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Nikolaus Friedreich (1877) was aware of heart disease in his patients but thought it was unrelated to the neurological disorder. In 1946, Dorothy Russell considered cardiomyopathy an integral part of Friedreich ataxia (FA). In addition to sparse inflammatory infiltration, sections show fibrosis and capillary hyperplasia. We examined the left ventricular walls of 41 homozygous FA patients aged 10–87 and 21 controls aged 2–69. An antibody to CD34 enabled quantitative capillary profile counts for a comparison with cardiomyocyte counts in the same field. Mean capillary counts in normals were 1926±341/mm2, and the median ratio of capillaries to cardiomyocytes was 1.0 (interquartile range [IQR]: 0.9-1.2). In FA, however, the number of cardiomyocytes/mm2 was less, and the median ratio of capillaries to heart fibers was 2.0 (IQR 1.4-2.4). There was a significant correlation of the higher guanine-adenine-adenine trinucleotide length (shorter allele, GAA1) with the younger age of onset, shorter disease duration, and lower cardiomyocyte counts. The ratio of capillaries to heart fibers was higher in patients with long GAA1 repeat expansions (e.g., 3.31 in GAA1 of 1200). Double-label immunofluorescence for CD34 and S100A4 revealed co-expression in endothelial cells, supporting endothelial-to-mesenchymal transition in the pathogenesis of cardiac fibrosis (supported by Friedreich’s Ataxia Research Alliance).
The presentation will enable the learner to:
1.Describe endothelial-to-mesenchymal transition in the pathogenesis of cardiac fibrosis in Friedreich cardiomyopathy
In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of
was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.
TiO2 nanomaterials with platelet or nanosheet morphologies can offer improved properties for photocatalytic applications, but established methods to produce them typically require structure-directing agents since anatase-phase TiO2 does not have a layered structure. In the present work, the preparation of TiO2 nanosheets by the chemical oxidation of TiS2 nanosheets is demonstrated. Electrochemical exfoliation of bulk TiS2 into TiS2 nanosheets, followed by the hydrothermal treatment at 180 °C for 14 h is performed. The results show that polycrystalline TiO2 nanosheets with the anatase structure are formed, and that the nanosheet morphology can still be maintained after the hydrothermal treatment. The TiO2 nanosheets show good photocatalytic activity for the degradation of methylene blue, but the performance is negatively affected by the residual carbon black that was needed in the TiS2 electrode to enable electrochemical exfoliation. These results show that conversion of TiS2 nanosheets to TiO2 nanosheets is a promising synthetic strategy but highlights how the interfacial properties of the obtained materials could be affected by ancillary components in the preparation method.
Spatiotemporal analysis is an important tool to monitor changes of tuberculosis (TB) epidemiology, identify high-risk regions and guide resource allocation. However, there are limited data on the contributing factors of TB incidence. This study aimed to investigate the spatiotemporal pattern of TB incidence and its associated factors in mainland China during 2005–2013. Global Moran's I test, Getis-Ord Gi index and heat maps were used to examine the spatial clustering and seasonal patterns. Generalized Linear Mixed Model was applied to identify factors associated with TB incidence. TB incidence presented high geographical variations with two main hot spots, while a generally consistent seasonal pattern was observed with a peak in late winter. Furthermore, we found province-level TB incidence increased with the proportion of the elderly but decreased with Gross Demographic Product per capita and the male:female ratio. Meteorological factors also influenced TB incidence. TB showed obvious spatial clustering in mainland China and both the demographic and socio-economic factors and meteorological measures were associated with TB incidence. These results provide the related information to identify the high-risk districts and the evidence for the government to develop corresponding control measures.
We investigated the first presence of qnrA among Shigella sonnei clinical isolates in Jiangsu Province, China. The qnrA-positive isolates coexisted with the mutation in gyrA at codon 83, these isolates were resistant to nalidixic acid and 22·2% (2 of 9) of them were resistant to norfloxacin.
The E2F transcription factor family is distributed widely in eukaryotes and has been well studied among mammals. In the present study, the E2F transcription factor 4 (E2F4) gene was isolated from fat bodies of Antheraea pernyi and sequenced. E2F4 comprised a 795 bp open reading frame encoding a deduced amino acid sequence of 264 amino acid residues. The recombinant protein was expressed in Escherichia coli (Transetta DE3), and anti-E2F4 antibodies were prepared. The deduced amino acid sequence displayed significant homology to an E2F4-like protein from Bombyx mori L. Quantitative real-time polymerase chain reaction analysis revealed that E2F4 expression was highest in the integument, followed by the fat body, silk glands, and haemocytes. The expression of E2F4 was upregulated in larvae challenged by bacterial (Escherichia coli, Micrococcus luteus), viral (nuclear polyhedrosis virus), and fungal (Beauveria bassiana) pathogens. These observations indicated that E2F4 is an inducible protein in the immune response of A. pernyi and probably in other insects.
