Composition and strain relaxation of In x Ga1-x N graded core-shell nanorods.

Two In x Ga1-x N nanorod samples with graded In compositions of x = 0.5-0 (Ga-rich) and x = 0.5-1 (In-rich) grown by molecular beam epitaxy were studied using transmission electron microscopy. The nanorods had a wurtzite crystal structure with growth along [Formula: see text] and core-shell structures with an In-rich core and Ga-rich shell. Energy-dispersive x-ray analysis confirmed grading over the entire compositional range and showed that the axial growth rate was primarily determined by the In flux, and the radial growth rate by the Ga flux. There was no evidence of misfit dislocations due to grading, but the strain due to the lattice mismatch between the In-rich core and Ga-rich shell was relaxed by edge dislocations at the core-shell interface with Burgers vectors [Formula: see text] and [Formula: see text].

Shrinking microbubbles with microfluidics: mathematical modelling to control microbubble sizes.

Microbubbles have applications in industry and life-sciences. In medicine, small encapsulated bubbles (<10 µm) are desirable because of their utility in drug/oxygen delivery, sonoporation, and ultrasound diagnostics. While there are various techniques for generating microbubbles, microfluidic methods are distinguished due to their precise control and ease-of-fabrication. Nevertheless, sub-10 µm diameter bubble generation using microfluidics remains challenging, and typically requires expensive equipment and cumbersome setups. Recently, our group reported a microfluidic platform that shrinks microbubbles to sub-10 µm diameters. The microfluidic platform utilizes a simple microbubble-generating flow-focusing geometry, integrated with a vacuum shrinkage system, to achieve microbubble sizes that are desirable in medicine, and pave the way to eventual clinical uptake of microfluidically generated microbubbles. A theoretical framework is now needed to relate the size of the microbubbles produced and the system's input parameters. In this manuscript, we characterize microbubbles made with various lipid concentrations flowing in solutions that have different interfacial tensions, and monitor the changes in bubble size along the microfluidic channel under various vacuum pressures. We use the physics governing the shrinkage mechanism to develop a mathematical model that predicts the resulting bubble sizes and elucidates the dominant parameters controlling bubble sizes. The model shows a good agreement with the experimental data, predicting the resulting microbubble sizes under different experimental input conditions. We anticipate that the model will find utility in enabling users of the microfluidic platform to engineer bubbles of specific sizes.

Distinguishing cubic and hexagonal phases within InGaN/GaN microstructures using electron energy loss spectroscopy.

3D InGaN/GaN microstructures grown by metal organic vapor phase epitaxy (MOVPE) and molecular beam epitaxy (MBE) have been extensively studied using a range of electron microscopy techniques. The growth of material by MBE has led to the growth of cubic GaN material. The changes in these crystal phases has been investigated by Electron Energy Loss Spectroscopy, where the variations in the fine structure of the N K-edge shows a clear difference allowing the mapping of the phases to take place. GaN layers grown for light emitting devices sometimes have cubic inclusions in the normally hexagonal wurtzite structures, which can influence the device electronic properties. Differences in the fine structure of the N K-edge between cubic and hexagonal material in electron energy loss spectra are used to map cubic and hexagonal regions in a GaN/InGaN microcolumnar device. The method of mapping is explained, and the factors limiting spatial resolution are discussed.

Turn costs change the value of animal search paths.

The tortuosity of the track taken by an animal searching for food profoundly affects search efficiency, which should be optimised to maximise net energy gain. Models examining this generally describe movement as a series of straight steps interspaced by turns, and implicitly assume no turn costs. We used both empirical- and modelling-based approaches to show that the energetic costs for turns in both terrestrial and aerial locomotion are substantial, which calls into question the value of conventional movement models such as correlated random walk or Lévy walk for assessing optimum path types. We show how, because straight-line travel is energetically most efficient, search strategies should favour constrained turn angles, with uninformed foragers continuing in straight lines unless the potential benefits of turning offset the cost.

Kinetics of surfactant desorption at an air-solution interface.

The kinetics of re-equilibration of the anionic surfactant sodium dodecylbenzene sulfonate at the air-solution interface have been studied using neutron reflectivity. The experimental arrangement incorporates a novel flow cell in which the subphase can be exchanged (diluted) using a laminar flow while the surface region remains unaltered. The rate of the re-equilibration is relatively slow and occurs over many tens of minutes, which is comparable with the dilution time scale of approximately 10-30 min. A detailed mathematical model, in which the rate of the desorption is determined by transport through a near-surface diffusion layer into a diluted bulk solution below, is developed and provides a good description of the time-dependent adsorption data. A key parameter of the model is the ratio of the depth of the diffusion layer, H(c), to the depth of the fluid, H(f), and we find that this is related to the reduced Péclet number, Pe*, for the system, via H(c)/H(f) = C/Pe*(1/2). Although from a highly idealized experimental arrangement, the results provide an important insight into the "rinse mechanism", which is applicable to a wide variety of domestic and industrial circumstances.

A comparison of the legal frameworks supporting water management in Europe and China.

This paper has compared the legal frameworks supporting water management in Europe and China, with special focus on integrated river basin management (IRBM) to identify synergies and opportunities in policymaking and implementation. The research shows that China has committed to the efficient management of water resources through various policy tools during the current period. This commitment, however, has often been interrupted and distorted by politics, resulting in the neglect of socioeconomic and environmental priorities. The European legal framework supporting water management underwent a complex and lengthy development, but with the adoption of the Water Framework Directive provides a policy model on which to develop an integrated and sustainable approach to river basin management, elements of which may help to meet the demands of the emerging 21st century Chinese society on these critical natural resources.

Survival of, and competition between, oligodendrocytes expressing different alleles of the Plp gene.

Mutations in the X-linked Plp gene lead to dysmyelinating phenotypes and oligodendrocyte cell death. Here, we exploit the X inactivation phenomenon to show that a hierarchy exists in the influence of different mutant Plp alleles on oligodendrocyte survival. We used compound heterozygote mice to study the long-term fate of oligodendrocytes expressing either the jimpy or rumpshaker allele against a background of cells expressing a Plp-null allele. Although mutant and null oligodendrocytes were generated in equal numbers, the proportion expressing the mutant allele subsequently declined, but whereas those expressing the rumpshaker allele formed a reduced but stable population, the number of jimpy cells fell progressively. The age of decline in the jimpy cells in different regions of the CNS correlated with the temporal sequence of myelination. In compound heterozygotes expressing rumpshaker and jimpy alleles, oligodendrocytes expressing the former predominated and were more abundant than when the rumpshaker and null alleles were in competition. Thus, oligodendrocyte survival is not determined solely by cell intrinsic factors, such as the conformation of the misfolded PLP, but is influenced by neighboring cells, possibly competing for cell survival factors.

Axonal swellings and degeneration in mice lacking the major proteolipid of myelin.

Glial cells produce myelin and contribute to axonal morphology in the nervous system. Two myelin membrane proteolipids, PLP and DM20, were shown to be essential for the integrity of myelinated axons. In the absence of PLP-DM20, mice assembled compact myelin sheaths but subsequently developed widespread axonal swellings and degeneration, associated predominantly with small-caliber nerve fibers. Similar swellings were absent in dysmyelinated shiverer mice, which lack myelin basic protein (MBP), but recurred in MBP*PLP double mutants. Thus, fiber degeneration, which was probably secondary to impaired axonal transport, could indicate that myelinated axons require local oligodendroglial support.

Curvature- and fluid-stress-driven tissue growth in a tissue-engineering scaffold pore.

Cell proliferation within a fluid-filled porous tissue-engineering scaffold depends on a sensitive choice of pore geometry and flow rates: regions of high curvature encourage cell proliferation, while a critical flow rate is required to promote growth for certain cell types. When the flow rate is too slow, the nutrient supply is limited; when it is too fast, cells may be damaged by the high fluid shear stress. As a result, determining appropriate tissue-engineering-construct geometries and operating regimes poses a significant challenge that cannot be addressed by experimentation alone. In this paper, we present a mathematical theory for the fluid flow within a pore of a tissue-engineering scaffold, which is coupled to the growth of cells on the pore walls. We exploit the slenderness of a pore that is typical in such a scenario, to derive a reduced model that enables a comprehensive analysis of the system to be performed. We derive analytical solutions in a particular case of a nearly piecewise constant growth law and compare these with numerical solutions of the reduced model. Qualitative comparisons of tissue morphologies predicted by our model, with those observed experimentally, are also made. We demonstrate how the simplified system may be used to make predictions on the design of a tissue-engineering scaffold and the appropriate operating regime that ensures a desired level of tissue growth.

