Chronic Progressive External Ophthalmoplegia Is Associated with a Novel Mutation in the Mitochondrial tRNA(Asn) Gene

Chronic progressive external ophthalmoplegia (CPEO) is caused by a decreased oxidative phosphorylation (OXPHOS) activity due to large-scale deletions of the mitochondrial genome in 50 % of the patients. The deletions encompass structural OXPHOS genes as well as tRNA genes, required for their expression so that the pathogenesis could be due to the deleted OXPHOS subunits or to an impaired mitochondrial translation. We have analyzed the mitochondrial genome of a patient presenting with CPEO for single base substitutions and discovered a novel heteroplasmic mutation in the tRNAAsn gene at position 5692 that converts a highly conserved adenine into a guanine. This mutation is unique because it is located at the transition of the anticodon loop to the anticodon stem and it leads to an additional base pair, thus reducing the number of loop-forming nucleotides from seven to five. Our findings suggest that CPEO can be caused by a single base substition in a mitochondrial tRNA gene so that the mitochondrial protein synthesis becomes the rate limiting step in OXPHOS fidelity

Wavelet solution of variable order pseudodifferential equations

Sobolev spaces H m(x)(I) of variable order 0<m(x)<1 on an interval I⊂ℝ arise as domains of Dirichlet forms for certain quadratic, pure jump Feller processes X t∈ℝ with unbounded, state-dependent intensity of small jumps. For spline wavelets with complementary boundary conditions, we establish multilevel norm equivalences in H m(x)(I) and prove preconditioning and wavelet matrix compression results for the variable order pseudodifferential generators A of X. Sufficient conditions on A to satisfy a Gårding inequality in H m(x)(I) and time-analyticity of the semigroup T t associated with the Feller process X t are established. As application, wavelet-based algorithms of log-linear complexity are obtained for the valuation of contingent claims on pure jump Feller-Lévy processes X t with state-dependent jump intensity by numerical solution of the corresponding Kolmogoroff equation

Impact of carbon dioxide versus air pneumoperitoneum on peritoneal cell migration and cell fate

Background: Postoperative systemic immune function is suppressed after open abdominal surgery, as compared with that after minimally invasive abdominal surgery. As a first line of defense, peritoneal macrophages (PMo) and polymorphonuclear neutrophil granulocytes (PMNs) are of primary importance in protecting the body from microorganisms. Previous studies have shown changes in these cell populations over time after open versus laparoscopic surgery. This study aimed to investigate the dynamics of cell recruitment and clearance of peritoneal cells. Methods: Female NMRI mice (33 ± 2 g) were randomly assigned to carbon dioxide (CO2) or air insufflation. Intravasal cells with phagocytic capabilities were selectively stained by intravenous injection of the fluorescent dye PKH26 24 h before surgery. Gas was insufflated into the peritoneal cavity through a catheter, and the pneumoperitoneum was maintained for 30 min. Peritoneal lavage was performed 1, 3, 8, or 24 h after surgery. Apoptotic cells were assessed by flow cytometry using a general caspase substrate. Results: The total peritoneal cell count did not differ between groups. The PKH26-positive PMo level was significantly increased after CO2, as compared with air, at 1 h and 24 h. The ratio of apoptotic PMo did not differ between the groups. In the peritoneal lavage, polymorphonuclear leukocytes (PMNs) were tripled in the air group, as compared with the CO2 group, whereas the ratio of apoptotic PMNs was significantly decreased. There was a higher fraction of PKH26-positive PMNs after air exposure, as compared with that after CO2. Conclusions: Air exposure triggered a higher transmigration rate of PMNs from the blood compartment into the peritoneal cavity and decreased PMN apoptosis, as compared with CO2. The lower proportion of PKH26-positive peritoneal macrophages in the air group might have been attributable to a higher inflammatory stimulation than in the CO2 group, leading to increased emigration of PMo to draining lymph nodes. All the findings underscore a complex cell-specific regulation of cell recruitment and clearance in the peritoneal compartmen

Direct extreme UV-lithographic conversion of metal xanthates into nanostructured metal sulfide layers for hybrid photovoltaics

We present a versatile strategy toward the preparation of nanostructured metal sulfide layers, which exploits the photosensitivity of metal xanthates as a powerful tool for lithographic structuring. Using extreme ultraviolet interference lithography (EUV-IL), we successfully realized well-defined column and comb nanostructures. This approach provides new pathways to fabricate highly ordered structured metal sulfide layers with periodicities far below 100 nm for potential application in hybrid solar cells. © 2013 The Royal Society of Chemistry

Opicapone in UK clinical practice: effectiveness, safety and cost analysis in patients with Parkinson's disease.

Aim: This subanalysis of the OPTIPARK study aimed to confirm the effectiveness and safety of opicapone in patients with Parkinson's disease and motor fluctuations in clinical practice specifically in the UK and to assess the impact of opicapone on treatment costs. Methods: Patients received opicapone added to levodopa for 6 months. Clinical outcomes were assessed at 3 and 6 months and treatment costs at 6 months. Results: Most patients' general condition improved at 3 months, with sustained improvements reported at 6 months. Opicapone improved motor and non-motor symptoms at both timepoints, was generally well tolerated and reduced total treatment costs by GBP 3719. Conclusion: Opicapone added to levodopa resulted in clinical improvements and reduced treatment costs across UK clinical practice

quasiharmonic equations of state for dynamically-stabilized soft-mode materials

We introduce a method for treating soft modes within the analytical framework of the quasiharmonic equation of state. The corresponding double-well energy-displacement relation is fitted to a functional form that is harmonic in both the low- and high-energy limits. Using density-functional calculations and statistical physics, we apply the quasiharmonic methodology to solid periclase. We predict the existence of a B1--B2 phase transition at high pressures and temperatures

Evidence of a high incidence of subclinically affected calves in a herd of cattle with fatal cases of Bovine Neonatal Pancytopenia (BNP).

