Journal articles: 'RD optimization'

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Selby, D. A. "Marketing event optimization." IBM Journal of Research and Development 51, no. 3.4 (May 2007): 409–19. http://dx.doi.org/10.1147/rd.513.0409.

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Kanagasabai, L. "Real Power Loss Reduction by Rock Dove Optimization and Fuligo Septica Optimization Algorithms." Journal of Engineering Sciences 7, no. 2 (2020): E1—E6. http://dx.doi.org/10.21272/jes.2020.7(2).e1.

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This paper aims to use the Rock Dove (RD) optimization algorithm and the Fuligo Septica optimization (FSO) algorithm for power loss reduction. Rock Dove towards a particular place is based on the familiar (sight) objects on the traveling directions. In the formulation of the RD algorithm, atlas and range operator, and familiar sight operators have been defined and modeled. Every generation number of Rock Dove is reduced to half in the familiar sight operator and Rock Dove segment, which hold the low fitness value that occupying the lower half of the generation will be discarded. Because it is implicit that the individual’s Rock Dove is unknown with familiar sights and very far from the destination place, a few Rock Doves will be at the center of the iteration. Each Rock Dove can fly towards the final target place. Then in this work, the FSO algorithm is designed for real power loss reduction. The natural vacillation mode of Fuligo Septica has been imitated to develop the algorithm. Fuligo Septica connects the food through swinging action and possesses exploration and exploitation capabilities. Fuligo Septica naturally lives in chilly and moist conditions. Mainly the organic matter in the Fuligo Septica will search for the food and enzymes formed will digest the food. In the movement of Fuligo Septica it will spread like a venous network, and cytoplasm will flow inside the Fuligo Septica in all ends. THE proposed RD optimization algorithm and FSO algorithm have been tested in IEEE 14, 30, 57, 118, and 300 bus test systems and simulation results show the projected RD and FSO algorithm reduced the real power loss. Keywords: optimal reactive power, transmission loss, Rock Dove, Fuligo Septica.

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Agrafiotis, D. K. "Multiobjective optimization of combinatorial libraries." IBM Journal of Research and Development 45, no. 3.4 (May 2001): 545–66. http://dx.doi.org/10.1147/rd.453.0545.

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Aydin, Cem Savas, Senim Ozgurler, Mehmet Bulent Durmusoglu, and Mesut Ozgurler. "Response surface approach to robust design of assembly cells through simulation." Assembly Automation 38, no. 4 (September 3, 2018): 450–64. http://dx.doi.org/10.1108/aa-08-2017-093.

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Purpose This paper aims to present a multi-response robust design (RD) optimization approach for U-shaped assembly cells (ACs) with multi-functional walking-workers by using operational design (OD) factors in a simulation setting. The proposed methodology incorporated the design factors related to the operation of ACs into an RD framework. Utilization of OD factors provided a practical design approach for ACs addressing system robustness without modifying the cell structure. Design/methodology/approach Taguchi’s design philosophy and response surface meta-models have been combined for robust simulation optimization (SO). Multiple performance measures have been considered for the study and concurrently optimized by using a multi-response optimization (MRO) approach. Simulation setting provided flexibility in experimental design selection and facilitated experiments by avoiding cost and time constraints in real-world experiments. Findings The present approach is illustrated through RD of an AC for performance measures: average throughput time, average WIP inventory and cycle time. Findings are in line with expectations that a significant reduction in performance variability is attainable by trading-off optimality for robustness. Reductions in expected performance (optimality) values are negligible in comparison to reductions in performance variability (robustness). Practical implications ACs designed for robustness are more likely to meet design objectives once they are implemented, preventing changes or roll-backs. Successful implementations serve as examples to shop-floor personnel alleviating issues such as operator/supervisor resistance and scepticism, encouraging participation and facilitating teamwork. Originality/value ACs include many activities related to cell operation which can be used for performance optimization. The proposed framework is a realistic design approach using OD factors and considering system stochasticity in terms of noise factors for RD optimization through simulation. To the best of the authors’ knowledge, it is the first time a multi-response RD optimization approach for U-shaped manual ACs with multi-functional walking-workers using factors related to AC operation is proposed.

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Abramov, A. M., and A. S. Kovalev. "Strength calculation and optimization of axle housing form." Izvestiya MGTU MAMI 4, no. 2 (January 20, 2010): 12–14. http://dx.doi.org/10.17816/2074-0530-69523.

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The article describes strength calcualtion on the casted axle housing of the truck using FEM-software and its further form optimization with topology optimization software, performed for RD center of KAMAZ JSC. The optimization provided 17% mass reduction of the casting.

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Bournas, R. M. "Optimization of TCP segment size for file transfer." IBM Journal of Research and Development 41, no. 3 (May 1997): 357–66. http://dx.doi.org/10.1147/rd.413.0357.

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Cascaval, C., E. Duesterwald, P. F. Sweeney, and R. W. Wisniewski. "Performance and environment monitoring for continuous program optimization." IBM Journal of Research and Development 50, no. 2.3 (March 2006): 239–48. http://dx.doi.org/10.1147/rd.502.0239.

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Katircioglu, K., T. M. Brown, and M. Asghar. "An SQL-based cost-effective inventory optimization solution." IBM Journal of Research and Development 51, no. 3.4 (May 2007): 433–45. http://dx.doi.org/10.1147/rd.513.0433.

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Xiao, Wu, Yan Yan Zhou, Shou Cheng Du, and Gao Hong He. "Process Parameters Optimization of the MTBE Reactive Distillation by Orthogonal Numberical Test and Least Square Method." Advanced Materials Research 550-553 (July 2012): 947–52. http://dx.doi.org/10.4028/www.scientific.net/amr.550-553.947.

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Because of the large number of operating and equipment parameters of the reactive distillation(RD) and a strong coupling between them, it is difficult to find the optimal process parameters. A novel hybrid method on process parameters optimization of methyl tertiary butyl ether (MTBE) RD was developed in the paper. MTBE RD process was firstly simulated with Aspen Plus. Then based on the MTBE RD model, sensitivity analysis of various parameters was accomplished to determine the key decision parameters. After that, the orthogonal numerical tests were performed in feasible fields to obtain nearly optimal parameters. Finally, with the orthogonal numerical test results, the least square method was used to regress equation, which showed the relationship between objective function and the key decision parameters, thus determining the optimal operating parameters and equipment parameters. Results of analysis indicated that the combination of orthogonal numerical test and the least square method can be attractive since the number of tests was reduced substantially while the specification of the products can be met.

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Poindexter, D. J., S. R. Stiffler, P. T. Wu, P. D. Agnello, T. Ivers, S. Narasimha, T. B. Faure, et al. "Optimization of silicon technology for the IBM System z9." IBM Journal of Research and Development 51, no. 1.2 (January 2007): 5–18. http://dx.doi.org/10.1147/rd.511.0005.

