Dissertations / Theses on the topic 'Molecular probes'
To see the other types of publications on this topic, follow the link: Molecular probes.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Molecular probes.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Nathubhai, Amit. "Molecular probes for mammalian chitinases." Thesis, University of Bath, 2010. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.518107.
Full textAbstract:
Chitin is a glycopolymer consisting of +-(1, 4)-linked N-acetyl-D-glucosamine residues that occurs widely in nature and is a constituent of many organisms that are pathogenic to humans, including insects, fungi, and parasitic nematodes. As these organisms depend on the ability to break down chitin at key points of their life-cycle, inhibitors of the enzymes termed chitinases that catalyse the hydrolysis of chitin, are of considerable interest as potential drugs and insecticides. Although chitin is absent from mammalian physiology, two human chitinases along with several chitin-binding proteins (chi-lectins) have been associated with the onset or transmission of several major human diseases such as asthma, Legionnaire’s disease and osteoarthritis. Therefore, selective inhibitors of chitinases are now of considerable interest as new drug leads and biochemical probes. Until recently, few broad spectrum chitinase inhibitors had been identified. The natural cyclopentapeptide, argifin, has been shown to be a potent inhibitor of several bacterial-type family 18 chitinases including Aspergillus fumigatus chitinase B1 (AfChiB1). With the aid of high resolution X-ray structures we have designed and prepared linear fragments of the natural product cyclopentapeptide argifin using a combination of SPPS and solution phase synthesis. This has allowed us to determine that the Nmethyl guanylurea motif serves as a starting point for the generation of novel, drug-like, peptidomimetic inhibitors family 18 chitinases. We have also demonstrated that the cis configuration about the Arg(MC)-N-MePhe peptide bond is essential to retain any significant biological activity. This dipeptide motif is also found in another naturally occurring cyclopentapeptide, banyasin A, extracted from the cyanobacteruim Nostoc sp. Banyasin A also contains a rare +-amino acid, 3-amino-2-methyl-5E-octenoic acid (Amoa), in which the stereochemistry at the C3 and C5 of Amoa has not been resolved. The diastereoselective synthesis of Amoa for the preparation of banyasin A has also been established using chiral oxazolidinone-based aldol chemistry, which has allowed us to successfully prepare a single diastereoisomer of the natural product cyclopentapeptide incorporating this +-amino acid. New methodology for the preparation of argifin has also been developed to reduce the propensity towards the formation of undesired side products and to prepare the natural product on a larger scale.
2
Sapkal, S. "Spectroscopic investigation of molecular probes." Thesis(Ph.D.), CSIR-National Chemical Laboratory, Pune, 2021. http://dspace.ncl.res.in:8080/xmlui/handle/20.500.12252/6010.
Full text
3
Wang, Lei. "Molecular Probes for Pancreatic Cancer Imaging." PDXScholar, 2016. http://pdxscholar.library.pdx.edu/open_access_etds/3108.
Full textAbstract:
Pancreatic ductal adenocarcinoma (PDAC) has the poorest five-year survival rate of any cancer. Currently, there are no effective diagnostics or chemotherapeutics. Surgical resection is the only curative therapy. However, most patients experience recurrence due largely to challenges in assessing tumor margin status in the operating room. Molecular probes that selectively highlight pancreatic cancer tissue, having the potential to improve PDAC margin assessment intraoperatively, are urgently needed. In this work, a series of red and near-infrared fluorescent probes is reported. Two were found to distribute to normal pancreas following systemic administration. One selectively accumulates in genetically modified mouse models of PDAC, providing cancer-specific fluorescence. In contrast to the small molecule probes reported previously, it possesses inherent affinity for PDAC cells and tissue, and thus does not require conjugation to targeting agents. Moreover, the probe exhibits intracellular accumulation and enables visualization of four levels of structure including the whole organ, tissue, individual cells and subcellular organelles. It can thus promote new strategies for precision image-guided surgery, pancreatic cancer detection, the monitoring of therapeutic outcomes and basic research.
4
Willcocks, T. C. "Mapping of human genes with molecular probes." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370272.
Full text
5
James, David Thomas. "Developing structural probes for designed molecular architectures." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/10732.
Full textAbstract:
This thesis is concerned with the development of techniques to probe and control molecular morphology in organic semiconductors and investigate structure-property relationships. An angle-dependent polarised Raman technique is developed to probe molecular order and orientation in 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pentacene) thin lms, and applied to understand the role of blending with polystyrene on morphology and charge transport properties in inkjet-printed organic field-effect transistors (OFETs). Compared to pristine devices, blending improves film uniformity in terms of device coverage and molecular orientation and increases saturation mobility from [Mathematical formula appears here. To view, please open pdf attachment]. A zone-casting apparatus is developed to systematically control the grain size and molecular orientation of TIPS-pentacene thin films. Processing parameters such as solvent, solution temperature, substrate temperature and casting speed are systematically controlled to study film coverage, grain size, alignment and orientation, and applied to investigate charge transport properties in TIPS-pentacene and 6,13-bis(triethylsilylethynyl) pentacene (TES-pentacene) OFETs. Casting speed and grain orientation strongly influence device performance. TIPS- pentacene shows higher mobilities and grain-boundary-limited transport while TES-pentacene charge transport is limited by crystal orientation. The anisotropic structural and optical properties of TIPS-pentacene and TES-pentacene films are characterised using polarised UV-visible absorption and Raman spectroscopy. Evidence for J- and H-aggregation is found from a packing-induced red-shifted and blue-shifted absorption transition, respectively. Angle-dependent polarised Raman spectroscopy is used to probe the molecular orientation and order in the films. The pentacene long-axis orientation is found to be ±(50-60)° relative to the zone-casting direction for both materials, while TIPS-pentacene shows a higher Raman anisotropy than TES-pentacene. Quantum-chemical studies are performed on a range of conjugated polymer systems. Using simulated structure-property relationships, the effect of side chain placement & positioning, blending with small molecules, thermal annealing and heavy-atom substitution on the opto- electronic and charge transport properties of the polymers are discussed.
6
Caries, Christopher Cain. "Organometallics : a platform for molecular imaging probes /." May be available electronically:, 2009. http://proquest.umi.com/login?COPT=REJTPTU1MTUmSU5UPTAmVkVSPTI=&clientId=12498.
Full text
7
Chang, Yuan-Pin. "Novel probes of angular momentum polarization." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:d3880edf-436a-415e-8a74-6b1c0fd26e65.
