Identifying Hepatocellular Carcinoma (HCC) cells with cancer stem cell-like properties.

Hepatocellular Carcinoma (HCC) is a challenging condition to treat in the clinic due to its distinct tumor phenotype, aggressive growth, and chemotherapy resistance. Cancer Stem Cells (CSCs) are a poorly differentiated subpopulation of cells within the tumor microenvironment, and role of CSCs in tumor initiation and chemotherapy resistance is not well understood in HCC. In this study, we have successfully identified HCC cells with CSC-like properties that showed resistance to Doxorubicin. Using the established serum free culture techniques, we have enriched CSC-like cells among hepatocellular cancer cells. These enriched cells exhibit all CSC-like properties i.e. self-renewal capability, anchorage independent growth with retained proliferation property and resistance to Doxorubicin. We confirmed expression of CSC surface markers (EpCAM, CD90, CD44, CD133) and functional markers (ALDH activity and dye exclusion properties) in enriched HCC-CSCs. Preliminary in vivo data in our mouse models supports that spheroid forming CSCs show higher rate of tumor proliferation compared to untreated (non-spheroid forming) HCC cells. Wnt/β- catenin pathway components were also found to be overexpressed in CSCs when compared to non spheroids. Analysis of 24 paired human specimens from HCC tissues by IHC showed higher EpCAM expression, and Western Blot analysis suggested concomitant changes in β-catenin and EpCAM levels. In conclusion: (1) we have successfully induced and identified HCC cells with CSClike properties; (2) Aberrant β-catenin up-regulation mediated Wnt/β-catenin signaling activation was observed in enriched hepatoma spheroids

The New Human Capital Disclosures in Form 10-Ks of Large and Small S&P 500 Companies

Since 2020, the U.S. Securities and Exchange Commission has required a U.S.-listed company to describe its human capital (HC) management in Form 10-K to the extent such information is material to understanding its business. Instead of mandating the form or content of the disclosure or defining what HC is, the SEC relies on the registrants to use the principles-based approach in determining the details to be provided. The current research examined the HC disclosures of the 100 largest and 100 smallest S&P 500 companies to study the nature and level of the disclosures in their Form 10-Ks. The results showed that different companies disclosed different HC attributes under a variety of themes. There was a lack of quantitative details in most companies’ disclosures, and there was a significant disparity in the amount of information provided and the level of emphasis placed on the different HC attributes and themes by different companies. Company size was positively associated with some themes of HC disclosure but negatively associated with a few other themes

Wnt/β-Catenin mediated cancer stem cell activation in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with variable presentation, high chemotherapy resistance and early tumor recurrence. In this dissertation, we have systematically enriched, identified and characterized HCC cancer stem cells (CSCs) from 3 different HCC cell lines (Hepa1-6, HepG2, and Hep3B) using in vitro serum-free culture method. Enriched spheroids acquired CSC properties, primarily self-renewal capability, spheroid formation ability, and drug resistance. Heterogeneous CSCs enriched from Hepa1-6 cells demonstrated higher tumor initiation and proliferation capability in vivo, compared to control HCC cells in orthotopic immunocompetent mouse model. EpCAM+ CSCs were significantly enriched within heterogeneous Hepa1-6 CSC spheroids. Consequently, we studied the fate of EpCAM+ CSCs in orthotopic immunocompetent mouse model with 3 different liver microenvironments i.e. control normal liver, steatosis (fatty liver induced), and nonalcoholic steatohepatitis (NASH). EpCAM+ CSC mediated HCC carcinogenesis was observed in NASH livers, but failed to develop in control and steatosis liver microenvironment. This is the first study evaluating CSCs in immunocompetent mouse model and demonstrated the importance of liver microenvironment for EpCAM+ CSC mediated tumor initiation. We then performed a lineage tracking study by stably incorporating copGFP or mCherry in Hepa1-6 cells by lentivirus transduction, and examined the origin of tumors in NASH liver microenvironment using orthotopic C57L/J immunocompetent mouse model. Our findings suggest that tumor growth was dose dependent and most tumor nodules arose from copGFP expressing EpCAM+ CSCs. The Wnt/β-catenin pathway components were also found to be overexpressed in CSCs when compared to control. Human HCC specimen analyses suggested concomitant changes in β-catenin and EpCAM levels. Gene analyses of step-wise spheroid formation process identified possible dedifferentiation mechanisms regulated by β-catenin in CSC spheroids. Loss of function analysis by siRNA mediated transient knockdown of β-catenin confirmed its role in spheroid enrichment and doxorubicin resistance. Canonical Wnt pathway study using chemical inhibitors identified β-catenin mediated CSC activation was regulated at nuclear level, and not at the cytoplasmic GSK3β destruction complex level. Analysis of human and mouse tumors suggested that constitutive activation of β-catenin transcription failed to respond to NOTUM, a feedback inhibitor of canonical Wnt/β-catenin signaling

