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Bryant, William Barton. "Caspases and caspase regulators in Lepidoptera and Diptera." Diss., Manhattan, Kan. : Kansas State University, 2009. http://hdl.handle.net/2097/2612.
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Howle, Christopher Roy. "Decay processes of photoexcited molecules in the VUV : comparison with ion/molecule reactions." Thesis, University of Birmingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421712.
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Rennie, Emma E. "Decay mechanisms of photoexcited molecular ions." Thesis, Heriot-Watt University, 1997. http://hdl.handle.net/10399/658.
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Mendive, Tapia David. "Computational modelling of excited state decay in polyatomic molecules." Thesis, Imperial College London, 2013. http://hdl.handle.net/10044/1/11149.
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The introduction of general numerical methods in the form of widely available software can have a dramatic effect on the development of a scientific field. In electronic structure theory, for example, general-purpose programs (such as Gaussian, ADF, MOLPRO,. . . ) combined with better computational resources have in part led to molecular electronic structure calculations becoming a ubiquitous tool in chemical research. Similarly, quantum dynamics methods based on coupled time-evolving Gaussian basis sets and molecular potential energy surfaces calculated on-the-fly hold out similar promise in the study of non-adiabatic processes, because of their generality and freedom from ad hoc assumptions. Therefore, the aim of this thesis is to investigate the convergence and applicability of quantum dynamics calculations with a fully variational coupled Gaussian basis set description, termed variational Multi-Con guration Gaussian (vMCG). It is suggested that the vMCG approach provides a way to balance accuracy against computational cost for molecules of comparable size by choosing the number of coupled Gaussian product basis functions and a middle way forward between grid-based and trajectory surface hopping approaches to non-adiabatic molecular quantum dynamics calculations. In order to prove the suitability of vMCG we show its application to three problems of chemical interest: the study of fulvene excited state decay, the prediction of a coherent control mechanism for the same system and the benchmarking of an electronic population dynamics model for electronic transitions when occurring through a conical intersection. In the long term, the development of vMCG is expected to have a major impact, allowing nonadiabatic dynamics simulations to be made not only by theoreticians, but also by non-specialists and experimentalists in both industry and academia.Chapter 1: Modelling Excited State Decay [Diagrams appear here. To view, please open pdf attachment] This chapter introduces and reviews the current state-of-the-art modelling of non-adiabatic processes in molecular systems. This is a challenging topic since the simulation must treat simultaneously the motion of the nuclei and the electrons, which are coupled together. It is concluded that a wide range of methodologies are available. However, when looking for a general tool for the study of non-adiabatic processes, quantum dynamics methods based on coupled time-evolving Gaussian basis sets such as the Direct Dynamics variational Multi-Con guration Gaussian (DD-vMCG) wavepacket method, as well as to other related methods - such as Ab Initio Multiple Spawning (AIMS, FMS)[1, 2] and Multi-Con gurational Ehrenfest (MCE)[3, 4] - seem to be an especially suitable choice because of their generality and freedom from ad hoc assumptions. Chapter 2: variational Gaussian nuclear wavepackets [Diagrams appear here. To view, please open pdf attachment] This chapter describes three possible time-evolving Gaussian basis sets for use in non-adiabatic quantum dynamics based on the Direct Dynamics variational Multi-Con guration Gaussian (DD-vMCG) wavepacket method. These general model representations are compared using model calculations in a simple harmonic oscillator and describing their connections to other work. It is suggested that the fully variational nuclear wavefunction, termed vMCG (variational Multi-Con guration Gaussian) is a very convenient formulation leading towards a realistic sampling of the phase space without the initial conditions (i.e. initial disposition and momentum) being so important when using a su cient amount of coupled Gaussian basis functions. Chapter 3: Fulvene S1/S0 Excited State Decay [Diagrams appear here. To view, please open pdf attachment] The vMCG (variational Multi-Con guration Gaussian) approach described in Chapter 2 is benchmarked in a realistic system by modelling the radiationless decay from an electronic excited state through an extended conical intersection seam. As a benchmark system, we model the radiationless decay of fulvene from its rst electronic excited state and monitor two associated properties: the spatial extent to which the conical intersection seam is sampled and the timescale and stepwise nature of the population transfer. We illustrate how the use of a fully variational nuclear wavefunction provides a way to balance accuracy against computational cost for molecules of comparable size by choosing the number of coupled Gaussian product basis functions. Chapter 4: Controlling Fulvene S1/S0 Decay [Diagrams appear here. To view, please open pdf attachment] Direct quantum dynamics simulations using the vMCG (variational Multi- Con guration Gaussian) approach were performed in order to model the control of the stepwise population transfer in fulvene. As shown in Chapter 3, ultra-fast internal conversion takes place centred on the higher-energy planar/sloped region of the S1/S0 conical intersection seam. Therefore, two possible schemes for controlling whether stepwise population transfer occurs or not | either altering the initial geometry distribution or the initial momentum composition of the photo-excited wavepacket - were explored. In both cases, decay took place instead in the lower-energy twisted/peaked region of the crossing seam, switching o the stepwise population transfer. This absence of re-crossing is a direct consequence of the change in the position on the intersection at which decay occurs and its consequences should provide an experimentally observable fingerprint of this system. Chapter 5: A population transfer model for intramolecular electron transfer [Diagrams appear here. To view, please open pdf attachment] The aim of this chapter is to further prove the applicability of the vMCG (variational Multi-Con guration Gaussian) approach by benchmarking an approximate population dynamics model in Jahn-Teller systems. The socalled Density Matrix Non-Equilibrium Fermi Golden Rule (DM-NFGR) can be seen as a simpli ed version of vMCG, in which the nite Gaussian basis set and on-the-fly evaluation of the nuclear Hamiltonian are eliminated via use of the density matrix formalism and a perturbational treatment of the equations. This has three clear advantages: firstly, it allows us to extend the maximum molecular size considerably; secondly, we can relate the population dynamics to an analytical time-dependent rate expression; and finally, temperature effects can be included in the simulations. Benchmark calculations for the 2,6-bis(methylene) adamantyl (BMA) radical cation support the reliability of the results.
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Xiong, Ting. "Modeling of Decay Rate for Molecules at an Island Surface." PDXScholar, 1995. https://pdxscholar.library.pdx.edu/open_access_etds/5198.
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The decay rates for molecules at rough surfaces are studied via an island surface model, with particular emphasis on the effect due to the distribution of surface roughness. Two extreme cases are studied when the surface islands distribute themselves evenly and when they coalesce to form local clusters at the molecule-substrate interface. The optical properties of the interfacial layer in these two cases are described by the Maxwell-Garnett and the fractal-cluster models, respectively. Among other results, it is found that both enhancement and suppression of the surface-induced decay rates are possible due to the presence of roughness, with more dramatic suppression taking place when the surface islands coalesce to form clusters.
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Beelman, Clare Ann 1969. "The control ofmRNA decay in Saccharomyces cerevisiae." Diss., The University of Arizona, 1996. http://hdl.handle.net/10150/289588.
