Engineering considerations for practical lithium-air electrolytes.

Lithium-air batteries promise exceptional energy density while avoiding the use of transition metals in their cathodes, however, their practical adoption is currently held back by their short lifetimes. These short lifetimes are largely caused by electrolyte breakdown, but despite extensive searching, an electrolyte resistant to breakdown has yet to be found. This paper considers the requirements placed on an electrolyte for it to be considered usable in a practical cell. We go on to examine ways, through judicious cell design, of relaxing these requirements to allow for a broader range of compounds to be considered. We conclude by suggesting types of molecules that could be explored for future cells. With this work, we aim to broaden the scope of future searches for electrolytes and inform new cell design.

Spiers Memorial Lecture: Lithium air batteries - tracking function and failure.

The lithium-air battery (LAB) is arguably the battery with the highest energy density, but also a battery with significant challenges to be overcome before it can be used commercially in practical devices. Here, we discuss experimental approaches developed by some of the authors to understand the function and failure of lithium-oxygen batteries. For example, experiments in which nuclear magnetic resonance (NMR) spectroscopy was used to quantify dissolved oxygen concentrations and diffusivity are described. 17O magic angle spinning (MAS) NMR spectra of electrodes extracted from batteries at different states of charge (SOC) allowed the electrolyte decomposition products at each stage to be determined. For instance, the formation of Li2CO3 and LiOH in a dimethoxyethane (DME) solvent and their subsequent removal on charging was followed. Redox mediators have been used to chemically reduce oxygen or to chemically oxidise Li2O2 in order to prevent electrode clogging by insulating compounds, which leads to lower capacities and rapid degradation; the studies of these mediators represent an area where NMR and electron paramagnetic resonance (EPR) studies could play a role in unravelling reaction mechanisms. Finally, recently developed coupled in situ NMR and electrochemical impedance spectroscopy (EIS) are used to characterise the charge transport mechanism in lithium symmetric cells and to distinguish between electronic and ionic transport, demonstrating the formation of transient (soft) shorts in common lithium-oxygen electrolytes. More stable solid electrolyte interphases are formed under an oxygen atmosphere, which helps stabilise the lithium anode on cycling.

A Questionnaire-based Study Exploring Participant Perspectives in a Perinatal Human Challenge Trial.

BACKGROUND: Pregnant women have historically been excluded from most medical research, including human challenge studies. The proof-of-concept Lactamica 9 human challenge study investigated whether nasal inoculation of pregnant women with commensal bacteria leads to horizontal transmission to the neonate. Given the unique practical and ethical considerations of both human challenge studies and interventional research involving pregnant women and their newborns, we sought to investigate the motivations, concerns and experiences of these volunteers. METHODS: Pre- and post-participation questionnaires were given to all participants in the Lactamica 9 study. These fully anonymized qualitative and Semi-quantitative questionnaires used forced Likert scales, word association and free-text questions. RESULTS: Pre- and post-participation questionnaires were completed by 87.1% (27/31) and 62.5% (15/24) of eligible participants, respectively. Almost all pre-participation respondents agreed with altruistic motivations for participation, and most concerns were related to discomfort from study procedures, with few concerned about the theoretical risks of inoculation to themselves (5/27; 18.5%) or their baby (6/27; 22.2%). Participants most frequently associated the study intervention with the terms "bacteria," "natural," "protective" and "safe." For the post-participation questionnaire, 93.3% (14/15) found all study procedures acceptable, and qualitative feedback was almost entirely positive, with particular emphasis on the research team's flexibility, approachability and friendliness. CONCLUSIONS: The successful completion of the Lactamica 9 study demonstrates that human challenge research in healthy pregnant women can be acceptable and feasible. Participants' initial concerns of potential discomfort were outweighed by predominantly altruistic motivations and perception of the intervention as "natural."

A method for detailed movement pattern analysis of tadpole startle response.