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Gresh, D. L., D. P. Connors, J. P. Fasano, and R. J. Wittrock. "Applying supply chain optimization techniques to workforce planning problems." IBM Journal of Research and Development 51, no. 3.4 (May 2007): 251–61. http://dx.doi.org/10.1147/rd.513.0251.

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Alzahrani, Ibrahim R., and Randa Allafi. "Integrating Ebola optimization search algorithm for enhanced deep learning-based ransomware detection in Internet of Things security." AIMS Mathematics 9, no. 3 (2024): 6784–802. http://dx.doi.org/10.3934/math.2024331.

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<abstract> With the widespread use of Internet, Internet of Things (IoT) devices have exponentially increased. These devices become vulnerable to malware attacks with the enormous amount of data on IoT devices; as a result, malware detection becomes a major problem in IoT devices. A reliable and effective mechanism is essential for malware detection. In recent years, research workers have developed various techniques for the complex detection of malware, but accurate detection continues to be a problem. Ransomware attacks pose major security risks to corporate and personal information and data. The owners of computer-based resources can be influenced by monetary losses, reputational damage, and privacy and verification violations due to successful assaults of ransomware. Therefore, there is a need to swiftly and accurately detect the ransomware. With this motivation, the study designs an Ebola optimization search algorithm for enhanced deep learning-based ransomware detection (EBSAEDL-RD) technique in IoT security. The purpose of the EBSAEDL-RD method is to recognize and classify the ransomware to achieve security in the IoT platform. To accomplish this, the EBSAEDL-RD technique employs min-max normalization to scale the input data into a useful format. Also, the EBSAEDL-RD technique makes use of the EBSA technique to select an optimum set of features. Meanwhile, the classification of ransomware takes place using the bidirectional gated recurrent unit (BiGRU) model. Then, the sparrow search algorithm (SSA) can be applied for optimum hyperparameter selection of the BiGRU model. The wide-ranging experiments of the EBSAEDL-RD approach are performed on benchmark data. The obtained results highlighted that the EBSAEDL-RD algorithm reaches better performance over other models on IoT security. </abstract>

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Dani, Fatimatuz Zahro Diah Putri. "OPTIMIZATION OF RESEARCH AND DEVELOPMENT AGENCY’S RESEARCH RESULTS INTO THE FORM OF DEVELOPMENT PRODUCTS." Natapraja 10, no. 1 (November 10, 2022): 29–43. http://dx.doi.org/10.21831/natapraja.v10i1.47398.

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This study aims to mapping and identifying research and use of research into development products carried out by the Research and Development (RD) Agency of the Ministry of Religion during 2018-2020. In addition, this study also aims to analyze what obstacles can hinder and what solutions can be given in optimizing the utilization of the research results of the RD Ministry of Religion in product development. The research method used in this study is a qualitative method, with typology method and analyzed using qualitative descriptive. Data collection used document studies as secondary data and in-depth interviews with several stakeholders as primary data. The scope of this research are the central work unit and regional work unit in the Ministry of Religion whose main task is to conduct RD. The findings of this study indicate that the utilization of RD of the Ministry of Religion in the form of product development has not been optimal yet. This is indicated by data showing that from 330 studies conducted, 25% of these studies have been developed into a product while the remaining 75% has not been utilized as a product development. Five classifications of constraints were also identified in this study, financial, operational, socialization, human resources and policy constraints. Human resource constraints and policy constraints are the most inhibiting factors in the use of research. Once these constraints are identified.

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Jin, Zujin, Gang Cheng, Yusong Pang, Shichang Xu, and Dunpeng Yuan. "Multi-Objective Parameter Optimization of Flexible Support System of Optical Mirror." Applied Sciences 11, no. 17 (August 31, 2021): 8071. http://dx.doi.org/10.3390/app11178071.

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During the processing of an optical mirror, the performance parameters of the bottom support system would affect the surface forming accuracy of the mirror. The traditional bottom support system has a large unadjustable support stiffness, which increases the difficulty of unloading the impact force generated by the grinding disc. In response to this scenario, a flexible support system (FSS) consisting of 36 support cylinders with beryllium bronze reeds (BBRs) and rolling diaphragms (RDs) as key components is designed. It is necessary to analyze the key components of the support cylinder to reduce its axial movement resistance, ensure a consistent force output of each support point. First, the internal resistance model of a flexible support cylinder is established, and the main factors of internal resistance are then analyzed. Thereafter, the multi-objective structural parameters of the BBR and RD are simulated in ANSYS using the control variable method. The optimal structural parameters of BBR and RD are determined by simulation. Finally, experiments are performed on the RD ultimate pressure, internal resistance of the support cylinder, and consistency of the force output of the FSS. The experimental results show that the support cylinder with the optimized design has good force output consistency, which provides a theoretical basis for the application of FSS in optical mirror processing.

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Muller, S., and C. Supatgiat. "A quantitative optimization model for dynamic risk-based compliance management." IBM Journal of Research and Development 51, no. 3.4 (May 2007): 295–307. http://dx.doi.org/10.1147/rd.513.0295.

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Korevaar, P., U. Schimpel, and R. Boedi. "Inventory budget optimization: Meeting system-wide service levels in practice." IBM Journal of Research and Development 51, no. 3.4 (May 2007): 447–64. http://dx.doi.org/10.1147/rd.513.0447.

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Better, M., F. Glover, and M. Laguna. "Advances in analytics: Integrating dynamic data mining with simulation optimization." IBM Journal of Research and Development 51, no. 3.4 (May 2007): 477–87. http://dx.doi.org/10.1147/rd.513.0477.

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Wang Yue-Gang, Wen Chao-Bin, Zuo Zhao-Yang, Yang Jia-Sheng, and Guo Zhi-Bin. "Adaptive chaotic ant colony optimization-RD based gravity matching aided navigation." Acta Physica Sinica 63, no. 8 (2014): 089101. http://dx.doi.org/10.7498/aps.63.089101.

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Ding, Zihang, Junwei Xie, and Zhengjie Li. "Adaptive Transmit Beamspace Optimization Design based on RD-log-FDA Radar." Journal of Systems Engineering and Electronics 33, no. 1 (February 2022): 91–96. http://dx.doi.org/10.23919/jsee.2022.000010.

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Repiský, Jozef. "OPTIMIZATION OF INVESTMENT STRATEGY FOR THE ACQUISITION OF MEANS OF MECHANIZATION." RURAL DEVELOPMENT 2019 2021, no. 1 (January 24, 2022): 414–18. http://dx.doi.org/10.15544/rd.2021.071.

