Excellence in Research and Innovation for Humanity

International Science Index

Commenced in January 1999 Frequency: Monthly Edition: International Paper Count: 13

Medical, Health, Biomedical, Bioengineering and Pharmaceutical Engineering

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  • 13
    Evaluation of the Impact of Dataset Characteristics for Classification Problems in Biological Applications

    Availability of high dimensional biological datasets such as from gene expression, proteomic, and metabolic experiments can be leveraged for the diagnosis and prognosis of diseases. Many classification methods in this area have been studied to predict disease states and separate between predefined classes such as patients with a special disease versus healthy controls. However, most of the existing research only focuses on a specific dataset. There is a lack of generic comparison between classifiers, which might provide a guideline for biologists or bioinformaticians to select the proper algorithm for new datasets. In this study, we compare the performance of popular classifiers, which are Support Vector Machine (SVM), Logistic Regression, k-Nearest Neighbor (k-NN), Naive Bayes, Decision Tree, and Random Forest based on mock datasets. We mimic common biological scenarios simulating various proportions of real discriminating biomarkers and different effect sizes thereof. The result shows that SVM performs quite stable and reaches a higher AUC compared to other methods. This may be explained due to the ability of SVM to minimize the probability of error. Moreover, Decision Tree with its good applicability for diagnosis and prognosis shows good performance in our experimental setup. Logistic Regression and Random Forest, however, strongly depend on the ratio of discriminators and perform better when having a higher number of discriminators.

    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.
    Oncogene Identification using Filter based Approaches between Various Cancer Types in Lung

    Lung cancer accounts for the most cancer related deaths for men as well as for women. The identification of cancer associated genes and the related pathways are essential to provide an important possibility in the prevention of many types of cancer. In this work two filter approaches, namely the information gain and the biomarker identifier (BMI) are used for the identification of different types of small-cell and non-small-cell lung cancer. A new method to determine the BMI thresholds is proposed to prioritize genes (i.e., primary, secondary and tertiary) using a k-means clustering approach. Sets of key genes were identified that can be found in several pathways. It turned out that the modified BMI is well suited for microarray data and therefore BMI is proposed as a powerful tool for the search for new and so far undiscovered genes related to cancer.

    Computational Design of Inhibitory Agents of BMP-Noggin Interaction to Promote Osteogenesis
    Bone growth factors, such as Bone Morphogenic Protein-2 (BMP-2) have been approved by the FDA to replace grafting for some surgical interventions, but the high dose requirement limits its use in patients. Noggin, an extracellular protein, blocks the effect of BMP-2 by binding to BMP. Preventing the BMP-2/noggin interaction will help increase the free concentration of BMP-2 and therefore should enhance its efficacy to induce bone formation. The work presented here involves computational design of novel small molecule inhibitory agents of BMP-2/noggin interaction, based on our current understanding of BMP-2, and its known putative ligands (receptors and antagonists). A successful acquisition of such an inhibitory agent of BMP-2/noggin interaction would allow clinicians to reduce the dose required of BMP-2 protein in clinical applications to promote osteogenesis. The available crystal structures of the BMPs, its receptors, and the binding partner noggin were analyzed to identify the critical residues involved in their interaction. In presenting this study, LUDI de novo design method was utilized to perform virtual screening of a large number of compounds from a commercially available library against the binding sites of noggin to identify the lead chemical compounds that could potentially block BMP-noggin interaction with a high specificity.
    Realignment of f-actin Cytoskeleton in Osteocytes after Mechanical Loading
    F-actin fibrils are the cytoskeleton of osteocytes. They react in a dynamic manner to mechanical loading, and strength and reposition their efforts to reinforce the cells structure. We hypothesize that f-actin is temporarly disrupted after loading and repolymerizes in a new orientation to oppose the applied load. In vitro studies are conducted to determine f-actin disruption after varying mechanical stimulus parameters that are known to affect bone formation. Results indicate that the f-actin cytoskeleton is disrupted in vitro as a function of applied mechanical stimulus parameters and that the f-actin bundles reassemble after loading induced disruption within 3 minutes after cessation of loading. The disruption of the factin cytoskeleton depends on the magnitude of stretch, the numbers of loading cycles, frequency, the insertion of rest between loading cycles and extracellular calcium. In vivo studies also demonstrate disruption of the f-actin cytoskeleton in cells embedded in the bone matrix immediately after mechanical loading. These studies suggest that adaptation of the f-actin fiber bundles of the cytoskeleton in response to applied loads occurs by disruption and subsequent repolymerization.
    Identification of Complex Sense-antisense Gene's Module on 17q11.2 Associated with Breast Cancer Aggressiveness and Patient's Survival

