scholarly journals Multiphysics and Multiscale Analysis for Chemotherapeutic Drug

2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Linan Zhang ◽  
Sung Youb Kim ◽  
Dongchoul Kim

This paper presents a three-dimensional dynamic model for the chemotherapy design based on a multiphysics and multiscale approach. The model incorporates cancer cells, matrix degrading enzymes (MDEs) secreted by cancer cells, degrading extracellular matrix (ECM), and chemotherapeutic drug. Multiple mechanisms related to each component possible in chemotherapy are systematically integrated for high reliability of computational analysis of chemotherapy. Moreover, the fidelity of the estimated efficacy of chemotherapy is enhanced by atomic information associated with the diffusion characteristics of chemotherapeutic drug, which is obtained from atomic simulations. With the developed model, the invasion process of cancer cells in chemotherapy treatment is quantitatively investigated. The performed simulations suggest a substantial potential of the presented model for a reliable design technology of chemotherapy treatment.

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 757
Author(s):  
Maged Sultan Alhammadi ◽  
Abeer Abdulkareem Al-mashraqi ◽  
Rayid Hussain Alnami ◽  
Nawaf Mohammad Ashqar ◽  
Omar Hassan Alamir ◽  
...  

The study sought to assess whether the soft tissue facial profile measurements of direct Cone Beam Computed Tomography (CBCT) and wrapped CBCT images of non-standardized facial photographs are accurate compared to the standardized digital photographs. In this cross-sectional study, 60 patients with an age range of 18–30 years, who were indicated for CBCT, were enrolled. Two facial photographs were taken per patient: standardized and random (non-standardized). The non-standardized ones were wrapped with the CBCT images. The most used soft tissue facial profile landmarks/parameters (linear and angular) were measured on direct soft tissue three-dimensional (3D) images and on the photographs wrapped over the 3D-CBCT images, and then compared to the standardized photographs. The reliability analysis was performed using concordance correlation coefficients (CCC) and depicted graphically using Bland–Altman plots. Most of the linear and angular measurements showed high reliability (0.91 to 0.998). Nevertheless, four soft tissue measurements were unreliable; namely, posterior gonial angle (0.085 and 0.11 for wrapped and direct CBCT soft tissue, respectively), mandibular plane angle (0.006 and 0.0016 for wrapped and direct CBCT soft tissue, respectively), posterior facial height (0.63 and 0.62 for wrapped and direct CBCT soft tissue, respectively) and total soft tissue facial convexity (0.52 for both wrapped and direct CBCT soft tissue, respectively). The soft tissue facial profile measurements from either the direct 3D-CBCT images or the wrapped CBCT images of non-standardized frontal photographs were accurate, and can be used to analyze most of the soft tissue facial profile measurements.


Author(s):  
Harri Makkonen ◽  
Jorma J. Palvimo

AbstractAndrogen receptor (AR) acts as a hormone-controlled transcription factor that conveys the messages of both natural and synthetic androgens to the level of genes and gene programs. Defective AR signaling leads to a wide array of androgen insensitivity disorders, and deregulated AR function, in particular overexpression of AR, is involved in the growth and progression of prostate cancer. Classic models of AR action view AR-binding sites as upstream regulatory elements in gene promoters or their proximity. However, recent wider genomic screens indicate that AR target genes are commonly activated through very distal chromatin-binding sites. This highlights the importance of long-range chromatin regulation of transcription by the AR, shifting the focus from the linear gene models to three-dimensional models of AR target genes and gene programs. The capability of AR to regulate promoters from long distances in the chromatin is particularly important when evaluating the role of AR in the regulation of genes in malignant prostate cells that frequently show striking genomic aberrations, especially gene fusions. Therefore, in addition to the mechanisms of DNA loop formation between the enhancer bound ARs and the transcription apparatus at the target core promoter, the mechanisms insulating distally bound ARs from promiscuously making contacts and activating other than their normal target gene promoters are critical for proper physiological regulation and thus currently under intense investigation. This review discusses the current knowledge about the AR action in the context of gene aberrations and the three-dimensional chromatin landscape of prostate cancer cells.


Author(s):  
H. X. Liang ◽  
Q. W. Wang ◽  
L. Q. Luo ◽  
Z. P. Feng

Three-dimensional numerical simulation was conducted to investigate the flow field and heat transfer performance of the Cross-Wavy Primary Surface (CWPS) recuperators for microturbines. Using high-effective compact recuperators to achieve high thermal efficiency is one of the key techniques in the development of microturbine in recent years. Recuperators need to have minimum volume and weight, high reliability and durability. Most important of all, they need to have high thermal-effectiveness and low pressure-losses so that the gas turbine system can achieve high thermal performances. These requirements have attracted some research efforts in designing and implementing low-cost and compact recuperators for gas turbine engines recently. One of the promising techniques to achieve this goal is the so-called primary surface channels with small hydraulic dimensions. In this paper, we conducted a three-dimensional numerical study of flow and heat transfer for the Cross-Wavy Primary Surface (CWPS) channels with two different geometries. In the CWPS configurations the secondary flow is created by means of curved and interrupted surfaces, which may disturb the thermal boundary layers and thus improve the thermal performances of the channels. To facilitate comparison, we chose the identical hydraulic diameters for the above four CWPS channels. Since our experiments on real recuperators showed that the Reynolds number ranges from 150 to 500 under the operating conditions, we implemented all the simulations under laminar flow situations. By analyzing the correlations of Nusselt numbers and friction factors vs. Reynolds numbers of the four CWPS channels, we found that the CWPS channels have superior and comprehensive thermal performance with high compactness, i.e., high heat transfer area to volume ratio, indicating excellent commercialized application in the compact recuperators.