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Corbin, J. S. "Finite element analysis for Solder Ball Connect (SBC) structural design optimization." IBM Journal of Research and Development 37, no. 5 (September 1993): 585–96. http://dx.doi.org/10.1147/rd.375.0585.

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Hathaway, D. J., R. R. Habra, E. C. Schanzenbach, and S. J. Rothman. "Circuit placement, chip optimization, and wire routing for IBM IC technology." IBM Journal of Research and Development 40, no. 4 (July 1996): 453–60. http://dx.doi.org/10.1147/rd.404.0453.

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Naveh, Y., Y. Richter, Y. Altshuler, D. L. Gresh, and D. P. Connors. "Workforce optimization: Identification and assignment of professional workers using constraint programming." IBM Journal of Research and Development 51, no. 3.4 (May 2007): 263–79. http://dx.doi.org/10.1147/rd.513.0263.

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Cai, Fu, Yushu Zhang, Huiqing Ming, Na Mi, Shujie Zhang, Hui Zhang, Yanbing Xie, and Xianli Zhao. "Comparison of the Roles of Optimizing Root Distribution and the Water Uptake Function in Simulating Water and Heat Fluxes within a Maize Agroecosystem." Water 10, no. 8 (August 17, 2018): 1090. http://dx.doi.org/10.3390/w10081090.

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Roots are an important water transport pathway between soil and plant. Root water uptake (RWU) plays a key role in water and heat exchange between plants and the atmosphere. Inaccurate RWU schemes in land surface models are one crucial reason for decreased model performance. Despite some types of RWU functions being adopted in land surface models, none have been certified as suitable for maize farmland ecosystems. Based on 2007–2009 data observed at the maize agroecosystem field station in Jinzhou, China, the RWU function and root distribution (RD) in the Common Land Model (CoLM) were optimized and the effects of the optimizations on model performance were compared. Results showed that RD parameters calculated with root length density were more practical relative to root biomass in reflecting soil water availability, and they improved the simulation accuracy for water and heat fluxes. The modified RWU function also played a significant role in optimizing the simulation of water and heat fluxes. Similarly, the respective and integrated roles of two optimization schemes in improving CoLM performance were significant during continuous non-precipitation days, especially during the key water requirement period of maize. Notably, the improvements were restrained within a threshold of soil water content, and the optimizations were inoperative outside this threshold. Thus, the optimized RWU function and the revised RD introduced into the CoLM model are applicable for simulation of water and heat fluxes for maize farmland ecosystems in arid areas.

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Manikandan, M., G. Thiyagarajan, S. Thenmozhi, S. K. Natarajan, J. Bhuvaneswari, and N. K. Prabhakaran. "Optimization of Irrigation and Fertigation Scheduling for Sustainable Sugarcane Initiative (SSI) through Subsurface Drip Irrigation in Western Zone of Tamil Nadu." Current Agriculture Research Journal 7, no. 1 (April 9, 2019): 117–21. http://dx.doi.org/10.12944/carj.7.1.14.

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Sustainable Sugarcane Initiative (SSI) under Sub Surface Drip Irrigation (SSDI) is gaining momentum among the farmers because of more output with less input. Even though the benefits of SSI under SSDI are realized by farmers, development of optimal irrigation and fertigation schedule is need of the hour for Western Agro-climatic zone of Tamil Nadu. Field trials were carried out at Agricultural Research Station, Bhavanisagar from 2014 to 2017 to develop an optimal irrigation and fertigation schedule for SSI for Western Agro-climatic zone. The experiment was taken in a randomized block design with three replications. The experiment consisted of eight treatments of which six treatments comprised of SSDI with three irrigation regimes of 100, 80 and 60 percent pan evaporation and two fertigation levels of 100 and 75 percent of recommended N & K and two treatments in surface drip irrigation (SDI) with 100 percent pan evaporation (PE) + 100 percent RD and 100 percent PE + 75 percent RD of N&K through fertigation. The results of this study revealed that SSDI with 60 per cent PE + 100 per cent RD of N&K through fertigation recorded lower water use (1004 mm) and higher WUE (113 kg/ha-mm). However, significantly higher and comparable yield of sugarcane (148 t/ha) was recorded in SSDI with 100 per cent PE + 100 per cent RD of N&K through fertigation and surface drip irrigation with 100 per cent PE + 100 per cent RD of N&K through fertigation. The net return (Rs. 2,09,405 per ha) and B:C ratio (2.6) was higher in SSDI with 100per cent PE + 100 per cent RD of N&K through fertigation treatment.

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Xu, Yangli, Guangyao Han, Guoqin Huang, Tingting Li, Jiaxu Xia, and Donghai Guo. "Properties Evaluations of Topology Optimized Functionally Graded Lattice Structures Fabricated by Selective Laser Melting." Materials 16, no. 4 (February 17, 2023): 1700. http://dx.doi.org/10.3390/ma16041700.

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Owning to their lightweight characteristic and high performance, functionally graded lattice structures (FGLSs) show great potential in orthopedics, automotive industries and aerospace applications. Here, two types of uniform lattice structures (ULSs) with RD = 0.50 and 0.20, and two types of FGLSs with RD = 0.30–0.50 and RD = 0.20–0.40, were designed by topology optimization and fabricated by SLM technology. Subsequently, their surface morphology, compressive deformation behavior and energy absorption abilities were evaluated by use of the finite element method (FEM) and compression tests. From these results, both elastic modulus and yield strength of specimens decreased with the lowering of the RD value. ULSs had a uniform deformation behavior with bending and bulking of struts, while FGLSs presented a mixed deformation behavior of different layers. Additionally, the energy absorption capability (Wv) of specimens was proportional to the RD value. When the value of RD increased from 0.20 to 0.50, the Wv of specimens increased from 0.3657 to 1.7469 MJ/m3. Furthermore, mathematical models were established successfully to predict the mechanical properties of FGLSs with percentage deviations < 10%. This work provides a comprehensive understanding regarding how to design and manufacture FGLSs with the properties desired for satisfying the demand of different application scenarios.

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Liu, Yu, Qin Yu Gao, Lian Xin Liu, and Guang Xia Shi. "Study on Industry Process of the Rubber Anti-Oxidant RD." Applied Mechanics and Materials 79 (July 2011): 99–104. http://dx.doi.org/10.4028/www.scientific.net/amm.79.99.

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This paper studied on the industry synthesis process of anti-oxidant RD ((2,2,4- trimethyl-1,2-dihydro- quinoline polymer (C12H15N)n.n=2-4)) .The content of dimer, trimer and tetramer of RD were taken as the inspection targets, used the orthogonal design method, and take the ratios of keto-amine, the reaction time, the reaction temperatures and the ratios of catalyst acid-amine as inspect factors to optimized reaction condition. The result indicated that the best ratio of keto-amine is 6.5:1, the reaction time is 6 hours, the range of the reaction temperature is 115-120°C, the beat ratio of acid-amine is 0.2: 1 (the proportion is the concentration ratio for mole). Under the optimization conditions, the yield stability of RD.

