Rozprawy doktorskie: „DNA systems”

1

Oster, Christine. "Microparticular and nanoparticular DNA delivery systems as adjuvants for DNA immunization". [S.l.] : [s.n.], 2004. http://archiv.ub.uni-marburg.de/diss/z2004/0493/.

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2

Ma, Long. "Investigation of DNA conformation and enzyme-DNA systems using fluorescence techniques". Thesis, University of Edinburgh, 2012. http://hdl.handle.net/1842/7836.

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As a structural analogue of adenine (6-aminopurine), 2-aminopurine (2AP) is a powerful fluorescent probe, when substituted in DNA in place of the natural adenine. Time-resolved fluorescence measurements of 2AP-labeled oligonucleotides, together with steady-state spectroscopy give us an in-depth view of DNA-enzyme interactions, especially the conformational dynamics in solution phase. Herein, this technique has been extended to the study of the transient unzipping of DNA bases, to investigate the structure of three-way junction (3WJ), and the role of base unzipping in the mechanism of human flap endonuclease (FEN). Seven 2AP-labelled 3WJs were investigated, each containing only one 2AP base in place of adenine. In four of the 3WJs, 2AP was placed in the long duplex region of an arm; while in the other three 3WJs, 2AP was placed near or in the branch point. Comparative time-resolved fluorescence measurements on the 3WJs and corresponding ssDNA and dsDNA controls were made to study the base dynamics, in particular the possibility of unzipping in the vicinity of the branch point. In combination with single-molecule FRET measurements and molecular dynamics simulations, the local and global structure of a DNA 3WJ in solution could be unraveled. It was found to adopt a Y-shaped, pyramidal structure, in which the bases adjacent to the branch point are unzipped, despite the full Watson-Crick complementarity of the molecule. Human flap endonuclease (hFEN) is divalent metal ion-dependent phosphodiesterase. hFEN carries out structure-specific hydrolysis of 5’ bifurcated DNA endonucleolytically. Cleavage occurs at a position one nucleotide into the downstream duplex region. Previous structural, biochemical and modeling studies suggested a double-nucleotide unzipping mechanism at single/double strand junctions for scissile phosphate placement. To confirm this mechanism, 2AP time-resolved fluorescence spectroscopy was used to investigate nucleotide unzipping in hFEN substrates. 2AP was substituted at positions +1 and -1 (relative to the scissile phosphodiester) respectively, in double flap substrates. A series of hFEN mutants including Y40A, R100A, K93A, were used in this study. In the experiments, ssDNA, dsDNA substrates, DNA substrate-enzyme complexes were investigated in order to elucidate the enzyme-induced distortion of the substrate at the +1 and -1 positions. TseI is a thermophilic type II restriction enzyme which has ideal activity at an elevated temperature. It is able to recognise and cut the 5 bp palindromic sequence of 5’-GCWGC-3’ (W=A or T). A range of biophysical methods have been applied to investigate this enzyme, including size-exclusion chromatography; fluorescence anisotropy (Kd value determination); denaturing HPLC for DNA cleavage analysis on matched and mismatched substrates; fluorescence-based activity assay (KM, Vmax, kcat, specificity constant values determination); steady-state fluorescence measurements (DNA-enzyme interaction study). The DNA cleavage characteristics of TseI were fully studied and it was found that it cuts A:A and T:T mismatches in CAG and CTG repeats. This potentially makes it a useful tool for exploring unusual DNA structures containing super-long CAG and CTG repeats which are involved in the aetiology of some neurodegenerative diseases, such as Huntington’s disease (HD). EcoP15I is a type III restriction-modification enzyme whose recognition sequence is 5-CAGCAG-3’. Methyltransferase EcoP15I (M.EcoP15I) adds a methyl group to the second adenine, in the presence of cofactor S-adenosyl methionine (SAM). SDS-PAGE, densitometry and size-exclusion HPLC were applied to confirm that EcoP15I adopts a Res1Mod2 stoichiometry in solution. The large structural distortion of its substrate (base flipping) by M.EcoP15I was investigated by both steady-state and time-resolved fluorescence. Also, nine 120 mer DNA duplexes, each containing two reversely oriented recognition sites were used to study matched and mismatched sequence cleavage by R.EcoP15 and a cleavage pattern was revealed.

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3

Yanagishima, Taiki. "DNA-colloid systems and micro-rheology". Thesis, University of Cambridge, 2013. https://www.repository.cam.ac.uk/handle/1810/265566.

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We investigate the behaviour of DNA-colloid systems using micro-rheology, with a view to demonstrating the efficacy of passive particle-tracking methodologies and developing entirely new systems. Chapter 1 introduces the fields of DNA coated colloids (DNACCs) and passive micro-rheology, with a particular fo cus on the challenges of creating an equilibrating DNACC system and the practicalities and limitations of passive microrheology in gaining access to valid rheological information. In Chapter 2, we present a newly developed realtime monitoring algorithm for complex moduli in optical tweezer micro-rheology sys,tems. Further to eliminating high frequency artefacts, our method is memory light and computationally efficient. Chapter 3 investigates the dynamics of ADNA coated colloids using Brownian Dynamics simulation and a theoretical model, also applying the algorithm developed in Chapter 2. A two-regime diffusivity is identified, in contrast to previous works, which simply found an increased hydrodynamic size. Chapter 4 looks at tuning the hydrophobicity of silica particles using poly(L)lysinepolyethylene glycol (PLL-PEG). We find an incubation pH dependence on their coverage. From analysing video microscopy trajectories, PLL-PEG coated beads sedimented onto A-DNA brushes are found to be significantly more diffusive. In Chapter 5, we int roduce an entirely new DNACC system, the functionalised fd bacteriophage, where high aspect ratio filamentous virions are coated with short oligonucleotides. Aggregation behaviour is confirmed with Atomic Force Microscopy and Dynamic Light Scattering, and systems where rods can act as a linker between spherical particles are also briefly investigated.

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4

Ait-Ghezala, Ahmed 1976. "Software systems for a DNA sequencer". Thesis, Massachusetts Institute of Technology, 2000. http://hdl.handle.net/1721.1/8931.

