Moment stability analysis method for determining safety factors for articulated concrete blocks

Department Head: Luis A. Garcia.2010 Summer.Includes bibliographical references.Articulated concrete block (ACB) revetment systems are widely used for channel lining and embankment protection. Available information pertaining to testing and analysis of ACB systems was identified. Current approaches for prediction of ACB system stability are based on a moment stability analysis and utilize shear stress to account for all hydrodynamic forces. Assumptions utilized in the moment stability analysis derivations were identified and the applicability to channelized and steep-slope conditions was investigated. The assumption of equal lift and drag forces was determined to be non-conservative and the most influential to computed safety factors. A database of twenty-four tests encompassing both channelized and overtopping conditions was compiled from available data for three ACB systems. Safety factors were computed using the current state-of-the-practice design methodology for each test. The current design methodology proved accurate at predicting the point of instability for five out of the nine total tested ACB installations. A new safety factor design methodology was developed using a moment stability analysis coupled with the computation of hydrodynamic forces using both boundary shear stress and flow velocity. Lift coefficients were calibrated for each of the three ACB systems within the database. Safety factors were computed using the new safety factor method and the calibrated lift coefficients. The new safety factor design method proved accurate at predicting stability for eight of the nine total tested ACB installations

Mindfulness and Affective Responses to Treadmill Walking in Individuals with Low Intrinsic Motivation to Exercise

International Journal of Exercise Science 11(5): 609-624, 2018. An aversion to the sensations of physical exertion can deter engagement in physical activity. This is due in part to an associative focus in which individuals are attending to uncomfortable interoceptive cues. The purpose of this study was to test the effect of mindfulness on affective valence, ratings of perceived exertion (RPE), and enjoyment during treadmill walking. Participants (N=23; Mage=19.26, SD = 1.14) were only included in the study if they engaged in no more than moderate levels of physical activity and reported low levels of intrinsic motivation. They completed three testing sessions including a habituation session to determine the grade needed to achieve 65% of heart rate reserve (HRR); a control condition in which they walked at 65% of HRR for 10 minutes and an experimental condition during which they listened to a mindfulness track that directed them to attend to the physical sensations of their body in a nonjudgmental manner during the 10-minute walk. ANOVA results showed that in the mindfulness condition, affective valence was significantly more positive (p = .02, np2 = .22), enjoyment and mindfulness of the body were higher (p \u3c .001, np2 = .36 and .40, respectively), attentional focus was more associative (p \u3c .001, np2 =.67) and RPE was minimally lower (p = .06, np2 =.15). Higher mindfulness of the body was moderately associated with higher enjoyment (p \u3c .05, r =.44) in the mindfulness but not the control condition. Results suggest that mindfulness during exercise is associated with more positive affective responses

Community Structure in Congressional Cosponsorship Networks

We study the United States Congress by constructing networks between Members of Congress based on the legislation that they cosponsor. Using the concept of modularity, we identify the community structure of Congressmen, as connected via sponsorship/cosponsorship of the same legislation, to investigate the collaborative communities of legislators in both chambers of Congress. This analysis yields an explicit and conceptually clear measure of political polarization, demonstrating a sharp increase in partisan polarization which preceded and then culminated in the 104th Congress (1995-1996), when Republicans took control of both chambers. Although polarization has since waned in the U.S. Senate, it remains at historically high levels in the House of Representatives.Comment: 8 pages, 4 figures (some with multiple parts), to appear in Physica A; additional background info and explanations added from last versio

