In silico Simulations for DNA Shuffling Experiments

DNA shuffling is a powerful method used for in vitro evolute molecules with specific functions and has application in areas such as, for example, pharmaceutical, medical and agricultural research. The success of such experiments is dependent on a variety of parameters and conditions that, sometimes, can not be properly pre-established. Here, two computational models predicting DNA shuffling results is presented and their use and results are evaluated against an empirical experiment. The in silico and in vitro results show agreement indicating the importance of these two models and motivating the study and development of new models.

Anticancer Effect of Doxorubicin Loaded Heparin based Super-paramagnetic Iron oxide Nanoparticles against the Human Ovarian Cancer Cells

This study determines the effect of naked and heparinbased super-paramagnetic iron oxide nanoparticles on the human cancer cell lines of A2780. Doxorubicin was used as the anticancer drug, entrapped in the SPIO-NPs. This study aimed to decorate nanoparticles with heparin, a molecular ligand for 'active' targeting of cancerous cells and the application of modified-nanoparticles in cancer treatment. The nanoparticles containing the anticancer drug DOX were prepared by a solvent evaporation and emulsification cross-linking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 110±15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of DOX from the SPIO-NPs was successful. Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell toxicity than the individual HP and confocal microscopy analysis confirmed excellent cellular uptake efficiency. These results indicate that HP based SPIO-NPs have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.

Induction of Alternative Oxidase Activity in Candida albicans by Oxidising Conditions

Candida albicans ATCC 10231 had low endogenous activity of the alternative oxidase compared with that of C. albicans ATCC 10261. In C. albicans ATCC 10231 the endogenous activity declined as the cultures aged. Alternative oxidase activity could be induced in C. albicans ATCC 10231 by treatment with cyanide, but the induction of this activity required the presence of oxygen which could be replaced, at least in part, with high concentrations of potassium ferricyanide. We infer from this that the expression of the gene encoding the alternative oxidase is under the control of a redoxsensitive transcription factor.

Rigorous Electromagnetic Model of Fourier Transform Infrared (FT-IR) Spectroscopic Imaging Applied to Automated Histology of Prostate Tissue Specimens

Fourier transform infrared (FT-IR) spectroscopic imaging is an emerging technique that provides both chemically and spatially resolved information. The rich chemical content of data may be utilized for computer-aided determinations of structure and pathologic state (cancer diagnosis) in histological tissue sections for prostate cancer. FT-IR spectroscopic imaging of prostate tissue has shown that tissue type (histological) classification can be performed to a high degree of accuracy [1] and cancer diagnosis can be performed with an accuracy of about 80% [2] on a microscopic (≈ 6μm) length scale. In performing these analyses, it has been observed that there is large variability (more than 60%) between spectra from different points on tissue that is expected to consist of the same essential chemical constituents. Spectra at the edges of tissues are characteristically and consistently different from chemically similar tissue in the middle of the same sample. Here, we explain these differences using a rigorous electromagnetic model for light-sample interaction. Spectra from FT-IR spectroscopic imaging of chemically heterogeneous samples are different from bulk spectra of individual chemical constituents of the sample. This is because spectra not only depend on chemistry, but also on the shape of the sample. Using coupled wave analysis, we characterize and quantify the nature of spectral distortions at the edges of tissues. Furthermore, we present a method of performing histological classification of tissue samples. Since the mid-infrared spectrum is typically assumed to be a quantitative measure of chemical composition, classification results can vary widely due to spectral distortions. However, we demonstrate that the selection of localized metrics based on chemical information can make our data robust to the spectral distortions caused by scattering at the tissue boundary.

