Solar sailing

An introduction to solar sailing is presented. The physical principles are briefly reviewed along with an introduction to the historical context of solar sailing. Potential solar sail configurations are briefly introduced, while placing these in the context of the current hardware development programmes. Following the introduction to solar sailing we progress onto a discussion of solar sail orbital dynamics in a planet-centred environment. The development of solar sail trajectory generation is presented, from Earth escape trajectories through to lunar fly-by trajectories and more accurate Earth escape methods. Much of this work relies on assumptions to generate near-optimal solutions rather than true globally optimal solutions, which are computationally difficult to determine for multiple revolution trajectories. Many of these traditional planet-centred solar sail applications, such as Earth escape, also require rapid attitude slew manoeuvres to achieve. This first lecture is based on theory development and application with a view towards future missions, such as planetary sample return

Small-body encounters using solar sail propulsion

Cometary Rendezvous and Flybys have large V requirements, which impose almost unattainable, and sometimes prohibitive, demands on the propellant budget of conventional, chemical propulsion. Ion Propulsion is a viable alternative, but as the number and difficulty of target objectives increases then the potential of this technology becomes rapidly less attractive. Solar sails exhibit an extremely high effective specific impulse over long mission durations. No propellant is required so that large changes in V could be realised without necessitating the introduction of complex gravity assists, which prolong mission duration and restrict launch opportunities. The endurance of the structures and materials are thus the only limiting factors dictating the number and range of bodies with which the solar-sail propelled vehicle can encounter throughout its lifetime. In this paper we have analysed a number of high-energy, small-body mission scenarios using a parameterised approach to sail control representation. The sail cone and clock angle histories were characterised by linear interpolation across a set of discrete nodes. The optimal control problem was thus transcribed to a Non-Linear Programming problem to select the optimal controls at the nodes that minimised the transfer time while enforcing the cartesian end-point boundary constraints (6 states for rendezvous, 3 for flypast). The Fortran77 optimisation package NPSOL 5.0 was used for this purpose with the variational equations of motion formulated in modified equinoctial orbital elements and integrated using a variable-order, adaptive step-size Adams-Moulton-Bashforth method. We present optimal rendezvous trajectories to Short-Period Comets such as 46P/Wirtanen in 484 days with a sail characteristic acceleration of 1.9 mms-2, and with 2P/Encke in 574 days with a characteristic acceleration of 1.0 mms-2. An analysis using high-performance sails has been conducted to permit fast flyby intercepts of newly discovered Long Period Comets (LPCs). Previous examples adopted were C/1995 O1/Hale- Bopp, C/1995 Y1/Hyakutake, C/1999 T1/McNaught-Hartley, C/1999 F1/Catalina, C/1999 N2/Lynn and C/1999 H1/Lee, to demonstrate the feasibility of a late launch to quickly intercept a new LPC using a solar sail. Since the time between discovery of a new LPC such as Hale-Bopp and perihelion passage was less then 2 years, this then leaves a very short time-span for orbit determination, preparation, planning and operational phases. Preliminary mission analysis shows that a Hale-Bopp perihelion flypast could have been achieved, with a sail characteristic acceleration of 5.0 mms-2, by launching just 209 days before comet perihelion passage. With a characteristic acceleration of 2.0 mms-2 Hale-Bopp could also have been intercepted at its descending node by launching 270 days before nodal descent. The sail could then have returned to rendezvous with the Earth 261 days later, giving a minimum total mission turn-around time of 531 days. An alternative, dual flyby scenario has been investigated, to continue on to C/1997 D1/Mueller, after which solar system escape was reached and arrival at Heliopause would occur in 12 years. Solar Electric Propulsion has been adopted as the primary propulsion system for the DAWN dual asteroid rendezvous mission scheduled for launch in 2006. The objective of this mission is to rendezvous with inner main-belt asteroids, Vesta and Ceres. We have also investigated solar sail adaptation to this mission, for the same launch date and 11 month orbiter stay-times. We have extended the mission objectives to two further asteroids, Lucina and Lutetia, with the aim of demonstrating a Mainbelt Asteroid Survey scenario