Full textAbstract:
New dynamical applications of quantum beat spectroscopy (QBS) to molecular dynamics are employed to probe the angular momentum polarization effects in photodissociation and molecular collisions. The magnitude and the dynamical behaviour of angular momentum alignment and orientation, two types of polarization, can be measured via QBS technique on a shot-by-shot basis. The first part of this thesis describes the experimental studies of collisional angular momentum depolarization for the electronically excited state radicals in the presence of the collider partners. Depolarization accompanies both inelastic collisions, giving rise to rotational energy transfer (RET), and elastic collisions. Experimental results also have a fairly good agreement with the results of quasi-classical trajectory scattering calculations. Chapter 1 provides the brief theories about the application of the QBS technique and collisional depolarization. Chapter 2 describes the method and instrumentation employed in the experiments of this work. In Chapter 3, the QBS technique is used to measure the total elastic plus elastic depolarization rate constants under thermal conditions for NO(A,v=0) in the presence of He, Ar, N2, and O2. In the case of NO(A) with Ar, and particularly with He, collisional depolarization is significantly smaller than RET, reflecting the weak long-range forces in these systems. In the case of NO(A)+N2/O2, collisional depolarization and RET are comparable, reflecting the relatively strong long-range forces in these systems. In Chapter 4, the QBS technique is used to measure the elastic and inelastic depolarization and total RET rate constants for OH(A,v=0) under thermal conditions in the presence of He and Ar, as well as the total depolarization rate constants under superthermal conditions. In the case of OH(A)+He, elastic depolarization is sensitive to the N rotational state, and inelastic depolarization is strongly dependent on the collision energy. In the case of OH(A)+Ar, elastic depolarization is insensitive to N, and inelastic depolarization is less sensitive to the collision energy, reflecting that the relatively strong long-range force in OH(A)+Ar system. The second part of this thesis describes the experimental studies of photodissociation under thermal conditions. Chapter 5 provides a brief introduction about several polarization parameter formalisms used for photodissociation, and the incorporation of the QBS technique to measure these polarization parameters. In this thesis, most polarization parameters of the molecular photofragments are measured using the LIF method, and the QBS technique is used as a complementary tool to probe these polarization parameters. In Chapter 6, rotational orientation in the OH(X,v=0) photofragments from H2O2 photodissociation using circularly polarized light at 193 nm is observed. Although H2O2 can be excited to both the A and B electronic states by 193 nm, the observed orientation is only related to the A state dynamics. A proposed mechanism about the coupling between a polarized photon and the H2O2 parent rotation is simulated, and the good agreement between the experimental and simulation results further confirms the validity of this mechanism. In Chapter 7, rotational orientation in the NO(X,v) photofragments from NO2 photodissociation using circularly polarized light at 306 nm (v=0,1,2) and at 355 nm (v=0,1) is observed. Two possible mechanisms, the parent molecular rotation and the coherent effect between multiple electronic states, are discussed. NOCl is photodissociated using circularly polarized light at 306 nm, and NO(X,v) rotational distributions (v=0,1) and rotational orientation (v=0) are measured. For the case of NOCl, the generation of orientation is attributed to the coherent effect.
8
Kujala, Naresh Gandhi Yu Ping. "Frequency domain fluorescent molecular tomography and molecular probes for small animal imaging." Diss., Columbia, Mo. : University of Missouri--Columbia, 2009. http://hdl.handle.net/10355/7021.
Full textAbstract:
Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 26, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Ping Yu. Vita. Includes bibliographical references.
9
Mastrodonato, Cristiano Matteo. "Elaboration of fluorescent molecular probes and molecular-based nanoparticles for bioimaging purposes." Thesis, Bordeaux, 2017. http://www.theses.fr/2017BORD0652/document.
Full textAbstract:
Les techniques de fluorescence sont des outils de choix pour l’étude et la compréhension fine des processus biologiques. Ceci requiert toutefois l’utilisation de sondes fluorescentes parfaitement adaptées au but visé et répondant aux différentes exigences requises pour l’application visée. Dans ce cadre, nous nous sommes plus particulièrement intéressés à l’élaboration de sondes biphotoniques de pH adaptées à une mesure très sensible de faibles variations de pH autour du pH neutre. Les variations et gradients de pH sont en effet impliqués dans un certain nombre de processus biologiques importants et peuvent être associées à des dysfonctionnements liés à certaines maladies. Dans ce cadre, nous avons développé de nouvelles sondes fluorescentes de pH fluorescentes présentant à la fois un comportement ratiométrique, une forte sensibilité autour du pH neutre et facilement excitables dans le proche IR par absorption à deux photons. Ces sondes de structure quadrupolaire et bolamamphiphile permettent ainsi la détection ratiométrique du pH dans des environnements biologiques au moyen d'une excitation biphotonique dans le proche IR. En parallèle, nous nous sommes intéressés à l’élaboration de nanoparticules hyperbrillantes dédiées à l’imagerie biologique par microscopie de fluorescence induite par excitation à deux photons. Nous nous sommes plus particulièrement attachées au design de nanoparticules organiques fluorescentes constituées de molécules organiques de bas poids moléculaire (FONs). Cette approche offre en effet une grande flexibilité et la possibilité d’accéder à des nanosondes ayant des brillances comparables aux très populaires quantum dots mais moins toxiques et plus facilement dégradables. L’ingénierie moléculaire des fluorophores utilisés pour la préparation des FON est cruciale puisqu’elle influence fortement à la fois les propriétés photophysiques (brillance, couleur…) et leur propriétés physico-chimiques (stabilité chimique et structurale, stabilité colloïdale). Dans ce contexte, une librairie de nouveaux chromophores dipolaires a été synthétisée et utilisées pour la préparation de FON par la méthode de nano-précipitation. Leurs propriétés ont été étudiées afin de déterminer la relation entre la structure du chromophore et les propriétés globales des nanoparticules constituées de ces colorants. Ce travail a permis d’identifier les paramètres structuraux permettant d’accéder à des nanoparticules présentant à la fois une brillance exceptionnelle, une émission modulable du vert au rouge et proche IR et une remarquable stabilité colloïdale. Ces nanoparticules présentent des potentialités majeures pour l’imagerie in vivo par excitation et détection dans le proche IRFluorescence-based techniques are popular tools for the study and understanding of biological processes. This has prompted continuous research aimed at the development of a wide range of fluorescent probes specifically designed for specific applications. Among them, fluorescent pH probes are of much interest as pH variations or gradients are involved in many biological events and anomalous alterations are often related to the onset of dysfunctions and diseases. In this framework we have developed a series of promising two-photon pH fluorescent molecular probes. These quadrupolar bolaamphiphilic probes are of great interest, as they combine a steep pH dependence of their optical properties close to neutral pH, ratiometric behavior and large response to two-photon (2P) excitation in the NIR region. As such they offer much promise for ratiometric detection of the pH in biological environments and in situ monitoring of acidification. In parallel, we have been interest in the design of ultrabright nanoparticles for bioimaging purpose (in particular highly sensitive optical imaging). We chose to focus on Fluorescent Organic Nanoparticles made of organic molecules with low molecular weight (FONs) as they offer a flexible route and promising alternatives to toxic quantum dots. In this case the design of the dye used as building blocks of the FONs is of crucial importance and strongly influence the chemical and physical properties of the nanoparticles generated, such as their one and two-photon brightness and both their structural and colloidal stability. In that context a library of novel dipolar chromophores have been synthesized and used to prepare FONs using the nanoprecipitation method. Their properties were thoroughly investigated in order to determine the relationship between the molecular design of the isolated dye and the overall properties of the nanoparticles made of these dyes. As a result, Hyperbright FONs emitting in the green to NIR region and combining giant brightness and remarkable stability have been achieved. They offer major promise for bioimaging based on both excitation and detection in the NIR region
10
Lenaerts, Jeremy. "Molecular beacons as hybridisation probes in microbial ecology." Thesis, University of Exeter, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493638.
