Line Capacity Research Articles

Распределенная система станций подзарядки для энергообеспечения группы БпЛА мультикоптерного типа

A steady trend towards the development of electric power systems leads to their continuous enlargement and sophistication. As a result, new ways of their control appear. In this regard, the existing models and complexes for adequacy assessment may work inadequately and ineffectively in terms of the obtained results adequacy. To assess the current state of the existing models and complexes, we reviewed and analyzed the domestic and foreign software and computer systems. In particular, we considered mathematical models of minimizing the power shortage. This work is based on the problem of modifying mathematical models of minimizing the power shortage used in adequacy assessment of the electric power systems of one of the complexes under consideration. As a modification of mathematical models, it is proposed to exclude the existing method of using the line capacities and start using correct accounting for the maximum permissible active power flow in controlled sections. The experimental part reflected in the paper concerns the testing of options for models to minimize the power shortage, as well as the proposed modifications on various systems, including those consisting of three and seven reliability zones with a variable number of controlled sections and power lines included in them. The results of the study have shown that the proposed modifications are efficient and can be used in the future. The authors also obtained the most adequate results in terms of the physical laws of electric power system operation due to the model of minimizing the power shortage with quadratic losses which takes into account the limitations of power transmission over controlled sections.

Abstract 2753: Muc4 is a biomarker of metastasis in TNBC and its downregulation by blocking soluble TNF prevents metastasis in combination with immunotherapy

Abstract Triple negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers and has the worst survival rate. Immunotherapy is a new treatment option but resistance is frequent. We have demonstrated that TNF induces trastuzumab resistance through mucin 4 (MUC4) upregulation and it is an independent biomarker of poor response to therapy in HER2+ breast cancer. MUC4 is a transmembrane glycoprotein involved in metastasis (MTS) dissemination. Here, we evaluated the impact of the axis TNF/MUC4 on the invasive capacity of TNBC cell lines and in a preclinical model of spontaneous MTS. Finally, we assessed the clinical impact of MUC4 expression in TNBC patients. TNF blockade was achieved with etanercept (E), which blocks the soluble (sTNF) and transmembrane isoform of TNF, or with the dominant negative protein INB03 (DN) which neutralizes only sTNF. BT-549 and MDA-MB-231 human TNBC cell lines treated with E or DN exhibit a decrease in MUC4 expression. To assess the impact of TNF blockade on tumor cells and its effect on the tumor microenvironment, we collected conditioned media (CM) from MDA-MB-231 and BT-549 cells treated with E or DN which were used to evaluate the invasive capacity of the TNBC cell lines. The invasion of BT-549 and MDA-MB-231 was impaired with CM-Eta (p≤0.01) and CM-DN (p≤0.01 and p≤0.05, respectively). Female BALB/c mice bearing the TNBC LMM3 tumors were treated with IgG, DN, anti-PD-1 antibodies or DN+anti-PD-1 for two weeks. After the treatments we performed surgery to remove the primary tumor and the animals were sacrificed 2 weeks later. No effect on tumor growth was observed. However, the DN+anti-PD-1 group was the only one with less of 3 MTS per lung (p≤0.05). We obtained tumor extracts and found that the tumors of the animals treated with DN or DN+anti-PD-1 had decreased MUC4 expression measured by Western blot. We determined the presence of TILs by H & E and the expression of MUC4, Ki67, PD-L1 (SP142), androgen receptor (AR) and cytokeratin 5 by immunohistochemistry in a cohort of 56 early TNBC patients. MUC4 expression was inversely correlated with TILs presence (p=0.0003). Since TILs are associated with good prognosis, we evaluated the effect of BT-549-CM and MDA-MB-231-CM on T cell migration. CM-DN from both cell lines increased T cell migration compared to control CM (p≤0.01). MUC4 expression was inversely correlated with Ki67 (≥30%, p=0.036), PD-L1 (p=0.001) and AR (p=0.047) in our cohort. Moreover, MUC4 proved to be an independent predictor of poor overall survival (p=0.02), and is associated with a higher MTS risk (p=0.005). MUC4 is associated with poorly-infiltrated TNBC, and sTNF blockade downregulates its expression decreasing MTS when combined with anti-PD-1. We propose the TNF as a new target for the treatment of TNBC, and MUC4 as a predictive biomarker to guide a combined treatment of TNF blockers with immunotherapy. Citation Format: Florencia Luciana Mauro, Sofia Bruni, Agustina Dupont, Gloria Inurrigarro, Silvina Figurelli, Sabrina Barchuk, Daniel Lopez Della Vecchia, Rosalia Cordo Russo, Ernesto Gil Deza, Maria Florencia Mercogliano, Roxana Schillaci. Muc4 is a biomarker of metastasis in TNBC and its downregulation by blocking soluble TNF prevents metastasis in combination with immunotherapy [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 2753.

