Formation of Methane Hydrate in the Presence of Natural and Synthetic Nanoparticles

Natural gas hydrates occur widely on the ocean-bed and in permafrost regions, and have potential as an untapped energy resource. Their formation and growth, however, poses major problems for the energy sector due to their tendency to block oil and gas pipelines, whereas their melting is viewed as a potential contributor to climate change. Although recent advances have been made in understanding bulk methane hydrate formation, the effect of impurity particles, which are always present under conditions relevant to industry and the environment, remains an open question. Here we present results from neutron scattering experiments and molecular dynamics simulations that show that the formation of methane hydrate is insensitive to the addition of a wide range of impurity particles. Our analysis shows that this is due to the different chemical natures of methane and water, with methane generally excluded from the volume surrounding the nanoparticles. This has important consequences for our understanding of the mechanism of hydrate nucleation and the design of new inhibitor molecules

Fixed-Parameter Tractable Distances to Sparse Graph Classes

We show that for various classes $\mathcal{C}$ of sparse graphs, and several measures of distance to such classes (such as edit distance and elimination distance), the problem of determining the distance of a given graph $\small{G}$ to $\mathcal{C}$ is fixed-parameter tractable. The results are based on two general techniques. The first of these, building on recent work of Grohe et al. establishes that any class of graphs that is slicewise nowhere dense and slicewise first-order definable is FPT. The second shows that determining the elimination distance of a graph $\small{G}$ to a minor-closed class $\mathcal{C}$ is FPT. We demonstrate that several prior results (of Golovach, Moser and Thilikos and Mathieson) on the fixed-parameter tractability of distance measures are special cases of our first method

Does a SLAP lesion affect shoulder muscle recruitment as measured by EMG activity during a rugby tackle?

Background: The study objective was to assess the influence of a SLAP lesion on onset of EMG activity in shoulder muscles during a front on rugby football tackle within professional rugby players. Methods: Mixed cross-sectional study evaluating between and within group differences in EMG onset times. Testing was carried out within the physiotherapy department of a university sports medicine clinic. The test group consisted of 7 players with clinically diagnosed SLAP lesions, later verified on arthroscopy. The reference group consisted of 15 uninjured and full time professional rugby players from within the same playing squad. Controlled tackles were performed against a tackle dummy. Onset of EMG activity was assessed from surface EMG of Pectorialis Major, Biceps Brachii, Latissimus Dorsi, Serratus Anterior and Infraspinatus muscles relative to time of impact. Analysis of differences in activation timing between muscles and limbs (injured versus non-injured side and non injured side versus matched reference group). Results: Serratus Anterior was activated prior to all other muscles in all (P = 0.001-0.03) subjects. In the SLAP injured shoulder Biceps was activated later than in the non-injured side. Onset times of all muscles of the noninjured shoulder in the injured player were consistently earlier compared with the reference group. Whereas, within the injured shoulder, all muscle activation timings were later than in the reference group. Conclusions: This study shows that in shoulders with a SLAP lesion there is a trend towards delay in activation time of Biceps and other muscles with the exception of an associated earlier onset of activation of Serratus anterior, possibly due to a coping strategy to protect glenohumeral stability and thoraco-scapular stability. This trend was not statistically significant in all cases

The use of standardized patients for mock oral board exams in neurology: a pilot study

BACKGROUND: Mock oral board exams, fashioned after the live patient hour of the American Board of Psychiatry and Neurology exam, are commonly part of resident assessment during residency training. Exams using real patients selected from clinics or hospitals are not standardized and do not allow comparisons of resident performance across the residency program. We sought to create a standardized patient mock oral board exam that would allow comparison of residents' clinical performance. METHODS: Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process. RESULTS: Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general. CONCLUSION: Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency

An epigenome-wide association study of Alzheimer's disease blood highlights robust DNA hypermethylation in the HOXB6 gene