Premature arrest of myelin formation in transgenic mice with increased proteolipid protein gene dosage.

Proteolipid protein (PLP) is an integral membrane protein of CNS myelin. Mutations of the X chromosome-linked PLP gene cause glial cell death and myelin deficiency in jimpy mice and other neurological mutants. As part of an attempt to rescue these mutants by transgenic complementation, we generated normal mouse lines expressing autosomal copies of the entire wild-type PLP gene. Surprisingly, increase of the PLP gene dosage in nonmutant mice with only 2-fold transcriptional overexpression results in a novel phenotype characterized by severe hypomyelination and astrocytosis, seizures, and premature death. This demonstrates that precise control of the PLP gene is a critical determinant of terminal oligodendrocyte differentiation. Dysmyelination of PLP transgenic mice provides experimental evidence that Pelizaeus-Merzbacher disease, previously associated with a partial duplication of the human X chromosome, can be caused by doubling of the PLP gene dosage.

Assembly of CNS myelin in the absence of proteolipid protein.

Two proteolipid proteins, PLP and DM20, are the major membrane components of central nervous system (CNS) myelin. Mutations of the X-linked PLP/DM20 gene cause dysmyelination in mouse and man and result in significant mortality. Here we show that mutant mice that lack expression of a targeted PLP gene fail to exhibit the known dysmyelinated phenotype. Unable to encode PLP/DM20 or PLP-related polypeptides, oligodendrocytes are still competent to myelinate CNS axons of all calibers and to assemble compacted myelin sheaths. Ultrastructurally, however, the electron-dense 'intraperiod' lines in myelin remain condensed, correlating with its reduced physical stability. This suggests that after myelin compaction, PLP forms a stabilizing membrane junction, similar to a "zipper." Dysmyelination and oligodendrocyte death emerge as an epiphenomenon of other PLP mutations and have been uncoupled in the PLP null allele from the risk of premature myelin breakdown.

Peripheral demyelination and neuropathic pain behavior in periaxin-deficient mice.

The Prx gene in Schwann cells encodes L- and S-periaxin, two abundant PDZ domain proteins thought to have a role in the stabilization of myelin in the peripheral nervous system (PNS). Mice lacking a functional Prx gene assemble compact PNS myelin. However, the sheath is unstable, leading to demyelination and reflex behaviors that are associated with the painful conditions caused by peripheral nerve damage. Older Prx-/- animals display extensive peripheral demyelination and a severe clinical phenotype with mechanical allodynia and thermal hyperalgesia, which can be reversed by intrathecal administration of a selective NMDA receptor antagonist We conclude that the periaxins play an essential role in stabilizing the Schwann cell-axon unit and that the periaxin-deficient mouse will be an important model for studying neuropathic pain in late onset demyelinating disease.

A transgenic rat model of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy in humans and has been associated with a partial duplication of chromosome 17 (CMT type 1A). We have generated a transgenic rat model of this disease and provide experimental evidence that CMT1A is caused by increased expression of the gene for peripheral myelin protein-22 (PMP22, gas-3). PMP22-transgenic rats develop gait abnormalities caused by a peripheral hypomyelination, Schwann cell hypertrophy (onion bulb formation), and muscle weakness. Reduced nerve conduction velocities closely resemble recordings in human patients with CMT1A. When bred to homozygosity, transgenic animals completely fail to elaborate myelin. We anticipate that the CMT rat model will facilitate the identification of a cellular disease mechanism and serve in the evaluation of potential treatment strategies.

Myelinated, synapsing cultures of murine spinal cord--validation as an in vitro model of the central nervous system.