Full textAbstract:
Microorganisms are of fundamental importance to global biogeochemical cycling, yet aspects of their ecology are poorly understood. Within the present methods used to study microbial ecology are limitations with regards to sensitivity, applicability and automation. This study aimed to investigate the potential application of novel nucleic acid probes (molecular beacons and locked nucleic acid probes) in microbial ecology.
11
Allen, Nicholas Denby. "Transgenes as molecular probes of mouse developmental genetics." Thesis, University of Cambridge, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335023.
Full text
12
Shchepinova, Maria M. "Molecular probes for monitoring mitochondrial movement and function." Thesis, University of Glasgow, 2016. http://theses.gla.ac.uk/7835/.
Full textAbstract:
This thesis explores two distinct parts of mitochondrial physiology: the role of mitochondria in generation of reactive oxygen species (ROS) and mitochondrial morphology and dynamics within cells. The first area of research is covered in Chapters 1-8. Mitochondrial biofunctionality and ROS production are discussed in Chapter 1, followed by the strategy of targeting bioactive compounds to mitochondria by linking them to lipophilic triphenylphosphonium cations (TPP) (Chapter 2). ROS sensors relevant to the research are reviewed in Chapter 3. Chapter 4 presents design and synthesis of novel probes for superoxide detection in mitochondria (MitoNeo-D), cytosol (Neo-D) and extracellular environment (ExCellNeo-D). The results of biological validation of MitoNeo-D and Neo-D performed in the MRC MBU in Cambridge are presented in Chapter 5. A dicationic hydrogen peroxide sensor that utilizes in situ click chemistry is discussed in Chapter 6. Preliminary work on the synthesis of mitochondria-targeted superoxide generators, which led to the development of mitochondria-targeted analogue of paraquat, MitoPQ, is presented in Chapter 7. A set of bifunctional probes (BCN-Mal, BCN-E-BCN and Mito-iTag) for assessing the redox states of protein thiols is discussed in Chapter 8 along with their biological validation. The second part of the thesis is aimed at the study of mitochondrial morphology and dynamics and is presented in Chapters 9-11. Chapter 9 provides background on the classes of fluorophores relevant to the research, the phenomenon of fluorescence quenching and the principle of photoactivation with examples of photoactivatable fluorophores. Next, the background on mitochondrial morphology and heterogeneity is presented in Chapter 10, followed by the ways of imaging and tracking mitochondria within cells by conventional fluorophores and by photoactivatable fluorophores exploiting super-resolution microscopy. Chapter 11 presents the design and synthesis of four photoactivatable fluorophores for mitochondrial tracking, MitoPhotoRhod110, MitoPhotoNIR, Photo-E+, MitoPhoto-E+, along with results of biological validation of MitoPhotoNIR. The results and discussion concludes with Chapter 12, which is a summary and suggestions for future work, followed by the chemistry experimental procedures (Chapter 13), materials and methods for biological experiments (Chapter 14) and references.
13
Cowell, Sheena. "Development of molecular probes responsive to matrix metalloproteinases." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/23890.
Full textAbstract:
Matrix metalloproteinases (MMPs) have been identified as biomarkers for cancer, offering prognostic potential. However, they lack non-invasive detection. This thesis highlights the work carried out on the design, synthesis and development of 19F MRI probes for the molecular imaging of MMP activity. The design of these MMP-activated imaging agents was based on the paramagnetic effects of gadolinium(III) on the NMR/MRI signal of a CF3 group in close proximity to the metal cation. 1st generation probes were prepared, incorporating MMP-2 selective peptide substrates SPAYYTA or SLAYYTA as a linker between gadolinium(III)-DOTA and Asp[(trifluoromethoxy)benzylamide]-OH. Attempts to monitor MMP-2 mediated peptide hydrolysis via HPLC and fluorescent assays proved problematic. The use of 68Ga and its complexation to DOTA provided a highly sensitive assay for the assessment of the peptide compounds. Using this method, assay conditions were optimised to observe on average 20% peptide cleavage over 2 hours with MMP-2, with selectivity observed against MMP-9 and MMP-14. The original gadolinium analogues of these compounds were then analysed by 19F NMR spectroscopy, successfully demonstrating a change in signal upon incubation with MMP-2. Development of the probes was then carried out to improve their clinical potential. Two pathways were explored; increasing compound reactivity through the introduction of spacer groups and increasing 19F sensitivity via increased local concentrations of fluorine, carried out utilising activated cell penetrating peptides (ACPPs). The latter method proved more successful, displaying similar reactivity and selectivity to 1st generation compounds. These ACPP probes are still in the early stages of development, with scope for future investigation. The transferability of 1st generation MMP-2-activated probes was also investigated via the production of a compound of analogous design, incorporating an MMP-14 selective substrate RIGFLR. Testing and development revealed this compound required incorporation of a two amino acid spacer group (SG) in order to demonstrate partial MMP-14 selectivity.
14
Savage, Michelle L. "Synthesis and development of light-activated molecular probes." Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:3532bd21-ad68-4e8e-9e77-9fd6b620d4f3.
