Line Expansion Research Articles

Effects of field line expansion on Alfvén waves and vortices

Context. Simulations and observations of the solar atmosphere often reveal the presence of torsional Alfvén waves and vortices with sufficient power to heat the solar corona and accelerate the solar wind. Aims. We challenge the long-held view that low-frequency Alfvén waves are suppressed due to inhomogeneities and steep spatial gradients in the atmosphere. Alfvén waves and vortices in a stratified solar atmosphere are modelled with the aim of calculating and comparing their energy flux for different field line geometries. Methods. We show that the general problem of linear Alfvén wave propagation along field lines of arbitrary geometry can be reduced to a set of Klein–Gordon equations for the perturbations of the magnetic field and velocity. Solutions and corresponding energy fluxes are constructed for three cases with different expansion rates of the field lines in the lower atmosphere. Results. Expansion rates that are associated with cut-off free propagation in the lower atmosphere suppress the perturbation amplitudes and the corresponding energy flux. These include the uniform field model and the thin flux tube model. A counterexample with an intermediate field line expansion rate and non-vanishing cut-offs exhibits consistently large perturbation amplitudes and unrestricted energy flux across the entire frequency spectrum. Conclusions. Field lines with different expansion rates and geometries in the lower atmosphere can significantly alter the amplitudes of the Alfvén waves and vortices and the extent of the energy flux entering the corona.

A cooperative approach for generation and lines expansion planning in microgrid‐based active distribution networks

AbstractWith the growth of the load in the electricity networks, sufficient investment in the generation and lines expansion should be made in order to provide the energy needed by consumers with the lowest possible investment and operation costs. This issue is especially important in distribution networks, which are faced with the uncertainties of renewable energy generation and the development of microgrids and related issues.In this article, the planning of generation and lines expansion has been modeled with the aim of minimizing the total costs of microgrids, based on the cooperative approach. For this purpose, a bi‐level model has been developed; on the upper level, microgrids make investment decisions with a cooperative approach, and a constrained stochastic formulation has been developed with considering operational uncertainties on the lower level. Also, in this article, in order to ensure the supply of critical loads in island conditions, the self‐sufficiency index is defined. Three case studies have been considered to ensure the effectiveness of the developed model. In case 1, each microgrid will be able to supply its load only by generating of its units and purchasing from the retail market. In case 2, the possibility of trading with other microgrids in a non‐cooperative approach will also be available to the microgrids operators, and in case 3, microgrids can exchange energy with other microgrids in a cooperative manner. The simulation results showed that due to the possibility of using nearby microgrid resources, the cost of microgrid load supply in case 2 was reduced by 4.84% compared to case 1. Also, this cost in case 3 was reduced by 5.23% and 0.38%, respectively, compared to cases 1 and 2, due to the use of a cooperative manner in microgrid load providing.

Autonomous Control of Voltage and Frequency in Parallel Inverters of Microgrid

Integration of Distribution Generations (DGs) provides flexibility in power transmission. DGs reduce expenditure, expansion of transmission lines and transmission loss. DGs can work separately from the main grid with local loads and form a microgrid. In grid-connected mode, the voltage and frequency of the microgrid are regulated by the main grid. Voltage and frequency regulation in the islanding microgrid are crucial. This paper presents voltage and frequency control techniques for parallel inverters in microgrid. The proposed model works on close loop control of inverters and it can be used for plug-and-play operation of microgrid. The Microgrid model is developed in MATLAB/Simulink and the performance of the system is analyzed in grid-connected mode and isolation mode.

Energy expansion planning with a human evolutionary model

This study presents a novel method for planning the expansion of transmission lines and energy storage systems while considering the interconnectedness of electricity and gas networks. We developed a two-level stochastic planning model that addresses both the expansion of transmission and battery systems in the electrical grid and the behavior of the gas network. This research explores the challenges and effects of integrating high levels of renewable energy sources while ensuring security within both networks. Our model uses a stochastic mixed-integer non-linear programming approach. To solve this complex model, we applied the Human Evolutionary Model (HEM). We tested our approach on two case studies: a simple 6-node network and the more complex IEEE RTS 24-bus network for the electricity grid, combined with 5-node and 10-node gas networks, respectively. The results demonstrate the effectiveness of our model, particularly in scenarios where connections in the power and gas networks are disrupted, preventing load shedding even when integrated network connections are cut.

