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Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.
Among several potential animal models that can be used for adipogenic studies, Wagyu cattle is the one that presents unique molecular mechanisms underlying the deposit of substantial amounts of intramuscular fat. As such, this review is focused on current knowledge of such mechanisms related to adipose tissue deposition using Wagyu cattle as model. So abundant is the lipid accumulation in the skeletal muscles of these animals that in many cases, the muscle cross-sectional area appears more white (adipose tissue) than red (muscle fibers). This enhanced marbling accumulation is morphologically similar to that seen in numerous skeletal muscle dysfunctions, disease states and myopathies; this might indicate cross-similar mechanisms between such dysfunctions and fat deposition in Wagyu breed. Animal models can be used not only for a better understanding of fat deposition in livestock, but also as models to an increased comprehension on molecular mechanisms behind human conditions. This revision underlies some of the complex molecular processes of fat deposition in animals.
The thermal conductivity, bulk modulus, thermal expansion and heat capacity for
bulk β-Ga2O3 are calculated from lattice
dynamics using both a quasi-harmonic approximation and an anharmonic
force-constant approach involving a solution of the linearized Boltzmann
transport equation. The role of anharmonicity in
β-Ga2O3 is determined to be small, which
leads to the weak volume dependence of the calculated thermal conductivity. The
negligible anharmonic contribution to the overall thermal conductivity is
consistent with both thermal expansion measurements and also with comparisons
between the quasi-harmonic and anharmonic methods. Phonon-mode-dependent
Grüneisen parameters are found to be weakly dependent on temperature.
Negative values of the mode Grüneisen parameters are found for certain
low energy optical modes, but their net effect on the overall thermal expansion
is insignificant. Bulk modulus as well as heat capacity are also given and found
to be in agreement with experimental results.
Direct numerical simulations of flows in cylinders subjected to both rapid rotation and axial precession are presented and analysed in the context of a stability theory based on the triadic resonance of Kelvin modes. For a case that was chosen to provide a finely tuned resonant instability with a small nutation angle, the simulations are in good agreement with the theory and previous experiments in terms of mode shapes and dynamics, including long-time-scale regularization of the flow and recurrent collapses. Cases not tuned to the most unstable triad, but with the nutation angle still small, are also in quite good agreement with theoretical predictions, showing that the presence of viscosity makes the physics of the triadic-resonance model robust to detuning. Finally, for a case with
nutation angle for which it has been suggested that resonance does not occur, the simulations show that a slowly growing triadic resonance predicted by theory is in fact observed if sufficient evolution time is allowed.
A review is presented of Synchrotron X-ray Topography and KOH etching studies carried out on n type 4H-SiC offcut substrates before and after homo-epitaxial growth to study defect replication and strain relaxation processes and identify the nucleation sources of both interfacial dislocations (IDs) and half-loop arrays (HLAs) which are known to have a deleterious effect on device performance. We show that these types of defects can nucleate during epilayer growth from: (1) short segments of edge oriented basal plane dislocations (BPDs) in the substrate which are drawn by glide into the epilayer; and (2) segments of half loops of BPD that are attached to the substrate surface prior to growth which also glide into the epilayer. It is shown that the initial motion of the short edge oriented BPD segments that are drawn from the substrate into the epilayer is caused by thermal stress resulting from radial temperature gradients experienced by the wafer whilst in the epi-chamber. This same stress also causes the initial glide of the surface half-loop into the epilayer and through the advancing epilayer surface. These mobile BPD segments provide screw oriented segments that pierce the advancing epilayer surface that initially replicate as the crystal grows. Once critical thickness is reached, according to the Mathews-Blakeslee model , these screw segments glide sideways under the action of the mismatch stress leaving IDs and HLAs in their wake. The origin of the mismatch stress is shown to be associated with lattice parameter differences at the growth temperature, arising from the differences in doping concentration between substrate and epilayer.
