Relational Grade Research Articles

OPTIMIZATION OF WEAR STUDIES ON LASER CLADDED AZ61 MAGNESIUM ALLOY WITH NANO-TITANIUM DIOXIDE USING GREY RELATIONAL ANALYSIS

Laser cladding (LC) is mostly employed to enhance the wear resistance of magnesium alloy substrates. Adding nanoparticles will further strengthen the tribo surface properties, making them suitable for applications requiring lightweight components. This work investigated a dry sliding wear analysis for the laser-cladded AZ61 magnesium alloy with TiO2 nanoparticles at different volume ratios through the LC method. The spatial dispersion of the TiO2 nanoparticles in the AZ61 magnesium alloy microstructure was analyzed using scanning electron microscopy (SEM). The reinforcement ratio, sliding speed, and normal load were selected to study the tribo performance of the cladded surface. Coefficient of friction (COF) and wear loss analyses were performed using a pin on the disc dry sliding wear test. The effect of dry sliding variables on reinforcement ratio was analyzed with an orthogonal array experimental design. Grey relational analysis (GRA) studied multiple wear test responses to reveal optimal conditions to decrease the wear and friction coefficient of the AZ61 laser cladded surface. The reinforcement percentage of nanoceramic TiO2 particles in the AZ61 alloy surface was the most significant factor, contributing 97.76%, followed by a contribution of 0.26% by sliding speed and a normal load of 1.82%, confirmed with the grey relational grade. Both SEM and GRA confirmed that the reinforcement ratio of 10% exhibited lower wear loss and friction coefficient. The revealed wear mechanism operating on the worn surface of laser-cladded AZ61 magnesium alloy was micro-grooving exerted by a counter surface at all sliding conditions. This study shows that the LC of magnesium alloys will be preferred in sliding seal and lightweight gear applications.

Abstract P4-01-38: A single arm phase II trial of Palbociclib in combination with Tamoxifen as first line therapy for metastatic hormone receptor positive breast cancer

Abstract Background: Palbociclib is a CDK4/6 inhibitor used to treat metastatic hormone receptor-positive (HR+) breast cancer (MBC) in combination with endocrine therapy. Tamoxifen is an effective treatment for HR+ MBC, with different toxicity profile compared with aromatase inhibitors (AI) and fulvestrant. Preclinical data demonstrated synergy for the combination of tamoxifen and palbociclib, being effective in a model of acquired tamoxifen resistance. Methods: We conducted a non-randomized, open-label, single-arm, multicenter, phase II trial of palbociclib in combination with tamoxifen in patients with HR+/HER2 - advanced BC, with no prior therapy for MBC. Ovarian suppression was recommended for pre-menopausal women. Primary objective was progression free survival, PFS. Secondary objectives: objective response rate, ORR (CR or PR) based on RECIST 1.1 or MDA Criteria (for patients with bone only disease); safety and tolerability (using CTCAE v4); clinical benefit rate, CBR (CR, PR or SD lasting min 24 weeks); 2-year overall survival. Correlative objectives: proteomic analysis of plasma exosomes to identify mechanisms of primary and secondary resistance to tamoxifen/palbociclib. Results: Between 6/30/2016 and 7/02/2019, we enrolled 49 patients (47 evaluable): 23 pts with de-novo metastatic disease and 24 pts with recurrent BC (12 pts were on adjuvant treatment with AI at time of recurrence and 12 pts on surveillance). As of 6/30/2022 data cut-off, 2 pts were still on treatment. This is an updated analysis with median follow-up time of 24 months (range 8-51). Median age was 60 (range 39-82). The median PFS was 19.8 months with 95% CI (8-41) for pts with de-novo MBC and 7 months (2-12) for pts with recurrent BC. The ORR was 30% overall, 39% for pts with de novo MBC, 21% for pts with recurrent BC. CBR was 64% overall, 77% for pts with de novo MBC and 50% for pts with recurrent BC. CBR was 65% for white pts and 55% for AA pts. Best response per RECIST1.1: 14 pts (34%) had PR, 18 pts (44%) had SD, 9 pts (22%) had PD. All 6 pts with bone only disease had SD. The most common drug related grade ≥ 3 AE was neutropenia (51%), transient and manageable by dose modifications, no cases of febrile neutropenia. Four patients (8%) developed thromboembolic events (grades 2, 3, 4) and discontinued treatment. One patient died while on treatment from PD. More than 800 exosome proteins were detected in the samples analyzed so far. Exosomal protein networks in pretreatment samples predicted treatment response with 89% sensitivity and 95% specificity in unsupervised clustering. Data on correlative objectives will be presented in a separate abstract. Conclusions: The combination of palbociclib and tamoxifen showed tolerable, expected safety profile. This may be an alternative approach for selected patients in first line treatment of HR+ MBC, especially those who present with de-novo metastatic disease and are intolerant to AI; although this small study indicates a lower PFS. Table 1: Baseline Demographics Citation Format: Oana C. Danciu, Kent Hoskins, Jennifer Weiss, Cristina I. Truica, Anne Blaes, Deimante Tamkus, Jatin Rana, Tandra Pavankumar, Lauren Green, Yu Gao, Menggang Yu, Qianqian Zhao, Deborah Toppmeyer, Ruth O’Regan, Kari B. Wisinski. A single arm phase II trial of Palbociclib in combination with Tamoxifen as first line therapy for metastatic hormone receptor positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-38.

