Development and characterization of positively selected brain-adapted SIV

HIV is found in the brains of most infected individuals but only 30% develop neurological disease. Both viral and host factors are thought to contribute to the motor and cognitive disorders resulting from HIV infection. Here, using the SIV/rhesus monkey system, we characterize the salient characteristics of the virus from the brain of animals with neuropathological disorders. Nine unique molecular clones of SIV were derived from virus released by microglia cultured from the brains of two macaques with SIV encephalitis. Sequence analysis revealed a remarkably high level of similarity between their env and nef genes as well as their 3' LTR. As this genotype was found in the brains of two separate animals, and it encoded a set of distinct amino acid changes from the infecting virus, it demonstrates the convergent evolution of the virus to a unique brain-adapted genotype. This genotype was distinct from other macrophage-tropic and neurovirulent strains of SIV. Functional characterization of virus derived from representative clones showed a robust in vitro infection of 174xCEM cells, primary macrophages and primary microglia. The infectious phenotype of this virus is distinct from that shown by other strains of SIV, potentially reflecting the method by which the virus successfully infiltrates and infects the CNS. Positive in vivo selection of a brain-adapted strain of SIV resulted in a near-homogeneous strain of virus with distinct properties that may give clues to the viral basis of neuroAIDS

A Networks-Science Investigation into the Epic Poems of Ossian

In 1760 James Macpherson published the first volume of a series of epic poems which he claimed to have translated into English from ancient Scottish-Gaelic sources. The poems, which purported to have been composed by a third-century bard named Ossian, quickly achieved wide international acclaim. They invited comparisons with major works of the epic tradition, including Homer's Iliad and Odyssey, and effected a profound influence on the emergent Romantic period in literature and the arts. However, the work also provoked one of the most famous literary controversies of all time, colouring the reception of the poetry to this day. The authenticity of the poems was questioned by some scholars, while others protested that they misappropriated material from Irish mythological sources. Recent years have seen a growing critical interest in Ossian, initiated by revisionist and counter-revisionist scholarship and by the two-hundred-and-fiftieth anniversary of the first collected edition of the poems in 1765. Here we investigate Ossian from a networks-science point of view. We compare the connectivity structures underlying the societies described in the Ossianic narratives with those of ancient Greek and Irish sources. Despite attempts, from the outset, to position Ossian alongside the Homeric epics and to distance it from Irish sources, our results indicate significant network-structural differences between Macpherson's text and those of Homer. They also show a strong similarity between Ossianic networks and those of the narratives known as Acallam na Sen\'orach (Colloquy of the Ancients) from the Fenian Cycle of Irish mythology.Comment: Accepted for publication in Advances in Complex system

A convenient band-gap interpolation technique and an improved band line-up model for InGaAlAs on InP

The band-gap energy and the band line-up of InGaAlAs quaternary compound material on InP are essential information for the theoretical study of physical properties and the design of optoelectronics devices operating in the long-wavelength communication window. The band-gap interpolation of In1-x-y Ga (x) Al (y) As on InP is known to be a challenging task due to the observed discrepancy of experimental results arising from the bowing effect. Besides, the band line-up results of In1-x-y Ga (x) Al (y) As on InP based on previously reported models have limited success by far. In this work, we propose an interpolation solution using the single-variable surface bowing estimation interpolation method for the fitting of experimentally measured In1-x-y Ga (x) Al (y) As band-gap data with various degree of bowing using the same set of input parameters. The suggested solution provides an easier and more physically interpretable way to determine not only lattice matched, but also strained band-gap energy of In1-x-y Ga (x) Al (y) As on InP based on the experimental results. Interpolated results from this convenient method show a more favourable match to multiple independent experiment data sets measured under different temperature conditions as compared to those obtained from the commonly used weighted-sum approach. On top of that, extended framework of the model-solid theory for the band line-up of In1-x-y Ga (x) Al (y) As/InP heterostructure is proposed. Our model-solid theory band line-up result using the proposed extended framework has shown an improved accuracy over those without the extension. In contrast to some previously reported works, it is worth noting that the band line-up result based on our proposed extended model-solid theory has also shown to be more accurate than those given by Harrison's mode

Energy Reallocation to Breeding Performance through Improved Nest Building in Laboratory Mice.

