally, a systems-approach to boat wake impact management using uniform boat wake policies is likely to be the most effective for consistent shoreline protection

Effects on vital signs after twenty minutes of vaping compared to people exposed to second-hand vapor

Introduction: Very little is known about the immediate physiological implications of vaping or inhaling second-hand vapor. This study used a quantitative approach to understand the short-term physiological implications of vape use and exposure to sec-ond-hand vapor for people who do not vape. Material and methods: One hundred and forty-eight people participated in the study, 75 self-identified as non-vapers and 73 self-identified as people who vape. All participants were over the age of 18. Participants used or were exposed to non-flavored e-juice without nicotine in Sorin® vape devices. Heart rate, blood pressure, respiratory rate, blood oxygenation, blood glucose and pulmonary function tests were assessed. Physiological parameters were assessed prior to vape use or exposure to vapor and again after 20 minutes of vaping.Results: Findings indicated there were no significant changes in most health parameters except blood pressure which was reduced in both groups. Heart rate was also significantly reduced for vaping participants.Conclusion: Vaping without flavorings or nicotine do not appear to have an immediate negative health impact on vital signs. The physiological effects of long-term exposure and/or vape use requires additional investigation. Information was established regarding the physiological effects of non-flavored, non-nicotine vaping so future studies can compare the effects of vaping with assorted flavors and nicotine concentrations to the effects of vaping only the base ingredients (vegetable glycerin and propylene glycol). New knowledge was gleaned relating to exposure to vapor, a phenomenon not previously examined but common espe-cially among non-vaping people who attend social events where people are vaping

Evaluation of the INCREMENT-CPE, Pitt Bacteremia and qPitt Scores in Patients with Carbapenem-Resistant Enterobacteriaceae Infections Treated with Ceftazidime–Avibactam

Background The aim of this study was to evaluate the predictive performance of the INCREMENT-CPE (ICS), Pitt bacteremia score (PBS) and qPitt for mortality among patients treated with ceftazidime–avibactam for carbapenem-resistant Enterobacteriaceae (CRE) infections. Methods Retrospective, multicenter, cohort study of patients with CRE infections treated with ceftazidime–avibactam between 2015 and 2019. The primary outcome was 30-day all-cause mortality. Predictive performance was determined by assessing discrimination, calibration and precision. Results In total, 109 patients were included. Thirty-day mortality occurred in 18 (16.5%) patients. There were no significant differences in discrimination of the three scores [area under the curve (AUC) ICS 0.7039, 95% CI 0.5848–0.8230, PBS 0.6893, 95% CI 0.5709–0.8076, and qPitt 0.6847, 95% CI 0.5671–0.8023; P > 0.05 all pairwise comparisons]. All scores showed adequate calibration and precision. When dichotomized at the optimal cut-points of 11, 3, and 2 for the ICS, PBS, and qPitt, respectively, all scores had NPV > 90% at the expense of low PPV. Patients in the high-risk groups had a relative risk for mortality of 3.184 (95% CI 1.35–8.930), 3.068 (95% CI 1.094–8.606), and 2.850 (95% CI 1.016–7.994) for the dichotomized ICS, PBS, and qPitt, scores respectively. Treatment-related variables (early active antibiotic therapy, combination antibiotics and renal ceftazidime–avibactam dose adjustment) were not associated with mortality after controlling for the risk scores. Conclusions In patients treated with ceftazidime–avibactam for CRE infections, mortality risk scores demonstrated variable performance. Modifications to scoring systems to more accurately predict outcomes in the era of novel antibiotics are warranted

Army Decade in Space

In the twelve short years since the announcement of the SMDC-ONE satellite initiative by Lieutenant General Kevin Campbell, then Commanding General of U.S. Army Space and Missile Defense Command (SMDC), SMDC has put in place an active program of satellite technology development and a Low Earth Orbit Investment Strategy that holds great promise for providing low-cost, responsive data from space as the next major evolution in technology to enable Multi-Domain Operations for the Army of 2028 and beyond. The first fruits of that initiative were seen ten years ago with launch and successful mission of the first SMDC-ONE satellite. This small satellite strategy has gained traction with Army and DoD leadership who embrace the small satellite paradigm. This paper discusses Army progress and lessons learned in the past ten years of small satellite efforts, discusses relationships with other organizations and looks forward to potential capabilities enabled by technology advancements and innovative partnerships

The clustering of galaxies in the SDSS-III Baryon Oscillation Spectroscopic Survey: measuring structure growth using passive galaxies