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Thesis (M.Eng. and S.B.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2000.
Includes bibliographical references (leaf 49).
The initiative to complete the sequencing of the human genome is bringing the need for high-throughput sequencing capabilities to the forefront. We at the BioMEMS engineering group at the Whitehead Institute are designing and building a new sequencing machine that uses a 384 glass "chip" to dramatically increase sequencing rates. This thesis describes the design and implementation of two of the machine's software components. The first is a prototype application for the control of a robot used to automate sample loading. The second is a software filter that allows us to generate quality scores from data processed by Trout using Phred. I present the algorithm used to perform the filtering and show that the results are comparable to the processing of data with the Plan- Phred processing package.
by Ahmed Ait-Ghezala.
M.Eng.and S.B.

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5

Mok, Kenneth W. C. "Characterization of lipid-based DNA delivery systems". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ34590.pdf.

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6

Davies, Owen Richard. "DNA vaccine delivery systems for pulmonary administration". Thesis, University of Nottingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415695.

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7

Turowski, Daniel J. "Assembly and characterization of mesoscale DNA material systems based on periodic DNA origami arrays". The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1374169645.

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8

Chan, Michelle M. (Michelle Mei Wah). "DNA methylation in early mammalian development". Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/81580.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references.
All the cells in the body contain the same genome yet showcase drastically different phenotypes. This is the result of different transcriptional programs, which are partly controlled by epigenetic modifications, including DNA methylation. In this thesis, I analyze genome-scale DNA methylation profiles across pre-implantation development to identify the targets and characterize the dynamics of global demethylation that lead to totipotency and the subsequent changes to embryonic specification. In Chapter 1, I validate and refine the decades old model for DNA methylation in mouse embryogenesis, identify many retrotransposons with active DNA methylation signatures at fertilization, and discover many, novel differentially methylated regions between the gametes that exist transiently during early development. Notably, the majority of epigenetic events unique to mammalian pre-implantation development are characterized in mouse. In Chapter 2, 1 describe the DNA methylation dynamics in human preimplantation development and show that the regulatory principles that operate in mouse are conserved, though some of their targets are species-specific and define regions of local divergence. Finally, in Chapter 3, I compare DNA methylation dynamics of fertilization to an artificial reprogramming process, somatic cell nuclear transfer, in mouse, and find that most dynamics are conserved but occur at a smaller magnitude after artificial reprogramming. I conclude this thesis with a summary of the chapters and a brief discussion of ongoing and future work.
by Michelle M. Chan.
Ph.D.

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9

Sarella, Hananiel. "DNA Pattern Matching on Loosely Coupled figurable Systems". Cincinnati, Ohio : University of Cincinnati, 2004. http://www.ohiolink.edu/etd/view.cgi?acc%5Fnum=ucin1105408305.

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10

Jarvius, Jonas. "DNA Tools and Microfluidic Systems for Molecular Analysis". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7079.

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11

Dosanjh, Harvinder Singh. "Biophysical studies of triplex and quadruplex DNA systems". Thesis, Institute of Cancer Research (University Of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409306.

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12

Quick, Joshua. "Real-time pathogen surveillance systems using DNA sequencing". Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8135/.

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Microbiological research has uncovered the basis of fermentation, infectious disease, vaccination and antibiotics. Now, a technological revolution leveraging DNA, the code of life, has allowed us to unravel cellular and evolutionary processes in exquisite detail. Today our need for new innovation is still great. The modern world is a challenging environment: over-population, climate change and highly mobile populations create a high risk of pandemic disease especially from viruses and many bacteria are now resistant to our life saving antibiotic drugs due to overuse. In hospitals, the spread of pathogens can be rapid and life threatening. Whole-genome sequencing has the power to identify the source of infections and determine whether clusters of cases belong to an outbreak. Portable, real-time nanopore sequencing enables sequencing to be performed near the patient, even in resource-limited settings. Integrating with existing datasets allows digital surveillance able to detect outbreaks earlier while they can still be contained. Early demonstrations of the power of whole-genome sequencing for outbreak surveillance have made it an area of intense interest and further development in laboratory methods and infrastructure will make it an important tool that can be deployed in response to future outbreaks.

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13

Dolan, David William Peter. "A systems biology approach to DNA damage repair". Thesis, University of Newcastle upon Tyne, 2013. http://hdl.handle.net/10443/2172.

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The presence of DNA double-stranded breaks in a mammalian cell typically activates the Non-Homologous End Joining (NHEJ) pathway to repair the damage and signal to downstream systems that govern cellular decisions such as apoptosis or senescence. The signalling system also stimulates effects such as the generation of reactive oxygen species (ROS) which in turn feed back into the damage response. Although the overall process of NHEJ is well documented, and much is known about downstream processes that together constitute the DNA damage response (DDR), we know little of the dynamics and how the system operates as a whole. To further our understanding of this we have constructed computational models which integrate current knowledge of the DNA repair process and key downstream signalling systems. The models are coded in Systems Biology Mark-up Language and BioNetGen Language and are quantified as far as possible with experimental data generated within our own laboratories or otherwise gathered from the literature. They are designed to simulate the observed stochastic dynamics of repair by DNA Protein Kinase (DNA-PK) dependent NHEJ (D-NHEJ) and back-up NHEJ mechanisms (B-NHEJ) following damage induced by gamma irradiation in human fibroblasts and the response this causes in the p53-p21 senescence signalling pathway. We have used the models to investigate a number of issues relevant to the study of ageing cells. Our work suggests that this observed heterogeneity in the repair of DNA damage foci that is influenced by levels of damage cannot be explained solely by inherent stochasticity in the NHEJ system. We find that the presence of multiple repair mechanisms and the modulation of key repair factors by oxidation along with further damage inducing feedback triggered by p53 and changes brought about by cellular processes such as senescence all play a cumulative role in causing the differences between stressed and unstressed cells. Our model highlights the importance of Ku oxidation which leads to increased Ku dissociation rates from DNA damage foci and shifts in favour of the less efficient B-NHEJ system. Furthermore we have utilised the model to investigate the role that various levels of DNA damage and repair have on the maintenance of the important p53 oscillations in a cell. We find that, contrary to the current view, p53 levels are affected by temporal dynamics of DNA damage and have used our model to inform the design of further experimental work to investigate the effect of iii maintained low levels of DNA damage induced by frequent low pulses of γ irradiation on the p53 mediated DDR.

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14

SARELLA, HANANIEL. "DNA PATTERN MATCHING ON LOOSELY COUPLED RECONFIGURABLE SYSTEMS". University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1105408305.