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Bernstein, K., J. E. Bertsch, L. G. Heller, E. J. Nowak, and F. R. White. "Reduced-voltage power/performance optimization of the 3.6-volt PowerPC 601 Microprocessor." IBM Journal of Research and Development 39, no. 1.2 (January 1995): 33–42. http://dx.doi.org/10.1147/rd.391.0033.

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Meyerson, B. S. "Silicon:germanium-based mixed-signal technology for optimization of wired and wireless telecommunications." IBM Journal of Research and Development 44, no. 3 (May 2000): 391–407. http://dx.doi.org/10.1147/rd.443.0391.

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Zhou, Fujie, Sheng Hu, Susan T. Chrysler, Yangwoo Kim, Ivan Damnjanovic, Alireza Talebpour, and Alejandro Espejo. "Optimization of Lateral Wandering of Automated Vehicles to Reduce Hydroplaning Potential and to Improve Pavement Life." Transportation Research Record: Journal of the Transportation Research Board 2673, no. 11 (June 6, 2019): 81–89. http://dx.doi.org/10.1177/0361198119853560.

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The deployment of automated vehicles (AVs) has many potential benefits, such as reductions in congestion and emissions, and safety improvements. However, two notable aspects of AVs are their impact on roadway hydroplaning and pavement life. Since most AVs are programmed to follow a set path and maintain a lateral position in the center of the lane, over time, significant rutting will occur in asphalt surfaced pavements. This study measured AV lateral wandering patterns and compared them with human driven vehicles. Both wandering patterns could be modeled with a normal distribution but have significantly different standard deviations. AVs have a standard deviation for the lateral traffic wander pattern at least three times smaller than human driven vehicles. The influences of AVs with smaller lateral wandering on pavement rutting and fatigue life were analyzed with the Texas Mechanistic-Empirical Flexible Pavement Design system. The research discovered that AVs would shorten pavement fatigue life by 20%. Additionally, pavement rut depths (RD) increased by 13% and reached critical values of the RD 30% earlier. Deeper ruts formed more quickly leading to thicker water films on wet roads, and consequently, a much higher risk of hydroplaning. The research also calculated maximum tolerable RDs at different hydroplaning speeds. AVs have a much smaller tolerable RD human driven vehicles because of a greater water film in the rutted wheel path. This research thus proposed an optimal AV lateral wandering pattern: a uniform distribution. A uniformly distributed lateral wandering pattern for AVs prolongs pavement fatigue life, reduces pavement RD, and decreases hydroplaning potential.

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Caporale, Marco, Christina Cousens, Patrizia Centorame, Chiara Pinoni, Marcelo De las Heras, and Massimo Palmarini. "Expression of the Jaagsiekte Sheep Retrovirus Envelope Glycoprotein Is Sufficient To Induce Lung Tumors in Sheep." Journal of Virology 80, no. 16 (August 15, 2006): 8030–37. http://dx.doi.org/10.1128/jvi.00474-06.

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ABSTRACT Jaagsiekte sheep retrovirus (JSRV) is the causative agent of ovine pulmonary adenocarcinoma (OPA). The expression of the JSRV envelope (Env) alone is sufficient to transform a variety of cell lines in vitro and induce lung cancer in immunodeficient mice. In order to determine the role of the JSRV Env in OPA tumorigenesis in sheep, we derived a JSRV replication-defective virus (JS-RD) which expresses env under the control of its own long terminal repeat (LTR). JS-RD was produced by transiently transfecting 293T cells with a two plasmid system, involving (i) a packaging plasmid, with the putative JSRV packaging signal deleted, expressing the structural and enzymatic proteins Gag, Pro, and Pol, and (ii) a plasmid which expresses env in trans for JS-RD particles and provides the genomes necessary to deliver JSRV env upon infection. During the optimization of the JS-RD system we determined that both R-U5 (in the viral 5′ LTR) and the env region are important for JSRV particle production. Two independent experimental transmission studies were carried out with newborn lambs. Four of five lambs inoculated with JS-RD showed OPA lesions in the lungs at various times between 4 and 12 months postinoculation. Abundant expression of JSRV Env was detected in tumor cells of JS-RD-infected animals and PCR assays confirmed the presence of the deleted JS-RD genome. These data strongly suggest that the JSRV Env functions as a dominant oncoprotein in the natural immunocompetent host and that JSRV can induce OPA in the absence of viral spread.

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Xuhui, WENG, LEI Wuhu, and REN Xiaodong. "Nonlinear unmixing of hyperspectral images based on double-bi rd flock optimization." Journal of Applied Optics 40, no. 6 (2019): 1059–66. http://dx.doi.org/10.5768/jao201940.0602003.

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Wasilkowski, G. W., and H. Woźniakowski. "Complexity of Weighted Approximation over Rd." Journal of Complexity 17, no. 4 (December 2001): 722–40. http://dx.doi.org/10.1006/jcom.2001.0601.

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Al-Shareeda, Mahmood A., Selvakumar Manickam, Murtaja Ali Saare, and Navaneethan C. Arjuman. "Proposed security mechanism for preventing fake router advertisement attack in IPv6 link-local network." Indonesian Journal of Electrical Engineering and Computer Science 29, no. 1 (January 1, 2022): 518. http://dx.doi.org/10.11591/ijeecs.v29.i1.pp518-526.

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The design of router discovery (RD) is a trust mechanism to confirm the legitimacy of the host and router. Fake router advertisement (RA) attacks have been made possible by this RD protocol design defect. Studies show that the standard RD protocol is vulnerable to a fake RA attack where the host will be denied a valid gateway. To cope with this problem, several prevention techniques have been proposed in the past to secure the RD process. Nevertheless, these methods have a significant temporal complexity as well as other flaws, including the bootstrapping issue and hash collision attacks. Thus, the SecMac-secure router discovery (SecMac-SRD) technique, which requires reduced processing time and may thwart fake RA assaults, is proposed in this study as an improved secure RD mechanism. SecMac-SRD is built based on a UMAC hashing algorithm with ElGamal public key distribution cryptosystem that hides the RD message exchange in the IPv6 link-local network. Based on the obtained expected results display that the SecMac-SRD mechanism achieved less processing time compared to the existing secure RD mechanism and can resist fake RA attacks. The outcome of the expected results clearly proves that the SecMac-SRD mechanism effectively copes with the fake RA attacks during the RD process.

