Low-Power Instrument Transformers (LPITs) are becoming the first choice for distributed measurement systems for medium voltage networks. However, there are still a lot of challenges related to their ...operation. Such challenges include their accuracy variation when several influence quantities are acting on them. Among the most significant influence quantities are temperature, electromagnetic field, humidity, etc. Another aspect that increases the importance of studying the LPITs' accuracy behavior is that, once installed, they cannot be calibrated for several years; hence, one cannot compensate for in-field conditions. Hence, this work aims at introducing a simple type test for a specific LPIT, the Rogowski coil. First, an experimental setup to assess the effect of temperature, humidity, and positioning on the power quality accuracy performance of the Rogowski coil is described. Second, from the results and the experience of the authors it has been possible to design a specific type test. The test has the aim of finding the limits of the accuracy variations of a single Rogowski coil. Afterwards, such limits can be used to compensate for the in-field measurements, obtaining an overall higher accuracy. The results of this work may contribute to the always-evolving standardization work on LPITs.
Multiple Myeloma (MM) is a hematological cancer characterized by proliferation of malignant plasma cells in the bone marrow (BM). MM represents the second most frequent hematological malignancy, ...accounting 1% of all cancer and 13% of hematological tumors, with ~9,000 new cases per year. Patients with monoclonal gammopathy of undetermined significance (MGUS) and asymptomatic smoldering MM (SMM) usually evolve to active MM in the presence of increased tumor burden, symptoms and organ damage. Despite the role of high dose chemotherapy in combination with autologous stem cell transplantation and the introduction of new treatments, the prognosis of MM patients is still poor, and novel therapeutic approaches have been tested in the last years, including new immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies (mAbs). CD38 is a glycoprotein with ectoenzymatic functions, which is expressed on plasma cells and other lymphoid and myeloid cell populations. Since its expression is very high and uniform on myeloma cells, CD38 is a good target for novel therapeutic strategies. Among them, immunotherapy represents a promising approach. Here, we summarized recent findings regarding CD38-targeted immunotherapy of MM in pre-clinical models and clinical trials, including (i) mAbs (daratumumab and isatuximab), (ii) radioimmunotherapy, and (iii) adoptive cell therapy, using chimeric antigen receptor (CAR)-transfected T cells specific for CD38. Finally, we discussed the efficacy and possible limitations of these therapeutic approaches for MM patients.
Power system stability is a task that every system operator (SO) is required to achieve daily to ensure an uninterruptible power supply. Especially at the transmission level, for each SO it is of ...utmost importance to ensure proper exchange of information with other SOs, mainly in case of contingencies. However, in the last years, two major events led to the splitting of Continental Europe into two synchronous areas. These events were caused by anomalous conditions which involved in one case the fault of a transmission line and in the other a fire outage in proximity to high-voltage lines. This work analyzes these two events from the measurement point of view. In particular, we discuss the possible impact of estimation uncertainty on control decisions based on measurements of instantaneous frequency. For this purpose, we simulate five different configurations of phasor measurement units (PMUs), as characterized by different signal models, processing routines, and estimation accuracy in the presence of off-nominal or dynamic conditions. The objective is to establish the accuracy of the frequency estimates in transient conditions, more specifically during the resynchronization of the Continental Europe area. Based on this knowledge, it is possible to set more suitable conditions for resynchronization operations: the idea is to consider not only the frequency deviation between the two areas but also to take into account the respective measurement uncertainty. As confirmed by the analysis of the two real-world scenarios, such an approach would allow for minimizing the probability of adverse or even dangerous conditions such as dampened oscillations and inter-modulations.