Optimization of performance and emission characteristics of a diesel engine in dual-fuel mode with LPG using adaptive-neuro fuzzy inference system model

In this work, a dual-fuel engine was tested. The engine was converted to run on a dual fuel system, using diesel as the ignition source and liquefied petroleum gas (LPG) at varying flow rates depending on the load. The engine was modified so that LPG could be used as fuel and diesel could be used as ignition source. The engine parameters were optimized with the help of Adaptive Neuro Fuzzy Inference Systems (ANFIS). Diesel engine performance and emission characteristics when running on LPG as a secondary fuel have been modelled using ANFIS. ANFIS combines the self-learning of ANN with the reasoning of Fuzzy Inference System (FIS). The five layers of ANFIS model contains fuzzification, product, normalized, defuzzification, and output. ANFIS predicts GRG using injection pressure, LPG flow rate, and braking power. Grey relational analysis was used to converts multi-objective to single-objective optimization with Grey Relational Coefficient, grey relational grade (GRG) and Rank. ANFIS prediction modelling uses gradient descent and least squares to train parameters. Functional signals are used till the defuzzification layer. To reduce inaccuracy, outcome parameters are regulated using least squares. The backward pass uses gradient descent to improve parameters. The results were shown using Surface plots representing the effect of input parameters on the GRG value. According to the results of the performance evaluation, the ANFIS projected data was consistent with the experimental data, with an overall correlation coefficient of 0.99415. The optimum operating conditions are found to be 194.32 bar injection pressure, 1 LPM LPG flowrate and 1.13 BP with 0.835084 Optimum GRG.

Fabrication and multi- performance optimization of mechanical properties of novel Babbitt-Ilmenite metal matrix composite using entropy based hybrid Taguchi-grey relational analysis

In the present study, a Babbitt-Ilmenite composite was developed via stir casting and the mechanical properties (hardness and tensile strength) of the composite were optimized using the Taguchi philosophy. The effects of variations in the percentage weight of Ilmenite, stirring speed and aging time on the mechanical properties of the composite were studied. Energy dispersive spectroscopy analysis confirmed the presence of Ilmenite in the metal matrix and uniform dispersal of Ilmenite in Babbitt was established via scanning electron microscopy. A Morphological analysis of the fractured tensile specimen was conducted to ascertain the type of failure. The Taguchi methodology and analysis of variance technique were proposed to predict the optimum levels of controllable parameters and to determine their percentage contribution to the optimization of mechanical properties of the composite. The percentage weight of Ilmenite and stirring speed were found to have significant effect on hardness while aging time was a significant parameter for the tensile strength of the composite. The predicted results were validated by confirmation experiments with a deviations of 1.6% and 2.1% for hardness and tensile strength respectively for single objective optimization. The weights of the responses were determined objectively and the multi-performance optimization of mechanical properties of the composite was performed using entropy based grey relational analysis (EGRA). The percentage weight of Ilmenite was only significant parameter with contribution of 30.65% for multi-performance optimization of mechanical attributes of composite using hybrid Taguchi grey relation analysis (TGRA). An overall improvement of 0.445 and 0.105 in the grey relation grade was reported using EGRA and TGRA respectively. The study concludes that the Babbitt/Ilmenite composite has superior mechanical properties both for single and multi-objective optimized conditions than the unreinforced tin Babbitt. The developed composite can be used for bearings in crankshafts, connecting rods and axles of automobiles.