Exogenous Plant-Based Nutraceutical Supplementation and Peripheral Cell Mononuclear DNA Damage Following High Intensity Exercise

Plant-based nutraceuticals are categorised as nutritional supplements which contain a high concentration of antioxidants with the intention of minimising the deleterious effect of an oxidative insult. The primary aim of this novel study was to determine the effect of exogenous barley-wheat grass juice (BWJ) on indices of exercise-induced oxidative stress. Ten (n = 10) apparently healthy, recreationally trained (V̇O2max 55.9 ± 6 mL·kg−1·min−1), males (age 22 ± 2 years, height 181 ± 6 cm, weight 87 ± 8 kg, body mass index (BMI) 27 ± 1) volunteered to participant in the study. In a randomised, double-blinded, placebo-controlled crossover design, participants consumed either a placebo, a low dose (70 mL per day) of BWJ, or a high dose (140 mL per day) of BWJ for 7-days. Experimental exercise consisted of a standard maximal oxygen uptake test until volitional fatigue. DNA damage, as assessed by the single cell gel electrophoresis comet assay, increased following high intensity exercise across all groups (time × group; p < 0.05, Effect Size (ES) = 0.7), although there was no selective difference for intervention (p > 0.05). There was a main effect for time in lipid hydroperoxide concentration (pooled-group data, pre- vs. post-exercise, p < 0.05, ES = 0.2) demonstrating that exercise increased lipid peroxidation. Superoxide dismutase activity (SOD) increased by 44.7% following BWJ supplementation (pooled group data, pre- vs. post). The ascorbyl free radical (p < 0.05, ES = 0.26), α-tocopherol (p = 0.007, ES = 0.2), and xanthophyll (p = 0.000, ES = 0.5), increased between the pre- and post-exercise time points indicating a main effect of time. This study illustrates that a 7-day supplementation period of a novel plant-derived nutraceutical product is insufficient at attenuating exercise-induced oxidative damage. It is possible that with a larger sample size, and longer supplementation period, this novel plant-based nutraceutical could potentially offer effective prophylaxis against exercise-induced oxidative stress; as such, this justifies the need for further research

Effectiveness of Exercise on Fatigue and Sleep Quality in Fibromyalgia: A Systematic Review and Meta-analysis of Randomized Trials

Objectives: To determine the effects of exercise on fatigue and sleep quality in fibromyalgia (primary aim) and to identify which type of exercise is the most effective in achieving these outcomes (secondary aim). Data Sources: PubMed and Web of Science were searched from inception until October 18, 2018. Study Selection: Eligible studies contained information on population (fibromyalgia), intervention (exercise), and outcomes (fatigue or sleep). Randomized controlled trials (RCT) testing the effectiveness of exercise compared with usual care and randomized trials (RT) comparing the effectiveness of 2 different exercise interventions were included for the primary and secondary aims of the present review, respectively. Two independent researchers performed the search, screening, and final eligibility of the articles. Of 696 studies identified, 17 RCTs (nZ1003) were included for fatigue and 12 RCTs (nZ731) for sleep. Furthermore, 21 RTs compared the effectiveness of different exercise interventions (nZ1254). Data Extraction: Two independent researchers extracted the key information from each eligible study. Data Synthesis: Separate random-effect meta-analyses were performed to examine the effects from RCTs and from RTs (primary and secondary aims). Standardized mean differences (SMD) effect sizes were calculated using Hedges’ adjusted g. Effect sizes of 0.2, 0.4, and 0.8 were considered small, moderate, and large. Compared with usual care, exercise had moderate effects on fatigue and a small effect on sleep quality (SMD, e0.47; 95% confidence interval [CI], e0.67 to e0.27; P<.001 and SMD, e0.17; 95% CI, e0.32 to e0.01; PZ.04). RTs in which fatigue was the primary outcome were the most beneficial for lowering fatigue. Additionally, meditative exercise programs were the most effective for improving sleep quality. Conclusions: Exercise is moderately effective for lowering fatigue and has small effects on enhancing sleep quality in fibromyalgia. Meditative exercise programs may be considered for improving sleep quality in fibromyalgi

Preclinical Evaluation of AZ12601011 and AZ12799734, Inhibitors of Transforming Growth Factor β Superfamily Type 1 Receptors.