Full textAbstract:
Judicious addition of photolabile caging groups (PCGs) to protect biologically im- portant molecules, has enabled the development of many powerful chemical tools for the study of biological processes. These tools have the potential to be activated in a cellular setting by irradiation with light of appropriate wavelengths, restoring functionality, with excellent spatial and temporal control. This D. Phil. dissertation highlights two biologically relevant examples where PCGs can be applied: (i) 4,5-dimethoxynitrobenzyl (DMNB) caged derivatives of GSH and ESG, were synthesised and uncaging of the DMNB group at 350 nm to reveal the free α-carboxylic acid of the glycine residue was demonstrated. These molecules have the potential to probe the binding mode within the KefC KTN binding domain, a ligand-gated K+ efflux system, critical for bacterial response to electrophilic assault. The molecules are currently with collaborators awaiting further evaluation. (ii) The wavelength-dependent application of PCGs toward the study of protein post- translational modifications (PTMs) was developed. PTMs modulate protein function and have a ubiquitous role in a diverse range of cellular functions. A wavelength selective sequential pair of PCGs was developed and demonstrated in a tripeptide, using the diethylamino coumarin (DEACM), which was cleaved at 420 nm, and the DMNB caging group, which was subsequently cleaved at 350 nm. A chromatically orthogonal pair of PCGs, with possible applications in both organic synthesis and biological systems, incorporating the BODIPY-based and DEACM caging groups, which could be cleaved at 530 nm and 420 nm, respectively, was also developed. Photolysis was conducted on a tripeptide and hexapeptide and an in vitro application was demonstrated where when caged, the peptide was not susceptible to peptidolysis when incubated with enzymes. Following irradiation at 420 nm, the DEACM group was uncaged and the peptide underwent peptidolysis in the presence of Endoproteinase AspN, whereas following irradiation at 530 nm to uncage the BODIPY group, the peptide underwent peptidolysis in the presence of Endoproteinase LysC. These results not only provide conclusive evidence of the ability of this pair of caging groups to act in a wavelength orthogonal sense but also demonstrates the potential applicability of the pair to biochemical studies. This pair of PCGs represents the first example of an orthogonal pair of caging groups where both PCGs could be cleaved, at wavelengths longer than 400 nm, in a sequence independent manner.
15
Gawel, Justyna M. "Targeted molecular probes for investigating biological redox processes." Thesis, University of Glasgow, 2015. http://theses.gla.ac.uk/7000/.
Full textAbstract:
This thesis explores molecular probes for understanding redox biology and oxidative stress. It is divided into eleven chapters and a reference section. The first two chapters comprise the general background of mitochondria, oxidative stress and strategies for targeting bioactive molecules to mitochondria (Chapter 1) and to the extracellular environment (Chapter 2). The work presented in Chapters 3-5 includes the synthesis of extracellulary-targeted antioxidants (ExCell antioxidants) in the University of Glasgow. The targeting strategy is novel and was confirmed by biological work performed in the Mitochondrial Biology Unit in Cambridge. The strategy of targeting compounds to mitochondria by linking bioactive groups to a lipophilic triphenylphosphonium (TPP) cation is known and was applied in novel ways in this work (Chapters 6-9). TPP-viologen conjugates related to the herbicide, paraquat, were synthesized and one of these, MitoPQ, efficiently generates superoxide selectively in mitochondria. Other probes were prepared for assessing the redox states of mitochondrial thiols and for generating mitochondrial protein perthiols. Preliminary work is presented on strategies for delivering molecular cargoes to mitochondria, so that the cargo is retained in the mitochondrial matrix. Chapter 10 is a summary and suggestions for future work and this is followed by a complete chemistry experimental and materials and methods for biological experiments (Chapter 11) and references.
16
Martinez, Diaz Karen. "Polymer linker DNA probe design, characterization and comparison with molecular beacons." [Gainesville, Fla.] : University of Florida, 2005. http://purl.fcla.edu/fcla/etd/UFE0010881.
Full text
17
Peng, Hanjing. "Development of Bacterial Quorum Sensing Inhibitors and Molecular Probes." Digital Archive @ GSU, 2012. http://digitalarchive.gsu.edu/chemistry_diss/73.
Full textAbstract:
Bacterial quorum sensing is regarded as a novel target for the design of antimicrobials. Based on lead structures identified from HTS, 39 analogues have been synthesized and evaluated in Vibrio haveyi. Potent inhibitors with IC50 values at single-digit micromolar concentrations for AI-2 mediated quorum sensing have been identified. On the second project, post-synthesis modifications of DNA provide easy functionalizations for expanded applications such as aptamer selection. A CBT-modified thymidine analogue (CBT-TTP) has been synthesized and used for enzymatic incorporation into DNA. Post-synthesis modifications through condensation with 1,2-aminothiol for installation of a boronic acid moiety or a fluorophore have been achieved. On the third project, H2S has been recognized as an important gasotransmitter and its concentration is relevant to a variety of diseases. A novel fluorescent probe (DNS-Az) has been developed for quantitation of H2S in aqueous solutions. This probe has been used to measure H2S concentrations in the blood.
18
Sim, Neil. "Molecular imaging probes for N-methyl-D-aspartate receptors." Thesis, Durham University, 2014. http://etheses.dur.ac.uk/10816/.
Full textAbstract:
The non-invasive detection of neuronal transmission is of prime importance in order to understand brain function better. This will aid cognitive neuroscience, as well as medical science, in the early detection of diseased states. Herein, approaches to molecular imaging of the NMDA receptor, a receptor subtype of the excitatory neurotransmitter glutamate, through the use of targeted contrast agents, is described. Initially, a series of NMDA receptor-targeted MRI contrast agents was developed based upon a known competitive NMDA receptor antagonist, appended to an N-linked ‘Gd-DOTA’ core that possesses a fast-exchanging water molecule. Their use as responsive MR imaging probes was evaluated in vitro using a neuronal cell line model, and three contrast agents showed large enhancements in cellular relaxation rates. In order to confirm NMDA receptor localisation, derivatives of the lead compounds were also prepared. The derivatives contained a biotin moiety, which allowed direct visualisation of the cell-surface receptors, after addition of an AvidinAlexaFluor®-488 conjugate. Using these derivatives, the specificity and reversibility (in the presence of glutamate) of binding at the NMDA receptor was demonstrated in living cells using laser scanning confocal microscopy. In an attempt to generate a single-component NMDA receptor-targeted optical imaging agent, a very bright europium complex conjugated to an NMDA receptor-binding moiety was synthesised. Unfortunately, upon incubation with a neuronal cell line model, complex localisation appeared to be dictated by the ligand structure and not by the receptor-binding moiety. One emerging imaging technique with potential applications in neuronal imaging is photoacoustic imaging. Two NMDA receptor-targeted photoacoustic imaging agents were synthesised and their ability to label NMDA receptors assessed in vitro. Finally, preliminary in vivo evaluation of the most promising photoacoustic imaging agent is described.
