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Cancer is the main contributor for mortality in the world. Conventional therapy that available as the treatment options are chemotherapy, radiotherapy and surgery. However, these treatments are hardly cell-specific most of the time. Nowadays, extensive research and investigations are made to develop cell-specific approaches prior to cancer treatment. Some of them are photodynamic therapy, hyperthermia, immunotherapy, stem cell transplantation and targeted therapy. This review article will be focusing on the development of gene therapy in cancer. The objective of gene therapy is to correct specific mutant genes causing the excessive proliferation of the cell that leads to cancer. There are lots of explorations in the approach to modify the gene. The delivery of this therapy plays a big role in its success. If the inserted gene does not find its way to the target, the therapy is considered a failure. Hence, vectors are needed and the common vectors used are viral, non viral or synthetic, polymer based and lipid based vectors. The advancement of gene therapy in cancer treatment will be focussing on the top three cancer cases in the world which are breast, lung and colon cancer. In breast cancer, the discussed therapy are CRISPR/Cas9, siRNA and gene silencing whereas in colon cancer miRNA and suicide gene therapy and in lung cancer, replacement of tumor suppressor gene, CRISPR/Cas9 and miRNA.
Assuntos
Terapia Genética , Neoplasias , Humanos , Terapia Genética/métodos , Neoplasias/terapia , Neoplasias/genética , Animais , Vetores Genéticos , Sistemas CRISPR-Cas/genéticaRESUMO
Efficiently managing multiple process parameters is critical for achieving optimal performance in additive manufacturing. This study investigates the relationship between eight key parameters in fused deposition modeling (FDM) and their impact on responses like average surface roughness (Ra), tensile strength (TS), and flexural strength (FS) of carbon fiber-reinforced polyamide 12 (PA 12-CF) material. The study integrates response surface methodology (RSM), grey relational analysis (GRA), and grey wolf optimization (GWO) to achieve this goal. A total of 51 experiments were planned using a definitive screening design (DSD) based on response RSM. The printing process parameters, including layer thickness, infill density, and build orientation, significantly affect Ra, TS, and FS. GRA combines responses into a single measure, grey relational grade (GRG), and a regression model is developed. GWO is then employed to optimize GRG across parameters. Comparison with GRA-optimized parameters demonstrates GWO's ability to discover refined solutions, reducing average surface roughness to 4.63 µm and increasing tensile strength and flexural strength to 88.5 MPa and 103.12 MPa, respectively. Practical implications highlight the significance of GWO in industrial settings, where optimized parameters lead to reduced costs and improved product quality. This integrated approach offers a systematic methodology for optimizing FDM processes, ensuring robustness and efficiency in additive manufacturing applications.
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In recent years, fused deposition modeling (FDM) based on material extrusion additive manufacturing technology has become widely accepted as a cost-effective method for fabricating engineering components with net-shapes. However, the limited exploration of the influence of FDM process parameters on surface roughness parameters, i.e., Ra (average surface roughness), Rq (root mean square surface roughness), and Rz (maximum height of the profile) across different sides (bottom, top, and walls) poses a challenge for the fabrication of functional parts. This research aims to bridge the knowledge gap by analyzing surface roughness under various process parameters and optimizing it for nylon carbon fiber printed parts. A definitive screening design (DSD) was employed for experimental runs. The Pareto chart highlighted the significant effects of layer height, part orientation, and infill density on all surface roughness parameters and respective sides. The surface morphology was analyzed through optical microscopy. Multi-response optimization was performed using an integrated approach of composited desirability function and entropy. The findings of the present study hold significant industrial applications, enhancing the quality and performance of 3D printed parts. From intricate prototypes to durable automotive components, the optimized surfaces contribute to production of functional and visually appealing products across various sectors.
