Differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and CH1641 scrapie

With increased awareness of the diversity of transmissible spongiform encephalopathy (TSE) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. Exposure to bovine spongiform encephalopathy (BSE) has been associated with the human TSE, variant Creutzfeldt–Jakob disease, emphasizing the necessity in distinguishing low-risk TSE types from BSE. TSE type discrimination in ruminants such as cattle, sheep, goats and deer, requires the application of several prion protein (PrP)-specific antibodies in parallel immunochemical tests on brain homogenates or tissue sections from infected animals. This study uses in a single incubation step, three PrP-specific antibodies and fluorescent Alexa dye-labelled anti-mouse Fabs on a Western blot. The usual amount of brain tissue needed is 0.5 mg. This multiplex application of antibodies directed towards three different PrP epitopes enabled differential diagnosis of all established main features of classical scrapie, BSE and Nor98-like scrapie in sheep and goats, as well as the currently known BSE types C, H and L in cattle. Moreover, due to an antibody-dependent dual PrP-banding pattern, for the first time CH1641 scrapie of sheep can be reliably discriminated from the other TSE isolate types in sheep

Generalizations of Sturmian sequences associated with NN-continued fraction algorithms

Given a positive integer $N$ and $x$ irrational between zero and one, an $N$-continued fraction expansion of $x$ is defined analogously to the classical continued fraction expansion, but with the numerators being all equal to $N$. Inspired by Sturmian sequences, we introduce the $N$-continued fraction sequences $\omega(x,N)$ and $\hat{\omega}(x,N)$, which are related to the $N$-continued fraction expansion of $x$. They are infinite words over a two letter alphabet obtained as the limit of a directive sequence of certain substitutions, hence they are $S$-adic sequences. When $N=1$, we are in the case of the classical continued fraction algorithm, and obtain the well-known Sturmian sequences. We show that $\omega(x,N)$ and $\hat{\omega}(x,N)$ are $C$-balanced for some explicit values of $C$ and compute their factor complexity function. We also obtain uniform word frequencies and deduce unique ergodicity of the associated subshifts. Finally, we provide a Farey-like map for $N$-continued fraction expansions, which provides an additive version of $N$-continued fractions, for which we prove ergodicity and give the invariant measure explicitly.Comment: 23 pages, 2 figure

Flow rate influence on sediment depth estimation in sewers using temperature sensors

Enhancing sediment accumulation monitoring techniques in sewers will enable a better understanding of the build-up processes to develop improved cleaning strategies. Thermal sensors provide a solution to sediment depth estimation by passively monitoring temperature fluctuations in the wastewater and sediment beds, which allows evaluation of the heat-transfer processes in sewer pipes. This study analyses the influence of the flow conditions on heat-transfer processes at the water–sediment interface during dry weather flow conditions. For this purpose, an experimental campaign was performed by establishing different flow, temperature patterns, and sediment depth conditions in an annular flume, which ensured steady flow and room-temperature conditions. Numerical simulations were also performed to assess the impact of flow conditions on the relationships between sediment depth and harmonic parameters derived from wastewater and sediment-bed temperature patterns. Results show that heat transfer between water and sediment occurred instantaneously for velocities greater than 0.1 m/s, and that sediment depth estimations using temperature-based systems were barely sensitive to velocities between 0.1 and 0.4 m/s. A depth estimation accuracy of ±7 mm was achieved. This confirms the ability of using temperature sensors to monitor sediment build-up in sewers under dry weather conditions, without the need for flow monitoring

The transcription factor GATA6 is essential for early extraembryonic development

The gene coding for the murine transcription factor GATA6 was inactivated by insertion of a beta-galactosidase marker gene. The analysis of heterozygote GATA6/lacZ mice shows two inductions of GATA6 expression early in development. It is first expressed at the blastocyst stage in part of the inner mass and in the trophectoderm. The second wave of expression is in parietal endoderm (Reichert's membrane) and the mesoderm and endoderm that form the heart and gut. Inactivation leads to a lethality shortly after implantation (5.5 days postcoitum). Chimeric experiments show this to be caused by an indirect effect on the epiblast due to a defect in an extraembryonic tissue

Variability in disease phenotypes within a single PRNP genotype suggests the existence of multiple natural sheep scarpie strains within Europe

Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the PRNP genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrPd), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, ‘long’ or ‘short’ PrPd profiling. The groups made did not respond to the geographical origin of the cases and did not correlate with the vacuolar lesion profiles, which showed a high individual variability. Discriminatory IHC and WB methods coincided to detect a ‘CH1641-like’ case but otherwise correlated poorly in the classification of disease phenotypes. No other polymorphisms of the PRNP gene were found that could account for the pathological differences, except perhaps for a sheep from Spain with a mutation at codon 103 and a unique pathological phenotype. Preliminary evidence indicates that those different IHC phenotypes correlate with distinct biological properties on bioassay, suggesting that they are indicative of strain diversity. We therefore conclude that natural scrapie strains exist and that they can be revealed by detailed pathological examinations, which can be harmonized between laboratories to produce comparable results

Direct evidence of the failure of electric-dipole approximation in second-harmonic generation from a chiral polymer film

Second-harmonic generation from Langmuir-Blodgett films of a polythiophene is strongly influenced by the chirality of the polymer. The polarization dependence of the process cannot be explained in the elec.-dipole approxn. Evidence of contributions beyond elec. dipoles is obtained directly from individual second-harmonic signal

Severe tracheal and bronchial collapse in adults with type II mucopolysaccharidosis

Background: Mucopolysaccharidosis type II (MPSII) patients frequently suffer from dyspnoea caused by restrictive airway disease due to skeletal abnormalities as well as glycosaminoglycans (GAG) accumulation at different levels of the airway, including the trachea. In this study we describe the extent of the tracheal and bronchial narrowing, the changes in airway diameter during respiration and the effects of these obstructions on respiratory function in adult MPSII patients. Methods: Five adult MPSII patients (mean age 40 years) were included. Pulmonary function tests and in- and expiratory chest CT scans were obtained. Cross-sectional areas of trachea and main bronchi were measured at end-inspiration and -expiration and percentage collapse was calculated. Results: There was diffuse narrowing of the entire intra-thoracic trachea and main bronchi and severe expiratory collapse of the trachea in all patients. At 1 cm above the aortic arch the median % collapse of the trachea was 68 (range 60 to 77 %), at the level of the aortic arch 64 (range 21-93 %), for the main bronchi this was 58 (range 26-66 %) on the left and 44 (range 9-76 %) on the right side. The pulmonary function tests showed that this airway collapse results in obstructive airway disease in all patients, which was severe (forced expiratory volume <50 % of predicted) in four out of five patients. Conclusion: In adult MPS II patients, central airways diameters are strikingly reduced and upon expiration there is extensive collapse of the trachea and main bronchi. This central airways obstruction explains the severe respiratory symptoms in MPSII patients