Efficiency Alteration of Francis Turbines by travelling Bubble Cavitation

The setting level of a hydraulic machine, specially for low head machines, is decided with respect to the possible alteration of the efficiency due to the cavity development. This alteration can easily be noticed by following the evolution of the efficiency 'eta' as a function of the Thoma number 'sigma' leading to the so-called 'eta'-'sigma' cavitation curves. Observation of the cavity extent in the flow passage of the runner allows to associate the drop of efficiency with a particular type of cavity development. However, depending on the type of cavities this drop cannot be very easily explained. Obviously, for a leading edge attached cavity corresponding to high head operating points, the presence of the vapour phase on the blade suction sicle limits the pressure at the vapour tensile strength value which causes the flow alteration. In the case of travelling bubble cavitation, corresponding to the outlet cavitation at the nominal head, previous experiments with a 2-D NACA profile show that the modification of the mean pressure field is mainly due to the bubble dynamics. The aim of this paper is to present the results and the analysis of two experiments intending to explain the influence of the nuclei content on the mean pressure field correction due to the bubble dynamics

Mechanism of the Efficiency Drop due to traveling Bubble Cavitation

The setting level of a hydraulic machine, specially for low head machines, is decided with respect to the possible alteration of the efficiency due to the cavity development. In the case of traveling bubble cavitation, corresponding to the outlet cavitation at the nominal head, the physical phenomenon underlying such an efficiency alteration is not very clear, even though a strong dependence of this drop with the volume of cavities have been noticed. The aim of this paper is to present the results of an experiment intending to explain physically the influence of bubble cavitation on the performance of a hydraulic profile

A Study of Spatial Reasoning Skills in Carpenters’ Training

One difficulty with the Swiss dual system is the gap between the practical work in the company and the theoretical teaching at school. In this article, we examine the case of carpenters. We observe that the school-workplace gap exists and materializes through the importance given to drawing classes at school, while carpenters almost never draw at their workplace. The existence of the drawing classes are justified by their contribution to the development of spatial skills, which are essential to carpenters. To gain a clearer view on spatial skills for carpenters, we performed a large-scale (n=512) field study on spatial skills, in which carpenters were compared with logistics apprentices and high school students. We report the results of this study and show that carpenters’ spatial skills are higher than the two other populations’ but that they do not improve between the end of the first year and the end of their apprenticeship. Those results give us indications on how to build a future learning environment to improve the training of carpenters

Clinical profile of patients with ATP1A3 mutations in alternating hemiplegia of childhood-a study of 155 patients.

BACKGROUND: Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype. METHODS: Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically formulated questionnaire and analysed relative to the mutational ATP1A3 gene data for each patient. RESULTS: In total, 34 different ATP1A3 mutations were detected in 85 % (132/155) patients, seven of which were novel. In general, mutations were found to cluster into five different regions. The most frequent mutations included: p.Asp801Asn (43 %; 57/132), p.Glu815Lys (16 %; 22/132), and p.Gly947Arg (11 %; 15/132). Of these, p.Glu815Lys was associated with a severe phenotype, with more severe intellectual and motor disability. p.Asp801Asn appeared to confer a milder phenotypic expression, and p.Gly947Arg appeared to correlate with the most favourable prognosis, compared to the other two frequent mutations. Overall, the comparison of the clinical profiles suggested a gradient of severity between the three major mutations with differences in intellectual (p = 0.029) and motor (p = 0.039) disabilities being statistically significant. For patients with epilepsy, age at onset of seizures was earlier for patients with either p.Glu815Lys or p.Gly947Arg mutation, compared to those with p.Asp801Asn mutation (p < 0.001). With regards to the five mutation clusters, some clusters appeared to correlate with certain clinical phenotypes. No statistically significant clinical correlations were found between patients with and without ATP1A3 mutations. CONCLUSIONS: Our results, demonstrate a highly variable clinical phenotype in patients with AHC2 that correlates with certain mutations and possibly clusters within the ATP1A3 gene. Our description of the clinical profile of patients with the most frequent mutations and the clinical picture of those with less common mutations confirms the results from previous studies, and further expands the spectrum of genotype-phenotype correlations. Our results may be useful to confirm diagnosis and may influence decisions to ensure appropriate early medical intervention in patients with AHC. They provide a stronger basis for the constitution of more homogeneous groups to be included in clinical trials

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice.

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe