Cyclized NDGA modifies dynamic α-synuclein monomers preventing aggregation and toxicity.

Growing evidence implicates α-synuclein aggregation as a key driver of neurodegeneration in Parkinson's disease (PD) and other neurodegenerative disorders. Herein, the molecular and structural mechanisms of inhibiting α-synuclein aggregation by novel analogs of nordihydroguaiaretic acid (NDGA), a phenolic dibenzenediol lignan, were explored using an array of biochemical and biophysical methodologies. NDGA analogs induced modest, progressive compaction of monomeric α-synuclein, preventing aggregation into amyloid-like fibrils. This conformational remodeling preserved the dynamic adoption of α-helical conformations, which are essential for physiological membrane interactions. Oxidation-dependent NDGA cyclization was required for the interaction with monomeric α-synuclein. NDGA analog-pretreated α-synuclein did not aggregate even without NDGA-analogs in the aggregation mixture. Strikingly, NDGA-pretreated α-synuclein suppressed aggregation of naïve untreated aggregation-competent monomeric α-synuclein. Further, cyclized NDGA reduced α-synuclein-driven neurodegeneration in Caenorhabditis elegans. The cyclized NDGA analogs may serve as a platform for the development of small molecules that stabilize aggregation-resistant α-synuclein monomers without interfering with functional conformations yielding potential therapies for PD and related disorders

Prognozowanie uszkodzeń statków powietrznych dla celów obsługi konserwacyjnej na podstawie ich parametrów oraz danych z eksploatacji

Aircraft maintenance and repair organizations (MROs) have to be competitive and attractive for both existing and new customers. The aircraft ground time at MROs should be as short as possible and cost effective without reducing the quality of the work. Process optimization in MROs requires the continuous improvement of processes and the elimination of non-value-added activities during maintenance checks. There is, on the one hand, an obligation to follow the prescribed procedures and, on the other hand, pressure for time and cost reduction. The aircraft servicing process has been analysed according to a lean methodology. The optimization of logistics processes is recognized as the most promising method for reducing the maintenance service time and costs of spare parts. The probability of aircraft faults is calculated on the basis of historic data from previously completed service projects. Aircraft parameters, such as aircraft type, operator, aircraft age, flight hours, flight cycles, engine type and operation location, are taken into consideration in the fault forecasting. The fault probability is used as an indicator for defining a priority list for the accomplishment of jobs included in the aircraft maintenance service. The proposed methodology was validated and confirmed on four different projects.Organizacje zajmujące się konserwacją i naprawami statków powietrznych (MRO) muszą dbać o swoją konkurencyjność i atrakcyjność zarówno dla istniejących jak i nowych klientów. Czas trwania obsługi naziemnej w MRO powinien być jak najkrótszy a konserwacja powinna pociągać za sobą jak najmniejsze koszty, bez konieczności obniżania jakości pracy. Optymalizacja procesów przeprowadzanych w MRO wymaga ciągłego doskonalenia oraz eliminacji nieuzasadnionych czynności przeglądowych. Z jednej strony pracownicy MRO muszą przestrzegać określonych procedur, z drugiej zaś strony, ciąży na nich presja redukcji czasu i kosztów obsługi. Proces obsługi statku powietrznego analizowano zgodnie z metodologią szczupłego utrzymania ruchu. Optymalizację procesów logistycznych uznaje się za najbardziej obiecujący sposób redukcji czasu obsługi serwisowej oraz kosztów części zamiennych. Prawdopodobieństwo wystąpienia uszkodzeń statku powietrznego obliczano na podstawie danych historycznych z uprzednio przeprowadzonych prac obsługowych. W prognozowaniu uszkodzeń, uwzględniano takie parametry statku powietrznego, jak typ statku, jego operator, wiek, liczba godzin w powietrzu, liczba cykli lotów, typ silnika oraz miejsce stacjonowania. Prawdopodobieństwo wystąpienia uszkodzeń wykorzystano jako wskaźnik do hierarchizacji zadań obsługi technicznej statku powietrznego. Przydatność proponowanej metodologii zweryfikowano i potwierdzono na przykładzie czterech różnych projektów

Comparing surface topography parameters of rough surfaces obtained with spectral moments and deterministic methods

Understanding contact between rough surfaces is of critical importance to the design of many engineering applications. Contact models rely on material properties and surface topography of the contacting surfaces as input parameters. Hence, the relevance of the contact models is dependent on their inherent assumptions and the accuracy with which the input parameters are determined. We have evaluated the difference between the surface topography parameters calculated with a statistical and deterministic approach for actual engineering surfaces. We have found topography values that change up to 300% depending on the method used, and attribute this to the stringent definition of an asperity-peak in the case of deterministic analysis as opposed to statistical analysis, which not only considers asperity-peaks but also asperity-shoulders

Sterilization of polypropylene membranes of facepiece respirators by ionizing radiation

Ionizing radiation has been identified as an option for sterilization of disposable filtering facepiece respirators in situations where the production of the respirators cannot keep up with demand. Gamma radiation and high energy electrons penetrate deeply into the material and can be used to sterilize large batches of masks within a short time period. In relation to reports that sterilization by ionizing radiation reduces filtration efficiency of polypropylene membrane filters on account of static charge loss, we have demonstrated that both gamma and electron beam irradiation can be used for sterilization, provided that the respirators are recharged afterwards

Size- and Time-Dependent Particle Removal Efficiency of Face Masks and Improvised Respiratory Protection Equipment Used during the COVID-19 Pandemic

Size- and time-dependent particle removal efficiency (PRE) of different protective respiratory masks were determined using a standard aerosol powder with the size of particles in the range of an uncoated SARS-CoV-2 virus and small respiratory droplets. Number concentration of particles was measured by a scanning mobility particle sizer. Respiratory protective half-masks, surgical masks, and cotton washable masks were tested. The results show high filtration efficiency of FFP2, FFP3, and certified surgical masks for all sizes of tested particles, while protection efficiency of washable masks depends on their constituent fabrics. Measurements showed decreasing PRE of all masks over time due to transmission of nanoparticles through the mask-face interface. On the other hand, the PRE of the fabric is governed by deposition of the aerosols, consequently increasing the PRE

Possibilities of Maintenance Service Process Analyses and Improvement Through Six Sigma, Lean and Industry 4.0 Implementation

Part 7: Lean Organization for Industry 4.0International audienceThe paper deals with problems concerning a maintenance process realized by maintenance service companies. In the paper the concept of wastes identification in such companies is presented. Then, a case study company is analysed. The company designs, manufactures, implements and performs maintenance processes of installations used in products control, sorting and packing in clients’ factories. The analysed problems concern data collection as well as their analysis in order to improve the maintenance company efficiency. The authors propose to implement the Six Sigma methodology to collect and analyse data, elements of the Lean concept to identify wastes and Industry 4.0 concept in order to improve the maintenance service processes