A series of catalytic reactions has been performed in our laboratory using olivine-type silicates (OTS) and SiC as catalysts for the conversion of carbon-containing molecules (such as acetylene, CO and methanol) to small organic molecules (C2H4, C3H3, CH3O) and also polycyclic aromatic hydrocarbons (PAHs). Experimentally, small-to-medium-sized gas-phase compounds such as PAHs, reaction intermediates and hydrocarbon compounds were detected in situ using the time-of-light mass-spectrometry technique. Solid deposition on the catalyst surface was examined by high-resolution transmission electron microscopy and thermo-gravimetric analysis techniques. Our laboratory results show that the conversion of acetylene to PAHs, the CO disproportionation reaction for producing CO2 and carbon deposition (graphitic and carbon nanostructures), and also the transformation of methanol to hydrocarbon compounds can easily be achieved with OTS as a catalyst. Furthermore, the conversion of acetylene to PAHs could also be achieved by SiC as the catalyst. It is proposed that these catalytic reactions mimic similar chemical processes in circumstellar envelopes (CSEs).
For this study, threonine (Thr) deficiency was hypothesised to exacerbate the intestinal damage induced by feed withdrawal with coccidial infection because of its high obligatory requirement by the gut; two dietary Thr treatments (0·49 and 0·90 %) were applied to chicks from 0 to 21 d of age. At 13 d of age, feed was withdrawn for 24 h from one-half of birds of each dietary treatment with subsequent gavage of a 25× dose of coccidial vaccine. Overall, there were four treatments with eight replicate cages per treatment. Under combined challenge, birds fed the Thr-deficient diet had 38 % lower 13–21-d body weight gain (P≤0·05) compared with birds fed the Thr-control diet. At 21 d, the challenged group fed low Thr had higher number of oocysts (+40 %, P=0·03) and lower crypt depth (−31 %, P<0·01). In addition, birds fed the low-Thr diet had higher gut permeability as measured after 2 h of administration of fluorescein isothiocyanate-dextran (3–5 kDa, P<0·01), which may be attributed to decreased IgA production (P=0·03) in the ileum. In caecal tonsils, the challenged group fed low Thr had lower CD3:Bu-1 ratio (P≤0·05), along with a tendency for lower CCR9 mRNA expression in birds fed the low-Thr diet (P=0·10). In addition, Thr deficiency tended to increase IL-10 mRNA expression regardless of infection (P=0·06), but did not change interferon-γ mRNA expression upon coccidial infection (P>0·05). Overall, Thr deficiency worsened the detrimental effects of combined feed withdrawal and coccidial infection on growth performance and oocyst shedding by impairing intestinal morphology, barrier function, lymphocyte profiles and their cytokine expressions.
Lipases are ubiquitous enzymes in nature, which play a crucial role in fat metabolism by catalyzing the hydrolysis of triacylglycerol to free fatty acids and glycerol. However, reports concerning insect lipase are rare. In this study, we studied the expression and activity of a lipase-related protein from Antheraea pernyi (ApLRP). Recombinant ApLRP was expressed in Escherichia coli cells and used to raise rabbit anti-ApLRP polyclonal antibodies. ApLRP mRNA and protein expression were abundant in the midgut and malpighian tubules, respectively. After challenge with four different microorganisms (E. coli, Beauveria bassiana, Micrococcus luteus and nuclear polyhedrosis virus), the expression levels of ApLRP mRNA in midgut were inducted significantly compared with the control. The different pathogens induced different ApLRP gene expression patterns. The optimum temperature and pH for the enzyme's activity were 35°C and 7.0, respectively. ApLRP activity was stimulated in the presence of Mg2+, Na+, Ca2+ and b-mercaptoethanol; while Zn2+, Cu2+ and Fe3+ inhibited its activity. Detergents such as SDS, glycerol and Tween-20 increased the lipase activity by 20–30%. Our results indicated that ApLRP might play an important role in the innate immunity of insects.
Maize in Canada is grown mainly in the south-eastern part of the country. No comprehensive studies on Canadian maize yield levels have been done so far to analyse the barriers of obtaining optimal yields associated with cultivar, environmental stress and agronomic management practices. The objective of the current study was to use a modelling approach to analyse the gaps between actual and potential (determined by cultivar, solar radiation and temperature without any other stresses) maize yields in Eastern Canada. The CSM–CERES–Maize model in DSSAT v4·6 was calibrated and evaluated with measured data of seven cultivars under different nitrogen (N) rates across four sites. The model was then used to simulate grain yield levels defined as: yield potential (YP), water-limited (YW, rainfed), and water- and N-limited yields with N rates 80 kg/ha (YW, N-80N) and 160 kg/ha (YW, N-160N). The options were assessed to further increase grain yield by analysing the yield gaps related to water and N deficiencies. The CSM–CERES–Maize model simulated the grain yields in the experiments well with normalized root-mean-squared errors <0·20. The model was able to capture yield variations associated with varying N rates, cultivar, soil type and inter-annual climate variability. The seven calibrated cultivars used in the experiments were divided into three grades according to their simulated YP: low, medium and high. The simulation results for the 30-year period from 1981 to 2010 showed that the average YP was 15 000 kg/ha for cultivars with high yield potential. The YP is generally about 6000 kg/ha greater than the actual yield (YA) at each experimental site in Eastern Canada. Two-thirds of this gap between YP and YA is probably associated with water stress, as a gap of approximately 4000 kg/ha between the YW and the YP was simulated. This gap may be reduced through crop management, such as introducing irrigation to improve the distribution of available water during the growing season. The simulated yields indicated a gap of about 3000 and 1000 kg/ha between YW and YW,N-80N for cultivars with high YP and low YP, respectively. The gap between YW and YW,N-160N decreased to <2000 kg/ha for high Yp cultivars with little difference for the low Yp cultivars. The different yield gaps among cultivars suggest that cultivars with high YP require high N rates but cultivars with low YP may need only low N rates.
