Towards the prediction of mutations in genomic sequences

Bio-systems are inherently complex information processing systems. Furthermore, physiological complexities of biological systems limit the formation of a hypothesis in terms of behavior and the ability to test hypothesis. More importantly the identification and classification of mutation in patients are centric topics in today's cancer research. Next generation sequencing (NGS) technologies can provide genome-wide coverage at a single nucleotide resolution and at reasonable speed and cost. The unprecedented molecular characterization provided by NGS offers the potential for an individualized approach to treatment. These advances in cancer genomics have enabled scientists to interrogate cancer-specific genomic variants and compare them with the normal variants in the same patient. Analysis of this data provides a catalog of somatic variants, present in tumor genome but not in the normal tissue DNA. In this dissertation, we present a new computational framework to the problem of predicting the number of mutations on a chromosome for a certain patient, which is a fundamental problem in clinical and research fields. We begin this dissertation with the development of a framework system that is capable of utilizing published data from a longitudinal study of patients with acute myeloid leukemia (AML), who's DNA from both normal as well as malignant tissues was subjected to NGS analysis at various points in time. By processing the sequencing data at the time of cancer diagnosis using the components of our framework, we tested it by predicting the genomic regions to be mutated at the time of relapse and, later, by comparing our results with the actual regions that showed mutations (discovered at relapse time). We demonstrate that this coupling of the algorithm pipeline can drastically improve the predictive abilities of searching a reliable molecular signature. Arguably, the most important result of our research is its superior performance to other methods like Radial Basis Function Network, Sequential Minimal Optimization, and Gaussian Process. In the final part of this dissertation, we present a detailed significance, stability and statistical analysis of our model. A performance comparison of the results are presented. This work clearly lays a good foundation for future research for other types of cancer.^

Ultrastructural basis and function of iridescent blue colour of fruits in Elaeocarpus

Iridescent colour, caused by physical effects (thin-film interference, diffraction and Tyndall scattering), is relatively common in animals but exceedingly rare among plants1. Some benthic marine algae produce blue to violet iridescence2,3, and the upper leaf surfaces of a few vascular plants from the shady environments of humid tropical forests are iridescent blue4–6. Blue fruit colour has been assumed to be caused by anthocyanins7. A survey of such fruits (26 species in 18 genera) in Costa Rica, India, Florida and Malaysia, showed this to be the case, except for the iridescent colour in fruits of Elaeocarpus angustifolius Blume (Elaeocarpaceae). There I show that the colour is caused by a remarkable structure in the epidermis, and provide evidence for its selective advantage.

A novel neural network based system for assessing risks associated with information technology security breaches

Security remains a top priority for organizations as their information systems continue to be plagued by security breaches. This dissertation developed a unique approach to assess the security risks associated with information systems based on dynamic neural network architecture. The risks that are considered encompass the production computing environment and the client machine environment. The risks are established as metrics that define how susceptible each of the computing environments is to security breaches. ^ The merit of the approach developed in this dissertation is based on the design and implementation of Artificial Neural Networks to assess the risks in the computing and client machine environments. The datasets that were utilized in the implementation and validation of the model were obtained from business organizations using a web survey tool hosted by Microsoft. This site was designed as a host site for anonymous surveys that were devised specifically as part of this dissertation. Microsoft customers can login to the website and submit their responses to the questionnaire. ^ This work asserted that security in information systems is not dependent exclusively on technology but rather on the triumvirate people, process and technology. The questionnaire and consequently the developed neural network architecture accounted for all three key factors that impact information systems security. ^ As part of the study, a methodology on how to develop, train and validate such a predictive model was devised and successfully deployed. This methodology prescribed how to determine the optimal topology, activation function, and associated parameters for this security based scenario. The assessment of the effects of security breaches to the information systems has traditionally been post-mortem whereas this dissertation provided a predictive solution where organizations can determine how susceptible their environments are to security breaches in a proactive way. ^

A static traffic assignment model combined with an artificial neural network delay model

