Nanostructuring with Structural-Compositional Dual Heterogeneities Enhances Strength-Ductility Synergy in Eutectic High Entropy Alloy.

A lamellar (L12 + B2) AlCoCrFeNi2.1 eutectic high entropy alloy (EHEA) was severely deformed by a novel hybrid-rolling process. During hybrid-rolling, the deformation was carried out in two stages, namely cryo-rolling followed by warm-rolling at 600 °C. The strain (ε) imparted in each of these steps was identical ~1.2, resulting in a total strain of ε~2.4 (corresponding to 90% reduction in thickness). The novel processing strategy resulted in an extremely heterogeneous microstructure consisting of retained lamellar and transformed nanocrystalline regions. Each of these regions consisted of different phases having different crystal structures and chemical compositions. The novel structure-composition dual heterogeneous microstructure originated from the stored energy of the cryo-rolling which accelerated transformations during subsequent low temperature warm-rolling. The dual heterogeneous microstructure yielded an unprecedented combination of strength (~2000 MPa) and ductility (~8%). The present study for the first time demonstrated that dual structure-composition heterogeneities can be a novel microstructural design strategy for achieving outstanding strength-ductility combination in multiphase high entropy alloys.

Nanoparticles of methylene blue enhance photodynamic therapy.

Breast cancer is the most commonly diagnosed cancer and the second leading cause of death related to cancer among women worldwide. Screening and advancements in treatment have improved survival rate of women suffering from this ailment. Novel therapeutic techniques may further reduce cancer related mortality. One of several emerging therapeutic options is Photodynamic Therapy (PDT) that uses light activated photosensitizer (PS) inducing cell death by apoptosis and/or necrosis. Nanotechnology has made contribution to improve photosensitizer for PDT, increasing the efficiency of therapy using gold and silver nanoparticles. Efforts have been done to develop better mechanism to improve PS and consequently PDT effects. In this study, we investigate the efficacy of the PDT using gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) when mixed to methylene blue (MB) in the treatment of the human breast adenocarcinoma cell line (MDA-MB-468). The MDA-MB-468 was treated in the presence of different MB concentrations with/without AuNPs or AgNPs. The colloidal solution of AgNPs showed a plasmon resonance band at 411 nm in UV-visible range and a bimodal size distribution. The results of viability analysis showed that cells treated with nanoparticles exhibited higher cytotoxicity than cells treated with only MB, improving the efficiency of the treatment in the tumor cells. The cytotoxicity effect of MB associated with AgNPs on MDA-MB-468 cell line could be related to increased reactive oxygen species production due to the release of Ag+ ions from nanoparticles surface, suggesting that the association between FS and AgNPs has potential as a PDT agent.

Simultaneous Strength-Ductility Enhancement of a Nano-Lamellar AlCoCrFeNi2.1 Eutectic High Entropy Alloy by Cryo-Rolling and Annealing.

Nano-lamellar (L12 + B2) AlCoCrFeNi2.1 eutectic high entropy alloy (EHEA) was processed by cryo-rolling and annealing. The EHEA developed a novel hierarchical microstructure featured by fine lamellar regions consisting of FCC lamellae filled with ultrafine FCC grains (average size ~200-250 nm) and B2 lamellae, and coarse non-lamellar regions consisting of ultrafine FCC (average size ~200-250 nm), few coarse recrystallized FCC grains and rather coarse unrecrystallized B2 phase (~2.5 µm). This complex and hierarchical microstructure originated from differences in strain-partitioning amongst the constituent phases, affecting the driving force for recrystallization. The hierarchical microstructure of the cryo-rolled and annealed material resulted in simultaneous enhancement in strength (Yield Strength/YS: 1437 ± 26 MPa, Ultimate Tensile Strength/UTS: 1562 ± 33 MPa) and ductility (elongation to failure/ef ~ 14 ± 1%) as compared to the as-cast as well as cold-rolled and annealed materials. The present study for the first time demonstrated that cryo-deformation and annealing could be a novel microstructural design strategy for overcoming strength-ductility trade off in multiphase high entropy alloys.

FTIR study of secondary structure changes in Epidermal Growth Factor by gold nanoparticle conjugation.