Evaluation of a New Method for Detection of Kidney Stone during Laparoscopy Using 3D Conceptual Modeling

Minimally invasive surgery (MIS) is now being widely used as a preferred choice for various types of operations. The need to detect various tactile properties, justifies the key role of tactile sensing that is currently missing in MIS. In this regard, Laparoscopy is one of the methods of minimally invasive surgery that can be used in kidney stone removal surgeries. At this moment, determination of the exact location of stone during laparoscopy is one of the limitations of this method that no scientific solution has been found for so far. Artificial tactile sensing is a new method for obtaining the characteristics of a hard object embedded in a soft tissue. Artificial palpation is an important application of artificial tactile sensing that can be used in different types of surgeries. In this study, a new method for determining the exact location of stone during laparoscopy is presented. In the present study, the effects of stone existence on the surface of kidney were investigated using conceptual 3D model of kidney containing a simulated stone. Having imitated palpation and modeled it conceptually, indications of stone existence that appear on the surface of kidney were determined. A number of different cases were created and solved by the software and using stress distribution contours and stress graphs, it is illustrated that the created stress patterns on the surface of kidney show not only the existence of stone inside, but also its exact location. So three-dimensional analysis leads to a novel method of predicting the exact location of stone and can be directly applied to the incorporation of tactile sensing in artificial palpation, helping surgeons in non-invasive procedures.

Bone Generation through Mechanical Loading

Bones are dynamic and responsive organs, they regulate their strength and mass according to the loads which they are subjected. Because, the Wnt/β-catenin pathway has profound effects on the regulation of bone mass, we hypothesized that mechanical loading of bone cells stimulates Wnt/β-catenin signaling, which results in the generation of new bone mass. Mechanical loading triggers the secretion of the Wnt molecule, which after binding to transmembrane proteins, causes GSK-3β (Glycogen synthase kinase 3 beta) to cease the phosphorylation of β-catenin. β-catenin accumulation in the cytoplasm, followed by its transport into the nucleus, binding to transcription factors (TCF/LEF) that initiate transcription of genes related to bone formation. To test this hypothesis, we used TOPGAL (Tcf Optimal Promoter β-galactosidase) mice in an experiment in which cyclic loads were applied to the forearm. TOPGAL mice are reporters for cells effected by the Wnt/β-catenin signaling pathway. TOPGAL mice are genetically engineered mice in which transcriptional activation of β- catenin, results in the production of an enzyme, β-galactosidase. The presence of this enzyme allows us to localize transcriptional activation of β-catenin to individual cells, thereby, allowing us to quantify the effects that mechanical loading has on the Wnt/β-catenin pathway and new bone formation. The ulnae of loaded TOPGAL mice were excised and transverse slices along different parts of the ulnar shaft were assayed for the presence of β-galactosidase. Our results indicate that loading increases β-catenin transcriptional activity in regions where this pathway is already primed (i.e. where basal activity is already higher) in a load magnitude dependent manner. Further experiments are needed to determine the temporal and spatial activation of this signaling in relation to bone formation.

The Effect of Press Fit on Osseointegration of Acetabular Cup

The primary cause of Total Hip Replacement (THR) failure for younger patients is aseptic loosening. This complication is twice more likely to happen in acetabular cup than in femoral stem. Excessive micromotion between bone and implant will cause loosening and it depends in patient activities, age and bone. In this project, the effects of different metal back design of press fit on osseointegration of the acetabular cup are carried out. Commercial acetabular cup designs, namely Spiked, Superfix and Quadrafix are modelled and analyzed using commercial finite element software. The diameter of acetabular cup is based on the diameter of acetabular rim to make sure the component fit to the acetabular cavity. A new design of acetabular cup are proposed and analyzed to get better osseointegration between the bones and implant interface. Results shows that the proposed acetabular cup designs are more stable compared to other designs with respect to stress and displacement aspects.