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Control of mRNA degradation is an important step in the regulation of gene expression. In Saccharomyces cerevisiae, pathways of mRNA decay have been determined and have provided a framework for understanding how mRNA decay is controlled. I have studied how the process of translation affects the decay mechanism of a yeast transcript and I have isolated and characterized yeast mutants that exhibit reduced rates of mRNA decay. The process of translation has been shown to affect mRNA decay rates in eukaryotes. However, using a MFA2 mRNA that cannot be translated due to insertion of secondary structure in its 5' untranslated region, I have determined that translation of the MFA2 mRNA is not required for its degradation. This observation demonstrates that translation of an mRNA, per se, is not required for the normal kinetics or mechanism of mRNA decay. Additionally, I have demonstrated that the translational inhibitor, cycloheximide, reduces the rate at which the MFA2 transcript is decapped. Inhibition of decapping occurs even on MFA2 transcripts that cannot be translated due to insertion of secondary structure. This result suggests that the general stabilizing effects of translational inhibitors on mRNAs may not be due to the inhibition of translation of these transcripts. The identification of mRNA decay pathways in yeast, deadenylation-dependent decapping and deadenylation-independent decapping, provided a basis by which gene products required for mRNA decay through these pathways could be identified. To this end, a screen of mutant yeast strains was undertaken. I have isolated and characterized two mutants, mrt1 and mrt3, that exhibit reduced rates of deadenylation-dependent decapping on several yeast transcripts. This result suggests that the MRT1 and MRT3 gene products promote deadenylation-dependent mRNA decapping. A third mutant, dcp1, was also isolated, and the wild-type DCP1 gene was identified. Characterization of dcp1/ mutants by myself and others revealed that the DCP1 gene encodes the decapping enzyme, or an essential component of the decapping enzyme, required for both deadenylation-dependent and deadenylation-independent mRNA decapping. This result demonstrates that the DCP1 gene product, Dcp1p, is required for all known mRNA decapping in yeast.
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Tucker, Morgan Dean. "Deadenylation and mRNA decay in Saccharomyces cerevisiae." Diss., The University of Arizona, 2001. http://hdl.handle.net/10150/289856.
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The process of mRNA turnover is a critical component of the regulation of gene expression. In the past few years, a discrete set of pathways for the degradation of polyadenylated mRNAs, in eukaryotic cells have been described. The major pathway of mRNA degradation in yeast occurs by deadenylation of the mRNA, which primarily leads to a decapping reaction, thereby exposing the mRNA to rapid 5' to 3' exonucleolytic degradation. A critical step in the primary pathway is decapping, since it effectively terminates the mRNA's existence and is the site of numerous control inputs. I discuss the properties of the decapping enzyme and how its activity is regulated to give rise to differential mRNA turnover. The major pathways of mRNA turnover in eukaryotic cells are initiated by shortening of the poly(A) tail. In this work, I demonstrate by several criteria that CCR4 and CAF1 encode critical components of the major cytoplasmic deadenylase in yeast. First, both Ccr4p and Caf1p are required for normal mRNA deadenylation in vivo. Second, both proteins localize to the cytoplasm. Third, Caf1p co-purifies with poly(A) specific exonuclease activity, and this activity is dependent on the presence of Ccr4p. Interestingly, because Ccr4p and Caf1p have been shown previously to interact with transcription factors, these results suggest an unexpected link between mRNA synthesis and turnover. Both the Ccr4 and Caf1 proteins have significant homology to known exonucleases, in this work I demonstrate by several criteria that CCR4 encodes the catalytic subunit of the deadenylase. First, over-expression of Ccr4p rescues the deadenylation defects of a caf1Δ strain, indicating that Caf1p is not essential for deadenylation. Second, purification of Ccr4p co-purifies with poly(A) specific exonuclease activity, and this activity is not dependent on the presence of Caf1p. Third, point mutants in predicted catalytic residues of the Ccr4p exonuclease domain result in deadenylation defects in vivo and in vitro. The strong conservation of Ccr4p and Caf1p in other eukaryotes suggests that they will function in the process of deadenylation in other organisms.
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Vigrow, Anne. "Molecular analysis of the dry rot fungus Serpula lacrymans." Thesis, University of Abertay Dundee, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306791.
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Ferraiuolo, Maria A. "The role of eIF4AIII and 4E-T in mRNA decay /." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103156.
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Translational control is crucial to balancing the cell's protein output and genetic expression. The substrate of the translational machinery---messenger RNA (mRNA)---is itself subject to regulation. The lifetime of an mRNA is limited and therefore mRNA decay is a critical step in the regulation of gene expression. Translation and mRNA decay are intimately related processes as they both handle the cell economy. mRNAs are generally in a balancing act between the translational and the repression/decay machinery, which ultimately decides the fate of an mRNA and its protein expression rate. In fact, translation affects the rate of mRNA decay. For instance, aberrant messages which contain a premature-termination codon (PTC) require ribosome scanning in order to read the message, discover the mistake, and essentially prompt its destruction. Here, a relationship between the nuclear translation-like factor---eIF4AIII, the nuclear import factor of cIF4E---4E-T, and mRNA decay was discovered. eIF4AIII is a nuclear protein that interacts physically or functionally with translation initiation factors eIF4G and eIF4B, respectively, and shares strikingly high identity with the initiation factors eIF4AI/II. This work demonstrates that eIF4AIII but not eIF4AI is required for nonsense-mediated decay (NMD). NMD is a surveillance mechanism in eukaryotes which degrades the mRNA when a PTC is present. NMD is a splicing and translation-dependent event in mammalians. We show eIF4AIII is deposited at the exon-exon junction during splicing, is a shuttling protein, and is necessary for NMD. At steady state, 4E-T is predominantly cytoplasmic and is concentrated in bodies that conspicuously resemble the recently described Processing bodies (P-bodies), which are sites of mRNA decay. We demonstrate that 4E-T colocalizes with mRNA decapping factors in bona fide P-bodies and that its binding partner, eIF4E, is tethered to P-bodies in a 4E-T dependent manner. Moreover, 4E-T controls mRNA half life. We demonstrate that 4E-T interaction with eIF4E represses translation, which is thought to be a prerequisite for targeting of mRNAs to P-bodies. Hence, analysis of prospective translation factors has led to elucidation of mRNA decay pathways.
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Dougherty, Julie Ann. "Decay of Beta-Globin mRNA in Erythroid Cells." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397499022.
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Buth, Christian. "Non-Hermitian perturbation theory for the electronic decay of excited and ionized molecules and identification of the electronic decay processes in the Auger decay of core-ionized Xenon-Fluorides." [S.l. : s.n.], 2002. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB10236341.
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Presnyak, Vladimir. "Effects of Codon Usage on mRNA Translation and Decay." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1427387336.
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McDowell, Helen Elizabeth. "Molecular analysis of wet rot organisms : application to conservation of maritime artifacts." Thesis, University of Abertay Dundee, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.316045.
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Kinney, Emma. "Decoupling of HSV1 Vhs protein mRNA decay and translation stimulation." Thesis, University of Missouri - Kansas City, 2013. http://pqdtopen.proquest.com/#viewpdf?dispub=1543940.
