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This present work is aimed to optimize the machining parameters and study the effect of powder mixed dielectric fluid on EDM process. TOPSIS method of optimization is adopted to identify the optimal machining parameters. HCHCr die steel is preferred as machining material. Ni, Zr and Ni+Zr were selected as powder inclusion in dielectric fluid due to hard and ductile nature. L9 array Taguchi DOE is preferred to perform the experiments with parameters like peak off time, pulse off time and pulse current. TOPSIS study revealed that, third level of powder dielectric fluid (Ni+Zr), 7A peak current, 9 μs pulse on time and 2 μs pulse off time were specified as optimal condition. Pulse on time (Ton) was having high impact on MRR and Ra while performing machining operation on HCHCr die steel. SEM analysis was done to find the effect of powder mixed dielectric fluid while EDAX analysis was done to ensure the presence of powder inclusion.

To meet the demands of the manufacturing industry, a more robust approach is needed for current manufacturing processes. Machining of very hard materials with excellent dimensional accuracy and surface integrity is a challenging task, Currently, the electrical discharge machining (EDM) process is the optimal solution for machining such materials. Electrical discharge drilling machines find applications in various sectors such as aerospace, automobile and medicine. In this research, two different brass electrode geometries are considered: tubular electrode tool (TET) and double D tubular electrode tool (DDTET) on an SS202 work-piece. The input parameters of peak current (PI), pulse time ON (PONT), and pulse time OFF (POFFT) were varied. The output response measured and compared were material removal rate (MRR) and over cut (OC). The Taguchi technique was used to design the l16 orthogonal array (OA) experiment, and analysis of variance (ANOVA) was employed for result analysis using Minitab20 statistical software package. The results showed that the DDTET method produced significantly better MRR and OC improvements of 21.66 % and 2.28 % respectively. Additionally, a study was conducted on the formation of the recast layer (RL) and the heat affected zone (HAZ). [ABSTRACT FROM AUTHOR]

Myeloproliferative neoplasms (MPNs) are characterized by an increased production of blood cells due to the acquisition of mutations such as JAK2V617F. TGF‐β, whose secretion is increased in MPN patients, is known to negatively regulate haematopoietic stem cell (HSC) proliferation. Using an isogenic JAK2V617F or JAK2 wild‐type UT‐7 cell line we observed that JAK2V617F cells resist to TGF‐β antiproliferative activity. Although TGF‐β receptors and SMAD2/3 expressions are similar in both cell types, TGF‐β‐induced phosphorylation of SMAD2/3 is reduced in UT‐7 JAK2V617F cells compared with JAK2 WT cells. We confirmed that JAK2V617F mutated cells are resistant to the antiproliferative effect of TGF‐β in a competitive assay as we observed a positive selection of JAK2V617F cells when exposed to TGF‐β. Using cell lines, CD34‐positive cells from MPN patients and bone marrow cells from JAK2V617F knock‐in mice we identified a down regulation of the SHP‐1 phosphatase, which is required for the regulation of HSC quiescence by TGF‐β. The transduction of SHP‐1 cDNA (but not a phosphatase inactive cDNA) restores the antiproliferative effect of TGF‐β in JAK2V617F mutated cells. Finally, SC‐1, a known agonist of SHP‐1, antagonized the selection of JAK2V617F mutated cells in the presence of TGF‐β. In conclusion, we show a JAK2‐dependent down regulation of SHP‐1 in MPN patients' cells which is related to their resistance to the antiproliferative effect of TGF‐β. This may participate in the clonal selection of cancer cells in MPNs. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AMLs), as the name suggests, often develop suddenly and are very progressive forms of cancer. Unlike in acute promyelocytic leukemia, a subtype of AML, the outcomes in most other AMLs remain poor. This is mainly attributed to the acquired drug resistance and lack of targeted therapy. Different studies across laboratories suggest that the cellular mechanisms to impart therapy resistance are often very dynamic and should be identified in a context‐specific manner. Our review highlights the progress made so far in identifying the different cellular mechanisms of mutation‐independent therapy resistance in AML. It reiterates that for more effective outcomes cancer therapies should acquire a more tailored approach where the protective interactions between the cancer cells and their niches are identified and targeted. [ABSTRACT FROM AUTHOR]

The boiler efficiency is improved with the help of economizer it is one of the main accessory part in the boiler. Boiler feed water is preheated with the entry of reused flue gas through economizer. This present work is planned to analyse the overall heat flux and overall heat transfer in the boiler economizer. Higher amount of flue gases passing around the economizer to preheat the feed water at the same time much more heat is transferred. The heat transfer is analysed by statistical method with influence of different process parameters. Economizer fin dimensions are major consideration to taken for this analysis and estimate the overall heat flux and overall heat transfer. The process parameters of this study are named as thickness of the fin (3.5 mm, 4 mm, 4.5 mm, and 5 mm), height of the fin (4 mm, 5 mm, 6 mm, and 7 mm), fin gap (12 mm, 14 mm, 16 mm, and 18 mm, and tube diameter (44 mm, 46 mm, 48 mm, and 50 mm). The response values are finding as overall heat flux and overall heat transfer. [ABSTRACT FROM AUTHOR]

Stainless steel (SS316L) is applied in numerous fields due to its intrinsic properties. In this study, micro-dimples were fabricated on SS316L. The effects of laser process parameters, such as frequency, average power, and pulse duration, on the average dimple diameter, dimple distance, and dimple depth were studied using an L9 orthogonal array. The analysis of variance (ANOVA) and multi-objective optimization technique, principal-component-analysis-coupled grey relational grade (GRG), was used to optimize laser process parameters on output responses. The optimal machining parameter settings obtained for the highest GRG peak value of 0.2642 are 15 kHz (frequency), 12 W (average power), and 1500 ns (pulse duration). The ANOVA results showed that average power is the most influential factor, contributing 86.40 % to performance measures (average dimple diameter (φ), dimple distance (d), and depth (l). Moreover, the effect of process parameters was studied using mean effect plots, and the micro-dimple quality was analysed using SEM micrographs. [ABSTRACT FROM AUTHOR]

Summary: The standard of care for patients with acute promyelocytic leukaemia (APL) relapsing after front‐line treatment with arsenic trioxide (ATO)‐based regimens remains to be defined. A total of 67 patients who relapsed after receiving ATO‐based up‐front therapy and were also salvaged using an ATO‐based regimen were evaluated. The median (range) age of patients was 28 (4–54) years. While 63/67 (94%) achieved a second molecular remission (MR) after salvage therapy, three (4·5%) died during salvage therapy. An autologous stem cell transplant (auto‐SCT) was offered to all patients who achieved MR, 35/63 (55·6%) opted for auto‐SCT the rest were administered an ATO + all‐trans retinoic acid maintenance regimen. The mean (SD) 5‐year Kaplan–Meier estimate of overall survival and event‐free survival of those who received auto‐SCT versus those who did not was 90·3 (5·3)% versus 58·6 (10·4)% (P = 0·004), and 87·1 (6·0)% versus 47·7 (10·3)% (P = 0·001) respectively. On multivariate analysis, failure to consolidate MR with an auto‐SCT was associated with a significantly increased risk of relapse [hazard ratio (HR) 4·91, 95% confidence interval (CI) 1·56–15·41; P = 0·006]. MR induction with ATO‐based regimens followed by an auto‐SCT in children and young adults with relapsed APL who were treated with front‐line ATO‐based regimens was associated with excellent long‐term survival. [ABSTRACT FROM AUTHOR]