X-Ray Intensity Measurement Using Frequency Output Sensor for Computed Tomography

Quality of 2D and 3D cross-sectional images produce by Computed Tomography primarily depend upon the degree of precision of primary and secondary X-Ray intensity detection. Traditional method of primary intensity detection is apt to errors. Recently the X-Ray intensity measurement system along with smart X-Ray sensors is developed by our group which is able to detect primary X-Ray intensity unerringly. In this study a new smart X-Ray sensor is developed using Light-to-Frequency converter TSL230 from Texas Instruments which has numerous advantages in terms of noiseless data acquisition and transmission. TSL230 construction is based on a silicon photodiode which converts incoming X-Ray radiation into the proportional current signal. A current to frequency converter is attached to this photodiode on a single monolithic CMOS integrated circuit which provides proportional frequency count to incoming current signal in the form of the pulse train. The frequency count is delivered to the center of PICDEM FS USB board with PIC18F4550 microcontroller mounted on it. With highly compact electronic hardware, this Demo Board efficiently read the smart sensor output data. The frequency output approaches overcome nonlinear behavior of sensors with analog output thus un-attenuated X-Ray intensities could be measured precisely and better normalization could be acquired in order to attain high resolution.

PMF, Cesium and Rubidium Nanoparticles Induce Apoptosis in A549 Cells

Cancer becomes one of the leading cause of death in many countries over the world. Fourier-transform infrared (FTIR) spectra of human lung cancer cells (A549) treated with PMF (natural product extracted from PM 701) for different time intervals were examined. Second derivative and difference method were taken in comparison studies. Cesium (Cs) and Rubidium (Rb) nanoparticles in PMF were detected by Energy Dispersive X-ray attached to Scanning Electron Microscope SEM-EDX. Characteristic changes in protein secondary structure, lipid profile and changes in the intensities of DNA bands were identified in treated A549 cells spectra. A characteristic internucleosomal ladder of DNA fragmentation was also observed after 30 min of treatment. Moreover, the pH values were significantly increases upon treatment due to the presence of Cs and Rb nanoparticles in the PMF fraction. These results support the previous findings that PMF is selective anticancer agent and can produce apoptosis to A549 cells.

Calculation of the Forces Acting on the Knee Joint When Rising from Kneeling Positions (Effects of the Leg Alignment and the Arm Assistance on the Knee Joint Forces)

Knee joint forces are available by in vivo measurement using an instrumented knee prosthesis for small to moderate knee flexion but not for high flexion yet. We created a 2D mathematical model of the lower limb incorporating several new features such as a patello-femoral mechanism, a thigh-calf contact at high knee flexion and co-contracting muscles' force ratio, then used it to determine knee joint forces arising from high knee flexions in four kneeling conditions: rising with legs in parallel, with one foot forward, with or without arm use. With arms used, the maximum values of knee joint force decreased to about 60% of those with arms not used. When rising with one foot forward, if arms are not used, the forward leg sustains a force as large as that sustained when rising with legs parallel.

A Ring-Shaped Tri-Axial Force Sensor for Minimally Invasive Surgery

This paper presents the design of a ring-shaped tri-axial fore sensor that can be incorporated into the tip of a guidewire for use in minimally invasive surgery (MIS). The designed sensor comprises a ring-shaped structure located at the center of four cantilever beams. The ringdesign allows surgical tools to be easily passed through which largely simplified the integration process. Silicon nanowires (SiNWs) are used aspiezoresistive sensing elementsembeddedon the four cantilevers of the sensor to detect the resistance change caused by the applied load.An integration scheme with new designed guidewire tip structure having two coils at the distal end is presented. Finite element modeling has been employed in the sensor design to find the maximum stress location in order to put the SiNWs at the high stress regions to obtain maximum output. A maximum applicable force of 5 mN is found from modeling. The interaction mechanism between the designed sensor and a steel wire has been modeled by FEM. A linear relationship between the applied load on the steel wire and the induced stress on the SiNWs were observed.

A Trainable Neural Network Ensemble for ECG Beat Classification

This paper illustrates the use of a combined neural network model for classification of electrocardiogram (ECG) beats. We present a trainable neural network ensemble approach to develop customized electrocardiogram beat classifier in an effort to further improve the performance of ECG processing and to offer individualized health care. We process a three stage technique for detection of premature ventricular contraction (PVC) from normal beats and other heart diseases. This method includes a denoising, a feature extraction and a classification. At first we investigate the application of stationary wavelet transform (SWT) for noise reduction of the electrocardiogram (ECG) signals. Then feature extraction module extracts 10 ECG morphological features and one timing interval feature. Then a number of multilayer perceptrons (MLPs) neural networks with different topologies are designed. The performance of the different combination methods as well as the efficiency of the whole system is presented. Among them, Stacked Generalization as a proposed trainable combined neural network model possesses the highest recognition rate of around 95%. Therefore, this network proves to be a suitable candidate in ECG signal diagnosis systems. ECG samples attributing to the different ECG beat types were extracted from the MIT-BIH arrhythmia database for the study.

