20 resultados para NEXT-GENERATION SEQUENCING

em Digital Commons at Florida International University


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This work is the first work using patterned soft underlayers in multilevel three-dimensional vertical magnetic data storage systems. The motivation stems from an exponentially growing information stockpile, and a corresponding need for more efficient storage devices with higher density. The world information stockpile currently exceeds 150EB (ExaByte=1x1018Bytes); most of which is in analog form. Among the storage technologies (semiconductor, optical and magnetic), magnetic hard disk drives are posed to occupy a big role in personal, network as well as corporate storage. However; this mode suffers from a limit known as the Superparamagnetic limit; which limits achievable areal density due to fundamental quantum mechanical stability requirements. There are many viable techniques considered to defer superparamagnetism into the 100's of Gbit/in2 such as: patterned media, Heat-Assisted Magnetic Recording (HAMR), Self Organized Magnetic Arrays (SOMA), antiferromagnetically coupled structures (AFC), and perpendicular magnetic recording. Nonetheless, these techniques utilize a single magnetic layer; and can thusly be viewed as two-dimensional in nature. In this work a novel three-dimensional vertical magnetic recording approach is proposed. This approach utilizes the entire thickness of a magnetic multilayer structure to store information; with potential areal density well into the Tbit/in2 regime. ^ There are several possible implementations for 3D magnetic recording; each presenting its own set of requirements, merits and challenges. The issues and considerations pertaining to the development of such systems will be examined, and analyzed using empirical and numerical analysis techniques. Two novel key approaches are proposed and developed: (1) Patterned soft underlayer (SUL) which allows for enhanced recording of thicker media, (2) A combinatorial approach for 3D media development that facilitates concurrent investigation of various film parameters on a predefined performance metric. A case study is presented using combinatorial overcoats of Tantalum and Zirconium Oxides for corrosion protection in magnetic media. ^ Feasibility of 3D recording is demonstrated, and an emphasis on 3D media development is emphasized as a key prerequisite. Patterned SUL shows significant enhancement over conventional "un-patterned" SUL, and shows that geometry can be used as a design tool to achieve favorable field distribution where magnetic storage and magnetic phenomena are involved. ^

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Next-generation integrated wireless local area network (WLAN) and 3G cellular networks aim to take advantage of the roaming ability in a cellular network and the high data rate services of a WLAN. To ensure successful implementation of an integrated network, many issues must be carefully addressed, including network architecture design, resource management, quality-of-service (QoS), call admission control (CAC) and mobility management. ^ This dissertation focuses on QoS provisioning, CAC, and the network architecture design in the integration of WLANs and cellular networks. First, a new scheduling algorithm and a call admission control mechanism in IEEE 802.11 WLAN are presented to support multimedia services with QoS provisioning. The proposed scheduling algorithms make use of the idle system time to reduce the average packet loss of realtime (RT) services. The admission control mechanism provides long-term transmission quality for both RT and NRT services by ensuring the packet loss ratio for RT services and the throughput for non-real-time (NRT) services. ^ A joint CAC scheme is proposed to efficiently balance traffic load in the integrated environment. A channel searching and replacement algorithm (CSR) is developed to relieve traffic congestion in the cellular network by using idle channels in the WLAN. The CSR is optimized to minimize the system cost in terms of the blocking probability in the interworking environment. Specifically, it is proved that there exists an optimal admission probability for passive handoffs that minimizes the total system cost. Also, a method of searching the probability is designed based on linear-programming techniques. ^ Finally, a new integration architecture, Hybrid Coupling with Radio Access System (HCRAS), is proposed for lowering the average cost of intersystem communication (IC) and the vertical handoff latency. An analytical model is presented to evaluate the system performance of the HCRAS in terms of the intersystem communication cost function and the handoff cost function. Based on this model, an algorithm is designed to determine the optimal route for each intersystem communication. Additionally, a fast handoff algorithm is developed to reduce the vertical handoff latency.^

