Predictive modelling of human walking over a complete gait cycle

An inverse dynamics multi-segment model of the body was combined with optimisation techniques to simulate normal walking in the sagittal plane on level ground. Walking is formulated as an optimal motor task subject to multiple constraints with minimisation of mechanical energy expenditure over a complete gait cycle being the performance criterion. All segmental motions and ground reactions were predicted from only three simple gait descriptors (inputs): walking velocity, cycle period and double stance duration. Quantitative comparisons of the model predictions with gait measurements show that the model reproduced the significant characteristics of normal gait in the sagittal plane. The simulation results suggest that minimising energy expenditure is a primary control objective in normal walking. However, there is also some evidence for the existence of multiple concurrent performance objectives. Keywords: Gait prediction; Inverse dynamics; Optimisation; Optimal motor tas

Rapid, Heuristic Discovery and Design of Promoter Collections in Non-Model Microbes for Industrial Applications

This is the author accepted manusript. The final version is available from American Chemical Society via the DOI in this recordAccession Codes: The sequence data for the four Geobacillus spp. used in this study have been submitted to the NCBI Sequence Read Archive and are available under the accession number PRJNA521450.Well-characterized promoter collections for synthetic biology applications are not always available in industrially relevant hosts. We developed a broadly applicable method for promoter identification in atypical microbial hosts that requires no a priori understanding of cis-regulatory element structure. This novel approach combines bioinformatic filtering with rapid empirical characterization to expand the promoter toolkit and uses machine learning to improve the understanding of the relationship between DNA sequence and function. Here, we apply the method in Geobacillus thermoglucosidasius, a thermophilic organism with high potential as a synthetic biology chassis for industrial applications. Bioinformatic screening of G. kaustophilus, G. stearothermophilus, G. thermodenitrificans, and G. thermoglucosidasius resulted in the identification of 636 100 bp putative promoters, encompassing the genome-wide design space and lacking known transcription factor binding sites. Eighty of these sequences were characterized in vivo, and activities covered a 2-log range of predictable expression levels. Seven sequences were shown to function consistently regardless of the downstream coding sequence. Partition modeling identified sequence positions upstream of the canonical -35 and -10 consensus motifs that were predicted to strongly influence regulatory activity in Geobacillus, and artificial neural network and partial least squares regression models were derived to assess if there were a simple, forward, quantitative method for in silico prediction of promoter function. However, the models were insufficiently general to predict pre hoc promoter activity in vivo, most probably as a result of the relatively small size of the training data set compared to the size of the modeled design space

Progressive ataxia with oculo-palatal tremor and optic atrophy

The final publication is available at Springer via doi: 10.​1007/​s00415-013-7136-

Does BCR/ABL1 positive Acute Myeloid Leukaemia Exist?

The BCR/ABL1 fusion gene, usually carried by the Philadelphia chromosome (Ph) resulting from t(9;22)(q34;q11) or variants, is pathognomonic for chronic myeloid leukaemia (CML). It is also occasionally found in acute lymphoblastic leukaemia (ALL) mostly in adults and rarely in de novo acute myeloid leukaemia (AML). Array Comparative Genomic Hybridization (aCGH) was used to study six Ph(+)AML, three bi-lineage and four Ph(+)ALL searching for specific genomic profiles. Surprisingly, loss of the IKZF1 and/or CDKN2A genes, the hallmark of Ph(+)ALL, were recurrent findings in Ph(+)AML and accompanied cryptic deletions within the immunoglobulin and T cell receptor genes. The latter two losses have been shown to be part of 'hot spot' genome imbalances associated with BCR/ABL1 positive pre-B lymphoid phenotype in CML and Ph(+)ALL. We applied Significance Analysis of Microarrays (SAM) to data from the 'hot spot' regions to the Ph(+)AML and a further 40 BCR/ABL1(+) samples looking for differentiating features. After exclusion of the most dominant markers, SAM identified aberrations unique to de novo Ph(+)AML that involved relevant genes. While the biological and clinical significance of this specific genome signature remains to be uncovered, the unique loss within the immunoglobulin genes provides a simple test to enable the differentiation of clinically similar de novo Ph(+) AML and myeloid blast crisis of CML. © 2013 John Wiley & Sons Ltd and Crown

A demonstration of 'broken' visual space

It has long been assumed that there is a distorted mapping between real and ‘perceived’ space, based on demonstrations of systematic errors in judgements of slant, curvature, direction and separation. Here, we have applied a direct test to the notion of a coherent visual space. In an immersive virtual environment, participants judged the relative distance of two squares displayed in separate intervals. On some trials, the virtual scene expanded by a factor of four between intervals although, in line with recent results, participants did not report any noticeable change in the scene. We found that there was no consistent depth ordering of objects that can explain the distance matches participants made in this environment (e.g. A > B > D yet also A < C < D) and hence no single one-to-one mapping between participants’ perceived space and any real 3D environment. Instead, factors that affect pairwise comparisons of distances dictate participants’ performance. These data contradict, more directly than previous experiments, the idea that the visual system builds and uses a coherent 3D internal representation of a scene

Obesity and immune function relationships.

The immunological processes involved in the collaborative defence of organisms are affected by nutritional status. Thus, a positive chronic imbalance between energy intake and expenditure leads to situations of obesity, which may influence unspecific and specific immune responses mediated by humoral and cell mediated mechanisms. Furthermore, several lines of evidence have supported a link between adipose tissue and immunocompetent cells. This interaction is illustrated in obesity, where excess adiposity and impaired immune function have been described in both humans and genetically obese rodents. However, limited and often controversial information exist comparing immunity in obese and non-obese subjects as well as about the cellular and molecular mechanisms implicated. In general terms, clinical and epidemiological data support the evidence that the incidence and severity of specific types of infectious illnesses are higher in obese persons as compared to lean individuals together with the occurrence of poor antibody responses to antigens in overweight subjects. Leptin might play a key role in linking nutritional status with T-cell function. The complexities and heterogeneity of the host defences concerning the immune response in different nutritional circumstances affecting the energy balance require an integral study of the immunocompetent cells, their subsets and products as well as specific and unspecific inducer/regulator systems. In this context, more research is needed to clarify the clinical implications of the alterations induced by obesity on the immune function

Wanted dead or alive : high diversity of macroinvertebrates associated with living and ’dead’ Posidonia oceanica matte

The Mediterranean endemic seagrass Posidonia oceanica forms beds characterised by a dense leaf canopy and a thick root-rhizome ‘matte’. Death of P. oceanica shoots leads to exposure of the underlying matte, which can persist for many years, and is termed ‘dead’ matte. Traditionally, dead matte has been regarded as a degraded habitat. To test whether this assumption was true, the motile macroinvertebrates of adjacent living (with shoots) and dead (without shoots) matte of P. oceanica were sampled in four different plots located at the same depth (5–6 m) in Mellieha Bay, Malta (central Mediterranean). The total number of species and abundance were significantly higher (ANOVA; P<0.05 and P<0.01, respectively) in the dead matte than in living P. oceanica matte, despite the presence of the foliar canopy in the latter. Multivariate analysis (MDS) clearly showed two main groups of assemblages, corresponding to the two matte types. The amphipods Leptocheirus guttatus and Maera grossimana, and the polychaete Nereis rava contributed most to the dissimilarity between the two different matte types. Several unique properties of the dead matte contributing to the unexpected higher number of species and abundance of motile macroinvertebrates associated with this habitat are discussed. The findings have important implications for the conservation of bare P. oceanica matte, which has been generally viewed as a habitat of low ecological value.peer-reviewe