The transforming growth factor β (TGFβ) superfamily includes TGFβ, activins, inhibins, and bone morphogenetic proteins (BMPs). These extracellular ligands have essential roles in normal tissue homeostasis by coordinately regulating cell proliferation, differentiation, and migration. Aberrant signaling of superfamily members, however, is associated with fibrosis as well as tumorigenesis, cancer progression, metastasis, and drug-resistance mechanisms in a variety of cancer subtypes. Given their involvement in human disease, the identification of novel selective inhibitors of TGFβ superfamily receptors is an attractive therapeutic approach. Seven mammalian type 1 receptors have been identified that have context-specific roles depending on the ligand and the complex formation with the type 2 receptor. Here, we characterize the biologic effects of two transforming growth factor β receptor 1 (TGFBR1) kinase inhibitors designed to target TGFβ signaling. AZ12601011 [2-(2-pyridinyl)-4-(1H-pyrrolo[3,2-c]pyridin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidine]; structure previously undisclosed] and AZ12799734 [4-({4-[(2,6-dimethyl-3-pyridinyl)oxy]-2-pyridinyl}amino)benzenesulfonamide] (IC50 = 18 and 47 nM, respectively) were more effective inhibitors of TGFβ-induced reporter activity than SB-431542 [4-[4-(1,3-benzodioxol-5-yl)-5-(2-pyridinyl)-1H-imidazol-2-yl]benzamide] (IC50 = 84 nM) and LY2157299 [4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline-6-carboxamide monohydrate]] (galunisertib) (IC50 = 380 nM). AZ12601011 inhibited phosphorylation of SMAD2 via the type 1 receptors activin A receptor type 1B (ALK4), TGFBR1, and activin A receptor type 1C (ALK7). AZ12799734, however, is a pan TGF/BMP inhibitor, inhibiting receptor-mediated phosphorylation of SMAD1 by activin A receptor type 1L, bone morphogenetic protein receptor type 1A, and bone morphogenetic protein receptor type 1B and phosphorylation of SMAD2 by ALK4, TGFBR1, and ALK7. AZ12601011 was highly effective at inhibiting basal and TGFβ-induced migration of HaCaT keratinocytes and, furthermore, inhibited tumor growth and metastasis to the lungs in a 4T1 syngeneic orthotopic mammary tumor model. These inhibitors provide new reagents for investigating in vitro and in vivo pathogenic processes and the contribution of TGFβ- and BMP-regulated signaling pathways to disease states

Technology requirements of exploration beyond Neptune by solar sail propulsion

This paper provides a set of requirements for the technology development of a solar sail propelled Interstellar Heliopause Probe mission. The mission is placed in the context of other outer solar systems missions, ranging from a Kuiper Belt mission through to an Oort cloud mission. Mission requirements are defined and a detailed parametric trajectory analysis and launch date scan performed. Through analysis of the complete mission trade space a set of critical technology development requirements are identified which include an advanced lightweight composite High-Gain Antenna, a high-efficiency Ka-band travelling-wave tube amplifier and a radioisotope thermoelectric generator with power density of approximately 12 W/kg. It is also shown that the Interstellar Heliopause Probe mission necessitates the use of a spinning sail, limiting the direct application of current hardware development activities. A Kuiper Belt mission is then considered as a pre-curser to the Interstellar Heliopause Probe, while it is also shown through study of an Oort cloud mission that the Interstellar Heliopause Probe mission is the likely end-goal of any future solar sail technology development program. As such, the technology requirements identified to enable the Interstellar Heliopause Probe must be enabled through all prior missions, with each mission acting as an enabling facilitator towards the next

An octameric PqiC toroid stabilises the outer-membrane interaction of the PqiABC transport system

