Elimination of the reaction rate 'scale effect': application of the Lagrangian reactive particle-tracking method to simulate mixing-limited, field-scale biodegradation at the Schoolcraft (MI, USA) site

This is the peer reviewed version of the following article: [Ding, D., Benson, D. A., Fernàndez‐Garcia, D., Henri, C. V., Hyndman, D. W., Phanikumar, M. S., & Bolster, D. (2017). Elimination of the reaction rate “scale effect”: Application of the Lagrangian reactive particle‐tracking method to simulate mixing‐limited, field‐scale biodegradation at the Schoolcraft (MI, USA) site. Water Resources Research, 53, 10,411–10,432. https://doi.org/10.1002/2017WR021103], which has been published in final form at https://doi.org/10.1002/2017WR021103. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Measured (or empirically fitted) reaction rates at groundwater remediation sites are typically much lower than those found in the same material at the batch or laboratory scale. The reduced rates are commonly attributed to poorer mixing at the larger scales. A variety of methods have been proposed to account for this scaling effect in reactive transport. In this study, we use the Lagrangian particle-tracking and reaction (PTR) method to simulate a field bioremediation experiment at the Schoolcraft, MI site. A denitrifying bacterium, Pseudomonas Stutzeri strain KC (KC), was injected to the aquifer, along with sufficient substrate, to degrade the contaminant, carbon tetrachloride (CT), under anaerobic conditions. The PTR method simulates chemical reactions through probabilistic rules of particle collisions, interactions, and transformations to address the scale effect (lower apparent reaction rates for each level of upscaling, from batch to column to field scale). In contrast to a prior Eulerian reaction model, the PTR method is able to match the field-scale experiment using the rate coefficients obtained from batch experiments.Peer ReviewedPostprint (author's final draft

Evaluating the role of sediment‐bacteria interactions on Escherichia coli concentrations at beaches in southern Lake Michigan

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102640/1/jgrc20481.pd

Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis

Objectives: To evaluate the risk of venous thromboembolic events associated with the use of progestin-only contraception and whether that risk differs with the mode of drug delivery (oral, intrauterine, or depot injection). Design: Systematic review and meta-analysis of randomised controlled trials and observational studies. Data sources: Pubmed, Embase, Cochrane Library, and reference lists of relevant reviews. Study selection: Randomised controlled trials and case-control, cohort, and cross sectional studies with venous thromboembolic outcome for progestin-only contraception reported relative to a non-hormone comparator group. Data extraction: Data were extracted by two independent investigators, and consensus for inclusion was reached after assessment by additional investigators. Results: Among the 2022 unique references identified by all searches, eight observational studies fulfilled inclusion criteria. A total of 147 women across all studies were diagnosed with a venous thromboembolic event while taking progestin-only contraception, and the summary measure for the adjusted relative risk of a venous thromboembolic episode for users versus non-users of a progestin-only contraceptive was, based on the random effects model, 1.03 (95% CI 0.76 to 1.39). Subgroup analysis confirmed there was no association between venous thromboembolic risk and progestin-only pills (relative risk 0.90 (0.57 to 1.45)) or a progestin intrauterine device (0.61 (0.24 to 1.53)). The relative risk of a venous thromboembolic event for users of an injectable progestin versus non-users was 2.67 (1.29 to 5.53). Conclusions: Published data assessing the risk of venous thromboembolism in women prescribed progestin-only contraception are limited. In this meta-analysis of eight observational studies, the use of progestin-only contraception was not associated with an increased risk of venous thromboembolism compared with non-users of hormonal contraception. The potential association between injectable progestins and thrombosis requires further study

Parametric investigations of short length hydro-dynamically lubricated conical journal bearing

Due to the growing need for compact size fluid film bearings, efforts are being made to explore the performance of hydro-dynamically lubricated short length conical journal bearing. The combined radial and axial load carrying features of these bearings emerge as a better option to replace the two separate bearings (journal and thrust pad bearings) employed in turbo-machines and other applications. Thus, in this study, attempts have been made to investigate the performance of conical hydrodynamic journal bearing by using finite element analysis. The bearings have been investigated for semi-cone angle (γ = 10°), aspect ratio (λ = 0.5, 0.8, 1.0), journal speed (v = 2.6, 5.2 m/s) and load variations in terms of eccentricity ratio (ε) up to 0.6. Results have been presented in terms of radial and axial load carrying capacity, stiffness coefficients, damping coefficients and threshold speed. Results from the present study reveal that load carrying capacity is improved with higher aspect ratio; whereas threshold speed decreases with the increase of eccentricity ratio and aspect ratio

Reliability of measuring abductor hallucis muscle parameters using two different diagnostic ultrasound machines