As traffic congestion continues to worsen in large urban areas, solutions are urgently sought. However, transportation planning models, which estimate traffic volumes on transportation network links, are often unable to realistically consider travel time delays at intersections. Introducing signal controls in models often result in significant and unstable changes in network attributes, which, in turn, leads to instability of models. Ignoring the effect of delays at intersections makes the model output inaccurate and unable to predict travel time. To represent traffic conditions in a network more accurately, planning models should be capable of arriving at a network solution based on travel costs that are consistent with the intersection delays due to signal controls. This research attempts to achieve this goal by optimizing signal controls and estimating intersection delays accordingly, which are then used in traffic assignment. Simultaneous optimization of traffic routing and signal controls has not been accomplished in real-world applications of traffic assignment. To this end, a delay model dealing with five major types of intersections has been developed using artificial neural networks (ANNs). An ANN architecture consists of interconnecting artificial neurons. The architecture may either be used to gain an understanding of biological neural networks, or for solving artificial intelligence problems without necessarily creating a model of a real biological system. The ANN delay model has been trained using extensive simulations based on TRANSYT-7F signal optimizations. The delay estimates by the ANN delay model have percentage root-mean-squared errors (%RMSE) that are less than 25.6%, which is satisfactory for planning purposes. Larger prediction errors are typically associated with severely oversaturated conditions. A combined system has also been developed that includes the artificial neural network (ANN) delay estimating model and a user-equilibrium (UE) traffic assignment model. The combined system employs the Frank-Wolfe method to achieve a convergent solution. Because the ANN delay model provides no derivatives of the delay function, a Mesh Adaptive Direct Search (MADS) method is applied to assist in and expedite the iterative process of the Frank-Wolfe method. The performance of the combined system confirms that the convergence of the solution is achieved, although the global optimum may not be guaranteed.

Social network structure as a critical success condition for open source software project communities

In recent years, a surprising new phenomenon has emerged in which globally-distributed online communities collaborate to create useful and sophisticated computer software. These open source software groups are comprised of generally unaffiliated individuals and organizations who work in a seemingly chaotic fashion and who participate on a voluntary basis without direct financial incentive. ^ The purpose of this research is to investigate the relationship between the social network structure of these intriguing groups and their level of output and activity, where social network structure is defined as (1) closure or connectedness within the group, (2) bridging ties which extend outside of the group, and (3) leader centrality within the group. Based on well-tested theories of social capital and centrality in teams, propositions were formulated which suggest that social network structures associated with successful open source software project communities will exhibit high levels of bridging and moderate levels of closure and leader centrality. ^ The research setting was the SourceForge hosting organization and a study population of 143 project communities was identified. Independent variables included measures of closure and leader centrality defined over conversational ties, along with measures of bridging defined over membership ties. Dependent variables included source code commits and software releases for community output, and software downloads and project site page views for community activity. A cross-sectional study design was used and archival data were extracted and aggregated for the two-year period following the first release of project software. The resulting compiled variables were analyzed using multiple linear and quadratic regressions, controlling for group size and conversational volume. ^ Contrary to theory-based expectations, the surprising results showed that successful project groups exhibited low levels of closure and that the levels of bridging and leader centrality were not important factors of success. These findings suggest that the creation and use of open source software may represent a fundamentally new socio-technical development process which disrupts the team paradigm and which triggers the need for building new theories of collaborative development. These new theories could point towards the broader application of open source methods for the creation of knowledge-based products other than software. ^

Neural network based off-line handwritten text recognition system

This dissertation introduces a new system for handwritten text recognition based on an improved neural network design. Most of the existing neural networks treat mean square error function as the standard error function. The system as proposed in this dissertation utilizes the mean quartic error function, where the third and fourth derivatives are non-zero. Consequently, many improvements on the training methods were achieved. The training results are carefully assessed before and after the update. To evaluate the performance of a training system, there are three essential factors to be considered, and they are from high to low importance priority: (1) error rate on testing set, (2) processing time needed to recognize a segmented character and (3) the total training time and subsequently the total testing time. It is observed that bounded training methods accelerate the training process, while semi-third order training methods, next-minimal training methods, and preprocessing operations reduce the error rate on the testing set. Empirical observations suggest that two combinations of training methods are needed for different case character recognition. Since character segmentation is required for word and sentence recognition, this dissertation provides also an effective rule-based segmentation method, which is different from the conventional adaptive segmentation methods. Dictionary-based correction is utilized to correct mistakes resulting from the recognition and segmentation phases. The integration of the segmentation methods with the handwritten character recognition algorithm yielded an accuracy of 92% for lower case characters and 97% for upper case characters. In the testing phase, the database consists of 20,000 handwritten characters, with 10,000 for each case. The testing phase on the recognition 10,000 handwritten characters required 8.5 seconds in processing time.

2007 Cumulative Annual Report for the Coastal Water Quality Monitoring Network

This report summarizes the existing data from the FIU Coastal Water Quality Monitoring Network for calendar year January 1 – December 31, 2007. This includes water quality data collected from 28 stations in Florida Bay, 22 stations in Whitewater Bay, 25 stations in Ten Thousand Islands, 25 stations in Biscayne Bay, 49 stations on the Southwest Florida Shelf (Shelf), and 28 stations in the Cape Romano-Pine Island Sound area. Each of the stations in Florida Bay were monitored on a monthly basis with monitoring beginning in March 1991; Whitewater Bay monitoring began in September 1992; Biscayne Bay monthly monitoring began September 1993; the SW Florida Shelf was sampled quarterly beginning in spring 1995; and monthly sampling in the Cape Romano-Pine Island Sound area started January 1999.

2007 Cumulative Annual Report for the Coastal Water Quality Monitoring Network

This report summarizes the existing data from the FIU Coastal Water Quality Monitoring Network for calendar year January 1 – December 31, 2007. This includes water quality data collected from 28 stations in Florida Bay, 22 stations in Whitewater Bay, 25 stations in Ten Thousand Islands, 25 stations in Biscayne Bay, 49 stations on the Southwest Florida Shelf (Shelf), and 28 stations in the Cape Romano-Pine Island Sound area. Each of the stations in Florida Bay were monitored on a monthly basis with monitoring beginning in March 1991; Whitewater Bay monitoring began in September 1992; Biscayne Bay monthly monitoring began September 1993; the SW Florida Shelf was sampled quarterly beginning in spring 1995; and monthly sampling in the Cape Romano-Pine Island Sound area started January 1999.

Conformational dynamics associated with ligand binding to vertebrate hexa-coordinate hemoglobins

Neuroglobin (Ngb) and cytoglobin (Cygb) are two new additions to the globin family, exhibiting heme iron hexa-coordination, a disulfide bond and large internal cavities. These proteins are implicated in cytoprotection under hypoxic-ischemic conditions, but the molecular basis of their cytoprotective function is unclear. Herein, a photothermal and spectroscopic study of the interactions of diatomic ligands with Ngb, Cygb, myoglobin and hemoglobin is presented. The impact of the disulfide bond in Ngb and Cygb and role of conserved residues in Ngb His64, Val68, Cys55, Cys120 and Tyr44 on conformational dynamics associated with ligand binding/dissociation were investigated. Transient absorption and photoacoustic calorimetry studies indicate that CO photo-dissociation from Ngb leads to a volume expansion (13.4±0.9 mL mol-1), whereas a smaller volume change was determined for Ngb with reduced Cys (ΔV=4.6±0.3 mL mol-1). Furthermore, Val68 side chain regulates ligand migration between the distal pocket and internal hydrophobic cavities since Val68Phe geminate quantum yield is ∼2.7 times larger than that of WT Ngb. His64Gln and Tyr44Phe mutations alter the thermodynamic parameters associated with CO photo-release indicating that electrostatic/hydrogen binding network that includes heme propionate groups, Lys 67, His64, and Tyr 44 in Ngb modulates the energetics of CO photo-dissociation. In Cygb, CO escape from the protein matrix is fast (< 40 ns) with a ΔH of 18±2 kcal mol-1 in Cygbred, whereas disulfide bridge formation promotes a biphasic ligand escape associated with an overall enthalpy change of 9±4 kcal mol-1. Therefore, the disulfide bond modulates conformational dynamics in Ngb and Cygb. I propose that in Cygb with reduced Cys the photo-dissociated ligand escapes through the hydrophobic tunnel as occurs in Ngb, whereas the CO preferentially migrates through the His64 gate in Cygbox. To characterize Cygb surface 1,8-ANS interactions with Cygb were investigated employing fluorescence spectroscopy, ITC and docking simulations. Two 1,8-ANS binding sites were identified. One binding site is located close to the extended N-terminus of Cygb and was also identified as a binding site for oleate. Furthermore, guanidinium hydrochloride-induced unfolding studies of Cygb reveal that the disulfide bond does not impact Cygb stability, whereas binding of cyanide slightly increases the protein stability.