Manifestations of Drag Reduction by Polymer Additives in Decaying, Homogeneous, Isotropic Turbulence

The existence of drag reduction by polymer additives, well established for wall-bounded turbulent flows, is controversial in homogeneous, isotropic turbulence. To settle this controversy we carry out a high-resolution direct numerical simulation (DNS) of decaying, homogeneous, isotropic turbulence with polymer additives. Our study reveals clear manifestations of drag-reduction-type phenomena: On the addition of polymers to the turbulent fluid we obtain a reduction in the energy dissipation rate, a significant modification of the fluid energy spectrum especially in the deep-dissipation range, a suppression of small-scale intermittency, and a decrease in small-scale vorticity filaments.Comment: 4 pages, 3 figure

Spreading and shortest paths in systems with sparse long-range connections

Spreading according to simple rules (e.g. of fire or diseases), and shortest-path distances are studied on d-dimensional systems with a small density p per site of long-range connections (``Small-World'' lattices). The volume V(t) covered by the spreading quantity on an infinite system is exactly calculated in all dimensions. We find that V(t) grows initially as t^d/d for t>t^*$, generalizing a previous result in one dimension. Using the properties of V(t), the average shortest-path distance \ell(r) can be calculated as a function of Euclidean distance r. It is found that \ell(r) = r for r<r_c=(2p \Gamma_d (d-1)!)^{-1/d} log(2p \Gamma_d L^d), and \ell(r) = r_c for r>r_c. The characteristic length r_c, which governs the behavior of shortest-path lengths, diverges with system size for all p>0. Therefore the mean separation s \sim p^{-1/d} between shortcut-ends is not a relevant internal length-scale for shortest-path lengths. We notice however that the globally averaged shortest-path length, divided by L, is a function of L/s only.Comment: 4 pages, 1 eps fig. Uses psfi

Electrical energy absorption in the human head from a cellular telephone

Journal ArticleThe antenna of a cellular telephone in close proximity to the human head for a variety of time periods raises questions. This research uses finite-difference time-domain (FDTD) method to calculate the power deposition from a cellular telephone on a high-resolution model of a human head as measured by the specific absorption rates (SAR) in W/kg. Visualization has been used to verify the modeling for simulation, assisted in analyzing the data and understanding the physical aspects controlling the power absorption

Nonequilibrium Phase Transitions in a Driven Sandpile Model

We construct a driven sandpile slope model and study it by numerical simulations in one dimension. The model is specified by a threshold slope \sigma_c\/, a parameter \alpha\/, governing the local current-slope relation (beyond threshold), and $j_{\rm in}$, the mean input current of sand. A nonequilibrium phase diagram is obtained in the \alpha\, -\, j_{\rm in}\/ plane. We find an infinity of phases, characterized by different mean slopes and separated by continuous or first-order boundaries, some of which we obtain analytically. Extensions to two dimensions are discussed.Comment: 11 pages, RevTeX (preprint format), 4 figures available upon requs

Design and Construction of a Tesla Transformer by using Microwave Oven Transfer for Experimentation

This paper has focused on the step-by-step design of a high frequency medium size (1-3 kW) air-cored resonance transformer commonly called tesla coil, that can be easily used for measurements and general research. Therefore, the task is to minimize the number of stochastic and unknown parameters influencing the device functionality and pointing out pros and cons of each solution. The physical dimension of the tesla transformer has been chosen due to cost effectiveness and availability of the regarding components. This design has mainly two units’ viz., a power supply and tesla coil. The power supply which fed the Tesla coil having voltage rating 12kV and current rating 120mA has been designed by using three microwave oven components. These components are assembled as dual MOTs voltage doubler circuit and necessary simulation has been carried out by using MicroSim Schematics for the verification of performance. Keywords:Microwave Oven , Transformer, Multi mini Capacitors, MicroSim Schematics, Toroid, Tesla Coil CAD