Synthesis of Tetrahedrite Zincian Nanocomposites via solvothermal process at low temperature

This study presents a novel hydrothermal method for synthesizing Cu11Zn1Sb4S13 (tetrahedrite, zincian) nanoparticles at a low temperature of 185 °C for a 6 h annealing at 400 °C for 2 h. CuCl2, ZnCl2, SbNO3, and CH4N2S, and NaBH4 were used for the innovative synthesis of Cu11Zn1Sb4S13 (Tetrahedrite, Zincian) Copper Zinc Antimony Sulfide nanoparticles ink. Structural, morphological and optical properties (optical energy gap) were studied for thin-film Cu11Zn1Sb4S13 deposited the nanoparticles via drop-casting method onto glass substrates are investigated. The structure and characterization of Cu11Zn1Sb4S13 by XRD powder diffraction provide evidence for a cubic structure. The optical calculations indicate that the absorption coefficient (α > 104 cm−1) and optical energy gap Eg are equivalent to 1.68 eV. Comparative work of Crystalline diameters of synthesis was obtained from XRD diffraction powder. The Debye-Scherrer procedure, modified Scherrer procedure and Williamson–Hall inspection are used to examine the individual participatory of the crystalline diameters, lattice stress and dislocation to isotropic line expansion widening reflection peaks of Cu11Zn1Sb4S13 nanoparticles. The modified Scherrer approach is appropriate, with all points along the fitting line. The crystallite size estimated from XRD was 5.798 nm and the particle size calculated from the FESEM method 8–9 nm. This slight difference reflects a spherical shape of the nanoparticles.

Analysis of an Al-Sn-Cu alloy by calibration-free laser-induced breakdown spectroscopy under varying sample temperature conditions

This study investigates the impact of sample temperature Ts on Laser-Induced Breakdown Spectroscopy (LIBS) emission characteristics and Calibration-Free LIBS (CF-LIBS) quantitative analysis in vacuum and air. Using an aluminum‑tin‑copper alloy, we analyze spectral lines within a 20 °C to 170 °C temperature range. Evaluation encompasses emission line intensities, plasma parameters, expansion imagery, and laser ablation crater morphologies. CF-LIBS analysis underlines that elevated Ts maintains quantitative accuracy even for minor elements with weak lines. In atmospheric conditions, tin segregation occurs, yet CF-LIBS remains robust. These results highlight CF-LIBS's potential for varied applications by mitigating Ts-induced effects.

The Role Of Business Diversification, Education And Development Activities On Business Performance Of Construction Companies Listed In Indonesian Stock Exchange

The aim of this research is to analyze the development of companies in the capital market, especially in the accounting aspect. The companies in this study consist of a large number of subsidiaries, associated companies, and multi-group companies. This is an applied study that uses developments in accounting doctrine, particularly those that influence balance sheet analysis, comparison of financial statements over time, and ratios. The analysis results indicate an increase in stock prices, followed by a general decline the following year, likely due to changes in the economic cycle. Regarding the debt situation, there has been a significant increase. Despite this, increases continued, reaching figures that would be difficult to maintain in the future. The following year, the figure decreased due to the crisis and the disinvestment process mentioned earlier. From this analysis, it appears that the construction group experienced significant challenges in managing their debt and assets over the period, which is reflected in their share price movements, turnover, and results. The composition and variations of the group's balance sheet showed major changes during the period, mainly due to the expansion of lines of activity that required large investments in permanent structures. This situation is unsustainable and requires significant disinvestment. This shows that the capital and financial management of these groups play a very important role in maintaining the stability and growth of their companies. Additionally, we must carefully make investment decisions and manage debt to avoid creating unwanted risks in the future.

