Cancer cell recognition--mechanical phenotype

The major characteristics of cancer metastasis is the ability of the primary tumor cells to migrate by way of the blood or lymph vessels and to form tumors at multiple, distant sites. There are evidences that cancer progression is characterized by disruption and/or reorganization of cytoskeleton (i.e. cellular scaffold). This is accompanied by various molecular alterations influencing the overall mechanical resistance of cells. Current approach in diagnosis focuses mainly on microbiological, immunological, and pathological aspects rather than on the biomechanics of diseases. The determination of mechanical properties of an individual living cell has became possible with the development of local measurement techniques, such as atomic force microscopy, magnetic or optical tweezers. The advantage of them lies in the capability to measure living cells at a single cell level and in liquid conditions, close to natural environment. Here, we present the studies on mechanical properties of single cells originating from various cancers. The results show that, independently of the cancer type (bladder, melanoma, prostate, breast and colon), single cells are characterized by the lower Young's modulus, denoting higher deformability of cancerous cells. However, the obtained Young's modulus values were dependent on various factors, like the properties of substrates used for cell growth, force loading rate, or indentation depth. Their influence on elastic properties of cells was considered. Based on these findings, the identification of cancerous cells based on their elastic properties was performed. These results proved the AFM capability in recognition of a single, mechanically altered cell, also in cases when morphological changes are not visible. The quantitative analysis of cell deformability carried out using normal (reference) and cancerous cells and, more precisely, their characterization (qualitative and quantitative) can have a significant impact on the development of methodological approaches toward precise identification of pathological cells and would allow for more effective detection of cancer-related changes.     

Topography of Schwann cell with atomic force microscope

The peripheral nerve injury is very common, its repair and regeneration is a significant challenge in nerve tissue engineering. Schwann cells cytoskeleton remolding for the migration, myelination, and directional neurites outgrowth, in the peripheral nerve system (PNS), increases its importance to investigate. In this study, we used an atomic force microscope (AFM) to investigate the live and fixed RN-22 Schwann cell topography. We provided the RN-22 Schwann cell cytoskeleton structural variation within the cell. A comparison was made between the live and fixed RN-22 Schwann cell cytoskeleton structural details. This study may help for a better understanding of PNS.     

Near infrared Raman spectroscopic characterization of blood plasma of normal,oral premalignant and malignant conditions—a pilot study

The metabolic end products from cells/tissues that are released into the circulating blood stream and any changes in their level because of pathological conditions may be used as markers in disease diagnosis. Raman spectroscopy has been exploited to characterize the biomolecules present in the blood plasma of clinically confirmed normal group, premalignant (Oral Sub Mucous Fibrosis) and malignant (Oral Squamous Cell Carcinoma) at 784.15 nm. Raman spectral signatures show relatively less intense Raman bands of phenylalanine, lipid and antioxidant beta carotene but higher intense bands for proteins, DNA base components and amino acids (tyrosine and tryptophan) for malignant group than that of normal group. However premalignant group possess high intense Raman bands for amino acids (tyrosine and tryptophan) at 830, 1020 and 1620 cm⁻¹ and protein peaks at 913, 978 and 1646 cm⁻¹ when compared to that of malignant and normal group. Principal component analysis coupled with linear discriminant analysis (PCA‐LDA) yielded a diagnostic sensitivity of 96.3% and 91.2%, and a specificity of 80.0% and 96.7% in the classification of normal from premalignant and normal from malignant, respectively. This indicates that Raman spectroscopy of blood plasma has the potential in classifying normal and oral malignancy conditions. Copyright © 2015 John Wiley & Sons, Ltd.     

