Product assembly is usually one of the last steps in the entire production process. This activity is typically entrusted to assembly workers because it is generally not possible to automate every type of product. For complex products, assembly can take a long time until the fitter learns the procedure and is able to assemble the product on his own. This contribution presents a cus-tom-developed system that enables controlled assembly of the extruder and can be used for complex and diverse products. The system serves to guide the fitter precisely and shows him which part to use at which time. The proposed system will show and describe on the display all necessary assembly steps and parts. Two-step verification is used to ensure that the correct part is picked from the stack. The contribution is supported by the implementation of a case study in a small company with a sample of 30 employees, which demonstrates that the proposed system shortens the extruder assembly time and significantly reduces the error rate. The presented solution is scalable and flexible, as it can be easily adapted to display the assembly steps of another product.

Objectives of this study were to investigate effects of repeated superstimulation on the success of ovum-pick up and in vitro production of embryos (OPU-IVP) and donor health and evaluate the efficiency of a modified SOF sequential medium in producing viable embryos. Over 1 y, six cross-bred beef heifers and three beef cows were subjected to superstimulations and OPU-IVP. Oocytes recovered were used for in vitro embryo production and the resulting embryos were transferred as fresh or frozen-thawed. Number of follicles, oocytes recovered, cleavage and blastocyst rates substantially varied among individuals. However, repeated trials did not significantly affect the efficiency of OPU-IVP. The pregnancy rates (PR) 22 to 30 d after embryo transfer for in vitro-derived fresh embryos was similar to that of fresh in vivo embryos, whereas transfer of in vitro-derived frozen embryos reduced PR compared to frozen-thawed in vivo embryos. All recipient heifers diagnosed pregnant delivered a viable calf, suggesting developmental competence of the embryos. Repeated OPU-IVP had no apparent deleterious effects, as all donors had viable calves after ET. We concluded that multiple OPU-IVP cycles can be effectively performed for a prolonged interval to maximize embryo production from elite donors without compromising their reproductive health.

Niemann-Pick type C (NPC) disease is a childhood autosomal recessive inherited rare neuro-degenerative disease, characterized by the accumulation of cholesterol and glycosphingolipids, implicating the autophagy-lysosome system. Inhibition of soluble epoxide hydrolase (sEH), an enzyme that metabolizes epoxy fatty acids (EpFAs) to 1,2-diols, exerts beneficial effects in mod-ulating inflammation and autophagy, critical features of the NPC disease. This study aimed to evaluate the effects of UB-EV-52 a sEH inhibitor (sEHi) in the Npc mouse model by administering for 4 weeks (5 mg/kg/day). Behavioral and cognitive assays (open field test (OF), elevated plus maze (EPM), novel object recognition test (NORT) and object location test (OLT) demonstrated that treatment produced an improvement in short- and long-term memory as well as in spatial memory. Moreover, the treatment with UB-EV-52 increased body weight and the lifespan by 25% and re-duced gene expression of the inflammatory markers (i.e. Il-1β and Mcp1) and improved oxidative stress (OS) markers (iNOS and Hmox1) in the treated Npc mice group. Regarding the autophagic markers, we surprisingly found significantly reduced levels of the ratio LC3B-II/LC3B-I and a significant reduction of brain protein levels of lysosomal-associated membrane protein-1 (LAMP-1) in Npc mice treated group compared to non-treated. Lipid profile analysis showed a significant reduction in lipid storage in the liver and some slight changes in brain tissue in treated Npc mice compared to non-treated groups. Thus, Our results suggest that the pharmacological inhibition of sEH ameliorates most of NPC’s characteristic traits in mice, demonstrating that sEH can be considered a potential therapeutic target for this condition.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Abstract：Ballast pick-up velocity is a crucial parameter in the design of a slurry system in excavating devices, it influences transportation stability, safety, and economy of the system. In this study, a vertical pipe hydraulic experiment with different ballast sizes under water condition was conducted to investigate the ballast pick-up velocity in the shield slurry system. Thereafter, the coupling method of computational fluid dynamics and the discrete element method (CFD-DEM) was employed to establish a numerical model of the ballast pick-up velocity in the shield slurry system, and its applicability was verified by comparing the experiment results. Additionally, the ballast pick-up process under actual working conditions was studied, and the influence of ballast size and concentration on pick-up velocity was investigated. Overall, the primary findings of the study are as follows: 1) The numerical method can be applied to predict both the single ballast and ballast group pick-up velocity. 2) The pick-up process of the ballast group can be divided into four stages. 3) The conveying velocity of the ballast should be higher than the pick-up velocity of the single ballast to facilitate smooth discharge. 4) For a certain increase in ballast concentration, the pick-up velocity tends to be stable.

Hypercholesterolemia accelerates atherosclerosis, and extensive research has been undertaken to ameliorate this abnormality. Plant sterols have been shown to inhibit cholesterol absorption and lower plasma cholesterol level since the 1950s. This ingredient has recently been reappraised as a food additive that can be taken daily in a preclinical period to prevent hypercholesterolemia, considering that cardiovascular-related diseases are the top cause of death globally even with clinical interventions. Intestinal cholesterol handling is still elusive, making it difficult to clarify the mechanism for plant sterol-mediated inhibition. Notably, although the small intestine absorbs cholesterol, it is also the organ that excretes it abundantly, via trans-intestinal cholesterol efflux (TICE). In this review, we show a model where the brush border membrane (BBM) of intestinal epithelial cells stands as the dividing ridge for cholesterol fluxes, making cholesterol absorption and TICE inversely correlated. With this model, we tried to explain the plant sterol-mediated inhibitory mechanism. As well as cholesterol, plant sterols diffuse into the BBM but are effluxed back to the lumen rapidly. We propose that repeated plant sterol shuttling between the BBM and lumen promotes cholesterol efflux, and plant sterol in the BBM may disturb the trafficking machineries that transport cholesterol to the cell interior.

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with a low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology ranging from clinical activity to genealogical reconstruction of families/populations along the centuries, creation of databases, and molecular/genetic research, has been modelled on the characteristics of the Calabrian population for more than three decades. This methodology allows to the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, in this population it has been reported a higher prevalence of several hereditary neurodegenerative diseases such as Alzheimer’s disease, Frontotemporal dementia, Parkinson’s disease, Niemann Pick type C disease, Spino-cerebellar ataxia, Creutzfeldt–Jakob disease and Gerstmann Straussler Scheincker disease. Thus, Calabria constitutes a model for the study of neurodegenerative diseases, a sort of "outdoor laboratory" useful for the advancement of knowledge in this field. Here, we summarize and discuss some results of research data supporting the view that Calabria is a genetic isolate and could represent a useful model for the study and characterization of neurodegenerative diseases.