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In this study, IN718 metal matrix composites (MMCs), with TiN content of 0–30 vol %, have been fabricated using laser powder bed fusion (L-PBF). The process has been carried out with varying scanning speeds of 500–800 mm/s, while maintaining constant laser power (100 W), hatch overlap (⁓ 50%) and layer thickness (⁓ 25 μm). A 2D numerical model has been established using the phase-field (PF) method to understand the role of driving forces (e.g., Marangoni force, thermal buoyancy force and recoil pressure) and deformation of melt pool behavior at different scanning speeds. In addition, the particle tracing model was coupled in the PF model to understand the motion of the reinforced particles. The microstructure of the fusion zone (or melt pool) has been predicted by evaluating the temperature gradient, solidification rate, and cooling rate. The solidification map of IN718 alloys indicated the microstructure of the fusion zone to be columnar dendrites at both the scanning speeds (500 mm/s and 800 mm/s). Depending upon the scanning speed, various defects (keyhole, balling and fusion defects) were observed in the fabricated composites. At 500 mm/s, the fabricated composite exhibited the lowest porosity (⁓ 0.27 vol%). The mechanical properties of MMCs were evaluated in terms of micro-hardness and wear resistance. The micro-hardness of MMCs increased with an increase in the TiN content and decrease in the scanning speed. The wear resistance of IN718 MMCs was found to improve when the TiN content was increased (up to 20% vol. %). [ABSTRACT FROM AUTHOR]

Radioresistance towards radiation therapy has generated the need for the development of radiosensitizers as a potential drug. KRAS mutation brings radioresistance in tumor cells. The present work proves sensitization of cancer cells towards radiotherapy through inhibition of KRAS activation. Acquiring a drug repurposing approach, the in-silico screening revealed that pixantrone, an antineoplastic drug, possesses a high affinity towards KRAS G12C and G12D subtypes. The SPR study suggests that maximum affinity of pixantrone was observed with KRAS G12C>WT>G12D and G12S. Pixantrone potentially inhibited the KRAS activation in stable transfectants G12C and G12D cell lines and radiosensitized distinct KRAS mutant subtype cells. The combination of pixantrone with radiation causes enhanced dsDNA breaks along with enhanced ATM expression, and increased late apoptosis. The preclinical studies on NCr-fox1nu xenograft mice showed potent inhibition of tumor progression and prolonged survival of mcie due to the radiosensitizing effect of pixantrone. Radiation-induced activation of key effector proteins of RAS downstream pathways, like MAPK and PI3K/Akt/mTOR pathways, were downregulated in tumor cells upon combination treatment. Interestingly, a robust upregulation of senescence marker p21 was observed in the tumor cells in combination treatment. These findings reveal a convergence between KRAS signaling, pixantrone treatment, and radiation conferring tumor cell death. [Display omitted] • Oncogenic KRAS causes radioresistance in tumor cells. • Pixantrone inhibits mutant KRAS and radiosensitizes cancer cells. • Radiation treatment upregulates MAPK and PI3K/Akt prosurvival pathway proteins in xenograft model. • Pixantrone in combination with radiation causes suppression of prosurvival pathway proteins, inhibiting tumor growth. [ABSTRACT FROM AUTHOR]

Using the synchrotron radiation source Indus-1, we have performed the angle dependent reflectance measurements in the soft X-ray region, on etched silicon (1 1 1) wafer and silicon dioxide wafer. The data so obtained is used to evaluate the optical constants `δ' and `β' in the wavelength region 80–200 A˚ for the two materials. The results are compared with the tabulated data of Henke et al. and other reported experimental results. It has been found that the data for silicon is in close agreement with the tabulated data away from the silicon L absorption edge with significant deviations near the edge. The experimentally obtained β values for silicon dioxide are consistent with the Henke's tabulated data where as the δ values show an upward trend with a shift of 9% from the tabulated values.The experimental data is also compared with energy dependent measurements done by Filatova et al. on non crystalline silicon dioxide and it is found that our data although match closely with that of Filatova's below 140 A˚, but after 140 A˚, Filatova's values for δ show a downward trend while our data follow the same upward trend as the tabulated values of Henke et al. [Copyright &y& Elsevier]