A Static Traffic Assignment Model Combined with an Artificial Neural Network Delay Model

As traffic congestion continues to worsen in large urban areas, solutions are urgently sought. However, transportation planning models, which estimate traffic volumes on transportation network links, are often unable to realistically consider travel time delays at intersections. Introducing signal controls in models often result in significant and unstable changes in network attributes, which, in turn, leads to instability of models. Ignoring the effect of delays at intersections makes the model output inaccurate and unable to predict travel time. To represent traffic conditions in a network more accurately, planning models should be capable of arriving at a network solution based on travel costs that are consistent with the intersection delays due to signal controls. This research attempts to achieve this goal by optimizing signal controls and estimating intersection delays accordingly, which are then used in traffic assignment. Simultaneous optimization of traffic routing and signal controls has not been accomplished in real-world applications of traffic assignment. To this end, a delay model dealing with five major types of intersections has been developed using artificial neural networks (ANNs). An ANN architecture consists of interconnecting artificial neurons. The architecture may either be used to gain an understanding of biological neural networks, or for solving artificial intelligence problems without necessarily creating a model of a real biological system. The ANN delay model has been trained using extensive simulations based on TRANSYT-7F signal optimizations. The delay estimates by the ANN delay model have percentage root-mean-squared errors (%RMSE) that are less than 25.6%, which is satisfactory for planning purposes. Larger prediction errors are typically associated with severely oversaturated conditions. A combined system has also been developed that includes the artificial neural network (ANN) delay estimating model and a user-equilibrium (UE) traffic assignment model. The combined system employs the Frank-Wolfe method to achieve a convergent solution. Because the ANN delay model provides no derivatives of the delay function, a Mesh Adaptive Direct Search (MADS) method is applied to assist in and expedite the iterative process of the Frank-Wolfe method. The performance of the combined system confirms that the convergence of the solution is achieved, although the global optimum may not be guaranteed.

Social Network Structure as a Critical Success Condition for Open Source Software Project Communities

In recent years, a surprising new phenomenon has emerged in which globally-distributed online communities collaborate to create useful and sophisticated computer software. These open source software groups are comprised of generally unaffiliated individuals and organizations who work in a seemingly chaotic fashion and who participate on a voluntary basis without direct financial incentive. The purpose of this research is to investigate the relationship between the social network structure of these intriguing groups and their level of output and activity, where social network structure is defined as 1) closure or connectedness within the group, 2) bridging ties which extend outside of the group, and 3) leader centrality within the group. Based on well-tested theories of social capital and centrality in teams, propositions were formulated which suggest that social network structures associated with successful open source software project communities will exhibit high levels of bridging and moderate levels of closure and leader centrality. The research setting was the SourceForge hosting organization and a study population of 143 project communities was identified. Independent variables included measures of closure and leader centrality defined over conversational ties, along with measures of bridging defined over membership ties. Dependent variables included source code commits and software releases for community output, and software downloads and project site page views for community activity. A cross-sectional study design was used and archival data were extracted and aggregated for the two-year period following the first release of project software. The resulting compiled variables were analyzed using multiple linear and quadratic regressions, controlling for group size and conversational volume. Contrary to theory-based expectations, the surprising results showed that successful project groups exhibited low levels of closure and that the levels of bridging and leader centrality were not important factors of success. These findings suggest that the creation and use of open source software may represent a fundamentally new socio-technical development process which disrupts the team paradigm and which triggers the need for building new theories of collaborative development. These new theories could point towards the broader application of open source methods for the creation of knowledge-based products other than software.

Analysis and comparison of network performance with different network parameters

The purpose of this study was to analyze the network performance by observing the effect of varying network size and data link rate on one of the most commonly found network configurations. Computer networks have been growing explosively. Networking is used in every aspect of business, including advertising, production, shipping, planning, billing, and accounting. Communication takes place through networks that form the basis of transfer of information. The number and type of components may vary from network to network depending on several factors such as requirement and actual physical placement of the networks. There is no fixed size of the networks and they can be very small consisting of say five to six nodes or very large consisting of over two thousand nodes. The varying network sizes make it very important to study the network performance so as to be able to predict the functioning and the suitability of the network. The findings demonstrated that the network performance parameters such as global delay, load, router processor utilization, router processor delay, etc. are affected. The findings demonstrated that the network performance parameters such as global delay, load, router processor utilization, router processor delay, etc. are affected significantly due to the increase in the size of the network and that there exists a correlation between the various parameters and the size of the network. These variations are not only dependent on the magnitude of the change in the actual physical area of the network but also on the data link rate used to connect the various components of the network.