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Herpes Simplex Virus Type 1 is a member of the alphaherpesvirinae subfamily within the family Herpesviridae. This virus has both a lytic and latent cycle. Primary infection occurs when the virus enters epithelial cells around the mucosal lining of the nose and mouth. Within the epithelial cells, the virus undergoes an active lytic infection, causing an ulcerated blister, more famously known as a 'cold sore' or 'fever blister'. Once HSV enters the nearby sensory neurons the genome is transported to the neuronal cell body where its latency associated transcripts are activated and the virus remains in a dormant latent cycle until reactivation, when the virus is transported back down the axon to the epithelial cells at or near the site of initial infection. The Virion Host Shutoff protein is a tegument protein from HSV1 and acts as a ribonuclease, degrading both cellular and viral mRNAs, making the course of viral infection more efficient. A study by Saffran, Read and Smiley uncovered an unexpected new function of Vhs: stimulation of translation from some IRESs. An IRES is a section of mRNA with a high level of secondary structure, capable of inducing cap-independent translation. In similar experiments utilizing a bicistronic reporter transcript, I sought to discover whether or not these two functions of the Vhs protein could be de-coupled. Experiments involved dually transfecting HeLa cells with different Vhs mutants across a range of Vhs plasmid concentrations and the bicistronic reporter construct. Levels of reporter activity were measured from cell lysates 36 hours after transfections and provided a measurement of the control at the level of translation. As the cellular Bip IRES element was present between the cistrons, the 3' cistron provided a measure of IRES stimulation. The Results revealed examples of Vhs mutants in which the two activities had been separated. It is unknown what role IRES stimulation could play during Herpesvirus infection, although it is interesting to note that some HSV1 genes have IRES like elements within the 5' UTR. Future experiments can be done to investigate whether or not Vhs is actively recruiting transcription initiation factors to these IRES elements.
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Mazzochette, Mark Joseph. "Shedding Light on Decay Kinetics of Critical Wastewater Bacteria with Molecular Tools." Thesis, Virginia Tech, 2013. http://hdl.handle.net/10919/23165.
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Decay kinetics of bacteria in biological wastewater treatment systems are vital to efficient design and operation of treatment plants. Of special concern are decay characteristics of fecal indicator organisms, which can aid design of wastewater treatment processes to eliminate fecal pathogens. This study focuses on characterizing the decay of three strains of the key fecal indicator bacterium, Escherichia coli, and comparing microbial techniques for quantifying decay rates. Traditional metrics for monitoring decay include volatile solids and plate counts, which may not provide the full picture of specific decay dynamics. In particular, the viable-but-not-culturable growth phase is challenging to assay. Recently, more specific molecular techniques have been developed, such as DNA and RNA extraction with qPCR and RT-qPCR, ATP assays and live/dead cell-staining. However, these assays have not been widely accepted or bench-marked against traditional techniques. It is expected that molecular assays will generate kinetic constants that better reflect the viability and activity of the bacteria as they decay, generating a more integrated understanding of the decay process. Cells grown in pure culture were spiked into microreactors and subjected to a variety of time/temperature treatments in both buffered pure culture and sludge matrices. These scenarios were intended to mimic on a small scale typical waste treatment processes, more specifically pasteurization, thermophilic digestion and land application. Results indicate decay curves similar to traditional curves but with constants that vary with respect to the strains and the characterization methods used. The foundation laid by this work can be utilized in further studies involving other organisms in a variety of environmental scenarios.Master of Science
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Richards, Elliott Grant. "The Role of Decay Accelerating Factor in the Pathogenesis of Endometriosis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1619689609524397.
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Stewart, Beverly. "Computational chemistry applied to the excited state decay of molecular photonic devices." Thesis, University of Newcastle Upon Tyne, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538922.
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Caló, A. (Antonio). "Electron spectroscopy of atoms and molecules using synchrotron radiation, UV radiation and electron impact." Doctoral thesis, University of Oulu, 2007. http://urn.fi/urn:isbn:9789514286650.
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The present thesis investigates the electronic structure of selected atoms and molecules in vapor phase. Electron spectroscopy is applied for studying the electronic transitions following excitation and ionization with electron and photon bombardment. The work focuses on the photoionization and Auger decay of selected noble gasses, and on the photoionization and Auger decay of core ionized or resonant excited alkali halide molecules. The experimental results are compared with theoretical predictions.
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Chen, Ying-Hsin. "UNDERSTANDING MECHANISMS THAT COUPLE TRANSLATION ELONGATION AND MRNA DECAY." Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case1522684403630693.
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Watkin, S. "Excitation and decay of stark mixed n=2 states of atomic hydrogen." Thesis, University of Stirling, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.354060.
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Bucci, Robert Joseph. "Molecular based identification of wood decay fungi from two field sites in Mississippi." Master's thesis, Mississippi State : Mississippi State University, 2008. http://library.msstate.edu/etd/show.asp?etd=etd-06182008-141603.
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Skoglund, Lena. "Molecular Mechanisms of Frontotemporal Lobar Degeneration." Doctoral thesis, Uppsala universitet, Institutionen för folkhälso- och vårdvetenskap, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-9550.
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The aim of this thesis was to identify genetic factors involved in frontotemporal lobar degeneration (FTLD), a neurodegenerative disorder clinically characterised by a progressive change in personality, behaviour and language. FTLD is a genetically complex disorder and a positive family history is found in up to 40% of the cases. In 10-20% of the familial cases the disease can be explained by mutations in the gene encoding the microtubule associated protein tau (MAPT). In the first study we describe the clinical and neuropathological features of a Finnish family with FTLD caused by a mutation in MAPT. We also provide evidence that the pathogenic mechanism of this mutation is through altered splicing of MAPT transcripts. Recently, mutations in the gene encoding progranulin (PGRN) were identified as a major cause of FTLD. In the second study we describe a Swedish family with FTLD caused by a frameshift mutation in PGRN. We provide a clinical and neuropathological description of the family, as well as evidence that the pathogenicity of this mutation is through nonsense-mediated decay of the mutant mRNA transcripts and PGRN haploinsufficiency. In the third study we describe a novel PGRN splice site mutation and a previously described PGRN frameshift mutation, found in a mutation screen of 51 FTLD patients. We describe the clinical and neuropathological characteristics of the mutation carriers and demonstrate that haploinsufficiency is the pathogenic mechanism of the two mutations. In the fourth study we investigate the prevalence of PGRN and MAPT gene dosage alterations in 39 patients with FTLD. No gene dosage alterations were identified, indicating that variations in copy number of the PGRN and MAPT genes are not a common cause of disease, at least not in this FTLD patient collection.
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Noah, Ramsey S. "Bimolecular recombination and complete photocurrent decay in metallophthalocyanine thin films." California State University, Long Beach, 2013.
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Thomas, Marshall Peter. "Novel Roles for Ribonucleic Acids in Programmed Cell Death." Thesis, Harvard University, 2014. http://nrs.harvard.edu/urn-3:HUL.InstRepos:13094353.
