Neuro-electromagnetic imaging of the human visual cortex

Methods of solving the neuro-electromagnetic inverse problem are examined and developed, with specific reference to the human visual cortex. The anatomy, physiology and function of the human visual system are first reviewed. Mechanisms by which the visual cortex gives rise to external electric and magnetic fields are then discussed, and the forward problem is described mathematically for the case of an isotropic, piecewise homogeneous volume conductor, and then for an anisotropic, concentric, spherical volume conductor. Methods of solving the inverse problem are reviewed, before a new technique is presented. This technique combines prior anatomical information gained from stereotaxic studies, with a probabilistic distributed-source algorithm to yield accurate, realistic inverse solutions. The solution accuracy is enhanced by using both visual evoked electric and magnetic responses simultaneously. The numerical algorithm is then modified to perform equivalent current dipole fitting and minimum norm estimation, and these three techniques are implemented on a transputer array for fast computation. Due to the linear nature of the techniques, they can be executed on up to 22 transputers with close to linear speedup. The latter part of the thesis describes the application of the inverse methods to the analysis of visual evoked electric and magnetic responses. The CIIm peak of the pattern onset evoked magnetic response is deduced to be a product of current flowing away from the surface areas 17, 18 and 19, while the pattern reversal P100m response originates in the same areas, but from oppositely directed current. Cortical retinotopy is examined using sectorial stimuli, the CI and CIm ;peaks of the pattern onset electric and magnetic responses are found to originate from areas V1 and V2 simultaneously, and they therefore do not conform to a simple cruciform model of primary visual cortex

Effect of MLC tracking latency on conformal volumetric modulated arc therapy (VMAT) plans in 4D stereotactic lung treatment

AbstractBackground and purposeThe latency of a multileaf collimator (MLC) tracking system used to overcome respiratory motion causes misalignment of the treatment beam with respect to the gross tumour volume, which may result in reduced target coverage. This study investigates the magnitude of this effect.Material and methodsSimulated superior–inferior breathing motion was used to construct histograms of isocentre offset with respect to the gross tumour volume (GTV) for a variety of tracking latencies. Dose distributions for conformal volumetric modulated arc therapy (VMAT) arcs were then calculated at a range of offsets and summed according to these displacement histograms. The results were verified by delivering the plans to a Delta4 phantom on a motion platform.ResultsIn the absence of an internal target margin, a tracking latency of 150ms reduces the GTV D95% by approximately 2%. With a margin of 2mm, the same drop in dose occurs for a tracking latency of 450ms. Lung V13Gy is unaffected by a range of latencies. These results are supported by the phantom measurements.ConclusionsAssuming that internal motion can be modelled by a rigid translation of the patient, MLC tracking of conformal VMAT can be effectively accomplished in the absence of an internal target margin for substantial breathing motion (4s period and 20mm peak–peak amplitude) so long as the system latency is less than 150ms

Twistor Strings with Flavour

We explore the tree-level description of a class of N=2 UV-finite SYM theories with fundamental flavour within a topological B-model twistor string framework. In particular, we identify the twistor dual of the Sp(N) gauge theory with one antisymmetric and four fundamental hypermultiplets, as well as that of the SU(N) theory with 2N hypermultiplets. This is achieved by suitably orientifolding/orbifolding the original N=4 setup of Witten and adding a certain number of new topological 'flavour'-branes at the orientifold/orbifold fixed planes to provide the fundamental matter. We further comment on the appearance of these objects in the B-model on CP(3|4). An interesting aspect of our construction is that, unlike the IIB description of these theories in terms of D3 and D7-branes, on the twistor side part of the global flavour symmetry is realised geometrically. We provide evidence for this correspondence by calculating and matching amplitudes on both sides.Comment: 38+12 pages; uses axodraw.sty. v2: References added, minor clarification

