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Background Breast Cancer (BC) patients who do not obtain pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) present higher rate of relapse and worse overall survival. Recent evidence suggests that chemotherapy (CT) efficacy relies on the capacity of chemotherapeutic agents to interact with the immune system. BC features a unique tumor microenvironment (TME) comprising of multiple immune cell types including Macrophages that share a double-edged relationship with cancer as they get polarised from M1 (anti-tumour) to M2 (Pro-tumour). Pro-tumour M2 macrophages are referred to as tumor-associated macrophages (TAMs) and are implicated extensively in angiogenesis, metastasis and therapy resistance. Establishing role of TAMs, facilitates the emergence of novel strategies that exploit them as theranostic targets/tools of interest for treating cancer. Utility of using Drugs like Zoledronic Acid, Trabectedin, Rebastinib in combination with 5-fu have shown promising anti-TAM activity and improved response to CT in clinical trials. In this study, we have characterized presence of M2-TAM and its correlation to NACT response in matched primary and residual tumours by examining expression of several biomarkers. Methods Treatment naïve primary and their matched residual tumour specimens from 45 women treated at a single center were accessed through IERB approved protocols. The study included locally advanced HR+HER2-ve and TNBC tumours treated with standard NACT regimes between 2018 to 2020. To determine the association of TAM population with response to NACT, expression levels of CD68 (pan macrophage marker) & CD163 (marker of М2 macrophages), were detected by immunohistochemistry (IHC) and represented as combined H score. We also performed gene expression of chemokines, inflammatory cytokines and interleukins involved in M1-M2 polarization by q-RT-PCR. Residual Cancer Burden Scoring was used to assess response and patients were divided into three groups (complete responders, partial responders and non-responders). Univariate and multi variate analysis were performed between gene expression groups and IHC groups with clinicopathological parameters. Findings from this study was validated on public data bases like TCGA, METABRIC and GEO. Results: 20% of all patients included in the study were complete responders. We arrived at a Macrophage Polarisation Score (MPS) by Gene expression and also a combined H score by IHC. MPS and H-score had a positive correlation (p=0.083) overall. Interestingly, Combined analysis of H-Score and MPS with response to treatment showed a greater and statistically significant correlation with residual tumours as compared to treatment naïve tumours (p=0.009). We also observed that high MPS and high combined H score in residual tumours were associated with increased tumour size and LVI (p=0.055 and p=0.03). Other clinicopathological parameters like receptor status, grade and stage at diagnosis were not significantly associated with H score or MPS. Taken together we found that 11% of patients who exhibited high TAM score by both H sascore and MPS fell into the non-responders category. We therefore report TAMs in residual tumours being more indicative for response to therapy compared to primary tumours. Conclusion Although primary tumours are useful for building predictive models to therapy response, we have demonstrated that there is utility in examining residual tumours as well for choice to adjuvant chemotherapy, since the tumour is constantly evolving through the NACT period. More work to arrive at a “TAM score” that could aid in choice of additional adjuvant treatment strategies is underway. We believe our work is helping us to move one step closer to Precision Medicine in a low and middle income country like India that has a higher burden of locally advanced disease. Our analysis also lends itself to becoming a clinical test since it is performed on an FFPE specimen Citation Format: Lohita Krishna, Aruna Korlimarla, B S Srinath, Anugnya Ranjolkar, Sudipta Nascar, Hari PS, Durga Devi, Nidhi l, Rekha V Kumar. Tumour associated macrophages in Breast Cancer - Are they critical players in response to Neo Adjuvant Chemotherapy? [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 P2-21-10.

Purpose Young premenopausal women develop breast cancer (BC) within 5–10 years of the last childbirth, known as post-partum breast cancers (PPBC), often present with aggressive disease. The exact mechanisms that lead to poor prognosis in these patients are largely unknown. Methods We have evaluated the association of clinical and reproductive factors with BC in a cohort of women ≤ 45 years (N = 155) with long-term follow-up. Based on duration since last childbirth (LCB), grouped patients into PPBC1 (LCB ≤ 5 years), PPBC2 (LCB between 6 and 10 years), PPBC3 (LCB > 10 years), and NPBC (age-matched nulliparous BC patients). We compared disease-free survival and hazard associated with recurrence/metastasis between the groups. RNA sequencing of tumor samples was performed from three parous groups (n = 10), and transcriptomic data were analyzed for differentially expressed genes and altered pathways. Results Women in the PPBC1 group had an early menarche and late age at first and last childbirth compared to other groups. Survival analysis within lymph node-positive tumors showed that PPBC1 tumors had a worse prognosis than PPBC2 and NPBC tumors (p = 0.015 and p = 0.026, respectively). Clustering of the differentially expressed genes between the groups showed distinct expression in early PPBC (E-PPBC) tumors. Pathway analysis revealed upregulation of invasive-related pathways along with T cell exhaustion, extracellular matrix remodeling, angiogenesis, and epithelial-to-mesenchymal transition in E-PPBC tumors. Conclusion Early PPBC is a unique subtype with aggressive clinical features and distinct biology. Further research is needed to accurately project the risk of recurrence and optimal treatment strategies in these young patients.