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Apoptosis is a tightly coordinated program to shut down and dismantle a cell, characterized by mitochondrial outer membrane permeabilization (MOMP), caspase activation to cleave hundreds of proteins, DNA fragmentation, and blocked translation. Little is known about the fate of RNA as cells die, even though apoptosis has been intensively studied for decades. Here I show that mRNAs, but not noncoding RNAs (ncRNAs), are rapidly and globally degraded during apoptosis. The decay occurs in many cell types responding to diverse apoptotic stimuli. mRNA decay is triggered early in apoptosis, preceding membrane lipid scrambling, genomic DNA fragmentation and modifications to translation initiation factors that might cause translational arrest. mRNA decay depends on MOMP and is amplified by effector caspase activity. 3' truncated mRNA decay intermediates with nontemplated uridylate-rich tails are generated during apoptosis and degraded by the 3' to 5' exonuclease DIS3L2. Knockdown of DIS3L2 reduces apoptotic mRNA decay and partially rescues cell death. I propose that global mRNA decay is a new hallmark of apoptosis caused by the concerted action of several nucleases.
I also report a new role for RNA and DNA in directing cytotoxic leukocyte proteases to their substrates. When cytotoxic lymphocytes recognize and attack infected or cancerous cells, they deliver the granzyme (Gzm) serine proteases into the target cell. The Gzms cleave diverse protein substrates to orchestrate cell death. RNA binding proteins are highly enriched in unbiased proteomic screens of Gzm protein substrates. I hypothesized that the Gzms are guided to nucleic acid binding protein targets via direct binding to RNA or DNA. Using fluorescence polarization, I show that the Gzms and related leukocyte proteases bind to RNA and DNA with low nanomolar affinity. Nucleic acid binding by the Gzms facilitates their cleavage of RNA and DNA binding proteins, and guides them into target cell nuclei and onto neutrophil extracellular traps. Nucleic acid binding provides an elegant mechanism to confer protease substrate specificity for cleavage of nucleic acid-binding proteins that play essential roles in cellular gene expression and cell proliferation.
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Kopelke, Sören [Verfasser], and Lorenz S. [Akademischer Betreuer] Cederbaum. "Quenching of Molecular Photodissociation by Interatomic Coulombic Decay / Sören Kopelke ; Betreuer: Lorenz S. Cederbaum." Heidelberg : Universitätsbibliothek Heidelberg, 2011. http://d-nb.info/117978300X/34.
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Serdar, Lucas D. "The Functional Relationship between the Nonsense-Mediated mRNA Decay Pathway and the Prematurely Terminating Ribosome." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554304118763865.
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Hendricks, Gabriel L. "Modulating Influenza and Heparin Binding Viruses’ Pathogenesis with Extrinsic Receptor Decoy Liposomes: A Dissertation." eScholarship@UMMS, 2013. http://escholarship.umassmed.edu/gsbs_diss/674.
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Influenza is a severe disease in humans and animals, causing upwards of 40,000 deaths every year in America alone. Influenza A virus (IAV) also causes periodic pandemics every 10 to 50 years, killing millions of people. Despite this, very few effective therapies are available. All strains of IAV are prone to developing resistance to antibodies due to the high mutation rate in the viral genome. Because of this mutation rate, a yearly vaccine must be generated before every flu season, and efficacy varies year to year. IAV has also mutated to escape several of the clinically-approved small molecule inhibitors. A therapeutic agent that targets a highly conserved region of the virus could bypass resistance and also be effective against multiple strains of IAV. IAV attachment is mediated by many individually weak hemagglutinin–sialic acid interactions that all together make a strong attachment to a host cell. Polymerized sialic acid analogs can recreate these interactions and block infection. However, they are not ideal therapeutics due to solubility issues and in vivo toxicity. We used liposomes as a novel means for delivery of the sialic acid-containing glycan, sialylneolacto-N-tetraose c (LSTc). LSTcbearing decoy liposomes form multivalent, polymer-like interactions with IAV. Decoy liposomes competitively bind IAV in hemagglutination inhibition assays and inhibit infection of target cells in a dose-dependent manner. LSTc decoy liposomes co-localize with IAV, while control liposomes do not. Inhibition is specific, as inhibition of Sendai virus and respiratory syncytial virus is not observed. In contrast, monovalent LSTc does not bind IAV or inhibit infectivity. LSTc decoy liposomes prevent the spread of IAV during multiple rounds of replication in vitro and extend survival of mice challenged with a lethal dose of virus. Considering the conservation of the hemagglutinin binding pocket and the ability of decoy liposomes to form high-avidity interactions with IAV hemagglutinin, our decoy liposomes have potential as a new therapeutic agent against emerging strains.
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Dorstyn, Loretta Esterina. "The identification and characterisation of two novel Drosophila caspases, DRONC and DECAY." Title page, contents and abstract only, 2001. http://web4.library.adelaide.edu.au/theses/09PH/09phd718.pdf.
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Includes a list of publications co-authored by the author during the preparation of this thesis. Thesis amendments in back leaf. Includes bibliographical references (leaves 123-168). The studies described concentrate on the cloning and characterisation of the two Drosophila caspases, DRONC and DECAY
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Yang, Feng. "Endoribonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polysome-bound substrate." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1111267563.
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Thesis (Ph. D.)--Ohio State University, 2005.Title from first page of PDF file. Document formatted into pages; contains xviii, 216 p.; also includes graphics (some col.) Includes bibliographical references (p. 196-216). Available online via OhioLINK's ETD Center
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Inhester, Ludger [Verfasser], Helmut [Akademischer Betreuer] Grubmüller, Jörg [Akademischer Betreuer] Enderlein, and Ulf [Akademischer Betreuer] Saalmann. "Auger decay in double core ionized molecules / Ludger Inhester. Gutachter: Helmut Grubmüller ; Jörg Enderlein ; Ulf Saalmann. Betreuer: Helmut Grubmüller." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2013. http://d-nb.info/1044768398/34.
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Schnorr, Kirsten [Verfasser], and Robert [Akademischer Betreuer] Moshammer. "XUV Pump-Probe Experiments on Electron Rearrangement and Interatomic Coulombic Decay in Diatomic Molecules / Kirsten Schnorr ; Betreuer: Robert Moshammer." Heidelberg : Universitätsbibliothek Heidelberg, 2014. http://d-nb.info/1177811189/34.
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Jia, Jieshuang. "Study of molecules with nonsense mutation correction capacity." Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S009/document.
