Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study

Background: Human prion diseases are rare and usually rapidly fatal neurodegenerative disorders, the most common being sporadic Creutzfeldt-Jakob disease (sCJD). Variants in the PRNP gene that encodes prion protein are strong risk factors for sCJD but, although the condition has similar heritability to other neurodegenerative disorders, no other genetic risk loci have been confirmed. We aimed to discover new genetic risk factors for sCJD, and their causal mechanisms. Methods: We did a genome-wide association study of sCJD in European ancestry populations (patients diagnosed with probable or definite sCJD identified at national CJD referral centres) with a two-stage study design using genotyping arrays and exome sequencing. Conditional, transcriptional, and histological analyses of implicated genes and proteins in brain tissues, and tests of the effects of risk variants on clinical phenotypes, were done using deep longitudinal clinical cohort data. Control data from healthy individuals were obtained from publicly available datasets matched for country. Findings: Samples from 5208 cases were obtained between 1990 and 2014. We found 41 genome-wide significant single nucleotide polymorphisms (SNPs) and independently replicated findings at three loci associated with sCJD risk; within PRNP (rs1799990; additive model odds ratio [OR] 1·23 [95% CI 1·17-1·30], p=2·68 × 10-15; heterozygous model p=1·01 × 10-135), STX6 (rs3747957; OR 1·16 [1·10-1·22], p=9·74 × 10-9), and GAL3ST1 (rs2267161; OR 1·18 [1·12-1·25], p=8·60 × 10-10). Follow-up analyses showed that associations at PRNP and GAL3ST1 are likely to be caused by common variants that alter the protein sequence, whereas risk variants in STX6 are associated with increased expression of the major transcripts in disease-relevant brain regions. Interpretation: We present, to our knowledge, the first evidence of statistically robust genetic associations in sporadic human prion disease that implicate intracellular trafficking and sphingolipid metabolism as molecular causal mechanisms. Risk SNPs in STX6 are shared with progressive supranuclear palsy, a neurodegenerative disease associated with misfolding of protein tau, indicating that sCJD might share the same causal mechanisms as prion-like disorders. Funding: Medical Research Council and the UK National Institute of Health Research in part through the Biomedical Research Centre at University College London Hospitals National Health Service Foundation Trust

Vergleichende Lebenszykluskostenanalyse für Fußgängerbrücken aus unterschiedlichen Werkstoffen

Bei Infrastrukturobjekten können im Laufe der Nutzungsdauer erhebliche Kosten für Instandhaltungsmaßnahmen anfallen. Die Wahl der baulichen Variante sollte deshalb nicht nur anhand des Anschaffungspreises sondern unter Berücksichtigung der entstehenden Folgekosten erfolgen. Vor diesem Hintergrund wurde in einer Studie mit der Deutschen Bahn AG und der Peter Maier Leichtbau GmbH untersucht, welcher Werkstoff für Fußgängerbrücken die beste Gesamtwirtschaftlichkeit verspricht. Dabei wurde die Gesamtwirtschaftlichkeit anhand einer Lebenszykluskosten-Analyse beurteilt. Untersucht wurden Fußgängerbrücken als sog. Personenüberführungen aus den konventionellen Brückenbaustoffen Holz, Stahl und Stahlbeton sowie aus dem Werkstoff Aluminium. Als Vergleichswert für die Lebenszykluskosten wurde die Annuität herangezogen. Unsicherheiten bei der Kostenprognose wurden mit Hilfe von Sensitivitätsanalysen eingegrenzt. Für das im Rahmen der Untersuchung betrachtete System stellte sich die Aluminiumbrücke als die wirtschaftlichste Variante heraus

Induction motors angular rotor eccentricity diagnosis by analyzing vibroperturbing forces

Методами математичного моделювання досліджено зміни величин і характеру електромагнітних віброзбуджуючих сил, які виникають при появі кутового ексцентриситету ротора асинхронного двигуна. Досліджено допустимі діапазони величин кутового ексцентриситету, при яких можлива подальша експлуатація машин без обмежень. Показано, що для забезпечення процесу вібраційної діагностики кутового ексцентриситету потрібно використання двох датчиків, які розташовані на протилежних торцях осердя статора двигуна в одній площині.Rotor angular eccentricity of induction motor is damage, which should be investigated in a three-dimensional setting, because the value of air gap varies along the length of induction motor, which requires significant computational power of computers. However, in order to simplify the analysis of vibroperturbing forces, it can be analyzed in two-dimensional planes staged as a set in which the rotor is shifted relative to the stator in the radial direction. Vibration sensors located on the surface of the stator, take off diagnostic information in only one of these planes. Sensor signals are located in one plane at different ends of the stator core. So enough to explore displacement of the rotor relative to the stator in a two-dimensional formulation of these two planes. Diagnostic signs of angular eccentricity appearance, which can be used in systems of vibrodiagnosis, were determined: a significant increase in noise and rotary teeth harmonics spectrum of vibroperturbing forces in one of the sensors, which is located in the zone of minimum air gap of induction motor; the absence rotational harmonics in vibroperturbing forces spectrum. Permissible range of angular eccentricity values at which there is possible further using of machines without restrictions were investigated. It is proved that the rotor angular eccentricity is dangerous kind of damage due to the appearance of longitudinal torque of force, which leads to accelerated wearing of motor bearings