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By integrating the research and resources of hundreds of scientists from dozens of institutions, network-level science is fast becoming one scientific model of choice to address complex problems. In the pursuit to confront pressing environmental issues such as climate change, many scientists, practitioners, policy makers, and institutions are promoting network-level research that integrates the social and ecological sciences. To understand how this scientific trend is unfolding among rising scientists, we examined how graduate students experienced one such emergent social-ecological research initiative, Integrated Science for Society and Environment, within the large-scale, geographically distributed Long Term Ecological Research (LTER) Network. Through workshops, surveys, and interviews, we found that graduate students faced challenges in how they conceptualized and practiced social-ecological research within the LTER Network. We have presented these conceptual challenges at three scales: the individual/project, the LTER site, and the LTER Network. The level of student engagement with and knowledge of the LTER Network was varied, and students faced different institutional, cultural, and logistic barriers to practicing social-ecological research. These types of challenges are unlikely to be unique to LTER graduate students; thus, our findings are relevant to other scientific networks implementing new social-ecological research initiatives.

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Personalized recommender systems aim to assist users in retrieving and accessing interesting items by automatically acquiring user preferences from the historical data and matching items with the preferences. In the last decade, recommendation services have gained great attention due to the problem of information overload. However, despite recent advances of personalization techniques, several critical issues in modern recommender systems have not been well studied. These issues include: (1) understanding the accessing patterns of users (i.e., how to effectively model users' accessing behaviors); (2) understanding the relations between users and other objects (i.e., how to comprehensively assess the complex correlations between users and entities in recommender systems); and (3) understanding the interest change of users (i.e., how to adaptively capture users' preference drift over time). To meet the needs of users in modern recommender systems, it is imperative to provide solutions to address the aforementioned issues and apply the solutions to real-world applications. ^ The major goal of this dissertation is to provide integrated recommendation approaches to tackle the challenges of the current generation of recommender systems. In particular, three user-oriented aspects of recommendation techniques were studied, including understanding accessing patterns, understanding complex relations and understanding temporal dynamics. To this end, we made three research contributions. First, we presented various personalized user profiling algorithms to capture click behaviors of users from both coarse- and fine-grained granularities; second, we proposed graph-based recommendation models to describe the complex correlations in a recommender system; third, we studied temporal recommendation approaches in order to capture the preference changes of users, by considering both long-term and short-term user profiles. In addition, a versatile recommendation framework was proposed, in which the proposed recommendation techniques were seamlessly integrated. Different evaluation criteria were implemented in this framework for evaluating recommendation techniques in real-world recommendation applications. ^ In summary, the frequent changes of user interests and item repository lead to a series of user-centric challenges that are not well addressed in the current generation of recommender systems. My work proposed reasonable solutions to these challenges and provided insights on how to address these challenges using a simple yet effective recommendation framework.^

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As the Web evolves unexpectedly fast, information grows explosively. Useful resources become more and more difficult to find because of their dynamic and unstructured characteristics. A vertical search engine is designed and implemented towards a specific domain. Instead of processing the giant volume of miscellaneous information distributed in the Web, a vertical search engine targets at identifying relevant information in specific domains or topics and eventually provides users with up-to-date information, highly focused insights and actionable knowledge representation. As the mobile device gets more popular, the nature of the search is changing. So, acquiring information on a mobile device poses unique requirements on traditional search engines, which will potentially change every feature they used to have. To summarize, users are strongly expecting search engines that can satisfy their individual information needs, adapt their current situation, and present highly personalized search results. ^ In my research, the next generation vertical search engine means to utilize and enrich existing domain information to close the loop of vertical search engine's system that mutually facilitate knowledge discovering, actionable information extraction, and user interests modeling and recommendation. I investigate three problems in which domain taxonomy plays an important role, including taxonomy generation using a vertical search engine, actionable information extraction based on domain taxonomy, and the use of ensemble taxonomy to catch user's interests. As the fundamental theory, ultra-metric, dendrogram, and hierarchical clustering are intensively discussed. Methods on taxonomy generation using my research on hierarchical clustering are developed. The related vertical search engine techniques are practically used in Disaster Management Domain. Especially, three disaster information management systems are developed and represented as real use cases of my research work.^