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Gao, Hongchang. "Distributed Stochastic Nested Optimization for Emerging Machine Learning Models: Algorithm and Theory." Proceedings of the AAAI Conference on Artificial Intelligence 37, no. 13 (June 26, 2023): 15437. http://dx.doi.org/10.1609/aaai.v37i13.26804.

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Traditional machine learning models can be formulated as the expected risk minimization (ERM) problem: minw∈Rd Eξ [l(w; ξ)], where w ∈ Rd denotes the model parameter, ξ represents training samples, l(·) is the loss function. Numerous optimization algorithms, such as stochastic gradient descent (SGD), have been developed to solve the ERM problem. However, a wide range of emerging machine learning models are beyond this class of optimization problems, such as model-agnostic meta-learning (Finn, Abbeel, and Levine 2017). Of particular interest of my research is the stochastic nested optimization (SNO) problem, whose objective function has a nested structure. Specifically, I have been focusing on two instances of this kind of problem: stochastic compositional optimization (SCO) problems, which cover meta-learning, area-under-the-precision recall-curve optimization, contrastive self-supervised learning, etc., and stochastic bilevel optimization (SBO) problems, which can be applied to meta-learning, hyperparameter optimization, neural network architecture search, etc. With the emergence of large-scale distributed data, such as the user data generated on mobile devices or intelligent hardware, it is imperative to develop distributed optimization algorithms for SNO (Distributed SNO). A significant challenge for optimizing distributed SNO problems lies in that the stochastic (hyper-)gradient is a biased estimation of the full gradient. Thus, existing distributed optimization algorithms when applied to them suffer from slow convergence rates. In this talk, I will discuss my recent works about distributed SCO (Gao and Huang 2021; Gao, Li, and Huang 2022) and distributed SBO (Gao, Gu, and Thai 2022; Gao 2022) under both centralized and decentralized settings, including algorithmic details about reducing the bias of stochastic gradient, theoretical convergence rate, and practical machine learning applications, and then highlight challenges for future research.

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Lougee-Heimer, R. "The Common Optimization INterface for Operations Research: Promoting open-source software in the operations research community." IBM Journal of Research and Development 47, no. 1 (January 2003): 57–66. http://dx.doi.org/10.1147/rd.471.0057.

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Iwut, Iwan, Gelar Budiman, and Ledya Novamizanti. "Optimization of Discrete Cosine Transform-Based Image Watermarking by Genetics Algorithm." Indonesian Journal of Electrical Engineering and Computer Science 4, no. 1 (October 1, 2016): 91. http://dx.doi.org/10.11591/ijeecs.v4.i1.pp91-103.

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data in an image file is needed by its owner to set his ownership in a logo as a watermark embedded in the image file. Hiding the logo in the image was done in several methods. One of the method is domain transform using 2D-DCT in which data is embedded in frequency domain of the image. First, the host RGB image is converted to certain color space. The available and chosen color spaces are RGB, YCbCr or NTSC. The layer in which the watermark is embedded also can be selected. The available choices are 1st layer, 2nd layer, 3rd layer, 1st & 2nd layer, 2nd & 3rd layer, 1st & 3rd layer and all layers. After the selected layer of image in certain color space is transformed in block based to frequency domain by DCT, one bit watermark is embedded on the AC coefficient of each block such a way that the bit is represented by specific value called delta in a zigzag and vary length of pixel. The vary parameters optimized by Genetics Algorithm are selected color space, selected layer, block size, length of pixel to be embedded by one bit watermark, and delta. Bit “1” is represented by +delta, and bit “0” is represented by –delta in vary length of pixel after zigzag. The simulation result performs that GA is useful to search the value of parameter that produces controllable the combination between robustness, invisibility and capacity. Thus, GA improves the method by determining the exact value of parameter achieving BER, PSNR and payload.

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Shakhmardanov, Murad Z., Aida S. Abusueva, Vladimir V. Nikiforov, Yuri N. Tomilin, and Svetlana V. Burova. "Incidence of brucellosis in the Republic of Dagestan in 2019." Epidemiology and Infectious Diseases 25, no. 3 (March 1, 2021): 112–16. http://dx.doi.org/10.17816/eid50362.

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BACKGROUND: Currently, brucellosis continues to pose a serious problem for public health and agriculture in Russia. In 2019, the number of Russian cases of bovine brucellosis increased by 14%, and the number of first-time identified poor points for small cattle brucellosis increased by 52%. Epizootics of the disease are registered mainly in North Caucasus and Southern Federal districts, and the maximum number of newly detected brucellosis in humans is recorded in the Republic of Dagestan (RD). AIMS: This study aimed to present the characteristics of brucellosis incidence in the RD in 2019 and optimization of preventive measures. MATERIALS AND METHODS: The study used state information on the incidence of brucellosis, mechanisms, ways, factors of pathogen transmission, and epidemic control activities of the infection in 2019 in the RD, provided by the S.M. Magomedov Republican Center of Infectious Diseases, Prevention and Fight Against AIDS and the Office of the Federal Service for Veterinary and Phytosanitary Surveillance of the RD. Statistical and epidemiological research methods were applied. RESULTS: In 2019, 163 new cases of brucellosis were registered in the RD, which was 52 (+47%) cases more than those in the same period in 2018, and the number of new cases of chronic brucellosis significantly increased (p 0.05). Individuals aged 41 years were more likely to get sick, patients were predominantly men (n = 135, 82.8%), rural residents accounted for 84.2%, and 56.1% were owners of personal livestock. Brucellosis was registered in 40 territories of the RD. The incidence rate was six times higher in rural areas than in urban areas. In humans, the source of infection was sheep and goats in 58.8% and cattle in 41.2% of cases. The main factor in the persistently high incidence of brucellosis in the RD was unsatisfactory examination and specific prevention among cattle, goats, and sheep. CONCLUSIONS: Thus, the epizootological and epidemiological situation of brucellosis in the RD should be considered unstable at present. With respect to the future of the brucellosis situation in the RD, the incidence of brucellosis in animals and humans will depend on the completeness of the implementation of plans for disease prevention.

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Dorroh, J. R., and Guillermo Ferreyra. "A Free Boundary Problem in Rd with Both Smooth and Nonsmooth Fit." SIAM Journal on Control and Optimization 36, no. 2 (March 1998): 579–89. http://dx.doi.org/10.1137/s0363012996301440.

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Ali, Syed Sadiq, Agus Arsad, SK Safdar Hossain, Avijit Basu, and Mohammad Asif. "Energy Optimization and Effective Control of Reactive Distillation Process for the Production of High Purity Biodiesel." Processes 9, no. 8 (July 30, 2021): 1340. http://dx.doi.org/10.3390/pr9081340.