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15

Ishihara, Yoshihiro. "DNA-inspired materials for 'bottom-up' nanotechnology". Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112640.

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DNA is a remarkable material that is both an inspiration for polymer nanotechnology and a versatile building block for assembling well-defined nanostructures. To create polymeric materials that would be useful in nanotechnology, we synthesized block copolymers containing thymine and diamidopyridine side chains. These DNA-mimetic polymers self-assembled into spherical aggregates in solution, held together by hydrogen bonding interactions. We have reported the first example of a block copolymer micellar aggregate that is capable of selective recognition of small-molecule guests, with concomitant changes in its aggregation behavior.
In the field of DNA-mediated materials, the ordering of gold nanoparticle (AuNP) arrays can be hindered by the lability of AuNP-DNA linkages. In the search of an indefinitely stable AuNP-DNA linkage, three dendritic thiol-terminated DNA strands were synthesized, and were bound to AuNPs. A preliminary AuNP-DNA linkage lability study showed potential in forming nonlabile AuNP-DNA linkages through the use of dendritic thiol-modified DNA.

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16

Tison, Christopher Kirby. "Programmable, isothermal disassembly of DNA-linked colloidal particles". Diss., Atlanta, Ga. : Georgia Institute of Technology, 2009. http://hdl.handle.net/1853/28189.

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Thesis (M. S.)--Materials Science and Engineering, Georgia Institute of Technology, 2009.
Committee Chair: Milam, Valeria; Committee Member: Boyan, Barbara; Committee Member: Li, Mo; Committee Member: McDevitt, Todd; Committee Member: Sandhage, Ken.

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17

Turlington, Ralph Donald III. "Mitigating security issues in the evolving DNA synthesis industry". Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/80897.

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Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, 2013.
This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (p. 102-108).
DNA synthesis technologies are advancing at exponential rates, with production of ever longer, more complex, and less expensive sequences of double stranded DNA. This has fostered development of industrial scale design, construction, and sale of synthetic DNA. The tools and methods of synthesis used to create beneficial genetic material can also be used to construct dangerous pathogens. To prevent unknown actors from ordering potentially dangerous genetic material, the largest DNA synthesis firms formed two industry associations that require members to screen the DNA sequences ordered and the customers ordering sequences. The firms also worked with the U.S. Health and Human Services to formulate voluntary screening guidelines for synthetic double stranded DNA. As DNA synthesis technology advances and diffuses, this centralized voluntary approach may become less effective. This thesis identifies strengths and weakness in the current voluntary regime and offers recommendations to improve security in the DNA synthesis industry. It describes the origins and current status of DNA synthesis technologies and the structure of the DNA synthesis industry. Then, it describes the formation of voluntary screening consortia and the U.S. and international guidelines that address security issues in DNA synthesis. Finally, this thesis compares DNA synthesis with other potentially "dual use" technologies, concludes that regulatory approaches may not enhance security in this area, and suggests that governments should focus on education and outreach.
by Ralph Donald Turlington III.
S.M.in Technology and Policy

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18

Politi, Antonio. "Systems biology perspectives on calcium signaling and DNA repair". Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2008. http://dx.doi.org/10.18452/15730.

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Der erste Teil dieser Arbeit konzentriert sich auf die Mechanismen hormoninduzierter Ca2+-oszillationen, und wie diese von Konzentrationsschwankungen des Ca2+-freisetzenden Botenstoffes Inositol-1,4,5-trisphosphat (IP3) beinflusst werden. Wir konnten zeigen, dass IP3-Oszillationen die Frequenzkodierung des äußeren Stimulus durch Ca2+-Ozillationen deutlich verstärken. Zwei Mechanismen für das Entstehen der IP3-Oszillationen wurden untersucht: es zeigte sich, dass die Aktivierung der Phospholipase C durch Ca2+ der wahrscheinlichste Mechanismus ist. Um die Rolle der IP3-Oszillationen genauer zu verstehen, wurde ein Modell für den Stoffwechsel des IP3-Vorläufers Phosphatidylinositol-4,5-bisphosphat (PIP2) entwickelt. Es zeigt sich, dass die scheinbar nutzlosen Phosphorylierungs/Dephosphorylierungszyklen eine wichtige Rolle für den PIP2-Haushalt spielen. Durch Nachliefern von PIP2 während der Stimulierung ermöglichen sie anhaltende Ca2+-signale. Der zweite Teil der Arbeit beschäftigt sich mit einem DNS-Reparaturweg, der Reparatur mittels Entfernung von Nukleotiden (NER). Dieser Reparaturmechanismus ist äußerst vielseitig und entfernt Pyrimidinpaare, die durch UV-Strahlung erzeugt wurden, oder Schäden, die durch chemische Agentien erzeugt wurden. Es wurde ein mathematisches Model erarbeitet, das die Grundeigenschaften der NER beschreiben soll. Erstens wurde untersucht, wie die Bindungs- und Freisetzungskinetik der Reparaturfaktoren mit den strukturellen Eigenschaften des Systems, beispielsweise der Bindungsreihenfolge, zusammenhängt. Zweitens wurden anhand von in vivo gemessenen Rekrutierungskinetiken dreier Proteinfaktoren die Modellparameter bestimmt. Das so angepasste Modell sagt unter anderem eine Sättigung der NER durch den Verbrauch des Erkennungsfaktors vorher. Die theoretischen Untersuchungen deuten darauf hin, dass ein sequentieller Anlagerungsmechanismus im Hinblick auf Effizienz und auf Spezifität gegenüber den beschädigten Substrat große Vorteile bringen kann.
The first part of this thesis focuses on the mechanisms of hormone induced Ca2+ oscillations and how these depend on fluctuations in the concentration of the Ca2+-releasing messenger, inositol 1,4,5-trisphosphate (IP3). We were able to show that IP3 oscillations greatly enhances the ability to frequency encode the hormone stimulus by Ca2+ oscillations. Two mechanisms for the generation of IP3-oscillations have been investigated, we could show that Ca2+-activation of phospholipase C is the most probable mechanism. To better understand the role of IP3-oscillations a detailed model for the phosphoinositide pathway has been developed. The model illustrates the importance of futile (de)phosphorylation cycles for regenerating phosphatidylinositol-4,5-bisphophat during stimulation, an essential property to support long-lasting Ca2+ signals. The second part of the thesis is devoted to nucleotide excision repair (NER). It is a versatile DNA repair mechanism that can remove lesions such as UV light induced pyrimidine dimers and bulky adducts caused by chemical agents. To understand the mechanisms underlying the protein assembly during NER and the performance of repair, a mathematical model, delineating hallmarks and general characteristics of NER, has been developed. First, the binding and dissociation kinetics of repair factors are related to the structural properties of the system, such as the sequential order in which the factors enter repair. Second, using in vivo kinetic data for the recruitment of three different proteins at local damaged nuclei, the model parameters are determined and the dynamic behavior of the repair process is scrutinized in detail. The observed saturation of NER is predicted to rely on the high engagement of the recognition factor in repair. The theoretical analysis of repair performance indicates that a sequential assembly process is remarkably advantageous in terms of repair efficiency and can show a marked selectivity for the damaged substrate.