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Les mutations non-sens représentent environ 10% des mutations trouvées dans les maladiesgénétiques héréditaires. Les ARNm portant une mutation non-sens sont dégradés par un mécanismeappelé nonsense-mediated mRNA decay (NMD) pour empêcher la synthèse de protéines tronquéesqui pourraient être toxiques ou non-fonctionnelles pour la cellule. Plusieurs stratégies ont étédéveloppées pour sauver une mutation non-sens. Dans notre laboratoire, nous étudions deux d'entreelles qui sont (i) l'inhibition du NMD et (ii) l'activation de la translecture du PTC qui est un mécanismeconduisant à l'incorporation d'un acide aminé à la position du PTC. Pour trouver de nouveauxmoyens thérapeutiques pour les maladies génétiques héréditaires, notre laboratoire a testédifférentes molécules par criblage, pour identifier celles qui ont la capacité d'inhiber le NMD. Chaquemolécule sélectionnée par le crible est étudiée afin de mesurer son efficacité d'inhibition du NMD etd'activation de la translecture. Nous avons ainsi montré que i'amlexanox non seulement inhibe NMDmais active également la translecture du PTC. Cependant, l'efficacité de I'amlexanox reste modeste.Nous avons donc recherché d'autres familles de molécules qui sont capables de sauver une mutationnon-sens et qui ont une efficacité de correction des mutations non sens meilleure ou démontrentune plus grande spécificité. Dans mon étude, j'ai trouvé deux familles de protéines particulières quesont les inducteurs d'apoptose et les inhibiteurs du cytosquelette. J'ai trouvé que les inducteursd'apoptose peuvent inhiber le NMD en activant les caspases qui clivent les facteurs du NMD (UPF1 etUPF2). J'ai aussi montré que les inhibiteurs du cytosquelette peuvent inhiber le NMD et que certainsd'entre eux peuvent activer la translecture de PTC en induisant les facteurs du NMD (UPF1 et / ouUPF3X) à se concentrer dans les P-bodies et/ou dans d'autres foyers cytoplasmiques. Les rendementsde ces molécules sur l'inhibition du NMD sont similaires ou meilleure que I'amlexanox. Les inducteursd'apoptose et les inhibiteurs du cytosquelette nous démontrent qu'il est possible de trouver desmolécules très différentes capables de corriger des mutations non sens avec une bonne efficacitéNonsense mutations represent approximately 10% of mutations found in the inherited geneticdiseases. mRNAs harboring a nonsense mutation are rapidly degraded by a quality-controlmechanism called nonsense-mediated mRNA decay (NMD) to prevent the synthesis of toxic or nonfunctionaltruncated proteins. Some stratégies have been developed to correct nonsense mutations.In our lab, we study 2 of them which are (i) the NMD inhibition and (ii) the PTC-readthroughactivation which is a mechanism leading to the incorporation of an amino-acid at the PTC position. Todesign new therapeutic tools for the inherited genetic diseases, our lab tested molecules byscreening to find ones with the capacity of NMD inhibition. For each molecules selected in thescreen, we measure the efficiency of NMD inhibition and PTC-readthrough activation of thesemolecules in cell lines harboring a nonsense mutation. We have shown that amlexanox not onlyinhibits NMD but also activâtes PTC readthrough. But the efficacy of amlexanox is still low. Wewanted to find other families of molecules capable of rescuing the expression of nonsense mutationcontainingmRNA with a higher efficacy or with some specificity. In my study, I found two spécialfamilies, one is the family of apoptosis inducers and the other is the family of cytoskeleton inhibitors.I found that apoptosis inducers can inhibit NMD by activating caspase pathway and cleave NMDfactors (UPF1 and UPF2). I also found that cytoskeleton inhibitors can inhibit NMD and some of themcan activate PTC-readthrough by inducing NMD factors (UPF1 or/and UPF3X) to concentrate in Pbodiesor in other cytoplasmic foci. The efficiencies of these molecules on NMD inhibition are similaror higher than amlexanox. Apoptosis inducers and cytoskeleton inhibitors demonstrated thatmolecules which can inhibit NMD or/and activate PTC-readthrough can be found and candemonstrate a higher correction of nonsense mutation efficiency than the existing molecules(ataluren or amlexanox for example)
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Perrie, W. "Polarisation correlation in the two-photon decay of metastable atomic deuterium and a test of Bell's inequality." Thesis, University of Stirling, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.370538.
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Gunnell, Mark K. "The Detection and Molecular Evolution of Francisella tularensis Subspecies." BYU ScholarsArchive, 2015. https://scholarsarchive.byu.edu/etd/5696.
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Francisella tularensis is the etiological agent of tularemia, a zoonotic disease with worldwide prevalence. F. tularensis is a highly pathogenic organism and has been designated as a potential biothreat agent. Currently there are four recognized subspecies of F. tularensis: tularensis (type A), holarctica (type B), mediasiatica, and novicida. In addition, genomic studies have further subdivided type A tularensis into two subclassifications, type A.I and type A.II. These two subclassifications differ in geographic distribution with type A.I appearing mainly in the Eastern United States and type A.II appearing mainly in the Western United States. Because of differences of virulence among the subspecies, it is important to be able to quickly identify each of the subspecies rapidly and accurately. This work describes the development of a multiplex real-time polymerase chain reaction (PCR) assay which was shown to be ~98% successful at identifying the known subspecies of F. tularensis. Furthermore, F. tularensis is thought be a genome in decay (losing genes) because of the relatively large number of pseudogenes present in its genome. We hypothesized that the observed frequency of gene loss/pseudogenes may be an artifact of evolution in response to a changing environment, and that genes involved in virulence should be under strong positive selection. Eleven arbitrarily chosen virulence genes were screened for positive selection along with 10 arbitrarily chosen housekeeping genes. Analyses of selection yielded one housekeeping gene and 7 virulence genes which showed significant evidence of positive selection. Our results suggest that while the loss of functional genes through disuse could be accelerated by negative selection, the genome decay in Francisella could also be the byproduct of adaptive evolution, as evidenced by several of its virulence genes which are undergoing strong, positive selection.
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Smith, Jenna E. "Investigation of the mRNP and Transcriptome Regulated by Nonsense-Mediated RNA Decay." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1421428941.
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Lopes, Josiane Millani. "Podzols of Ilha Comprida (SE, Brazil): organic matter chemistry and decay features." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/11/11140/tde-03052016-185358/.