2009 ◽  
Vol 185 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Farideh Sabeh ◽  
Ryoko Shimizu-Hirota ◽  
Stephen J. Weiss

Tissue invasion during metastasis requires cancer cells to negotiate a stromal environment dominated by cross-linked networks of type I collagen. Although cancer cells are known to use proteinases to sever collagen networks and thus ease their passage through these barriers, migration across extracellular matrices has also been reported to occur by protease-independent mechanisms, whereby cells squeeze through collagen-lined pores by adopting an ameboid phenotype. We investigate these alternate models of motility here and demonstrate that cancer cells have an absolute requirement for the membrane-anchored metalloproteinase MT1-MMP for invasion, and that protease-independent mechanisms of cell migration are only plausible when the collagen network is devoid of the covalent cross-links that characterize normal tissues.


Author(s):  
Mehdi Nikkhah ◽  
Jeannine S. Strobl ◽  
Bhanu Peddi ◽  
Adedamola Omotosho ◽  
Masoud Agah

In this paper we are investigating three dimensional (3-D) silicon-based microenvironments as potential platforms for breast cancer diagnostics. We have developed isotropically etched microstructures with a wide range of geometrical patterns for this purpose. Our results indicate that with the etched surface ratio of ∼65%, it is possible to capture 80–90% of the cancer cells within each silicon chip. After treatment of the cells with mitomycin C (to block the cell growth) more number of the cells are trapped inside the etched features for longer cultures times (72 h) suggesting that there is a directed motility and attraction of the cells toward the etched cavities and by optimally designing the etched features, the proposed platforms can be potentially used for diagnostics purposes.


2021 ◽  
Vol 17 ◽  
Author(s):  
Chu Xin Ng ◽  
Cheng Foh Le ◽  
Sau Har Lee

Background: Anticancer peptides (ACPs) have received increasing attention as a promising class of novel anticancer agents owing to its potent and rapid cytotoxic properties. In this study, we aim to investigate the effects of cationicity and hydrophobicity in modulating the cytotoxicity of PtxC, a class of ACP from the leafy mistletoe Phoradendron tomentosum against the MDA-MB-231 and Vero cells. Method: We designed a series of four PtxC analogues (PA1 – PA4) by residual substitutions with specific amino acids to introduce the specific charge and hydrophobicity alterations to the analogues. The cytotoxicity strength of the PtxC analogues on MDA-MB-231 and Vero cells were tested by using MTT assay at 24 hours post treatment. Results: PA1, PA2 and PA4 displayed marked increases in cytotoxicity against both MDA-MB-231 and Vero cells and can be ranked in the order of PA2 > PA4 > PA1 > PtxC > PA3. Sequence-activity relationship analyses of the designed analogues showed that an increase in the level of cationicity and hydrophobicity correlated well with the enhanced cytotoxic activity of PtxC analogues. This was observed with PA1 (netC +8) and PA2 (netC +10) in comparison to PtxC (netC +7). Similar finding was observed for PA4 (GRAVY +0.070) in contrast to PtxC (GRAVY -0.339). Three-dimensional modelling predicted a double α-helix structure in PtxC class of ACP. The larger first helix in PA2 and PA4 was suggested to be responsible for the enhanced cytotoxicity observed. Conclusion: The critical role of cationicity and hydrophobicity in enhancing cytotoxicity of PtxC class of ACPs were clearly demonstrated in our study. The current findings could be extrapolated to benefit peptide design strategy in other classes of ACPs toward the discovery of highly potent ACPs against cancer cells as potential novel therapeutic agents.


Author(s):  
D. Croccolo ◽  
T. M. Brugo ◽  
M. De Agostinis ◽  
S. Fini ◽  
G. Olmi

As electronics keeps on its trend towards miniaturization, increased functionality and connectivity, the need for improved reliability capacitors is growing rapidly in several industrial compartments, such as automotive, medical, aerospace and military. Particularly, recent developments of the automotive compartment, mostly due to changes in standards and regulations, are challenging the capabilities of capacitors in general, and especially film capacitors. Among the required features for a modern capacitor are the following: (i) high reliability under mechanical shock, (ii) wide working temperature range, (iii) high insulation resistance, (iv) small dimensions, (v) long expected life time and (vi) high peak withstanding voltage. This work aims at analyzing the key features that characterize the mechanical response of the capacitor towards temperature changes. Firstly, all the key components of the capacitor have been characterized, in terms of strength and stiffness, as a function of temperature. These objectives have been accomplished by means of several strain analysis methods, such as strain gauges, digital image correlation (DIC) or dynamic mechanical analysis (DMA). All the materials used to manufacture the capacitor, have been characterized, at least, with respect to their Young’s modulus and Poisson’s ratio. Then, a three-dimensional finite element model of the whole capacitor has been set up using the ANSYS code. Based on all the previously collected rehological data, the numerical model allowed to simulate the response in terms of stress and strain of each of the capacitor components when a steady state thermal load is applied. Due to noticeable differences between the thermal expansion coefficients of the capacitor components, stresses and strains build up, especially at the interface between different components, when thermal loads are applied to the assembly. Therefore, the final aim of these numerical analyses is to allow the design engineer to define structural optimization strategies, aimed at reducing the mechanical stresses on the capacitor components when thermal loads are applied.


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