Conformation of protein is vital to its function, but may get affected when processing to manufacture products. It is therefore important to understand structural changes during each step of production. In this study, we investigate secondary structure changes in the targeting protein Epidermal Growth Factor (EGF) during synthesis of theranostic bifunctional nanoparticle, devised for Photodynamic therapy of breast cancer. We acquired FTIR spectra of EGF; unconjugated, post treatment with α-lipoic acid, attached to gold nanoparticle, and bound to the bifunctional nanoprobe. We observed decreasing disordered structures and turns, and increasing loops, as the synthesis process progressed. There was an overall increase in ß-sheets in final product compared to pure EGF, but this increase was not linear and fluctuated. Previous crystal structure studies on EGF-EGFR complex have shown loops and ß-sheets to be important in the binding interaction. Since our study found increase in these structures in the final product, no adverse effect on binding function of EGF was expected. This was confirmed by functional assays. Such studies may help modify synthesis procedures, and thus secondary structures of proteins, enabling increased functionality and optimum results.

Elastic modulus and hydraulic permeability of MDCK monolayers.

The critical role of cell mechanics in tissue health has led to the development of many in vitro methods that measure the elasticity of the cytoskeleton and whole cells, yet the connection between these local cell properties and bulk measurements of tissue mechanics remains unclear. To help bridge this gap, we have developed a monolayer indentation technique for measuring multi-cellular mechanics in vitro. Here, we measure the elasticity of cell monolayers and uncover the role of fluid permeability in these multi-cellular systems, finding that the resistance of fluid transport through cells controls their force-response at long times.

A preliminary Raman spectroscopic study of urine: diagnosis of breast cancer in animal models.

Prognosis of breast cancer, the most common cancer in females worldwide, has been shown to improve with early detection. Owing to disadvantages like low sensitivity, specificity, tedious sample preparation, long output times and inter-observer variance of currently available screening/diagnostic tools, rapid and objective alternatives such as Raman spectroscopy (RS) are being extensively explored. Body fluid (serum and saliva) based RS assays have shown promising results in diagnosis of oral, lung and nasopharyngeal cancers. The current study aims to explore the feasibility of breast cancer diagnosis using urine based RS. In this study, spectra were acquired from unprocessed as well as concentrated urine of controls (C) and breast tumor bearing (T) rats and analyzed using Principal Component Analysis (PCA) and Principal Component-Linear Discriminant Analysis (PC-LDA). Classification efficiencies of 80% and 72% using unprocessed urine and 78% and 91% using concentrated urine for C and T rats were achieved. Thus, results suggest the possibility of breast cancer diagnosis using urine based RS. Further, spectra were also acquired from concentrated urine samples collected prior to breast tumor development (TT) in rats and from rats that did not develop tumors despite carcinogen treatment (NTT). Concentrated urine of NTT rats could be classified as 'normal' (C or NTT) with ∼83% efficiency whereas concentrated urine from visibly and palpably normal rats that eventually developed tumor (TT rats) could be classified as 'abnormal' (TT or T) with ∼72.5% efficiency using PC-LDA. These results suggest the possibility of detecting biochemical changes occurring prior to tumor development using urine based RS.

Swiss bare mice: a suitable model for transcutaneous in vivo Raman spectroscopic studies of breast cancer.

Breast cancer is the most common cancer affecting females worldwide. As early detection results in better prognosis, screening tools for breast cancer are being explored. Raman spectroscopy, a rapid, objective, and noninvasive tool, has shown promising results in the diagnosis of several cancers including breast cancer. For development as a screening tool, a study of spectral signatures associated with breast cancer progression is imperative. However, such studies are not possible in human subjects. Hence, there is a need for a suitable animal model, which is conducive to transcutaneous in vivo Raman spectroscopic measurements of breast with minimal interference from skin and hair and has contribution from functional mammary epithelium of breast. In this study, rodent models like C57, Swiss albino, Swiss bare, agouti mice, and Sprague-Dawley rats were evaluated. Among these models, transcutaneous breast spectra of hairless Swiss bare mice have the best signal-to-noise ratio and were closest to reported ex vivo as well as intraoperative in vivo human breast spectra. Principal component-linear discriminant analysis of several anatomical sites confirms minimal skin interference and suggests contribution from functional mammary epithelium of breast. Moreover, transcutaneous spectra from normal breast and breast tumors of Swiss bare mice could be classified with 99% efficiency, which is better than the previous reports. Thus, Swiss bare mice model may be better suited for transcutaneous in vivo Raman spectroscopic studies of breast physiology and pathology, especially breast cancer. Prospectively, in addition to cancer progression, breast-to-bone metastasis can also be studied, since these anatomical sites can be uniquely classified.