Optimization of dry sliding wear behaviour of industrial wastes reinforced aluminium based metal matrix composites

AbstractMarble dust and basalt powder are industrial waste generated during the machining of marble stone and basalt rock. This paper presents an approach for the optimization of dry sliding wear parameters of aluminium 7075 reinforced with marble dust and basalt powder hybrid metal matrix composite using Taguchi based grey relational analysis. In this work, the composite is fabricated by stir casting technique and the wear parameters namely load, sliding velocity and sliding distance are optimized with consideration of multi responses such as wear rate and coefficient of friction. Experiments are conducted as per Taguchi's L9 orthogonal array. A grey relational analysis is carried out and grey relational grade is obtained. Based on the grey relational grade, optimum level of wear parameters has been identified by analysis of variance. The test results are validated by conducting the confirmation test. Experimental results have shown that the sliding velocity is the most effective factor among the control parameters on dry sliding wear, followed by the sliding distance and load. Finally, the micro structural investigations on the worn surfaces are performed by scanning electron microscope.

MACHINABILITY STUDIES OF WROUGHT TITANIUM ALLOY Ti-6Al-4V BASED ON ORTHOGONAL ARRAY DESIGN

This research focuses on wrought Ti-6Al-4V machining using coated carbide inserts under flood cooling to study the machinability characteristics. Machining parameters are optimized, and mathematical models are developed for correlations. Surface roughness lies between 0.215[Formula: see text][Formula: see text]m and 0.830[Formula: see text][Formula: see text]m and even below 1[Formula: see text][Formula: see text]m during machining. Flank wear lies within 0.033–0.16[Formula: see text]mm which is below the 0.2[Formula: see text]mm criteria of wear. Cutting temperature lies between 31∘C and 158∘C. The reduction of cutting temperature and chip serration under flood cooling and the subsequent transfer of heat from the shear zones help to generate good surface finish and may be due to the evolution of a lower wear rate. Abrasion, chipping, adhesion and built-up-edge are seen as major mechanisms of wear. The optimal conditions are found to be a depth of cut of 0.1[Formula: see text]mm, 0.1[Formula: see text]mm/rev feed rate and 70[Formula: see text]m/min cutting speed. There is an improvement in results at optimal conditions of 38.42% for Ra, 60.86% for VBc and 27% for [Formula: see text], respectively, than initial parametric conditions. Further, grey relational grade has been improved by 0.263. Machinability models developed through quadratic regression are observed to be significant.

A new strategy for the reinforcement of paraffin-based fuels based on cellular structures: The armored grain — Ballistic characterization

Slow regression rate of the solid fuel is the main limitation for the use of hybrid rocket engines in high thrust applications. Paraffin-based fuels tackle this limitation thanks to the entrainment mass transfer. In this study, ballistic behaviors of conventional polymeric fuel (ABS) and paraffin-based blends are studied and compared with those of the armored grains. These latter are a new generation of fuels featuring 3D printed cellular structures embedded in the wax-based grain. The ballistic characterization focuses on the evaluation of the regression rate (rf) and its dependence on the oxidizer mass flux. Relative ballistic grading of the formulations is pursued via thickness over time methods and an optical technique for rf determination. The armored grains are reinforced by gyroid structures that are 3D printed using three different polymers (ABS, PLA, and Nylon 6) and two relative densities (10% and 15%). Despite the slow burning behavior of the printing polymers, the embedded reinforcement enhances the rf of the paraffin-based formulations, with percent increases ranging from +48% to +91%. This result could be explained by the uneven and irregular texture of the burning surface promoting turbulence (and therefore, propellant mixing) and convective heat transfer. For both the armored grains and the paraffin-based formulations, blending the pristine paraffin wax with polymeric additives results in more viscous formulations and in a rf reduction. Armored grain combustion performance makes this novel fuel an interesting candidate for high-thrust hybrid rockets.

Randomised phase II trial of adaptive image guided radiotherapy in muscle invasive bladder cancer: Late toxicity and cancer outcomes.