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The most frequent soils in the São Paulo State Coastal Plain are Podzols, characterized by strong to moderate hydromorphic to well-drained podzolization with very well developed podzol-B horizons (Bh or Bhm). Podzolization processes include the effects of hydrology and rooting on profile morphology and the subsequent effects of improved drainage. A Podzol chrono-hydrosequence was described in detail on a cliff at the south coast of Ilha Comprida, a Holocene barrier island, and allowed a subdivision into four distinct groups: poorly-drained profiles, profiles with well-drained B horizons, strongly rooted profiles and superposed profiles. The morphological description and some observations about the exposure cliff were essential for grouping and differentiating the podzol profiles. Some well-drained podzols have OM-depleted mottles that are related to selective decomposition of organic matter (OM) by microorganisms. Such mottles are frequently associated to root channels. Seventeen profiles were studied, thirteen had depletion mottles scattered along the profile. Most of these mottles are whitish and are located preferentially in the horizons of transition between the E and B horizons, particularly in conditions of good drainage. Such mottles have certain morphological differences and may be grouped according to similarities in their morphology and their position in the profile. Distinct groups are: (a) concentric OM-depleted mottles; (b) circular/tubular OM-depleted mottles (burrows); (c) dotted OM-depleted mottles; (d) ghost OM-depleted mottles; (e) irregular OM-depleted mottles and (f) Fe-depleted mottles. The chemical composition of soil organic matter was studied in detail using pyrolysis in combination with gas chromatography/mass spectrometry (Py-GC/MS). Samples of all horizons of the distinct profiles studied were taken, as well as from the center of the mottle (M) and from the direct surroundings (S). The processes involved in the genesis of Podzols in the sandy coastal plain are directly related to drainage, the contribution of dissolved organic matter (DOM), the contribution of organic matter derived from roots, the chemical composition of organic matter and its decomposition by microorganisms, causing a large variation in adjacent Podzols. The well-drained Podzols differ in characteristics from the poorly drained ones in composition and deposition of OM, as well as its decomposition, which is directly related to the activity of groups of microorganisms. They also differ in the relative contribution of OM-derived from roots and DOM. There is a wide variation in the characteristics of decomposition by microorganisms between the profiles of Podzols permanently exposed to air and marine spray (the cliffs) on Ilha Comprida and those inland (pits). There are therefore two main processes that change the morphology of Podzols (OM and composition): (a) change in drainage and rooting, and (b) exposure to air.Os solos mais frequentes na Planície Costeira do Estado de São Paulo são os podzóis, caracterizados por podzolização com hidromorfismo forte a moderado a bem drenado com horizontes B-podzol muito bem desenvolvidos (Bh ou Bhm). O processo de podzolização inclui os efeitos da hidrologia e do enraizamento no perfil e os efeitos subsequentes da drenagem melhorada. Uma crono-hidrosequencia de podzóis foi descrita em detalhes em um barranco na costa sul da Ilha Comprida, uma ilha barreira do Holoceno, e permitiu uma subdivisão em quatro grupos distintos: perfis mal drenados, perfis com horizonte B bem drenados, perfis fortemente enraizados e perfis superpostos. A descrição morfológica e algumas observações sobre o barranco exposto foram essenciais para o agrupamento e diferenciar os perfis de podzóis. Alguns desses podzóis bem drenados possuem manchas esbranquiçadas que estão relacionadas com a seletiva decomposição da matéria orgânica (MO) por microorganismos. Tais manchas são freqüentemente associadas aos canais radiculares. Foram estudados dezessete perfis, dos quais treze apresentaram manchas de esgotamento espalhadas ao longo do perfil. A maioria destas manchas são esbranquiçadas e estão localizadas preferencialmente nos horizontes de transição entre os horizontes E e B, particularmente em condições de boa drenagem. Tais manchas possuem algumas diferenças morfológicas e puderam ser agrupadas de acordo com semelhanças na sua morfologia e da sua posição no perfil. Os grupos são: (a) manchas concêntricas de depleção da MO; (b) manchas circulares/tubularess de depleção da MO (tocas); (c) manchas pontilhadas de depleção da MO; (d) manchas fantasmas de depleção da MO; (e) manchas irregulares de depleção da MO; e (f) manchas de depleção de Fe. A composição química da matéria orgânica do solo foi estudada em detalhe por pirólise em combinação com cromatografia em fase gasosa/espectrometria de massa (Py-CG/EM). Amostras de todos os horizontes dos perfis estudados foram coletadas, bem como amostras do centro das manchas (M) e do solo adjacente (S). Os processos envolvidos na gênese de podzóis da planície costeira arenosa estão diretamente relacionados com a drenagem, a contribuição de matéria orgânica dissolvida (MOD), a contribuição de matéria orgânica derivada de raízes, a composição química da matéria orgânica e sua decomposição por microorganismos, causando uma grande variação no podzóis. Os podzóis bem drenados diferem em características dos mal drenados em composição e deposição de MO, bem como a sua decomposição, que está directamente relacionada com a actividade dos grupos de microrganismos. Eles também diferem na contribuição relativa da MO derivada de raízes e MOD. Existe uma grande variação nas características da decomposição por microorganismos entre os perfis de podzóis permanentemente expostas ao ar e spray marinho (falésias) na Ilha Comprida e os do interior (trincheiras). Há, portanto, dois processos principais que alteram a morfologia de podzóis (composição da MO): (a) mudança na drenagem e enraizamento, e (b) a exposição ao ar.
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Kamelgarn, Marisa Elizabeth. "MUTATIONS OF FUS CAUSE AGGREGATION OF RNA BINDING PROTEINS, DISRUPTIONS IN PROTEIN SYNTHESIS, AND DYSREGULATION OF NONSENSE MEDIATED DECAY." UKnowledge, 2019. https://uknowledge.uky.edu/toxicology_etds/27.
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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron death and subsequent muscle atrophy. Approximately 15% of ALS cases are inheritable, and mutations in the Fused in Sarcoma (FUS) gene contribute to approximately 5% of these cases, as well as about 2% of sporadic cases. FUS performs a diverse set of cellular functions, including being a major regulator of RNA metabolism. FUS undergoes liquid- liquid phase transition in vitro, allowing for its participation in stress granules and RNA transport granules. Phase transition also contributes to the formation of cytoplasmic inclusions found in the cell bodies of FUS ALS patients motor neurons. The nature of these inclusions has remained elusive, as the proteins localized to them have not been identified. Additionally, the functional consequence of the accumulation of cytoplasmic FUS inclusions has not been established, nor is it understood how they contribute to selective motor neuron death.
We carried out two related, but independent studies to characterize the proteins that may be included in FUS-positive inclusions. In this first study, we utilized immunoprecipitation of wild-type and mutant FUS in the presence and absence of RNase, followed by LC MS/MS. The identified proteins represent those that directly or indirectly interact with FUS, with relatively high affinity that can be pulled down with immunoprecipitation. A wide variety of interacting proteins were identified and they are involved in a multitude of pathways including: chromosomal organization, transcription, RNA splicing, RNA transport, localized translation, and stress response. Their interaction with FUS varied greatly in their requirements for RNA. Most notably, FUS interacted with hnRNPA1 and Matrin-3, proteins also known to cause familial ALS. Immunofluorescent staining of proteins interacting with mutant FUS were localized to cytoplasmic inclusions. We concluded that mis-localization of these proteins potentially lead to their dysregulation or loss of function, thus contributing to FUS pathogenesis.
In the second study, we developed a protocol to isolate dynamic FUS inclusions and employed LC MS/MS to identify all proteins associated with FUS inclusions. We identified a cohort of proteins involved in translation, splicing, and RNA export to be associated with the FUS inclusions. Further pathway and disease association analysis suggested that proteins associated with translation and RNA quality control pathways may be the most significant. Protein translation assays using both N2A and ALS patient fibroblasts demonstrated suppression of protein biosynthesis in mutant FUS expressing cells. However, translation initiation was not impaired. To understand how protein synthesis is suppressed by mutant FUS mediated defects in RNA metabolism, we examined changes in a well conserved RNA turnover pathway namely: nonsense mediated decay (NMD). We found that NMD is hyperactivated in cells expressing mutant FUS, likely due to chronic suppression of protein translation shifting the pathways autoregulatory circuit to allow for hyperactivation. We concluded that mutant FUS suppresses protein biosynthesis and disrupts NMD regulation. These defects together likely contribute to motor neuron death.
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Maximowitsch, Egle [Verfasser], and Tatiana [Akademischer Betreuer] Domratcheva. "Molecular mechanisms of spectral tuning and excited-state decay in phytochrome photoreceptors / Egle Maximowitsch ; Betreuer: Tatiana Domratcheva." Heidelberg : Universitätsbibliothek Heidelberg, 2020. http://d-nb.info/1210647702/34.
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Forrest, Megan E. "Regulation of Mammalian Messenger RNA Stability via the Open Reading Frame." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1579862741902687.
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Gangras, Pooja. "Understanding the Role of Exon Junction Complex-dependent Nonsense Mediated mRNA Decay in Zebrafish Embryonic Development." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574765848602854.