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Fused deposition modeling (FDM) is the most economical additive manufacturing (AM) technology available for fabricating complex part geometries. However, the involvement of numerous control process parameters and dimensional instabilities are challenges of FDM. Therefore, this study investigated the effect of 3D printing parameters on dimensional deviations, including the length, width, height, and angle of polylactic acid (PLA) printed parts. The selected printing parameters include layer height, number of perimeters, infill density, infill angle, print speed, nozzle temperature, bed temperature, and print orientation. Three-level definitive screening design (DSD) was used to plan experimental runs. The results revealed that infill density is the most consequential parameter for length and width deviation, while layer height is significant for angle and height deviation. The regression models developed for the four responses are non-linear quadratic. The optimal results are obtained considering the integrated approach of desirability and weighted aggregated sum product assessment (WASPAS). The optimal results include a layer height of 0.1 mm, a total of six perimeters, an infill density of 20%, a fill angle of 90°, a print speed of 70 mm/s, a nozzle temperature of 220 °C, a bed temperature of 70 °C, and a print orientation of 90°. The current study provides a guideline to fabricate assistive devices, such as hand and foot orthoses, that require high dimensional accuracies.
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End-milling operation of steel grade material is a challenging task as it is hard-to-cut material. Proper selection of cutting tools, cutting conditions, and cutting process parameters is important to improve productivity, surface quality, and tool life. Therefore, the present study investigated the end-milling operation of AISI 1522H steel grade under minimum-quantity lubrication (MQL) conditions using a novel blend of vegetable oils, namely canola and olive oil. Cutting process parameters considered were spindle speed (s), feed rate (f), depth of cut (d), width of cut (w), and cutting conditions (c), while responses were average surface roughness (Ra), cutting forces (Fc), tool wear (TW), and material removal rate (MRR). Experimental runs were designed based on the definitive screening design (DSD) method. Analysis of variance (ANOVA) results show that feed rate significantly affects all considered responses. Nonlinear prediction models were developed for each response variable, and their validity was also verified. Finally, multi-response optimization was performed using the combinative distance-based assessment (CODAS) method coupled with criteria importance through inter-criteria correlation (CRITIC). The optimized parameters found were: s = 1200 rpm, f = 320 mm/min, d = 0.6 mm, w = 8 mm, and c = 100 mL/h. Further, it was compared with other existing multi-response optimization methods and induced good results.
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The utilization of composite materials is increasing at a growing rate in almost all types of products, due to their strength-to-stiffness ratio. From this perspective, natural waste composites, i.e., wood waste composites, have also been investigated for their effective and sustainable employment. This paper deals with the application of hard and soft wood waste (i.e., acacia and cedar wood) with epoxy resin polymer to develop high strength and thermally stable wood composites. Mechanical (tensile, flexural, impact, and hardness) and thermal properties of samples are studied using Differential Scanning Calorimeter (DSC) and Thermo Gravimetric Analysis (TGA), respectively. The properties are evaluated by varying the type of wood waste and its percentage by weight. Based on the Taguchi Orthogonal Array Mixture Design, eighteen experiments are investigated. Analysis of variance (ANOVA) results show that wood waste type and wood waste content have a significant effect on all mechanical properties. From the TGA analysis, it is predicted that both types of wood waste composites exhibit similar thermal-induced degradation profiles in terms of the initial and final degradation temperatures. From the DSC results, higher glass transition temperature Tg is detected in 10% of the hardwood waste composite, and a reducing tendency of glass transition temperature Tg is observed with exceeding wood waste content. Moreover, hardwood waste at 10% demonstrated improved decomposition temperature Td, due to strong adhesion between waste and matrix.