Influences of tissue composition and structural features of biological media on the ultrasonic nonlinearity parameter

The Acoustic nonlinearity parameter is an important parameter innonlinear acoustics.In this article,the nonlinearity parameter B/A of normaland eight kinds of pathological porcine liver tissues were measured by finiteamplitude insert-substitution method.The mixture law for nonlinearityparameter is used to analyze and predict the volume fractions of the compo-nents in a given tissue.It was found that the nonlinearity parameter is sensitiveto the pathological forms of biological tissues and the values of B/A dependon the tissue composition and structural features.     

Experimental study on fluid selection for a stable Taylor cone formation via micro-PIV measurement

In this study, the visualization of the flow inside a Taylor cone formed during an electrohydrodynamic (EHD) spraying is conducted to analyze its stability among five liquid candidates. A micro-PIV with a micro-nozzle is used for the visualization, and the physical properties as well as measured values are utilized in the analysis. First, in forming the Taylor cone, the electrohydrodynamic force is required to be sufficiently large in order to overcome the surface tension of the liquid. Thus, among the five liquids tested here, three, in this case IPA, EtOH, and MeOH, form a Taylor cone due to the relatively low surface tension levels as compared to the others. Once electrohydrodynamic jetting occurs, the average and maximum velocities become monotonically proportional to the average current. As the velocities are the smallest in using IPA, the circulation flow becomes superior to the extrusive flow, which yields the stable formation of a Taylor cone. Also, low fluctuation of the instantaneous currents supports the stable formation of IPA. Consequently, IPA shows the most stable formation of the Taylor cone in our condition due to the lowest average current and low-level surface tension. Eventually, micro-PIV would be a good tool in choosing an optimal fluid for stable EHD spraying.     

Driven Diffusive Systems of Active Filament Bundles

The cytoskeleton is an important subsystem of cells that is involved for example in cell division and locomotion. It consists of filaments that are cross-linked by molecular motors that can induce relative sliding between filaments and generate stresses in the network. In order to study the effects of fluctuations on the dynamics of such a system we introduce here a new class of driven diffusive systems mimicking the dynamics of active filament bundles where the filaments are aligned with respect to a common axis. After introducing the model class we first analyze an exactly solvable case and find condensation. For the general case we perform a mean-field analysis and study the behavior on large length scales by coarse-graining. We determine conditions for condensation and establish a relation between the hopping rates and the tension generated in the bundle.     

Synthesis,Characterization, Electrical Conductivity and Fluorescence Properties of Polyimine Bearing Phenylacetylene Units

In this study, a Schiff base was synthesized by the condensation reaction of 4-bromobenzaldehyde and 4-aminophenol. Then, phenylacetylene substituted Schiff base monomer (IPA) was obtained by HBr elimination reaction of IPA with phenylacetylene through Sonogashira reaction. IPA was polymerized via chemical oxidative polycondensation reaction. FT-IR and NMR measurements were used for the structural analyses of the synthesized substances. Fluorescence and UV–Vis analyses were carried out for optical characterization. Electrochemical characteristics, electrical conductivities and thermal properties were determined using cyclic voltammetry (CV), four-point probe conductometer, TG-DTA and DSC methods. The main purpose of the present study was to investigate the effects of phenylacetylene bearing units on the properties of conjugated aromatic polyimines. The spectral analysis signified a green light emission behavior when irradiated at different wavelengths. Combined with fluorescent behavior and good thermal stability, the electrical conductivity was found to be very crucial for π-conjugated polymer.     

Application of Euler Neural Networks with Soft Computing Paradigm to Solve Nonlinear Problems Arising in Heat Transfer