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Biodiesel is a promising renewable energy option that significantly reduces the emission of greenhouse gases and other toxic byproducts. However, a major challenge in the industrial scale production of biodiesel is the desired product purity. To this end, reactive distillation (RD) processes, which involve simultaneous removal of the byproduct during the transesterification reaction, can drive the equilibrium towards high product yield. In the present study, we first optimized the heat exchange network (HEN) for a high purity RD process leading to a 34% reduction in the overall energy consumption. Further, a robust control scheme is proposed to mitigate any feed disturbance in the process that may compromise the product purity. Three rigorous case studies are performed to investigate the effect of composition control in the cascade with the temperature control of the product composition. The cascade control scheme effectively countered the disturbances and maintained the fatty acid mono-alkyl ester (FAME) purity.

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He, Liqiang, Shuhua Xiong, Ruolan Yang, Xiaohai He, and Honggang Chen. "Low-Complexity Multiple Transform Selection Combining Multi-Type Tree Partition Algorithm for Versatile Video Coding." Sensors 22, no. 15 (July 25, 2022): 5523. http://dx.doi.org/10.3390/s22155523.

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Despite the fact that Versatile Video Coding (VVC) achieves a superior coding performance to High-Efficiency Video Coding (HEVC), it takes a lot of time to encode video sequences due to the high computational complexity of the tools. Among these tools, Multiple Transform Selection (MTS) require the best of several transforms to be obtained using the Rate-Distortion Optimization (RDO) process, which increases the time spent video encoding, meaning that VVC is not suited to real-time sensor application networks. In this paper, a low-complexity multiple transform selection, combined with the multi-type tree partition algorithm, is proposed to address the above issue. First, to skip the MTS process, we introduce a method to estimate the Rate-Distortion (RD) cost of the last Coding Unit (CU) based on the relationship between the RD costs of transform candidates and the correlation between Sub-Coding Units’ (sub-CUs’) information entropy under binary splitting. When the sum of the RD costs of sub-CUs is greater than or equal to their parent CU, the RD checking of MTS will be skipped. Second, we make full use of the coding information of neighboring CUs to terminate MTS early. The experimental results show that, compared with the VVC, the proposed method achieves a 26.40% reduction in time, with a 0.13% increase in Bjøontegaard Delta Bitrate (BDBR).

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Castro, P., and A. Onteniente. "AB1150 ECONOMIC IMPACT ASSOCIATED TO BIOLOGICAL THERAPY / SYNTHETIC FAME OPTIMIZATION IN A COHORT OF PATIENTS WITH CHRONIC INFLAMMATORY RHEUMATIC DISEASES TREATED BY OBJECTIVES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1865.2–1866. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5354.

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Background:Therapeutic decision-making for biologic-therapies/ synthetic FAME (BT/SD) dose optimization, should be based on optimal disease activity results according to a treatment strategy by objectives. The goal of BT optimization is to guarantee long-term effectiveness and safety, maximising economic savingsObjectives:To evaluate BT optimization patterns in patients with rheumatic diseases (RD) and associated economic savings.Methods:An observational and prospective study, which included a cohort of patients with rheumatoid arthritis (RA), spondyloarthropathies (SA) and psoriatic arthritis (PsA) treated with BT from January 2014 to December 2019. BT optimization, achieved by reducing or prolonging the interval at least one dose, was indicated when patients have more than 6 months of treatment and are in clinical remission (DAS28 <2.6 for RA and PsA, and BASDAI<2 for SA) or minimal clinical activity (DAS28<3.2 for RA and PsA, and BASDAI<4 for SA).Variables were described as frequencies and means. Diagnosis, BT (abatacept, adalimumab, apremilast, baricitinib, certolizumab, etanercept, golimumab, ixekizumab, secukinumab, tocilizumab, tofacitinib, and ustekinumab), dose regimens, total treatment duration, time on BT optimization (TO) and treatment costs were collected.Cost savings were calculated per patient by comparing optimization treatment costs to conventional treatment and globally by comparing real cost to theoretical conventional doses cost.Results:A total of 260 patients were included in the study. Switching were observed in 32.7%. From all patients, 53% were candidates for BT optimization (according to diagnosis: 60.9% with RA, followed by 52.2% with SA and 43.4% with PsA)A 40% of patients with BT optimization were treated with adalimumab and etanercept being also the most common BT used in RD treatmentBT optimization allowed a pharmaceutical saving of€ 177,539.40per year against the use of conventional therapy, resulting in a reduction of the total cost of€1,065,236.40in the last 6 years. The saving per patient / year was € 707.63 for RA; € 850,40 for SA and of €493,21 for the PsA.Conclusion:Therapeutic decision-making based on validated disease activity scales has allowed the BT optimization in approximately 53% of patients with RD.BT optimization allowed a pharmaceutical saving of € 177,539.40 per year being higher in the SA (€ 850.40) followed by the RA (€ 707.63) and finally the PsA (€ 493.21)The BT optimization allows to reduce costs maintaining the effectiveness and safety.Disclosure of Interests:None declared

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Hamza, Ahmed M., Mohamed Abdelazim, Abdelrahman Abdelazim, and Djamel Ait-Boudaoud. "HEVC Rate-Distortion Optimization with Source Modeling." Electronic Imaging 2021, no. 10 (January 18, 2021): 259–1. http://dx.doi.org/10.2352/issn.2470-1173.2021.10.ipas-259.

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The Rate-Distortion adaptive mechanisms of MPEG-HEVC (High Efficiency Video Coding) and its derivatives are an incremental improvement in the software reference encoder, providing a selective Lagrangian parameter choice which varies by encoding mode (intra or inter) and picture reference level. Since this weighting factor (and the balanced cost functions it impacts) are crucial to the RD optimization process, affecting several encoder decisions and both coding efficiency and quality of the encoded stream, we investigate an improvement by modern reinforcement learning methods. We develop a neural-based agent that learns a real-valued control policy to maximize rate savings by input signal pattern, mapping pixel intensity values from the picture at the coding tree unit level, to the appropriate weighting-parameter. Our testing on reference software yields improvements for coding efficiency performance across different video sequences, in multiple classes of video.

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Samigullina, R. R., V. I. Mazurov, and E. A. Trofimov. "Characteristics of complex therapy of immuno-inflammatory rheumatic diseases in COVID-19 pandemic conditions." Russian Medical Inquiry 5, no. 5 (2021): 260–67. http://dx.doi.org/10.32364/2587-6821-2021-5-5-260-267.