This is the final version. Available from the publisher via the DOI in this record.A growing number of epigenome-wide association studies have demonstrated a role for DNA methylation in the brain in Alzheimer's disease. With the aim of exploring peripheral biomarker potential, we have examined DNA methylation patterns in whole blood collected from 284 individuals in the AddNeuroMed study, which included 89 nondemented controls, 86 patients with Alzheimer's disease, and 109 individuals with mild cognitive impairment, including 38 individuals who progressed to Alzheimer's disease within 1 year. We identified significant differentially methylated regions, including 12 adjacent hypermethylated probes in the HOXB6 gene in Alzheimer's disease, which we validated using pyrosequencing. Using weighted gene correlation network analysis, we identified comethylated modules of genes that were associated with key variables such as APOE genotype and diagnosis. In summary, this study represents the first large-scale epigenome-wide association study of Alzheimer's disease and mild cognitive impairment using blood. We highlight the differences in various loci and pathways in early disease, suggesting that these patterns relate to cognitive decline at an early stage.Alzheimer's Society, United KingdomMedical Research Council (MRC)NIH, United States, R01 grantAlzheimer's Research U

Apraxia and motor dysfunction in corticobasal syndrome

Background: Corticobasal syndrome (CBS) is characterized by multifaceted motor system dysfunction and cognitive disturbance; distinctive clinical features include limb apraxia and visuospatial dysfunction. Transcranial magnetic stimulation (TMS) has been used to study motor system dysfunction in CBS, but the relationship of TMS parameters to clinical features has not been studied. The present study explored several hypotheses; firstly, that limb apraxia may be partly due to visuospatial impairment in CBS. Secondly, that motor system dysfunction can be demonstrated in CBS, using threshold-tracking TMS, and is linked to limb apraxia. Finally, that atrophy of the primary motor cortex, studied using voxel-based morphometry analysis (VBM), is associated with motor system dysfunction and limb apraxia in CBS.   Methods: Imitation of meaningful and meaningless hand gestures was graded to assess limb apraxia, while cognitive performance was assessed using the Addenbrooke's Cognitive Examination - Revised (ACE-R), with particular emphasis placed on the visuospatial subtask. Patients underwent TMS, to assess cortical function, and VBM.   Results: In total, 17 patients with CBS (7 male, 10 female; mean age 64.4+/2 6.6 years) were studied and compared to 17 matched control subjects. Of the CBS patients, 23.5% had a relatively inexcitable motor cortex, with evidence of cortical dysfunction in the remaining 76.5% patients. Reduced resting motor threshold, and visuospatial performance, correlated with limb apraxia. Patients with a resting motor threshold <50% performed significantly worse on the visuospatial sub-task of the ACE-R than other CBS patients. Cortical function correlated with atrophy of the primary and pre-motor cortices, and the thalamus, while apraxia correlated with atrophy of the pre-motor and parietal cortices.   Conclusions: Cortical dysfunction appears to underlie the core clinical features of CBS, and is associated with atrophy of the primary motor and pre-motor cortices, as well as the thalamus, while apraxia correlates with pre-motor and parietal atrophy

Improved mapping strategy to better inform policy on the control of schistosomiasis and soil-transmitted helminthiasis in Sierra Leone

