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Introducción: la capacidad física de trabajo (CFT) se describe como el conjunto de tareas utilizadas para llevar a cabo las actividades de la vida diaria comparada con individuos sanos; incluye fuerzas de agarre y de abdomen, equilibrio, flexibilidad, velocidad de marcha y capacidad aeróbica. Por eso la CFT y el índice de masa muscular esquelético (IMME) tienen relación entre sí y son susceptibles de mejorar si se realiza entrenamiento físico. Objetivo: determinar si un programa de entrenamiento supervisado y controlado una vez a la semana durante seis meses es efectivo para cambiar la CFT y el IMME en sujetos mayores de 18 años. Métodos: estudio observacional, analítico, de cohorte retrospectiva, de 565 pacientes que asistieron a un programa de entrenamiento supervisado y controlado una vez a la semana durante seis meses. Resultados: hay mejoría de la media de la CFT en -8.59 puntos al finalizar la intervención (P=0.000) y aumento del IMME en -0.06 puntos (P=0.002). Conclusiones: este estudio sugiere que una intervención de una hora guiada y supervisada una vez a la semana durante seis meses brinda beneficios en variables de la CFT con mejoría del IMME, que se explica por cambios en la microestructura muscular (mejoría en la capacidad de realizar un trabajo por unidad de masa muscular).

A model predictive control (MPC) strategy based on optimal switching sequence concepts is presented for direct power control of grid-connected three-level neutral-point clamped converters. The proposed control strategy explicitly considers the modulator in its formulation along with the model of the system. Through two well-formulated optimal control problems, the proposed strategy is shown to optimally achieve control of the average trajectory of the active and reactive powers as well as the dc-link capacitor voltages without using weighting factors to tradeoff both control targets. Experimental results demonstrate this strategy produces improved steady-state performance with a well-defined output voltage spectrum and fixed-switching frequency while maintaining the inherent fast dynamic responses of MPC strategies.

Secondary control strategies in hybrid ac/dc microgrids have been conventionally designed independently for each side of the microgrid, neglecting the interaction between the ac and dc sides due to the power transferred through the interlinking converter. This has a negative effect on the power sharing and dynamic response of the system. In this article, a novel distributed secondary control strategy for hybrid ac/dc-microgrids is presented which coordinates the control actions of the ac and dc sides. The proposed control scheme simultaneously regulates ac-voltage magnitude and frequency, as well as the dc-voltage magnitude, by including the interlinking converters in the control strategy via a distributed consensus approach. This improves the power-sharing accuracy and secondary control restoration of the variables in both ac and dc sides of the microgrid. Moreover, the proposed methodology avoids the circulating currents which are typically produced in systems with multiple interlinking converters. Several simulation and experimental tests, such as load impacts and plug-and-play capability, are presented to validate the performance of the proposed control strategy using a 24-kW hybrid ac/dc-microgrid laboratory prototype.

Background. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and is responsible for more than 12,000 deaths per year in the US. In addition to primary tumors, the liver is a common site for metastases of many types of cancer, including colorectal, and pancreatic cancer. The life expectancy and outlook for people with liver metastases are typically poor.Annamycin (ANN) is a novel anthracycline of our design that is clinically evaluated as a liposome formulated drug product, L-ANN. ANN and L-ANN display unique organotropism that differs from doxorubicin (DOX). In addition, ANN was shown to have increased potency against multidrug resistant cancer cell lines, and, importantly, L-ANN appeared to be non-cardiotoxic. Objective. The objective of this study was to analyze the pharmacokinetics of two formulations of ANN in the liver in comparison with DOX and to determine its tumoricidal potential in an HCC model in situ and in an experimental model of liver metastasis. Methods. The pharmacokinetics and tissue-organ distribution studies of L-ANN, free ANN, or DOX were performed in mice and rats. The levels of ANN and DOX in plasma and tissue homogenates were assessed using LC/MS. The antitumor efficacy of L-ANN was studied using HEPA 1-6 hepatocellular carcinoma models (subcutaneous, orthotopic, and experimental liver metastatic models) and compared with CT26 colon cancer liver metastasis experiments.Results. ANN exhibited dramatically higher accumulation in the liver parenchyma when compared to DOX (6-fold higher AUC values). We found that the increased liver uptake of the drug had a direct effect on activity of the drug in vivo. First, we observed clear, dose-dependent inhibition of the subcutaneous tumor growth after systemic (IV) administration of L-ANN. Next, remarkable activity of L-ANN was observed in orthotopic models. For instance, significant inhibition of the tumor growth and extension of the survival of L-ANN treated mice vs. vehicle-receiving animals was observed in HEPA 1-6 models (median survival 29.5 vs 50 days (p Citation Format: Rafal J. Zielinski, Krzysztof Grela, Shaohua Peng, Edd Felix, Roberto Cardenas-Zuniga, Damian Grybowski, Stanislaw Skora, Izabela Fokt, Waldemar Priebe. Exploration of Annamycin Organotropism to Target Primary and Metastatic Liver Cancers. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4947.