Multifactorial evolutionary algorithm for optimal reconfiguration capability of distribution networks

Most existing studies on distribution network reconfiguration (DNRC) are predominantly based on a fixed initial topology and optimize switch operations to achieve various objectives, without considering the flexible allocation of backup lines. This paper proposes a novel problem of optimizing the reconfiguration capability of distribution networks (DNs) by considering the expansion of power lines under resource constraints. The reconfiguration capability reflects the ability of a DN to respond to uncertainties and disturbances by adjusting its topology. A novel metric based on the number of spanning trees is proposed to quantify the reconfiguration capability of a DN. Moreover, an optimization model is formulated to maximize the reconfiguration capability of a DN subject to resource constraints on line expansions. To solve this model efficiently, a multifactorial evolutionary algorithm (MFEA) is developed, which can optimize multiple tasks with different expansion line quantities simultaneously by exploiting knowledge transfer across tasks. The proposed metric, model, and algorithm are validated on two case studies using the IEEE 33-bus and 70-bus test systems, and the results show their effectiveness and superiority over existing methods.

Synergies and competition: Examining flexibility options in the European electricity market

The electricity market transitions from a market clearing in which flexible generation meets inflexible demand to one in which inflexible generation meets flexible demand. Consequently, new types of flexibility are needed to balance generation and demand. This paper mainly aims to analyse competition and synergy between various flexibility options in the electricity market. The developed European electricity market model maximises the joint socio-economic welfare of the electricity and the hydrogen market. Transmission grid,- storage expansion, electric vehicle demand side flexibility and hydrogen sector coupling are flexibility options. This work examines the implementation of different flexibility options in the bidding zones Austria and Germany. Austria, with a very high storage capacity in the alpine arc and Germany, with massive wind turbine capacities serve as representative case study. Results show that the storage location heavily influences the corresponding socio-economic welfare increase. Hence, location-dependent synergy and competition between storage and transmission line expansion can occur. In contrast, sector coupled hydrogen production and storage expansion compete with each other as both will reduce very low electricity prices. Demand-side flexibility primarily benefits end-users while producer surplus reduces. In combination with storage expansion, further positive synergistic effects for end-users occur. The combination of storage expansion and demand-side flexibility can replace transmission line expansion and vice versa if used comprehensively. Further efforts could address the evaluation of these effects if the individual flexibility providers aim for something other than a system-wide but individual optimum.

Compound 225# inhibits the proliferation of human colorectal cancer cells by promoting cell cycle arrest and apoptosis induction.

Colorectal cancer (CRC) ranks as the second leading cause of cancer‑related death worldwide due to its aggressive nature. After surgical resection, >50% of patients with CRC require adjuvant therapy. As a result, eradicating cancer cells with medications is a promising method to treat patients with CRC. In the present study, a novel compound was synthesized, which was termed compound 225#. The inhibitory activity of compound 225# against CRC was determined by MTT assay, EdU fluorescence labeling and colony formation assay; the effects of compound 225# on the cell cycle progression and apoptosis of CRC cells were detected by flow cytometry and western blotting; and the changes in autophagic flux after the administration of compound 225# were detected using the double fluorescence fusion protein mCherry‑GFP‑LC3B and western blotting. The results demonstrated that compound 225# exhibited antiproliferative properties, inhibiting the proliferation and expansion of CRC cell lines in a time‑ and dose‑dependent manner. Furthermore, compound 225# triggered G2/M cell cycle arrest by influencing the expression of cell cycle regulators, such as CDK1, cyclin A1 and cyclin B1, which is also closely related to the activation of DNA damage pathways. The cleavage of PARP and increased protein expression levels of PUMA suggested that apoptosis was triggered after treatment with compound 225#. Moreover, the increase in LC3‑II expression and stimulation of autophagic flux indicated the activation of an autophagy pathway. Notably, compound 225# induced autophagy, which was associated with endoplasmic reticulum (ER) stress. In accordance with the in vitro findings, the in vivo results demonstrated that compound 225# effectively inhibited the growth of HCT116 tumors in mice without causing any changes in their body weight. Collectively, the present results demonstrated that compound 225# not only inhibited proliferation and promoted G2/M‑phase cell cycle arrest and apoptosis, but also initiated cytoprotective autophagy in CRC cells by activating ER stress pathways. Taken together, these findings provide an experimental basis for the evaluation of compound 225# as a novel potential medication for CRC treatment.