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The rapid spread of a new coronavirus infection (COVID-19) requires innovative solutions, including tactics optimization in using genetically engineered and targeted drugs in patients with immuno-inflammatory rheumatic diseases (RD). The authors studied the characteristics of the complex therapy of immuno-inflammatory RD in the COVID-19 pandemic conditions, analyzed the COVID-19 course in patients with RD who received combined therapy with genetically engineered and basic synthetic anti-rheumatic drugs and were under follow-up from March 2020 to March 2021. The researchers found that synthetic basic (methotrexate, leflunomide, etc.), targeted synthetic (tofacitinib, baricitinib, apremilast) and biologic disease-modifying antirheumatic drugs used in the RD treatment, except high-dose glucocorticoids and anti-B cell drugs (rituximab), do not have a negative effect and are not associated with a severe COVID-19 course. The use of interleukin-6 (IL-6) inhibitors is the standard pathogenetic therapy for cytokine release syndrome in COVID-19. Proactive therapy with IL-6 inhibitors provides inhibition of systemic inflammation and contributes to the suppression of cytokine storm syndrome, preventing the development of multiple organ failure and fatal outcome. KEYWORDS: rheumatic diseases, cytokine storm, multiple organ failure, genetically engineered biological drugs, interleukin-6, COVID-19. FOR CITATION: Samigullina R.R., Mazurov V.I., Trofimov E.A. Characteristics of complex therapy of immuno-inflammatory rheumatic diseases in COVID-19 pandemic conditions. Russian Medical Inquiry. 2021;5(5):260–267 (in Russ.). DOI: 10.32364/2587-6821-2021- 5-5-260-267.

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Jurko, Jozef, Katarína Paľová, Peter Michalík, and Martin Kondrát. "Optimization of Sustainable Production Processes in C45 Steel Machining Using a Confocal Chromatic Sensor." Lubricants 12, no. 3 (March 16, 2024): 99. http://dx.doi.org/10.3390/lubricants12030099.

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Metal machining production faces a myriad of demands encompassing ecology, automation, product control, and cost reduction. Within this framework, an exploration into employing a direct inspection of the machined area within the work zone of a given machine through a confocal chromatic sensor was undertaken. In the turning process, parameters including cutting speed (A), feed (B), depth of cut (C), workpiece length from clamping (D), and cutting edge radius (E) were designated as input variables. Roundness deviation (Rd) and tool face wear (KM) parameters were identified as output factors for assessing process performance. The experimental phase adhered to the Taguchi Orthogonal Array L27. Confirmatory tests revealed that optimizing process parameters according to the Taguchi method could enhance the turning performance of C45 steel. ANOVA results underscored the significant impact of cutting speed (A), feed (B), depth of cut (C), and workpiece length from clamping (D) on turning performance concerning Rd and KM. Furthermore, initial regression models were formulated to forecast roundness variation and tool face wear. The proposed parameters were found to not only influence the machined surface but also affect confocal sensor measurements. Consequently, we advocate for the adoption of these optimal cutting conditions in product production to bolster turning performance when machining C45 steel.

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Janati, Ali, Djavad Ghoddoosi Nejad, Mehdi Ariafar, Seyyedeh Roghayyeh Mirshojaee, Mohammad Mahdavi Moghaddam, Saaied Ghodousi Nejad, Majid Ghodousi Nejad, Morteza Arab Zozani, Ali Vafaee, and Elham Baghban Baghestan. "Optimization of Nurse Numbers in Emergency Department of a District Hospital in a Developing Country Iran, 2014." Modern Applied Science 10, no. 5 (March 10, 2016): 41. http://dx.doi.org/10.5539/mas.v10n5p41.

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Background: this study aims to optimize nurse numbers in emergency department of a district hospital in Iran using linear programming.Material and methods: through observation and checklist data about average patient arrival, delivery time of care services needed for patients and number of nurses were obtained. Using linear programming optimum number of nurse needed for right delivery of services was calculated.Results: optimum number of nurses was calculated as 12 nurses, but because of some issues in 3rd shift, real number of nurses needed for a 24 hours period is equal to 16 (12+4) nurses (12 as minimum needed plus nurses who stay and don’t leave the 3rd shift till tomorrow morning).Conclusion: Using LP models can be useful for estimating optimum number of nurses for different wards of hospitals, so they can reduce their costs and reach more productivity.

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Saleh, Mustafa, Saqib Anwar, Abdulrahman M. Al-Ahmari, and Abdullah Yahia AlFaify. "Prediction of Mechanical Properties for Carbon fiber/PLA Composite Lattice Structures Using Mathematical and ANFIS Models." Polymers 15, no. 7 (March 30, 2023): 1720. http://dx.doi.org/10.3390/polym15071720.

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This study investigates the influence of design, relative density (RD), and carbon fiber (CF) incorporation parameters on mechanical characteristics, including compressive modulus (E), strength, and specific energy absorption (SEA) of triply periodic minimum surface (TPMS) lattice structures. The TPMS lattices were 3D-printed by fused filament fabrication (FFF) using polylactic acid (PLA) and carbon fiber-reinforced PLA(CFRPLA). The mechanical properties of the TPMS lattice structures were evaluated under uniaxial compression testing based on the design of experiments (DOE) approach, namely, full factorial design. Prediction modeling was conducted and compared using mathematical and intelligent modeling, namely, adaptive neuro-fuzzy inference systems (ANFIS). ANFIS modeling allowed the 3D printing imperfections (e.g., RD variations) to be taken into account by considering the actual RDs instead of the designed ones, as in the case of mathematical modeling. In this regard, this was the first time the ANFIS modeling utilized the actual RDs. The desirability approach was applied for multi-objective optimization. The mechanical properties were found to be significantly influenced by cell type, cell size, CF incorporation, and RD, as well as their combination. The findings demonstrated a variation in the E (0.144 GPa to 0.549 GPa), compressive strength (4.583 MPa to 15.768 MPa), and SEA (3.759 J/g to 15.591 J/g) due to the effect of the studied variables. The ANFIS models outperformed mathematical models in predicting all mechanical characteristics, including E, strength, and SEA. For instance, the maximum absolute percent deviation was 7.61% for ANFIS prediction, while it was 21.11% for mathematical prediction. The accuracy of mathematical predictions is highly influenced by the degree of RD deviation: a higher deviation in RD indicates a lower accuracy of predictions. The findings of this study provide a prior prediction of the mechanical behavior of PLA and CFRPLA TPMS structures, as well as a better understanding of their potential and limitations.

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Wang, Zhiqiong, Junchang Xin, and Pei Wang. "Alternative Tuples Based Probabilistic Skyline Query Processing in Wireless Sensor Networks." Mathematical Problems in Engineering 2015 (2015): 1–10. http://dx.doi.org/10.1155/2015/813507.