The increasing demand for higher power density and more efficient electric drives, in particular, from the automotive industry, has pushed engineers investigating new solutions. Recently, wide bandgap devices have been proposed to improve performances of classical ac/dc converters, mainly in terms of power conversion efficiency. In this article, an alternative approach is proposed, aiming to obtain the desired improvements in the overall drive performances using a more complex power conversion system, based on standard silicon devices. In particular, a modification of the modular multilevel converter (MMC) is proposed in order to eliminate the submodule voltage ripple that would otherwise limit the MMC applicability in low voltage, variable frequency electric drives. This article introduces the design procedure and the analytical modeling of this novel topology together with the validation of the theoretical claims via simulations and experimental tests.

The problems associated with active power oscillations (APOs) in grid-connected converters are well-known. Imbalances in the grid usually produce double-frequency oscillations in the dc-link voltage and current which could reduce the useful life of solar panels, batteries, and capacitors connected to this point. Moreover, as reported in the literature, double-frequency reactive power oscillations (RPOs) also produce adverse effects in distribution systems, and it is desirable to eliminate or mitigate them. When a four-leg power converter is connected to an unbalanced grid, the zero-sequence current provides extra degrees of freedom to compensate or even eliminate the power oscillations at the converter dc-link side. In this paper, a new methodology to regulate these double-frequency power components is proposed. It is based on a closed-loop vector control approach, where the active power oscillations (APOs) at converter side are transformed into a synchronous frame rotating at twice the grid frequency and regulated using the zero-sequence current. To avoid overcurrent produced by the circulation of positive-, negative-, and zero-sequence components a current limiter is also proposed in this paper. Experimental results obtained with a 4-kW four-leg power converter prototype are presented and discussed in this paper.

Distributed control schemes have transformed frequency and voltage regulation into a local task in distributed generators (DGs) rather than by a central secondary controller. A distributed scheme is based on information shared among neighboring units; thus, the microgrid performance is affected by issues induced by the communication network. This paper presents a distributed predictive control applied to the secondary level of microgrids. The model used for prediction purposes is based on droop and power transfer equations; however, communication features, such as connectivity and latency, are also included, thus making the controller tolerant to electrical and communication failures. The proposed controller considers the frequency and voltage regulation control objectives and consensus over the real and reactive power contributions from each power unit in the microgrid. The experimental and simulation results show that the proposed scheme (i) responds properly to load variations, working within operating constraints, such as generation capacity and voltage range; (ii) maintains the control objectives when a power unit is disconnected and reconnected without any user updating in the controllers; and (iii) compensates for the effects of communication issues over the microgrid dynamics.

A distributed control system is proposed which uses the Conservative Power Theory (CPT) and a consensus algorithm to share imbalance and harmonics between different converters in three-phase four-wire droop-controlled Microgrids (MGs). The CPT is used to identify the balanced, unbalanced and distorted components of the currents and powers in the system. Control loops based on virtual impedance and implemented in the stationary a-b-c frame are then used to distribute these components between the various converters in the MG. The magnitudes of the virtual impedances are adaptively calculated using a novel consensus-based distributed control scheme with the aim of sharing imbalances and harmonics according to the residual VA capacity of each converter whilst regulating the imbalance and distortion at their output to meet the appropriate IEEE power quality standards. Extensive simulations show that the proposed distributed control has excellent performance, and experimental validation is provided using a laboratory-scale 4-wire MG.

Collaborative control of power converters operating in microgrids with unbalanced single-phase loads is difficult to achieve, considering that the voltages and currents have positive-, negative-, and zero-sequence components. In this paper, a new control scheme for collaborative control of four-leg microgrids is proposed. The main advantage of the proposed methodology is simplicity, because the sharing of the powers produced by the positive-, negative-, and zero-sequence voltage and currents is simple to achieve using the easy to implement and well-known droop control algorithms, i.e., as those based on $P$ – $\omega$ and $Q$ – $v$ droop control. The proposed droop algorithms do not require high bandwidth communication channels and the application of virtual impedances, whose design usually demands extensive simulation work, is not required. Three secondary control systems are also analyzed, discussed, and implemented in this paper to regulate the frequency, voltage, and phase at the point of common coupling (PCC), to achieve a balanced 50-Hz three-phase voltage supply in the PCC during steady-state operation. For these secondary control systems, single-phase phase-locked loop based on quadrature signal generators are implemented. Small signal modeling and design are discussed in this paper. A microgrid prototype of $\approx$ 5 kW, implemented using two power converters of 3 kW (each), is used to experimentally validate the proposed algorithms.