Prolonged space flight, specifically microgravity, presents a problem for space exploration. Animal models with altered connections of the vestibular ear, and thus altered gravity sensation, would allow the examination of the effects of microgravity and how various countermeasures can establish normal function. We describe an experimental apparatus to monitor the effects of ear manipulations to generate asymmetric gravity input on the tadpole escape response. To perform the movement pattern analysis, an imaging apparatus was developed that uses a high-speed camera to obtain time-resolved, high-resolution images of tadpole movements. Movements were recorded in a temperature-controlled test chamber following mechanical stimulation with a solenoid actuator, to elicit a C-start response. Temperature within the test cell was controlled with a recirculating water bath. Xenopus laevis embryos were obtained using a standard fertilization technique. Tadpole response to a controlled perturbation was recorded in unprecedented detail and the approach was validated by describing the distinct differences in response between normal and one-eared tadpoles. The experimental apparatus and methods form an important element of a rigorous investigation into the response of the tadpole vestibular system to mechanical and biochemical manipulations, and can ultimately contribute to improved understanding of the effects of altered gravity perception on humans.

The wake structure and thrust performance of a rigid low-aspect-ratio pitching panel.

Thrust performance and wake structure were investigated for a rigid rectangular panel pitching about its leading edge in a free stream. For Re(C) = O(10(4)), thrust coefficient was found to depend primarily on Strouhal number St and the aspect ratio of the panel AR. Propulsive efficiency was sensitive to aspect ratio only for AR less than 0.83; however, the magnitude of the peak efficiency of a given panel with variation in Strouhal number varied inversely with the amplitude to span ratio A/S, while the Strouhal number of optimum efficiency increased with increasing A/S. Peak efficiencies between 9 % and 21 % were measured. Wake structures corresponding to a subset of the thrust measurements were investigated using dye visualization and digital particle image velocimetry. In general, the wakes divided into two oblique jets; however, when operating at or near peak efficiency, the near wake in many cases represented a Kármán vortex street with the signs of the vortices reversed. The three-dimensional structure of the wakes was investigated in detail for AR = 0.54, A/S = 0.31 and Re(C) = 640. Three distinct wake structures were observed with variation in Strouhal number. For approximately 0.20 < St < 0.25, the main constituent of the wake was a horseshoe vortex shed by the tips and trailing edge of the panel. Streamwise variation in the circulation of the streamwise horseshoe legs was consistent with a spanwise shear layer bridging them. For St > 0.25, a reorganization of some of the spanwise vorticity yielded a bifurcating wake formed by trains of vortex rings connected to the tips of the horseshoes. For St > 0.5, an additional structure formed from a perturbation of the streamwise leg which caused a spanwise expansion. The wake model paradigm established here is robust with variation in Reynolds number and is consistent with structures observed for a wide variety of unsteady flows. Movies are available with the online version of the paper.

Thrust performance of unsteady propulsors using a novel measurement system, and corresponding wake patterns.

An apparatus is described for the measurement of unsteady thrust and propulsive efficiency produced by biologically inspired oscillating hydrodynamic propulsors. Force measurement is achieved using a strain-gauge-based force transducer, augmented with a lever to amplify or attenuate the applied force and control the measurement sensitivity and natural frequency of vibration. The lever can be used to tune the system to a specific application and it is shown that, using the lever, the stiffness can be made to increase more rapidly than the measurement sensitivity decreases. Efficiency is computed from measurements of the time-averaged power imparted to the fluid. The apparatus is applied to two different propulsors, demonstrating the versatility of the system; wake visualizations are examined, which provide insight into the physical mechanisms of efficient propulsion.

On the evolution of the wake structure produced by a low-aspect-ratio pitching panel.

Flow visualization is used to interrogate the wake structure produced by a rigid flat panel of aspect ratio (span/chord) 0.54 pitching in a free stream at a Strouhal number of 0.23. At such a low aspect ratio, the streamwise vorticity generated by the plate tends to dominate the formation of the wake. Nevertheless, the wake has the appearance of a three-dimensional von Kármán vortex street, as observed in a wide range of other experiments, and consists of horseshoe vortices of alternating sign shed twice per flapping cycle. The legs of each horseshoe interact with the two subsequent horseshoes in an opposite-sign, then like-sign interaction in which they become entrained. A detailed vortex skeleton model is proposed for the wake formation.

Neuronal fractalkine expression in HIV-1 encephalitis: roles for macrophage recruitment and neuroprotection in the central nervous system.

