Rubble Pile Asteroids Walsh, Kevin J
Annual review of astronomy and astrophysics,
09/2018, Letnik:
56, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The moniker rubble pile is typically applied to all Solar System bodies >200 m and <∼10 km in diameter; in this size range, there is an abundance of evidence that nearly every object is bound ...primarily by self-gravity, with significant void space or bulk porosity between irregularly shaped constituent particles. The understanding of this population is derived from wide-ranging population studies of derived shape and spin, decades of observational studies in numerous wavelengths, evidence left behind from impacts on planets and moons, and the in situ study of a few objects via spacecraft flyby or rendezvous. The internal structure, however, which is responsible for the name rubble pile, is never directly observed but belies a violent history. Many or most of the asteroids on near-Earth orbits and those most accessible for rendezvous and in situ study are likely by-products of the continued collisional evolution of the main asteroid belt.
Soft actuators are the components responsible for producing motion in soft robots. Although soft actuators have allowed for a variety of innovative applications, there is a need for design tools that ...can help to efficiently and systematically design actuators for particular functions. Mathematical modeling of soft actuators is an area that is still in its infancy but has the potential to provide quantitative insights into the response of the actuators. These insights can be used to guide actuator design, thus accelerating the design process. Here, we study fluid-powered fiber-reinforced actuators, because these have previously been shown to be capable of producing a wide range of motions. We present a design strategy that takes a kinematic trajectory as its input and uses analytical modeling based on nonlinear elasticity and optimization to identify the optimal design parameters for an actuator that will follow this trajectory upon pressurization. We experimentally verify our modeling approach, and finally we demonstrate how the strategy works, by designing actuators that replicate the motion of the index finger and thumb.
Hybrid drugs for malaria Walsh, J J; Bell, A
Current pharmaceutical design,
09/2009, Letnik:
15, Številka:
25
Journal Article
Recenzirano
Malaria continues to devastate much of the tropics and sub-tropics in spite of the availability of a number of antimalarial drugs. Part of this problem is due to the disadvantages of the drugs in ...use, which include (depending on the drug) side effects, reduced efficacy due to resistance, and high cost. Multiple traditional and novel approaches to the discovery and design of new antimalarial agents are likely to be required to furnish the new drugs necessary for improved malaria control. This review will address one novel and emerging approach, namely the development of hybrid antimalarial agents composed of two distinct antimalarial moieties joined covalently. Particular emphasis will be placed on the properties of the hybrids' design, including biological activity, advantages over other approaches, and the potential to address issues relating to resistance, solubility and formulation/delivery. The review will discuss the synthetic methodology used to form the hybrid and the ease by which it may be cleaved to form the independent components in vivo. The molecules discussed include hybrids of (i) artemisinins or other endoperoxide-based agents and quinolines (e.g. trioxaquines), (ii) chloroquine or other aminoquinolines and resistance-reversing or other agents, and (iii) peptidase inhibitors and other agents. The actual and potential advantages and disadvantages of such hybrids in relation to established single drugs or drug combinations will be discussed critically and promising future directions highlighted.
Earth-surface processes operate across erosionally dominated landscapes and deliver sediment to depositional systems that can be preserved over a range of timescales. The geomorphic and stratigraphic ...products of this source-to-sink sediment transfer record signals of external environmental forcings, as well as internal, or autogenic, dynamics of the sedimentary system. Here, we evaluate environmental signal propagation across sediment-routing systems with emphasis on sediment supply, Qs, as the carrier of up-system forcings. We review experimental, numerical, and natural examples of source-to-sink sediment routing and signal propagation during three timescales: (1) historic, which includes measurement and monitoring of events and processes of landscape change and deposition during decades to centuries; (2) centuries to several millions of years, referred to as intermediate timescale; and (3) deep time. We discuss issues related to autogenic dynamics of sediment transport, transient storage, and release that can introduce noise, lags, and/or completely mask signals of external environmental forcings. We provide a set of conceptual and practical tools for evaluating sediment supply within a source-to-sink context, which can inform interpretations of signals from the sedimentary record. These tools include stratigraphic and sediment-routing system characterization, sediment budgets, geochronology, detrital mineral analysis (e.g., thermochronology), comparative analog approaches, and modeling techniques to measure, calculate, or estimate the magnitude and frequency of external forcings compared to the characteristic response time of the sediment-routing systems.
The presence of diabetic foot ulcers is strongly associated with an increased risk of death. In this study, we investigate whether the effects of diabetes-associated complications can explain the ...apparent relationship between diabetic foot ulcers and death.
We analysed data from 414 523 people with diabetes enrolled in practices associated with The Health Improvement Network in the United Kingdom. Our methods were designed to control for potential confounders in order to isolate the relationship between diabetic foot ulcers and death. Using proportional hazards models and the area under the receiver operator curve, we evaluated the effects of diabetic foot ulcers and the covariates on death.