This paper proposes a distributed predictive secondary control strategy to share imbalance in three-phase, three-wire isolated AC Microgrids. The control is based on a novel approach where the imbalance sharing among distributed generators is controlled through the control of single-phase reactive power. The main characteristic of the proposed methodology is the inclusion of an objective function and dynamic models as constraints in the formulation. The controller relies on local measurements and information from neighboring distributed generators, and it performs the desired control action based on a constrained cost function minimization. The proposed distributed model predictive control scheme has several advantages over solutions based on virtual impedance loops or based on the inclusion of extra power converters for managing single-phase reactive power among distributed generators. In fact, with the proposed technique the sharing of imbalance is performed directly in terms of single-phase reactive power and without the need for adding extra power converters into the microgrid. Contrary to almost all reported works in this area, the proposed approach enables the control of various microgrid parameters within predefined bands, providing a more flexible control system. Extensive simulation and Hardware in the Loop studies verify the performance of the proposed control scheme. Moreover, the controller’s scalability and a comparison study, in terms of performance, with the virtual impedance approach were carried out.

© 1986-2012 IEEE. In this work, a model predictive control (MPC) strategy based on optimal switching sequence (OSS) concepts is proposed for a grid-connected three-level neutral-point clamped converter. The proposed cascaded-OSS-MPC strategy does not require a weighting factor to balance the dc-link capacitor voltages and optimally controls both the grid currents and the capacitor voltages even during disturbances and large step changes in the references. The resulting MPC strategy allows operating the converter with a predefined harmonic spectrum, fixed switching frequency, and fast and robust dynamic response. Besides, an efficient optimization algorithm is also introduced to reduce the computational burden typically observed in this kind of MPC strategies. Experimental and simulation results are provided to demonstrate the effectiveness and high-quality performance of the proposed strategy.

Back-To-Back Modular Multilevel Converter (BTB MMC) was proposed as an attractive alternative for medium-voltage drive application to decrease the inherent problem of high floating capacitor voltage fluctuations produced at low frequency machine operation. Recently the variation of DC-Link reference between the MMC and a control strategy based in control the machine side MMC as a current source was introduced to decrease the mitigation variables using during low frequency operation. However, it does not solve the problem to obtain the minimal capacitor voltage fluctuation during the entire machine operation. This paper propose a new method to obtain the minimum capacitor voltage fluctuation of the MMC modules during the entire machine operation range including an additional AC signal between the system common link. The proposed control strategy and overall performance of the system are verified by computational simulation.

In this work, a continuous-control-set model predictive control (CCS-MPC) strategy, with a saturation scheme for protection, is presented for regulating the circulating currents of a modular multilevel matrix converter (M3C). The proposed approach is based on a state-space model of the M3C and allows protection and better utilization of the devices through a saturation scheme, which directly limits the arm currents and cluster output voltages by integrating the corresponding bounds as constraints of the CCS-MPC formulation. In order to solve the inherent optimization problem associated with the CCS-MPC, an active-set algorithm is implemented. Experimental and simulation results from a 27-cell M3C prototype validate the proposed strategy and illustrate the good performance achieved with the methodology presented in this work.

In aerospace applications, a ground power unit has to provide balanced and sinusoidal $\text{400}\,\text{Hz}$ phase-to-neutral voltages to unbalanced and nonlinear single-phase loads. Compensation of high-order harmonics is complex, as the ratio between the sampling frequency and compensated harmonics can be very small. Thus, multiple superimposed resonant controllers or proportional-integral (PI) nested controllers in multiple $dq$ frames are not good alternatives. The first approach cannot ensure stability, while the second cannot track the sinusoidal zero-sequence components typically present in unbalanced systems, and unattainably high bandwidth at the inner current control loop is typically required. In this paper, a simple methodology for designing a single-loop, multiple resonant controller for simultaneous mitigation of several high-order harmonics, ensuring stability, is presented. Experimental results, based on a 6 kW four-leg neutral point clamped converter, validate the proposed controller design, showing excellent steady-state and transient performance.

The modular multilevel matrix converter ( ${{\text{M}}^{\text{3}}}{\text{C}}$ ) is an ac-to-ac converter topology suitable for the control of high-power variable-speed drives. The control of this converter is complex, particularly when the two ac system frequencies are similar or identical because large voltage oscillations can be produced in the floating capacitors within the ${{\text{M}}^{\text{3}}}{\text{C}}$ . This paper proposes a new vector control system based on nested controllers to regulate the ${{\text{M}}^{\text{3}}}{\text{C}}$ over the full range of frequencies. The proposed control scheme is especially useful to mitigate or eliminate the oscillations that arise when the frequencies are similar. An extensive discussion of the model and control of the ${{\text{M}}^{\text{3}}}{\text{C}}$ is presented in this work. The effectiveness of the proposed vector control system is demonstrated through simulation studies and experimental validation tests conducted with a 27-cell-5kW ${{\text{M}}^{\text{3}}}{\text{C}}$ prototype.

