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Background: alpha-Synuclein (alpha Syn) is believed to play a central role in Parkinson's disease (PD) neuropathology and is considered a target for disease modification. UB-312 is a synthetic alpha Syn peptide conjugated to a T helper peptide and is expected to induce antibodies specifically against oligomeric and fibrillar alpha Syn, making UB-312 a potential immunotherapeutic for synucleopathies. Objective: To investigate the safety, tolerability, and immunogenicity of UB-312 vaccination in healthy participants and to determine a safe and immunologically optimal dose for the first-in-patient study. Methods: Fifty eligible healthy participants were enrolled in a 44-week, randomized, placebo-controlled, double-blind study. Participants in seven cohorts were randomized to three intramuscular UB-312 or placebo injections at weeks 1, 5, and 13 (doses ranging between 40 and 2000 mu g). Safety and tolerability were assessed by adverse events, clinical laboratory, vital signs, electrocardiograms, and neurological and physical examinations. Immunogenicity was assessed by measuring serum and cerebrospinal fluid (CSF) anti-aSyn antibody concentrations. Results: Twenty-three participants received all three vaccinations of UB-312. Most adverse events were mild, transient, and self-resolving. Common treatment-emergent adverse events included headache, nasopharyngitis, vaccination-site pain, lumbar puncture-site pain, and fatigue. UB-312 induced dose- and time-dependent antibody production. Antibodies were detectable in serum and CSF of all participants receiving the 300/300/300 mu g UB-312 dose regimen. The average CSF/serum ratio was 0.2%. Conclusions: UB-312 was generally safe, well tolerated, and induced anti-aSyn antibodies in serum and CSF of healthy participants. The 100 and 300 mu g doses are selected for further evaluation in participants with PD. (C) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Polyetheretherketone (PEEK) is a new type of special engineering plastic that has broad market potentials due to its particular microstructure and mechanical properties. However, few data can be found in the literatures devoted to the mechanical properties and machinability of PEEK, especially in the superprecision field. For the first time, the microscopic mechanical properties and machinability of glassfiber-reinforced PEEK (GF/PEEK), which is one typical derivative of pure PEEK, are studied. The nanoindentation experiment was performed to analyze the microscopic mechanical properties of GF/PEEK. The machinability was studied by single-point diamond turning (SPDT) on the GF/PEEK surface, the roughness and form accuracy of the machined surface were obtained in the following test. Experimental results indicate that GF/PEEK has good microscopic mechanical properties and machinability. Полиэфирэфиркетон новый вид специального конструкционного пластика, который благодаря особой микроструктуре и механическим свойствам имеет большие возможности выхода на рынок. Однако в литературе можно найти не так много данных, относящихся к механическим свойствам и обрабатываемости полиэфирэфиркетона, особенно в сверхточной области. Впервые проведено исследование обрабатываемости и механических свойств на микроскопическом уровне полиэфирэфиркетона, упрочненного стекловолокном, который является типичным производным чистого полиэфирэфиркетона. Выполнено наноиндентирование с целью анализа механических свойств материала на микроскопическом уровне. Обрабатываемость материала изучали с помощью одноточечной алмазной обточки по его поверхности, при испытании были получены значения шероховатости и точности формы обработанной поверхности. Экспериментальные результаты свидетельствуют о хороших механических свойствах и обрабатываемости полиэфирэфиркетона, упрочненного стекловолокном.