Glyphosate is now the most widely used herbicide; after years of frequent utilization, resistant weeds were selected, mainly due to widespread adoption of glyphosate-resistant crops and no-tillage sowing system. Increasing difficulty in controlling Chloris polydactyla with glyphosate has been noticed in agricultural areas. Here, the susceptibility level of various C. polydactyla accessions from Brazil is examined. Two whole-plant studies were conducted to confirm the presence and extent of glyphosate susceptibility among accessions, which involved the application of seven glyphosate doses on four accessions. The four accessions showed different glyphosate susceptibilities. The “Matão” accession presented major tolerance for glyphosate compared to “Palotina” accessions. “Jaboticabal” plants showed an intermediary susceptibility. The resistance factor (RF) was 3.76 between the “Matão” and “Palotina” accessions. All biotypes died at 2,880 g ae ha−1 glyphosate.
We assessed for vancomycin-resistant Staphylococcus aureus (VRSA) precursor organisms in southeastern Michigan, an area known to have VRSA. The prevalence was 2.5% (pSK41-positive methicillin-resistant S. aureus, 2009–2011) and 1.5% (Inc18-positive vancomycin-resistant Enterococcus, 2006–2013); Inc18 prevalence significantly decreased after 2009 (3.7% to 0.82%). Risk factors for pSK41 included intravenous vancomycin exposure.
Infect Control Hosp Epidemiol 2014;35(12):1531–1534
Making confident statements about the evolution of an ice-sheet–shelf system with a numerical model requires the capability to reproduce the migration of the grounding line. Here we show that the shallow-ice approximation/shallow-shelf approximation hybrid-type Parallel Ice Sheet Model (PISM), with its recent improvements, is capable of modeling the grounding line motion in a perturbed ice-sheet–shelf system. The model is set up according to the three-dimensional Marine Ice-Sheet Model Intercomparison Project (MISMIP3d), and simulations are carried out across a broad range of spatial resolutions. Using (1) a linear interpolation of the grounding line with locally interpolated basal friction and (2) an improved driving-stress computation across the grounding line, the reversibility of the grounding line (i.e. its retreat after an advance forced by a local perturbation of basal resistance) is captured by the model even at medium and low resolutions (∆x > 10 km). The transient model response is qualitatively similar to that of higher-order models but reveals a higher initial sensitivity to perturbations on very short timescales. Our findings support the application of PISM to the Antarctic ice sheet from regional up to continental scales and on relatively low spatial resolutions.
Of the 13 US vancomycin-resistant Staphylococcus aureus (VRSA) cases, 8 were identified in southeastern Michigan, primarily in patients with chronic lower-extremity wounds. VRSA infections develop when the vanA gene from vancomycin-resistant enterococcus (VRE) transfers to S. aureus. Incl8-like plasmids in VRE and pSK41-like plasmids in S. aureus appear to be important precursors to this transfer.
Identify the prevalence of VRSA precursor organisms.
Prospective cohort with embedded case-control study.
Southeastern Michigan adults with chronic lower-extremity wounds.
Adults presenting to 3 southeastern Michigan medical centers during the period February 15 through March 4, 2011, with chronic lower-extremity wounds had wound, nares, and perirectal swab specimens cultured for S. aureus and VRE, which were tested for pSK41-like and Incl8-like plasmids by polymerase chain reaction. We interviewed participants and reviewed clinical records. Risk factors for pSK41-positive S. aureus were assessed among all study participants (cohort analysis) and among only S. aureus-colonized participants (case-control analysis).
Of 179 participants with wound cultures, 26% were colonized with methicillin-susceptible S. aureus, 27% were colonized with methicillin-resistant S. aureus, and 4% were colonized with VRE, although only 17% consented to perirectal culture. Six participants (3%) had pSK41-positive S. aureus, and none had Incl8-positive VRE. Having chronic wounds for over 2 years was associated with pSK41-positive S. aureus colonization in both analyses.
Colonization with VRSA precursor organisms was rare. Having long-standing chronic wounds was a risk factor for pSK41-positive S. aureus colonization. Additional investigation into the prevalence of VRSA precursors among a larger cohort of patients is warranted.