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As uncertainty is the inherent character of sensing data, the processing and optimization techniques for Probabilistic Skyline (PS) in wireless sensor networks (WSNs) are investigated. It can be proved that PS is not decomposable after analyzing its properties, so in-network aggregation techniques cannot be used directly to improve the performance. In this paper, an efficient algorithm, called Distributed Processing of Probabilistic Skyline (DPPS) query in WSNs, is proposed. The algorithm divides the sensing data into candidate data (CD), irrelevant data (ID), and relevant data (RD). The ID in each sensor node can be filtered directly to reduce data transmissions cost, since, only according to both CD and RD, PS result can be correctly obtained on the base station. Experimental results show that the proposed algorithm can effectively reduce data transmissions by filtering the unnecessary data and greatly prolong the lifetime of WSNs.

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Bardia, Aditya, Ciara Catherine O'Sullivan, Reshma L. Mahtani, Sibel Blau, Nihal E. Abdulla, Azka Ali, Rani Bansal, et al. "An open-label, multicenter, phase 2 study to evaluate the safety and efficacy of BB-1701, a novel antibody drug conjugate (ADC) targeting human epidermal growth factor receptor 2 (HER2), in previously treated patients with HER2-positive (HER2+) or HER2-low unresectable or metastatic breast cancer (BC)." Journal of Clinical Oncology 42, no. 16_suppl (June 1, 2024): TPS1122. http://dx.doi.org/10.1200/jco.2024.42.16_suppl.tps1122.

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TPS1122 Background: Treatment options for patients (pts) with unresectable or metastatic BC have improved with the development of novel targeted therapies including trastuzumab deruxtecan (T-DXd), an ADC directed against HER2 with a cytotoxic topoisomerase I inhibitor as a payload. Currently, there are limited treatment options for pts with HER2+ or HER2-low metastatic BC that has progressed on T-DXd. BB-1701 is an ADC consisting of a monoclonal antibody targeting HER2 with eribulin (microtubule inhibitor) as a payload that is capable of exerting a bystander effect. A first-in-human dose-finding Study 101 of BB-1701 is ongoing. Here we describe Study 205, an open label, multicenter, phase 2 study of BB-1701 in pts with HER2+ or HER2-low unresectable or metastatic BC who have disease progression after treatment with T-DXd. Methods: Study 205 (NCT06188559) includes dose-optimization and dose-expansion parts for BB-1701. Eligible pts must have histologically confirmed HER2+ or HER2-low, unresectable or metastatic BC, with measurable disease per RECIST v1.1. Prior treatment must include 1–3 prior chemotherapy-based regimens for unresectable or metastatic BC, including T-DXd. The primary objectives of the dose-optimization part include determining the recommended dose (RD) and evaluating safety and tolerability of BB-1701. The RD will be assessed by randomly assigning ~50 pts into 1 of 3 dosing cohorts (1.6 mg/kg on day 1 Q3W, 0.8 mg/kg on days 1 and 8 Q3W, and 1.2 mg/kg on day 1 Q3W; IV) in a 2:2:1 ratio. Randomization will be stratified by HER2 status (HER2+ vs. HER2-low) documented prior to T-DXd treatment. The dose-expansion part will enroll ~85 pts at RD; the primary objective includes evaluating the efficacy of BB-1701 at the RD. In both study parts, secondary objectives include assessment of additional efficacy measures (i.e., duration of response [DOR], progression free survival [PFS], overall survival [OS], disease control rate [DCR], clinical benefit rate [CBR], and time to response [TTR]), and pharmacokinetics. Efficacy endpoints will be assessed per RECIST v1.1 by the investigator during the dose-optimization part or by Blinded Independent Central Review during the dose-expansion part. Safety assessments will consist of recording, monitoring, and grading of adverse events (AEs) based on CTCAE v5.0, AEs of special interest, and serious AEs. In both study parts, exploratory objectives will include evaluation of biomarkers of response to BB-1701 and BB-1701 immunogenicity; other efficacy measures (i.e., PFS on the next line of therapy) and population pharmacokinetics will be analyzed in the dose-expansion part only. Pt enrollment is currently open. Clinical trial information: NCT06188559 .

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Sherman, Eric Jeffrey, Macarena Ines De La Fuente, Rona Yaeger, Frank Yung-Chin Tsai, Filip Janku, Nicholas A. Butowski, Carl E. Allen, et al. "Dose optimization of novel BRAF inhibitor FORE8394 based on PK and efficacy results." Journal of Clinical Oncology 41, no. 16_suppl (June 1, 2023): 3106. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.3106.

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3106 Background: FORE8394 is a selective inhibitor of class 1 (V600) and 2 (activating non-V600) BRAF alterations that avoids paradoxical MAPK pathway activation. Consistent with the paradigm shift to optimal dosing vs identifying the maximal tolerated dose, integrated pharmacokinetic (PK), genomics, safety, and efficacy data, and exposure-response modeling were used to identify the recommended dose (RD). Methods: In a single arm phase 1/2a study, patients (pts) age ≥3 years with advanced solid or CNS tumors with BRAF alterations received FORE8394 900-3600 mg/day with or without the PK enhancer cobicistat (cobi) until progression. Efficacy pts had class 1 or 2 BRAF alterations & ≥1 post-baseline assessment (mITT); the BRAF V600 MAPKi naïve, non CRC subset provided a homogenous subset to also inform dose selection. PK was evaluated after single and repeated dosing. Results: To date, 110 pts (age range 4-86 years) received ≥1 dose of FORE8394; 58% had ≥2 prior lines of therapy, 25% had prior MAPKi. PK was independent of age or weight. Cobi increased FORE8394 exposure 2-3-fold. Exposure increased with dose, with less than proportional increase at doses >900 mg BID. Higher Cmax and trough levels were achieved with QD vs BID/TID. Objective (confirmed) responses were observed at all doses; however, objective response rate (ORR) was greatest (50%) at 900mg QD + cobi, with no further increases in ORR at higher doses. Dose-limiting toxicities were only observed at doses ≥1500 mg/day + cobi: 1500-1800 mg/day (4) and 2700-3600 mg/day (1). Similarly, treatment-emergent adverse events (TEAEs) ≥Grade 3 (G3) increased at the higher doses. Only 1 pt discontinued FORE8394 due to treatment-related AE (G3 bilirubin; 3600 mg/day). Conclusions: Based on the entirety of safety, PK, and efficacy data, the optimal RD of FORE8394 in Phase 2 is 900 mg QD + cobi in pts ≥10 years old. This achieved targeted efficacious exposures with robust antitumor activity and favorable safety. This dose optimization is consistent with current guidelines, avoids higher exposure that may lead to higher toxicity and compromise dose intensity. QD dosing also allows for a convenient dosing regimen. A Phase 2 study at the RD is ongoing in pts with recurrent V600E BRAF-mutated primary CNS tumors and advanced solid or CNS tumors with BRAF fusions. Clinical trial information: NCT02428712 . [Table: see text]

Journal articles on the topic 'RD optimization'

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