A δ-free approach to quantization of transmission lines connected to lumped circuits

The quantization of systems composed of transmission lines connected to lumped circuits poses significant challenges, arising from the interaction between continuous and discrete degrees of freedom. A widely adopted strategy, based on the pioneering work of Yurke and Denker, entails representing the lumped circuit contributions using Lagrangian densities that incorporate Dirac δ-functions. However, this approach introduces complications, as highlighted in the recent literature, including divergent momentum densities, necessitating the use of regularization techniques. In this work, we introduce a δ-free Lagrangian formulation for a transmission line capacitively coupled to a lumped circuit without the need for a discretization of the transmission line or mode expansions. This is achieved by explicitly enforcing boundary conditions at the line ends in the principle of least action. In this framework, the quantization and the derivation of the Heisenberg equations of the network are straightforward. We obtain a reduced model for the lumped circuit in the quantum Langevin form, which is valid for any coupling strength between the line and the lumped circuit. We apply our approach to an analytically solvable network consisting of a semi-infinite transmission line capacitively coupled to an LC circuit and study the behavior of the network as the coupling strength varies.

Abstract 6781: Maintaining the tumor microenvironment: Serum-free cell culture for an advanced 3D in vitro tissue model

Abstract Cancer research has made significant progress in recent years, especially in the field of immunotherapy that uses immune modulators. A significant portion of these novel therapeutic strategies focuses on manipulating the tumor microenvironment (TME). The TME is a complex structure that comprises various cellular elements, including cancer cells, immune cells, and structural components, such as secreted factors and extracellular matrix proteins. However, replicating the human TME in experimental murine models has proved challenging. Therefore, researchers have started to develop ex vivo cultivation protocols of tumor tissues, particularly precision-cut slices (PCS), that offer a three-dimensional representation of the TME. It is essential to select the best culture conditions to ensure the preservation of the TME that closely resembles the in vivo conditions. To further this research, a serum-free cell culture medium has been developed to propagate primary epithelial tumor cells originating from pancreatic, renal, and ovarian tissues. The optimized media formulation was successfully employed in the derivation and expansion of tumor cell lines, sourced from both primary and xenotransplanted tumors. An additional serum-free cell culture medium has been designed to cultivate primary lung cancer cells. Suitable culturing conditions have been introduced that maintain TME composition ex vivo cultured PCS prepared from fresh non-small cell lung carcinoma (NSCLC) tissue. Lung TumorMACS Medium and a serum-containing medium were compared, and it was found that the cellular composition of PCS cultivated in Lung TumorMACS was comparable to the original composition. At the same time, PCS cultivated in Lung TumorMACS showed a lower expression of stress genes, compared to the serum-containing alternative. Citation Format: Alina Siebenmorgen, Christian Wöhle, Katharina Lamfried, Lilian Martinez Carrera, Bianca Heller, Katharina Lupar, Giovanna Bergamini, Daniel Poeckel, Olaf Hardt, Benjamin Theek. Maintaining the tumor microenvironment: Serum-free cell culture for an advanced 3D in vitro tissue model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6781.

Abstract 4256: Autologous organoids and T cell co-cultures as a powerful personalized platform for immunotherapy development

Abstract Recent advances in cancer immunotherapy have had a positive impact on the life expectancy of patients for an extensive range of clinical indications. With new treatment strategies and druggable targets being identified at an increasing pace, the number of patients eligible for cancer immunotherapy is expected to expand steadily. However, promising therapeutic developments face hurdles in translating preclinical findings into therapy since conventional 2D cancer models hold low clinical predictive value. We developed an innovative alternative, building on the discovery that adult stem cells proliferate and organize into three-dimensional organotypic structures when they are embedded into extracellular matrix. Patient-derived organoids are generated from normal and malignant tissues and stored as high-quality biobanks that yield highly reproducible results. HUB Organoids® recapitulate complex characteristics of the parental tissue, including molecular heterogeneity, as well as morphological and functional traits. Since cancer progression and response to immunotherapy are governed by immune cell interactions in the tumor microenvironment, we developed an assay in which colorectal (CRC) and non-small cell lung cancer (NSCLC) tumor organoids are co-cultured with paired tumor infiltrating lymphocytes (TIL) that are simultaneously expanded as a source of tumor reactive cells. Paired resources allow for the screening of immune-modulatory therapies under physiologic conditions, not depending on peptide-pulsing and alloreactivity. We quantify tumor organoid killing and TILs reactivity by combining imaging-based analysis of apoptotic cells with flow cytometry to measure cytokine release by cytotoxic TILs. Here, we show that our system is robust and reproducible with an establishment rate of 75%, allowing for expansion of TILs that preserve T cell receptor repertoires. First line expansion of both PDO and TIL components can be used to effectively build coculture models and probe the tumor and immune components, respectively. Our system offers a powerful tool for the development and validation of cancer immunotherapy and can help to stratify cancer patients for susceptibility to various types of immunotherapies. We certify that the research use of each of the HBS marked above was conducted according to the expectations of each institution. Citation Format: Claudia Beaurivage, BanuPriya Sridharan, Sumeyra Mucuk, Kimberly Nadwodny, Derek Poore, Anna Schepers, Farzin Pourfarzad, Sylvia F. Boj. Autologous organoids and T cell co-cultures as a powerful personalized platform for immunotherapy development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4256.

Data-driven optimization for seismic-resilient power network planning

Many regions of the planet are exposed to seismic hazards that can cause devastating consequences on power systems. Due to these systems’ crucial role, the evaluation and planning for their safe and reliable operation are paramount. This paper develops a novel data-driven optimization framework to assess the power network’s seismic resilience and plan cost-effective investments for its enhancement. Under a robust optimization scheme, an earthquake attacker–defender model finds the worst-case realization of random earthquake network contingencies within an uncertainty set defined with a large number of scenarios generated by state-of-the-art engineering methods. Moreover, data-driven stochastic-robust optimization is employed in a two-stage seismic-resilient power network planning model, leveraging multiple seismic sources’ distributional information. Transmission line expansions and siting and sizing of battery energy storage systems are decided in the first stage, while the second stage decides operational variables. Experiments on a 281-node Chilean power system provide insights for seismic-resilient planning and demonstrate the efficiency of the proposed approach.

Advanced Framework for Integrating Risks into an Organizational Setting

The phrase "Industry 4.0" refers to the fourth wave of industrial change, which includes areas like smart cities that aren't often thought of as stand-alone industrial applications. Water power, steam power, and mechanization were all introduced during the start of the first industrial revolution. The second industrial revolution that followed was marked by the expansion of mass production and assembly lines made possible by the use of electricity. The third industrial revolution was sparked by the development of electronics, information technology, and automation. This was followed by the fourth industrial revolution, which was defined by the appearance of systems of cyber-physical. The goal of the scientific discipline of human performance is to increase a system's overall performance as well as the wellbeing of the people who are a part of it. A comprehensive search yielded a total of 336 scholarly papers, out of which 37 were examined using a human-centered system of work paradigm as described in the body of HFE literature. Within the frames of the macro- and microergonomics work system paradigms, difficulties related to technological growth were analyzed. We outline the essential components of an organizational maturity model using the study that was done. Within the unique context of the manufacturing industry's fast technological improvements, this model seeks to improve the overall performance of sociotechnical work system.