19
Crane, Peter. "Protein based molecular probes by unnatural amino acid incorporation." Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:772076fc-00f2-4ca7-bfa9-3da1ce7093cb.
Full textAbstract:
The "tag & modify" strategy for protein modification relies upon the genetic incorporation of an uncommon or unnatural amino acid into a protein backbone, followed by a chemo-selective modification to yield differentially modified proteins. This thesis describes the creation of a protein-based glycoconjugate tool for interrogating biological function. In Chapter 2, the unnatural amino acid, azidohomoalanine was genetically incorporated into a library of distance defined Np276 proteins via a selective pressure incorporation. Methods to prevent the common post translational modification N-terminal gluconylation were identified, including preliminary work on a small molecule intervention. The proteins were subsequently characterised with respect to other members of the (limited) family of pentapeptide repeat protein and the key biophysical parameters (TM, stability) with relate to it being a multivalent scaffold were investigated. In Chapter 3, An initial investigation into obtaining a selective amine modification initially via N-hydroxysuccinimide esters, led to the discovery (and characterisation) of a clear selectivity for N-terminal proline Isothiocyanate modification. The dual modification of proteins via the N-term Pro & the ubiquitous (glyco) copper(I)-catalysed azide alkyne cycloaddition was subsequently used to generate homogenously dual modified Np276 scaffolds. In Chapter 4, these proteins were then used in a FACS assay against a murine sialoadhesin - chinese hamster ovary cell line, the results showing promise for the further development of multivalent glycated probes of function.
20
Zhu, Wenxia. "Development of Molecular Imaging Probes for Positron Emission Tomography." Case Western Reserve University School of Graduate Studies / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=case1333944487.
Full text
21
Torode, Thomas Adrian. "Molecular probes for the cell walls of brown algae." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/12218/.
Full textAbstract:
The brown algae are an abundant source of renewable biomass that do not require arable land or fresh water for cultivation. Cell walls of the brown algae contain a range of unique polysaccharides with useful bioactivities; namely the sulphated fucans and alginate. The generation and characterisation of ten new monoclonal antibodies (MAbs) towards components of brown algal cell walls are described. Four MAbs, BAM1 to BAM4, recognise un-sulphated (BAM1) and sulphated (BAM2/3/4) structures of the sulphated fucans. Six MAbs, GIN1 to GIN6, recognise different structures of the alginate, ranging from high mannuronate content (GIN4) to high guluronate content (GIN6). The combination of these new MAbs, pre-existing knowledge of the brown algal cell walls and, techniques commonly used in land plant cell walls have allowed an extensive study of cell wall architecture in the brown algae. The extraction and fractionation of the cell wall has revealed that the sulphated fucans and alginate are distributed throughout the cell wall architecture and that there are differences in cell wall architecture between orders of the brown algae. Investigation into the abundance of sulphated fucans in the intertidal zone showed trends for increased sulphated fucan content higher up the intertidal zone (as determined by BAM3 and BAM4), but also revealed a ubiquitously distributed set of sulphated fucans (as determined by BAM1 and BAM2). Within tissues of the algae; sulphate fucans and alginate are spatially distributed both in terms of abundance and incorporation into the cell wall architecture – and these traits are shared between species of Fucus. Use of indirect immunohistochemistry allowed dissection of the sulphated fucan and alginate distribution in muro (in wall); revealing cell type specificity and patterning of the polysaccharides.
22
Vaccaro, Carlos. "Use of luminescence energy transfer probes to detect genetic variants." Thesis, University of North Texas, 2004. https://digital.library.unt.edu/ark:/67531/metadc4566/.
Full textAbstract:
The purpose of this research was to study the hybridization of molecular beacons under different conditions and designs. Data collected suggest that the inconsistency found in the emission intensity of several of these probes may be caused by 3 important factors: length of the probe, nucleotide sequence and, the formation of an alternative complex structure such as a dimer. Of all three factors, dimer formation is the most troublesome, since it reduces the emission of the reporter molecules. A new probe design was used to reduce dimer formation. The emission signal of the improved probe was several folds stronger than those probes with the early design.
In this research, dimer formation is detected, furthermore a new probe with a different design was tested. If dimer formation can be reduced molecular beacons can be integrated into more complex hybridization systems providing an important tool in research and diagnosis of genetic disorders.
23
Exton, S. P. "Synthesis and characterisation of novel luminescent probes." Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.368774.
Full text
24
Duer, Melinda J. "The parametric probes of ligand field theory." Thesis, University of Cambridge, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.304165.
Full text
25
Jain, Mudita 1968. "Algorithms for physical mapping using unique probes." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/290622.
Full textAbstract:
DNA molecules are sequences of characters over a four letter alphabet. Determining the text of the DNA sequence contained in human cells is the goal of the Human Genome Project. The structure of a DNA sequence is reconstructed from a set of shorter fragments sampled from it at unknown locations, as it is usually too long to be determined directly. We consider the problem when the the fragments are very long, and each fragment has a fingerprint consisting of the presence of two or three pre-selected, smaller sequences called probes within it. These probes have a unique location along the original DNA sequence. The fingerprints contain false negative and false positive errors, and the fragments may be chimeric. A physical map of a DNA sequence is a reconstruction of the order of the probes and fragments along it. In short, given a collection of fragments, with fingerprints for each fragment taken from a collection of probes, and parameters that bound the rates of false negatives, false positives, and chimeras in the input data, the problem is to find the most likely probe ordering. Physical mapping is NP-complete when the input data contains errors. To construct physical maps we first determine neighbourhoods of probes and clones that are highly likely to be adjacent on the original DNA sequence. We then use a new, versatile integer linear programming formulation of the problem, to derive heuristics for ordering probes within neighbourhoods. This formulation provides a single, uniform representation for diverse data such as end-clone probes and in-situ hybridization, and provides a natural medium for the integration of previously constructed maps with newer data. We also present an ordering heuristic based upon end-clone data. Finally, we connect these local permutations into a larger, more global probe permutation. For this we use heuristics that have at their core previously mapped data. All heuristics are implemented and evaluated by comparing the computed probe orderings to the original probe orderings for simulated data.
26
Sulistyowati, Emy. "Development of molecular probes to distinguish vesicular-arbuscular mycorrhizal fungi." Title page, Summary and Contents only, 1995. http://web4.library.adelaide.edu.au/theses/09A/09as949.pdf.
Full textAbstract:
Bibliography: leaves 71-79. Almost 80 percent of plant taxa develop vesicular-arbuscular mycorrhizae (VAM) which are symbiotic associations between plant roots and soil fungi. The fungi are biotropic-obligate symbionts. Identification of VAM fungi is currently based on spore characteristics. Molecular techniques provide tools for better and more accurate identification of species, as well as for the examination of genetic variability occuring between individual spores of a single species.