Abstract 3158: TUSC2 suppresses energy metabolism in lung cancer cells with opposite effects in normal bronchial epithelial cells

Abstract Introduction: TUSC2 (TUmor Suppressor Candidate 2) is a tumor suppressor gene from the human 3p21.3 chromosomal region frequently deleted in lung cancers. Independently of deletion, reduced expression of TUSC2 is observed in ~ 80% of lung cancers, mesothelioma, breast, head-and neck, osteosarcoma, glioblastoma, and other cancers, suggesting a critical anti-tumor role of TUSC2. TUSC2 resides in mitochondria and is involved mitochondrial respiration/energy metabolism, ROS production, Ca2+ flux to/from mitochondria, etc. Studies on tumor-bearing mice treated with TUSC2-containing plasmid encapsulated in lipid nanoparticles (quaratusugene ozeplasmid) and Phase I and II clinical trials of quar oze in lung cancer patients provides a strong rationale to further study the tumor-protective mechanisms of TUSC2 protein. Main scientific question. We asked if and how human lung cancer cells, A549 and H358, that have ~80-90% decrease in TUSC2 expression, change their energy metabolism in response to re-introduction of TUSC2 as compared to Beas2B, a normal bronchial epithelial cell line. Cancer cells rely heavily on anaerobic glycolysis, while normal epithelial cells use mitochondrial respiration as a primary way of energy production. Methods: Transient transfection of TUSC2-expressing plasmid to 3 cell lines; qPCR to confirm TUSC2 delivery; Seahorse analysis of energy production that measures in real time Oxygen Consumption Rate (OCR) and Extracellular Acidification Rate (ECAR) in different conditions. Results: All three cell lines demonstrated high transfection efficiency. Seahorse analysis revealed that TUSC2 re-introduction to TUSC2-deficient cancer cells consistently suppressed both glycolytic and mitochondrial ATP production, thus leaving cells without sufficient energy to support their vital functions. We found a significant decrease in basal and maximal respiration, spare respiratory capacity, ATP production, glycolysis and glycolytic capacity in cancer cell lines transfected with TUSC2-expressing plasmid. Unlike cancer cells, both glycolytic and mitochondrial metabolism of normal epithelial cells Beas2B were significantly strengthened after the introduction of TUSC2, suggesting a beneficial role of TUSC2 for the metabolic health of normal cells. The experiments were repeated four times; Student T-test was used to calculate statistical significance. Therapeutic Significance: These experiments suggest that TUSC2 plasmid delivery to cancer patients, and thus quar oze therapeutic use, may target and disrupt the metabolism of cancer cells, triggering either senescence or apoptotic pathways, while on the other hand, supporting the metabolism of normal epithelial cells. These data have high therapeutic significance, suggesting that one of the anti-tumor mechanisms of quar oze action in patients is the suppression of cancer cell metabolism resulting in cancer cell death. Citation Format: Jane Tonello, Mark Berger, Anil Shanker, Alla Ivanova. TUSC2 suppresses energy metabolism in lung cancer cells with opposite effects in normal bronchial epithelial cells [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 3158.

