Synergy Model Research Articles

Contracting with cost synergies: Continuous-time double-sided moral hazard

We study optimal effort and compensation in two continuous-time double-sided models with cost synergies. In the co-work synergy model, cost synergies exist between two agents with ongoing effort: each agent's effort reduces his colleague's marginal cost of effort. The agents completely divide the project's cash flow. In the optimal contract, the agent with higher productivity and a bigger cost-reduction influence claims a larger fraction of the cash flow. In the chain synergy model, one agent exerts initial effort to start the project, and her colleague exerts ongoing effort to manage it. The upfront effort reduces the marginal cost of her colleague's ongoing effort. The timing of optimal payments reflects cost synergies across agents and the timing of efforts: Upfront effort corresponds to early payments. We show that the introduction of cost synergies not only alters the allocation of the cash flow but also improves the expected social surplus. This study suggests that cost synergies increase efficiency for a broad set of contracting problems involving teams.

The Effect of the Orientation, Analysis, Synthesis, Investigation, Synergy (OASIS) Model on Students' Cognitive Learning Outcomes in Kinetic Gas Theory

Based on the results of a preliminary study at SMA Negeri 1 Cihaurbeuti, it is known that students' cognitive learning outcomes are still classified as poor, one of which is the kinetic gas theory material which still has not reached the minimum completeness criteria, namely 70, because the learning method still uses the lecture method. Apart from that, the lack of innovation in the use of models in physics learning causes physics learning to become less interesting for students so that cognitive learning outcomes need to be improved. One of the solutions taken by researchers to overcome this problem is to apply the Orientation, Analysis, Synthesis, Investigation, Synergy (OASIS) learning model. The aim of this research is to analyze the influence of the OASIS learning model on students' cognitive learning outcomes in class XI gas kinetic theory material at SMA Negeri 1 Cihaurbeuti. The research method used is quasi experimental design because this research is educational research with the object used being humans. The research design applied is nonequivalent control group design, where the two classes of research samples will undergo tests before and after being given treatment. The population in this research is all 7 classes of class To measure cognitive learning outcomes (C1, C2, C3), students were tested before treatment (pretest) and after being given treatment (posttest) in the form of a description of 6 questions on the main material of the kinetic theory of gases. The data analysis technique that will be used is the prerequisite test including the normality test and homogeneity test, as well as hypothesis testing using the t test with a significance level showing that (4.06>1.67) which means is accepted and is rejected, so it can be concluded that the OASIS learning model has an effect on students' cognitive learning outcomes in gas kinetic theory material.

Novel Combination Therapy for Heart Failure: Trimebutine-Methoxsalen Identified through Synergistic Network Virtual Screening and Experimental Validation.

Combination therapy is increasingly favored by pharmaceutical companies and researchers as an effective way to quickly discover new drugs with excellent efficacy, especially in the treatment of complex diseases. Previously, we successfully developed a computational screening method to identify such combinations, although it fell short in elucidating their synergistic mechanisms. In this work, we have transitioned to a highest single agent (HSA) synergy model for network screening, which streamlines the discovery of promising combinations and facilitates the investigation of their synergistic effects. Through this refined approach, the trimebutine-methoxsalen combination emerged as a promising candidate for heart failure (HF) treatment, exhibiting significant in vitro cardioprotective effects and effectively mitigating isoproterenol (ISO)-induced structural remodeling in the mouse heart. Further mechanistic studies have demonstrated that trimebutine and methoxsalen could synergistically inhibit intracellular calcium overload in myocardial cells and reduce the production of ROS, thus exerting cardioprotective effects. Overall, this study introduces an advanced computational strategy that not only identifies a novel combination therapy against HF but also sheds light on its underlying synergistic mechanisms.