In this study, a novel application of neurocomputing technique is presented for solving nonlinear heat transfer and natural convection porous fin problems arising in almost all areas of engineering and technology, especially in mechanical engineering. The mathematical models of the problems are exploited by the intelligent strength of Euler polynomials based Euler neural networks (ENN’s), optimized with a generalized normal distribution optimization (GNDO) algorithm and Interior point algorithm (IPA). In this scheme, ENN’s based differential equation models are constructed in an unsupervised manner, in which the neurons are trained by GNDO as an effective global search technique and IPA, which enhances the local search convergence. Moreover, a temperature distribution of heat transfer and natural convection porous fin are investigated by using an ENN-GNDO-IPA algorithm under the influence of variations in specific heat, thermal conductivity, internal heat generation, and heat transfer rate, respectively. A large number of executions are performed on the proposed technique for different cases to determine the reliability and effectiveness through various performance indicators including Nash–Sutcliffe efficiency (NSE), error in Nash–Sutcliffe efficiency (ENSE), mean absolute error (MAE), and Thiel’s inequality coefficient (TIC). Extensive graphical and statistical analysis shows the dominance of the proposed algorithm with state-of-the-art algorithms and numerical solver RK-4.     

Comparison of mechanical properties of normal and malignant thyroid cells

Cancer is a disease of uncontrolled cell proliferation causing approximately 13% of deaths worldwide. Cancer cell mechanics is currently an important topic of investigation in cancer diagnostics as a possible tool to distinguish malignant cells from normal cells in addition to increasing our understanding of pathophysiology of the disease. Our study, based on Atomic Force Microscopy (AFM) measurements on cells, shows that malignant thyroid cells are 3- to 5-fold softer in comparison to primary normal thyroid cells depending on duration between cell seeding and AFM experiments. These results reveal cultivation period as an important factor that influences cell mechanics and which must be considered when comparing cells. Investigation of actin cytoskeleton by fluorescent labelling revealed differences in organization of actin between malignant and normal thyroid cells, which may be directly contributing to alteration of cell mechanics in cancer cells.     

Vibrations of rectangular plates reinforced by any number of beams of arbitrary lengths and placement angles

This paper presents an analytical method for the vibration analysis of plates reinforced by any number of beams of arbitrary lengths and placement angles. Both the plate and stiffening beams are generally modeled as three-dimensional (3-D) structures having six displacement components at a point, and the coupling at an interface is generically described by a set of distributed elastic springs. Each of the displacement functions is here invariably expressed as a modified Fourier series, which consists of a standard Fourier cosine series plus several supplementary series/functions used to ensure and improve uniform convergence of the series representation. Unlike most existing techniques, the current method offers a unified solution to the vibration problems for a wide spectrum of stiffened plates, regardless of their boundary conditions, coupling conditions, and reinforcement configurations. Several numerical examples are presented to validate the methodology and demonstrate the effect on modal parameters for a stiffened plate with various boundary conditions, coupling conditions, and reinforcement configurations.     

The effect of a magnetic field on a 2D problem of fibre-reinforced thermoelasticity rotation under three theories

In the present paper,we introduce the coupled theory(CD),Lord-Schulman(LS) theory,and Green-Lindsay(GL) theory to study the influences of a magnetic field and rotation on a two-dimensional problem of fibre-reinforced thermoelasticity.The material is a homogeneous isotropic elastic half-space.The method applied here is to use normal mode analysis to solve a thermal shock problem.Some particular cases are also discussed in the context of the problem.Deformation of a body depends on the nature of the force applied as well as the type of boundary conditions.Numerical results for the temperature,displacement,and thermal stress components are given and illustrated graphically in the absence and the presence of the magnetic field and rotation.     

Recent advances in liver sinusoidal endothelial ultrastructure and fine structure immunocytochemistry

Ultrastructure reports have described that liver sinusoidal endothelial cell (LSEC)s contain a cytoskeletal framework of filamentous actin. Small G protein has emerged as an important regulator of the actin cytoskeleton, and consequently, of cell morphology and motility. We investigated actin filaments in relation to SEF in LSECs using a heavy meromyosin-decorated reaction and thereby elucidated the roles of small G protein and actin cytoskeleton in the morphological and functional alterations of SEF. Caveolin-1 expression has also been found in fenestrations with many characteristics of liver sinusoidal endothelial cells. Currently, fenestral studies and human disease are revealing ways to increase the liver sieve's porosity, which is reduced through pathological mechanisms. Hepatic sinusoidal endothelial dysfunction, which is known to impair endothelium-dependent relaxation in the liver microcirculation, contributes to increased intrahepatic vascular resistance.     