The E. coli Paraquat Inducible (Pqi) Pathway is a putative Gram-negative phospholipid transport system. The pathway comprises three components: an integral inner membrane protein (PqiA), a periplasmic spanning MCE family protein (PqiB) and an outer membrane lipoprotein (PqiC). Interactions between all complex components, including stoichiometry, remain uncharacterised; nevertheless, once assembled into their quaternary complex, the trio of Pqi proteins are anticipated to provide a continuous channel between the inner and outer membranes of diderms. Here, we present X-ray structures of both the native and a truncated, soluble construct of the PqiC lipoprotein, providing insight into its biological assembly, and utilise neutron reflectometry to characterise the nature of the PqiB-PqiC-membrane interaction. Finally, we employ phenotypic complementation assays to probe specific PqiC residues, which imply the interaction between PqiB and PqiC is less intimate than previously anticipated.</p

Structure of the MlaC-MlaD complex reveals molecular basis of periplasmic phospholipid transport

The Maintenance of Lipid Asymmetry (Mla) pathway is a multicomponent system found in all gram-negative bacteria that contributes to virulence, vesicle blebbing and preservation of the outer membrane barrier function. It acts by removing ectopic lipids from the outer leaflet of the outer membrane and returning them to the inner membrane through three proteinaceous assemblies: the MlaA-OmpC complex, situated within the outer membrane; the periplasmic phospholipid shuttle protein, MlaC; and the inner membrane ABC transporter complex, MlaFEDB, proposed to be the founding member of a structurally distinct ABC superfamily. While the function of each component is well established, how phospholipids are exchanged between components remains unknown. This stands as a major roadblock in our understanding of the function of the pathway, and in particular, the role of ATPase activity of MlaFEDB is not clear. Here, we report the structure of E. coli MlaC in complex with the MlaD hexamer in two distinct stoichiometries. Utilising in vivo complementation assays, an in vitro fluorescence-based transport assay, and molecular dynamics simulations, we confirm key residues, identifying the MlaD β6-β7 loop as essential for MlaCD function. We also provide evidence that phospholipids pass between the C-terminal helices of the MlaD hexamer to reach the central pore, providing insight into the trajectory of GPL transfer between MlaC and MlaD

Association Analysis of Canonical Wnt Signalling Genes in Diabetic Nephropathy

Several studies have provided compelling evidence implicating the Wnt signalling pathway in the pathogenesis of diabetic nephropathy. Gene expression profiles associated with renal fibrosis have been attenuated through Wnt pathway modulation in model systems implicating Wnt pathway members as potential therapeutic targets for the treatment of diabetic nephropathy. We assessed tag and potentially functional single nucleotide polymorphisms (SNPs; n = 31) in four key Wnt pathway genes (CTNNB1, AXIN2, LRP5 and LRP6) for association with diabetic nephropathy using a case-control design.SNPs were genotyped using Sequenom or Taqman technologies in 1351 individuals with type 1 diabetes (651 cases with nephropathy and 700 controls without nephropathy). Cases and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Adjustment for multiple testing was performed by permutation testing.Following logistic regression analysis adjusted by collection centre, duration of T1D, and average HbA1c as covariates, a single SNP in LRP6 (rs1337791) was significantly associated with DN (OR = 0.74; CI: 0.57-0.97; P = 0.028), although this was not maintained following correction for multiple testing. Three additional SNPs (rs2075241 in LRP6; rs3736228 and rs491347 both in LRP5) were marginally associated with diabetic nephropathy, but none of the associations were replicated in an independent dataset. Haplotype and subgroup analysis (according to duration of diabetes, and end-stage renal disease) also failed to reveal an association with diabetic nephropathy.Our results suggest that analysed common variants in CTNNB1, AXIN2, LRP5 and LRP6 are not strongly associated with diabetic nephropathy in type 1 diabetes among white individuals. Our findings, however, cannot entirely exclude these genes or other members of the Wnt pathway, from involvement in the pathogenesis of diabetic nephropathy as our study had limited power to detect variants with small effect size