On the use of inversion formulae for the synthesis of discrete PID controllers

This paper presents a new set of formulae for the design of discrete proportional-integral-derivative (PID) controllers under requirements on steady-state performance and robustness specifications, such as the phase and the gain margins, as well as the gain crossover frequency. The proposed technique has the advantage of avoiding trial-and error procedures or approximations connected to an a posteriori discretisation. This method can also be implemented as a graphical design procedure in the Nyquist plane

Effect of quasi-bound states on coherent electron transport in twisted nanowires

Quantum transmission spectra of a twisted electron waveguide expose the coupling between traveling and quasi-bound states. Through a direct numerical solution of the open-boundary Schr\"odinger equation we single out the effects of the twist and show how the presence of a localized state leads to a Breit-Wigner or a Fano resonance in the transmission. We also find that the energy of quasi-bound states is increased by the twist, in spite of the constant section area along the waveguide. While the mixing of different transmission channels is expected to reduce the conductance, the shift of localized levels into the traveling-states energy range can reduce their detrimental effects on coherent transport.Comment: 8 pages, 9 color figures, submitte

Direct digital design of PIDF controllers with ComPlex zeros for DC-DC buck converters

This paper presents a new direct digital design method for discrete proportional integral derivative PID + filter (PIDF) controllers employed in DC-DC buck converters. The considered controller structure results in a proper transfer function which has the advantage of being directly implementable by a microcontroller algorithm. Secondly, it can be written as an Infinite Impulse Response (IIR) digital filter. Thirdly, the further degree of freedom introduced by the low pass filter of the transfer function can be used to satisfy additional specifications. A new design procedure is proposed, which consists of the conjunction of the pole-zero cancellation method with an analytical design control methodology based on inversion formulae. These two methods are employed to reduce the negative effects introduced by the complex poles in the transfer function of the buck converter while exactly satisfying steady-state specifications on the tracking error and frequency domain requirements on the phase margin and on the gain crossover frequency. The proposed approach allows the designer to assign a closed-loop bandwidth without constraints imposed by the resonance frequency of the buck converter. The response under step variation of the reference value, and the disturbance rejection capability of the proposed control technique under load variations are also evaluated in real-time implementation by using the Arduino DUE board, and compared with other methods

A Novel MIMO Control for Interleaved Buck Converters in EV DC Fast Charging Applications

This brief proposes a new multiple input multiple output (MIMO) control for off-board electric vehicle (EV) dc fast chargers. The proposed feedback matrix design avoids multiple tuning of controllers in multiple and interconnected loops while improving the performance of interleaved dc buck converters over classical PI/PID controls. The innovative features of the presented strategy are the reference current monotonic tracking from any initial state of charge with an arbitrarily fast settling time and the fast compensation of both load variations and imbalances among the legs. Numerical results validate the performance improvements of the proposed discrete-time MIMO algorithm for interleaved buck converters over classical PI/PID controls. Full-scale hardware-in-the-loop (HIL) and scaled-down prototype experimental results prove the feasibility and effectiveness of the proposal

Dual-Active-Bridge Model and Control for Supporting Fast Synthetic Inertial Action

This article proposes a dual-active-bridge control to support the fast synthetic inertial action in DC microgrids. First of all, the selection of the isolated DC/DC converter to link an energy storage system with the DC bus in a microgrid is analyzed and the advantages of the dual-active-bridge converter controlled by a single-phase shift modulation justify its selection. An active front-end can be then adapted to connect the DC bus with an AC grid. Secondly, this paper presents the design of a discrete PI controller for supporting fast synthetic inertial action. In particular, a discrete dual-active-bridge model based on the transferred power between both converter bridges, which overcomes the approximations of the output current linearization model, is proposed. Moreover, the article introduces a novel equation set to directly and dynamically tune discrete PI parameters to fulfill the design frequency specifications based on the inversion formulae method. In this way, during the voltage/power transients on the DC bus, the controller actively responds and recovers those transients within a grid fundamental cycle. Since the developed set of control equations is very simple, it can be easily implemented by a discrete control algorithm, avoiding the use of offline trial and error procedures which may lead to system instability under large load variations. Finally, the proposed control system is evaluated and validated in PLECS simulations and hardware-in-the-loop tests

Citrullination: the loss of tolerance and development of autoimmunity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and pannus formation, which can lead to severe destruction of cartilage and bone. Several self proteins have been suggested to be disease-driving autoantigens. Moreover the presence of autoantibodies to citrullinated proteins in sera of patients with RA enhances the strength of this hypothesis. Proteins are encoded by a limited number of genes in our genome. Post-translational modifications such as phosphorylation, glycosylation and citrullination can increase the morphological and the functional diversity of the proteome

Citrullination: the loss of tolerance and development of autoimmunity in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and pannus formation, which can lead to severe destruction of cartilage and bone. Several self proteins have been suggested to be disease-driving autoantigens. Moreover the presence of autoantibodies to citrullinated proteins in sera of patients with RA enhances the strength of this hypothesis. Proteins are encoded by a limited number of genes in our genome. Post-translational modifications such as phosphorylation, glycosylation and citrullination can increase the morphological and the functional diversity of the proteome

Strategies for Improved pDNA Loading and Protection Using Cationic and Neutral LNPs with Industrial Scalability Potential Using Microfluidic Technology