27
Stanton-Humphreys, Megan. "Design, synthesis and application of novel light-activated molecular probes." Thesis, University of Oxford, 2010. http://ora.ox.ac.uk/objects/uuid:1d0905c4-7fba-4796-92a5-848715204950.
Full textAbstract:
Caged compounds are biologically active molecules that are rendered inert by masking an important functionality with a photolabile protecting, ‘caging’, group. The caging group can be removed by irradiation with light to reveal the active compound with restored pharmacological activity with high spatial and temporal control. This technology provides an ideal tool for the study of many chemical, physiological and biological systems. This DPhil dissertation highlights several projects in which caging technology has been employed to address biological problems and questions. The first example of spatially controlled mitochondrial inactivation is reported - a tool for the study of the role of mitochondria in Ca2+ signalling. Caged TRPV1 agonists and antagonists have been developed to probe TRPV1, specifically the location of the agonist-binding site. T cell activation has been controlled with light as a tool to gain insight into the adaptive immune response. Caged sodium channel blockers have been investigated. Wavelength-orthogonal photolysis in a neuronal system has been demonstrated using the neurotransmitters glutamate and GABA - this represents a significant advancement in caging technology. This dissertation also includes investigations into the development of novel caging groups.
28
Guo, Qi. "Improving the discovery of molecular imaging probes through biomathematical modelling." Thesis, University of Oxford, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543482.
Full text
29
Bacigalupo, Maria Candelaria Rogart. "Locked nucleic acid analogues for novel exciplex-based molecular probes." Thesis, University of Manchester, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538490.
Full text
30
Fediv, V. I. "Quantum dot as the basis of multimodal molecular imaging probes." Thesis, БДМУ, 2021. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/18844.
Full text
31
Ogawa, Michihiro. "Photovoltaic devices and molecular imaging probes based on polymeric nanomaterials." 京都大学 (Kyoto University), 2010. http://hdl.handle.net/2433/120889.
Full text
32
Hedayat, Farzaneh. "Investigation of the molecular probes for PM oxidative capacity measurements." Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/98552/1/Farzaneh_Hedayat_Thesis.pdf.
Full textAbstract:
This thesis improved our understanding of the performance of various assays that are employed to investigate the oxidative potential (OP) of the particulate matter (PM) generated from combustion sources. The OP is expressed through the concentration of reactive oxygen species produced by diesel and biodiesel fuels. Although the combustion of the biofuel generates a lower amount of PM, the particles have a higher OP, with the increase being proportional to the oxygen content of the biofuel. Oxygen content does not only influence the OP of the particle phase but also influences the OP of the gas phase.document.getElementsByName("c12_disable_contact")[0].checked = true;
33
Bielanska, Magdalena M. "Telomeric probes for FISH, technical aspects and clinical applications." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape16/PQDD_0026/MQ37095.pdf.
Full text
34
Hirata, Nao. "Molecular Imaging Probes and Radiation-Activated Prodrugs Targeting Tumor Hypoxic Microenvironments: Molecular Design, Synthesis, and Evaluation." 京都大学 (Kyoto University), 2009. http://hdl.handle.net/2433/84827.
Full textAbstract:
Kyoto University (京都大学)0048
新制・課程博士
博士(工学)
甲第14870号
工博第3138号
新制||工||1470(附属図書館)
27292
UT51-2009-K666
京都大学大学院工学研究科物質エネルギー化学専攻
(主査)教授 西本 清一, 教授 大江 浩一, 教授 中條 善樹
学位規則第4条第1項該当
35
Shi, Chao. "Molecular fiber sensor probes based on surface enhanced Raman scattering (SERS) /." Diss., Digital Dissertations Database. Restricted to UC campuses, 2009. http://uclibs.org/PID/11984.
Full text
36
Bai, Ge. "Cell Permeability Studies of AApeptides and Novel Molecular Probes for AD." Scholar Commons, 2016. http://scholarcommons.usf.edu/etd/6173.
Full textAbstract:
Alzheimer's diseases(AD) has been discovered and under research for more than 70 years, However there is no cure for these progressive and devastating diseases. Based on the following hypothsis: Aß metabolite problem/over production result in the accumulation, and lead to aggregation is the cause of Alzheimer’s disease. AApeptide and Melatonin derivatives can bind to Aß and block the aggregation of β amyloid monomers, decrease the toxicity of Aß to neurons and slow the progressive of Alzheimer’s diseases. In addition, AApeptide which mimic transmembrane peptide Tat will have similar transmembrane function. We have set up our goals as follows: 1) Using newly discovered peptidomimetics, AApeptides. We moved on to research to discover their potential of transmembrane activity and anti-Alzheimer's acitiviy. 2) In Addition, studies of small molecule melatonin derivatives were also progressed. Methods include in this research includes bioorganic synthesis, identification of spectroscopy and relative assays targeting on biological efficiency of Anti-Alzheimer’s diseases. The details of which will be described in Chapters. In conclusions, two sets of transmembrane peptidomimetics for drug transportation has been successfully evaluated and potential of AA peptide small molecules, melatonin derivativesare also evaluated. These works have gained good progress in research between AApeptide and Alzheimer’s Diseases. These works also established basis of research in developing peptidomimimetics as potential pharmacies against Alzheimer’s diseases.
37
Adams, Elizabeth L. "Developing molecular probes in arabinoxylan structural analysis using Atomic Force Microscopy." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393318.
Full text
38
Wainman, Yéléna Alexandra. "Developing novel chemical probes for molecular imaging of glycans in cancer." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708565.
Full text
39
Yang, Chaoyong. "Molecular engineering of nucleic acid probes for intracellular imaging and bioanalysis." [Gainesville, Fla.] : University of Florida, 2006. http://purl.fcla.edu/fcla/etd/UFE0015562.
Full text
40
Moorhouse, Alan. "Molecular hydrogen line ratios as probes of shocks in dense clouds." Thesis, University of Edinburgh, 1990. http://hdl.handle.net/1842/28656.