Biosensor Measurement of Urea Coonncentration in Human Blood Serum

An application of the highly biosensor based on pH-sensitive field immobilized urease for urea analysis was demo The main analytical characteristics of the bios determined; the conditions of urea measureme blood were optimized. A conceptual possibility biosensor for detection of urea concentratio patients suffering from renal insufficiency was sensitive and selective effect transistor and monstrated in this work. iosensor developed were ment in real samples of ility of application of the tion in blood serum of as shown.

PCR based Detection of Food Borne Pathogens

Many high-risk pathogens that cause disease in humans are transmitted through various food items. Food-borne disease constitutes a major public health problem. Assessment of the quality and safety of foods is important in human health. Rapid and easy detection of pathogenic organisms will facilitate precautionary measures to maintain healthy food. The Polymerase Chain Reaction (PCR) is a handy tool for rapid detection of low numbers of bacteria. We have designed gene specific primers for most common food borne pathogens such as Staphylococci, Salmonella and E.coli. Bacteria were isolated from food samples of various food outlets and identified using gene specific PCRs. We identified Staphylococci, Salmonella and E.coli O157 using gene specific primers by rapid and direct PCR technique in various food samples. This study helps us in getting a complete picture of the various pathogens that threaten to cause and spread food borne diseases and it would also enable establishment of a routine procedure and methodology for rapid identification of food borne bacteria using the rapid technique of direct PCR. This study will also enable us to judge the efficiency of present food safety steps taken by food manufacturers and exporters.

Influence of Microstructural Features on Wear Resistance of Biomedical Titanium Materials

The field of biomedical materials plays an imperative requisite and a critical role in manufacturing a variety of biological artificial replacements in a modern world. Recently, titanium (Ti) materials are being used as biomaterials because of their superior corrosion resistance and tremendous specific strength, free- allergic problems and the greatest biocompatibility compared to other competing biomaterials such as stainless steel, Co-Cr alloys, ceramics, polymers, and composite materials. However, regardless of these excellent performance properties, Implantable Ti materials have poor shear strength and wear resistance which limited their applications as biomaterials. Even though the wear properties of Ti alloys has revealed some improvements, the crucial effectiveness of biomedical Ti alloys as wear components requires a comprehensive deep understanding of the wear reasons, mechanisms, and techniques that can be used to improve wear behavior. This review examines current information on the effect of thermal and thermomechanical processing of implantable Ti materials on the long-term prosthetic requirement which related with wear behavior. This paper focuses mainly on the evolution, evaluation and development of effective microstructural features that can improve wear properties of bio grade Ti materials using thermal and thermomechanical treatments.

Scatterer Density in Nonlinear Diffusion for Speckle Reduction in Ultrasound Imaging: The Isotropic Case

This paper proposes a method for speckle reduction in medical ultrasound imaging while preserving the edges with the added advantages of adaptive noise filtering and speed. A nonlinear image diffusion method that incorporates local image parameter, namely, scatterer density in addition to gradient, to weight the nonlinear diffusion process, is proposed. The method was tested for the isotropic case with a contrast detail phantom and varieties of clinical ultrasound images, and then compared to linear and some other diffusion enhancement methods. Different diffusion parameters were tested and tuned to best reduce speckle noise and preserve edges. The method showed superior performance measured both quantitatively and qualitatively when incorporating scatterer density into the diffusivity function. The proposed filter can be used as a preprocessing step for ultrasound image enhancement before applying automatic segmentation, automatic volumetric calculations, or 3D ultrasound volume rendering.