Sustainable manufacturing production synergy and circular economy model under low carbon energy based on thermal energy cycle and blockchain technology

With the intensification of global climate change and resource depletion, the use of low-carbon energy and the exploration of circular economy model become more and more important. As an efficient way to use energy, thermal energy cycle has wide application potential in manufacturing industry. This study aims to build a sustainable manufacturing production synergy and circular economy model under low-carbon energy based on thermal energy recycling and blockchain technology, in order to improve the resource utilization efficiency of manufacturing industry, reduce carbon emissions, and achieve double benefits of economy and environment. Through literature analysis and case studies, key elements of thermal energy recycling and blockchain technology are integrated to design and simulate a new collaborative manufacturing system. The system uses thermal energy recycling technology to convert waste heat recovery into reusable energy, and combines blockchain technology to achieve real-time monitoring of energy flows and production processes to improve transparency and efficiency. The model simulation results show that after the introduction of heat recovery and blockchain management, the energy utilization efficiency in the manufacturing process is greatly improved, and the overall carbon emissions are significantly reduced. The transparent data sharing mechanism helps all participants optimize production decisions and improve the flexibility and response speed of collaborative production.

Synergy model and financial bookkeeping administration through technopreneurship education: does it impact on increasing the competitiveness of MSMES?

This synergy model refers to collaboration between technology and business expertise in the context of technopreneurship education. A modern approach through technopreneurship education can help MSMEs adopt an effective financial bookkeeping system, including the use of technology in carrying. This research aims to determine and analyze the synergy and administration model of financial bookkeeping through technopreneurship education which has an impact on increasing the competitiveness of Micro, Small and Medium Enterprises (MSMEs). This research was carried out at the Culinary Food MSMEs located in Gowa Regency and Makassar City, South Sulawesi Province. The data analysis method in this research uses qualitative data analysis. This research method aims to get general answers about cause and effect by analyzing the factors that cause phenomena in the concepts raised in this research. Data collection was carried out by distributing questionnaires and interviews with informants from Micro, Small and Medium Enterprises (MSMEs). The steps in qualitative analysis techniques start from data reduction, data presentation and drawing conclusions. The research results show that the synergy model that was designed has a positive impact, but the synergy model through technopreneurship education is less effective in being implemented by MSMEs so that the competitiveness of MSMEs is not optimal. Apart from that, MSMEs tend to carry out financial administration manually and irregularly so that bookkeeping administration through technopreneurship does not have an impact on increasing competitiveness. Meanwhile, technopreneurship education is very useful and has an impact, but the competitiveness of MSMEs has not fully increased.

Air Pollution and Mortality in India: Investigating the Nexus of Ambient and Household Pollution Across Life Stages.

Air pollution in India is a foremost environmental risk factor that affects human health. This study first investigates the geographical distribution of ambient and household air pollution (HAP) and then examines the associated mortality risk. Data on fine particulate matter (PM2.5) concentration has been extracted from the Greenhouse Gas Air Pollution Interactions and Synergies (GAINS) model. HAP, mortality and socio-demographic data were extracted from the National Family and Health Survey-5, India, 2019-2021. Regression models were applied to see the difference in age-group mortality by different pollution parameters. The districts with PM2.5 concentration above the National Ambient Air Quality Standard (NAAQS) level of 40μg/m3 show a higher risk of neonatal (OR-1.86, CI 1.418-2.433), postneonatal (OR-2.04, CI 1.399-2.971), child (OR-2.19, CI 0.999-4.803) and adult death (OR-1.13, CI 1.060-1.208). The absence of a separate kitchen shows a higher probability of neonatal (OR: 1.18, CI 1.074-1.306) and adult death (OR-1.06, CI 1.027-1.088). The interaction between PM2.5 levels above NAAQS and HAP leads toa substantial rise in mortality observed for neonatal (OR 1.19 CI 1.051-1.337), child (OR 1.17 CI 1.054-1.289), and adult (OR 1.13 CI 1.096-1.168) age groups. This study advocates that there is a strong positive association between ambient and HAP and mortality risk. PM2.5 pollution significantly contributes to the mortality risk in all age groups. Children are more vulnerable to HAP than adults. In India, policymakers should focus on reducing the anthropogenic PM2.5 emission at least to reach the NAAQS, which can substantially reduce disease burden and, more precisely, mortality.