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19

Mazumder, Anjali. "Planning in forensic DNA identification using probabilistic expert systems". Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526507.

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20

Chandrashekhar, Mangesh. "Biological and physicochemical studies on polymer-DNA delivery systems". Thesis, University of Nottingham, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.395573.

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21

Chim, Ya Tsz Anne. "Direct nanoscale visualisation of DNA systems for gene therapy". Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435370.

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22

Mi, Rongjuan. "DNA deamination repair enzymes in bacterial and human systems". Connect to this title online, 2008. http://etd.lib.clemson.edu/documents/1239895684/.

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23

Pant, Pradeep. "Theoretical studies on the structure and dynamics of symmetric nucleic acids and recognition patterns in DNA- ligand/protein systems". Thesis, IIT Delhi, 2019. http://eprint.iitd.ac.in:80//handle/2074/8087.

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Adams, Curtis W. "Analysis of regulatory systems in two different gram⁻ bacteria /". Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/11484.

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Anderson, Richard John. "Novel delivery systems for vaccination with bacterial antigens". Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362376.

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26

Khan, Rishi Lee. "Engineering systems neuroscience modeling of a key adaptive brain control system involved in hypertension /". Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 281 p, 2007. http://proquest.umi.com/pqdweb?did=1362523091&sid=21&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Ghorbani, Mohammadmersad. "Computational analysis of CpG site DNA methylation". Thesis, Brunel University, 2013. http://bura.brunel.ac.uk/handle/2438/8217.

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Epigenetics is the study of factors that can change DNA and passed to next generation without change to DNA sequence. DNA methylation is one of the categories of epigenetic change. DNA methylation is the attachment of methyl group (CH3) to DNA. Most of the time it occurs in the sequences that G is followed by C known as CpG sites and by addition of methyl to the cytosine residue. As science and technology progress new data are available about individual’s DNA methylation profile in different conditions. Also new features discovered that can have role in DNA methylation. The availability of new data on DNA methylation and other features of DNA provide challenge to bioinformatics and the opportunity to discover new knowledge from existing data. In this research multiple data series were used to identify classes of methylation DNA to CpG sites. These classes are a) Never methylated CpG sites,b) Always methylated CpG sites, c) Methylated CpG sites in cancer/disease samples and non-methylated in normal samples d) Methylated CpG sites in normal samples and non-methylated in cancer/disease samples. After identification of these sites and their classes, an analysis was carried out to find the features which can better classify these sites a matrix of features was generated using four applications in EMBOSS software suite. Features matrix was also generated using the gUse/WS-PGRADE portal workflow system. In order to do this each of the four applications were grid enabled and ported to BOINC platform. The gUse portal was connected to the BOINC project via 3G-bridge. Each node in the workflow created portion of matrix and then these portions were combined together to create final matrix. This final feature matrix used in a hill climbing workflow. Hill climbing node was a JAVA program ported to BOINC platform. A Hill climbing search workflow was used to search for a subset of features that are better at classifying the CpG sites using 5 different measurements and three different classification methods: support vector machine, naïve bayes and J48 decision tree. Using this approach the hill climbing search found the models which contain less than half the number of features and better classification results. It is also been demonstrated that using gUse/WS-PGRADE workflow system can provide a modular way of feature generation so adding new feature generator application can be done without changing other parts. It is also shown that using grid enabled applications can speedup both feature generation and feature subset selection. The approach used in this research for distributed workflow based feature generation is not restricted to this study and can be applied in other studies that involve feature generation. The approach also needs multiple binaries to generate portions of features. The grid enabled hill climbing search application can also be used in different context as it only requires to follow the same format of feature matrix.

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Picard, Colette Lafontaine. "Dynamics of DNA methylation and genomic imprinting in arabidopsis". Thesis, Massachusetts Institute of Technology, 2019. https://hdl.handle.net/1721.1/122539.

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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2019
Cataloged from PDF version of thesis.
Includes bibliographical references (pages 210-226).
DNA methylation is an epigenetic mark that is highly conserved and important in diverse cellular processes, ranging from transposon silencing to genomic imprinting. In plants, DNA methylation is both mitotically and meiotically heritable, and changes in DNA methylation can be generationally stable and have long-lasting consequences. This thesis aims to improve understanding of DNA methylation dynamics in plants, particularly across generations and during reproduction. In the first project, I present an analysis of the generational dynamics of gene body methylation using recombinant inbred lines derived from differentially methylated parents. I show that while gene body methylation is highly generationally stable, changes in methylation state occur nonrandomly and are enriched in regions of intermediate methylation.
Important DNA methylation changes also occur during seed development in flowering plants, and these changes underlie genomic imprinting, the phenomenon of parent-of-origin specific gene expression. In plants, imprinting occurs in the endosperm, a seed tissue that functions analogously to the mammalian placenta. Imprinted expression is linked to DNA methylation patterns that serve to differentiate the maternally- and paternally-inherited alleles, but the mechanisms used to achieve imprinted expression are often unknown. I next explore imprinted expression and DNA methylation in Arabidopsis lyrata, a close relative of the model plant Arabidopsis thaliana. I find that the majority of imprinted genes in A. lyrata endosperm are also imprinted in A. thaliana, suggesting that imprinted expression is generally conserved. Surprisingly, a subset of A. lyrata imprinted genes are associated with a novel DNA methylation pattern and may be regulated by a different mechanism than their A.
thaliana counterparts. I then explore the genetics of paternal suppression of the seed abortion phenotype caused by mutation of a maternally expressed imprinted gene. Finally, I present the first large single-nuclei RNA-seq dataset generated in plants, reporting data from 1,093 individual nuclei obtained from developing seeds. I find evidence of previously uncharacterized cell states in endosperm, and examine imprinted expression at the single-cell level. Together, these projects contribute to our understanding of DNA methylation and imprinting dynamics during plant development, and highlight the strong generational stability of certain DNA methylation patterns.
by Colette Lafontaine Picard.
Ph. D.
Ph.D. Massachusetts Institute of Technology, Computational and Systems Biology Program

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29

Wilson, Aubrey Marie Mueller. "Transgene Delivery via Microelectromechanical Systems". BYU ScholarsArchive, 2012. https://scholarsarchive.byu.edu/etd/3936.