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Zagorodskikh, Sergey. "Single-photon multiple ionisation of atoms and molecules investigated by coincidence spectroscopy : Site-specific effects in acetaldehyde and carbon dioxide." Doctoral thesis, Uppsala universitet, Molekyl- och kondenserade materiens fysik, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-301128.
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In this thesis, multiple ionisation processes of free atoms and molecules upon single photon absorption are studied by means of a versatile multi-electron-ion coincidence spectroscopy method based on a magnetic bottle, primarily in combination with synchrotron radiation. The latter offered the possibility to access not only valence but also core levels, revealing processes, which promote the target systems into different charge states. One study focuses on double and triple ionisation processes of acetaldehyde (ethanal) in the valence region as well as single and double Auger decay of initial 1s core vacancies. The latter are investigated site-selectively for the two chemically different carbon atoms of acetaldehyde, scrutinising theoretical predictions specifically made for that system. A related study concentrates on core-valence double ionisation spectra of acetaldehyde, which have been investigated in the light of a previously established empirical model, and which have been used as test cases for analysing this kind of spectra by means of quantum chemical electronic structure methods of increasing sophistication. A third study investigates site-specific fragmentation upon 1s photoionisation of acetaldehyde using a magnetic bottle augmented with an in-line ion time-of-flight mass spectrometer. Experimental evidence is presented that bond rupture occurs with highest probability in the vicinity of the initial charge localisation and possible mechanisms are discussed. A site-specificity parameter P∆ is introduced to show that differences in fragmentation behavior between initial ionisations at chemically different carbon atoms probably persist even for identical internal energy contents in the nascent dications. In another study where both electrons and ions from Auger decay of core-excited and core-ionised states of CO2 are detected in coincidence, it is confirmed that O2+ is formed specifically in Auger decay from the C1s → π* and O1s → π* resonances, suggesting a decisive role of the π* orbital in the molecular rearrangement. Also, the molecular rearrangement is found to occur by bending in the resonant states, and O2+ is produced by both single and double Auger decay. A new version of the multi-electron-ion coincidence method, where the ion time-of-flight spectrometer is mounted perpendicularly to the electron flight tube, which affects less the electron resolution and which allows for position sensitive detection of the ions, is employed in combination with tunable soft X-rays to reveal the branching ratios to final Xen+ states with 2 < n < 9 from pure 4d-1, 4p-1, 4s-1, 3d-1 and 3p-1 Xe+ hole states. The coincident electron spectra give information on the Auger cascade pathways.Byte av lokal vid disputation till Polhemssalen.
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Woodward, Lauren A. "Examining the Effects of Translation on the Exon Junction Complex." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1574724716785331.
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Uwimpuhwe, Henriette. "Molecular analysis of decay accelerating factor as a potential susceptibility factor to developing treatment resistant extraocular muscle involvement in Myasthenia Gravis." Master's thesis, University of Cape Town, 2009. http://hdl.handle.net/11427/3208.
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Includes abstract.Includes bibliographical references (leaves 73-83).
Myasthenia gravis (MG) is an autoimmune disorder in which auto-antibodies directed at the acetylcholine receptors (AChR) of the neuromuscular junction (NMJ) block, alter or destroy their targets. The anti-AChR antibodies cause activation of the classical complement pathway leading to inflammatory injury at the NMJ. Decay Accelerating Factor (DAF), a member of complement regulatory proteins, prevents activation of autologous components of complement pathways. The absence of DAF, in knock-out mouse models, has been shown to significantly increase the susceptibility to experimental autoimmune MG. A previous study showed that a high proportion of South African MG patients of African genetic ancestry develop immunosuppressive therapyresistant extraocular muscle (EOM) dysfunction. We hypothesized that these patients have deficient DAF expression in their EOMs resulting in less protection from complement injury.
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Bulat, Muhammer. "Molecular cluster cations of carbon monoxide and carbon dioxide." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2010. http://dx.doi.org/10.18452/16246.
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Diese Dissertation handelt vom metastabilen Zerfall und von der Oberflächenwechselwirkung im hyperthermalen Energiebereich relativ schwach gebundener molekularer Kohlenmonoxid und Kohlendioxid Clusterkationen mit einer Edelstahloberfläche und einer Siliziumoberfläche. Im Rahmen dieser Arbeit wurde ein hierfür geeignetes spezielles Flugzeitmassenspektrometer entwickelt und aufgebaut. Entwurf, numerische Optimierung der Auflösung, ionenoptische Simulationen und Aufbau der jeweiligen Komponenten wie Elektronenquellen, Beschleuniger, Ablenkplatten, Massenfilter und Reflektron werden detailliert beschrieben. Das entwickelte Flugzeitmassenspektrometer besitzt mit einer kompakten Gesamtfluglänge von ~1.5m eine hohe Massenauflösung von m/Delta m = 3000. Es bietet die Möglichkeit, eine Massentrennung von Clusterionen mit einer Größe von bis zu n = 190 vorzunehmen. Diese massenselektierten Clusterionen können daraufhin auf metastabilen Zerfall und auf ihre Wechselwirkung mit einer Oberfläche untersucht werden. Dazu wurden Kohlendioxid-Clusterionen mit nThis thesis deals with the metastable decay and the surface scattering in the hyperthermal energy range of relatively weakly bound molecular cluster cations. With carbon monoxide and carbon dioxide two related model systems were chosen for a systematic size dependent study. Surface impact experiments were carried out with stainless steel and silicon surfaces. Results were obtained by a new, reflectron time-of-flight mass spectrometer (Re-TOFMS). Additional to the experimental data we present in this work a detailed description of the instrumental design considerations, numerical optimization, ion optical simulations. Hence each ion optical component like electron guns, accelerator, deflector, mass gate and reflectron are described. Despite the compact dimensions with a total flight length of ~1.5m the developed instrument possesses a high mass resolution above m/Delta m = 3000. Additionally it offers the possibility to perform mass separation of big cluster ions with sizes n
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Guedes, Ana Raquel Dias Pereira. "The role of SMG6 and PM/Sc 100 ribonucleases in messenger RNA degradation mechanisms." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/17151.
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Mestrado em Biologia Molecular e CelularEukaryotic gene expression comprises a series of interconnected steps, from transcription to protein synthesis, in which messenger RNAs (mRNAs) are the key intermediates. While the multitude of events that take place throughout the whole process allows for the production of proteins to be controlled at many levels, ensuring maximum efficiency and fidelity, it also makes gene expression susceptible to errors. Eukaryotic cells have developed intricate mRNA quality control mechanisms that recognize and degrade aberrant transcripts. Two examples of these mechanisms are the nonsense-mediated mRNA decay (NMD), which targets mRNAs with premature translation termination codons (PTCs), and the nonstop mRNA decay (NSD), which eliminates mRNAs lacking any in-frame translation termination codons. SMG6 and PM/Scl100 are both ribonucleases which have been implicated in mRNA degradation pathways. One of the mechanisms proposed for mammalian NMD involves an endonucleolytic cleavage of transcripts in the vicinity of the PTC catalyzed by SMG6. On the other hand, the human exosome, which includes the catalytic subunit PM/Scl100, has been associated not only with mRNA surveillance mechanisms, but also with normal mRNA turnover. However, questions relative to the specificity or indispensability of these enzymes in the pathways in which they participate have not yet been answered. The present work aimed to explore the role of SMG6 and PM/Scl100 ribonucleases in the degradation of normal or NSD- and NMD-sensitive mRNAs. The results obtained point to the involvement of SMG6, not only in NMD, but also in NSD and normal mRNA turnover. Moreover, they suggest that SMG6 plays an indirect role on the degradation of NMD targets. PM/Scl100 also appears to intervene in NMD, NSD and normal mRNA turnover; however, the results herein presented suggest that the main contribution to NMD-eliciting transcripts 3’→5’ degradation may be offered by other exoribonucleases.