<p>Abstract</p> <p>Background</p> <p>Diagnostic ultrasound provides a method of analysing soft tissue structures of the musculoskeletal system effectively and reliably. The aim of this study was to evaluate within and between session reliability of measuring muscle dorso-plantar thickness, medio-lateral length and cross-sectional area, of the abductor hallucis muscle using two different ultrasound machines, a higher end Philips HD11 Ultrasound machine and clinically orientated Chison 8300 Deluxe Digital Portable Ultrasound System.</p> <p>Methods</p> <p>The abductor hallucis muscle of both the left and right feet of thirty asymptomatic participants was imaged and then measured using both ultrasound machines. Interclass correlation coefficients (ICC) with 95% confidence intervals (CI) were used to calculate both within and between session intra-tester reliability. Standard error of the measurement (SEM) calculations were undertaken to assess difference between the actual measured score across trials and the smallest real difference (SRD) was calculated from the SEM to indicate the degree of change that would exceed the expected trial to trial variability.</p> <p>Results</p> <p>The ICCs, SEM and SRD for dorso-plantar thickness and medial-lateral length were shown to have excellent to high within and between-session reliability for both ultrasound machines. The between-session reliability indices for cross-sectional area were acceptable for both ultrasound machines.</p> <p>Conclusion</p> <p>The results of the current study suggest that regardless of the type ultrasound machine, intra-tester reliability for the measurement the abductor hallucis muscle parameters is very high.</p

Lovastatin Inhibits VEGFR and AKT Activation: Synergistic Cytotoxicity in Combination with VEGFR Inhibitors

BACKGROUND: In a recent study, we demonstrated the ability of lovastatin, a potent inhibitor of mevalonate synthesis, to inhibit the function of the epidermal growth factor receptor (EGFR). Lovastatin attenuated ligand-induced receptor activation and downstream signaling through the PI3K/AKT pathway. Combining lovastatin with gefitinib, a potent EGFR inhibitor, induced synergistic cytotoxicity in a variety of tumor derived cell lines. The vascular endothelial growth factor receptor (VEGFR) and EGFR share similar activation, internalization and downstream signaling characteristics. METHODOLOGY/PRINCIPAL FINDINGS: The VEGFRs, particularly VEGFR-2 (KDR, Flt-1), play important roles in regulating tumor angiogenesis by promoting endothelial cell proliferation, survival and migration. Certain tumors, such as malignant mesothelioma (MM), also express both the VEGF ligand and VEGFRs that act in an autocrine loop to directly stimulate tumor cell growth and survival. In this study, we have shown that lovastatin inhibits ligand-induced VEGFR-2 activation through inhibition of receptor internalization and also inhibits VEGF activation of AKT in human umbilical vein endothelial cells (HUVEC) and H28 MM cells employing immunofluorescence and Western blotting. Combinations of lovastatin and a VEGFR-2 inhibitor showed more robust AKT inhibition than either agent alone in the H28 MM cell line. Furthermore, combining 5 µM lovastatin treatment, a therapeutically relevant dose, with two different VEGFR-2 inhibitors in HUVEC and the H28 and H2052 mesothelioma derived cell lines demonstrated synergistic cytotoxicity as demonstrated by MTT cell viability and flow cytometric analyses. CONCLUSIONS/SIGNIFICANCE: These results highlight a novel mechanism by which lovastatin can regulate VEGFR-2 function and a potential therapeutic approach for MM through combining statins with VEGFR-2 inhibitors

Ageing-associated changes in transcriptional elongation influence longevity

Physiological homeostasis becomes compromised during ageing, as a result of impairment of cellular processes, including transcription and RNA splicing1-4. However, the molecular mechanisms leading to the loss of transcriptional fidelity are so far elusive, as are ways of preventing it. Here we profiled and analysed genome-wide, ageing-related changes in transcriptional processes across different organisms: nematodes, fruitflies, mice, rats and humans. The average transcriptional elongation speed (RNA polymerase II speed) increased with age in all five species. Along with these changes in elongation speed, we observed changes in splicing, including a reduction of unspliced transcripts and the formation of more circular RNAs. Two lifespan-extending interventions, dietary restriction and lowered insulin-IGF signalling, both reversed most of these ageing-related changes. Genetic variants in RNA polymerase II that reduced its speed in worms5 and flies6 increased their lifespan. Similarly, reducing the speed of RNA polymerase II by overexpressing histone components, to counter age-associated changes in nucleosome positioning, also extended lifespan in flies and the division potential of human cells. Our findings uncover fundamental molecular mechanisms underlying animal ageing and lifespan-extending interventions, and point to possible preventive measures