446 Background: The bladder is a mobile, deformable structure which makes radiotherapy (RT) delivery challenging. Plan of the day (POD) adaptive image guided RT and tumour boost dose escalation can optimise treatment. We aimed to define a feasible, safe schedule for muscle invasive bladder cancer (BC) using these techniques. Methods: RAIDER (ISRCTN 26779187) is a 3-arm, international phase II trial. Participants (pts) had unifocal T2-T4a urothelial BC and were randomized (1:1:2) to: standard whole bladder RT (WBRT), standard dose adaptive tumour focused RT (SART) or dose escalated adaptive tumour boost RT (DART). Two fractionation (f) schedules recruited independently. WBRT and SART dose was 64Gy/32f or 55Gy/20f and DART was 70Gy/32f or 60Gy/20f. For SART and DART, POD (small, medium, large) was chosen daily. Neoadjuvant chemotherapy (NAC) and concomitant radiosensitising therapy (CTh) were permitted. Primary endpoint is proportion of pts with RT related CTCAE grade≥3 (G≥3) toxicity 6-18 months (m) after RT. A non-comparative design to rule out >20% G≥3 toxicity in DART pts required 57 evaluable DART pts in each fractionation cohort (90% power, 5% 1-sided alpha). Adverse events (AE) are treatment emergent with RT relatedness assessed blind to treatment allocation. In each fractionation cohort, toxicity analysis is by treatment received in the evaluable population (pts with at ≥1 toxicity assessment between 6-18m). 3m local control was assessed by cystoscopic biopsy. Cancer outcomes are analysed by intention-to-treat with fractionation cohorts combined. Results: 345 pts were randomised (Oct 2015 - Apr 2020): 46/41 WBRT, 46/41 SART and 90/81 DART pts in 32f/20f cohorts respectively. Baseline characteristics for 32f/20f were median age 73 years (IQR 67, 79)/ 72 (67, 79); 83%/ 78% T2; 46%/ 52% had NAC and 71%/ 70% CTh. Median follow-up was 32f: 38.2m (IQR 26.2, 50.2), 20f: 42.1m (35.6, 50.1). 3588/6222 (58%) fractions delivered to SART and DART pts used small or large POD. Late toxicity outcomes are shown in table. RT related G≥3 in 20f DART was 1/58 (90% CI 0.1, 7.9) and in 32f DART was 0/57. 3m local control was achieved in 44/51 (86%) WBRT, 45/53 (85%) SART and 82/92(89%) DART. 2 year survival was 79% (95% CI: 69, 86) WBRT, 74% (63, 82) SART and 80% (73, 85) DART. Conclusions: Late G≥3 toxicity was low in all treatment groups. 20f and 32f DART was safe and feasible to deliver with toxicity rates below predefined thresholds. Local control for image guided (chemo)RT was good. CTCAE G≥3 and G≥2 treatment emergent toxicity 6-18m after RT. Clinical trial information: 26779187 . [Table: see text]

A pilot study of tazemetostat and pembrolizumab in advanced urothelial carcinoma (ETCTN 10183).

506 Background: Despite response to systemic therapy, few metastatic urothelial carcinoma (mUC) patients (pts) achieve durable responses. Mutations in the COMPASS-related proteins KMT2D, KMT2C, and KDM6A are found in 66% of UC patients suggesting histone regulation may be an acquired mechanism of tumor viability. We previously found regression of UC in mice when treated with EZH2 inhibitor, tazemetostat. In vivo administration of tazemtostat enhanced the immune response with direct regulation of cytokines and antigen recognition machinery (MHCI and MHCII). We hypothesized that restoration of epigenetic imbalance, combined with immunotherapy, may improve outcomes in mUC pts. Methods: ETCTN 10183 (NCT03854474) is a pilot study evaluating the efficacy of tazemetostat 800 mg BID + pembrolizumab 200 mg every 3 weeks for cisplatin-refractory (Cohort A) or cisplatin/chemo-ineligible advanced UC (Cohort B) pts, with N=12 pts in each cohort. The primary objective is to identify the recommended phase two dose (RP2D) of tazemetostat in combination with pembrolizumab. Secondary objectives include RECIST-based response rate, safety, and progression-free survival. The maximum planned treatment duration is 2 years. Translational objectives include defining total and COMPASS-related genes tumor mutational burden, tumor subtyping, TCR clonality, T cell infiltration, and PDL-1 expression. Results: In the safety lead-in phase, 6 mUC pts were treated. There were no dose-limiting toxicities (DLTs). The RP2D for tazemetostat was established at 800 mg BID. Here we report results of fully accrued cohort A (N=12); 67% males, 33% females, 83% white, 8.3% Black, and 25% Hispanic/Latino ethnicity. The primary sites of UC were: bladder (n=9, 75%), renal pelvis (n=2, 17%), and ureter (n=1, 8.3%). The median (interquartile range, IQR) time since primary diagnosis was 1.1 years (0.7, 1.9); 11/12 patients had non-nodal metastatic disease; 10/12 had 1 or more visceral/bone metastasis. Median number of treatment cycles was 5 (IQR: 3-11; range 1-35). Median duration on protocol treatment was 12 weeks (IQR: 7-30; range 3-107 weeks). Three pts had treatment related grade 3/4 AEs: grade 4 sepsis (n=1), grade 3 lymphopenia (n=2); anemia, increased alkaline-phosphatase, and HSV oral infection (n=1 each). Best response was partial response (PR) in 3 pts (25%) and 3 (25%) had stable disease. Median PFS was 3.1 months (95%CI: 2.3-NA), and median overall survival was 8.0 months (95% CI: 4.7 – NA). Conclusions: The RP2D dose for tazemetostat is 800 mg + 200 mg Pembrolizumab q 3 weeks. The combination was feasible, well tolerated, and resulted in durable responses in poor-risk chemo-refractory UC patients. Clinical trial information: 03854474 .