Using Data Mining Techniques for Finding Cardiac Outlier Patients

In this paper we used data mining techniques to identify outlier patients who are using large amount of drugs over a long period of time. Any healthcare or health insurance system should deal with the quantities of drugs utilized by chronic diseases patients. In Kingdom of Bahrain, about 20% of health budget is spent on medications. For the managers of healthcare systems, there is no enough information about the ways of drug utilization by chronic diseases patients, is there any misuse or is there outliers patients. In this work, which has been done in cooperation with information department in the Bahrain Defence Force hospital; we select the data for Cardiac patients in the period starting from 1/1/2008 to December 31/12/2008 to be the data for the model in this paper. We used three techniques for finding the drug utilization for cardiac patients. First we applied a clustering technique, followed by measuring of clustering validity, and finally we applied a decision tree as classification algorithm. The clustering results is divided into three clusters according to the drug utilization, for 1603 patients, who received 15,806 prescriptions during this period can be partitioned into three groups, where 23 patients (2.59%) who received 1316 prescriptions (8.32%) are classified to be outliers. The classification algorithm shows that the use of average drug utilization and the age, and the gender of the patient can be considered to be the main predictive factors in the induced model.

Modeling of Normal and Atherosclerotic Blood Vessels using Finite Element Methods and Artificial Neural Networks

Analysis of blood vessel mechanics in normal and diseased conditions is essential for disease research, medical device design and treatment planning. In this work, 3D finite element models of normal vessel and atherosclerotic vessel with 50% plaque deposition were developed. The developed models were meshed using finite number of tetrahedral elements. The developed models were simulated using actual blood pressure signals. Based on the transient analysis performed on the developed models, the parameters such as total displacement, strain energy density and entropy per unit volume were obtained. Further, the obtained parameters were used to develop artificial neural network models for analyzing normal and atherosclerotic blood vessels. In this paper, the objectives of the study, methodology and significant observations are presented.

On the Design of Shape Memory Alloy Locking Mechanism: A Novel Solution for Laparoscopic Ligation Process

The blood ducts must be occluded to avoid loss of blood from vessels in laparoscopic surgeries. This paper presents a locking mechanism to be used in a ligation laparoscopic procedure (LigLAP I), as an alternative solution for a stapling procedure. Currently, stapling devices are being used to occlude vessels. Using these devices may result in some problems, including injury of bile duct, taking up a great deal of space behind the vessel, and bile leak. In this new procedure, a two-layer suture occludes a vessel. A locking mechanism is also required to hold the suture. Since there is a limited space at the device tip, a Shape Memory Alloy (SMA) actuator is used in this mechanism. Suitability for cleanroom applications, small size, and silent performance are among the advantages of SMA actuators in biomedical applications. An experimental study is conducted to examine the function of the locking mechanism. To set up the experiment, a prototype of a locking mechanism is built using nitinol, which is a nickel-titanium shape memory alloy. The locking mechanism successfully locks a polymer suture for all runs of the experiment. In addition, the effects of various surface materials on the applied pulling forces are studied. Various materials are mounted at the mechanism tip to compare the maximum pulling forces applied to the suture for each material. The results show that the various surface materials on the device tip provide large differences in the applied pulling forces.

Beam Orientation Optimization Using Ant Colony Optimization in Intensity Modulated Radiation Therapy

In intensity modulated radiation therapy (IMRT) treatment planning, beam angles are usually preselected on the basis of experience and intuition. Therefore, getting an appropriate beam configuration needs a very long time. Based on the present situation, the paper puts forward beam orientation optimization using ant colony optimization (ACO). We use ant colony optimization to select the beam configurations, after getting the beam configuration using Conjugate Gradient (CG) algorithm to optimize the intensity profiles. Combining with the information of the effect of pencil beam, we can get the global optimal solution accelerating. In order to verify the feasibility of the presented method, a simulated and clinical case was tested, compared with dose-volume histogram and isodose line between target area and organ at risk. The results showed that the effect was improved after optimizing beam configurations. The optimization approach could make treatment planning meet clinical requirements more efficiently, so it had extensive application perspective.