HI in four star-forming low-luminosity E/S0 and S0 galaxies

We present HI data cubes of four low-luminosity early-type galaxies which are currently forming stars. These galaxies have absolute magnitudes in the range M_B=-17.9 to -19.9 (H_o=50 km/s/Mpc). Their HI masses range between a few times 10^8 and a few times 10^9 M_sun and the corresponding values for M_HI/L_B are between 0.07 and 0.42, so these systems are HI rich for their morphological type. In all four galaxies, the HI is strongly centrally concentrated with high central HI surface densities, in contrast to what is typically observed in more luminous early-type galaxies. In two galaxies (NGC 802 and ESO 118-G34), the kinematics of the HI suggests that the gas is in a strongly warped disk, which we take as evidence for recent accretion of HI. In the other two galaxies (NGC 2328 and ESO 027-G21) the HI must have been part of the systems for a considerable time. The HI properties of low-luminosity early-type galaxies appear to be systematically different from those of many more luminous early-type galaxies, and we suggest that these differences are due to a different evolution of the two classes. The star formation history of these galaxies remains unclear. Their UBV colours and Halpha emission-line strengths are consistent with having formed stars at a slowly-declining rate for most of the past 10^10 years. However, the current data do not rule out a small burst of recent star formation overlaid on an older stellar population.Comment: To appear in AJ, LateX, figures in gif format, paper also available at http://www.nfra.nl/~morganti/LowLu

Re-sensitization of Mycobacterium smegmatis to Rifampicin Using CRISPR Interference Demonstrates Its Utility for the Study of Non-essential Drug Resistance Traits

© 2021 Faulkner, Cox, Goh, van Bohemen, Gibson, Liebster, Wren, Willcocks and Kendall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). https://creativecommons.org/licenses/by/4.0/A greater understanding of the genes involved in antibiotic resistance in Mycobacterium tuberculosis (Mtb) is necessary for the design of improved therapies. Clustered regularly interspaced short palindromic repeat interference (CRISPRi) has been previously utilized in mycobacteria to identify novel drug targets by the demonstration of gene essentiality. The work presented here shows that it can also be usefully applied to the study of non-essential genes involved in antibiotic resistance. The expression of an ADP-ribosyltransferase (Arr) involved in rifampicin resistance in Mycobacterium smegmatis was silenced using CRISPRi and the impact on rifampicin susceptibility was measured. Gene silencing resulted in a decrease in the minimum inhibitory concentration (MIC) similar to that previously reported in an arr deletion mutant. There is contradictory evidence for the toxicity of Streptococcus pyogenes dCas9 (dCas9 Spy) in the literature. In this study the expression of dCas9 Spy in M. smegmatis showed no impact on viability. Silencing was achieved with concentrations of the aTc inducer lower than previously described and with shorter induction times. Finally, designing small guide RNAs (sgRNAs) that target transcription initiation, or the early stages of elongation had the most impact on rifampicin susceptibility. This study demonstrates that CRISPRi based gene silencing can be as impactful as gene deletion for the study of non-essential genes and further contributes to the knowledge on the design and induction of sgRNAs for CRISPRi. This approach can be applied to other non-essential antimicrobial resistance genes such as drug efflux pumps.Peer reviewe

Neogenin recruitment of the WAVE regulatory complex maintains adherens junction stability and tension

To maintain tissue integrity during epithelial morphogenesis, adherens junctions (AJs) must resist the mechanical stresses exerted by dynamic tissue movements. Junctional stability is dependent on actomyosin contractility within the actin ring. Here we describe a novel function for the axon guidance receptor, Neogenin, as a key component of the actin nucleation machinery governing junctional stability. Loss of Neogenin perturbs AJs and attenuates junctional tension. Neogenin promotes actin nucleation at AJs by recruiting the Wave regulatory complex (WRC) and Arp2/3. A direct interaction between the Neogenin WIRS domain and the WRC is crucial for the spatially restricted recruitment of the WRC to the junction. Thus, we provide the first example of a functional WIRS-WRC interaction in epithelia. We further show that Neogenin regulates cadherin recycling at the AJ. In summary, we identify Neogenin as a pivotal component of the AJ, where it influences both cadherin dynamics and junctional tension

Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production

Semi-synthetic derivatives of the tricyclic diterpene antibiotic pleuromutilin from the basidiomycete Clitopilus passeckerianus are important in combatting bacterial infections in human and veterinary medicine. These compounds belong to the only new class of antibiotics for human applications, with novel mode of action and lack of cross-resistance, representing a class with great potential. Basidiomycete fungi, being dikaryotic, are not generally amenable to strain improvement. We report identification of the seven-gene pleuromutilin gene cluster and verify that using various targeted approaches aimed at increasing antibiotic production in C. passeckerianus, no improvement in yield was achieved. The seven-gene pleuromutilin cluster was reconstructed within Aspergillus oryzae giving production of pleuromutilin in an ascomycete, with a significant increase (2106%) in production. This is the first gene cluster from a basidiomycete to be successfully expressed in an ascomycete, and paves the way for the exploitation of a metabolically rich but traditionally overlooked group of fungi

Predictive blood biomarkers and brain changes associated with age-related cognitive decline

Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and glial fibrillary acidic protein as promising biomarkers for Alzheimer's disease. While these blood biomarkers are promising for distinguishing people with Alzheimer's disease from healthy controls, their predictive validity for age-related cognitive decline without dementia remains unclear. Further, while tau phosphorylated at threonine 181 is a promising biomarker, the distribution of this phospho-epitope of tau in the brain is unknown. Here, we tested whether plasma levels of tau phosphorylated at threonine 181, amyloid-β, neurofilament light and fibrillary acidic protein predict cognitive decline between ages 72 and 82 in 195 participants in the Lothian birth cohorts 1936 study of cognitive ageing. We further examined post-mortem brain samples from temporal cortex to determine the distribution of tau phosphorylated at threonine 181 in the brain. Several forms of tau phosphorylated at threonine 181 have been shown to contribute to synapse degeneration in Alzheimer's disease, which correlates closely with cognitive decline in this form of dementia, but to date, there have not been investigations of whether tau phosphorylated at threonine 181 is found in synapses in Alzheimer's disease or healthy ageing brain. It was also previously unclear whether tau phosphorylated at threonine 181 accumulated in dystrophic neurites around plaques, which could contribute to tau leakage to the periphery due to impaired membrane integrity in dystrophies. Brain homogenate and biochemically enriched synaptic fractions were examined with western blot to examine tau phosphorylated at threonine 181 levels between groups (n = 10-12 per group), and synaptic and astrocytic localization of tau phosphorylated at threonine 181 were examined using array tomography (n = 6-15 per group), and localization of tau phosphorylated at threonine 181 in plaque-associated dystrophic neurites with associated gliosis were examined with standard immunofluorescence (n = 8-9 per group). Elevated baseline plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein predicted steeper general cognitive decline during ageing. Further, increasing tau phosphorylated at threonine 181 over time predicted general cognitive decline in females only. Change in plasma tau phosphorylated at threonine 181 remained a significant predictor of g factor decline when taking into account Alzheimer's disease polygenic risk score, indicating that the increase of blood tau phosphorylated at threonine 181 in this cohort was not only due to incipient Alzheimer's disease. Tau phosphorylated at threonine 181 was observed in synapses and astrocytes in both healthy ageing and Alzheimer's disease brain. We observed that a significantly higher proportion of synapses contain tau phosphorylated at threonine 181 in Alzheimer's disease relative to aged controls. Aged controls with pre-morbid lifetime cognitive resilience had significantly more tau phosphorylated at threonine 181 in fibrillary acidic protein-positive astrocytes than those with pre-morbid lifetime cognitive decline. Further, tau phosphorylated at threonine 181 was found in dystrophic neurites around plaques and in some neurofibrillary tangles. The presence of tau phosphorylated at threonine 181 in plaque-associated dystrophies may be a source of leakage of tau out of neurons that eventually enters the blood. Together, these data indicate that plasma tau phosphorylated at threonine 181, neurofilament light and fibrillary acidic protein may be useful biomarkers of age-related cognitive decline, and that efficient clearance of tau phosphorylated at threonine 181 by astrocytes may promote cognitive resilience