Power quality evaluation is the process of assessing the actual power network parameters with respect to the ideal conditions. However, several new assets and devices among the grid include mining ...the voltage and current quality. For example, the power converters needed for renewable energy sources' connection to the grid, electric vehicles, etc., are some of the main sources of disturbances that inject high-frequency components into the grid. Consequently, instrument transformers (ITs) should be capable of measuring distorted currents and voltages with the same level of accuracy guaranteed for the ideal frequency (50-60 Hz). This is not a simple task if one considers that several other influence quantities endlessly act on the ITs. To this purpose, considering the lack of a standard, this work presents a measurement setup and specific tests for testing a commonly used type of low-power current transformer, the Rogowski coil (RC). In particular, the accuracy performance (ratio error and phase displacement) of the RCs was evaluated when measuring distorted signals while other influence quantities affected the RCs. Such quantities included positioning, burden, and magnetic field. The results indicate which quantities (or combination of them) have the greatest effect on the RC's accuracy performance.
The use of capacitive dividers (CDs) in medium-voltage (MV) networks started as simple voltage detectors and as rough voltage measurement instruments for protective purposes. Now, with the spread of ...intelligent electronic devices and renewable energy sources at the distribution level, capacitive dividers are designed and installed to perform accurate voltage measurements. Such a requirement is mandatory when the power quality has to be assessed. Therefore, CDs are currently being used either for power frequency or for high-frequency (supraharmonic- or partial-discharge-level) measurements. In this paper, typical off-the-shelf CDs are studied and modeled to understand how they behave in a wide range of frequencies and when the temperature varies. To this purpose, specific setups and tests have been developed and performed. From the results, it is clear that with proper modeling of CDs, it is possible to exploit them for measuring phenomena in a wide range of frequencies, including the effects due to temperature variations and self-resonances.
In recent years, the introduction of real-time simulators (RTS) has changed the way of researching the power network. In particular, researchers and system operators (SOs) are now capable of ...simulating the complete network and of making it interact with the real world thanks to the hardware-in-the-loop (HIL) and digital twin (DT) concepts. Such tools create infinite scenarios in which the network can be tested and virtually monitored to, for example, predict and avoid faults or energy shortages. Furthermore, the real-time monitoring of the network allows estimating the status of the electrical assets and consequently undertake their predictive maintenance. The success of the HIL and DT application relies on the fact that the simulated network elements (cables, generation, accessories, converters, etc.) are correctly modeled and characterized. This is particularly true if the RTS acquisition capabilities are used to enable the HIL and the DT. To this purpose, this work aims at emphasizing the role of a preliminary characterization of the virtual elements inside the RTS system, experimentally verifying how the overall performance is significantly affected by them. To this purpose, a virtual phasor measurement unit (PMU) is tested and characterized to understand its uncertainty contribution. To achieve that, firstly, the characterization of a virtual PMU calibrator is described. Afterward, the virtual PMU calibration is performed, and the results clearly highlight its key role in the overall uncertainty. It is then possible to conclude that the characterization of the virtual elements, or models, inside RTS systems (omitted most of the time) is fundamental to avoid wrong results. The same concepts can be extended to all those fields that exploit HIL and DT capabilities.
Multiple myeloma (MM) is a hematologic malignancy characterized by the accumulation of bone marrow (BM) clonal plasma cells, which are strictly dependent on the microenvironment. Despite the ...improvement of MM survival with the use of new drugs, MM patients still relapse and become always refractory to the treatment. The development of new therapeutic strategies targeting both tumor and microenvironment cells are necessary. Oncolytic virotherapy represent a promising approach in cancer treatment due to tumor-specific oncolysis and activation of the immune system. Different types of human viruses were checked in preclinical MM models, and the use of several viruses are currently investigated in clinical trials in MM patients. More recently, the use of alternative non-human viruses has been also highlighted in preclinical studies. This strategy could avoid the antiviral immune response of the patients against human viruses due to vaccination or natural infections, which could invalid the efficiency of virotherapy approach. In this review, we explored the effects of the main oncolytic viruses, which act through both direct and indirect mechanisms targeting myeloma and microenvironment cells inducing an anti-MM response. The efficacy of the oncolytic virus-therapy in combination with other anti-MM drugs targeting the microenvironment has been also discussed.