A coordinated planning model for power system source-network-load-storage considering multiple types of energy storage

Conventional power systems often neglect the amalgamation of planning and scheduling during their preparatory phases, and their methodologies of construction and operation may fall short of the requisites posed by a future characterized by a high proportion of renewable energy integration. In this paper, an integrated planning and scheduling methodology has been developed for the source-network-load-storage power system, factoring in a diverse array of energy storage modalities. Initially, cost models and operational models are formulated encompassing unit retrofitting, line expansion, demand response (DR), energy storage configuration and operation, and penalties related to solar curtailment. Subsequently, the optimization functions and operational constraints of each facet are harmonized, culminating in a comprehensive coordinated planning and scheduling framework for the ‘source-network-load-storage’ power system. The final phase involves simulation analysis conducted on an IEEE-30 nodes power system case. Results illustrate that the integrated ‘source-network-load-storage’ approach exhibits varied efficacies in exploiting system flexibility resources, contingent upon the distinctive capacity-power configurations of multiple types of energy storage. Prudent calibration of energy storage parameters demonstrates the potential to mitigate network underutilization and enhance overall system economics. This corroborates the viability of the proposed ‘integrated planning and scheduling’ model for the power systems.

A multi-scenario evaluation of the energy transition mechanism in the Philippines towards decarbonization

The Philippines relies heavily on fossil fuels for energy, posing environmental issues. To counter this, the study suggests increasing the use of renewable energy sources like wind and solar power. By optimizing the electricity supply mix, the study shows that coal usage can be reduced by 37.23%, with solar power accounting for 20.07% and wind power accounting for 8.83% without using Battery Energy Storage System (BESS). By incorporating Battery Energy Storage Systems (BESS) and scaling up the utilization of solar and wind power, which is aligned with the country's 2030 target, coal consumption can be reduced by 30.44%. However, transmission expansion may have limited effects due to the country's archipelagic nature. Therefore, a decentralized approach is necessary to minimize coal usage and encourage renewable energy sources. The study uses linear programming optimization methods to explore scenarios that can mitigate climate change by increasing solar and wind power use, reducing coal usage, and investigating the benefits of transmission line expansion and energy storage integration for enhancing grid flexibility.

Research on Case-Based Reasoning for Energy-Efficient Rail Transit Emergency Timetables

The continuous expansion of rail transit lines has led to a significant increase in energy consumption. Choosing an appropriate timetable based on external conditions of train operation can reduce energy consumption by more than 5%. When emergencies occur in rail transit, external conditions change, rendering the original timetable unable to meet energy-saving requirements. This paper primarily explores how to quickly determine an energy-efficient timetable based on historical energy-saving timetable data and current external conditions using case-based reasoning methods. The paper represents emergency event timetable cases using a framework approach, and then employs a retrieval algorithm based on the grey correlation degree method to search for cases. The energy-efficient timetable for the target case is selected from the retrieved source cases, considering the one with the lowest energy consumption.

Assessment of Environmental and Social Impact of Benin-delta Power Transmission line Expansion Project

This study examined the environmental and social impacts and household vulnerability of the 107 km Benin-Delta (Ughelli) 330 kV power transmission line (TL) expansion project right of way (ROW). Questionnaires were administered to 56 communities and 344 households to obtain information on their livelihood and the perceived environmental and social impacts of the TL expansion. Results revealed the TL on land use, community socio-cultural and health Status, employment and opportunities, community agitation and social economic status, they were found to be high, low, beneficial, medium and low in that order. Loss of land and economic trees were identified as the highest impacts of the project. All communities within the sphere of influence of the project had encroached on the existing ROW. The most vulnerable groups affected by the project are the non-indigenous elderly, widows and female-headed households, children, herdsmen, unemployed and those that have lost their lands and are now without means of livelihood. The valuation of assets and losses suffered suggests the need for resettlement and compensation. Specific mitigation measures which could help ameliorate suffering of the economically vulnerable households should be put in place.

CD70/CD27 Signaling Promotes Expansion of Clonal Plasma Cells in Multiple Myeloma and Is a Promising Therapeutic Target in Advanced Disease

Introduction: Multiple Myeloma (MM) is a hematological malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow (BM). In the last decade, substantial advances in the treatment of MM patients have been made resulting in improved progression-free and overall survival rates. However, to date, MM remains incurable. CD70 and CD27 belong to the TNF receptor family. CD70 is the only known ligand for its receptor CD27. Physiologically, the CD70/CD27 interaction is involved in the regulation of immune cell expansion. However, numerous solid and hematological cancer types overexpress CD70. Aside, CD70 and CD27 co-expression has been described on leukemic stem cells (LSC) in acute myeloid leukemia patients where an autonomous signaling activation drives LSC self-renewal and expansion. While CD70/CD27 signaling plays a key role in the differentiation process of B lymphocytes into plasma cells, only little is known about its impact on myelomagenesis and MM progression. In this study, we analyzed the role of CD70/CD27 signaling in the pathogenesis of MM and studied the possibility to target CD70 by monoclonal antibodies to treat the disease. Materials and Methods: We evaluated CD70 and CD27 gene expression levels and its correlations with overall survival (OS), MM progression and high-risk molecular alterations using different databases (CoMMpass IA15, GSE6477). CD70 and CD27 protein expression patterns were analyzed in a newly established MM tissue microarray (TMA) and a collection of matched BM samples from initial and advanced disease stages (in collaboration with the Institutes of Pathology in Bern, Basel and Tübingen). To assess the functional role of CD70/CD27 signaling on MM initiation and expansion, we generated CD70 knock-out MM cell lines and newly established patient-derived xenografts (PDX) using CRISPR/Cas9 genome editing. CD70-expressing MM cell lines or patient-derived myeloma cells were grown in NOD/SCID (NSG) mice. Moreover, different monoclonal antibodies (Abs) and Ab-derivates were tested including a CD70 blocking antibody (αCD70) and an antibody-dependent cell-mediated cytotoxicity (ADCC) optimized antibody (cusatuzumab, ArgenX) that activates FcγR-expressing effector cells to assess the therapeutic potential of targeting CD70 in MM. Results: High CD70 gene expression levels correlate with increased MKI67 gene expression and elevated lactate dehydrogenase serum levels indicating a more rapid proliferation of CD70-expressing myeloma cells. In addition, high CD70 expression in MM patients correlated with shorter OS. Longitudinal analyses of CD70 gene expression in the precursor stages monoclonal gammopathy of undetermined significance and smoldering myeloma as well as MM and relapsed MM stages showed highest CD70 gene expression levels in relapsed MM patients. Assessment of the molecular background further revealed increased frequencies of the prognostically unfavorable genomic translocations t(4;14) and t(14;16), as well as gain/amplification of the chromosomal region 1q21 (1q+) in CD70 high expressing MM patients. In line with our previous findings, a TMA analysis of over 200 MM core biopsies as well as a longitudinal analysis of matched biopsies from patients at initial diagnosis and MM relapse indicated that CD70 was overexpressed in advanced disease. Functionally, we found that CD70/CD27 signaling promotes plasma cell survival inducing the expansion of MM cell lines and primary malignant plasma cells. CD70 blockade (αCD70) or CD70 knock-out (CD70 KO) resulted in a significant inhibition or complete abrogation of growth of a CD70-expressing MM patient-derived xenograft (PDX) (EMM01 CD70+) compared to controls (Figure 1). Interestingly, in vivo limiting dilution assays revealed that CD70+CD27+ double-positive myeloma subpopulations showed significantly higher cancer stem cell frequencies compared to CD70 negative fractions suggesting that CD70 expression might be related to an immature or stem-cell like phenotype. The ADCC-optimized CD70 specific antibody custatuzumab efficiently eliminated CD70-expressing MM cells in the presence of PBMC-derived natural killer (NK) cells in vitro and in a PDX model in vivo. Conclusion: Our results indicate that CD70-expressing MM cells have a stem-cell like phenotype and propagate the disease. Targeting CD70 is a promising new therapy especially in advanced disease.