    Sense-antisense gene pair (SAGP) is a pair of two oppositely transcribed genes sharing a common region on a chromosome. In the mammalian genomes, SAGPs can be organized in more complex sense-antisense gene architectures (CSAGA) in which at least one gene could share loci with two or more antisense partners. Many dozens of CSAGAs can be found in the human genome. However, CSAGAs have not been systematically identified and characterized in context of their role in human diseases including cancers. In this work we characterize the structural-functional properties of a cluster of 5 genes –TMEM97, IFT20, TNFAIP1, POLDIP2 and TMEM199, termed TNFAIP1 / POLDIP2 module. This cluster is organized as CSAGA in cytoband 17q11.2. Affymetrix U133A&B expression data of two large cohorts (410 atients, in total) of breast cancer patients and patient survival data were used. For the both studied cohorts, we demonstrate (i) strong and reproducible transcriptional co-regulatory patterns of genes of TNFAIP1/POLDIP2 module in breast cancer cell subtypes and (ii) significant associations of TNFAIP1/POLDIP2 CSAGA with amplification of the CSAGA region in breast cancer, (ii) cancer aggressiveness (e.g. genetic grades) and (iv) disease free patient-s survival. Moreover, gene pairs of this module demonstrate strong synergetic effect in the prognosis of time of breast cancer relapse. We suggest that TNFAIP1/ POLDIP2 cluster can be considered as a novel type of structural-functional gene modules in the human genome.

    Influence of Calcium Intake Level to Osteoporptic Vertebral bone and Degenerated Disc in Biomechanical Study

    The aim of the present study is to analyze the generation of osteoporotic vertebral bone induced by lack of calcium during growth period and analyze its effects for disc degeneration, based on biomechanical and histomorphometrical study. Mechanical and histomorphological characteristics of lumbar vertebral bones and discs of rats with calcium free diet (CFD) were detected and tracked by using high resolution in-vivo micro-computed tomography (in-vivo micro-CT), finite element (FE) and histological analysis. Twenty female Sprague-Dawley rats (6 weeks old, approximate weight 170g) were randomly divided into two groups (CFD group: 10, NOR group: 10). The CFD group was maintained on a refmed calcium-controlled semisynthetic diet without added calcium, to induce osteoporosis. All lumbar (L 1-L6) were scanned by using in vivo micro-CT with 35i.un resolution at 0, 4, 8 weeks to track the effects of CFD on the generation of osteoporosis. The fmdings of the present study indicated that calcium insufficiency was the main factor in the generation of osteoporosis and it induced lumbar vertebral disc degeneration. This study is a valuable experiment to firstly evaluate osteoporotic vertebral bone and disc degeneration induced by lack of calcium during growth period from a biomechanical and histomorphometrical point of view.

    Validation of an EEG Classification Procedure Aimed at Physiological Interpretation

    One approach to assess neural networks underlying the cognitive processes is to study Electroencephalography (EEG). It is relevant to detect various mental states and characterize the physiological changes that help to discriminate two situations. That is why an EEG (amplitude, synchrony) classification procedure is described, validated. The two situations are "eyes closed" and "eyes opened" in order to study the "alpha blocking response" phenomenon in the occipital area. The good classification rate between the two situations is 92.1 % (SD = 3.5%) The spatial distribution of a part of amplitude features that helps to discriminate the two situations are located in the occipital regions that permit to validate the localization method. Moreover amplitude features in frontal areas, "short distant" synchrony in frontal areas and "long distant" synchrony between frontal and occipital area also help to discriminate between the two situations. This procedure will be used for mental fatigue detection.

