Histone H3.3 beyond cancer: Germline mutations in Histone 3 Family 3A and 3B cause a previously unidentified neurodegenerative disorder in 46 patients

Although somatic mutations in Histone 3.3 (H3.3) are well-studied drivers of oncogenesis, the role of germline mutations remains unreported. We analyze 46 patients bearing de novo germline mutations in histone 3 family 3A (H3F3A) or H3F3B with progressive neurologic dysfunction and congenital anomalies without malignancies. Molecular modeling of all 37 variants demonstrated clear disruptions in interactions with DNA, other histones, and histone chaperone proteins. Patient histone posttranslational modifications (PTMs) analysis revealed notably aberrant local PTM patterns distinct from the somatic lysine mutations that cause global PTM dysregulation. RNA sequencing on patient cells demonstrated up-regulated gene expression related to mitosis and cell division, and cellular assays confirmed an increased proliferative capacity. A zebrafish model showed craniofacial anomalies and a defect in Foxd3-derived glia. These data suggest that the mechanism of germline mutations are distinct from cancer-associated somatic histone mutations but may converge on control of cell proliferation

A self-tuning closed-loop flux observer for sensorless torque control of standard induction machines

This paper proposes a self-tuning closed-loop flux observer, which provides field-oriented torque control for induction machines without a tachometer. The proposed algorithm combines the best features of harmonic detection and stator voltage integration through the use of a new tuning scheme. The observer accuracy and robustness is augmented by a parameter-independent accurate-speed detector, which analyzes magnetic saliency harmonics in the stator current. The harmonic-detection scheme provides accurate rotor-speed updates during steady-state operation down to 1-Hz source frequency. This additional speed information is used to tune the rotor-resistance parameter of the observer. The tuned observer exhibits improved dynamic performance, accurate steady-state speed control and an extended range of control near zero speed. The algorithm requires no special machine modifications and can be implemented on most existing low- and medium-performance drives. The closed-loop nature of the flux observer, combined with the harmonic-detection scheme, provides flux and speed error feedback, which significantly increases the robustness of sensorless control across the entire speed range

The use of titanium dioxide coatings deposited by APCVD on glass substrates to provide a dual action self cleaning

Over recent years there has been a rapid growth in the markets for large area coated glass products. Among the driving forces for this growth have been building design, energy efficiency, conservation needs, environmental issues, and associated legislation. Coatings produced by chemical vapor deposition (CVD) have now been on the market for many years and cover a wide range of applications such as low emmissivity coatings based on n-type semiconductors, reflective solar control coatings, and protective barrier layer coatings. The presentation details the challenges of using APCVD to deposit polycrystalline TiO2 films, on large area glass substrates for self-cleaning applications. Details of the coatings structure and properties are discussed. An investigation into the photodestruction of various organic contaminants including paraffin wax and stearic acid is presented along with the hydrophilic performance of the product when exposed to UV radiation. The presentation puts the properties of the film into context by detailing the use of scattering measurements and simulated dirt mixes to show the benefit of hydrophilic and photoactive coatings on maintaining the cleanliness of a glass substrate and how this relates to real-life performance