Research in central nervous system (CNS) biology and pathology requires in vitro models, which, to recapitulate the CNS in vivo, must have extensive myelin and synapse formation under serum-free (defined) conditions. However, finding such a model has proven difficult. The technique described here produces dense cultures of myelinated axons, with abundant synapses and nodes of Ranvier, that are suitable for both morphological and biochemical analysis. Cellular and molecular events were easily visualised using conventional microscopy. Ultrastructurally, myelin sheaths were of the appropriate thickness relative to axonal diameter (G-ratio). Production of myelinated axons in these cultures was consistent and repeatable, as shown by statistical analysis of multiple experimental repeats. Myelinated axons were so abundant that from one litter of embryonic mice, myelin was produced in amounts sufficient for bulk biochemical analysis. This culture method was assessed for its ability to generate an in vitro model of the CNS that could be used for both neurobiological and neuropathological research. Myelin protein kinetics were investigated using a myelin fraction isolated from the cultures. This fraction was found to be superior, quantitatively and qualitatively, to the fraction recovered from standard cultures of dissociated oligodendrocytes, or from brain slices. The model was also used to investigate the roles of specific molecules in the pathogenesis of inflammatory CNS diseases. Using the defined conditions offered by this culture system, dose-specific, inhibitory effects of inflammatory cytokines on myelin formation were demonstrated, unequivocally. The method is technically quick, easy and reliable, and should have wide application to CNS research.

Comparison of a standard and a detailed postmortem protocol for detecting Mycobacterium bovis in badgers.

A standard postmortem protocol, consisting of gross pathology, culture for mycobacteria and limited selective histopathology, was used in the randomised badger culling trial in Great Britain to detect Mycobacterium bovis infection. This standard protocol was compared with a more detailed protocol in which more tissues were examined grossly, more tissues were cultured, more culture slopes were seeded, the culture period was extended and tissues were examined routinely by histopathology. The standard protocol was more sensitive in badgers with gross visible lesions than in badgers with no gross visible lesions. When applied to the study population of badgers, the overall sensitivity of the standard protocol relative to the more detailed protocol was estimated to be 54.6 per cent (95 per cent confidence interval 44.9 to 69.8 per cent). Badgers with tuberculosis (tb) detected by the standard protocol had a mean of 7.6 tissues with microscopic lesions suspicious of tb. The additional badgers detected by the detailed protocol had a mean of 4.4 tissues with microscopic lesions suspicious of tb.

Precipitation within localised chromium-enriched regions in a Type 316H austenitic stainless steel.

A Type 316H austenitic stainless steel component containing Cr and impurity element-rich localised regions arising from component fabrication was aged for a prolonged period during service at a temperature of approximately 550 °C. These regions make up approximately 5% of the total volume of the microstructure. Previous work has shown that these regions contain ferrite and carbide precipitates and a finer austenite grain size than the adjacent matrix. The present study has used high-resolution transmission electron microscopy combined with compositional microanalysis to show that these regions have a highly complex microstructure containing G phase, chi phase and intragranular γ' precipitates within the austenite grains. There is phosphorus migration to the chi austenite phase boundary, and the basis for this equilibrium impurity segregation is discussed. A Cr-depleted region was observed surrounding the chi phase precipitates, and the impact of this on the other precipitates is considered. The diversity of precipitates in these Cr-rich regions means that they behave significantly differently to the bulk material under long-term creep conditions leading to preferred nucleation and growth of creep cavities and the formation of localised creep cracks during service.

Stochastic modelling of membrane filtration.

Membrane fouling during particle filtration occurs through a variety of mechanisms, including internal pore clogging by contaminants, coverage of pore entrances and deposition on the membrane surface. In this paper, we present an efficient method for modelling the behaviour of a filter, which accounts for different retention mechanisms, particle sizes and membrane geometries. The membrane is assumed to be composed of a series of, possibly interconnected, pores. The central feature is a conductivity function, which describes the blockage of each individual pore as particles arrive, which is coupled with a mechanism to account for the stochastic nature of the arrival times of particles at the pore. The result is a system of ordinary differential equations based on the pore-level interactions. We demonstrate how our model can accurately describe a wide range of filtration scenarios. Specifically, we consider a case where blocking via multiple mechanisms can occur simultaneously, which have previously required the study through individual models; the filtration of a combination of small and large particles by a track-etched membrane and particle separation using interconnected pore networks. The model is significantly faster than comparable stochastic simulations for small networks, enabling its use as a tool for efficient future simulations.