Advances in anticancer drug discovery are focusing on the invention of drugs that specifically prompt cell death and pose lesser toxicity to the customary cells. The proposal aims at evaluating the cytotoxic potential of the non-metallic carbon dot (CDs) nanoparticles as a selective anticancer drug against targeted human carcinoma cell lines of liver (HepG2) and breast (MCF-7) in vitro. CDs were synthesized by a chemogenic method from three different natural carbohydrate derivatives glucose (GCD), sucrose (SCD), and fructose (FCD) and were characterized by UV–Visible, Fluorescence, HRTEM, ATR-IR and Raman spectroscopic techniques. Further compared for their anticancer activity against above mentioned cells. The percent cell viability investigations showed a suitability of CDs for cytotoxic studies. The IC50 of the CDs nanoparticles (SCD, GCD, FCD) on HepG2 cells were

The metal casting process is one of the industry's most significant production processes and is also one of the eco-friendly techniques for making usable parts. Metal smelts are the main melting process that takes several stages. However, concerning increased energy consumption, longer casting periods, and major failures, the conventional casting process does have significant problems. New methods are being developed to address these deficiencies of classic casting procedures. The technique of microwave casting is one of the innovative methods that satisfy current needs in the business. The process involves complexity of understanding the heating rate, material interaction phenomenon etc. A 3-D model of the in situ casting process was generated through COMSOL multiphysics software tool. A complete simulation based studies were carried out to predict the thermal history of the metal melting. The simulation results obtained by considering various power levels (1500 W to 3500 W) to predict melting time, average heating rate, desired energy to melt the materials. It was observed that the role of electric field distribution inside the microwave applicator and distribution of the temperature in the charge play a important role at hot spot condition and also to increase in temperature in the charge. It is noted that energy decreases are 15.37% at 3500 W, 9.8% at 2000 W, 16.67% at 2500 W, and 13.6% at 3000 W. Finally, the simulation data showed that the heating of the bulk metal is rapid and consistent at specific location of the mold assembly.

This paper reports on a study of the high-temperature tribological performance of self-lubricating nickel-based composite clad. A porous and crack free clad containing matrix, reinforcement, and lubricant phase is developed on titanium 31 alloy using microwave irradiation. The microstructure of both NiCrSiB/WC and NiCrSiB/WC/Ag/BaF2 clad revealed very good metallurgical bonding with the substrate. The average microhardness of NiCrSiB/WC and NiCrSiB/WC/Ag/BaF2 clad is 710.58 HV and 650.25 HV respectively, is comparatively higher than the titanium 31 substrate (320 HV). The addition of Ag and BaF2 solid lubricants in the clad endowing clad to operate at a broad temperature range. Compared with the NiCrSiB/WC clad, solid lubricant encapsulate clad has shown very low friction coefficient and wear rates. The sliding wear characteristics of the clad were investigated by varying load and temperatures. The results revealed that oxide phases (NiO and Cr3O) and lubricant phases (Ag and BaWO4) formed at low and high temperatures are adequate to reduce delamination and material loss.

Parts-of-speech (POS) tagging is a method used to assign the POS tag for every word present in the text, and named entity recognition (NER) is a process to identify the proper nouns in the text and to classify the identified nouns into certain predefined categories. A POS tagger and a NER system for Kannada text have been proposed utilizing conditional random fields (CRFs). The dataset used for POS tagging consists of 147K tokens, where 103K tokens are used for training and the remaining tokens are used for testing. The proposed CRF model for POS tagging of Kannada text obtained 91.3% of precision, 91.6% of recall, and 91.4% of f-score values, respectively. To develop the NER system for Kannada, the data required is created manually using the modified tag-set containing 40 labels. The dataset used for NER system consists of 16.5K tokens, where 70% of the total words are used for training the model, and the remaining 30% of total words are used for model testing. The developed NER model obtained the 94% of precision, 93.9% of recall, and 93.9% of F1-measure values, respectively.