BACKGROUND: Bovine Neonatal Pancytopenia (BNP) is a disease of calves characterised by bone marrow trilineage hypoplasia, mediated by ingestion of alloantibodies in colostrum. Suspected subclinical forms of BNP have been reported, suggesting that observed clinical cases may not represent the full extent of the disease. However to date there are no objective data available on the incidence of subclinical disease or its temporal distribution. This study aimed to 1) ascertain whether subclinical BNP occurs and, if so, to determine the incidence on an affected farm and 2) determine whether there is evidence of temporal clustering of BNP cases on this farm. To achieve these aims, haematological screening of calves born on the farm during one calving season was carried out, utilising blood samples collected at defined ages. These data were then analysed in comparison to data from both known BNP-free control animals and histopathologically confirmed BNP cases. An ordinal logistic regression model was used to create a composite haematology score to predict the probabilities of calves being normal, based on their haematology measurements at 10–14 days old. RESULTS: This study revealed that 15% (21 of 139) of the clinically normal calves on this farm had profoundly abnormal haematology (<5% chance of being normal) and could be defined as affected by subclinical BNP. Together with clinical BNP cases, this gave the study farm a BNP incidence of 18%. Calves with BNP were found to be distributed throughout the calving period, with no clustering, and no significant differences in the date of birth of cases or subclinical cases were found compared to the rest of the calves. This study did not find any evidence of increased mortality or increased time from birth to sale in subclinical BNP calves but, as the study only involved a single farm and adverse effects may be determined by other inter-current diseases it remains possible that subclinical BNP has a detrimental impact on the health and productivity of calves under certain circumstances. CONCLUSIONS: Subclinical BNP was found to occur at a high incidence in a herd of cattle with fatal cases of BNP

Evaluation of exposure-specific risks from two independent samples: A simulation study

<p>Abstract</p> <p>Background</p> <p>Previous studies have proposed a simple product-based estimator for calculating exposure-specific risks (ESR), but the methodology has not been rigorously evaluated. The goal of our study was to evaluate the existing methodology for calculating the ESR, propose an improved point estimator, and propose variance estimates that will allow the calculation of confidence intervals (CIs).</p> <p>Methods</p> <p>We conducted a simulation study to test the performance of two estimators and their associated confidence intervals: 1) current (simple product-based estimator) and 2) proposed revision (revised product-based estimator). The first method for ESR estimation was based on multiplying a relative risk (RR) of disease given a certain exposure by an overall risk of disease. The second method, which is proposed in this paper, was based on estimates of the risk of disease in the unexposed. We then multiply the updated risk by the RR to get the revised product-based estimator. A log-based variance was calculated for both estimators. Also, a binomial-based variance was calculated for the revised product-based estimator. 95% CIs were calculated based on these variance estimates. Accuracy of point estimators was evaluated by comparing observed relative bias (percent deviation from the true estimate). Interval estimators were evaluated by coverage probabilities and expected length of the 95% CI, given coverage. We evaluated these estimators across a wide range of exposure probabilities, disease probabilities, relative risks, and sample sizes.</p> <p>Results</p> <p>We observed more bias and lower coverage probability when using the existing methodology. The revised product-based point estimator exhibited little observed relative bias (max: 4.0%) compared to the simple product-based estimator (max: 93.9%). Because the simple product-based estimator was biased, 95% CIs around this estimate exhibited small coverage probabilities. The 95% CI around the revised product-based estimator from the log-based variance provided better coverage in most situations.</p> <p>Conclusion</p> <p>The currently accepted simple product-based method was only a reasonable approach when the exposure probability is small (< 0.05) and the RR is ≤ 3.0. The revised product-based estimator provides much improved accuracy.</p

Lattice deformation at the sub-micron scale: X-ray nanobeam measurements of elastic strain in electron shuttling devices

The lattice strain induced by metallic electrodes can impair the functionality of advanced quantum devices operating with electron or hole spins. Here we investigate the deformation induced by CMOS-manufactured titanium nitride electrodes on the lattice of a buried, 10 nm-thick Si/SiGe Quantum Well by means of nanobeam Scanning X-ray Diffraction Microscopy. We were able to measure TiN electrode-induced local modulations of the strain tensor components in the range of $2 - 8 \times 10^{-4}$ with ~60 nm lateral resolution. We have evaluated that these strain fluctuations are reflected into local modulations of the potential of the conduction band minimum larger than 2 meV, which is close to the orbital energy of an electrostatic quantum dot. We observe that the sign of the strain modulations at a given depth of the quantum well layer depends on the lateral dimensions of the electrodes. Since our work explores the impact of device geometry on the strain-induced energy landscape, it enables further optimization of the design of scaled CMOS-processed quantum devices.Comment: 16 pages, 6 figure