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As the Web evolves unexpectedly fast, information grows explosively. Useful resources become more and more difficult to find because of their dynamic and unstructured characteristics. A vertical search engine is designed and implemented towards a specific domain. Instead of processing the giant volume of miscellaneous information distributed in the Web, a vertical search engine targets at identifying relevant information in specific domains or topics and eventually provides users with up-to-date information, highly focused insights and actionable knowledge representation. As the mobile device gets more popular, the nature of the search is changing. So, acquiring information on a mobile device poses unique requirements on traditional search engines, which will potentially change every feature they used to have. To summarize, users are strongly expecting search engines that can satisfy their individual information needs, adapt their current situation, and present highly personalized search results. In my research, the next generation vertical search engine means to utilize and enrich existing domain information to close the loop of vertical search engine's system that mutually facilitate knowledge discovering, actionable information extraction, and user interests modeling and recommendation. I investigate three problems in which domain taxonomy plays an important role, including taxonomy generation using a vertical search engine, actionable information extraction based on domain taxonomy, and the use of ensemble taxonomy to catch user's interests. As the fundamental theory, ultra-metric, dendrogram, and hierarchical clustering are intensively discussed. Methods on taxonomy generation using my research on hierarchical clustering are developed. The related vertical search engine techniques are practically used in Disaster Management Domain. Especially, three disaster information management systems are developed and represented as real use cases of my research work.

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Background The infraorder Anomura has long captivated the attention of evolutionary biologists due to its impressive morphological diversity and ecological adaptations. To date, 2500 extant species have been described but phylogenetic relationships at high taxonomic levels remain unresolved. Here, we reconstruct the evolutionary history—phylogeny, divergence times, character evolution and diversification—of this speciose clade. For this purpose, we sequenced two mitochondrial (16S and 12S) and three nuclear (H3, 18S and 28S) markers for 19 of the 20 extant families, using traditional Sanger and next-generation 454 sequencing methods. Molecular data were combined with 156 morphological characters in order to estimate the largest anomuran phylogeny to date. The anomuran fossil record allowed us to incorporate 31 fossils for divergence time analyses. Results Our best phylogenetic hypothesis (morphological + molecular data) supports most anomuran superfamilies and families as monophyletic. However, three families and eleven genera are recovered as para- and polyphyletic. Divergence time analysis dates the origin of Anomura to the Late Permian ~259 (224–296) MYA with many of the present day families radiating during the Jurassic and Early Cretaceous. Ancestral state reconstruction suggests that carcinization occurred independently 3 times within the group. The invasion of freshwater and terrestrial environments both occurred between the Late Cretaceous and Tertiary. Diversification analyses found the speciation rate to be low across Anomura, and we identify 2 major changes in the tempo of diversification; the most significant at the base of a clade that includes the squat-lobster family Chirostylidae. Conclusions Our findings are compared against current classifications and previous hypotheses of anomuran relationships. Many families and genera appear to be poly- or paraphyletic suggesting a need for further taxonomic revisions at these levels. A divergence time analysis provides key insights into the origins of major lineages and events and the timing of morphological (body form) and ecological (habitat) transitions. Living anomuran biodiversity is the product of 2 major changes in the tempo of diversification; our initial insights suggest that the acquisition of a crab-like form did not act as a key innovation.

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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.^

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Rare plant conservation efforts must utilize current genetic methods to ensure the evolutionary potential of populations is preserved. One such effort involves the Key Tree Cactus, Pilosocereus robinii, which is an endangered columnar cactus native to the Florida Keys. The populations have precipitously declined over the past decade because of habitat loss and increasing soil salinity from rising sea levels and storm surge. Next-generation DNA sequencing was used to assess the genetic structure of the populations. Twenty individuals representative of both wild and extirpated cacti were chosen for Restriction Site Associated DNA (RAD) analysis. Samples processed using the HindIII and NotIII restriction enzymes produced 82,382,440 high quality reads used for genetic mapping, from which 5,265 Single Nucleotide Polymorphisms (SNPs) were discovered. The analysis revealed that the Keys’ populations are closely related with little population differentiation. In addition, the populations display evidence of inbreeding and low genetic diversity.