Normal force exerted on vascular endothelial cells

Hemodynamic forces play an important role in the normal and pathological behavior of vascular endothelial cells as recent studies on the shear stress over the endothelium have shown. Based on computational investigation and scaling analysis, our study shows that the normal force contributes significantly to the total force on the endothelial cells even in large vessels. Therefore, our study suggests that the functions of endothelial cells are also affected by the normal forces exerted on them. The effects of the normal force are more pronounced for smaller vessels and/or less spread cells.     

Sol–gel derived ZnO nanoparticulate films for ultraviolet photodetector (UV) applications

Zinc oxide nanoparticles based UV detector was fabricated on thermally oxidized silicon substrate. ZnO nanoparticle films were deposited using sol–gel route. The seed solution was prepared using two different solvents (methanol and isopropyl alcohol (IPA)). The surface morphology of the prepared films was characterized by FESEM. Structural characterization along with optical measurements was carried out using XRD and UV–vis spectroscopy. For the UV photo-detector, ZnO thin film prepared in IPA is selected based on their structural and optical analysis. The changes in photo-response of ZnO thin film with respect to time was studied under the dark and variable UV intensities. It was observed that the photocurrent increased with a factor of 4.82 under 1.16 mW of UV intensity. It is believe that the synthesized ZnO thin films have potential to use in the ultraviolet photo-detector applications.     

Statistical characteristics of quasi-elastically scattered light in analysis of size of aggregated biological particles

The spectra of the intensity fluctuations of light scattered by large (erythrocytes of whole blood) and small (vesicles of surgical bile) particles in natural conditions were studied. It is shown that photon correlation spectroscopy can be used in analysis of variations in the size of biological particles in normal and pathological conditions and as an express method of noninvasive diagnostics of diseases.     

Methodological approaches for the free energy calculations in electroactive SAMs

We compare the Free Energy Perturbation (FEP) and Thermodynamic Integration (TI) approaches in slab-geometries where the electrostatic interactions are handled with the standard three-dimensionally Ewald summation technique. The comparison between FEP and TI is made through energy distributions in the analysis of the phase space sampling between the forward and backward directions, the reversibility of the perturbation, the number of windows and the consistency of the free energy decomposition into individual components. We report here free energy calculations in order to predict the shift in the redox potential in self-assembled monolayers (SAMs) as the coadsorbed chain length is changed. The reproduction of the free energies with respect to the electrolyte is tested on neutral and charged simulation cells.     

Coefficient of tangential restitution for viscoelastic spheres

The collision of frictional granular particles may be described by an interaction force whose normal component is that of viscoelastic spheres while the tangential part is described by the model by Cundall and Strack (Géotechnique 29, 47 (1979)) being the most popular tangential collision model in Molecular Dynamics simulations. Albeit being a rather complicated model, governed by 5 phenomenological parameters and 2 independent initial conditions, we find that it is described by 3 independent parameters only. Surprisingly, in a wide range of parameters the corresponding coefficient of tangential restitution, epsilont, is well described by the simple Coulomb law with a cut-off at epsilont = 0. A more complex behavior of the coefficient of restitution as a function on the normal and tangential components of the impact velocity, gn and gt, including negative values of epsilont, is found only for very small ratio gt/gn. For the analysis presented here we neglect dissipation of the interaction in normal direction.     