A phase II trial of intravesical chemoimmunotherapy with gemcitabine and bacillus Calmette-Guérin (BCG) for patients with BCG-exposed, high-grade, non-muscle–invasive bladder cancer.

TPS579 Background: The standard of care for high-risk non-muscle invasive bladder cancer (NMIBC) after exposure to induction only BCG or relapse >12 months after “adequate” BCG is retreatment with BCG. However, ~50% of patients will relapse within 6 months. Thus, there is a critical need to develop novel combination therapies to improve BCG immunotherapy efficacy. Combination BCG with immune checkpoint inhibition is associated with a ~12-18% risk of serious treatment-related adverse events and BCG combined with Mitomycin C (MMC) has unacceptable urinary toxicity. Intravesical Gemcitabine (GEM) is a common treatment for NMIBC, is well tolerated, has better efficacy after BCG than MMC, and, based on preclinical data, may synergistically enhance the efficacy of BCG by augmenting the immune tumor microenvironment. We completed a prospective Phase I trial of chemoimmunotherapy with gemcitabine and BCG in BCG-relapsed/BCG-exposed NMIBC that was well-tolerated (no treatment related grade ≥3 adverse events) with promising early efficacy (95% [19/20] 6-month complete response rate). No dose limiting toxicities were seen. The maximum tolerated dose (MTD) was 2000 mg gemcitabine and 50 mg TICE BCG. Methods: To address the need for more effective and less toxic bladder preserving treatment options by enhancing the effectiveness of BCG, we launched an investigator-initiated phase I/II trial of combination intravesical gemcitabine with BCG in patients with BCG-exposed NMIBC (NCT04179162). The Phase II portion is currently enrolling patients with BCG-exposed carcinoma in-situ (CIS ±Ta/T1) that recurred within 24 months of last BCG (BCG-exposed/BCG-relapsing NMIBC). Patients with BCG-unresponsive disease, contraindication to BCG, or prostatic/ureteral urothelial disease are excluded. Induction intravesical GEM (2000mg, twice weekly) is given weeks 1, 4, 7, and 10 and intravesical BCG (40mg, Tice strain, weekly) is given weeks 2, 3, 5, 6, 8, and 9. Responders receive SWOG maintenance BCG. The primary endpoint is clinical complete response (CR) at 6 months (absence of high-grade disease on cystoscopy/TURBT and negative cytology) using a Simon’s optimal 2-stage design testing the null hypothesis of a true CR of 55% at 6 months (based on historical outcomes of BCG alone) against a 1-sided alternative. In the first stage, the study would stop if ≤ 9/15 patients had a CR. In the second stage, the null hypothesis will be rejected if ≥ 29 CRs are observed in 43 total patients (type I error rate 5% and power of 80% if the true CR rate is 75%). Phase I patients treated at the MTD (14/25) are included in Phase II. Secondary outcomes include recurrence-free, progression-free, and cystectomy-free survival. Correlative studies explore immune and molecular predictors of response and resistance to chemoimmunotherapy in tumor tissue, urine, and blood. Clinical trial information: NCT04179162 .

Artificial neural network prediction and grey relational grade optimisation of friction stir processing

The study predicts friction stir process (FSP) parameters using an artificial neural network (ANN) model. A design of experiment (DoE) approach is used to conduct experiments on FSP and to evaluate the best operating parameters of FSP. ANN uses 30 neurons, 1 hidden layer, and an input and output layer in the Matlab® environment. ANN predicts the output parameters with R values of 0.999, 0.995, and 0.992 for training, validation, and test datasets, respectively, while the overall R-value is 0.997. GRA is used to optimize and rank the parameters of the processes and revealed that the rotational tool speed should be 1180 rpm, traverse feed rate 38 mm/min, and tool tilt angle 1° for best results. The optimized values obtained are 380 MPa, 3.8 µm, 138 HV, and 14% for tensile strength, grain size, microhardness, and elongation, respectively. According to the analysis of variance (ANOVA) and grey relational analysis, the order of influencing parameters on output factors was rotational speed (80%), followed by transverse feed (19%) and tool tilt angle (1%). An ANN is further used to predict using the two most significant parameters—rotational speed and traverse feed. The modified ANN has nearly the same R values as the original ANN. Thus modified ANN may be used for prediction.