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The invention of pronuclear microinjection initiated the field of transgenic research. Over 30 years later microinjection remains the most straight-forward and most commonly used transgene delivery option. In this work we address the current progress of microelectromechanical systems (MEMS) used as transgenic delivery mechanisms. The nanoinjector is a specially designed MEMS device which uses electrostatic charge to manipulate transgene molecules. The process of nanoinjection was designed as an alternative to microinjection which causes less damage to developing embryos, improves embryo survival, birth rates, and overall efficiency of injections. In vivo testing of nanoinjection demonstrates it is both safe and effective. Additionally nanoinjection has the potential to make transgenesis via yeast artificial chromosomes more practical as the nanoinjector may prevent shearing of the YAC molecules. A second nanoinjection protocol termed intracellular electroporetic nanoinjcetion (IEN) was designed to allow for cytoplasmic injections. Cytoplasmic injections are faster and easier than pronuclear injection and do not require the pronuclei to be visible; yet previous attempts to develop cytoplasmic injection have met with limited success. In IEN injections the nanoinjector is used to place transgenic molecules in the cytoplasm. The transgenes are then propelled through the cytoplasm and electroporated into the pronucleus using electrical pulses. Electroporation of whole embryos has not resulted in transgenic animals, but the MEMS device allows localized electroporation to occur within the cytoplasm, giving transgene access to the pronucleus before degradation can occur. In this report we describe the principles which allow for localized electroporation of the pronuclei including: the location of the pronuclei between 21-28 hours post-hCG treatment, modeling data predicting the voltages needed for localized electroporation of pronuclei, and data on the movement of transgenic DNA based on the voltages delivered by IEN. We further report results of an IEN versus microinjection comparative study in which IEN produced transgenic pups with viability, transgene integration, and expression rates statistically comparable to microinjection. The ability to perform injections without visualizing or puncturing the pronuclei will widely benefit transgenic research, and will be particularly advantageous for the production of transgenic animals with embryos exhibiting reduced pronuclear visibility.

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Garrett, Amanda Davanne. "Improving DNA evidence collection via quantitative analysis: a systems approach". Thesis, Boston University, 2013. https://hdl.handle.net/2144/12107.

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Thesis (M.A.)--Boston University
When collecting biological evidence from a crime scene, it is important to determine the most effective and robust collection method to ensure maximum DNA recovery. Some common biological collection methods include swabbing, cutting, scraping, and taping. Although these techniques have been a mainstay of forensic analysis, each of these methods have significant drawbacks, which include but are not limited to, the lack of surface area that may be processed, possible co-elution of PCR inhibitors, and non-optimized elution of cells from the substrate into solution. Therefore, a technique designed to optimize biological collection from items of interest, particularly large items, is necessary and not currently available for forensic use.

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Lambert, C. M. "Repair, replication and transfer systems in the plasmid NTP16". Thesis, University of Liverpool, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.377117.

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Bremner, K. Helen. "Application of nuclear localization sequences to non-viral gene delivery systems". Thesis, University of Birmingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273725.

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Speel, Ernst Jan Maria. "Detection systems for multiple-target in situ hybridization and immunocytochemistry". Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1995. http://arno.unimaas.nl/show.cgi?fid=7927.

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Aboluion, Niema Ali. "The construction of DNA codes using a computer algebra system". Thesis, University of South Wales, 2011. https://pure.southwales.ac.uk/en/studentthesis/the-construction-of-dna-codes-using-a-computer-algebra-system(d0ee33ce-c640-407d-868c-ba5eafa81909).html.

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Coding theory has several applications in Genetics and Bioengineering. This thesis concentrates on a specific application from Computational Biology. This concerns the construction of new DNA codes which satisfy certain combinatorial constraints, using an alphabet of four symbols. The interest in these codes arises because it is possible to synthesise short single strands of DNA known as oligonucleotides. The codes can be useful in the design of these oligonucleotides. For example, the codes are used in DNA computing, as bar codes in molecular libraries and in microarray technologies. The computer algebra system Magma, which deals successfully with coding theory computation, is applied initially to the construction of DNA codes sat- isfying a GC-content constraint and a minimum Hamming distance constraint. The constraints are specified to avoid unwanted hybridizations and to ensure uniform melting temperatures. Additionally, another constraint, known as a reverse-complement constraint, is added to further prevent unwanted hybridiza- tions. This additional constraint is studied using involutions in a permutation group. Codes constructed in this thesis are derived from linear codes over GF(4) and Z4 and additive codes over GF(4). Previous approaches to the construction of these codes are extended in several ways. Longer codes are constructed, the examination of cyclic and extended cyclic codes is more comprehensive, and cosets of codes are considered. In addition, attention is paid to the mapping from field or ring elements to the DNA nucleotides; different mappings can give different lower bounds. Further improvements have been made after the tech- niques of shortening and puncturing are applied to the table of best codes, and also by searching for codes in the tables that have an all-ones vector in their dual. The use of a database of best known linear codes is also considered. In many cases codes are obtained which are larger than the best codes currently known. In the case of codes of length greater than twenty, linear DNA codes have not been constructed previously and so all codes obtained are the best known re- sults. Generator polynomials are given for the codes constructed. Coset leaders are also given in cases where cosets of linear codes are used. Thus it is possible for the reader to construct the codes without repeating the work presented in the thesis. Additionally, files of codewords are available online when the codes constructed are the best known codes and have fewer than 50000 codewords.