Raman spectral signatures of mouse mammary tissue and associated lymph nodes: normal,tumor and mastitis

Raman spectroscopy involves the interaction of light with the molecular vibrations and therefore can provide information about molecular structure, tissue composition and changes in its environment. We explored whether Raman spectroscopy can reliably distinguish mammary tumors from normal mammary tissues and other pathological states in mice. We analyzed a large number of Raman spectra from the tumor and normal mammary glands of mice injected with 4T1 tumor cells, which were collected using a high‐resolution (less than 4 cm⁻¹) Raman spectrometer at a fixed (785 nm) laser excitation wavelength and with 60 mW of laser power. The spectra of normal and tumor mammary glands showed consistent differences in the intensity of certain Raman bands and loss of some bands in the tumor spectra. Multivariate statistical methods—principal component analysis (PCA) and discriminant functional analysis (DFA)—were used to separate the data into different groups of mammary tumors, mastitis, lymph nodes contralateral and tumor‐cell‐injected sides, and normal contralateral and tumor‐cell‐injected sides. We demonstrate that this spectroscopic technique has the feasibility of discriminating tumor and mastitis from normal tissues and other pathological states in a short period of time and may detect tumor transformation earlier than the standard histological examination stage. Copyright © 2006 John Wiley & Sons, Ltd.     

Orthogonal contributor number for the measurement of sound power

Orthogonal contributors to a global error represent a very efficient design method in terms of both sensing and control of noise radiation. In practice the price of a sensing system will be determined by the number of errors it must resolve. Therefore predicting the most efficient way of measuring radiation power is an important problem. Recently work has compared sensing the number of vibration modes to the number of orthogonal contributors to radiated power. The required number of vibration modes was based on the proximity of the structural mode resonance frequency and the excitation frequency. While ultimately this technique will result in a valid estimate of radiated power, it is shown here that the number of structural modes can be minimized by first considering orthogonal radiators based on structural mode amplitudes. Two disturbance cases are considered: a point force and an even disturbance coupling to each structural mode. Also, under these conditions the practicality of estimating the number of orthogonal radiators when it is assumed that each contributor is equal in amplitude is examined. Finally in an attempt to optimism the number of signals to be sensed, a variable error margin for the estimate of power, based on the ratio of the sound power at each frequency to the maximum peak in the considered frequency range is proposed and analyzed.     

Physics of cell elasticity,shape and adhesion

We review recent theoretical work that analyzes experimental measurements of the shape, fluctuations and adhesion properties of biological cells. Particular emphasis is placed on the role of the cytoskeleton and cell elasticity and we contrast the shape and adhesion of elastic cells with fluid-filled vesicles. In red blood cells (RBC), the cytoskeleton consists of a two-dimensional network of spectrin proteins. Our analysis of the wavevector and frequency dependence of the fluctuation spectrum of RBC indicates that the spectrin network acts as a confining potential that reduces the fluctuations of the lipid bilayer membrane. However, since the cytoskeleton is only sparsely connected to the bilayer, one cannot regard the composite cytoskeleton–membrane as a polymerized object with a shear modulus. The sensitivity of RBC fluctuations and shapes to ATP concentration may reflect topological defects induced in the cytoskeleton network by ATP. The shapes of cells that adhere to a substrate are strongly determined by the cytoskeletal elasticity that can be varied experimentally by drugs that depolymerize the cytoskeleton. This leads to a tension-driven retraction of the cell body and a pearling instability of the resulting ray-like protrusions. Recent experiments have shown that adhering cells exert polarized forces on substrates. The interactions of such “force dipoles” in either bulk gels or on surfaces can be used to predict the nature of self-assembly of cell aggregates and may be important in the formation of artificial tissues. Finally, we note that cell adhesion strongly depends on the forces exerted on the adhesion sites by the tension of the cytoskeleton. The size and shape of the adhesion regions are strongly modified as the tension is varied and we present an elastic model that relates this tension to deformations that induce the recruitment of new molecules to the adhesion region. In all these examples, cell shape and adhesion differ from vesicle shape and adhesion due to the presence of the elastic cytoskeleton and to the fact that active processes (ATP, molecular motors) within the cell modify cytoskeletal elasticity and tension.