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Three-dimensional printed plastic products developed through fused deposition modeling (FDM) endure long-term loading in most of the applications. The tensile creep behavior of such products is one of the imperative benchmarks to ensure dimensional stability under cyclic and dynamic loads. This research dealt with the optimization of the tensile creep behavior of 3D printed parts produced through fused deposition modeling (FDM) using polylactic acid (PLA) material. The geometry of creep test specimens follows the American Society for Testing and Materials (ASTM D2990) standards. Three-dimensional printing is performed on an open-source MakerBot desktop 3D printer. The Response Surface Methodology (RSM) is employed to predict the creep rate and rupture time by undertaking the layer height, infill percentage, and infill pattern type (linear, hexagonal, and diamond) as input process parameters. A total of 39 experimental runs were planned by means of a categorical central composite design. The analysis of variance (ANOVA) results revealed that the most influencing factors for creep rate were layer height, infill percentage, and infill patterns, whereas, for rupture time, infill pattern was found significant. The optimized levels obtained for both responses for hexagonal pattern were 0.1 mm layer height and 100% infill percentage. Some verification tests were performed to evaluate the effectiveness of the adopted RSM technique. The implemented research is believed to be a comprehensive guide for the additive manufacturing users to determine the optimum process parameters of FDM which influence the product creep rate and rupture time.
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Precise, economical and sustainable cutting operations are highly desirable in the advanced manufacturing environment. For this aim, the present study investigated the influence of cutting parameters (i.e., the cutting speed (c), feed rate (f), depth of cut (d) and positive rake angle (p)) and sustainable cutting conditions (dry and minimum quantity lubricant (MQL)) on cutting forces (i.e., feed force (Ff), tangential forces (Ft), radial force (Fr) and resultant cutting forces (Fc) and shape deviations (i.e., circularity and cylindricity) of a 6026-T9 aluminum alloy. The type of lubricant and insert used are virgin olive oil and uncoated tungsten carbide tool. Turning experiments were performed on a TAKISAWA TC-1 CNC lathe machine and cutting forces were measured with the help of a Kistler 9257B dynamometer. Shape deviations were evaluated by means of a Tesa Micro-Hite 3D DCC 474 coordinate measuring machine (CMM). Experimental runs were planned based on Taguchi mixture orthogonal array design L16. Analysis of variance (ANOVA) was performed to study the statistical significance of cutting parameters. Taguchi based signal to noise (S/N) ratios are applied for optimization of single response, while for optimization of multiple responses Taguchi based signal to noise (S/N) ratios coupled with multi-objective optimization on the basis of ratio analysis (MOORA) and criteria importance through inter-criteria correlation (CRITIC) are employed. ANOVA results revealed that feed rate, followed by a depth of cut, are the most influencing and contributing factors for all components of cutting forces (Ff, Ft, Fr, and Fc) and shape deviations (circularity and cylindricity). The optimized cutting parameters obtained for multi responses are c = 600 m/min, f = 0.1 mm/rev, d = 1 mm and p = 25°, while for cutting conditions, MQL is optimal.
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Welding distortion is a critical issue as it leads to severe deterioration of structural integrity of welded work piece and dimensional precision. This study aims at studying the effects of shielded metal arc welding (SMAW) parameters on the evolution of mechanical properties, including tensile strength, impact toughness, and hardness, along with angular distortion on a welded joint from SA 516 grade 70. Such parameters are analyzed and optimized by employing the Taguchi method and Grey relational analysis. SA 516 grade 70 is commercially used for fabrication of storage tanks, boilers and pressure vessels. SMAW is investigated with three levels of root gap, groove angle, electrode diameter, and pre-heat temperature, which were varied on a butt joint in flat (1 G) position to determine their effects on response variables at room temperature. Nine experiments were designed using a Taguchi L9 orthogonal array, welded according to American Society of Mechanical Engineers (ASME) section IX, and samples were prepared and tested as per ASTM A 370. The Taguchi method and Grey relational analysis were employed to observe the most significant parameters and optimal levels that synergically yield improved responses. Results are validated by conducting confirmatory experiments that show good agreement with optimum results.
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CASE: A 17-year-old male sustained an open fracture of the right medial malleolus (MM) with significant bone and soft tissue loss following a motor-vehicle accident. Following serial wound debridement, his ankle was effectively reconstructed with MM antiglide plate stabilization, iliac autogenous bone graft, and a free radial forearm soft tissue flap. CONCLUSIONS: Open MM fracture with bone and soft tissue loss is rare. It is feasible to treat this injury with a novel surgical reconstruction technique involving autogenous bicortical iliac bone graft and radial forearm free flap.