Nanoparticles composed of a magnetic iron oxide core surrounded by a metal shell have utility in a broad range of biomedical applications. However, the presence of surface energy differences between the two components makes wetting of oxide with metal unfavorable, precluding a “core–shell” structure of an oxide core completely surrounded by a thin metal shell. Three-dimensional island growth followed by island coalescence into thick shells is favored over the two-dimensional layer-by-layer growth of a thin, continuous metal coating of a true core–shell. Aqueous synthesis of gold-coated magnetite nanoparticles with analysis by infrared, energy-dispersive X-ray, and electron energy loss spectroscopies; high-resolution transmission electron microscopy; selected area electron diffraction; and high-angle annular dark-field scanning transmission electron microscopy showed two distinct morphologies that are inconsistent with an idealized core–shell. The majority were isolated ~16–22-nm-diameter nanoparticles consisting of ~7-nm-diameter magnetite and a thick deposition of gold, most often discontinuous, with some potentially “sandwiched” morphologies. A minority were aggregates of agglomerated magnetite decorated with gold but displaying significant bare magnetite. Both populations were successfully conjugated to fibrinogen and targeted to surface-activated platelets, demonstrating that iron oxide–gold nanoparticles produced by aqueous synthesis do not require an ideal core–shell structure for biological activity in cell labeling and targeting applications.
Predictions of marine ice-sheet behaviour require models able to simulate grounding-line migration. We present results of an intercomparison experiment for plan-view marine ice-sheet models. Verification is effected by comparison with approximate analytical solutions for flux across the grounding line using simplified geometrical configurations (no lateral variations, no buttressing effects from lateral drag). Perturbation experiments specifying spatial variation in basal sliding parameters permitted the evolution of curved grounding lines, generating buttressing effects. The experiments showed regions of compression and extensional flow across the grounding line, thereby invalidating the boundary layer theory. Steady-state grounding-line positions were found to be dependent on the level of physical model approximation. Resolving grounding lines requires inclusion of membrane stresses, a sufficiently small grid size (<500 m), or subgrid interpolation of the grounding line. The latter still requires nominal grid sizes of <5 km. For larger grid spacings, appropriate parameterizations for ice flux may be imposed at the grounding line, but the short-time transient behaviour is then incorrect and different from models that do not incorporate grounding-line parameterizations. The numerical error associated with predicting grounding-line motion can be reduced significantly below the errors associated with parameter ignorance and uncertainties in future scenarios.
The global mobile communication industry is growing rapidly. Today there are already more than 4 billion mobile phone subscribers worldwide , more than half the entire population of the planet. Obviously, this growth is accompanied by an increased energyconsumption of mobile networks. Global warming and heightened concerns for the environment of the planet require a special focus on the energy efficiency of these systems .
Many approaches to wireless energy-efficiency are limited to the power consumption of single nodes, e.g. a base station –. This scope is comparably easy to specify and to measure, but it fails to capture the network performance aspects (e.g. system throughput) implied by coverage and interference issues. Other methodologies are very broad, capturing the ICT industry in total . Recently an assessment framework for the power consumption of deployed wireless networks has been published, the mobile energyefficiency (MEE) network benchmarking service , based on metering all components of a network. However, for the energy efficiency it is not possible to directly compare, e.g. an Indian network with a Scandinavian network, therefore MEE has to introduce correction terms for the climate, for the number of base stations operated off-grid, and for the generations of equipment in the field.
However, the above approaches do not give insight into which parts of a network are most energy intensive or which provide the highest energy-saving potentials. There is a need for a simulation tool studying theoretically the effect of improvements in hardware, deployment strategies, and network management.
