Solar sail formation flying for deep-space remote sensing

In this paper we consider how 'near' term solar sails can be used in formation above the ecliptic plane to provide platforms for accurate and continuous remote sensing of the polar regions of the Earth. The dynamics of the solar sail elliptical restricted three-body problem (ERTBP) are exploited for formation flying by identifying a family of periodic orbits above the ecliptic plane. Moreover, we find a family of 1 year periodic orbits where each orbit corresponds to a unique solar sail orientation using a numerical continuation method. It is found through a number of example numerical simulations that this family of orbits can be used for solar sail formation flying. Furthermore, it is illustrated numerically that Solar Sails can provide stable formation keeping platforms that are robust to injection errors. In addition practical trajectories that pass close to the Earth and wind onto these periodic orbits above the ecliptic are identified

Functional characterization and identification of mouse Rad51d splice variants

<p>Abstract</p> <p>Background</p> <p>The homologous recombination (HR) pathway is vital for maintaining genomic integrity through the restoration of double-stranded breaks and interstrand crosslinks. The RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) are essential for this process in vertebrates, and the RAD51D paralog is unique in that it participates in both HR repair and telomere maintenance. RAD51D is also known to directly interact with the RAD51C and XRCC2 proteins. <it>Rad51d </it>splice variants have been reported in mouse and human tissues, supportive of a role for alternative splicing in HR regulation. The present study evaluated the interaction of the <it>Rad51d </it>splice isoform products with RAD51C and XRCC2 and their expression patterns.</p> <p>Results</p> <p>Yeast-2-hybrid analysis was used to determine that the <it>Mus musculus Rad51d </it>splice variant product RAD51DΔ7b (deleted for residues 219 through 223) was capable of interacting with both RAD51C and XRCC2 and that RAD51D+int3 interacted with XRCC2. In addition, the linker region (residues 54 through 77) of RAD51D was identified as a region that potentially mediates binding with XRCC2. Cellular localization, detected by EGFP fusion proteins, demonstrated that each of the splice variant products tested was distributed throughout the cell similar to the full-length protein. However, none of the splice variants were capable of restoring resistance of <it>Rad51d</it>-deficient cell lines to mitomycin C. RT-PCR expression analysis revealed that <it>Rad51dΔ3 </it>(deleted for exon 3) and <it>Rad51dΔ5 </it>(deleted for exon 5)transcripts display tissue specific expression patterns with <it>Rad51dΔ3 </it>being detected in each tissue except ovary and <it>Rad51dΔ5 </it>not detected in mammary gland and testis. These expression studies also led to the identification of two additional <it>Rad51d </it>ubiquitously expressed transcripts, one deleted for both exon 9 and 10 and one deleted for only exon 10.</p> <p>Conclusion</p> <p>These results suggest <it>Rad51d </it>alternative splice variants potentially modulate mechanisms of HR by sequestering either RAD51C or XRCC2.</p

Orbital Debris-Debris Collision Avoidance

We focus on preventing collisions between debris and debris, for which there is no current, effective mitigation strategy. We investigate the feasibility of using a medium-powered (5 kW) ground-based laser combined with a ground-based telescope to prevent collisions between debris objects in low-Earth orbit (LEO). The scheme utilizes photon pressure alone as a means to perturb the orbit of a debris object. Applied over multiple engagements, this alters the debris orbit sufficiently to reduce the risk of an upcoming conjunction. We employ standard assumptions for atmospheric conditions and the resulting beam propagation. Using case studies designed to represent the properties (e.g. area and mass) of the current debris population, we show that one could significantly reduce the risk of nearly half of all catastrophic collisions involving debris using only one such laser/telescope facility. We speculate on whether this could mitigate the debris fragmentation rate such that it falls below the natural debris re-entry rate due to atmospheric drag, and thus whether continuous long-term operation could entirely mitigate the Kessler syndrome in LEO, without need for relatively expensive active debris removal.Comment: 13 pages, 8 figures. Accepted for publication in Advances in Space Researc

MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease

MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing the common human condition tendinopathy as a model system to explore the cross-regulation of immediate inflammation and matrix synthesis by miRNA we observed that elevated IL-33 expression is a characteristic of early tendinopathy. Using in vitro tenocyte cultures and in vivo models of tendon damage, we demonstrate that such IL-33 expression plays a pivotal role in the transition from type 1 to type 3 collagen (Col3) synthesis and thus early tendon remodelling. Both IL-33 effector function, via its decoy receptor sST2, and Col3 synthesis are regulated by miRNA29a. Downregulation of miRNA29a in human tenocytes is sufficient to induce an increase in Col3 expression. These data provide a molecular mechanism of miRNA-mediated integration of the early pathophysiologic events that facilitate tissue remodelling in human tendon after injury

Responsiveness of serum C‐reactive protein, interleukin‐17A, and interleukin‐17F levels to ustekinumab in psoriatic arthritis: lessons from two phase III, multicenter, double‐blind, placebo‐controlled trials