Causality between multi-scale built environment and rail transit ridership in Beijing and Tokyo

Recent years have witnessed researchers' academic interests in the relationship between the built environment and rail transit ridership. However, few studies have analyzed it from a beyond-station scale and causal perspective. To fill this gap, this study uses Beijing and Tokyo as cases and utilizes Bayesian networks and generalized propensity score matching to achieve causal discovery and causal inference of built environment and ridership. Moreover, we innovatively consider the line-scale built environment factors. Evidence suggests that transit agencies should promote the overall accessibility of stations along the line to employment concentration areas more than single-station accessibility in Beijing. Meanwhile, the positive impact of bus-rail transit line cooperation on ridership is limited in Beijing. Planners should consider the capacity of rail transit lines. The causal inference results are mainly in line with previous correlation studies, but some interesting differences exist. For example, the net effect of dense pedestrian roads on ridership is negative, reminding policymakers that they should avoid expanding pedestrian paths without developing ridership-attracting resources. This study uses causal theories to emphasize the necessity of corridor-based and modest development.

Strategy for Enhancing Hosting Capacity of Distribution Lines Using a Vertical Photovoltaic System

Renewable energy sources are being increasingly deployed to achieve carbon neutrality, thereby boosting photovoltaic (PV) system adoptions. Accordingly, vertical PV systems designed for specific installations have been developed. We propose a strategy to enhance the PV hosting capacity of a connected distribution line (DL) by combining vertical installations with modules facing east-west and conventional PV systems with modules facing south at an installation angle of approximately 30°. The data were obtained from a real testbed located in South Korea, which is situated in a mid-latitude region. We analyzed the generation patterns of vertical and combined PV systems (vertical and conventional) to enhance the hosting capacity. The results showed that vertical PV combination ratios of 40–60% effectively flattened the peak generation curve. Additionally, the DL hosting capacity improved by 40% under real-world conditions. In an actual industrial scenario, the system feasibility was validated to be within the voltage maintenance range and thermal capacity of lines in South Korea, indicating that this approach can mitigate the need for additional line installations and renewable energy curtailments. Furthermore, the issue of Duck Curves in the power grid can be addressed by smoothing the power production of the PV systems, particularly during low-demand periods.

Renewable Energy Real-Time Carrying Capacity Assessment Method and Response Strategy under Typhoon Weather

Currently, the integration of distributed power supply into the power grid is steadily increasing. The grid’s carrying capacity serves as a crucial metric for evaluating the grid’s resilience following the widespread integration of distributed power supply. During typhoon conditions, if the power grid experiences line breakage and load loss faults, the grid’s framework is altered, rendering the conventional carrying capacity assessment method obsolete. This study introduces a method for assessing the risk of line carrying capacity and an index for line overload probability under typhoon conditions, integrating line and transformer capacity constraints to evaluate the grid’s carrying capacity risk. The probability of line failure is modeled during typhoon events, and a modified IEEE39 node example is employed to simulate a high-penetration grid in a typhoon scenario. Addressing the issue of inadequate intraday dispatch capability under insufficient carrying capacity, we propose a multi-timescale dispatch method and derive the optimal grid dispatch strategy using the viscous bacteria algorithm. The efficacy of the multi-timescale dispatch strategy in addressing the grid’s carrying capacity risk is validated through simulation, while the economic cost of mitigating the grid’s carrying capacity risk and the line overload probability is assessed across varying parameter values.

Train headway estimation for maglev with blocking time theory

As the commercialization of maglev trains continues to accelerate, effective improvement of maglev train operation has become a topic for researchers. The train headway of the maglev is the preparation basis for the train timetable and is also an essential factor affecting the line capacity utilization. This paper proposed an approach to estimate the train headway by considering the characteristics of partitioned control of maglev operations. First, we build the tracking model for maglev with the theory of blocking time, in which the train speed profile is the key input source. Then, a customized method is proposed to estimate the minimum headway of maglev trains. According to the experiment, we can effectively obtain the minimum train headway by the approach, and the result of improving the maglev line capacity utilization is verified.