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis and soil-transmitted helminthiasis (STH) are endemic in Sierra Leone confirmed by national mapping in 2008. To better inform planning of preventive chemotherapy strategy, another survey was conducted before mass drug administration (MDA) in seven districts according to the mapping results or local knowledge. Fifty-nine chiefdoms and one school in every chiefdom were selected. Thirty school children aged 9-14 years from each school (total: 1760) were examined by parasitological methods for infection with <it>Schistosoma mansoni </it>and STHs.</p> <p>Results</p> <p>The overall prevalence of <it>S. mansoni </it>was 40.2% (95% confidence interval (CI): 37.9-42.5%), particularly in Kailahun (63.3%), Kenema (46.7%), Koinadugu (41.9%) and Kono (71.7%). The results demonstrated the focal distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts with prevalence ranging from 0.0-63.3%, 3.3-90.0% and 0.0-67.9% respectively. The arithmetic mean intensity of <it>S. mansoni </it>infection was 95.4 epg (95% CI: 61.4-129.5 epg), Heavy mean intensity of infection was found in Kailahun (120.2 epg), Kenema (104.5 epg), Koinadugu (112.3 epg) and Kono (250.3 epg). Heavy or moderate infection with <it>S. mansoni </it>occurred in 20.7% of children examined. Hookworm prevalence was moderate: 31.2% (95% CI: 29.1-33.4%), but high in Bo (50.0%) and Tonkolili (56.7%). Hookworm intensity of infection was light with a mean epg of 53.0 (95% CI: 38.4-67.7 epg). Prevalence and intensity of <it>Ascaris lumbricoides </it>(1.5%, 17.8 epg) and <it>Trichuris trichiura </it>(2.5%, 20.3 epg) was low.</p> <p>Conclusions</p> <p>The prediction by previous spatial analysis that <it>S. mansoni </it>was highly endemic across north-eastern Sierra Leone was confirmed with a significant proportion of children heavily or moderately infected. The distribution of <it>S. mansoni </it>in Bo, Tonkolili and Bombali districts ranged widely, highlighting the importance of considering the nature of focal transmission in national mapping exercises. These results were used to refine the MDA for schistosomiasis control to chiefdom implementation units rather than the entire district in these 3 districts. The survey demonstrated that sufficient number of survey sites for schistosomiasis mapping in each district should be used to provide a better national planning of MDA activities, and that it is affordable with the contributions from all parties involved and national resources mobilized.</p

On malfunctioning software

Artefacts do not always do what they are supposed to, due to a variety of reasons, including manufacturing problems, poor maintenance, and normal wear-and-tear. Since software is an artefact, it should be subject to malfunctioning in the same sense in which other artefacts can malfunction. Yet, whether software is on a par with other artefacts when it comes to malfunctioning crucially depends on the abstraction used in the analysis. We distinguish between “negative” and “positive” notions of malfunction. A negative malfunction, or dysfunction, occurs when an artefact token either does not (sometimes) or cannot (ever) do what it is supposed to. A positive malfunction, or misfunction, occurs when an artefact token may do what is supposed to but, at least occasionally, it also yields some unintended and undesirable effects. We argue that software, understood as type, may misfunction in some limited sense, but cannot dysfunction. Accordingly, one should distinguish software from other technical artefacts, in view of their design that makes dysfunction impossible for the former, while possible for the latter

Snake Cytotoxins Bind to Membranes via Interactions with Phosphatidylserine Head Groups of Lipids

The major representatives of Elapidae snake venom, cytotoxins (CTs), share similar three-fingered fold and exert diverse range of biological activities against various cell types. CT-induced cell death starts from the membrane recognition process, whose molecular details remain unclear. It is known, however, that the presence of anionic lipids in cell membranes is one of the important factors determining CT-membrane binding. In this work, we therefore investigated specific interactions between one of the most abundant of such lipids, phosphatidylserine (PS), and CT 4 of Naja kaouthia using a combined, experimental and modeling, approach. It was shown that incorporation of PS into zwitterionic liposomes greatly increased the membrane-damaging activity of CT 4 measured by the release of the liposome-entrapped calcein fluorescent dye. The CT-induced leakage rate depends on the PS concentration with a maximum at approximately 20% PS. Interestingly, the effects observed for PS were much more pronounced than those measured for another anionic lipid, sulfatide. To delineate the potential PS binding sites on CT 4 and estimate their relative affinities, a series of computer simulations was performed for the systems containing the head group of PS and different spatial models of CT 4 in aqueous solution and in an implicit membrane. This was done using an original hybrid computational protocol implementing docking, Monte Carlo and molecular dynamics simulations. As a result, at least three putative PS-binding sites with different affinities to PS molecule were delineated. Being located in different parts of the CT molecule, these anion-binding sites can potentially facilitate and modulate the multi-step process of the toxin insertion into lipid bilayers. This feature together with the diverse binding affinities of the sites to a wide variety of anionic targets on the membrane surface appears to be functionally meaningful and may adjust CT action against different types of cells