A plan for spacecraft automated rendezvous

An automated rendezvous approach has been developed that utilizes advances in technology to reduce real-time/near real-time flight operations support personnel to an acceptable level that is near the minimum without jeopardizing the success of the mission. The on-board flight targeting uses a rule-based system to select the pursuit vehicle phasing orbits and uses precise navigation updates from the pursuit/target spacecraft made possible by the global positioning system receivers/processors on both spacecraft to adjust the phasing orbits and achieve rendezvous. The ascent-to-orbit targeting for the pursuit vehicle has been successfully decoupled from the on-orbit orbit transfer phasing targeting. Typical launch window data have been developed for the heavy lift launch vehicle and cargo transfer vehicle for a Space Station Freedom rendezvous mission

Enhancing Perception of Complex Sculptural Forms using Interactive Real-time Ray tracing

This paper looks at experiments into using real-time ray tracing to significantly enhance shape perception of complex three-dimensional digitally created structures. The author is a computational artist whose artistic practice explores the creation of intricate organic three-dimensional forms using simulation of morphogenesis. The generated forms are often extremely detailed, comprising tens of millions of cellular primitives. This often makes depth perception of the resulting structures difficult. His practice has explored various techniques to create presentable artefacts from the data, including high resolution prints, animated videos, stereoscopic installations, 3D printing and virtual reality. The author uses ray tracing techniques to turn the 3D data created from his morphogenetic simulations into visible artefacts. This is typically a time-consuming process, taking from seconds to minutes to create a single frame. The latest generation of graphics processing units offer dedicated hardware to accelerate ray tracing calculations. This potentially allows the generation of ray traced images, including self-shadowed complex structures and multiple levels of transparency, from new viewpoints at frame rates capable of real-time interaction. The author presents the results of his experiments using this technology with the aim of providing significantly enhanced perception of his generated three-dimensional structures by allowing user-initiated interaction to generate novel views, and utilizing depth cues such as stereopsis, depth from motion and defocus blurring. The intention is for these techniques to be usable to present new exhibitable works in a gallery context

An antibody raised against a pathogenic serpin variant induces mutant-like behaviour in the wild-type protein

A monoclonal antibody (mAb) that binds to a transient intermediate may act as a catalyst for the corresponding reaction; here we show this principle can extend on a macro molecular scale to the induction of mutant-like oligomerization in a wild-type protein. Using the common pathogenic E342K (Z) variant of α1-antitrypsin as antigen-whose native state is susceptible to the formation of a proto-oligomeric intermediate-we have produced a mAb (5E3) that increases the rate of oligomerization of the wild-type (M) variant. Employing ELISA, gel shift, thermal stability and FRET time-course experiments, we show that mAb5E3 does not bind to the native state of α1-antitrypsin, but recognizes a cryptic epitope in the vicinity of the post-helix A loop and strand 4C that is revealed upon transition to the polymerization intermediate, and which persists in the ensuing oligomer. This epitope is not shared by loop-inserted monomeric conformations. We show the increased amenity to polymerization by either the pathogenic E342K mutation or the binding of mAb5E3 occurs without affecting the energetic barrier to polymerization. As mAb5E3 also does not alter the relative stability of the monomer to intermediate, it acts in a manner similar to the E342K mutant, by facilitating the conformational interchange between these two states

Why national health research systems matter

Some of the most outstanding problems in Computer Science (e.g. access to heterogeneous information sources, use of different e-commerce standards, ontology translation, etc.) are often approached through the identification of ontology mappings. A manual mapping generation slows down, or even makes unfeasible, the solution of particular cases of the aforementioned problems via ontology mappings. Some algorithms and formal models for partial tasks of automatic generation of mappings have been proposed. However, an integrated system to solve this problem is still missing. In this paper, we present AMON, a platform for automatic ontology mapping generation. First of all, we show the general structure. Then, we describe the current version of the system, including the ontology in which it is based, the similarity measures that it uses, the access to external sources, etc

Endoplasmic reticulum dysfunction in neurological disease.