    Numerical Simulation of Restenosis in a Stented Coronary Artery
    Nowadays, cardiac disease is one of the most common cause of death. Each year almost one million of angioplasty interventions and stents implantations are made all over the world. Unfortunately, in 20-30% of cases neointimal proliferations leads to restenosis occurring within the following period of 3-6 months. Three major factors are believed to contribute mostly to the edge restenosis: (a) mechanical damage of the artery-s wall caused by the stent implantation, (b) interaction between the stent and the blood constituents and (c) endothelial growth stimulation by small (lower that 1.5 Pa) and oscillating wall shear stress. Assuming that this last actor is particularly important, a numerical model of restenosis basing on wall shear stress distribution in the stented artery was elaborated. A numerical simulations of the development of in-stent restenosis have been performed and realistic geometric patterns of a progressing lumen reduction have been obtained
    Application of Magnetic Circuit and Multiple-Coils Array in Induction Heating for Improving Localized Hyperthermia
    Aiming the application of localized hyperthermia, a magnetic induction system with new approaches is proposed. The techniques in this system for improving the effectiveness of localized hyperthermia are that using magnetic circuit and the multiple-coil array instead of a giant coil for generating magnetic field. Specially, amorphous metal is adopted as the material of magnetic circuit. Detail design parameters of hardware are well described. Simulation tool is employed for this work and experiment result is reported as well.
    Status of Thyroid Function and Iron Overload in Adolescents and Young Adults with Beta- Thalassemia Major Treated with Deferoxamine in Jordan
    Thyroid dysfunction is one of the most frequently reported complications of chronic blood transfusion therapy in patients with beta-thalassemia major (BTM). However, the occurrence of thyroid dysfunction and its possible association with iron overload in BTM patients is still under debate. Therefore, this study aimed to investigate the status of thyroid functions and iron overload in adolescent and young adult patients with BTM in Jordan population. Thirty six BTM patients aged 12-28 years and matched controls were included in this study. All patients have been receiving frequent blood transfusion to maintain pretransfusion hemoglobin concentration above 10 g dl-1 and deferoxamine at a dose of 45 mg kg-1 day-1 (8 h, 5-7 days/week) by subcutaneous infusion. Blood samples were drawn from patients and controls. The status of thyroid functions and iron overload was evaluated by measurements of serum free thyroxine (FT4), triiodothyronine (FT3), thyrotropin (TSH) and serum ferritin level. A number of some hematological and biochemical parameters were also measured. It was found that hematocrit, serum ferritin, hemoglobin, FT3 and zinc, copper mean values were significantly higher in the patients than in the controls (P< 0.05). On other hand, leukocyte, FT4 and TSH mean values were similar to that of the controls. In addition, our data also indicated that all of the above examined parameters were not significantly affected by the patient-s age and gender. Deferoxamine approach for removing excess iron from our BTM patient did not normalize the values of serum ferritin, copper and zinc, suggesting poor compliance with deferoxamine chelation therapy. Thus, we recommend the use of a combination of deferoxamine and deferiprone to reduce the risk of excess of iron in our patients. Furthermore, thyroid dysfunction appears to be a rare complication, because our patients showed normal mean levels for serum TSH and FT4. However, high mean levels of serum ferritin, zinc, copper might be seen as potential risk factors for initiation and development of thyroid dysfunctions and other diseases. Therefore, further studies must be carried out at yearly intervals with large sample number, to detect subclinical thyroid dysfunction cases.
    Automatic Segmentation of Thigh Magnetic Resonance Images

    Purpose: To develop a method for automatic segmentation of adipose and muscular tissue in thighs from magnetic resonance images. Materials and methods: Thirty obese women were scanned on a Siemens Impact Expert 1T resonance machine. 1500 images were finally used in the tests. The developed segmentation method is a recursive and multilevel process that makes use of several concepts such as shaped histograms, adaptative thresholding and connectivity. The segmentation process was implemented in Matlab and operates without the need of any user interaction. The whole set of images were segmented with the developed method. An expert radiologist segmented the same set of images following a manual procedure with the aid of the SliceOmatic software (Tomovision). These constituted our 'goal standard'. Results: The number of coincidental pixels of the automatic and manual segmentation procedures was measured. The average results were above 90 % of success in most of the images. Conclusions: The proposed approach allows effective automatic segmentation of MRIs from thighs, comparable to expert manual performance.

    A Numerical Investigation on the Dynamic Stall of a Wind Turbine Section Using Different Turbulent Models

    In this article, the flow behavior around a NACA 0012 airfoil which is oscillating with different Reynolds numbers and in various amplitudes has been investigated numerically. Numerical simulations have been performed with ANSYS software. First, the 2- D geometry has been studied in different Reynolds numbers and angles of attack with various numerical methods in its static condition. This analysis was to choose the best turbulent model and comparing the grids to have the optimum one for dynamic simulations. Because the analysis was to study the blades of wind turbines, the Reynolds numbers were not arbitrary. They were in the range of 9.71e5 to 22.65e5. The angle of attack was in the range of -41.81° to 41.81°. By choosing the forward wind speed as the independent parameter, the others like Reynolds and the amplitude of the oscillation would be known automatically. The results show that the SST turbulent model is the best choice that leads the least numerical error with respect the experimental ones. Also, a dynamic stall phenomenon is more probable at lower wind speeds in which the lift force is less.