Granule Cell Dispersion in Human Temporal Lobe Epilepsy: Proteomics investigation of neurodevelopmental migratory pathways

Granule cell dispersion (GCD) is a common pathological feature observed in the hippocampus of patients with Mesial Temporal Lobe Epilepsy (MTLE). Pathomechanisms underlying GCD remain to be elucidated, but one hypothesis proposes aberrant reactivation of neurodevelopmental migratory pathways, possibly triggered by febrile seizures. This study aims to compare the proteomes of basal and dispersed granule cells in the hippocampus of eight MTLE patients with GCD to identify proteins that may mediate GCD in MTLE. Quantitative proteomics identified 1882 proteins, of which 29% were found in basal granule cells only, 17% in dispersed only and 54% in both samples. Bioinformatics analyses revealed upregulated proteins in dispersed samples were involved in developmental cellular migratory processes, including cytoskeletal remodelling, axon guidance and signalling by Ras homologous (Rho) family of GTPases (P<0.01). The expression of two Rho GTPases, RhoA and Rac1, was subsequently explored in immunohistochemical and in situ hybridisation studies involving eighteen MTLE cases with or without GCD, and three normal post mortem cases. In cases with GCD, most dispersed granule cells in the outer-granular and molecular layers have an elongated soma and bipolar processes, with intense RhoA immunolabelling at opposite poles of the cell soma, while most granule cells in the basal granule cell layer were devoid of RhoA. A higher density and percentage of cells expressing RhoA was observed in cases with GCD than without GCD (P<0.004). In GCD cases, the density and percentage of cells expressing RhoA was significantly higher in the inner molecular layer than granule cell layer (P<0.026), supporting proteomic findings. In situ hybridisation studies using probes against RHOA and RAC1 mRNAs revealed fine peri- and nuclear puncta in granule cells of all cases. The density of cells expressing RHOA mRNAs were significantly higher in the inner molecular layer of cases with GCD than without GCD(P=0.05). In summary, our study has found limited evidence for ongoing adult neurogenesis in the hippocampus of patients with MTLE, but evidence of differential dysmaturation between dispersed and basal granule cells has been demonstrated, and elevated expression of Rho GTPases in dispersed granule cells may contribute to the pathomechanisms underpinning GCD in MTLE

Fracture and fatigue strength of grouted macadams

Grouted macadams form a class of material which provides significant advantages in comparison to both concrete and conventional asphalt, having both rut resistance and a degree of flexibility. This paper presents a series of laboratory tests on several grouted macadam mixtures, for stiffness, fatigue and low temperature fracture. The variables explored include binder grade and content, aggregate size and gradation, and grout strength. Although the material is found to perform fundamentally as an asphalt, there are several significant differences in the form of fatigue behavior found compared to that usually expected from an asphalt. In particular the effect of varying binder content is found to be markedly different. The results are discussed in terms of optimizing mixture design in order to obtain the most desirable combination of properties (stiffness, fatigue strength, low temperature fracture resistance). Discussion is also presented regarding the possible role of grouted macadams as base or binder courses within highway pavements, and the conclusion is drawn that they are likely to provide an economical solution in many circumstances owing to their superior mechanical properties

Open-source development experiences in scientific software: the HANDE quantum Monte Carlo project

The HANDE quantum Monte Carlo project offers accessible stochastic algorithms for general use for scientists in the field of quantum chemistry. HANDE is an ambitious and general high-performance code developed by a geographically-dispersed team with a variety of backgrounds in computational science. In the course of preparing a public, open-source release, we have taken this opportunity to step back and look at what we have done and what we hope to do in the future. We pay particular attention to development processes, the approach taken to train students joining the project, and how a flat hierarchical structure aids communicationComment: 6 pages. Submission to WSSSPE

The effect of using rest periods in 4PB tests on the fatigue life of grouted macadams

Four-point bending tests are commonly used to assess the fatigue resistance of bi-tuminous bound materials that are used in road pavements. However, it is difficult to establish a reliable relationship between the laboratory test results and the field performance of the mate-rial. In order to predict the real life of the pavement, shift factors are normally used to convert the fatigue results obtained in the laboratory onto the actual fatigue life of the material in the field. Those shift factors depend on the type of test used, the testing conditions and the type of mixture used. In this study, an attempt was made to establish a shift factor for grouted mac-adams, based on four-point bending fatigue test results carried out with rest periods between the loading cycles. The result obtained was used to define a fatigue criterion for pavement design with grouted macadams