Capacitor Bank Panel Design to Improve Industrial Power System Efficiency and Safety

Industrial loads generally use control equipment and power electronics that use semiconductor materials that are very sensitive to voltage fluctuations. As reactive power compensation, industries usually use capacitor banks to increase power factor, reduce losses and increase line capacity. But it turns out that the use of capacitor banks also causes problems related to capacitor bank switching during the energizing process. During the energizing process, transient voltages and currents will be generated which can potentially damage control equipment, power electronic equipment, switching equipment and the capacitor bank itself. The Capacitor Bank panel assembly process involves the preparation of components such as MCB (Miniature Circuit Breaker), MCCB (Molded Case Circuit Breaker), Capacitor Bank, and other components. After that, these components are carefully assembled according to the pre-prepared design. Next, the installation of the Capacitor Bank panel involves mounting the panel to the location according to the plan and connecting it to the building's main power system. Accurate wiring and meticulous testing are required to ensure that the panels function properly. Therefore, a good understanding of the assembly and installation process of Capacitor Bank panels is essential to ensure efficient, and safety.

An efficient hyperpath-based algorithm for the capacitated transit equilibrium assignment problem

This paper studied the capacitated transit equilibrium assignment problem (CTEAP), which particularly accounts for the capacity effect that impacts passengers' route choices in a transit network. Specifically, we impose strict capacity constraints on line segments to ensure that the passenger flow does not exceed the line capacity. By introducing associated Lagrange multipliers, we derived the generalised hyperpath cost function and established an equivalent variational inequality formulation. A solution framework is developed to solve CTEAP based on the Method of Multipliers. To handle destroyed Cartesian product structures, we transformed the master problem into a sequence of uncapacitated subproblems, which can be tackled by two modified Newton-type hyperpath-based algorithms. Numerical analyses were performed for a small Gentile network and a large Shenzhen transit network to evaluate the impacts of the capacity constraint on passenger flows and computation costs. Our results demonstrate the superiority of the proposed CTEAP model to prevent over-loaded flows, and show the promise of applying the hyperpath-based algorithm in the implementation of real-world networks.

Abstract B019: Investigating Cannabis sativa bioactive compounds as an anti-cancer treatment in high-grade serous ovarian cancer

Abstract B019: Investigating <i>Cannabis sativa</i> bioactive compounds as an anti-cancer treatment in high-grade serous ovarian cancer

Integrated genomic and proteomic analyses identify PYGL as a novel experimental therapeutic target for clear cell renal cell carcinoma

Sunitinib, the first-line targeted therapy for metastatic clear cell renal cell carcinoma (ccRCC), faces a significant challenge as most patients develop acquired resistance. Integrated genomic and proteomic analyses identified PYGL as a novel therapeutic target for ccRCC. PYGL knockdown inhibited cell proliferation, cloning capacity, migration, invasion, and tumorigenesis in ccRCC cell lines. PYGL expression was increased in sunitinib-resistant ccRCC cell lines, and CP-91149 targeting the PYGL could restore drug sensitivity in these cell lines. Moreover, chromatin immune-precipitation assays revealed that PYGL upregulation is induced by the transcription factor, hypoxia-inducible factor 1α. Overall, PYGL was identified as a novel diagnostic biomarker by combining genomic and proteomic approaches in ccRCC, and sunitinib resistance to ccRCC may be overcome by targeting PYGL.

Feasibility analysis of dynamic improvement of current carrying capacity of overhead lines

The demand for electricity in China has been increasing year by year. However, the construction of transmission lines is costly and has significant composite short-term peak characteristics. This article aims to study the feasibility of improving the conductor’s current capacity, analyze data characteristics of typical conductor states and micrometeorological data, figure out the real-time conductor’s current capacity based on the calculation model, analyze the margin for improving the CCC, and lift the power supply potential.