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Next generation networks are characterized by ever increasing complexity, intelligence, heterogeneous technologies and increasing user expectations. Telecommunication networks in particular have become truly global, consisting of a variety of national and regional networks, both wired and wireless. Consequently, the management of telecommunication networks is becoming increasingly complex. In addition, network security and reliability requirements require additional overheads which increase the size of the data records. This in turn causes acute network traffic congestions. There is no single network management methodology to control the various requirements of today's networks, and provides a good level of Quality of Service (QoS), and network security. Therefore, an integrated approach is needed in which a combination of methodologies can provide solutions and answers to network events (which cause severe congestions and compromise the quality of service and security). The proposed solution focused on a systematic approach to design a network management system based upon the recent advances in the mobile agent technologies. This solution has provided a new traffic management system for telecommunication networks that is capable of (1) reducing the network traffic load (thus reducing traffic congestion), (2) overcoming existing network latency, (3) adapting dynamically to the traffic load of the system, (4) operating in heterogeneous environments with improved security, and (5) having robust and fault tolerance behavior. This solution has solved several key challenges in the development of network management for telecommunication networks using mobile agents. We have designed several types of agents, whose interactions will allow performing some complex management actions, and integrating them. Our solution is decentralized to eliminate excessive bandwidth usage and at the same time has extended the capabilities of the Simple Network Management Protocol (SNMP). Our solution is fully compatible with the existing standards.

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Unique electrical and mechanical properties of single-walled carbon nanotubes (SWNTs) have made them one of the most promising candidates for next-generation nanoelectronics. Efficient utilization of the exceptional properties of SWNTs requires controlling their growth direction (e.g., vertical, horizontal) and morphologies (e.g., straight, junction, coiled). ^ In this dissertation, the catalytic effect on the branching of SWNTs, Y-shaped SWNTs (Y-SWNTs), was investigated. The formation of Y-shaped branches was found to be dependent on the composition of the catalysts. Easier carbide formers have a strong tendency to attach to the sidewall of SWNTs and thus enhance the degree of branching. Y-SWNTs based field-effect transistors (FETs) were fabricated and modulated by the metallic branch of the Y-SWNTs, exhibiting ambipolar characteristics at room temperature. A subthreshold swing of 700 mV/decade and an on/off ratio of 105 with a low off-state current of 10-13 A were obtained. The transport phenomena associated with Y- and cross-junction configurations reveals that the conduction mechanism in the SWNT junctions is governed by thermionic emission at T > 100 K and by tunneling at T < 100 K. ^ Furthermore, horizontally aligned SWNTs were synthesized by the controlled modification of external fields and forces. High performance carbon nanotube FETs and logic circuit were demonstrated utilizing the aligned SWNTs. It is found that the hysteresis in CNTFETs can be eliminated by removing absorbed water molecules on the CNT/SiO2 interface by vacuum annealing, hydrophobic surface treatment, and surface passivation. SWNT “serpentines” were synthesized by utilization of the interaction between drag force from gas flow and Van der Waals force with substrates. The curvature of bent SWNTs could be tailored by adjusting the gas flow rate, and changing the gas flow direction with respect to the step-edges on a single-crystal quartz substrate. Resistivity of bent SWNTs was observed to increase with curvature, which can be attributed to local deformations and possible chirality shift at curved part. ^ Our results show the successful synthesis of SWNTs having controllable morphologies and directionality. The capability of tailoring the electrical properties of SWNTs makes it possible to build an all-nanotube device by integrating SWNTs, having different functionalities, into complex circuits. ^

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Buffered crossbar switches have recently attracted considerable attention as the next generation of high speed interconnects. They are a special type of crossbar switches with an exclusive buffer at each crosspoint of the crossbar. They demonstrate unique advantages over traditional unbuffered crossbar switches, such as high throughput, low latency, and asynchronous packet scheduling. However, since crosspoint buffers are expensive on-chip memories, it is desired that each crosspoint has only a small buffer. This dissertation proposes a series of practical algorithms and techniques for efficient packet scheduling for buffered crossbar switches. To reduce the hardware cost of such switches and make them scalable, we considered partially buffered crossbars, whose crosspoint buffers can be of an arbitrarily small size. Firstly, we introduced a hybrid scheme called Packet-mode Asynchronous Scheduling Algorithm (PASA) to schedule best effort traffic. PASA combines the features of both distributed and centralized scheduling algorithms and can directly handle variable length packets without Segmentation And Reassembly (SAR). We showed by theoretical analysis that it achieves 100% throughput for any admissible traffic in a crossbar with a speedup of two. Moreover, outputs in PASA have a large probability to avoid the more time-consuming centralized scheduling process, and thus make fast scheduling decisions. Secondly, we proposed the Fair Asynchronous Segment Scheduling (FASS) algorithm to handle guaranteed performance traffic with explicit flow rates. FASS reduces the crosspoint buffer size by dividing packets into shorter segments before transmission. It also provides tight constant performance guarantees by emulating the ideal Generalized Processor Sharing (GPS) model. Furthermore, FASS requires no speedup for the crossbar, lowering the hardware cost and improving the switch capacity. Thirdly, we presented a bandwidth allocation scheme called Queue Length Proportional (QLP) to apply FASS to best effort traffic. QLP dynamically obtains a feasible bandwidth allocation matrix based on the queue length information, and thus assists the crossbar switch to be more work-conserving. The feasibility and stability of QLP were proved, no matter whether the traffic distribution is uniform or non-uniform. Hence, based on bandwidth allocation of QLP, FASS can also achieve 100% throughput for best effort traffic in a crossbar without speedup.