Sustainable Vegetable Oil-Based Minimum Quantity Lubrication Assisted Machining of AZ91 Magnesium Alloy: A Grey Relational Analysis-Based Study

The implementation of magnesium alloys in a multitude of industries has been proven to be a mere effect of their attractive light weight, corrosion resistant, and biodegradable properties. These traits allow these materials to portray an excellent sustainable machinability. However, with increasing demand, it is essential to explore sustainable means of increasing production while mitigating reductions in sustainability. The current work aims to assess and optimize the high-speed machinability of AZ91 with the use of a vegetable oil-based minimum quantity lubrication (MQL) system using the grey relational analysis (GRA) on the basis of chip morphology and tool wear. The investigation entailed a full factorial design with MQL flow rate, cutting speed, and feed rate as the control parameters and flank wear, land width, chip contact length, saw-tooth pitch, chip segmentation ratio, chip compression ratio, and shear angle as the output responses. The optimal control parameters predicted and experimentally confirmed were an MQL flow rate of 40 mL/h, cutting speed of 300 m/min, and feed rate of 0.3 mm/rev. The usage of said optimal parameters results in a grey relational grade improvement of 0.2675 in comparison to the referenced first experimental run. Moreover, the MQL flow rate was regarded as the critical variable with a contribution percentage of 20% for the grey relational grade.

Basic fibroblast growth factor/chitosan derivatives/collagen composite thermosensitive hydrogel promotes perio-dontal tissue regeneration in rats.

To investigate the feasibility of different thermosensitive composite hydrogels from chitosan derivatives as scaffold materials for periodontal tissue engineering. Three chitosan derivatives with different biological characteristics were prepared, namely, sulfonated chitosan (SCS), phosphorylated chitosan (PCS), and phosphorylated sulfonated chitosan (PSCS). Three thermosensitive composite hydrogels were constructed using basic fibroblast growth factor (bFGF), the chitosan derivatives, and collagen. Twenty male Wistar rats were randomly divided into control group, blank group, bFGF/SCS/collagen composite thermosensitive hydrogel group, bFGF/PCS/collagen compo-site thermosensitive hydrogel group, and bFGF/PSCS/collagen composite thermosensitive hydrogel group. Then, three-wall intrabony defects were established. The defects were treated with the different kinds of thermosensitive composite hydrogels. After 6 weeks of surgery, the animals were killed, and specimens were collected. Then, gross observation, hematoxylin-eosin staining, and Masson staining were performed. The bFGF/chitosan derivatives/collagen composite thermosensitive hydrogel groups and the control group had statistical differences in the relative alveolar bone height, relative epithelial down growth and grading count score of periodontal tissue regeneration (P<0.05). bFGF/chitosan derivatives/collagen composite thermosensitive hydrogels have good application prospects in periodontal tissue engineering.

Safety and preliminary efficacy of MIL93 in patients with advanced solid tumors: The monotherapy part of a phase 1 trial.