A cooperative control scheme based on the conservative power theory (CPT) is proposed, which can share imbalances in three-phase four-wire droop-controlled systems. By utilizing the CPT, the balanced, unbalanced, and distorted components of the currents and powers in a microgrid can be identified. Using control loops based on virtual impedances and implemented in the stationary a–b–c frame, the imbalances and harmonics are shared between the different four-leg inverters in the microgrid. A secondary control loop is implemented to regulate the maximum voltage imbalance/distortion at the point of common coupling or any other point in the microgrid. The theoretical background of the method is presented, and experimental validation is demonstrated using a laboratory-scale microgrid with two inverters operating at 5 kW.

The modular multilevel converter (MMC) has emerged as a suitable topology for high power drive applications. However, the voltage fluctuations of its floating capacitors increase the control complexity of the converter. In this study, the MMC dc-port voltage is manipulated to regulate the amplitude of these fluctuations to a constant value during the whole frequency range. The proposed approach has several advantages when compared with the conventional ones since it minimises the voltage fluctuation in the capacitor cells. Additionally, it decreases the common-mode voltage at low frequencies and the capacitor rms current, increasing their expected lifespan and reducing the winding insulation damages and the leakage currents in the bearing of the machine. The effectiveness of the proposed control strategy is validated with a laboratory-based prototype composed of 18 power cells, feeding a vector-controlled induction machine.

This paper presents two capacitor voltage balancing (CVB) strategies for modular multilevel converter (MMC) applications. Both balancing schemes are based on model predictive control and are designed to efficiently solve a constrained optimal control problem, where the predicted capacitor voltage errors are included in the cost function with the demanded output voltage of a cluster being forced through an equality constraint. The first method proposed in this paper computes specific modulation indexes for each module using the explicit solution of a relaxed version of the original optimization problem. The second approach proposed in this paper reduces the complexity of the original problem by linearizing the objective function and using an optimal sorting network based on a greedy algorithm to solve this approximation. Considering the structures of both solution approaches, they are integrated into modulation schemes based on phase-shifted and level-shifted pulsewidth modulation algorithms, respectively. Experimental results obtained from a nine-cell single-phase MMC prototype demonstrate the good performance achieved with the proposed methodologies, as well as the implementation simplicity offered by the proposed CVB algorithms.

Colorectal cancer (CRC) is a frequently occurring disease and the second most common cause of cancer deaths when men and women are combined. CRC metastasis is strongly associated with mortality. The liver and lungs are the most frequent sites of distant disease, accounting for ~70% and ~12% of cases, respectively. We hypothesize that anticancer agents that mimic the organotropism of metastatic CRC will be highly effective in treating CRC patients. Our studies have identified that Annamycin (ANN), a potent topoisomerase II poison that displays organotropism imitating that of metastatic CRC. ANN is an analog of doxorubicin (Dox) that shows unique properties. Notably, ANN is active against multidrug-resistant tumors and undergoes efficient uptake by lungs and liver. ANN is easily formulated in multilamellar liposomes (L-ANN), which further increases ANN levels in lungs and liver. Objective. The objective of this study was to assess the efficacy of L-ANN in experimental CRC liver and lung metastasis models. Methods. The efficacy of L-ANN was tested in syngeneic models of metastatic CRC established in lungs or liver. For lung metastasis model, CT26-Luc cells were injected intravenously (IV) into Balb/c mice, followed by weekly IV treatment of L-ANN (4 and 6 mg/kg). The liver metastatic model was established using intrasplenic injection protocol. Mice received six weekly IV injections of 4 mg/kg of L-ANN or vehicle. Bioluminescent imaging (BLI), Magnetic Resonance Imaging (MRI) or Computer Tomography (CT) were used to track tumor progression. Results. L-ANN exhibited robust antitumor activity in both models. In the lung metastasis model, a dose-dependent delay in the tumor progression was visualized by both BLI and CT scan in the L-ANN treated group. The delay correlated with 272% extension of survival in the group receiving 6 mg/kg L-ANN [median survival (MS) 79d for treated vs 29d vehicle, p Conclusion. In summary, the strategy to develop anticancer agents that imitate metastatic CRC organotropism appears to be highly promising and is supported by these results. Our previous in vivo studies of L-ANN in sarcoma lung metastasis models already led to initiation of multicenter clinical studies (NCT04887298). This study demonstrating L-ANN efficacy in CRC models provides convincing evidence for further preclinical development aimed at initiation of clinical studies in CRC metastatic patients. Citation Format: Rafal J. Zielinski, Krzysztof Grela Grela, Roberto Cardenas-Zuniga, Stanislaw Skora, Izabela Fokt, Edward Felix, Damian Grybowski, Waldemar Priebe. New approach to target metastatic colorectal cancer organotropism with L-Annamycin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4048.

Aptamers, synthetic single-strand oligonucleotides that are similar in function to antibodies, are promising as therapeutics because of their minimal side effects. However, the stability and bioavailability of the aptamers pose a challenge. We developed aptamers converted from RNA aptamer to modified DNA aptamers that target phospho-AXL with improved stability and bioavailability. On the basis of the comparative analysis of a library of 17 converted modified DNA aptamers, we selected aptamer candidates, GLB-G25 and GLB-A04, that exhibited the highest bioavailability, stability, and robust antitumor effect in in vitro experiments. Backbone modifications such as thiophosphate or dithiophosphate and a covalent modification of the 5'-end of the aptamer with polyethylene glycol optimized the pharmacokinetic properties, improved the stability of the aptamers in vivo by reducing nuclease hydrolysis and renal clearance, and achieved high and sustained inhibition of AXL at a very low dose. Treatment with these modified aptamers in ovarian cancer orthotopic mouse models significantly reduced tumor growth and the number of metastases. This effective silencing of the phospho-AXL target thus demonstrated that aptamer specificity and bioavailability can be improved by the chemical modification of existing aptamers for phospho-AXL. These results lay the foundation for the translation of these aptamer candidates and companion biomarkers to the clinic.

Modern variable-speed drives must be able to deal with ride-through faults with dips of 70–90% to ensure the continuity of the process without the energy store station discharge and carry out significant effects to its performance. So, the existent contingencies to such case are tripping-method from grid, robust DC-Link with higher capacitors and additional power electronic hardware. Nevertheless, they comprehend a common drawback for being costly in the industry. Therefore, the Power Loss Ride Through behaviour on variable-speed drives is an important feature which is a worst-case where the system can suffer dips near to 99% on grid. Recently, Modular Multilevel Cascade Converters have been applied in Variable-Speed Drives applications due to their capability to operate at high-power rates and features such as enhanced fault-ride through capability during critical dip voltage (e.g., 99% of amplitude) in grid. Therefore, this paper presents a control strategy based on a transition mechanism between outer control loops on the nested control of a Modular Multilevel Matrix Converter drive with the aim to improve the Power Loss Ride-Through performance through keeping the energy store station uniform and stable. Simulation results obtained using PLECS software are presented to validate the effectiveness of the proposed control strategy.

The adjustment of the DC-link voltage in proportion to the speed, except at very-low frequencies, can potentially overcome torque limitations in MMC-based AC motor drives. However, the grid- and motor-side converter require be equipped with FB cells. To reduce this requirement, this work proposes the use of Hybrid MMC converters. To further improve performance at very-low frequencies, it is proposed that the intermediate link, between the grid- and motor-side converter, be operated as AC link, instead of DC-link, but only at low speed. An AC link voltage having a relatively small amplitude and frequency, compared to nominal values of the motor, is sufficient to maintain the ripple as low as that of the nominal speed. Results shows that 50% and 25%, of the total number of cells in the grid- and motor-side converter, respectively, are required to be of the FB type. This may be a practical solution for medium power drives that require to operate at very-low frequencies without torque restrictions.

This paper presents a novel control strategy for the cascaded MMC for drive applications. The injection of high frequency circulating currents along with high frequency common-mode voltage is a frequent control strategy for the MMC in drive applications. However, this approach induces a voltage across the machine shaft and it will shorten the lifespan of the machine bearings. This paper proposes a novel control strategy to cancel the common-mode voltage seen by the machine using the cascaded MMC. Simulations results are presented to show the performance of the proposed controller.

This paper proposes a distributed control scheme for the economic dispatch of islanded AC microgrids. The control goal is the economical power-sharing of distributed generators considering the marginal cost of active and reactive power. The controller is developed in a finite-time protocol over a droop-free strategy, without restoration needs for frequency. Simulations through the software PLECS are provided for validation purposes; they show adequate behaviour of the controllers under impact loads and plug & play operation.

Cascaded H-bridge converters are widely used in the implementation of medium voltage static synchronous compensators (STATCOMs). This is because of the advantages of relatively high-power density and the improved utilisation of low-voltage semiconductor devices. Major concerns with this topology are (i) to ensure a proper balance of the individual DC capacitor voltage in its cells, and (ii) the balancing of the average DC voltage between its clusters. In the research literature, these issues are typically addressed by using centralised control approaches, meaning that both an extensive processing capability and multiple digital outputs and communication channels for the switching signals are required, increasing system complexity. In contrast to this trend, in this paper, a distributed control scheme based on a consensus algorithm is proposed to deal with these issues in a three-phase STATCOM based on a cascaded H-bridge converter. The main advantages of the proposed control scheme are: (i) it does not require a centralised controller, since the cells work autonomously in a cooperative fashion to achieve voltage regulation, distributing the control effort among the cells, and (ii) it increases the fault tolerance of the converter and thus, the reliability of the system by adequately considering its redundancy. Extensive simulation work is provided to validate this proposal, and the characteristics described above.