HIV-1 infection of the brain results in chronic inflammation, contributing to the neuropathogenesis of HIV-1 associated neurologic disease. HIV-1-infected mononuclear phagocytes (MP) present in inflammatory infiltrates produce neurotoxins that mediate inflammation, dysfunction, and neuronal apoptosis. Neurologic disease is correlated with the relative number of MP in and around inflammatory infiltrates and not viral burden. It is unclear whether these cells also play a neuroprotective role. We show that the chemokine, fractalkine (FKN), is markedly up-regulated in neurons and neuropil in brain tissue from pediatric patients with HIV-1 encephalitis (HIVE) compared with those without HIVE, or that were HIV-1 seronegative. FKN receptors are expressed on both neurons and microglia in patients with HIVE. These receptors are localized to cytoplasmic structures which are characterized by a vesicular appearance in neurons which may be in cell-to-cell contact with MPs. FKN colocalizes with glutamate in these neurons. Similar findings are observed in brain tissue from an adult patient with HIVE. FKN is able to potently induce the migration of primary human monocytes across an endothelial cell/primary human fetal astrocyte trans-well bilayer, and is neuroprotective to cultured neurons when coadministered with either the HIV-1 neurotoxin platelet activating factor (PAF) or the regulatory HIV-1 gene product Tat. Thus focal inflammation in brain tissue with HIVE may up-regulate neuronal FKN levels, which in turn may be a neuroimmune modulator recruiting peripheral macrophages into the brain, and in a paracrine fashion protecting glutamatergic neurons.

Expression of caspase-3 in brains from paediatric patients with HIV-1 encephalitis.

Apoptosis of neurones, macrophages, and microglia occurs in the brains of paediatric patients with human immunodeficiency virus (HIV) type 1 encephalitis, which is often associated with pre-mortem neurological disease (progressive encephalopathy). We have previously reported that TUNEL-positive neurones in brain tissue from paediatric patients with HIV type 1 encephalitis and progressive encephalopathy are strikingly devoid of the pro-apoptotic gene product Bax, in marked contrast to brain-resident macrophages and microglia. Using immunocytochemical methods, the present study demonstrate that neurones in patients with HIV type 1 encephalitis and progressive encephalopathy, as well as macrophages and microglia, but not astrocytes, overexpress caspase-3, a pro-apoptotic enzyme that is proteolytically activated downstream of Bax-Bcl-2 dysregulation. Co-localization of neuronal cytoplasmic caspase-3 and nuclear TUNEL staining, a marker for fragmented DNA, was also infrequently observed in brain tissue from patients with HIV type 1 encephalitis and progressive encephalopathy. These findings suggest that vulnerable neurones in brain tissue from patients with HIV virus type 1 encephalitis and progressive encephalopathy undergo apoptosis by a mechanism that involves upregulation of caspase-3 in a pathway that is independent of Bax-Bcl-2 dysregulation. Furthermore, caspase-3 upregulation in apoptotic neurones likely occurs prior to DNA fragmentation.

Expression of pro- and anti-apoptosis gene products in brains from paediatric patients with HIV-1 encephalitis.

We have previously demonstrated the presence of DNA fragmentation in neurons, macrophages and microglia consistent with apoptosis, but not in reactive astrocytes in brain tissue from paediatric patients with HIV-1 encephalitis (HIVE). To further understand the underlying mechanism(s) for these findings as they relate to gene-directed neural cell death, we studied the in-situ expression of the Bcl-2 family of proteins, including the pro-apoptosis gene product Bax, the anti-apoptosis gene product Bcl-2, and Bcl-x. We demonstrate significantly elevated numbers of Bax-positive microglia and macrophages immunoreactive in basal ganglia and cerebral cortex of children who had HIVE, in comparison to HIV-1 infected children without encephalitis or children who were seronegative for HIV-1. In contrast, patients with HIVE, but not HIV-1 without encephalitis, or seronegative controls, had increased expression of Bcl-2 and Bcl-x in reactive astrocytes in cortex and basal ganglia. In vitro studies using Western blot analysis demonstrated an up-regulation in the levels of Bax, and phosphorylated (i.e. inactive) Bcl-2 in HIV-1 infected macrophages, and in LPS-activated macrophages, relative to levels in virus-negative unstimulated macrophages. These results suggest that productive HIV-1 infection, or cellular activation, renders macrophages more vulnerable to apoptosis. Taken together, these findings suggest that brain-resident macrophages and microglia in patients with HIV-1 encephalitis are more prone to undergo apoptosis and that astrocytes in contrast may be resistant to apoptosis. This may represent a mechanism to limit microglial activation and the spread of productive HIV-1 infection in the CNS of children with HIV-1 encephalitis.