The main aim of the present study was to examine the effects of long-term supplementing diets with saturated or unprotected polyunsaturated fatty acids from two different plant oils rich in either n-3 or n-6 fatty acids (FAs) plus docosahexaenoic acid (DHA)-rich algae on mammary gene expression and milk fat composition in lactating dairy cows. Gene expression was determined from mammary tissue and milk epithelial cells. Eighteen primiparous German Holstein dairy cows in mid-lactation were randomly assigned into three dietary treatments that consist of silage-based diets supplemented with rumen-stable fractionated palm fat (SAT; 3.1% of the basal diet dry matter, DM), or a mixture of linseed oil (2.7% of the basal diet DM) plus DHA-rich algae (LINA; 0.4% of the basal diet DM) or a mixture of sunflower oil (2.7% of the basal diet DM) plus DHA-rich algae (SUNA; 0.4% of the basal diet DM), for a period of 10 weeks. At the end of the experimental period, the cows were slaughtered and mammary tissues were collected to study the gene expression of lipogenic enzymes. During the last week, the milk yield and composition were determined, and milk was collected for FA measurements and the isolation of milk purified mammary epithelial cells (MECs). Supplementation with plant oils and DHA-rich algae resulted in milk fat depression (MFD; yield and percentage). The secretion of de novo FAs in the milk was reduced, whereas the secretion of trans-10,cis-12-CLA and DHA were increased. These changes in FA secretions were associated in mammary tissue with a joint down-regulation of mammary lipogenic enzyme gene expression (stearoyl-CoA desaturase, SCD1; FA synthase, FASN) and expression of the regulatory element binding transcription factor (SREBF1), whereas no effect was observed on lipoprotein lipase (LPL) and glycerol-3-phosphate acyltransferase 1, mitochondrial (GPAM). A positive relationship between mammary SCD1 and SREBF1 mRNA abundances was observed, suggesting a similar regulation for these genes. Such data on mammary gene expression in lactating cows presenting MFD contribute to strengthen the molecular mechanisms that govern milk fat synthesis in the mammary glands. In purified MEC, the dietary treatments had no effect on gene expressions. Differences between mammary tissue and milk purified MEC gene expression were attributed to the effect of lipid supplements on the number of milk purified MEC and its RNA quality, which are determinant factors for the analysis of gene expression using milk cells.
National and international policies have encouraged the establishment of a representative network of marine protected areas (MPAs) in South Africa, with the aim of protecting marine biodiversity. The extent to which these marine and estuarine protected areas (EPAs) represent marine fish species and communities was assessed by comparing their species compositions with those of exploited areas, as sampled using four fishing techniques. Seven hundred fish species were sampled, representing one-third of South Africa's marine fishes. MPAs in coastal habitats scored c. 40% on the Bray-Curtis measure of similarity for species representativeness, but this score declined markedly for offshore ‘trawlable’ fishing grounds. The combined effects of sampling error, temporal variation and the effects of fishing on relative abundance suggest that 80% similarity would be the maximum achieveable. Forty-nine per cent of all fish species that were recorded were found in the 14 MPAs sampled. Redundancy in the MPA network was low, with fish species most commonly being represented in only one MPA or absent. There was greater redundancy in the 33 EPAs, with 40% of species being found in two or more EPAs, but many of these estuaries were adjacent to each other and embedded in large MPAs. Deep water fish communities (>80 m deep) and communities located on the west and south-east coasts of South Africa were most poorly represented by MPAs. Routine fishery surveys provide a robust and repeatable opportunity to assess species representativeness in MPAs, and the method used could form the basis of an operational definition of ‘representative’. In contrast to an assessment based on presence-absence data, this analysis of quantitative data presents a more pessimistic assessment of protection.
This paper describes a semi-automated conductive ink process used for packaging MEMS devices. The method is applied to packaging of MEMS sensors for wind tunnel testing. The primary advantage of the method is a reduction in surface topology between the package and the integrated MEMS sensors. In this paper we explore the relationship between trace dimensions, resistivity, and deposition parameters such as feed rate, tip-substrate separation and tip diameter. Using this procedure it is possible to generate interconnects between a PC board and MEMS sensor chip with a topology of less than 25 micrometers.