798 Background: Claudin18.2 (CLDN18.2) is specifically expressed in the tight junction of gastric epithelial cells, and has been identified as a promising target in gastric and pancreatic cancer as well as several other malignancies. MIL93 is a humanized afucosylated IgG1 monoclonal antibody targeting CLDN18.2 with enhanced ADCC function, which demonstrated superior activity compared with zolbetuximab in vitro and in vivo, respectively. We conducted a multicenter, dose escalation and expansion phase 1 study of MIL93 for advanced solid tumors. Methods: We enrolled pts aged 18 years or older with advanced solid tumors whose disease had progressed after standard systemic treatments in the monotherapy part of this study. Pts were required to have measurable lesion as per RECIST v1.1; ECOG PS score of 0-1 and adequate organ functions. In the dose escalation phase, 6 dose levels (0.3mg/kg, 1mg/kg, 3mg/kg, 10mg/kg, 20mg/kg and 30mg/kg, Q3W) of MIL93 were conducted for assessment. Accelerated titration was adopted for the first 2 dose levels, and the 3+3 design was used afterwards. In the dose expansion phase, pts with CLDN18.2-positive cancers received the selected RP2D. The primary objectives were the safety and tolerability, dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of MIL93. Secondary objectives included pharmacokinetics, immunogenicity and preliminary efficacy. Results: At the data cut-off date (August 9, 2022), 30 pts were enrolled from 6 centers in China. MIL93 was well-tolerated for the dosages tested (0.3mg/kg through 30mg/kg Q3W). DLT was observed in one pt during the 3-week window at 30mg/kg. However, none of the three additional patients at 30mg/kg had DLT, and MTD has not been reached. In further expansion study 9 additional pts were enrolled into the expansion phase at the 20 mg/kg Q3W dose and 3 pts were enrolled into the dose escalation at the 10mg/kg Q2W. The most common TEAE occurring in ≥20% of pts were nausea (60%), hypoalbuminemia (46.7%), vomiting (43.3%), anemia (36.7%), hyponatremia (33.3%), hypocalcemia (23.3%), decreased appetite (23.3%), asthenia (23.3%), aspartate aminotransferase increased (20.0%). Serious adverse events (SAEs) were observed in 9 (30%) pts, and MIL93-related SAEs occurred in 6 (20%) pts including hypoalbuminemia/hypoproteinemia, malnutrition, anorexia and vomiting. No treatment related Grade 4 or 5 event was reported. Among the 25 pts who had at least one post-treatment radiological evaluation, 2 gastric cancer pts who progressed on multiple lines of therapies achieved partial response (PR). The disease control rate (DCR) reached 44%. Conclusions: MIL93 had a manageable and tolerable safety profile in patients with advanced solid tumors and preliminary anti-tumor activity in 2 heavily pretreated gastric cancer pts. Combination of MIL93 and standard treatment in selected tumor types is currently underway. Clinical trial information: NCT04671875 .

Multi-response optimization of magnetic abrasive finishing process parameters on AISI H13 hot die steel using grey relational analysis

This paper presents a new approach for the optimization of machining parameters on magnetic abrasive finishing (MAF) of AISI H13 hot die steel with multiple responses based on the orthogonal array with grey relational analysis. The process has been explored widely for the finishing of plane surfaces on pillar drilling machine. Taguchi orthogonal arrays L27 Designs of experiment method was used for planning of experiments. Total of 27 Experiments were conducted on AISI H13 hot die steel to check the best factor level combination. Five process parameters such as abrasive size, cutting speed, finishing time, machining gap, and magnetic flux density are optimized using multiple responses such as surface roughness (Ra) and metal removal rate (MRR). The Grey Relational Analysis (GRA) was utilized to analyze the results to find the optimum condition and identify the significant parameters affecting the surface roughness and the metal removal rate on H13 hot die steel. Magnetic abrasive finishing machining parameters combination of experiment no. 14 has the highest grey relation grade (GRG) of 0.922. The ideal parameter combination to achieve optimum output are cutting speed of 118.24 m/min, abrasive mesh size of 600, finishing time of 10 min, Machining gap of 1 mm, and Magnetic flux density of 485 gauss. The surface roughness (Ra) value was improved from 0.753 µm to 0.452 µm.

Comparative analysis and optimization of thermodynamic behavior of combined gas-steam power plant using grey-taguchi and artificial neural network

In the published studies, to the best of the authors’ understanding, the grey Taguchi-based statistical technique has not been applied for the optimization of combined gas-steam power plants. In view of this, seven essential input parameters namely compressor inlet air temperature, pressure ratio, fuel temperature, volumetric flow rate of fuel, gas turbine maximum temperature, compressor efficiency, and turbine efficiency are chosen with the aim of determining the optimal combination of design variables that maximize the net power generation, thermal efficiency, exergetic effciency, and minimize the specific fuel consumption. Also, the impact weight of each parameter on output indicators has been evaluated. While the Taguchi approach helps to create an orthogonal array of L27 (3^7), the ANOVA method determines the contribution of each input argument on the objective function. Unlike the Taguchi and ANOVA optimization methodology, the grey relational analysis is performed to transform the multi-objective function into a single objective by way of estimating its grey relational grade. The most favorable combination of input parameters is determined as A1B1C1D1E3F3G3 and under this state, the optimum values of power generation, thermal efficiency, exergetic efficiency, and specific fuel consumption are found to be 259911 kW, 64.9 %, 66.27 %, and 0.1839 kg/kWh respectively. Moreover, the contribution ratio on the output characteristic of the combined cycle is found to be maximum for turbine efficiency (42.41 %) and minimum for fuel temperature (0.59 %). The effectiveness of the grey-Taguchi method is acknowledged and validated using an artificial neural network technique in MATLAB.