Purpose: In recent years, microfluidic technologies have become mainstream in producing gene therapy nanomedicines (NMeds) following the Covid-19 vaccine; however, extensive optimizations are needed for each NMed type and genetic material. This article strives to improve LNPs for pDNA loading, protection, and delivery, while minimizing toxicity. Methods: The microfluidic technique was optimized to form cationic or neutral LNPs to load pDNA. Classical “post-formulation” DNA addition vs “pre” addition in the aqueous phase were compared. All formulations were characterized (size, homogeneity, zeta potential, morphology, weight yield, and stability), then tested for loading efficiency, nuclease protection, toxicity, and cell uptake. Results: Optimized LNPs formulated with DPPC: Chol:DOTAP 1:1:0.1 molar ratio and 10 μg of DOPE-Rhod, had a size of 160 nm and good homogeneity. The chemico-physical characteristics of cationic LNPs worsened when adding 15 μg/mL of pDNA with the “post” method, while maintaining their characteristics up to 100 μg/mL of pDNA with the “pre” addition remaining stable for 30 days. Interestingly, neutral LNPs formulated with the same method loaded up to 50% of the DNA. Both particles could protect the DNA from nucleases even after one month of storage, and low cell toxicity was found up to 40 μg/mL LNPs. Cell uptake occurred within 2 hours for both formulations with the DNA intact in the cytoplasm, outside of the lysosomes. Conclusion: In this study, the upcoming microfluidic technique was applied to two strategies to generate pDNA-LNPs. Cationic LNPs could load 10x the amount of DNA as the classical approach, while neutral LNPs, which also loaded and protected DNA, showed lower toxicity and good DNA protection. This is a big step forward at minimizing doses and toxicity of LNP-based gene therapy

Airway deposition of extrafine inhaled triple therapy in patients with copd: A model approach based on functional respiratory imaging computer simulations

Introduction: There is a clear correlation between small airways dysfunction and poor clinical outcomes in patients with chronic obstructive pulmonary disease (COPD), and it is therefore important that inhalation therapy (both bronchodilator and anti-inflammatory) can deposit in the small airways. Two single-inhaler triple therapy (SITT) combinations are currently approved for the maintenance treatment of COPD: extrafine formulation beclomethasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB), and nonextrafine formulation fluticasone furoate/vilanterol/umeclidinium (FluF/VI/UMEC). This study evaluated the lung deposition of the inhaled corticosteroid (ICS), long-acting β2-agonist (LABA), and long-acting muscarinic antagonist (LAMA) components of these two SITTs. Materials and Methods: Lung deposition was estimated in-silico using functional respiratory imaging, a validated technique that uses aerosol delivery performance profiles, patients’ high-resolution computed tomography (HRCT) lung scans, and patient-derived inhalation profiles to simulate aerosol lung deposition. Results: HRCT scan data from 20 patients with COPD were included in these analyses, who had post-bronchodilator forced expiratory volume in 1 second (FEV1) ranging from 19.3% to 66.0% predicted. For intrathoracic deposition (as a percentage of the emitted dose), deposition of the ICS component was higher from BDP/FF/GB than FluF/VI/UMEC; the two triple therapies had similar performance for both the LABA component and the LAMA component. Peripheral deposition of all three components was higher with BDP/FF/GB than FluF/ VI/UMEC. Furthermore, the ratios of central to peripheral deposition for all three components of BDP/FF/GB were <1, indicating greater peripheral than central deposition (0.48 ±0.13, 0.48±0.13 and 0.49±0.13 for BDP, FF and GB, respectively; 1.96±0.84, 0.97±0.34 and 1.20±0.48 for FluF, VI and UMEC, respectively). Conclusions: Peripheral (small airways) deposition of all three components (ICS, LABA, and LAMA) was higher from BDP/FF/GB than from FluF/VI/UMEC, based on profiles from patients with moderate to very severe COPD. This is consistent with the extrafine formulation of BDP/FF/GB

Dysregulation of NF–Y splicing drives metabolic rewiring and aggressiveness in colon cancer

NF-Y is an evolutionarily conserved transcription factor that binds specifically to the CCAAT elements of eukaryotic genes, most of which frequently deregulated in cancer. NF-YA, the regulatory subunit of the NF-Y complex, has two isoforms generated by alternative splicing, NF-YAl and NF-YAs, which differ in the transactivation domain. Transcriptomic data from The Cancer Genome Atlas (TCGA) database highlighted a significant increase in the expression of NF-YAs at the expense of NF-YAl in colorectal cancer (CRC), compared to healthy tissues. Despite this, high NF-YAl levels predict lower patients’ survival and distinguish the mesenchymal molecular subtype CMS4, which is characterized by the worst prognosis. Through the analysis of 3D cellular models, we demonstrated that altered expression of genes related to extracellular matrix and epithelial-mesenchymal transition sustains enhanced migratory and invasive behavior of NF-YAl-transduced cells. Moreover, the integration of metabolomics, bioenergetics and transcriptional analyses demonstrated a direct role for NFYAl in metabolic flexibility of cancer cells that adjust their metabolism in response to environmental changes to potentiate migration. The zebrafish xenograft model confirmed the metastatic potential triggered by NF-YAl in CRC cells. Altogether, our data highlight the transcriptional role of NF-YAl in CRC aggressiveness and suggest splice-switching strategies to hinder NF-YAl-induced metastatic dissemination