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Ribonucleotide reductases (RNR) are essential enzymes that catalyze the reduction of ribonucleotides to 2'-deoxyribonucleotides, which is a critical step that produces precursors for DNA replication and repair. The inactivation of RNR, logically, would discontinue producing the precursors of the DNA of viral or cancer cells, which then would consequently end the cycle of DNA replication. Among different compounds that were found to be inhibitors of RNR, 2'-azido-2'-deoxynucleotide diphosphates (N3NDPs) have been investigated in depth as potent inhibitors of RNR. Decades of investigation has suggested that the inactivation of RNR by N3NDPs is a result of the formation of a nitrogen-centered radical (N·) that is covalently attached to the nucleotide at C3' and cysteine molecule C225 [3'-C(R-S-N·-C-OH)]. Biomimetic simulation reactions for the generation of the nitrogen-centered radicals similar to the one observed during the inactivation of the RNR by azionuclotides was investigated. The study included several modes: (i) theoretical calculation that showed the feasibility of the ring closure reaction between thiyl radicals and azido group; (ii) synthesis of the model azido nucleosides with a linker attached to C3' or C5' having a thiol or vicinal dithiol functionality; (iii) generation of the thiyl radical under both physiological and radiolysis conditions whose role is important in the initiation on RNR cascades; and (iv) analysis of the nitrogen-centered radical species formed during interaction between the thiyl radical and azido group by electron paramagnetic resonance spectroscopy (EPR). Characterization of the aminyl radical species formed during one electron attachment to the azido group of 2'-azido-2'-deoxyuridine and its stereospecifically labelled 1'-, 2'-, 3'-, 4'- or 5,6-[2H 2]-analogues was also examined. This dissertation gave insight toward understanding the mechanism of the formation of the nitrogen-centered radical during the inactivation of RNRs by azidonucleotides as well as the mechanism of action of RNRs that might provide key information necessary for the development of the next generation of antiviral and anticancer drugs.

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The ability to use Software Defined Radio (SDR) in the civilian mobile applications will make it possible for the next generation of mobile devices to handle multi-standard personal wireless devices and ubiquitous wireless devices. The original military standard created many beneficial characteristics for SDR, but resulted in a number of disadvantages as well. Many challenges in commercializing SDR are still the subject of interest in the software radio research community. Four main issues that have been already addressed are performance, size, weight, and power. ^ This investigation presents an in-depth study of SDR inter-components communications in terms of total link delay related to the number of components and packet sizes in systems based on Software Communication Architecture (SCA). The study is based on the investigation of the controlled environment platform. Results suggest that the total link delay does not linearly increase with the number of components and the packet sizes. The closed form expression of the delay was modeled using a logistic function in terms of the number of components and packet sizes. The model performed well when the number of components was large. ^ Based upon the mobility applications, energy consumption has become one of the most crucial limitations. SDR will not only provide flexibility of multi-protocol support, but this desirable feature will also bring a choice of mobile protocols. Having such a variety of choices available creates a problem in the selection of the most appropriate protocol to transmit. An investigation in a real-time algorithm to optimize energy efficiency was also performed. Communication energy models were used including switching estimation to develop a waveform selection algorithm. Simulations were performed to validate the concept.^