Mice are housed at temperatures (20-26°C) that increase their basal metabolic rates and impose high energy demands to maintain core temperatures. Therefore, energy must be reallocated from other biological processes to increase heat production to offset heat loss. Supplying laboratory mice with nesting material may provide sufficient insulation to reduce heat loss and improve both feed conversion and breeding performance. Naïve C57BL/6, BALB/c, and CD-1breeding pairs were provided with bedding alone, or bedding supplemented with either 8g of Enviro-Dri, 8g of Nestlets, for 6 months. Mice provided with either nesting material built more dome-like nests than controls. Nesting material improved feed efficiency per pup weaned as well as pup weaning weight. The breeding index (pups weaned/dam/week) was higher when either nesting material was provided. Thus, the sparing of energy for thermoregulation of mice given additional nesting material may have been responsible for the improved breeding and growth of offspring

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Technique for the Dry Transfer of Epitaxial Graphene onto Arbitrary Substrates

In order to make graphene technologically viable, the transfer of graphene films to substrates appropriate for specific applications is required. We demonstrate the dry transfer of epitaxial graphene (EG) from the C-face of 4H-SiC onto SiO2, GaN and Al2O3 substrates using a thermal release tape. We further report on the impact of this process on the electrical properties of the EG films. This process enables EG films to be used in flexible electronic devices or as optically transparent contacts.Comment: 8 pages, 4 figures and supplementary info regarding procedure for transfe

A statistical investigation of normal regional intra-subject heterogeneity of brain metabolism and perfusion by F-18 FDG and O-15 H(2)O PET imaging

BACKGROUND: The definite evaluation of the regional cerebral heterogeneity using perfusion and metabolism by a single modality of PET imaging has not been well addressed. Thus a statistical analysis of voxel variables from identical brain regions on metabolic and perfusion PET images was carried out to determine characteristics of the regional heterogeneity of F-18 FDG and O-15 H(2)O cerebral uptake in normal subjects. METHODS: Fourteen normal subjects with normal CT and/or MRI and physical examination including MMSE were scanned by both F-18 FDG and O-15 H(2)O PET within same day with head-holder and facemask. The images were co-registered and each individual voxel counts (Q) were normalized by the gloabl maximal voxel counts (M) as R = Q/M. The voxel counts were also converted to z-score map by z = (Q - mean)/SD. Twelve pairs of ROIs (24 total) were systematically placed on the z-score map at cortical locations 15-degree apart and identically for metabolism and perfusion. Inter- and intra-subject correlation coefficients (r) were computed, both globally and hemispherically, from metabolism and perfusion: between regions for the same tracer and between tracers for the same region. Moments of means and histograms were computed globally along with asymmetric indices as their hemispherical differences. RESULTS: Statistical investigations verified with data showed that, for a given scan, correlation analyses are expectedly alike regardless of variables (Q, R, z) used. The varieties of correlation (r's) of normal subjects, showing symmetry, were mostly around 0.8 and with coefficient of variations near 10%. Analyses of histograms showed non-Gaussian behavior (skew = -0.3 and kurtosis = 0.4) of metabolism on average, in contrast to near Gaussian perfusion. CONCLUSION: The co-registered cerebral metabolism and perfusion z maps demonstrated regional heterogeneity but with attractively low coefficient of variations in the correlation markers

International Veterinary Epilepsy Task Force Consensus Proposal: Outcome of therapeutic interventions in canine and feline epilepsy

Common criteria for the diagnosis of drug resistance and the assessment of outcome are needed urgently as a prerequisite for standardized evaluation and reporting of individual therapeutic responses in canine epilepsy. Thus, we provide a proposal for the definition of drug resistance and partial therapeutic success in canine patients with epilepsy. This consensus statement also suggests a list of factors and aspects of outcome, which should be considered in addition to the impact on seizures. Moreover, these expert recommendations discuss criteria which determine the validity and informative value of a therapeutic trial in an individual patient and also suggest the application of individual outcome criteria. Agreement on common guidelines does not only render a basis for future optimization of individual patient management, but is also a presupposition for the design and implementation of clinical studies with highly standardized inclusion and exclusion criteria. Respective standardization will improve the comparability of findings from different studies and renders an improved basis for multicenter studies. Therefore, this proposal provides an in-depth discussion of the implications of outcome criteria for clinical studies. In particular ethical aspects and the different options for study design and application of individual patient-centered outcome criteria are considered

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible