A Symplectic Integrator for Hill's Equations

Hill's equations are an approximation that is useful in a number of areas of astrophysics including planetary rings and planetesimal disks. We derive a symplectic method for integrating Hill's equations based on a generalized leapfrog. This method is implemented in the parallel N-body code, PKDGRAV and tested on some simple orbits. The method demonstrates a lack of secular changes in orbital elements, making it a very useful technique for integrating Hill's equations over many dynamical times. Furthermore, the method allows for efficient collision searching using linear extrapolation of particle positions.Comment: 15 pages, 2 figures; minor revisions; accepted for publication in the Astronomical Journa

Testing an integrated behavioural and biomedical model of disability in N-of-1 studies with chronic pain.

Background. Previous research has supported an integrated biomedical and behavioural model explaining activity limitations. However, further tests of this model are required at the within-person level, because while it proposes that the constructs are related within individuals, it has primarily been tested between individuals in large group studies. We aimed to test the integrated model at the within-person level. Method. Six correlational N-of-1 studies in participants with arthritis, chronic pain and walking limitations. Daily measures of theoretical constructs were collected using a handheld computer (PDA), activity was assessed by self-report and accelerometer, and data analysed using time-series analysis. Results. The biomedical model was not supported as pain-impairment did not predict activity, so the integrated model was supported partially. Impairment predicted intention to move around while perceived behavioural control (PBC) and intention predicted activity. PBC did not predict activity limitation in the expected direction. Conclusions. The integrated model of disability was partially supported within individuals, especially the behavioural elements. However, results suggest that different elements of the model may drive activity (limitations) for different individuals. The integrated model provides a useful framework for understanding disability and suggests interventions, and the utility of N-of-1 methodology for testing theory is illustrated

Bivalve Restoration Suitability Analysis

Cal Poly Humboldt Environmental Science and Management: ESM 475 Planning and Policy Capstone Practicum. The goal of this project is to provide Humboldt Baykeeper with a report of potential designs, sites, benefits, and stakeholder opinions related to developing a native Olympia oyster and clam garden restoration pilot project on Wigi. This suitability analysis will examine several different locations across the bay and compare the feasibility of (1) an Olympia oyster restoration, (2) an Olympia oyster living shoreline restoration for sea-level rise, and (3) a clam garden restoration. Based on our research, we will provide an analysis of four sites in North Humboldt Bay for various bivalve restoration strategies. The maps in this report display potential sites based on ecological and regulatory parameters for successful bivalve restoration. This potential pilot bivalve restoration project will provide multiple benefits to communities around Wigi, positively affecting bay ecology, sea-level rise mitigation, and Indigenous cultural practices. It also has the possibility of serving as a collaborative educational site for students across Humboldt County

Antiproteases as Therapeutics to Target Inflammation in Cystic Fibrosis

Cystic Fibrosis (CF) is the most common fatal inherited disease of Caucasians, affecting about 1 in 3000 births. Patients with CF have a recessive mutation in the gene encoding the CF transmembrane conductance regulator (CFTR). CFTR is expressed in the epithelium of many organs throughout the exocrine system, however, inflammation and damage of the airways as a result of persistent progressive endobronchial infection is a central feature of CF. The inflammatory response to infection brings about a sustained recruitment of neutrophils to the site of infection. These neutrophils release various pro-inflammatory compounds including proteases, which when expressed at aberrant levels can overcome the endogenous antiprotease defence mechanisms of the lung. Unregulated, these proteases can exacerbate inflammation and result in the degradation of structural proteins and tissue damage leading to bronchiectasis and loss of respiratory function. Other host-derived and bacterial proteases may also contribute to the inflammation and lung destruction observed in the CF lung. Antiprotease strategies to dampen the excessive inflammatory response and concomitant damage to the airways remains an attractive therapeutic option for CF patients

Archiva: Volume 4, Issue 2

https://digitalcommons.imsa.edu/archiva/1001/thumbnail.jp

Offshore workers and health behaviour change: an exploration using the Theoretical Domains Framework

Background: Previous research has identified the importance of promoting behaviour change within theoffshore workforce. This qualitative study sought to: identify self-care behaviours perceived to require behaviourchange within the offshore workforce, and explore perceived potential behavioural determinants.Materials and methods: This study included the perspectives of both offshore workers (OWs, n = 16) andhealthcare practitioners (HCPs, n = 12) from the global workforce. Telephone interviews were conducted,recorded electronically and transcribed. Transcripts were analysed independently by two researchers usinga Framework Approach and the Theoretical Domains Framework (TDF) to support coding.Results: Healthy eating and alcohol intake were behaviours perceived by OWs and HCPs to require changewithin the offshore workforce. Knowledge (e.g. availability of nutritional knowledge), intentions (e.g. role ofmotivation), memory, attention and decision process (e.g. effect of boredom), environmental context andresources (e.g. influence of environmental stressors), social influences (e.g. influence of others), emotion(e.g. influence of emotional state) and behavioural regulation (e.g. influence of willpower). TDF domainswere reported by both OWs and HCPs in relation to OWs’ healthy eating and physical activity behaviours.Conclusions: The determinants identified as mechanisms of behaviour may be targeted in future interventionswhich aim to promote engagement in self-care within the offshore workforce

N-Body Simulations of Growth from 1 km Planetesimals at 0.4 AU

We present N-body simulations of planetary accretion beginning with 1 km radius planetesimals in orbit about a 1 solar mass star at 0.4 AU. The initial disk of planetesimals contains too many bodies for any current N-body code to integrate; therefore, we model a sample patch of the disk. Although this greatly reduces the number of bodies, we still track in excess of 10^5 particles. We consider three initial velocity distributions and monitor the growth of the planetesimals. The masses of some particles increase by more than a factor of 100. Additionally, the escape speed of the largest particle grows considerably faster than the velocity dispersion of the particles, suggesting impending runaway growth, although no particle grows large enough to detach itself from the power law size-frequency distribution. These results are in general agreement with previous statistical and analytical results. We compute rotation rates by assuming conservation of angular momentum around the center of mass at impact and that merged planetesimals relax to spherical shapes. At the end of our simulations, the majority of bodies that have undergone at least one merger are rotating faster than the breakup frequency. This implies that the assumption of completely inelastic collisions (perfect accretion), which is made in most simulations of planetary growth at sizes 1 km and above, is inappropriate. Our simulations reveal that, subsequent to the number of particles in the patch having been decreased by mergers to half its initial value, the presence of larger bodies in neighboring regions of the disk may limit the validity of simulations employing the patch approximation.Comment: 19 pages, 32 figures, 5 tables, accepted to Icaru

Engineering of industrial biocatalysts

In the last 40 years advances in the protein engineering have prompted the application of biocatalysts in the synthesis of building blocks, fine and bulk active pharmaceutical chemicals for the agrochemical, food, biofuel and pharmaceutical industries. Computational chemistry methodologies are fueling the development of a new generation of rationally designed biocatalysts with enhanced selectivity and specificity at a fraction of the time and cost compared to traditional protocols such as directed evolution. We present two examples of rational enzyme design. Our first example is the study of the phenylacetone monooxygenase (PAMO), the most stable and thermo-tolerant member of the Baeyer–Villiger monooxygenases family. We solved the catalytic mechanism of this enzyme for the native substrate phenylacetone as well as for a linear non-native substrate 2-octanone, using molecular dynamics simulations, quantum mechanics and quantum mechanics/molecular mechanics calculations.1 By studying relevant PAMO variants we provide a theoretical basis for the preference of the enzyme for the native aromatic substrate over non-native linear substrates.2 The second example regards an (S)-selective-transaminase from Vibrio fluvialis (S-TAm), which offers an environmentally sustainable synthesis route for the production of pure chiral amines.3 By applying a rational enzyme engineering protocol we altered this enzyme towards better acceptance of bulky ketones, starting with no detectable activity of the WT. Our best S-TAm variant improved the reaction rate by \u3e 1716-fold and retained activity even at 50 °C. To obtain such an outstanding result we only screened 113 variants, a substantially lower number than those typically associated with directed evolution (104 to 107 clones). Both studies provide fundamental insights into the rational engineering of enzymes for industrial applications. (1) Carvalho, A. T. P.; Dourado, D. F. A. R.; Skvortsov, T.; Abreu, M. de; Ferguson, L. J.; Quinn, D. J.; Moody, T. S.; Huang, M. Catalytic Mechanism of Phenylacetone Monooxygenases for Non-Native Linear Substrates. Phys. Chem. Chem. Phys. 2017, 19 (39), 26851–26861. https://doi.org/10.1039/C7CP03640J. (2) Carvalho, A. T. P.; Dourado, D. F. A. R.; Skvortsov, T.; Abreu, M. de; Ferguson, L. J.; Quinn, D. J.; Moody, T. S.; Huang, M. Spatial Requirement for PAMO for Transformation of Non-Native Linear Substrates. Phys. Chem. Chem. Phys. 2018, 20 (4), 2558–2570. https://doi.org/10.1039/C7CP07172H. (3) Dourado, D. F. A. R.; Pohle, S.; Carvalho, A. T. P.; Dheeman, D. S.; Caswell, J. M.; Skvortsov, T.; Miskelly, I.; Brown, R. T.; Quinn, D. J.; Allen, C. C. R.; Huang, M; Moody, T. Rational Design of a (S)-Selective-Transaminase for Asymmetric Synthesis of (1S)-1-(1,1′-Biphenyl-2-Yl)Ethanamine. ACS Catal. 2016, 6 (11), 7749–7759. https://doi.org/10.1021/acscatal.6b0238

Low-Frequency High-Magnitude Mechanical Strain of Articular Chondrocytes Activates p38 MAPK and Induces Phenotypic Changes Associated with Osteoarthritis and Pain

Osteoarthritis (OA) is a debilitating joint disorder resulting from an incompletely understood combination of mechanical, biological, and biochemical processes. OA is often accompanied by inflammation and pain, whereby cytokines associated with chronic OA can up-regulate expression of neurotrophic factors such as nerve growth factor (NGF). Several studies suggest a role for cytokines and NGF in OA pain, however the effects of changing mechanical properties in OA tissue on chondrocyte metabolism remain unclear. Here, we used high-extension silicone rubber membranes to examine if high mechanical strain (HMS) of primary articular chondrocytes increases inflammatory gene expression and promotes neurotrophic factor release. HMS cultured chondrocytes displayed up-regulated NGF, TNFα and ADAMTS4 gene expression while decreasing TLR2 expression, as compared to static controls. HMS culture increased p38 MAPK activity compared to static controls. Conditioned medium from HMS dynamic cultures, but not static cultures, induced significant neurite sprouting in PC12 cells. The increased neurite sprouting was accompanied by consistent increases in PC12 cell death. Low-frequency high-magnitude mechanical strain of primary articular chondrocytes in vitro drives factor secretion associated with degenerative joint disease and joint pain. This study provides evidence for a direct link between cellular strain, secretory factors, neo-innervation, and pain in OA pathology