Full textAbstract:
This thesis is concerned with the structure of shocks occurring in dense regions of molec?ular clouds. These shocks are associated with the outflows from young stars, Herbig-Haro objects, expanding HII regions and the interaction of supernovae remnants with molecu?lar clouds. Momentum, mass and energy are imparted to the cloud. A full understanding of the shock process is thus needed if we are to understand the structure of molecular clouds and the impact on star formation. Emission from the near-infrared transitions of molecular hydrogen is commonly excited in these shocks. A major puzzle is that emis?sion is seen at velocities that would collisionally dissociate molecular hydrogen, and this is a central question that this thesis seeks to answer. This is approached observationally by trying to relate the observed emission to shock models. Fairly accurate semi-analytic derivations of the emission spectrum expected from hydrodynamic and magnetohydrodynamic molecular shocks are used to fully explore the parameter space of the initial conditions, without resort to expensive numerical calculations. The emission spectrum is then related to that observed. Most of this work is based on a spectroscopic multi-line study of the near-infrared H2 emission in two sources, the Orion outflow and the supernova remnant IC443. These observations are then compared with those expected from the models. In both sources it is found that planar hydrodynamic jump-type shocks (J) are consistent with the new observations. Whplanar magnetically moderated continuous shocks (C), which have been invoked to explain the emission from the shock in Orion, are not. Neither shock types can explain the intensities of CO rotational lines and the H2 line ratios simultaneously. The high velocities that are observed still present a problem. In IC443 the conclusion is the same but, in addition, the pressure needed to explain the observations is higher than that observed in the supernova remnant. It is suggested that this discrepancy may naturally occur when radiative shocks are driven through a clumpy medium. This approach of using line ratios as shock discriminators is extended by velocity resolved spectroscopy of three highly excited emission lines from Orion. These observa?tions demonstrate that there are no discernible differences in the line ratios with velocity despite the large change in the energies of the upper energy levels involved. It is discussed how this further constrains the shock type and limits the contribution from non-thermal excitation (such as fluorescence). The possible physical processes that could lead to high velocity, shocked molecular hydrogen are then discussed. Models proposed in the past are, it is argued, inadequate. It is then shown that the line ratios observed can be closely matched with non-planar continuous type shocks which occur in a bow shock. The densities and pressures needed are still high. The general conclusions are that previous plane parallel C-shock models invoked to explain the molecular shocks are inconsistent with the observations. The line ratios imply that either J-type shocks, in which the cooling takes a long time compared to the initial heating, or C-type bow shocks which produce a range of temperatures are responsible for the emission. It is finally suggested that C-shocks in gas with a very high magnetic field can produce the high velocity H2 emission observed without dissociating the molecules.
41
Chakraborty, Sourav. "Molecular Probes for Biologically Important Molecules: A Study of Thiourea, Hydroxyl radical, Peroxynitrite and Hypochlorous acid." ScholarWorks@UNO, 2010. http://scholarworks.uno.edu/td/1132.
Full textAbstract:
Numerous chemical species are important to the health of biological systems. Some species can be beneficial at low doses and harmful at high doses. Other species are highly reactive and trigger serious cell damage. Improved methods to detect the presence and activity of such species are needed. In this work, several biologically important species were studied using appropriate analytical techniques. Fluoride is an important species in human physiology. It strengthens teeth and gives protection against dental caries. However, elevated concentrations of fluoride in the body can lead to health problems such as dental and skeletal fluorosis. Reported fluoride sensors used fluorescence quenching methods in determining fluoride concentration. Our study explored synthesis and characterization of 1,8-bis(phenylthioureido) naphthalene (compound 1) as a fluoride sensing molecule. Compound 1 showed a remarkable 40 fold enhancement in fluorescence with 5 eq of fluoride addition. Compound 1 also showed possibility of visual colorimetric sensing with fluoride. Free radical mediated oxidations of biomolecules are responsible for different pathological conditions in the human body. Superoxide is generated in cells and tissues during oxidative burst. Moderately reactive superoxide is converted to peroxyl, alkoxyl and hydroxyl radicals by various enzymatic, chemical, and biochemical processes. Hydroxyl radical imparts rapid, non specific oxidative damage to biomolecules such as proteins and lipids. Superoxide also reacts with nitric oxide in cells to yield peroxynitrite, which is highly reactive and damages biomolecules. Both hydroxyl radical and peroxynitrite readily react with amino acids containing aromatic side chains. Low density lipoprotein (LDL) carries cholesterol in the human body. Elevated concentration of LDL is a potential risk factor for atherosclerosis. Previous research drew a strong correlation between oxidized low density lipoprotein (ox-LDL) and plaque formation in the arterial wall. More importantly, oxidative damage causes structural changes to the LDL protein (apo B-100) which might facilitate the uptake of LDL by macrophages. In this study LDL was exposed to various concentrations of hydroxyl radical peroxynitrite and hypochlorite. Thereafter oxidized amino acid residues in apo B-100 were mapped by LC-MS/MS methods. We found widely distributed oxidative modifications in the apo B-100 amino acid sequence.
42
Mackay, Martha. "The development of fluorescent probes targeting Caspase-3 for detecting apoptosis." Thesis, University of Edinburgh, 2014. http://hdl.handle.net/1842/17972.
Full textAbstract:
The design and development of fluorescent reporters focussed on highly sensitive, specific, and selective imaging of cancer targets is described. These novel optical molecular probes were synthesised with the aim of creating bio-imaging breakthroughs that will aid the clinical analysis of cancer. A specific target of the project was to develop fluorescent reporters for Caspases; intracellular endopeptidases that play an essential role in apoptosis. Lack of activation of the ‘Caspase Cascade’ causes uncontrolled proliferation of cells and has been deemed a ‘Hallmark of Cancer’. In particular, low Caspases-3/7 activities have been associated with a range of cancers, thus molecular detection of Caspases-3/7 activities could therefore lead to advances in oncology. A 14-member FRET library, based upon Caspases-3/7 specific peptide sequences, was initially developed. The cleavage rates and KM values were evaluated for Caspases-3/7, along with the cleavage rates for Cathepsin B, to determine the peptide with the greatest affinity and specificity for Caspase-3. Also developed was a set of internally quenched activity based molecular reporters constructed by attaching fluorophores to a tribranched dendron through the Caspase specific peptide, developed from the FRET Library. The KM values of the dendron probes with Caspase-3 were also evaluated. Furthermore, the dendron reporters were attached to cell penetrating peptides to enable delivery to intracellular Caspase and allow in situ detection of activated Caspase-3 within live cells. In addition, a new labelling moiety was developed enabling dual detection of reporters through fluorescence and MRI imaging. To achieve this, a perfluoro tag (C8F17) was tethered to a Cy5 dye to enable dual detection. The dual 19F-MRI/Cy5 dye was conjugated onto to a cell penetrating peptide to enable in vivo detection of the probe by 19F-MRI and fluorescent imaging.