Railway Line Capacity Relative to Additional Block Division

The article discusses the results of studies of railway line capacity relative to the application of additional block division using virtual blocks in the process of positioning a train reporting its position and train set integrity. The studies were conducted using the authors’ original simulation software enabling extensive parameterisation of infrastructure, including configuration of the train control system and signalling principles, by taking the actual characteristics of train movements into account based on data obtained from real-life measurements.

Optimal power flow of power system with Thyristor Controlled Series Compensation using moth flame optimization with locational marginal price

Consideration of transmission line capacity and the optimal power flow (OPF) determines the locational marginal price (LMP), which in turn determines the performance and profitability of a producing unit. Reducing the total cost of the generators can lead to a drop in the market price of electricity. It is recommended to use numerical and repetition-based approaches for solving power flow equations due to their nonlinear nature. In order to achieve the ideal power flow at an affordable price, this paper employs a Moth Flame Optimization (MFO) to solve the equations. We then enhance the MFO's structure to make it more effective at performing the simultaneous calculations of power passing through transmission lines. One FACTS tool that has been utilized to overcome this problem is the Thyristor Controlled Series Compensation (TCSC). Lastly, the proposed MFO algorithm would include the following parameters in its output: bus voltages, line losses, produced power, total generating expenditures, and generator profits. Testing the proposed method on the IEEE 57-BUS network also shows that it improves upon the OPF problem.

Ensuring Safe Working Conditions under the Influence of Vibroacoustic Factors on Train Crew Workers

Introduction. The increased intensity of noise and vibration of railway traffic may become not only an urgent problem in the field of occupational safety, but also a serious environmental problem in the near future due to the constant need to increase the weight of freight trains, the speed of passenger trains and the capacity of railway lines. Recently, a lot has been done to minimize the negative effects of noise and vibration in railway transport. However, the problem of exceeding the indicators of vibration noise factors remains relevant. Reducing the harmful effects helps to improve the working conditions of train crew employees and improve the comfortable conditions of transport passengers. As a rule, the main focus of the analysis is on the external impact of vibroacoustic factors on residential areas and less attention is paid to the impact on rolling stock. However, these studies do not provide a complete picture of how noise and vibration actually affect the train in motion. The aim of the study was to obtain the result of an analysis of the impact of vibroacoustic factors on train crew workers and to propose a method of comprehensive protection based on the use of vibration damping materials.Materials and Methods. In the course of the work, regulatory documents were studied, a comprehensive analysis of relevant information on this topic was carried out, and methods for calculating vibration and vibration acceleration were used. The values of the sound pressure levels were obtained using a SPM-101 sound level meter. The object of the study was a carriage of the "reserved seat" type in the process of movement. As part of the research plan, sound pressure was measured at selected sites and a class of working conditions was determined.Results. The result of the analysis of the impact of vibroacoustic factors on train crew workers indicated the need to strengthen comprehensive measures to protect them. The obtained calculation of the vibration force became the basis of the method proposed by the authors to minimize the harmful effects of vibroacoustic factors, which was based on the use of vibration and sound insulation materials suitable for the necessary acoustic parameters in the construction of the car. In particular, it was proposed to cover the floor of the car with dense rubber and the ceiling of the car with an inorganic fiber material for sound insulation. The work also provides an economic assessment of the effectiveness of measures to minimize harmful vibration noise effects.Discussion and Conclusion. The proposed methods for minimizing noise and vibration impacts can help reduce the level of sound pressure and vibration indicators to standard values, which will significantly reduce the negative impact of vibroacoustic factors on train crew workers and railway passengers. The considered complex for minimizing vibration and noise includes a set of methods in which affordable materials based on recycled substances have found application.

Isolation and expansion of pure and functional γδ T cells.