Activation of nuclear factor kappa B in brains from children with HIV-1 encephalitis.

Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system is associated with decreased neuronal density in discrete areas of the brain. Neuronal loss may occur via apoptosis, initiated by soluble neurotoxic factors secreted from HIV-1 infected macrophages and microglia. To examine further the molecular events involved in HIV-1 neuropathogenesis, we assessed the activity of NF kappa B, an inducible transcription factor involved in the activation of multiple proinflammatory, and potentially neurotoxic, genes. NF kappa B was analysed by immunocytochemistry using specific antisera to the NF kappa B p. 50 and p. 65 subunits. Brains from children with HIV-1 encephalitis and progressive encephalopathy were found to contain increased numbers of NF kappa B immunoreactive cells, relative to control brains (HIV-1 negative, or HIV-1 positive without encephalitis). Double-labelling studies using antibodies to CD68, or RCA-1 lectin, markers for cells of monocyte/macrophage lineage, revealed an increase in the number of microglia and macrophages with nuclear immunoreactivity for NF kappa B in association with HIV-1 encephalitis. NF kappa B positive multinucleated giant cells were also detected, as were cells which contained both NF kappa B and HIV-1 antigen. In contrast, the number of neurons and GFAP-positive astrocytes that were immunoreactive for NF kappa B was approximately the same in all groups of subjects. These data are consistent with the hypothesis that persistent, high-level activation of NF kappa B may promote the sustained production of neurotoxins by microglia and macrophages during HIV-1 encephalitis.

Apoptotic neurons in brains from paediatric patients with HIV-1 encephalitis and progressive encephalopathy.

The pathogenesis of human immunodeficiency virus type 1 (HIV-1) associated dementia in adults involves neuronal loss from discrete areas of the neocortex and subcortical regions, but the mechanism for neuronal death is poorly understood. Gene-directed cell death resulting in apoptosis is thought to be a normal feature of neuronal development, but little is known about neuronal apoptosis in disease states. We investigated whether HIV-1 infection of the central nervous system is spatially associated with apoptosis of neurons. Using an in situ technique to identify newly cleaved 3'-OH ends of DNA as a marker for apoptosis, we demonstrate the presence of apoptotic neurons in cerebral cortex and basal ganglia of children that had HIV-1 encephalitis with progressive encephalopathy. Furthermore, an association was observed between the localization of apoptotic neurons and perivascular inflammatory cell infiltrates containing HIV-1 infected macrophages and multinucleated giant cells. Apoptotic neurons and p24-positive macrophages were observed infrequently in cerebral cortex and basal ganglia in children with HIV-1 infection without encephalitis or clinical encephalopathy. In nine control (HIV-1 negative) brains, ranging from the first post-natal month of life to 16.5 years of age, infrequent neuronal apoptosis was observed in three cases. These findings suggest that neuronal apoptosis is unlikely to be associated with post-natal development except in early post-natal germinal matrix, and that it may instead represent the end result of specific pathological processes, such as HIV-1 encephalitis.

Influence of burn injury on protein metabolism in different types of skeletal muscle and the role of glucocorticoids.

BACKGROUND: Negative nitrogen balance after burn injury mainly indicates muscle catabolism, but the exact influence of burn on protein synthesis and breakdown in different types of skeletal muscle and the role of glucocorticoids in this metabolic response are unknown. STUDY DESIGN: A 30 percent body surface area flame burn was inflicted on rats. Protein turnover rates were measured in vitro in the white fast-twitch extensor digitorum longus (EDL) muscle and the red slow-twitch soleus muscle. To test the role of glucocorticoids, groups of rats were treated with the glucocorticoid receptor antagonist RU 38486 or vehicle. RESULTS: Burns resulted in reduced protein synthesis and stimulated protein breakdown, in particular myofibrillar protein breakdown, and the changes were substantially more pronounced in the EDL than in the soleus muscle. A burn-induced increase in muscle proteolysis was abolished by treatment with RU 38486, whereas the reduced protein synthesis was not affected by the glucocorticoid receptor antagonist. CONCLUSIONS: The results suggest that the white fast-twitch muscle is more sensitive to the effects of burn injury than the red slow-twitch muscle. Burn-induced muscle proteolysis may be mediated, at least in part, by glucocorticoids, whereas protein synthesis is probably regulated by other mechanisms.