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Hajderovic, Ajna. "IT-baserat DNA-register : Hur skulle ett heltäckande IT-baserat DNA-register kunna införas i Sverige för att acceptans av folket?" Thesis, Växjö University, School of Mathematics and Systems Engineering, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:vxu:diva-427.

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Syftet med denna uppsats är att undersöka hur ett heltäckande IT-baserat DNA-register skulle kunna införas i Sverige för att få acceptans av folket. För att få svar på min problemfråga använder jag mig av kvalitativ forskningsmetod. Metoden tillämpas i samband med olika intervjuer. Jag väljer också att arbeta efter deduktiv metod eftersom jag ville studera hur verkligheten kan relateras till teorierna inom det valda ämnet.

Vidare presenteras den befintliga teorin som finns om ett DNA-register. DNA står för deoxyribonucleic acid och är uppbyggd av celler och innehåller information om vår arvsmassa. I brottsutredningar används dock s.k. skräp eller nonsens DNA, där ingen genetisk information kan utläsas förutom könet. DNA-register är ett register som består av DNA-profiler från grova brottslingar. En DNA-profil presenteras i form av en sifferremsa. Med hjälp av det kan polisen binda ett spår till en person.

DNA-register består av två delar, misstankeregister och brottsregister. I misstankeregister registreras personer som är skäligen misstänkta för något allvarlig brott och i brottsregistret registreras brottslingar som döms till något allvarligt brott så som mord eller dråp.

Säkerheten kring ett datorsystem är väldigt viktigt att beakta, speciellt när det handlar om ett datorsystem så som DNA-register. Det som kan utgöra hot för att införa ett heltäckande IT-baserat DNA-register handlar om själva användarna dvs. vem som får använda detta system. De som skulle få använda ett heltäckande IT-baserat DNA-register är Statens Kriminaltekniska Laboratorium (SKL) och Rikspolisstyrelsen (RPS). Vidare handlar det om personlig integritet, men ett DNA-register innehåller inga känsliga personuppgifter. Dessutom får inte uppgifterna om den registrerades personliga egenskaper registreras. Att DNA-register inte utgör hot för den personliga integriteten har också bekräftats från några av de intervjuade personerna. Detta leder mig till följande slutsats.

Om ett heltäckande IT-baserat DNA-register skulle få acceptans av folket måste man ge rätt information angående DNA och det faktum att den personliga integriteten inte skulle kränkas i samband med införelsen.

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Wang, Dayou. "Information extraction from DNA pulsed-field gel electrophoresis patterns and it's application /". free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9988709.

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Salem, Heba Farouk. "Formulation of multicomponent DNA delivery systems to incorporate a targeting moiety". Thesis, University of Nottingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406981.

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38

Booth, S. C. "Studies on the effects of carcinogen ?-DNA interactions in microbial systems". Thesis, University of York, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.353573.

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Corsi, Josephine Charlotte. "An investigation into the transcription of DNA in DOPE-based systems". Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/179459/.

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Hillebrand, Malcolm. "Chaotic Dynamics of Polyatomic Systems with an Emphasis on DNA Models". Doctoral thesis, Faculty of Science, 2021. http://hdl.handle.net/11427/33834.

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In this work we investigate the chaotic behaviour of multiparticle systems, and in particular DNA and graphene models, by applying various numerical methods of nonlinear dynamics. Through the use of symplectic integration techniques—efficient routines for the numerical integration of Hamiltonian systems—we present an extensive analysis of the chaotic behaviour of the Peyrard-Bishop-Dauxois (PBD) model of DNA. The chaoticity of the system is quantified by computing the maximum Lyapunov exponent (mLE) across a spectrum of temperatures, and the effect of base pair disorder on the dynamics is investigated. In addition to the inherent heterogeneity due to the proportion of adenine-thymine (AT) and guanine-cytosine (GC) base pairs, the distribution of these base pairs in the sequence is analysed through the introduction of the alternation index. An exact probability distribution for arrangements of base pairs and their alternation index is derived through the use of Pólya counting theory. We find that the value of the mLE depends on both the base pair composition of the DNA strand and the arrangement of base pairs, with a changing behaviour depending on the temperature. Regions of strong chaoticity are probed using the deviation vector distribution, and links between strongly nonlinear behaviour and the formation of bubbles (thermally induced openings) in the DNA strand are studied. Investigations are performed for a wide variety of randomly generated sequences as well as biological promoters. Furthermore, the properties of these thermally induced bubbles are studied through large-scale molecular dynamics simulations. The distributions of bubble lifetimes and lengths in DNA are obtained and discussed in detail, fitted with simple analytical expressions, and a physically justified threshold distance for considering a base pair to be open is proposed and successfully implemented. In addition to DNA, we present an analysis of the dynamical stability of a planar model of graphene, studying the behaviour of the mLE in bulk graphene sheets as well as in finite width graphene nanoribbons (GNRs). The wellattested stability of the material manifests in a very small mLE, with chaos being a slow process in graphene. For both possible kinds of GNR, armchair and zigzag edges, the mLE decreases with increasing width, asymptotically reaching the bulk behaviour. This dependence of the mLE on both energy density and ribbon width is fitted accurately with empirical expressions.

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DI, MAURO Giuseppe. "Evolution of UV-photoreception and DNA repair systems in blind cavefish". Doctoral thesis, Università degli studi di Ferrara, 2019. http://hdl.handle.net/11392/2488148.