γδ T cells are important components of the immune system due to their ability to elicit a fast and strong response against infected and transformed cells. Because they can specifically and effectively kill target cells in an MHC independent fashion, there is great interest to utilize these cells in anti-tumor therapies where antigen presentation may be hampered. Since only a small fraction of T cells in the blood or tumor tissue are γδ T cells, they require extensive expansion to allow for fundamental, preclinical and ex vivo research. Although expansion protocols can be successful, most are based on depletion of other cell types rather than γδ T cell specific isolation, resulting in unpredictable purity of the isolated fraction. Moreover, the primary focus only lies with expansion of Vδ2+ T cells, while Vδ1+ T cells likewise have anti-tumor potential. Here, we investigated whether γδ T cells directly isolated from blood could be efficiently expanded while maintaining function. γδ T cell subsets were isolated using MACS separation, followed by FACS sorting, yielding >99% pure γδ T cells. Isolated Vδ1+ and Vδ2+ T cells could effectively expand immediately after isolation or upon freeze/thawing and reached expansion ratios between 200 to 2000-fold starting from varying numbers using cytokine supported feeder stimulations. MACS/FACS isolated and PHA stimulated γδ T cells expanded as good as immobilized antibody mediated stimulated cells in PBMCs, but delivered purer cells. After expansion, potential effector functions of γδ T cells were demonstrated by IFN-γ, TNF-α and granzyme B production upon PMA/ionomycin stimulation and effective killing capacity of multiple tumor cell lines was confirmed in killing assays. In conclusion, pure γδ T cells can productively be expanded while maintaining their anti-tumor effector functions against tumor cells. Moreover, γδ T cells could be expanded from low starting numbers suggesting that this protocol may even allow for expansion of cells extracted from tumor biopsies.

Unraveling the dynamics of hepatitis C virus adaptive mutations and their impact on antiviral responses in primary human hepatocytes.

Hepatitis C virus (HCV) infection remains a global health burden with 58 million people currently chronically infected. However, the detailed molecular mechanisms that underly persistence are incompletely defined. We utilized a long-term cell culture-adapted HCV, exhibiting enhanced replicative fitness in different human liver cell lines, in order to identify molecular principles by which HCV optimizes its replication fitness. Our experimental data revealed that cell culture adaptive mutations confer changes in the host response and usage of various host factors. The latter allows functional flexibility at different stages of the viral replication cycle. However, increased replicative fitness resulted in an increased activation of the innate immune system, which likely poses boundary for functional variation in authentic hepatocytes, explaining the observed attenuation of the adapted virus population in primary hepatocytes.

Power Flow Analysis of Distribution Systems with Large-Scale Wind and Conventional Energy Generation

This paper is devoted to the development of a methodology suitable to be used to determine the impact of the grid integration of wind farms in distribution networks that are also supplied with other classical generation facilities based on thermal and hydraulic energy. The methodology is based on an automated analysis system that varies the level of the electric generation for both the hydraulic and thermal generators by using PSS, Phyton and Matlab. The user can define multiple scenarios considering wind, thermal and hydraulic generators so the line capacity can be computed and compared in order to know where the systembottleneck is located and which situations occur. All the results computed can be analysed in a single or compared way by using tables and plots and considering the static rate of the distribution lines. The developed system can also be applied to the computation of the sensitivity of the power flow to the variation of the parameters that define the power system.

A Methodology for Rating Electricity Transmission Lines to Assess the Most Important or Critical Lines

The proposed method, based on three combined criteria—Sn—design capacity of the power line, LF, (line flow)—power flow in an electric transmission line, MVA, and the ratio of LF/Sn—allows for ranking electric transmission lines when calculations are performed in normal/pre-emergency modes. A combined set of criteria used to study critical/post-emergency N-k modes is developed. The simulations were performed on the real Baltic 330 kV electricity transmission system. The results reveal that when the power system operates in different load modes, most of the critical power lines determined by our method fall into the actual set of important/“critical” power transmission lines. This allows us to significantly reduce the number of simulated combinations and shorten the calculation time required for it. During the study of the Baltic electricity system, it was found that the developed method was accurate and efficient and suitable for the assessment of the reliability of real electricity transmission networks when planning operational and perspective work modes. The simulations results revealed the high reliability of the Baltic electricity system. The 330 kV electricity transmission network of the Baltic countries fully meets the N-2 criterion (usually, electricity transmission networks are designed to meet the N-1 criterion).