Kinetic Monte Carlo (KMC) methods have been a successful technique for accelerating time scales and increasing system sizes beyond those achievable with fully atomistic simulations. However, a requirement for its success is a priori knowledge of all relevant reaction pathways and their rate coefficients. This can be difficult for systems with complex chemistry, such as shock-compressed materials at high temperatures and pressures or phenolic spacecraft heat shields undergoing pyrolysis, which can consist of hundreds of molecular species and thousands of distinct reactions. In this work, we develop a method for first estimating a KMC model composed of elementary reactions and rate coefficients by using large datasets derived from a few molecular dynamics (MD) simulations of shock compressed liquid methane, and then using L1 regularization to reduce the estimated chemical reaction network. We find that the full network of 2613 reactions can be reduced by 89% while incurring approximately 9% error in the dominant species (CH4) population. We find that the degree of sparsity achievable decreases when similar accuracy is required for additional populations of species.
Deploying resistant cultivars is an economical and essential management method in controlling viral diseases, and there are several mutational resources for tobacco. In the present study, the inoculation of tobacco plants with tobacco viruses was performed in a greenhouse from 2011 to 2014 to identify mutants resistant to tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). The high-throughput screening included seeding uniformly, transplanting in seedbeds, inoculating by cloth brushes and reporting symptoms based on disease indices. A total of 4000 second generation segregating (M2) mutants of tobacco cultivar Zhongyan100 were screened. Seeds from highly resistant mutant M2 plants were selected and planted separately. The M3 were grown and mutational stability was measured. For TMV, ten highly resistant plants were selected in the M2 generation and the mutation rate was 0·012%. In the M3 generation, there were seven mutants with hereditary high resistance and, according to the results of real-time polymerase chain reaction, the N gene was detected in all seven M3. Two hereditary immune M4 mutants, one of which was a male sterile line, were identified and evaluated in the glasshouse and in the field. For CMV, seven highly resistant plants were selected from the M2 generation and the mutation rate was 0·009%. In the M3 generation, there was one mutant with hereditary high resistance. The results indicate that hereditary mutants may be identified in the M4 generation and back-crossed to wild-type Zhongyan100 to identify anti-viral genes.
In this paper, we introduce a diffuse interface model for describing the dynamics of mixtures involving multiple (two or more) phases. The coupled hydrodynamical system is derived through an energetic variational approach. The total energy of the system includes the kinetic energy and the mixing (interfacial) energies. The least action principle (or the principle of virtual work) is applied to derive the conservative part of the dynamics, with a focus on the reversible part of the stress tensor arising from the mixing energies. The dissipative part of the dynamics is then introduced through a dissipation function in the energy law, in line with Onsager's principle of maximum dissipation. The final system, formed by a set of coupled time-dependent partial differential equations, reflects a balance among various conservative and dissipative forces and governs the evolution of velocity and phase fields. To demonstrate the applicability of the proposed model, a few two-dimensional simulations have been carried out, including (1) the force balance at the three-phase contact line in equilibrium, (2) a rising bubble penetrating a fluid-fluid interface, and (3) a solid particle falling in a binary fluid. The effects of slip at solid surface have been examined in connection with contact line motion and a pinch-off phenomenon.
A non-destructive neutron scattering method was developed to precisely measure the uptake of total hydrogen in nuclear grade Zircaloy-4 cladding. The hydriding apparatus consists of a closed stainless steel vessel that contains Zircaloy-4 specimens and hydrogen gas. By controlling the initial hydrogen gas pressure in the vessel and the temperature profile, target hydrogen concentrations from tens of ppm to a few thousands of ppm have been successfully achieved. Following hydrogen charging, the hydrogen content of the hydrided specimens was measured using the vacuum hot extraction method (VHE), by which the samples with desired hydrogen concentration were selected for the neutron study. Small angle incoherent neutron scattering (SAINS) were performed in the High Flux Isotope Reactor (HFIR) at Oak Ridge National Laboratory (ORNL). Our study indicates that a very small amount (≈ 20 ppm) hydrogen in commercial Zircaloy-4 cladding can be measured very accurately in minutes for a wide range of hydrogen concentration by a nondestructive method. The hydrogen distribution in a tube sample was obtained by scaling the neutron scattering rate with a factor, which is determined by calibration process with direct chemical analysis method on the specimen. This scale factor can be used for future test with unknown hydrogen concentration, thus provide a nondestructive method for absolute hydrogen concentration determination.