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La luce ha dominato la biologia animale sin dall'origine della vita. Serve come fonte primaria di energia, ha un impatto sul metabolismo e coordina il comportamento degli animali. L'eccessiva esposizione alla luce solare rappresenta anche una delle principali fonti di danno per biomolecole complesse e quindi è alla base di patologie. È noto che la luce ha un effetto cruciale su molti aspetti della fisiologia di pesci, che vanno dallo sviluppo alla crescita, dalla determinazione del sesso al comportamento e alla riproduzione. Recenti scoperte hanno rivelato la presenza di diversi tipi di fotorecettori nei pesci. Gli estremi fenotipi dei pesci di grotta che si sono evoluti in completa assenza di luce sono una testimonianza di quanto la luce modella l’evoluzione dei pesci. Utilizzando zebrafish e due specie di pesci di grotta, Phreatichthys andruzzii e Astyanax mexicanus, evoluti in diverse nicchie ecologiche, abbiamo studiato l'evoluzione della percezione UV e il meccanismo di riparazione del danno al DNA causato da UV. Gli elementi principali di questi processi sono altamente conservati: i fotorecettori UV sono espressi negli occhi, nel cervello e nei tessuti periferici di quasi tutti i pesci, mentre le fotoliasi, enzimi di riparazione del DNA attivati dalla luce blu, sono essenzialmente conservati in tutto il regno animale. Confrontando meccanismi relazionati alla luce di specie che vivono nell’habitat di superficie con specie che risiedono nell'habitat di grotta, possiamo apprendere molti dettagli su come la luce e meccanismi biologici connessi evolvono in risposta alle loro condizioni ambientali. Nella seguente tesi, tentiamo di illustrare come l'uso di strumenti comportamentali, molecolari e computazionali conducano la risposta a questa domanda.
Light has dominated animal biology since the origin of life. It serves as the primary source of energy, has an impact on metabolism and coordinates the behavior of animals. Excess exposure to sunlight also represents a major source of damage for complex biomolecules and thereby underlies pathology. Light is known to have a crucial effect on many aspects of fish physiology ranging from development and growth to sex determination, behavior and reproduction. Recent discoveries have revealed the presence of different types of photoreceptors in fish. The extreme phenotypes of cavefish which have evolved in the complete absence of light are a testimony to how much light shapes fish evolution. Using the zebrafish and two species of cavefish, Phreatichthys andruzzii and Astyanax mexicanus, evolved in different ecological niches, we investigated the evolution of UV perception and DNA UV-damage repair mechanism. The main elements of these processes are highly conserved: UV photoreceptors are expressed in eye, brain and peripheral tissues of almost all fish, while the photolyases, blue-light activated DNA repair enzymes, are essentially preserved throughout the animal kingdom. Comparing the light-related mechanisms of species inhabiting surface habitat with species linving in subterranean habitat, we can learn much details about how light and related biological mechanisms evolve in response to their environmental conditions. In the following thesis, we attempt to illustrate how the use of behavioral, molecular and computational tools lead the answer on this question.

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42

Qian, Mengdi. "System Biology Analysis of the Role of DNA Repair in Cancer Treatment Outcome". Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1560212679611413.

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NASELLI, Flores. "NUTRIGENOMICS EFFECTS OF PHYTOCHEMICAL INDICAXANTHIN IN in vitro CELL SYSTEMS". Doctoral thesis, Università degli Studi di Palermo, 2014. http://hdl.handle.net/10447/90899.

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Nutrition plays a key role in many aspects of health, indeed epidemiological studies provide evidence that diet can play essential roles in reducing the risk of chronic diseases. Accumulating evidence indicates that dietary compounds (phytochemicals) from fruit and vegetables can modulate multiple cancer-inflammation pathways which are relevant for chemoprevention and are commonly deregulated by epigenetic mechanisms in cancer cells, including drug detoxification, cell cycle regulation, apoptosis induction. Epigenetic refers to heritable alterations in gene expression that do not involve modification of the underlying genetic DNA sequence. Although epigenetic changes are heritable in somatic cells, these modifications are also potentially reversible, which makes them attractive and promising avenues for tailoring cancer preventive and therapeutic strategies. The aim of this study was to investigate the antiproliferative potential of a Cactus pear pigment extract (Indicaxanthin) to assess the phenotypic effects on colorectal cancer cell lines and to investigate the biological function and/or epigenetic mechanisms for Indicaxanthin’s activity. The antiproliferative effects of Indicaxanthin (Ind), were investigated on a number of human cancer cell lines including hepatocarcinoma cells (HepG2, Ha22T, HUH 7), breast cancer cells (MCF7), cervix epithelial carcinoma (HeLa) and colorectal carcinoma cells (Caco2, LOVO1, DLD1, HT29, HCT116). Ind caused a clear dose-dependent decrease in the proliferation of Caco2, with minor effect on the other cell lines. Flow cytometric analysis showed a pro-apoptotic effect of the pigment at 48h in Caco2 cells. Incubation of proliferating Caco2 cells with Ind (10μl to 100μl ) remarkably reduced the global DNA 5-methyl cytosine methylation and caused a stable demethylation of the tumor suppressor p16INK4a gene promoter, with reactivation of the silenced mRNA expression and accumulation of p16INK4a protein. A decrease of the hyperphosphorylated retinoblastoma protein in favour of its hypophospohrylated status was observed, with unaltered level of the cycline-dependent kinase CDK4. Analysis of cell distribution in the cell cycle phases after Ind treatment showed arrest of Caco2 cells in the S- G2/M- phase. The effect of Ind on LINE-1 methylation levels in the other colorectal cancer cell lines was therefore explored as well as the effect of Ind on promoter methylation status of other genes implicated in colon carcinogenesis. Ind is able to alter the methylation status on global and specific gene level. To rationalize the mechanism of DNA methylation changes induced by Ind, the effect of the phytochemical on the activity and the level of DNA methyltransferase (DNMT) was evaluated. Ind induced a dose-dependent inhibition of DNMT activity on Caco2 cells, while did not affect DNMT1 and DNMT3b level. However a significant increment of DNMT3a was evident in Caco2 cell line. Aberrant expression of DNMTs and their isoforms has been found in many types of cancer and their contribution to aberrant DNA methylation has been proposed. Following this hypothesis, the effect of Ind on the expression of DNMT splice variant, was investigated. The expression of DNMT increased appreciably only in some cell lines with respect to only some DNMT genes after Ind treatment. DNA demethylation may take place as an active mechanism by the activity of specific enzymes. In order to assess whether Ind is able to induce an alteration in DNA demethylase expression, which may explain the effects of Ind on DNA methylation in the tested cell lines, the effect of Ind on the DNA demethylase expression was investigated. Ind induced an increased expression of some enzymes with demethylating activity (TET2, MBD4) relatively only in some cell lines. In this work it appears that the phytochemical Indicaxanthin induces different effects (both epigenetic and biochemical) on colorectal cancer cell lines tested (reduction of proliferation, induction of apoptosis, induction of cell cycle arrest, change in DNA methylation, alteration of gene expression). The effects brought by Ind, are often variable depending on the cell line used, such phenomenon can be attributed to the cell lines themselves. Furthermore from in silico molecular imaging tests, in this study it was supposed that epigenetic effects of Ind are not mediated by a direct alteration of DNMT expression, rather by an influence of Ind on their activities. Then, Ind binding the DNMT and altering their methyltransferase function could cause an imbalance of global DNA methylation.