Abstract B100: Netrin-1/Neogenin-1 interaction modulates pancreatic innervation to promote tumorigenesis and accelerates cancer progression

Abstract Background: Nerves are a major component of the tumor microenvironment, with active crosstalk between cancer cells and nerves that may contribute to cancer progression. Netrin1 (Ntn1) is an axon guidance molecule that is important during early neural development. Recent studies suggest that Ntn1 may also play a role in tumorigenesis but its role in pancreatic cancer is not well understood. We hypothesized that Ntn1 plays a pro-tumorigenic role in pancreatic ductal adenocarcinoma (PDAC) progression and metastasis in part through modulation of nerves in the microenvironment. Methods: Expression of Ntn1 and its receptor Neogenin1(Neo1) were investigated in mouse models of spontaneous PDAC (LSL-Kras+/G12D/Pdx1-Cre; KC, LSL-Kras+/G12D/LSL-Trp53+/R172H/Pdx1-Cre; KPC). The influence of Ntn1 on pancreatic cancer progression and innervation was evaluated by KC mice with or without conditional knockout of Ntn1 (LSL-Kras+/G12D/Pdx1-Cre/Netrin1fl/fl; KCN). Murine PDAC cell lines and organoids were used to examine the functional role of Ntn1 and Neo1 through genetic and pharmacological modulations. The capacity of these cell lines to generate metastasis and the effect on neurite outgrowth was studied in a co-culture system with Dorsal Root Ganglia (DRG). Results: Expression of Ntn1 was not observed in normal acinar cells or ductal cells, but was found in both PanIN lesions and PDAC. Neo1 expression was similar to Ntn1 and there was a positive correlation between the expression of Ntn1 and Neo1. A lower rate of PanIN progression was observed in KCN mice compared to KC mice. In the metastatic model, overexpression of Ntn1 increased tumor burden and decreased survival while injections of a neutralizing Ntn1 antibody or genetic knockdown of Neo1 improved both endpoints. Ntn1 and Neo1 were upregulated in pancreatic organoids upon KRAS activation. Recombinant Ntn1 (rNTN1) promoted organoid forming capacity and upregulate Sox2 and Sox9 gene expression, which was inhibited by genetic knockdown of Neo1 or an anti-Neo1 antibody, supporting a direct autocrine role in modulating stemness. Nerve fibers were significantly increased at the site of PDAC liver metastasis, with Ntn1 showing the highest expression level among neurotrophins, as it was significantly increased in metastatic PDAC cells. Consistent with this observation, we observed less innervation in KCN mice, which correlated with reduced PanIN progression. Co-culture of DRGs with PDAC cells that overexpressed Ntn1 resulted in much greater axonal elongation consistent with a role of Ntn1 in promoting innervation. Conclusion: The Netrin1/Neogenin1 interaction is an important regulator of PDAC progression, acting both directly on PDAC cells to promote stemness, and indirectly via modulating tumor innervation. Blockade of Ntn1/Neo1 interaction reduces the capacity of PDAC to metastasize to the liver and improves survival. Overall, targeting the Ntn1/Neo1 interaction may represent a potential new therapeutic approach for the treatment of pancreatic cancer. Citation Format: Yosuke Ochiai, Sunagawa Masaki, Ermanno Malagola, Hiroki Kobayashi, Feijing Wu, Ruth A. White, Leah B. Zamechek, Timothy C. Wang. Netrin-1/Neogenin-1 interaction modulates pancreatic innervation to promote tumorigenesis and accelerates cancer progression [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B100.