Parameters optimization of tungsten inert gas welding process on 304L stainless steel using grey based Taguchi method

Tungsten inert gas can be used to weld stainless steel due to its offering sound weld, narrow fusion zone, precise control weld’s shape and over penetration, spatter free, slagless, stable arc and low electrode wear. The goal of this study was to offer the best process parameters for improving the mechanical characteristics of the weld joint. The experimental analysis approach was applied in this work, and the experiment was carried out on 304L stainless steel using L16. The selected welding parameters were welding travel speed, current of welding, gas flow rate, arc length, and root gap. Rockwell hardness, tensile strength, and bending strength tests were the examined mechanical properties on the weld joint. Based on the grey based Taguchi method, the optimal level-settings of welding travel speed, current of welding, flow rate of gas, arc length, and root gap were obtained 2.7 mm s−1, 160 A, 14 l min−1, 3 mm, and 1 mm, respectively. The analysis result of ANOVA showed that the current has the greatest impact and it was followed by travel speed and root gap on weld joint quality with percentage contribution of 80.77%, 10.86%, and 5.98%, respectively. According to confirmation results, the average grey relational grade of 0.863 which was found between the confidence interval of 0.800 to 1.082 for the 95% confidence level, and the maximum Rockwell hardness, tensile strength and bending strength were obtained 101.38 HRB, 1425.8 MPa and 1648.6 MPa, respectively.

A novel approach for optimizing the processing of recycled coarse aggregates

This paper proposes an alternative method for processing the demolition waste into high-quality recycled coarse aggregate using the ball mill. Taguchi’s design of experiments based on orthogonal array was used to minimize the number of trials for saving material and time. Experiments were carried out based on L25 orthogonal array with three processing parameters: charge, revolution duration, and aggregate weight with five levels. The revolution speed of the ball mill was set to 60 revolutions per minute. The Taguchi method was then combined with grey relational analysis to achieve the best combination of processing parameters for producing high-quality aggregate. Experimental studies on water absorption, specific gravity, impact value, and abrasion value were used to assess the quality of recycled coarse aggregates. The best combination for each performance characteristic was achieved by using the mean of Signal to Noise ratio graphs. The optimal combination of processing parameter levels to generate superior quality recycled aggregates and the most significant processing parameter were identified based on the response table of means of grey relation grade.

Process parameters optimization for cold metal transfer-deposited IN625 single-layer bead features by entropy weightage-assisted grey-based Taguchi analysis

The selection of the right set of parameters for the desired bead geometry leads to minimize the discontinuous weld bead, weld cracks, porosity, and waviness. The present work focuses on the multi-response optimization for the cold metal transfer-deposited IN625 weld bead characteristics that include bead height, bead width, and penetration depth along with a mechanical property of micro-hardness. Effects of input parameters such as input current, travel speed, and standoff distance are being selected for the investigation by implementing grey relational analysis where entropy weightage method is applied for the calculation of overall grey relation grade. The multi-responses of minimum bead width and maximum bead height, penetration, and microhardness by grey relational analysis are optimized at 140 A current, 4 mm/s travel speed, and 4 mm standoff distance. Confirmatory experiments were also carried out giving the satisfactory validation. The evaluation of bead features optimization can be used for the development of wire arc additive manufacturing process in later stages.

Inflammation and Prostate Cancer: Pathological Analysis from Pros-IT CNR 2.

Extensive research effort has been devoted to investigating the link between inflammation and PCa. However, this relationship remains unclear and controversial. The aim of our multi-center study was to investigate this association by histologically evaluating the distribution of PI and PCA in prostate biopsy cores from patients of eight referral centers in Italy. We evaluated 2220 cores from 197 patients; all the frustules were re-evaluated by dedicated pathologists retrospectively. Pathologists assigned IRANI scores and determined the positions of PIs; pathologists also re-evaluated the presence of PCa and relative ISUP grade. PCa was recorded in 749/2220 (33.7%). We divided this sample into a PCa PI group (634/749 cores [84.7%]) and a non-PCa + PI group (1157/1471 cores [78.7%]). We observed a statistically significant difference in the presence of inflammation among cores with cancer (p < 0.01). Moreover, periglandular inflammation was higher in the cores with neoplasia, while stromal inflammation was higher in cores without neoplasia (38.5% vs. 31.1% and 55.4% vs. 63.5% p < 0.01). In our experience, there is evidence of an association between PI and PCa at a tissue level. Further studies are needed to confirm our findings and to identify patients who might benefit from target therapies to prevent PCa occurrence and/or progression.