Genomic Multiple Sclerosis Risk Variants Modulate the Expression of the ANKRD55–IL6ST Gene Region in Immature Dendritic Cells

Autoimmune; Multiple sclerosisAutoinmune; Esclerosis múltipleAutoimmune; Esclerosi múltipleIntronic single-nucleotide polymorphisms (SNPs) in the ANKRD55 gene are associated with the risk for multiple sclerosis (MS) and rheumatoid arthritis by genome-wide association studies (GWAS). The risk alleles have been linked to higher expression levels of ANKRD55 and the neighboring IL6ST (gp130) gene in CD4+ T lymphocytes of healthy controls. The biological function of ANKRD55, its role in the immune system, and cellular sources of expression other than lymphocytes remain uncharacterized. Here, we show that monocytes gain capacity to express ANKRD55 during differentiation in immature monocyte-derived dendritic cells (moDCs) in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). ANKRD55 expression levels are further enhanced by retinoic acid agonist AM580 but downregulated following maturation with interferon (IFN)-γ and lipopolysaccharide (LPS). ANKRD55 was detected in the nucleus of moDC in nuclear speckles. We also analyzed the adjacent IL6ST, IL31RA, and SLC38A9 genes. Of note, in healthy controls, MS risk SNP genotype influenced ANKRD55 and IL6ST expression in immature moDC in opposite directions to that in CD4+ T cells. This effect was stronger for a partially correlated SNP, rs13186299, that is located, similar to the main MS risk SNPs, in an ANKRD55 intron. Upon analysis in MS patients, the main GWAS MS risk SNP rs7731626 was associated with ANKRD55 expression levels in CD4+ T cells. MoDC-specific ANKRD55 and IL6ST mRNA levels showed significant differences according to the clinical form of the disease, but, in contrast to healthy controls, were not influenced by genotype. We also measured serum sgp130 levels, which were found to be higher in homozygotes of the protective allele of rs7731626. Our study characterizes ANKRD55 expression in moDC and indicates monocyte-to-dendritic cell (Mo–DC) differentiation as a process potentially influenced by MS risk SNPs.This research was supported by grants to KV from MINECO (SAF2016-74891-R), Instituto de Salud Carlos III (FIS-PI20/00123), Gobierno Vasco RIS3 (Ref. 2019222043), and Red Española de Esclerosis Múltiple (REEM; RD16/0015/0005). NV and LMV were supported by ISCIII (FIS-PI18/00572) and REEM (RD16/0015/0001). RTN is a recipient of a fellowship from the Secretaría Nacional de Ciencia y Tecnología e Innovación (SENACYT; Convocatoria Doctorado de Investigación Ronda III, 2018; Ref. BIDP-III-2018-12) of the Gobierno Nacional, República de Panamá

The Rare IL22RA2 Signal Peptide Coding Variant rs28385692 Decreases Secretion of IL-22BP Isoform-1, -2 and -3 and Is Associated with Risk for Multiple Sclerosis.

The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10-4). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%-60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS

Modulation Strategy for Multiphase Neutral-Point-Clamped Converters

This paper presents a novel modulation strategy for n-phase neutral-point-clamped (NPC) converters. The proposed modulation strategy is able to control and completely remove the low-frequency neutral-point (NP) voltage oscillations for any operation point and load types. Even when unbalanced and/or nonlinear loads are considered, the NP voltage remains under total control. Consequently, the strategy is very attractive for n-phase active filters. In addition, it enables the use of low-capacity film capacitors in NPC converters. The proposed modulation takes the carrier-based modulation strategy as a basis. It is formulated following a generalized approach that makes it expandable to n-phase NPC converters. In addition, the NP voltage is controlled directly using a closed-loop algorithm that does not rely on the use of the linear control regulators or the additional compensators used in other modulation algorithms. Therefore, no tuning of parameters is required and it performs optimally for any operating conditions and kind of loads, including unbalanced and nonlinear loads. Although the high-frequency harmonic content of the output voltages may increase, the weighted total harmonic distortion generated by the proposed strategy is similar to that of a standard sinusoidal pulse width modulated strategy. The proposed modulation algorithm has been tested in a four-leg NPC converter prototype performing as a three-and four-phase system and operating with balanced and unbalanced loads.Basque Country Government ETORTEK and GAITE

Generalized PWM-Based Method for Multiphase Neutral-Point-Clamped Converters with Capacitor Voltage Balance Capability