Synergy effects of cavitation and particle erosion based on the Erosion/Corrosion Research Center erosion model

This study presents a new synergy model that incorporates the accelerated motion of particles resulting from bubble collapse. The model uses the Erosion/Corrosion Research Center erosion model to predict the combined effect of cavitation and particle erosion on wall surfaces. The results show that, compared with the conventional erosion model, the synergy model reduces the error in the erosion mass loss by up to 24.60%. The significant improvement in prediction accuracy confirms the effectiveness of the synergy model. The severity of sample erosion is positively correlated with the cavitation-inducer angle. The synergy effect leads to an increase in the extent and severity of erosion. Smaller particles demonstrate a more pronounced synergy effect, resulting in significantly accelerated motion and a highly concentrated particle distribution. High erosion rates are associated with high-speed impacts and small-angle impact zones, primarily caused by high-speed cutting erosion. This study presents a novel prediction method for exploring the synergy effect of cavitation and particles on wall erosion and investigates the motion characteristics of particles under this effect.

The role of Islamic economics and social institutions during the time of Covid-19

PurposeThis study aims to examine the role of Islamic economic and social institutions during Covid-19 and try to propose a model that highlights Islamic economics and social institutions’ role in providing community economic, social and health recovery support.Design/methodology/approachThis research uses a qualitative approach with a multicase method. Interviews with the institutions including the Amil Zakat, Islamic Banks, Micro Waqf Banks and Islamic Cooperative (Baitul Maal wat Tamwil) were conducted in order to develop a model about how the integration between each institution in handling the effect of COVID-19.FindingsThe model shows the interaction roles of each Islamic institution and implementation in the long term and short term in handling the impact of Covid-19, particularly in the economic, social and health sectors. These institutions will assist the government in establishing community economic independence in the face of COVID-19, which has caused economic sluggishness or recession.Research limitations/implicationsThis study proposes the model of synergy using a qualitative approach. Future studies can develop the synergy model by employing a statistical and quantitative method, such as by employing analytical network process method.Originality/valueThis study adds the literature about empirical evidence on the role of each Islamic economic and social institution and develops new scenario model about integration of those institutions in overcoming economic and social problems during the COVID-19 pandemic. These interactions play a role in shaping the community’s economic independence in dealing with the economic downturn due to COVID-19.

Global scenarios of anthropogenic mercury emissions

Abstract. Anthropogenic mercury (Hg) emissions to the atmosphere are a long-lived hazard to human and environmental health. The UN Minamata Convention on Mercury is seeking to lower anthropogenic mercury emissions through a mix of policies from banning certain Hg uses to reducing unintentional Hg release from different activities. In addition to independent Hg policy, strategies to mitigate greenhouse gases, particulate matter (PM) and SO2 may also lower Hg emissions as a co-benefit. This study uses the Greenhouse Gas–Air Pollution Interactions and Synergies (GAINS) model to examine the effect of different clean air and climate policies on future global Hg emissions. The baseline scenario assumes current trends for energy use and Hg emissions as well as current legislation for clean air, mercury and climate policy. In addition, we explore the impact of the Minamata Convention, the co-benefits of climate and stringent air pollution policies, and maximum feasible reduction measures for Hg. Hg emission projections until 2050 show noticeable reductions in combustion sectors for all scenarios due to a decrease in global fossil fuel and traditional biomass use, leading to emission reductions of 33 % at baseline and up to 90 % when combining stringent climate controls and the most efficient Hg controls. Cement and non-ferrous metal emissions increase in all scenarios with current air pollution policy but could be reduced by up to 72 % and 46 %, respectively, in 2050 with stringent Hg-specific measures. Other emissions (including waste) are a significant source of uncertainty in this study, and their projections range between a 22 % increase and a 54 % decrease in 2050, depending on both climate and clean air policy. The largest absolute reduction potential for Hg abatement but also the largest uncertainties regarding absolute emissions lie in small-scale and artisanal gold production, where abatement measures could eliminate annual Hg emissions in the range of 601–1371 t (95 % confidence interval), although the uncertainties in the estimate are so high that they might eclipse reduction efforts in all other sectors. In total, 90 % of Hg emissions are covered by provisions of the Minamata Convention. Overall, the findings emphasize the necessity to implement targeted Hg control policies in addition to stringent climate, PM and SO2 policies to achieve significant reductions in Hg emissions.