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Roos, Anna-Karin. "Delivery of DNA vaccines against cancer /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-895-9/.

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Carrillo, Nunez Hamilton. "Localização eletrônica em cadeias duplas : aplicação ao DNA". [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/277016.

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Orientador: Peter Alexander Bleinroth Schulz
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Fisica Gleb Wataghin
Made available in DSpace on 2018-08-11T10:20:11Z (GMT). No. of bitstreams: 1 CarrilloNunez_Hamilton_M.pdf: 5573082 bytes, checksum: 82c48bf8cb538a5a4c7444d18080814b (MD5) Previous issue date: 2008
Resumo: Neste trabalho discutimos e comparamos diferentes definições de localização eletrônica em sistemas quase-1D: o caso estritamente 1D de cadeias de polianilinas e o DNA modelado como uma cadeia dupla. Em ambos os sistemas se estudou o comprimento de localização, obtido da condutância e do numero de participação, tentado estabelecer uma equivalência entre as duas quantidades. Para o sistema 1D a condutância foi obtida pelo método de matriz transferência. Entretanto, para o DNA a condutância se calcula usando o método recursivo das funções de Green, pois o método de matriz transferência para cadeias duplas apresenta instabilidades numéricas. O resultado obtido sugere um novo critério para analisar a extensão da função de onda em sistemas mesoscópicos dentro do regime difusivo de transporte como uma informação complementar para o comprimento de localização
Abstract: In this work we discuss and compare different definitions for localization of electronic states in quase-one-dimensional systems: the 1-D case of polianilines chains and DNA-like molecules. In order to establish ranges of equivalence, the localization length from both, the conductance and participation ratio, is computed. For the 1-D case the con-ductance is obtained by mean of the transfer matrix method, while the conductance for DNA-like double strands are calculated by mean of the recursive Green¿s function method since the transfer matrix method shows numerical instabilities. The final results suggest also criteria to infer the extension of wave function in mesoscopic systems with-in the diffusive transport regime as a complementary information to the localization length
Mestrado
Física da Matéria Condensada
Mestre em Física

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46

Beck, Corey Andreu. "Theoretical Studies of Solid and Liquid Water Systems". The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1337969878.

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Owen, Darerca. "An investigation into Escherichia coli chromosomal and plasmid genes inducible by DNA damage". Thesis, University of Liverpool, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.237514.

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Sjöland, Erik. "Exploring DNA Methylation: A fast approximative Singer-Engström-Schönhuth-Pachter optimization algorithm". Thesis, KTH, Optimeringslära och systemteori, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-44035.

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Das, Prolay. "Long-Range Charge Transfer in Plasmid DNA Condensates and DNA-Directed Assembly of Conducting Polymers". Diss., Georgia Institute of Technology, 2007. http://hdl.handle.net/1853/19856.

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Long-distance radical cation transport was studied in DNA condensates where linearized pUC19 plasmid was ligated to an oligomer and transformed into DNA condensates with spermidine. DNA condensates were detected by Dynamic Light Scattering and observed by Transmission Electron Microscopy. Introduction of charge into the condensates causes long-distance charge migration, which is detected by reaction at the remote guanines. The efficiency of charge migration in the condensate is significantly less than it is for the corresponding oligomer in solution. This result is attributed to a lower mobility for the migrating radical cation in the condensate, caused by inhibited formation of charge-transfer-effective states. Radical cation transport was also studied in DNA condensates made from an oligomer sandwiched between two linearized plasmids by double ligation. Unlike the single ligated plasmid condensates, the efficiency of charge migration in the double ligated plasmid-condensates is high, indicative of local structural and conformational transformation of the DNA duplexes. Organic monomer units having extended ð-conjugation as part of a long conducting polymer was synthesized and characterized. The monomer units were covalently attached to particular positions in DNA oligonucleotides by either the convertible nucleotide approach or by phosphoramidite chemistry. Successful attachment of the monomer units to DNA were confirmed by mass spectral analysis. The DNA-conjoined monomer units can self assemble in the presence of complementary sequences which act as templates that can control polymer formation and structure. By this method the para-direction of the polymer formation can be enforced and may be used to generate materials having nonrecurring, irregular structures.

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Sohbati, Mohammadreza. "Circuits and systems for DNA detection by ion-sensitive field effect transistor". Thesis, Imperial College London, 2014. http://hdl.handle.net/10044/1/25525.

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This thesis, after a review on the state-of-the-art sequencing and genotyping technologies, focuses on the semiconductor-based systems using pH change for DNA (Deoxyribonucleic acid) detection by ion-sensitive feld effect transistors (ISFETs). Accuracy and throughput, besides cost, are the key concerns in these systems, which are reflected on their signal-to-noise ratio and ability to process enormous measurement data at low levels for base-calling. Simulations are provided on the signal behaviour, supported by the literature review. The ISFETs have been investigated for their dimension and shape (single-plate vs mesh, and square vs octagonal). More complete formula and design methodology (to suppress the process variations and signal drift) have been provided for the ISFET operation by including the coupling effect. The experiment results, on 8 dies each containing 15 devices, showed the decoupling parasitics dependency on the sensing area perimeter. A buffer-shield structure has been proposed to improve the ISFET coupling. In addition, based on the ISFET drift analysis, measuring the biasing reference electrode current is recommended for the drift direction monitoring/prediction. Considering the two main applications of sequencing and genotyping, new readout configurations have been proposed to enhance the on-chip signal processing. Piecewise linear approximating (PLA), and temperature-insensitive continuous-time ΔpH to digital converter (TICTC), tackle the ISFET and temperature dependency. The TICTC has been designed for a resolution of 0.015pH, easily scalable and only dependent on the relative aspect ratio of its current mirrors. Its dynamic range is not limited despite operating in weak inversion. For very large-scale sequencing arrays, common-mode noise elimination using the back-gate has been proposed. It allows on-chip suppression of the background noise in the sequencing microchips, reducing the low-level processing load. Moreover, a pseudo-inverter-based readout has been designed that may allow improving the conversion resolution by current-mode comparison and indirect feedback to the ISFET gate.

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