The Natural History Museum Fossil Porifera Collection

This article provides updated information about the Porifera Collection at The Natural History Museum (NHM), London. With very little information available regarding fossil sponge digitization or any similar initiative, this paper covers the type and figured specimens and drawer label content data of the Porifera Collection and also describes the collection and its research potential. With approximately 71,000 specimens, of which more than 60% are Mesozoic, the NHM holdings offer the best Mesozoic sponge collection in the world and one of the most important due to its breadth and depth. The Porifera Collection covers all stratigraphic periods and all taxonomic groups and includes almost 3000 cited and figured specimens including types. Although most of the specimens come from the British Isles, worldwide samples are also present, with abundant specimens from other Commonwealth countries and from Antarctica.The attached document is the author(’s’) final accepted/submitted version of the journal article. You are advised to consult the publisher’s version if you wish to cite from it

Resolving the ancestry of Austronesian-speaking populations

There are two very different interpretations of the prehistory of Island Southeast Asia (ISEA), with genetic evidence invoked in support of both. The “out-of-Taiwan” model proposes a major Late Holocene expansion of Neolithic Austronesian speakers from Taiwan. An alternative, proposing that Late Glacial/postglacial sea-level rises triggered largely autochthonous dispersals, accounts for some otherwise enigmatic genetic patterns, but fails to explain the Austronesian language dispersal. Combining mitochondrial DNA (mtDNA), Y-chromosome and genome-wide data, we performed the most comprehensive analysis of the region to date, obtaining highly consistent results across all three systems and allowing us to reconcile the models. We infer a primarily common ancestry for Taiwan/ISEA populations established before the Neolithic, but also detected clear signals of two minor Late Holocene migrations, probably representing Neolithic input from both Mainland Southeast Asia and South China, via Taiwan. This latter may therefore have mediated the Austronesian language dispersal, implying small-scale migration and language shift rather than large-scale expansion

Discovery of biphenylacetamide-derived inhibitors of BACE1 using de novo structure-based molecular design

β-Secretase (BACE1), the enzyme responsible for the first and rate-limiting step in the production of amyloid-β peptides, is an attractive target for the treatment of Alzheimer’s disease. In this study, we report the application of the de novo fragment-based molecular design program SPROUT to the discovery of a series of nonpeptide BACE1 inhibitors based upon a biphenylacetamide scaffold. The binding affinity of molecules based upon this designed molecular scaffold was increased from an initial BACE1 IC50 of 323 μM to 27 μM following the synthesis of a library of optimized ligands whose structures were refined using the recently developed SPROUT-HitOpt software. Although a number of inhibitors were found to exhibit cellular toxicity, one compound in the series was found to have useful BACE1 inhibitory activity in a cellular assay with minimal cellular toxicity. This work demonstrates the power of an in silico fragment-based molecular design approach in the discovery of novel BACE1 inhibitors

Regret: A Theoretical and Conceptual Analysis

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73569/1/j.1468-5914.1987.tb00092.x.pd

Epididymis Response Partly Compensates for Spermatozoa Oxidative Defects in snGPx4 and GPx5 Double Mutant Mice

We report here that spermatozoa of mice lacking both the sperm nucleaus glutathione peroxidase 4 (snGPx4) and the epididymal glutathione peroxidase 5 (GPx5) activities display sperm nucleus structural abnormalities including delayed and defective nuclear compaction, nuclear instability and DNA damage. We show that to counteract the GPx activity losses, the epididymis of the double KO animals mounted an antioxydant response resulting in a strong increase in the global H2O2-scavenger activity especially in the cauda epididymis. Quantitative RT-PCR data show that together with the up-regulation of epididymal scavengers (of the thioredoxin/peroxiredoxin system as well as glutathione-S-transferases) the epididymis of double mutant animals increased the expression of several disulfide isomerases in an attempt to recover normal disulfide-bridging activity. Despite these compensatory mechanisms cauda-stored spermatozoa of double mutant animals show high levels of DNA oxidation, increased fragmentation and greater susceptibility to nuclear decondensation. Nevertheless, the enzymatic epididymal salvage response is sufficient to maintain full fertility of double KO males whatever their age, crossed with young WT female mice