In the current study, electro-deposition of hybrid coatings consisting of Cr simultaneously reinforced with nano-scale 3 mol% yttria-stabilized zirconia (YSZ) along with hexagonal boron nitride (Cr-YSZ-BN), graphene (Cr-YSZ-Gr), and diamond (Cr-YSZ-D) was performed using an environmentally-benign trivalent Cr bath. Abrasive wear with ploughing for scratch test is recognized as the dominant wear mechanism in coatings; on increasing the scratch speed, gross spallation occurs in the BN reinforced coatings. While graphene and diamond were strongly adherent to the substrate with no signs of delamination. During fretting, oxidative and three-body abrasive wear in wedge formation mode with severe crack networking was observed in Cr-YSZ-BN. Micro-ploughing was active with intermittent cracking in Cr-YSZ-Gr coatings, indicating lower wear (via solid-lubrication by graphene). Diamond added coating, on the other hand, exhibits fewer cracks with ploughing. High hardness and elastic modulus with a maximum of ~26 GPa and 245 GPa, respectively, were obtained for Cr-YSZ-D coating with a minimum wear rate of ~3.5×10−11 m3/Nm (fretting) and 3.8×10−5 mm3/Nm (scratching). Further, rigid sp3 hybridization of carbon atoms in Cr-YSZ-D leads to the strong interlocking between Cr matrix and diamond, thereby lowering the wear damage of the coating system. The unique combination and uniform dispersion of YSZ and diamond particles displayed enhanced friction and wear resistance (k ~ 1.4×10−3), primarily due to the inherent high hardness of diamond and matrix strengthening by nano and micro-scale particles. Therefore, Cr-YSZ-D coating system emerges out as a highly robust coating capable of providing enhanced damage tolerance towards wear for various tribological applications. • Synergistic YSZ reinforcement with BN, graphene, and diamond in Cr-matrix. • Reduced crystallite size (~15 nm) and high dislocation density (~1011 cm-2) in reinforced coatings. • High compressive residual stresses (~720–1230 MPa) in hybrid coatings. • High fretting damage tolerance (wear rate of ~3.5 × 10–11 m3/Nm) in Cr-YSZ-D hybrid coating. • Low micro-scratch damage (wear rate of 3.8 × 10-5 mm3/Nm) in Cr-YSZ-D hybrid coating. [ABSTRACT FROM AUTHOR]

Lung cancer is considered as leading cancer with the highest mortality. The KRAS -oncogenic mutations are dominant in lung carcinoma leading to poor prognosis and radioresistance, which is a major impediment to radiotherapy. Thus, KRAS mutant inhibitors that synergistically sensitize tumours to radiation are urgently needed. In pursuance of the search for a novel radiosensitizer, high-throughput screening of FDA-approved drugs was performed at active site of K-Ras. Prochlorperazine (PCZ), an antipsychotic drug, showed good binding affinity with KRAS-mutant proteins. PCZ binds to the GTP-binding pocket of KRAS -mutant protein and inhibits its constitutive activation by stabilizing the GDP-bound conformation of K-Ras mutants by 9 kcal/mol compared to WT. PCZ alongwith radiation decreased the clonogenic survival of KRAS -mutant NSCLC but not KRAS -WT cells. The combination treatment activates p-ATM, p53, and p21 proteins, leading to cell cycle arrest. PCZ with increasing radiation caused a linear increase in γH2AX foci, suggesting enhanced DSBs-associated apoptosis in radioresistant A549 cells. Pharmacokinetics study showed C max = 526 ng/ml at 30min, 4.6h half-life in plasma, and highest accumulation in tumours. PCZ and 10Gy irradiation synergistically radiosensitize mice xenografts via downregulation of Ras/Raf/MEK/ERK pathway. Our efforts have led to the discovery of PCZ as a lead compound. In preclinical analyses, treatment with PCZ alone and in combination with radiation led to regression of KRAS −G12S tumours. [Display omitted] • Oncogenic KRAS mutation in NSCLC associate with radioresistance and poor prognosis. • PCZ repurposing can shorten drug development time frame and possess clinical translation. • PCZ stabilized GDP-bound mutant K-Ras conformation and supress its activity. • PCZ selectively radiosensitizes KRAS mutant A549 over WT H1299 lung cancer cell. • PCZ renders radiosensitization in vivo in xenograft model via inhibiting Ras pathway. [ABSTRACT FROM AUTHOR]