Unveiling the critical roles of cellular metabolism suppression in antibiotic tolerance

Metabolic inhibitors are known to exhibit complex interactions with antibiotics in bacteria, potentially acting as antagonists by inducing cell dormancy and promoting cell survival. However, the specific synergistic or antagonistic effects of these inhibitors depend on factors like their mechanisms of action, concentrations, and treatment timings, which require further investigation. In our study, we systematically explored the synergistic interactions of various metabolic inhibitors—such as chloramphenicol (a translation inhibitor), rifampicin (a transcription inhibitor), arsenate (an ATP production inhibitor), and thioridazine (a PMF inhibitor)—in combination with ofloxacin. We conducted this investigation under pre-, co-, and post-treatment conditions, employing a wide concentration range and utilizing four distinct synergy models. Chloramphenicol, rifampicin, and arsenate consistently showed minimal synergy scores, indicating a notable antagonistic relationship with ofloxacin across all models and conditions. In contrast, thioridazine consistently demonstrated elevated synergy scores, especially in pre- and co-treatment scenarios, albeit its synergy decreased during post-treatment conditions. When multivariable linear regression analyses were used for all drugs and conditions examined, a correlation between the synergy of thioridazine and its ability to suppress cellular energy metabolism became evident, underscoring the potential utility of certain metabolic inhibitors as effective anti-persistence adjuvants.

Actors Synergy Model of The Ummah Economic Development Zone

The Ummah Economic Development Zone (ZPEU) is an initiative by the Kedah State Zakat Board (LZNK) through the paddy estate project, focusing on empowering farmers among the Asnaf in the agricultural sector. To strengthen the development of ZPEU, building strategic relationships among institutions involved in the rice production chain is a key strategy for increasing crop yields and improving the living standards of Asnaf. This paper aims to develop a synergy model for strategic relationships between stakeholders in the ZPEU project. This model fosters an environment where community and innovation can flourish, engaging all parties to create new jobs and enhance the standard of living for local communities through new products and services.

The Synergy Model of Quality Tools and Methods and Its Influence on Process Performance and Improvement

Implementing quality tools and methods creates a basic foundation for innovations, sustainability, optimization, and competitiveness in the era of Industry 4.0 and Quality 4.0. This paper aimed to investigate the use of quality tools and methods in the 24 divisions of a mother manufacturing company without the influence of external factors such as geographical location (America, Africa, Asia, and Europe). It was important for the mother manufacturing company to implement a uniform process standard for innovation and performance. Research methods focused on using the Kanban card, Ishikawa diagram, affinity diagram, Flowchart, 5S, OPL, layout, and Pareto analysis. It was determined in this research that the synergy (combination) of quality tools and methods in divisions improves the process performance. This hypothesis was confirmed by the results of implementing quality tools in processes within divisions. A top result was the new innovative model of synergy of the quality tools and methods for divisions of the parent company thus filling a gap in the scientific field. This model created the basis for the uniform process standard in all divisions. The results brought improvements in the processes such as material input inspection, spare parts production, production process, and product packaging. This model could be a proactive instrument for process innovation.

Hedgehog signaling mastery: R51211's promise in augmenting the therapeutic efficacy of sorafenib

Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer.

Conversational Speech Behaviors Are Context Dependent.

According to the interpersonal synergy model of spoken dialogue, interlocutors modify their communicative behaviors to meet the contextual demands of a given conversation. Although a growing body of research supports this postulation for linguistic behaviors (e.g., semantics, syntax), little is understood about how this model applies to speech behaviors (e.g., speech rate, pitch). The purpose of this study is to test the hypothesis that interlocutors adjust their speech behaviors across different conversational tasks with different conversational goals. In this study, 28 participants each engaged in two different types of conversations (i.e., relational and informational) with two partners (i.e., Partner 1 and Partner 2), yielding a total of 112 conversations. We compared six acoustic measures of participant speech behavior across conversational task and partner. Linear mixed-effects models demonstrated significant differences between speech feature measures in informational and relational conversations. Furthermore, these findings were generally robust across conversations with different partners. Results suggest that contextual demands influence speech behaviors. These findings provide empirical support for the interpersonal synergy model and highlight important considerations for assessing speech behaviors in individuals with communication disorders.

A novel combination therapy targets sonic hedgehog signaling by the dual inhibition of HMG-CoA reductase and HSP90 in rats with non-alcoholic steatohepatitis

Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-β, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders.