Objective: To evaluate the associations of C‐reactive protein (CRP) and circulating Th17‐associated cytokine levels with psoriatic arthritis (PsA) disease activity and therapeutic response to ustekinumab. Methods: Interleukin‐17A (IL‐17A), IL‐17F, IL‐23, and CRP concentrations were measured in serum samples collected as part of the 2 PSUMMIT phase III studies of ustekinumab in PsA (n = 927). In post hoc analyses, relationships of IL‐17A, IL‐17F, and CRP levels at baseline, week 4, and week 24 with baseline skin and joint disease activity and response to therapy were evaluated using generalized linear models and Pearson's product‐moment correlation tests. Results: Baseline serum levels of IL‐17A and IL‐17F were positively correlated with baseline skin disease scores (r = 0.39–0.62). IL‐23 levels were correlated with skin disease scores to a lesser extent (r = 0.26–0.31). No significant correlations were observed between these cytokine or CRP levels and baseline joint disease activity. There was no significant association of baseline levels of IL‐17A, IL‐17F, IL‐23, or CRP with therapeutic response to ustekinumab in either the skin or joints. Significant reductions from baseline in levels of IL‐17A, IL‐17F, and CRP were seen in patients treated with ustekinumab compared to those treated with placebo. Ustekinumab‐treated patients in whom 75% improvement in the Psoriasis Area and Severity Index score or 20% improvement according to the American College of Rheumatology criteria was achieved after 24 weeks of treatment had greater reductions in CRP level (geometric mean decreases of 51–58% versus 32–33%; P &lt; 0.05), but not IL‐17A or IL‐17F levels, than nonresponders. Conclusion: Baseline serum IL‐23/IL‐17 levels correlated with skin, but not joint, disease activity, suggesting tissue‐specific variation. However, neither baseline Th17‐associated cytokine levels nor CRP level were predictive of therapeutic response to ustekinumab in the skin or joints, despite rapid reductions in their levels following ustekinumab therapy

Bayesian inference reveals positive but subtle effects of experimental fishery closures on marine predator demographics

Global forage-fish landings are increasing, with potentially grave consequences for marine ecosystems. Predators of forage fish may be influenced by this harvest, but the nature of these effects is contentious. Experimental fishery manipulations offer the best solution to quantify population-level impacts, but are rare. We used Bayesian inference to examine changes in chick survival, body condition and population growth rate of endangered African penguins Spheniscus demersus in response to 8 years of alternating time–area closures around two pairs of colonies. Our results demonstrate that fishing closures improved chick survival and condition, after controlling for changing prey availability. However, this effect was inconsistent across sites and years, highlighting the difficultly of assessing management interventions in marine ecosystems. Nevertheless, modelled increases in population growth rates exceeded 1% at one colony; i.e. the threshold considered biologically meaningful by fisheries management in South Africa. Fishing closures evidently can improve the population trend of a forage-fish-dependent predator—we therefore recommend they continue in South Africa and support their application elsewhere. However, detecting demographic gains for mobile marine predators from small no-take zones requires experimental time frames and scales that will often exceed those desired by decision makers

The Meisenheimer complex as a paradigm in drug discovery: reversible covalent inhibition through C67 of the ATP binding site of PLK1

The polo kinase family are important oncology targets that act in regulating entry into and progression through mitosis. Structure-guided discovery of a new class of inhibitors of Polo-like kinase 1 (PLK1) catalytic activity that interact with Cys67 of the ATP binding site is described. Compounds containing the benzothiazole N-oxide scaffold not only bind covalently to this residue, but are reversible inhibitors through the formation of Meisenheimer complexes. This mechanism of kinase inhibition results in compounds that can target PLK1 with high selectivity, while avoiding issues with irreversible covalent binding and interaction with other thiol-containing molecules in the cell. Due to renewed interest in covalent drugs and the plethora of potential drug targets, these represent prototypes for the design of kinase inhibitory compounds that achieve high specificity through covalent interaction and yet still bind reversibly to the ATP cleft, a strategy that could be applied to avoid issues with conventional covalent binders

Impact of rising sea levels on Australian fur seals

Global warming is leading to many unprecedented changes in the ocean-climate system. Sea levels are rising at an increasing rate and are amplifying the impact of storm surges along coastlines. As variability in the timing and strength of storm surges has been shown to affect pup mortality in the Australian fur seal (Arctocephalus pusillus doriferus), there is a need to identify the potential impacts of increased sea level and storm surges on the breeding areas of this important marine predator in Bass Strait, south-eastern Australia. Using high-resolution aerial photography and topographic data, the present study assessed the impacts of future inundation levels on both current and potential breeding habitats at each colony. Inundation from storm surges, based on a predicted rise in sea level, was modeled at each colony from 2012 to 2100. As sea level increases, progressively less severe storm surge conditions will be required to exceed current inundation levels and, thus, have the potential for greater impacts on pup mortality at Australian fur seal colonies. The results of the present study indicate that by 2100, a 1-in-10 year storm will inundate more habitat on average than a present-day 1-in-100 year storm. The study highlights the site-specific nature of storm surge impacts, and in particular the importance of local colony topography and surrounding bathymetry with small, low-lying colonies impacted the most. An increased severity of storm surges will result in either an increase in pup mortality rates associated with storm surges, or the dispersal of individuals to higher ground and/or new colonies