The importance of glutamine (Gln) metabolism in multiple myeloma (MM) cells and its potential role as a therapeutic target are still unknown, although it has been reported that human myeloma cell ...lines (HMCLs) are highly sensitive to Gln depletion. In this study, we found that both HMCLs and primary bone marrow (BM) CD138+ cells produced large amounts of ammonium in the presence of Gln. MM patients have lower BM plasma Gln with higher ammonium and glutamate than patients with indolent monoclonal gammopathies. Interestingly, HMCLs expressed glutaminase (GLS1) and were sensitive to its inhibition, whereas they exhibited negligible expression of glutamine synthetase (GS). High GLS1 and low GS expression were also observed in primary CD138+ cells. Gln-free incubation or treatment with the glutaminolytic enzyme l-asparaginase depleted the cell contents of Gln, glutamate, and the anaplerotic substrate 2-oxoglutarate, inhibiting MM cell growth. Consistent with the dependence of MM cells on extracellular Gln, a gene expression profile analysis, on both proprietary and published datasets, showed an increased expression of the Gln transporters SNAT1, ASCT2, and LAT1 by CD138+ cells across the progression of monoclonal gammopathies. Among these transporters, only ASCT2 inhibition in HMCLs caused a marked decrease in Gln uptake and a significant fall in cell growth. Consistently, stable ASCT2 downregulation by a lentiviral approach inhibited HMCL growth in vitro and in a murine model. In conclusion, MM cells strictly depend on extracellular Gln and show features of Gln addiction. Therefore, the inhibition of Gln uptake is a new attractive therapeutic strategy for MM.
•Myeloma cells produce ammonium in the presence of glutamine, showing high glutaminase and low glutamine synthetase expression.•Myeloma cells show high expression of glutamine transporters and inhibition of ASCT2 transporter hinders myeloma growth.
Human myeloma cells express CD38 at high levels and grow in hypoxic niches inside the bone marrow. Myeloma cells respond to hypoxia with metabolic changes leading to aerobic glycolysis, thus reducing ...ATP and increasing NAD
. Our hypothesis is that these conditions favor the enzymatic pathways involved in the production of adenosine in the niche. Within the niche, NAD
is able to activate a discontinuous adenosinergic pathway that relies upon CD38, CD203a, and CD73 or TRACP, according to the environmental pH. The observed variability in adenosine concentrations in bone marrow aspirates is a result of the interactions taking place among myeloma and other cells in the bone marrow niche. A pilot study showed that adenosine profiles differ during disease progression. Adenosine levels were significantly higher in the bone marrow plasma of patients with symptomatic myeloma and correlated with ISS staging, suggesting that adenosine is produced in the myeloma niche at micromolar levels by an ectoenzymatic network centered on CD38. Adenosine levels increase with disease aggressiveness, a finding that supports adenosine as a potential marker of myeloma progression.
Summary
A deep elucidation of the mechanisms of action of anti‐CD38 monoclonal antibodies (mAbs), such as daratumumab (DARA), is required to identify patients with multiple myeloma (MM) who are more ...responsive to this treatment. In the present study, an autologous ex vivo approach was established, focussing on the role of the monocytes in the anti CD38‐mediated killing of MM cells. In bone marrow (BM) samples from 29 patients with MM, we found that the ratio between monocytes (CD14+) and MM cells (CD138+) influences the response to DARA. Further, the exposure of the BM samples to DARA is followed by the formation of a CD138+CD14+ double‐positive (DP) population, that quantitatively correlates with the anti‐MM cells killing. These effects were dependent on the presence of a CD14+CD16+ monocyte subset and on high CD16 expression levels. Lastly, the addition of a mAb neutralising the CD47/signal‐regulatory protein α (SIRPα) axis was able to increase the killing mediated by DARA. The effects were observed only in coincidence with high CD14+:CD138+ ratio, with a significant presence of the DP population and were correlated with CD16 expression. In conclusion, the present study underlines the critical role of the CD16+ monocytes in DARA anti‐MM killing effects and gives a rationale to test the combination of an anti‐CD47 mAb with anti‐CD38 mAbs.
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