Alzheimer's Disease in Lebanon: Exploring Genetic and Environmental Risk Factors-A Comprehensive Review.

Alzheimer's disease (AD) is a neurodegenerative condition that displays a high prevalence in Lebanon causing a local burden in healthcare and socio-economic sectors. Unfortunately, the lack of prevalence studies and clinical trials in Lebanon minimizes the improvement of AD patient health status. In this review, we include over 155 articles to cover the different aspects of AD ranging from mechanisms to possible treatment and management tools. We highlight some important modifiable and non-modifiable risk factors of the disease including genetics, age, cardiovascular diseases, smoking, etc. Finally, we propose a hypothetical genetic synergy model between APOE4 and TREM2 genes which constitutes a potential early diagnostic tool that helps in reducing the risk of AD based on preventative measures decades before cognitive decline. The studies on AD in Lebanon and the Middle East are scarce. This review points out the importance of genetic mapping in the understanding of disease pathology which is crucial for the emergence of novel diagnostic tools. Hence, we establish a rigid basis for further research to identify the most influential genetic and environmental risk factors for the purpose of using more specific diagnostic tools and possibly adopting a local management protocol.

Towards synergy: network facility development, whole process carbon reduction and pollution reduction, and regional disparities.

The in-depth implementation of the "Broadband China Strategy" is of great significance in promoting the synergistic governance of urban carbon reduction and pollution reduction. In this paper, based on the "Broadband China" pilot program implemented in China in 2014 as a quasi-natural experiment, the coupled synergy model is used to measure the carbon and pollution reduction synergy index based on the balanced panel data of 277 prefectural-level cities and above in China from 2006 to 2020, and the staggered and synthetic DID methods are applied to investigate the impact of the Broadband China strategy on carbon and pollution reduction synergy and its mechanism. strategy on carbon and pollution reduction synergy and its mechanism. The conclusions of the study show that (1) the Broadband China strategy significantly improves the synergistic governance of carbon reduction and pollution reduction. (2) The mechanism results show that Broadband China mainly realizes carbon and pollution synergistic governance by promoting source control and process innovation but does not have an effective mediating role in end-of-pipe treatment. (3) The results of heterogeneity analysis show that Broadband China weakens the traditional geographic advantage, narrows the carbon pollution synergistic governance gap at the national and regional levels, and significantly improves the regional carbon reduction and pollution reduction governance level. This paper examines the micro-mechanism of the Broadband China strategy on carbon pollution synergistic governance from the whole process of production activities, which provides a new perspective for the study of carbon pollution synergistic governance, and provides an empirical basis for carbon pollution synergistic governance in China.

Canopy garden model for synergy of land and sea area on Papan Island in Tojo Una Una Regency, Central Sulawesi

Pulau Papan is one part of the Togean archipelago, Kabupaten Tojo Una Una. Initially, the Pulau Papan area was part of Tiga Pulau Village, Walea Islands District and Malenge Village, Talatako District, because the people who lived in this area came from these two villages. However, in 2011 Pulau Papan was expanded along with the increase in the number of family heads by 638 people and became part of the Kadoda Village area, Talatako District. The aim of this research is to build synergy in destination development between sea space and land/island space by creating regional nodes that are beautiful and function for the public. The public function that is formed can be utilized by the community both as a public space and a functional area that is beneficial for the residents of Pulau Papan, for example a green area containing vegetables for the residents. This vegetable green area is needed because of the limited vegetables on Pulau Papan. The solution proposed in this research is to design a canopy garden model that can become a green structure in the Pulau Papan area. The canopy garden will function to synergize the arrangement of land and sea areas on Pulau Papan. This canopy garden modeling was obtained through a survey process of the Pulau Papan area, then determining the meeting points for the mobility of residents on Pulau Pulau Papan. The public function that is formed can be utilized by the community both as a public space and a functional area that is beneficial for the residents of Pulau Papan, for example a green area containing vegetables for the residents.