Endoplasmic reticulum (ER) dysfunction might have an important part to play in a range of neurological disorders, including cerebral ischaemia, sleep apnoea, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, the prion diseases, and familial encephalopathy with neuroserpin inclusion bodies. Protein misfolding in the ER initiates the well studied unfolded protein response in energy-starved neurons during stroke, which is relevant to the toxic effects of reperfusion. The toxic peptide amyloid β induces ER stress in Alzheimer's disease, which leads to activation of similar pathways, whereas the accumulation of polymeric neuroserpin in the neuronal ER triggers a poorly understood ER-overload response. In other neurological disorders, such as Parkinson's and Huntington's diseases, ER dysfunction is well recognised but the mechanisms by which it contributes to pathogenesis remain unclear. By targeting components of these signalling responses, amelioration of their toxic effects and so the treatment of a range of neurodegenerative disorders might become possible

Hepatorenal Syndrome: Aetiology, Diagnosis, and Treatment

Acute renal impairment is common in patients with chronic liver disease, occurring in approximately 19% of hospitalised patients with cirrhosis. A variety of types of renal impairment are recognised. The most important of these is the hepatorenal syndrome, a functional renal impairment due to circulatory and neurohormonal abnormalities that underpin cirrhosis. It is one of the most severe complications of cirrhosis with survival often measured in weeks to months. A variety of treatment options exist with early diagnosis and appropriate treatment providing the best hope for cure. This paper provides a comprehensive and up-to-date review of hepatorenal syndrome and lays out the topic according to the following sections: pathophysiology, historical developments, diagnostic criteria and limitations, epidemiology, precipitating factors, predictors, clinical and laboratory findings, prognosis, treatment options, prophylaxis, and conclusion

Dye-conjugated complementary lipophilic nucleosides as useful probes to study association processes by fluorescence resonance energy transfer

Modern supramolecular chemistry relies on the combination of diverse analytical techniques that can provide complementary information on complex self-assembly landscapes. Among them, resonance energy transfer, monitored by fluorescence emission spectroscopy, arises as a sensitive and convenient phenomenon to report binding intermolecular interactions. The use of molecular probes labelled with suitable complementary energy-transfer pairs can provide valuable information about the thermodynamics, kinetics and self-sorting characteristics of a particular self-assembled system. The objective of this work is to generate a set of nucleoside FRET probes that can be reliably employed to prove and analyse quantitatively H-bonding interactions between complementary Watson-Crick pairs. We first describe the preparation of a set of lipophilic nucleosides that are linked to a π-conjugated functional fragment. The bases include guanosine and 2-aminoadenosine as purine heterocycles, and cytidine and uridine as complementary pyrimidine bases. The π-conjugated moiety comprises either a short phenylene-ethynylene oligomer, a bithiophene, or a BODIPY dye. We then demonstrate that the last two chromophores constitute an energy donor-acceptor couple and that donor emission quenching can be related to the ratio of molecules bound to the complementary acceptor pair. Hence, fluorescence spectroscopy in combination with resonance energy transfer, is shown here to be a useful tool to study and quantify the association and self-sorting events between complementary and non-complementary nucleosides in apolar aromatic solvents, where the binding strength is considerably high, and sensitive techniques that employ low concentrations are demandedFunding from the European Research Council (ERC-Starting Grant 279548 PROGRAM-NANO) and MINECO (CTQ2014-57729-P) is gratefully acknowledged. E. F. would like to thank the Sharif University of Technology of Iran for financial support. D. S.M. would like to acknowledge Comunidad de Madrid for financial support through contract PEJ16/IND/AI-084

Economic evaluation evidence for resource-allocation decision making: bridging the gap for local decision makers using English case studies

Best-practice economic evaluation methods for health-related decision making at a national level in England are well established, and as a first principle generally involve attempting to maximise the amount of health generated from the health system’s budget. Such methods are applied in ways that are broadly transparent and accountable, often at arm’s length from explicit political pressures. At local levels of decision making, however, decision making is arguably less likely to be applied according to established overarching principles, is less transparent and is more subject to political pressures. This may be owing to a multiplicity of reasons, for example, undesirability/inappropriateness of such methods, or a failure to make the methods clear to local decision makers. We outline principles for economic evaluations and break down these methods into their component parts, considering their relevance in the English local context. These include taxonomies of decision-making frameworks, budgets, costs, outcome, and characterisations of cost effectiveness. We also explore the role of broader factors, including the relevance of assuming a single fixed budget, pressures resulting from political and budgetary cycles and affordability. We consider the data requirements to inform such deliberations. By setting out principles for economic evaluation methods in a clear language aimed at local decision making, a potential role for such methods can be established, which to date has failed to emerge. While the extent to which these methods can and should be applied are a matter for continued debate, the establishment of such a mutual understanding may assist in the improvement of methods for such decision making and the outcomes resulting from their application