Investigating the relationship between energy expenditure, walking speed and angle of turning in humans.

Recent studies have suggested that changing direction is associated with significant additional energy expenditure. A failure to account for this additional energy expenditure of turning has significant implications in the design and interpretation of health interventions. The purpose of this study was therefore to investigate the influence of walking speed and angle, and their interaction, on energy expenditure in 20 healthy adults (7 female; 28±7 yrs). On two separate days, participants completed a turning protocol at one of 16 speed- (2.5, 3.5, 4.5, 5.5 km∙h-1) and angle (0, 45, 90, 180°) combinations, involving three minute bouts of walking, interspersed by three minutes seated rest. Each condition involved 5 m of straight walking before turning through the pre-determined angle with the speed dictated by a digital, auditory metronome. Tri-axial accelerometry and magnetometry were measured at 60 Hz, in addition to gas exchange on a breath-by-breath basis. Mixed models revealed a significant main effect for speed (F = 121.609, P < 0.001) and angle (F = 19.186, P < 0.001) on oxygen uptake ([Formula: see text]) and a significant interaction between these parameters (F = 4.433, P < 0.001). Specifically, as speed increased, [Formula: see text] increased but significant increases in [Formula: see text] relative to straight line walking were only observed for 90° and 180° turns at the two highest speeds (4.5 and 5.5 km∙hr-1). These findings therefore highlight the importance of accounting for the quantity and magnitude of turns completed when estimating energy expenditure and have significant implications within both sport and health contexts.

Observation of antisite domain boundaries in Cu2ZnSnS4 by atomic-resolution transmission electron microscopy.

Atomic resolution transmission electron microscopy has been used to examine antisite defects in Cu2ZnSnS4 (CZTS) kesterite crystals grown by a hot injection method. High angle annular dark field (HAADF) imaging at sub-0.1 nm resolution, and lower magnification dark field imaging using reflections sensitive to cation ordering, are used to reveal antisite domain boundaries (ADBs). These boundaries, typically 5-20 nm apart, and extending distances of 100 nm or more into the crystals, lie on a variety of planes and have displacements of the type ½[110] or »[201], which translate Sn, Cu and Zn cations into antisite positions. It is shown that some ADBs describe a change in the local stoichiometry by removing planes of S and either Cu or Zn atoms, implying that these boundaries can be electrically charged. The observations also showed a marked increase in cation disorder in regions within 1-2 nm of the grain surfaces suggesting that growth of the ordered crystal takes place at the interface with a disordered shell. It is estimated that the ADBs contribute on average ∼0.1 antisite defect pairs per unit cell. Although this is up to an order of magnitude less than the highest antisite defect densities reported, the presence of high densities of ADBs that may be charged suggests these defects may have a significant influence on the efficiency of CZTS solar cells.

Dissecting the self-assembly kinetics of multimeric pore-forming toxins.

Pore-forming toxins are ubiquitous cytotoxins that are exploited by both bacteria and the immune response of eukaryotes. These toxins kill cells by assembling large multimeric pores on the cell membrane. However, a quantitative understanding of the mechanism and kinetics of this self-assembly process is lacking. We propose an analytically solvable kinetic model for stepwise, reversible oligomerization. In biologically relevant limits, we obtain simple algebraic expressions for the rate of pore formation, as well as for the concentration of pores as a function of time. Quantitative agreement is obtained between our model and time-resolved kinetic experiments of Bacillus thuringiensis Cry1Ac (tetrameric pore), aerolysin, Staphylococcus aureus α-haemolysin (heptameric pores) and Escherichia coli cytolysin A (dodecameric pore). Furthermore, our model explains how rapid self-assembly can take place with low concentrations of oligomeric intermediates, as observed in recent single-molecule fluorescence experiments of α-haemolysin self-assembly. We propose that suppressing the concentration of oligomeric intermediates may be the key to reliable, error-free, self-assembly of pores.