Among the patients, 20 737 developed diabetic foot ulcers; 5.0% of people with new ulcers died within 12 months of their first foot ulcer visit and 42.2% of people with foot ulcers died within 5 years. After controlling for major known complications of diabetes that might influence mortality, the correlation between diabetic foot ulcers and death remained strong with a fully adjusted hazard ratio of 2.48 (95% confidence interval: 2.43, 2.54). Geographic variance existed but was not spatially associated.
Diabetic foot ulcers are linked to an increased risk of death. This cannot be explained by other common risk factors. These results suggest that either there are major unknown risk factors associated with both diabetic foot ulcers and death, or that diabetic foot ulceration itself is a serious threat, which seems unlikely. A diabetic foot ulcer should be seen as a major warning sign for mortality, necessitating closer medical follow-up.
Engagement in regular bouts of exercise confers numerous positive effects on brain health across the lifespan. Acute bouts of exercise transiently improve cognitive function, while long-term exercise ...training stimulates brain plasticity, improves brain function, and helps to stave off neurological disease. The action of brain-derived neurotrophic factor (BDNF) is a candidate mechanism underlying these exercise-induced benefits and is the subject of considerable attention in the exercise-brain health literature. It is well established that acute exercise increases circulating levels of BDNF and numerous studies have sought to characterize this response for the purpose of improving brain health. Despite the interest in BDNF responses to exercise, little focus has been given to understanding the sources and mechanisms that underlie this response for the purpose of deliberately increasing circulating levels of BDNF. Here we review evidence to support that exploiting these mechanisms of BDNF release can help to optimize brain plasticity outcomes via exercise interventions, which could be especially relevant in the context of multimodal training (i.e., exercise and cognitive stimulation). Therefore, the purpose of this paper is to review the candidate sources of BDNF during exercise and the mechanisms of release. As well, we discuss strategies for maximizing BDNF responses to exercise, and propose novel research directions for advancing our understanding of these mechanisms.
Mast cell stabilizing drugs inhibit the release of allergic mediators from mast cells and are used clinically to prevent allergic reactions to common allergens. Despite the relative success of the ...most commonly prescribed mast cell stabilizer, disodium cromoglycate, in use for the preventative treatment of bronchial asthma, allergic conjunctivitis and vernal keratoconjunctivitis, there still remains an urgent need to design new substances that are less expensive and require less frequent dosing schedules. In this regard, recent developments towards the discovery of the next generation of mast cell stabilizing drugs has included studies on substances isolated from natural sources, biological, newly synthesized compounds and drugs licensed for other indications. The diversity of natural products evaluated range from simple phenols, alkaloids, terpenes to simple amino acids. While in some cases their precise mode of action remains unknown it has nevertheless sparked interest in the development of synthetic derivatives with improved pharmacological properties. Within the purely synthetic class of inhibitors, particular attention has been devoted to the inhibition of important signalling molecules including spleen TK and JAK3. The statin class of cholesterol‐lowering drugs as well as nilotinib, a TK inhibitor, are just some examples of clinically used drugs that have been evaluated for their anti‐allergic properties. Here, we examine each approach under investigation, summarize the test data generated and offer suggestions for further preclinical evaluation before their therapeutic potential can be realized.
Linked Articles
This article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/
10.1111/bph.2013.170.issue‐1
The increasing capabilities of exoskeletons and powered prosthetics for walking assistance have paved the way for more sophisticated and individualized control strategies. In response to this ...opportunity, recent work on human-in-the-loop optimization has considered the problem of automatically tuning control parameters based on realtime physiological measurements. However, the common use of metabolic cost as a performance metric creates significant experimental challenges due to its long measurement times and low signal-to-noise ratio. We evaluate the use of Bayesian optimization-a family of sample-efficient, noise-tolerant, and global optimization methods-for quickly identifying near-optimal control parameters. To manage experimental complexity and provide comparisons against related work, we consider the task of minimizing metabolic cost by optimizing walking step frequencies in unaided human subjects. Compared to an existing approach based on gradient descent, Bayesian optimization identified a near-optimal step frequency with a faster time to convergence (12 minutes, p < 0.01), smaller inter-subject variability in convergence time (± 2 minutes, p < 0.01), and lower overall energy expenditure (p < 0.01).
Voriconazole, a triazole antifungal agent, demonstrates wide interpatient variability in serum concentrations, due in part to variant CYP2C19 alleles. Individuals who are CYP2C19 ultrarapid ...metabolizers have decreased trough voriconazole concentrations, delaying achievement of target blood concentrations; whereas poor metabolizers have increased trough concentrations and are at increased risk of adverse drug events. We summarize evidence from the literature supporting this association and provide therapeutic recommendations for the use of voriconazole for treatment based on CYP2C19 genotype (updates at https://cpicpgx.org/guidelines/ and www.pharmgkb.org).
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