The wear reduction of moving components is highly desirable because wear limits their reliability and service life, mainly at elevated temperatures. This study produced thick clads of NiCrSiB/WC/MoS2/BaF2 by tungsten inert gas (TIG) and microwave hybrid heating (MHH) cladding techniques, which were compared for microstructural and high-temperature tribological properties. The clad samples were subjected to sliding contact using a pin on disc tribometer at 200∘C, 400∘C, 600∘C under 20 and 40[Formula: see text]N load. The worn surface was analyzed using FESEM, XRD and three-dimensional (3D) profilometer. The experimental results revealed a significant effect of the TIG current and MHH exposure time on the microhardness value, which predominantly depends on the morphological characteristics. The average hardness of TIG clads was found to be 1.2 times higher than the MHH clad. Because of the MoS2 and BaF2 encapsulation, the continuous lubricant layer formation compensated for improved wear resistance with good reliability and longer service life. This work provides significant insights into the wear behavior of TIG and MHH clads at elevated temperatures and the prospective applications in turbines, where inadequate wear resistance of titanium alloy is the major concern for its use.

In the present study, the mesoporous Ti-SBA-15-SO3H catalyst is synthesized by using the sol-gel method. Further, these materials have been characterized by different advanced analytical techniques such as Low angle X-ray diffraction (XRD), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM), Thermogravimetry/Differential thermal analysis (TG/DTA), N2 adsorption/desorption studies, Fourier transform infrared spectroscopy (FT-IR), UV–Vis diffuse reflectance spectroscopy (DRS), X-ray photoelectron spectroscopy (XPS), Temperature-programmed desorption of ammonia (NH3-TPD) and Lactic acid esterification catalytic activity studies. The Ti-SBA-15-SO3H catalyst is found to have a surface area of 457 m2/g, a pore volume of 0.12 cm3/g, a pore diameter of 3.16 nm, and a high acid density of 1.72 mmol/g. The optimum reaction conditions for lactic acid esterification with n-butanol are found to be a 1: 4 M ratio, 3 wt-% catalysts, 115 °C temperature, and 120 min reaction time to obtain 72% conversion. Further, the reusability tests reveal that the spent catalyst can be used for five successive runs without the loss of considerable activity. The pseudo-homogeneous model was able to describe the kinetics of this esterification with negligible error. The activation energy and equilibrium rate constant for Ti-SBA-15-SO3H is found to be Ea = 0.063 KJ/mol and K = 5.019 lit/mol min, respectively, to catalyze the esterification of lactic acid with n-butanol. A plausible mechanism for the catalytic activity is proposed.

In this present experimental work, magnesium matrix composites (MMCs) were manufactured by stir casting method. Magnesium is a metal which is more abundant and has very less density but the problems is it has better wear resistance and low hardness. To improve the properties of magnesium, ZrSiO4 ceramic powder are reinforced. The tribological and mechanical properties of composite materials were investigated. The effects of reinforcement on the mechanical properties of the composites were investigated by 0, 4 and 8 wt% of ZrSiO4 ceramic powder with a size of 40–60 µm. The primary aim is to investigate the mechanical and tribological behaviour of AZ91/ZrSiO4 composites. ZrSiO4 powders are added at required proportions to produce magnesium alloy (AZ91) matrix composites. AZ91 along with ZrSiO4 confirms fine mechanical properties. The demand of magnesium matrix composites has increased mainly due to its high specific strength, better damping properties, excellent cast ability and superior machining ability.

In the current scenario, integration of renewables, growth of non-linear industrial and commercial loads results in various power quality issues. Among commercial utilities connected to the grid, hospital-operated loads include sensitive, linear, non-linear, and unbalanced loads. These loads are diverse as well as prioritized, which also causes major power quality issues in the local distribution system. Due to its widespread divergence, it leads to harmonic injection and reactive power imbalance. Distribution Static Compensator (DSTATCOM) is proposed as a solution for harmonic mitigation, load balancing, reactive power imbalances, and neutral current compensation. The present work utilizes Interval Type-2 Fuzzy Logic Controller (IT2FLC) with Recursive Least Square (RLS) filter for generating switching pulses for IGBT switches in the DSTATCOM to improve power quality in the Local Distribution Grid. The proposed approach also shows superior performance over Type 1 fuzzy logic controller and Conventional PI controller in mitigating harmonics. For effective realization, the proposed system is simulated using MATLAB software.