This paper proposes a distributed controller for the incremental cost regulation of DC MGs. The strategy aims to reduce the operation costs of distributed generators in the short time-scale, using finite-time algorithms with second-order dynamics in a consensus protocol. From economic dispatch formulation, an equalisation of the incremental cost and its rate-of-change is yielded by the distributed protocol. The second-order protocol performs the consensus of shared local measurements/estimations of neighbouring generators. The performance is verified via simulations in the software PLECS. A comparison between 1st-order and 2nd-order controllers is made for load changing and Plug & Play operations. Results show a reduction in the setting-times and the overall costs of the MG.

In this paper, a novel control system for the Hexverter-based drive is proposed and analysed. Unlike previously proposed control schemes, the proposed one does not require the information of the machine variables to regulate the converter floating capacitors, as required in high-performance drive applications. The feasibility of the proposed control system is demonstrated by using simulation results of an Hexverter-based drive driving a medium-voltage machine, including the whole frequency range and high starting torque loads.

The Modular Multilevel Matrix Converter is a relatively new power converter topology appropriate for high-power Alternating Current (AC) to AC purposes. Several publications in the literature have highlighted the converter capabilities such as modularity, control flexibility, the possibility to include redundancy, and power quality. Nevertheless, the topology and control of this converter are relatively complex to design and implement, considering that the converter has a large number of cells and floating capacitors. Therefore multilayer nested control systems are required to maintain the capacitor voltage of each cell regulated within an acceptable range. There are no other review papers where the modelling, control systems and applications of the Modular Multilevel Matrix Converter are discussed. Hence, this paper aims to facilitate further research by presenting the technology related to the Modular Multilevel Matrix Converter, focusing on a comprehensive revision of the modelling and control strategies.

This paper describes a flexible testbed of a hybrid AC/DC microgrid developed for research purposes. The experimental setup is composed of 3 AC and 6 DC distributed generator units which are emulated by using three-legs inverters and settable output filters. The microgrid architecture allows to validate control schemes upstream of the modulation stage of each inverter, by using real-time targets and Mat-lab/Simulink interface. Two independent real-time communication networks can be used. The first one is based on optical fibre technology, whereas the second one is an Ethercat communication network. Both of them are used for instrumentation purposes and to implement the primary control level of the microgrid. To implement secondary control schemes into the microgrid (or higher control levels), an additional optical fibre-based network is used, allowing to emulate scenarios with or without communication issues such as latency, data-losses and topology changes. The built microgrid can be splitted into AC-side (3 and/or 4 wires), DC-side and interlinking-side, where both the AC and the DC side can be operated independently, according to the required electrical topology. In this testbed, several control schemes, such as proportional-integral, proportional-resonant or predictive controllers, have been investigated. Realised experimental tests include load changes, plug-and-play and communication issues scenarios.

Modular Multilevel Converters (MMC) are becoming increasingly popular for HVDC applications and in medium voltage grids and drives. On the contrary, in high-speed low-voltage drives MMCs are typically not considered a good option due to their relatively low power density. In this paper, a new topology is proposed, enhancing the MMC by coupling upper and lower arm sub-modules via Dual Active Bridge (DAB) converters, leading to a sensible reduction of the sub-module capacitance whilst keeping low control complexity. The resulting topology is applied to a high-speed low voltage permanent magnet drive, analyzing the drive startup and its practical operation. Finally, the theoretical claims are validated with simulation results.

Uninterruptible power supply units are system formed by power electronics converters to supply sinusoidal voltages to feed critical loads. In this paper, a fixed switching frequency model predictive control strategy is presented for the control of the output voltage in an LC filter connected to a three-level NPC converter. The control objectives of the system are the tracking of the voltage reference and balance of the voltages of the dc-link capacitors. The mathematical model of the converter and the LC filter is developed and the control strategy is explained. Simulation results obtained in the Matlab/Simulink enviroment are presented to validate the control strategy

