Multi-compartment microscopic diffusion imaging

This paper introduces a multi-compartment model for microscopic diffusion anisotropy imaging. The aim is to estimate microscopic features specific to the intra- and extra-neurite compartments in nervous tissue unconfounded by the effects of fibre crossings and orientation dispersion, which are ubiquitous in the brain. The proposed MRI method is based on the Spherical Mean Technique (SMT), which factors out the neurite orientation distribution and thus provides direct estimates of the microscopic tissue structure. This technique can be immediately used in the clinic for the assessment of various neurological conditions, as it requires only a widely available off-the-shelf sequence with two b-shells and high-angular gradient resolution achievable within clinically feasible scan times. To demonstrate the developed method, we use high-quality diffusion data acquired with a bespoke scanner system from the Human Connectome Project. This study establishes the normative values of the new biomarkers for a large cohort of healthy young adults, which may then support clinical diagnostics in patients. Moreover, we show that the microscopic diffusion indices offer direct sensitivity to pathological tissue alterations, exemplified in a preclinical animal model of Tuberous Sclerosis Complex (TSC), a genetic multi-organ disorder which impacts brain microstructure and hence may lead to neurological manifestations such as autism, epilepsy and developmental delay

Rigidity and volume preserving deformation on degenerate simplices

Given a degenerate $(n+1)$-simplex in a $d$-dimensional space $M^d$ (Euclidean, spherical or hyperbolic space, and $d\geq n$), for each $k$, $1\leq k\leq n$, Radon's theorem induces a partition of the set of $k$-faces into two subsets. We prove that if the vertices of the simplex vary smoothly in $M^d$ for $d=n$, and the volumes of $k$-faces in one subset are constrained only to decrease while in the other subset only to increase, then any sufficiently small motion must preserve the volumes of all $k$-faces; and this property still holds in $M^d$ for $d\geq n+1$ if an invariant $c_{k-1}(\alpha^{k-1})$ of the degenerate simplex has the desired sign. This answers a question posed by the author, and the proof relies on an invariant $c_k(\omega)$ we discovered for any $k$-stress $\omega$ on a cell complex in $M^d$. We introduce a characteristic polynomial of the degenerate simplex by defining $f(x)=\sum_{i=0}^{n+1}(-1)^{i}c_i(\alpha^i)x^{n+1-i}$, and prove that the roots of $f(x)$ are real for the Euclidean case. Some evidence suggests the same conjecture for the hyperbolic case.Comment: 27 pages, 2 figures. To appear in Discrete & Computational Geometr

The SYZ conjecture via homological mirror symmetry

These are expository notes based on a talk given at the Superschool on derived categories and D-branes at University of Alberta in July of 2016. The goal of these notes is to give a motivated introduction to the Strominger-Yau-Zaslow (SYZ) conjecture from the point of view of homological mirror symmetry.Comment: Contribution to the proceedings of the Superschool on derived categories and D-brane

A comparison of course-related stressors in undergraduate problem-based learning (PBL) versus non-PBL medical programmes

Background: Medical students report high levels of stress related to their medical training as well as to other personal and financial factors. The aim of this study is to investigate whether there are differences in course-related stressors reported by medical students on undergraduate problem-based learning (PBL) and non-PBL programmes in the UK. Method: A cross-sectional study of second-year medical students in two UK medical schools (one PBL and one non-PBL programme) was conducted. A 16-question self-report questionnaire, derived from the Perceived Medical Student Stress Scale and the Higher Education Stress Inventory, was used to measure course-related stressors. Following univariate analysis of each stressor between groups, multivariate logistic regression was used to determine which stressors were the best predictors of each course type, while controlling for socio-demographic differences between the groups. Results: A total of 280 students responded. Compared to the non-PBL students (N = 197), the PBL students (N = 83) were significantly more likely to agree that: they did not know what the faculty expected of them (Odds Ratio (OR) = 0.38, p = 0.03); there were too many small group sessions facilitated only by students resulting in an unclear curriculum (OR = 0.04, p < 0.0001); and that there was a lack of opportunity to explore academic subjects of interest (OR = 0.40, p = 0.02). They were significantly more likely to disagree that: there was a lack of encouragement from teachers (OR = 3.11, p = 0.02); and that the medical course fostered a sense of anonymity and feelings of isolation amongst students (OR = 3.42, p = 0.008). Conclusion: There are significant differences in the perceived course-related stressors affecting medical students on PBL and non-PBL programmes. Course designers and student support services should therefore tailor their work to minimise, or help students cope with, the specific stressors on each course type to ensure optimum learning and wellbeing among our future doctors

Experimental studies of g-ratio MRI in ex vivo mouse brain

This study aimed to experimentally evaluate a previously proposed MRI method for mapping axonal g-ratio (ratio of axon diameters, measured to the inner and outer boundary of myelin). MRI and electron microscopy were used to study excised and fixed brains of control mice and three mouse models of abnormal white matter. The results showed that g-ratio measured with MRI correlated with histological measures of myelinated axon g-ratio, but with a bias that is likely due to the presence of non-myelinated axons. The results also pointed to cases where the MRI g-ratio model simplifies to be primarily a function of total myelin content

Impact of foot-and-mouth disease on mastitis and culling on a large-scale dairy farm in Kenya