43
Torres, Martínez Ana. "Molecular nanogels as nanocarriers. Intracellular transport of photosensitizers and nitric oxide probes." Doctoral thesis, Universitat Jaume I, 2021. http://hdl.handle.net/10803/671255.
Full textAbstract:
The preparation of molecular nanogels is reported in this thesis. These new nanoparticles, formed by low molecular weight gelators, represent an exciting alternative to their polymeric counterparts considering their intrinsic characteristics (fully reversible stimuli-regulated assembly, easy biodegradation, excellent biocompatibility and tailored properties). Novel hydrogel@liposome particles were also obtained by molecular gel formation inside liposomes, merging the benefits of liposomal vehicles with the inherent characteristics of molecular gels. The capability of molecular nanogels to incorporate and release actives and act as intracellular carriers was demonstrated, improving the efficiency of photoactive molecules in their biomedical use. Photosensitizers (Rose Bengal and hypericin) showed enhanced cellular uptake and improved performance in photodynamic therapy for cancer. The encapsulation in the nanogels of nitric oxide probes lead to an enhanced cellular uptake of DAF-2 and an increased solubility in water of DAQ.En esta tesis se describe la preparación de nanogeles moleculares. Estas nuevas nanopartículas, formadas por gelantes de bajo peso molecular, son una alternativa a sus homólogos poliméricos por sus características intrínsecas (ensamblado completamente reversible y regulado por estímulos, fácil biodegradación, excelente biocompatibilidad y propiedades a medida). También se obtuvieron nuevos lipogeles moleculares formando un gel molecular dentro de un liposoma, lo que combina los beneficios de los liposomas como vehículos con las características inherentes de los geles moleculares. Se demostró la capacidad de los nanogeles moleculares para actuar como portadores intracelulares, mejorando la eficiencia de moléculas fotoactivas en su uso biomédico. Así, los fotosensibilizadores (Rosa de Bengala e hipericina) mostraron una mejora en la internalización celular y el rendimiento en terapia fotodinámica, mientras que para las sondas de óxido nítrico se vio una mayor internalización celular para DAF-2 y una mejora de la solubilidad para DAQ.
44
Jannasch, Anita. "High performance photonic probes and applications of optical tweezers to molecular motors." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-103696.
Full textAbstract:
Optical tweezers are a sensitive position and force transducer widely employed in physics and biology. In a focussed laser, forces due to radiation pressure enable to trap and manipulate small dielectric particles used as probes for various experiments. For sensitive biophysical measurements, microspheres are often used as a handle for the molecule of interest. The force range of optical traps well covers the piconewton forces generated by individual biomolecules such as kinesin molecular motors. However, cellular processes are often driven by ensembles of molecular machines generating forces exceeding a nanonewton and thus the capabilities of optical tweezers. In this thesis I focused, fifirst, on extending the force range of optical tweezers by improving the trapping e fficiency of the probes and, second, on applying the optical tweezers technology to understand the mechanics of molecular motors. I designed and fabricated photonically-structured probes: Anti-reflection-coated, high-refractive-index, core-shell particles composed of titania. With these probes, I significantly increased the maximum optical force beyond a nanonewton. These particles open up new research possibilities in both biology and physics, for example, to measure hydrodynamic resonances associated with the colored nature of the noise of Brownian motion. With respect to biophysical applications, I used the optical tweezers to study the mechanics of single kinesin-8. Kinesin-8 has been shown to be a very processive, plus-end directed microtubule depolymerase. The underlying mechanism for the high processivity and how stepping is affected by force is unclear. Therefore, I tracked the motion of yeast (Kip3) and human (Kif18A) kinesin-8s with high precision under varying loads. We found that kinesin-8 is a low-force motor protein, which stalled at loads of only 1 pN. In addition, we discovered a force-induced stick-slip motion, which may be an adaptation for the high processivity. Further improvement in optical tweezers probes and the instrument will broaden the scope of feasible optical trapping experiments in the future.
45
Wagner, Janine. "Migration of molecular probes from can coatings into foods and food simulants." Thesis, University of Leeds, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.496207.
Full text
46
Okoh, Okoh Adeyi. "The synthesis and evaluation of non-targeted near-infrared heptamethine molecular probes." Thesis, University of Central Lancashire, 2013. http://clok.uclan.ac.uk/9232/.
Full textAbstract:
Detecting and quantifying biomolecules is an important tool in biological research. Ideal dyes have to have a number of characteristics i.e. low toxicity and limited autofluorescence. The properties of near infrared dyes make these ideal for cell and tissue imaging. The work within this thesis focuses on the development of three families of NIR dyes (linear, rigid and substituted polymethine) and these are actively compared against the clinical standard Indocyanine Green (ICG) and its structural derivative New Indocyanine Green (IR-820). The ultimate aim being to identify dyes which can be used alongside the clinical standards. The compounds developed within this thesis are structurally based on the NIR heptamethine cyanine (Cy7) dyes. To expand, variations fall into three categories, linear, rigid and polymethine substituted, each being synthesised using either existing methodology or through the development of a novel cascade reaction. The photophysical properties of each dye have been evaluated experimentally, focusing on absorption and emission wavelengths, fluorescence quantum yields and Stokes shifts. It is noted that most dyes synthesised within this thesis, show comparable Stokes shift but increased fluorescence quantum yields when compared against ICG and IR-820. All dyes absorb and emit within the NIR region based on excitation at 785 nm. The growth inhibition characteristic is an important criterion which determines the practical use of the dyes in living cells. Most of the dyes which showed no growth inhibition were the dyes bearing the sulfonic acid group, suggesting the sulfonic acid limited cellular uptake as a result of decreased membrane permeability. Dyes possessing growth inhibitory characteristics all contain linear N-alkyl moieties. It is thus postulated that the increased lipophilicity of these molecules result in increased lipid distortion and subsequent toxicity.
47
Arnberg, Elise. "Investigation of molecular probes for pH determination with electrospray ionization mass spectrometry." Thesis, Uppsala universitet, Institutionen för kemi - BMC, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-381962.
Full text
48
Condie, Allison Gamble. "Development of Molecular Probes for Biomedical Imaging of Cancer and Neurological Disease." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1432726238.
Full text
49
Kim, Youngmi. "Molecular engineering of multifunctional nucleic acid probes for bioanalytical and biomedical applications." [Gainesville, Fla.] : University of Florida, 2008. http://purl.fcla.edu/fcla/etd/UFE0023647.
Full text
50
GAMBINO, GIUSEPPE. "High-relaxivity systems and molecular imaging probes for Magnetic Resonance Imaging applications." Doctoral thesis, Università del Piemonte Orientale, 2014. http://hdl.handle.net/11579/46171.
Full text