N-Acetylaspartate Drives Oligodendroglial Differentiation via Histone Deacetylase Activation

An unmet clinical goal in demyelinating pathologies is to restore the myelin sheath prior to neural degeneration. N-acetylaspartate (NAA) is an acetylated derivative form of aspartate, abundant in the healthy brain but severely reduced during traumatic brain injury and in patients with neurodegenerative pathologies. How extracellular NAA variations impact the remyelination process and, thereby, the ability of oligodendrocytes to remyelinate axons remains unexplored. Here, we evaluated the remyelination properties of the oligodendroglial (OL) mouse cell line Oli-neuM under different concentrations of NAA using a combination of biochemical, qPCR, immunofluorescence assays, and in vitro engagement tests, at NAA doses compatible with those observed in healthy brains and during brain injury. We observed that oligodendroglia cells respond to decreasing levels of NAA by stimulating differentiation and promoting gene expression of myelin proteins in a temporally regulated manner. Low doses of NAA potently stimulate Oli-neuM to engage with synthetic axons. Furthermore, we show a concentration-dependent expression of specific histone deacetylases essential for MBP gene expression under NAA or Clobetasol treatment. These data are consistent with the idea that oligodendrocytes respond to lowering the NAA concentration by activating the remyelination process via deacetylase activation

A design method to reduce pulsating torque in PM assisted synchronous reluctance machines with asymmetry of rotor barriers

In this paper a design method for ferrite assisted synchronous reluctance machine is proposed in order to reduce torque ripple and cogging torque. An asymmetrical layout of the rotor flux barriers is proposed in order to reduce the harmonics components of the pulsating torque. The proposed analytical method is validated, employing finite elements simulations, for pure synchronous reluctance (SyR) and permanent magnet assisted synchronous reluctance machines (PMSyR) considering different slot-pole configurations. Simulated machines present a cogging torque and a torque ripple reduction respectively up to 92% and up to 70%. Moreover the electromotive force waveform is improved too. These results are achieved without reducing nominal torque and without increasing machines production costs

Design of Low-Cost Synchronous Machine to Prevent Demagnetization

The request for high efficiency motor paves the way for the replacement of induction motors with permanent magnet synchronous motors. Although the efficiency is increased, for medium and high power, the current ripple causes significant additional losses in the magnet and lamination; and, high temperature can lead to demagnetization. In this paper, a new rotor topology is proposed and compared to a traditional surface permanent magnet rotor to reduce the magnet losses and protect them from demagnetization. A reference surface permanent magnet machine is compared with the proposed one in terms of performance and magnet losses. Both analytical and experimental analysis are carried out and discussed

Effects of the Magnetic Model of Interior Permanent Magnet Machine on MTPA, Flux Weakening and MTPV Evaluation

Interior permanent-magnet synchronous machines are widely spreading in automotive and vehicle traction applications, because of their high efficiency over a wide speed range. This capability can be achieved by appropriated control strategies: Maximum Torque per Ampere (MTPA), Flux Weakening (FW) and Maximum Torque per Volt (MTPV). However, these control trajectories are often based on an simplified magnetic model of the electrical machine. In order to improve the evaluation of machine output capabilities, nonlinear magnetic behavior must be modeled. This is not only related to the final application with a given drive and control structure, but also during the design process of the electric machine. In the design process, the output torque Vs. speed characteristic must be calculated following MTPA, MTPV and FW in the most accurate way to avoid significant error. This paper proposes a set of algorithms to compute MTPA, FW and MTPV curves for interior permanent-magnet synchronous machines taking into account the machines’ nonlinearities caused by iron saturation and compares differed approaches to highlight the torque–speed capabilities for the same machine following different methods. The algorithms are based on the maps of the equivalent inductances of a reference interior permanent-magnet synchronous machine and inductances maps were obtained via 2-D Finite Element Analysis over the machine’s operating points in id−iq reference plane. The effects of different 2-D finite element methods are also computed by both standard nonlinear magnetostatic simulations and Frozen Permeability simulations. Results show that the nonlinear model computed via frozen permeability is more accurate than the conventional linear and nonlinear models computed via standard magnetostatic simulations; for this reason, during the electrical machine design, it is important to check the expected performance employing a complete inductance map and frozen permeability

Compliance, Adherence and Concordance Differently Predict the Improvement of Uremic and Microbial Toxins in Chronic Kidney Disease on Low Protein Diet

In medicine, “compliance” indicates that the patient complies with the prescriber’s recommendations, “adherence” means that “the patient matches the recommendations” and “concordance” means “therapeutic alliance” between patient and clinician. While a low protein diet (LPD) is a cornerstone treatment of chronic kidney disease (CKD), monitoring the actual performance of LPD is a challenge. Patients. Fifty-seven advanced CKD adult patients were enrolled and LPD prescribed. Compliance was evaluated through the normalized protein catabolic rate (nPCR), adherence by the dietitian by means of a 24-h dietary recall and concordance by the nephrologist during consultations. Traditional parameters as well as total p-Cresyl Sulphate (t-PCS), total Indoxyl Sulphate (t-IS) and Lipoprotein-associated phspholipase A2 (Lp-PLA2) were compared between adherent/not adherent and concordant/not concordant subjects at enrolment and after two months. Results. nPCR, blood urea nitrogen, cholesterol and triglycerides significantly decreased in all patients. t-PCS and t-IS decreased among adherent subjects. Lp-PLA2, t-PCS, free-PCS and t-IS decreased among concordant subjects, while these increased in non-concordant ones. Conclusion. This study demonstrates that LPD may improve the control of traditional uremic toxins and atherogenic toxins in “adherent” and “concordant” patients. A comprehensive and multidisciplinary approach is needed to evaluate the compliance/adherence/concordance to LPD for optimizing nutritional interventions

Does Mediterranean Adequacy Index Correlate with Cardiovascular Events in Patients with Advanced Chronic Kidney Disease? An Exploratory Study

The Mediterranean Diet (MD) is a healthy dietary pattern, demonstrated to reduce the risk of cancer, diabetes, cardiovascular and neurodegenerative diseases, and early death. The Mediterranean Adequacy Index (MAI) is used to measure adherence to the MD in perspective studies in the general population and correlates with cardiovascular events. The aim of this study was to calculate the MAI among patients with advanced chronic kidney disease (CKD) and correlate it with traditional uremic, microbiota-derived, and proatherogenic toxins as well as nutritional status, quality of life, and cardiovascular events. A total of 60 adult patients with advanced CKD were enrolled and their MAI was calculated. According to the median value, patients were divided into lower (l-MAI, <1.80) and higher (h-MAI, ≥1.80) MAI groups. Biochemical parameters, microbiota-derived and proatherogenic toxins (p-Cresyl sulphate, Indoxyl-sulphate, and Lipoprotein-associated phospholipase A2), nutritional status, quality of life, and cardiovascular events that occurred in the previous three years were recorded. The mean value of the MAI was 2.78 ± 2.86. The MAI was significantly higher in foreigners (median (IQR) 6.38 (8.98) vs. 1.74 (1.67), p < 0.001) and diabetic patients. The l-MAI and h-MAI groups had similar routinary blood, p-Cresyl-sulphate, Indoxyl-sulphate, and Lp-PLA2 as well as nutritional status and quality of life parameters. The MAI was not associated with previous cardiovascular events and did not correlate with cardiovascular events in CKD patients. New and nephro-tailored indexes are warranted to evaluate nutritional therapy in CKD patients