Introduction: Cancer dependence on glucose metabolism has been recognized as a potential target for the development of new anticancer therapies. Ketogenic low-carbohydrate diet (KD) and aerobic glycolysis is known as a Wartburg effect are two approaches linked by a common aim to reduce cancer glucose metabolism. 2-Deoxy-D-glucose (2-DG) has been shown to inhibit glycolysis and in effect to inhibit glucose metabolism and tumor growth in vitro and in vivo in a wide range of cancer models. Anticancer effects of 2-DG can be impacted by several factors including competition of glucose from the food intake. Ketogenic diet has been proposed as a strategy to inhibit proliferation of cancer cells that are highly dependent on glucose for growth and survival by reducing glucose access from food intake and switch to lipid metabolism. Combination of both approaches seemed to be a logical step to increase overall antitumor effects. Objective: The objective of the study was to determine safe doses of 2-DG in mice fed with KD and determine potential toxic side effects of 2-DG in mice maintained on carbohydrate-reduced vs. regular diet. Methods: Female CD-1 mice were maintained on a regular grain-based or carbohydrates-reduced diet (Research Diets (20 % Kcal Protein, 60 % Kcal Fat, 20 % Kcal carbohydrate). Animals were dosed with 2-DG once a day five times a week by oral gavage (PO) or intraperitoneal (IP) injections. Animals were watched daily for the development of toxicity symptoms. Results: No toxic side effects in mice fed with a regular, chow-base diet and treated orally with 2-DG were noted during the six-week treatment (doses ranged from 0.25 to 2.0 g/kg, five times/week). In the contrary, 2-DG-treaded animals maintained on KD showed dose-dependent toxicity with median survival (MS) 10 and 11 days for 1.0 and 2.0 g/kg respectively. For mice receiving 2-DG at 0.5 g/kg MS was 28 days and only 20% mice died in the group receiving 0.25 g/kg. In separate experiments mice treated with 2-DG orally or by intraperitoneal injections IP (1.5 g/kg) showed similar MS of 11 days. Complete blood count analysis of 2-DG treated animals fed with KD revealed acute thrombocytopenia. Post-mortem analysis of dissected organs indicated the development of acute interstitial pneumonia in treated mice. Conclusion: A highly reproducible toxicity leading to a rapid death of all treated animals maintained on a ketogenic diet was observed for 2-DG at doses 1.0 and 2.0 g/kg administered PO or IP. The same doses appeared to be safe in mice fed with a regular diet. The combination treatment toxic effects include acute thrombocytopenia and acute interstitial pneumonia. Delineation of the exact mechanism of toxicity requires additional studies. This study provides an important insight on the apparent toxicity of 2-DG when combined with the ketogenic diet and should serve as a reference for any future studies aimed to combine the ketogenic diet with inhibitors of glycolysis or other metabolic inhibitors. Citation Format: Rafal Zielinski, Maria Poimenidou, Matthew Khuong, Krzysztof Grela, Roberto Cardenas-Zuniga, Stanislaw Skora, Izabela Fokt, Michael Gagea, Jody Swain, Sigmund Zhou, Waldemar Priebe. Ketogenic diet (KD) and targeting Warburg effect: Apparent toxicity of KD combination with 2-deoxy-D-glucose [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P129.

Introduction. Annamycin (ANN) is a non-cardiotoxic potent topoisomerase II poison structurally resembling doxorubicin (Dox). Specific structural modification altered ANN properties dramatically when compared with Dox. This novel drug also includes high activity against multidrug-resistant (MDR) tumors, unique subcellular distribution, and different tissue-organ distribution. Especially high differences have been noted in the lung uptake when compared with DOX. ANN is formulated in multilamellar liposomes (L-Annamycin, L-ANN), and such formulation additionally contributes to the high ANN lung uptake. Objective. The objective of this study was to reconfirm the unique tissue-organ distribution pattern in rats and explore ANN high lung uptake to target pulmonary sarcoma metastases by assessing the efficacy of L-ANN in the experimental models of lung metastases. Methods. Pharmacokinetics and biodistribution studies of ANN were performed in rats after bolus injection of L-ANN, free ANN, and Dox. Detection of Dox and ANN in plasma and different organs was accomplished using LC/MS/MS. In vivo efficacy was tested in two experimental lung metastatic models. The tumors were established by intravenous injection of MCA205 or K7M3 cells. The treatment consisted of weekly intravenous injections of 4 mg/kg of L-ANN or Dox. Metastatic nodules were visualized by computer tomography or bioluminescent imaging (BLI). Results. Pharmacokinetic and tissue-organ distribution of L-ANN in rats confirmed unusually high uptake of ANN in lungs: the Cmax of ANN was 30-fold higher than Dox after bolus administration of L-ANN or Dox. A remarkable extension of the survival was observed in two syngeneic sarcoma lung metastasis models. In the MCA205 fibrosarcoma model, the median survival of L-ANN treated mice was 87.5 days vs. 21 days for the vehicle-treated mice (p Citation Format: Rafal Zielinski, Krzysztof Grela, Roberto Cardenas-Zuniga, Stanislaw Skora, Izabela Fokt, Maria Poimenidou, Salah-Eddine Lamhamedi-Cherradi, Joseph Ludwig, Waldemar Priebe. Annamycin, a novel non-cardiotoxic anthracycline with high activity against sarcomas metastatic to lungs [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P218.