We explore the benefits of using a passively evolving population of galaxies to measure the evolution of the rate of structure growth between z=0.25 and z=0.65 by combining data from the SDSS-I/II and SDSS-III surveys. The large-scale linear bias of a population of dynamically passive galaxies, which we select from both surveys, is easily modeled. Knowing the bias evolution breaks degeneracies inherent to other methodologies, and decreases the uncertainty in measurements of the rate of structure growth and the normalization of the galaxy power-spectrum by up to a factor of two. If we translate our measurements into a constraint on sigma_8(z=0) assuming a concordance cosmological model and General Relativity (GR), we find that using a bias model improves our uncertainty by a factor of nearly 1.5. Our results are consistent with a flat Lambda Cold Dark Matter model and with GR.Comment: Accepted for publication in MNRAS (clarifications added, results and conclusions unchanged

The Vehicle, Fall 1987

Table of Contents Sketches in the SunRodger L. Patiencepage 3 Reflecting PoolRob Montgomerypage 5 Grandpa\u27s Porcelain DollRichard E. Hallpage 6 Tintype 1837Catherine Friemannpage 6 PhotographSteven M. Beamerpage 7 Washerwoman\u27s SongBob Zordanipage 8 Scrambled Eggs for D.O.Lynne A. Rafoolpage 8 my mother would sayMonica Grothpage 9 Retired by His ChildrenDan Von Holtenpage 10 I am the oldestMonica Grothpage 11 Ice on WheatRob Montgomerypage 12 The Nature of the RoseTroy Mayfieldpage 12 Past NebraskaDan Hornbostelpage 13 Five Minute Jamaican VacationChristy Dunphypage 14 PhotographSteven M. Beamerpage 14 The Angry PoemChristy Dunphypage 15 Road UnfamiliarChristy Dunphypage 15 raised voicesMonica Grothpage 16 Old Ladies & MiniskirtsKara Shannonpage 17 FreakspeakBob Zordanipage 18 PortraitDan Von Holtenpage 18 Mobile VacuumKathleen L. Fairfieldpage 19 Rev. Fermus DickSteve Hagemannpage 20 PhotographSteven M. Beamerpage 21 What\u27s the Name of That Flower?Richard Jesse Davispage 22 RequestChristy Dunphypage 23 SketchPaul Seabaughpage 24 ExperiencedMarilyn Wilsonpage 26 Leaving: Two ViewsTina Phillipspage 27 AntaeusDan Von Holtenpage 28 Misogyny at 19J. D. Finfrockpage 29 A Mental CrippleSteve Hagemannpage 32 AssociationsRhonda Ealypage 33 Banana BreadGail Bowerpage 34 Bill and JackBradford B. Autenpage 35 After Image No. 2Rob Montgomerypage 35 VrrooomBeth Goodmanpage 36 Mr. Modern LoverMolly Maddenpage 36 TravelogueRodger L. Patiencepage 37 Down the HighwayJoan Sebastianpage 38 A Retread HeavenRob Montgomerypage 41 StuporDan Von Holtenpage 42 Love Poem After a Seizure in Your BedBob Zordanipage 43 PalsyChristy Dunphypage 44 Interview with Mr. MatthewsBob Zordanipage 45 Chasing Down Hot Air Balloons on a Sunday MorningRob Montgomerypage 48https://thekeep.eiu.edu/vehicle/1049/thumbnail.jp

Mouse phenome database: curated data repository with interactive multi-population and multi-trait analyses.

The Mouse Phenome Database continues to serve as a curated repository and analysis suite for measured attributes of members of diverse mouse populations. The repository includes annotation to community standard ontologies and guidelines, a database of allelic states for 657 mouse strains, a collection of protocols, and analysis tools for flexible, interactive, user directed analyses that increasingly integrates data across traits and populations. The database has grown from its initial focus on a standard set of inbred strains to include heterogeneous mouse populations such as the Diversity Outbred and mapping crosses and well as Collaborative Cross, Hybrid Mouse Diversity Panel, and recombinant inbred strains. Most recently the system has expanded to include data from the International Mouse Phenotyping Consortium. Collectively these data are accessible by API and provided with an interactive tool suite that enables users\u27 persistent selection, storage, and operation on collections of measures. The tool suite allows basic analyses, advanced functions with dynamic visualization including multi-population meta-analysis, multivariate outlier detection, trait pattern matching, correlation analyses and other functions. The data resources and analysis suite provide users a flexible environment in which to explore the basis of phenotypic variation in health and disease across the lifespan