Foot and mouth disease (FMD) is a highly transmissible viral infection of cloven hooved animals associated with severe economic losses when introduced into FMD-free countries. Information on the impact of the disease in FMDV-endemic countries is poorly characterised yet essential for the prioritisation of scarce resources for disease control programmes. A FMD (virus serotype SAT2) outbreak on a large-scale dairy farm in Nakuru County, Kenya provided an opportunity to evaluate the impact of FMD on clinical mastitis and culling rate. A cohort approach followed animals over a 12-month period after the commencement of the outbreak. For culling, all animals were included; for mastitis, those over 18 months of age. FMD was recorded in 400/644 cattle over a 29-day period. During the follow-up period 76 animals were culled or died whilst in the over 18 month old cohort 63 developed clinical mastitis. Hazard ratios (HR) were generated using Cox regression accounting for non-proportional hazards by inclusion of time-varying effects. Univariable analysis showed FMD cases were culled sooner but there was no effect on clinical mastitis. After adjusting for possible confounders and inclusion of time-varying effects there was weak evidence to support an effect of FMD on culling (HR = 1.7, 95% confidence intervals [CI] 0.88-3.1, P = 0.12). For mastitis, there was stronger evidence of an increased rate in the first month after the onset of the outbreak (HR = 2.9, 95%CI 0.97-8.9, P = 0.057)

Serratamolide is a hemolytic factor produced by Serratia marcescens

Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use. © 2012 Shanks et al

A Compensatory Mutation Provides Resistance to Disparate HIV Fusion Inhibitor Peptides and Enhances Membrane Fusion

Fusion inhibitors are a class of antiretroviral drugs used to prevent entry of HIV into host cells. Many of the fusion inhibitors being developed, including the drug enfuvirtide, are peptides designed to competitively inhibit the viral fusion protein gp41. With the emergence of drug resistance, there is an increased need for effective and unique alternatives within this class of antivirals. One such alternative is a class of cyclic, cationic, antimicrobial peptides known as θ-defensins, which are produced by many non-human primates and exhibit broad-spectrum antiviral and antibacterial activity. Currently, the θ-defensin analog RC-101 is being developed as a microbicide due to its specific antiviral activity, lack of toxicity to cells and tissues, and safety in animals. Understanding potential RC-101 resistance, and how resistance to other fusion inhibitors affects RC-101 susceptibility, is critical for future development. In previous studies, we identified a mutant, R5-tropic virus that had evolved partial resistance to RC-101 during in vitro selection. Here, we report that a secondary mutation in gp41 was found to restore replicative fitness, membrane fusion, and the rate of viral entry, which were compromised by an initial mutation providing partial RC-101 resistance. Interestingly, we show that RC-101 is effective against two enfuvirtide-resistant mutants, demonstrating the clinical importance of RC-101 as a unique fusion inhibitor. These findings both expand our understanding of HIV drug-resistance to diverse peptide fusion inhibitors and emphasize the significance of compensatory gp41 mutations. © 2013 Wood et al

Aerobic capacity, activity levels and daily energy expenditure in male and female adolescents of the kenyan nandi sub-group

The relative importance of genetic and socio-cultural influences contributing to the success of east Africans in endurance athletics remains unknown in part because the pre-training phenotype of this population remains incompletely assessed. Here cardiopulmonary fitness, physical activity levels, distance travelled to school and daily energy expenditure in 15 habitually active male (13.9±1.6 years) and 15 habitually active female (13.9±1.2) adolescents from a rural Nandi primary school are assessed. Aerobic capacity ([Formula: see text]) was evaluated during two maximal discontinuous incremental exercise tests; physical activity using accelerometry combined with a global positioning system; and energy expenditure using the doubly labelled water method. The [Formula: see text] of the male and female adolescents were 73.9±5.7 ml(.) kg(-1.) min(-1) and 61.5±6.3 ml(.) kg(-1.) min(-1), respectively. Total time spent in sedentary, light, moderate and vigorous physical activities per day was 406±63 min (50% of total monitored time), 244±56 min (30%), 75±18 min (9%) and 82±30 min (10%). Average total daily distance travelled to and from school was 7.5±3.0 km (0.8-13.4 km). Mean daily energy expenditure, activity-induced energy expenditure and physical activity level was 12.2±3.4 MJ(.) day(-1), 5.4±3.0 MJ(.) day(-1) and 2.2±0.6. 70.6% of the variation in [Formula: see text] was explained by sex (partial R(2) = 54.7%) and body mass index (partial R(2) = 15.9%). Energy expenditure and physical activity variables did not predict variation in [Formula: see text] once sex had been accounted for. The highly active and energy-demanding lifestyle of rural Kenyan adolescents may account for their exceptional aerobic fitness and collectively prime them for later training and athletic success

The unwarped, resolved, deformed conifold: fivebranes and the baryonic branch of the Klebanov-Strassler theory

We study a gravity solution corresponding to fivebranes wrapped on the $S^2$ of the resolved conifold. By changing a parameter the solution continuously interpolates between the deformed conifold with flux and the resolved conifold with branes. Therefore, it displays a geometric transition, purely in the supergravity context. The solution is a simple example of torsional geometry and may be thought of as a non-K\"ahler analog of the conifold. By U-duality transformations we can add D3 brane charge and recover the solution in the form originally derived by Butti et al. This describes the baryonic branch of the Klebanov-Strassler theory. Far along the baryonic branch the field theory gives rise to a fuzzy two-sphere. This corresponds to the D5 branes wrapping the two-sphere of the resolved conifold in the gravity solution.Comment: 41 pages, 7 figure