Analysis of Coupling Coordination Degree of Digital Economy Industry Synergistic Development—Empirical Evidence Based on Urban Agglomerations in the Northern Region of China

With the rise of the national strategic position of Beijing-Tianjin-Hebei city cluster, Central Plains city cluster and Shandong Peninsula city cluster, inter-city cluster collaboration has become particularly important, and scientific evaluation of the level of digital economy industry synergistic development of major northern city clusters is conducive to cracking the dilemma of industrial synergy of major northern city clusters, and forming the pattern of high-quality integrated development. The data related to digital infrastructure, digital industrialization and industrial digitization of the Beijing-Tianjin-Hebei city cluster, the Central Plains city cluster and the Shandong Peninsula city cluster from 2013 to 2021 are selected, and the coupled synergy model is applied to evaluate the level of collaborative development of digital economy industries in major northern city clusters based on the analysis of digital economy industry development in major northern city clusters. The study found that: the coupling and coordination degree of digital economy industry of the three major northern city clusters from 2013 to 2021 has been improving, and the digital economy industry of the Beijing-Tianjin-Hebei city cluster will reach the intermediate level of coordination in 2021; in terms of the spatial synergy of the digital economy industry of the three city clusters, the synergy of the digital economy industry among the three clusters has reached the level of just barely dislocation, but the degree of industrial digitization synergy among the three clusters has obviously lags behind the level of digital infrastructure synergy and industrial digitalization synergy. Based on this, it puts forward countermeasures and suggestions to accelerate the top-level design of digital economy industry synergistic development in the major northern city clusters and to establish institutional mechanisms to support the synergistic development of digital economy industry in the cities.

Abstract 7130: Dysregulated DNA repaired elicited by type 1 PRMT inhibitor in clear cell renal cell carcinoma enables development of novel combination therapies

Abstract Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of kidney cancer, notorious for its resistance to treatment and dismal prognosis. Advanced or metastatic cases on average display an 8% 5-year survival rate. Given the considerable number of diagnoses in advanced stages, it is evident that we require innovative therapeutic approaches. Our lab has developed a methodology to establish cell lines from tumors and adjacent normal tissues sourced from patients. Consequently, we've amassed a collection of cell lines, including those from patient-derived ccRCC and normal kidney cells. Using these ccRCC models, we demonstrated that the type I protein arginine methyltransferase inhibitor, MS023, elicits a dysregulated DNA repair phenotype. RNA-Seq analysis of ccRCC cells treated with MS023 unveiled a marked downregulation of genes associated with the homologous recombination (HR) pathway for double-strand break repair and the Fanconi Anemia (FA) pathway for interstrand crosslink (ICL) repair. In a follow-up investigation using paired normal and cancerous cell lines from the same patient, we identified resistance to MS023 in normal kidney cells that is not mirrored in the corresponding ccRCC cell line. This hints at a potential therapeutic window and provides a strong rationale for clinical pursuit. Poly-ADP ribose polymerase (PARP) inhibitors are known to yield a synergistic effect when employed in HR-deficient diseases, such as BRCA-deficient breast cancers. Since MS023 induces an HR-deficient phenotype, we hypothesize that combining it with Talazoparib, a PARP inhibitor, will produce a similar synergistic effect. Additionally, mitomycin C (MMC) is a clinically approved compound that induces ICLs. As MS023 impedes ICL repair by downregulating crucial ICL-repairing genes, combining these two drugs should likewise generate a synergistic effect. Through a drug screen across two of our ccRCC cell lines, we discovered that the cells exhibit sensitivity to various PARP inhibitors. Employing synergy checkerboard assays and the highest single-agent model of synergy, we have found that the combination of MS023 and Talazoparib, as well as the combination of MS023 and MMC, demonstrate synergy, significantly reducing cellular viability at lower doses of the combination treatments compared to mono-treatment conditions at their respective doses. Preliminary in vivo studies using patient-derived xenograft models have revealed that both MS023 and Talazoparib are well-tolerated in mice, both when administered individually and in combination. Our current knowledge base indicates that MS023 holds promise for clinical investigation, both as a standalone treatment and in combination with Talazoparib or MMC. These results present an exciting opportunity to shed new light on the challenging therapeutic landscape faced by ccRCC patients today. Citation Format: Karen Arevalo, Joseph Walton, Jalna Meens, Angel Sau Ni Ng, Laurie Ailles. Dysregulated DNA repaired elicited by type 1 PRMT inhibitor in clear cell renal cell carcinoma enables development of novel combination therapies [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 7130.