Introduction: Annamycin (ANN) is a non-cardiotoxic potent topoisomerase II poison that is structurally related to doxorubicin (Dox) but it displays significantly different biological properties. ANN is formulated in multilamellar liposomes to enable effective in vivo administration as L-ANN. Pancreatic ductal adenocarcinoma (PDAC) represents a major challenge and is the deadliest cancer in decades. Pancreas drug uptake and retention remains a significant factor contributing to the chemoresistance of PDAC. Additionally, drug resistance on a cellular level further limits the therapeutic options for pancreatic cancer patients. Based on unique biological properties, we select L-ANN for detailed characterization of anti-tumor potency in preclinical PDAC models. Objective: The objective of this study was to validate the L-ANN exceptional uptake in pancreatic cancer cells and tumors and explore its high pancreas uptake to target PDACs by assessing the efficacy of L-ANN in the preclinical mouse models. Methods: The uptake, cytotoxicity, and L-ANN-induced apoptosis were studied in human MDA-PATC50 and MDA-PATC53 cell lines. L-ANN pharmacokinetics and tissue-organ distribution were analyzed in CD-1 mice after bolus administration of L-ANN, ANN or DOX. Subcutaneous and orthotopic MDA-PATC50 and MDA-PATC53 mouse models were used to assess activity of L-ANN in vivo. Results: Fluorescent microscopy and FACS analysis showed significantly higher uptake of ANN in MDA-PATC50 and MDA-PATC53 when compared to DOX-treated cells. Interestingly, ANN displayed distinct subcellular distribution with predominantly cytosolic localization. Average IC50 of ANN or DOX treated MDA-PATC50 and MDA-PATC53 cells were 25.1 nM and 41.9 nM for ANN and 32.8 nM and 130.4 nM for DOX respectively (72h exposure). Biodistribution study showed rapid L-Ann absorption in the pancreas. The Cmax of L-Ann was 15-fold higher than Dox after administration of L-ANN or Dox (both at 4 mg/kg) in pancreatic tissue. The subcutaneous models demonstrated dose-dependent reduction in tumor volumes after 3 doses of L-Ann in both PDAC models. Additionally, efficacy of L-ANN was assessed in two orthotopic PDAC models. MRI confirmed tumor volume reduction in L-Ann 3 mg/kg and 4 mg/kg doses in MDA-PATC50 model (p Citation Format: Ya'an Kang, Rafal Zielinski, Roberto Cardenas Zuniga, Radjendirane Venugopal, Maria Poimenidou, Magdalena Remiszewski, Shaohua Peng, Edd Felix, Krzysztof Grela, Stanislaw Skora, Van N. Nguyen, Izabela Fokt, Waldemar Priebe. High uptake, retention, and in vivo activity of L-Annamycin in pancreatic cancer models [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-066.

As part of our drug discovery program, we have developed structure-based modular designs of unique DNA-binding agents. The approach combines DNA intercalating and DNA “minor-groove-binding” modules. We have discovered compound WP1244 that potentially binds up to 10 bp long sequences of DNA. The unique and intriguing feature of WP1244 is its high CNS uptake combined with the picomolar to low nanomolar cytotoxicity against ependymoma and glioblastoma multiforme (GBM) cell lines and demonstrated in vivo activity in the orthotopic model of GBM. To improve water solubility and develop an IV formulation, we have synthesized WP1874, a mesylate salt of WP1244, and initiated its preclinical characterization. WP1874, similarly to its parental compound, shows high cytotoxicity in ependymoma, GBM, and medulloblastoma cell lines with IC50 in low nanomolar range and it was up to 100 to 200 times more potent than doxorubicin. Interestingly, WP1874 does not appear to be cytotoxic against normal kidney cells (VeroC1008) with IC50 > 10 μM. Preliminary pharmacokinetic and biodistribution studies performed in CD-1 mice with intact brains revealed enhanced penetration of WP1874 to the brain with Cmax 1.5-fold greater than in plasma. Respectively, WP1874 Cmax in the brain was 2.3 ug/g (~2.0 μM) vs. 1.5 μg/ml (1.3 μM) in plasma. Acute toxicity in intravenously administered WP1874 was LD50 >15mg/kg. No mortalities or any apparent toxicity symptoms were recorded for six intravenous weekly doses of WP1874 at 2.5 or 5 mg/kg in CD-1, Balb/c, or nude athymic mice. Intraperitoneal administration was well-tolerated up to 5 mg/kg given three times a week for four cycles. High CNS uptake, excellent cytotoxicity against different brain cancer cell lines, and low toxicity in vivo and in vitro against normal cells warrant further investigation of WP1874 as a mechanically unique potential anticancer agent against CNS malignancies.