This paper presents a generalized PWM-based control algorithm for multiphase neutral-point-clamped (NPC) converters. The proposed algorithm provides a zero-sequence to be added to the reference voltages that contributes to improve the performance of the converter by: i) regulating the neutralpoint (NP) current to eliminate/attenuate the low-frequency NP voltage ripples, ii) reducing the switching losses of the power semiconductors and iii) maximizing the range of modulation indices for linear operation mode. The control method is formulated following a carrier-based PWM approach. Hence, dealing with complex space-vector diagrams to solve the modulation problem for multiphase converters is avoided. The recursive approach means that it can be easily extended to n-phase converters without increasing the complexity and computational burden, making it especially attractive for digital implementation. The proposed method allows regulating the NP voltage without the need for external controllers; therefore, no parameter tuning is required. The algorithm has been tested in a four-leg NPC converter prototype performing as a three- and four-phase system and operating with balanced and unbalanced loads

Sensorless control strategy for light-duty EVs and efficiency loss evaluation of high frequency injection under standardized urban driving cycles

Sensorless control of Electric Vehicle (EV) drives is considered to be an effective approach to improve system reliability and to reduce component costs. In this paper, relevant aspects relating to the sensorless operation of EVs are reported. As an initial contribution, a hybrid sensorless control algorithm is presented that is suitable for a variety of synchronous machines. The proposed method is simple to implement and its relatively low computational cost is a desirable feature for automotive microprocessors with limited computational capabilities. An experimental validation of the proposal is performed on a full-scale automotive grade platform housing a 51¿kW Permanent Magnet assisted Synchronous Reluctance Machine (PM-assisted SynRM). Due to the operational requirements of EVs, both the strategy presented in this paper and other hybrid sensorless control strategies rely on High Frequency Injection (HFI) techniques, to determine the rotor position at standstill and at low speeds. The introduction of additional high frequency perturbations increases the power losses, thereby reducing the overall efficiency of the drive. Hence, a second contribution of this work is a simulation platform for the characterization of power losses in both synchronous machines and a Voltage Source Inverters (VSI). Finally, as a third contribution and considering the central concerns of efficiency and autonomy in EV applications, the impact of power losses are analyzed. The operational requirements of High Frequency Injection (HFI) are experimentally obtained and, using state-of-the-art digital simulation, a detailed loss analysis is performed during real automotive driving cycles. Based on the results, practical considerations are presented in the conclusions relating to EV sensorless control. Peer Reviewed Document type: Articl

Circulating Current Control for Modular Multilevel Converters with (N+1) Selective Harmonic Elimination - PWM

Modular multilevel converters (MMCs) require control of the circulating current, i_circ, to improve their operation and efficiency. This is particularly important when low switching frequency modulation techniques, such as selective harmonic elimination (SHE-PWM) are applied. This work provides a novel method to control the circulating current along with (N+1) SHE-PWM. Unlike the case of (2N+1) SHE-PWM, explicit redundant levels are not available and, therefore, different modulation indexes, m_1 and m_2, are employed in the upper and lower arms to obtain the desired modulation index m_a. Unlike previous (N+1) circulating current methods, the distances between m_a, m_1 and m_2 remain constant to not disturb the phase output voltage, with an interchange of m_1 and m_2 between the arms used to follow the desired i_circ. The control adjusts the dc component of the circulating current and the energy stored in the SMs to their references, while maintaining the energy balance between the upper and lower arms. Simulation tests and experimental results, obtained from a single-phase laboratory prototype MMC, validate the proposed control technique

Control strategies for combining local energy storage with wells turbine oscillating water column devices

This paper proposes three generator control strategies for Wells turbine-based floating oscillating wáter column (OWC) devices comprising electrical or mechanical energy storage systems. The first control strategy is indicated for low inertia turbine OWC devices that include ultracapacitors. This control law optimizes the power take-off efficiency by means of an instantaneous speed controller that allows variation of the turbine rotational speed in a wave-by-wave basis. In addition, the profile of the electrical power injected into the grid is smoothed, so that a high penetration of wave energy does not threaten the grid stability. The second and third control laws are developed for OWC systems comprising a flywheel. Quasi-constant and variable speed controllers are proposed. These control laws do not maximize the system efficiency but allow the use of simpler, smaller and cheaper power electronics. Additionally the power quality is also optimized. The development of the proposed control algorithms is accomplished by means of simulations and verified with an experimental test rig.European Commission - MARINET project (Marine Renewables Infrastructure Network) , KIC InnoEnergy through the CIPOWER (Controllable and Intelligent Power Components) projec