A expressão génica em eucariotas envolve uma série de etapas interligadas, desde a transcrição do material genético até à síntese da proteína correspondente, nas quais os RNAs mensageiros (mRNAs) são os intermediários cruciais. Embora a panóplia de eventos que ocorrem ao longo de todo o processo permita que a produção proteica seja controlada a vários níveis, também torna a expressão génica vulnerável a erros. As células eucarióticas desenvolveram mecanismos elaborados de controlo de qualidade do mRNA que reconhecem e degradam transcritos anómalos. Dois exemplos destes mecanismos são o decaimento do mRNA mediado por mutações nonsense (NMD), que detecta mRNAs com codões de terminação da tradução prematuros (PTCs), e o decaimento do mRNA nonstop (NSD), que elimina mRNAs que não possuem codões de terminação da tradução em fase na grelha de leitura. A SMG6 e a PM/Scl100 são ambas ribonucleases já implicadas em vias de degradação de mRNAs. Um dos mecanismos propostos para o NMD em mamíferos envolve a clivagem endonucleolítica dos transcritos na proximidade do PTC, catalizada pela SMG6. Por outro lado, o exossoma humano, que inclui a subunidade catalítica PM/Scl100, já foi associado não só a mecanismos de vigilância do mRNA, mas também ao turnover do mRNA. No entanto, questões relativas à especificidade ou indispensabilidade destas enzimas nos mecanismos nos quais participam ainda não têm resposta. O presente trabalho teve como objectivo explorar o papel das ribonucleases SMG6 e PM/Scl100 na degradação de mRNAs normais ou sensíveis ao NSD e ao NMD. Os resultados obtidos apontam para o envolvimento da SMG6, não só no NMD, mas também no NSD e no turnover do mRNA. Para além disso, sugerem também que a SMG6 desempenha um papel indirecto na degradação de alvos do NMD. A PM/Scl100 também parece intervir no NMD, no NSD e no turnover do mRNA; no entanto, os resultados aqui apresentados sugerem que a principal contribuição para a degradação 3’→5’ de transcritos que desencadeiam o NMD é oferecida por outras exoribonucleases.
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Sweet, Thomas Jeffrey. "New Insights Into the Relationship Between Messenger RNA Translation and Degradation." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1321298653.
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Råberg, Ulrika. "Fungal degradation and discolouration of Scots pine : a molecular approach /." Uppsala : Swedish University of Agricultural Sciences, 2006. http://diss-epsilon.slu.se/archive/00001268/.
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Thesis (doctoral)--Swedish University of Agricultural Sciences, 2006.Thesis documentation sheet inserted. Errata sheet inserted. Appendix reprints four papers and manuscripts co-authored with others. Includes bibliographical references. Issued also electronically via World Wide Web in PDF format; online version lacks appendix.
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Hassan, Faizule. "Adenovirus Mediated Delivery of Decoy Hyper Binding Sites for Sequestration of an Oncogenic Transcription Factor HMGA as a Potential Novel Cancer Therapy and Antibacterial Activity of Local Mushrooms." Miami University / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=miami1511449587326648.
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Merrikh, Christopher N. "Characterization of New Factors in the 18S Nonfunctional Ribosomal RNA Decay Pathway in S. cerevisiae: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/613.
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The molecular biology revolution of the 1960s has given rise to an enormous body of literature describing, in great detail, the inner workings of the cell. Over the course of the past 50 years, and countless hours at the bench, biologists have used the implications of basic research to produce vaccines, antibiotics, and other therapies that have improved both the quality and duration of our lives. Despite these incredible advances, basic questions remain unanswered. In even the simplest model organism, hundreds of essential genes have never been studied. Moreover, the central dogma of molecular biology—DNA to RNA to Protein—is understood largely in terms of how the cell functions under ideal conditions. What happens when things go wrong?
This study seeks to characterize one of the cell’s contingency plans—a quality control measure for the eukaryotic ribosome. Today, despite the abundance of ribosomes in all cells, we are only beginning to understand the details of how they function, and the mechanisms that monitor their behavior. Recently, inactivated ribosomes were shown to be destroyed by the cell's own quality control measures, potentially preventing them from harming the cell. This system, dubbed 18S Nonfunctional rRNA Decay, is known to utilize a pair of ribosome-binding proteins to carry out its function. Yet the pathway still functions, albeit more slowly, in the absence of these two proteins, suggesting that other components must exist. The work discussed here is largely concerned with identifying these other factors, characterizing their activities, and determining how the 18S Nonfunctional rRNA Decay pathway impacts the health of the cell.
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Beaulieu, Samuel. "Probing femtosecond and attosecond electronic and chiral dynamics : high-order harmonic generation, XUV free induction decay, photoelectron spectroscopy and Coulomb explosion." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0063/document.
Full textAbstract:
Ce manuscrit de thèse s'articule autour de l'étude de l'interaction entre des impulsions lumineuses ultra brèves et des atomes ainsi que des molécules polyatomiques et chirales en phase gazeuse. En utilisant des techniques développées en physique attoseconde ainsi qu'en femtochimie, notre objectif général est de parvenir à une meilleure compréhension des dynamiques ultrarapides photoinduites dans la matière. Pour ce faire, nous avons développé des sources de lumière à ultra brèves dans le proche infrarouge et l’infrarouge moyen, qui ont été utilisées pour construire une source de rayons X dans la fenêtre de l’eau, basée surla génération d'harmoniques d’ordre élevé (GHOE), ainsi que pour l’étude de nouveaux canaux de GHOE impliquant des états hautement excités (Rydberg). Cette dernière étude a démontré une émission harmonique via l'ionisation depuis des états de Rydberg et la recombinaison radiative sur l'état fondamental, attirant ainsi notre intérêt pour le rôle des états de Rydberg en physique des champs forts. Cela nous a conduit à étudier la décroissance libre de l’induction XUV de paquets d'ondes électroniques comme une nouvelle technique de spectroscopie 2D. De plus, nous avons découvert que l'interaction entre un laser intense et un atome préparé dans une superposition cohérente d'états électroniques peut conduire à la génération de lignes hyper-Raman concomitantes avec la GHOE standard. Ce mécanisme avait été prédit lors des premiers calculs théoriques de GHOE, mais n'avait jamais été démontré expérimentalement. Par la suite, nous nous sommes intéressé à l’étude de systèmes moléculaires, dans lesquelles une excitation électronique induite par la lumière peut déclencher des dynamiques nucléaires. Nous avons étudié la photo isomérisation non-adiabatique de l’acétylène cationique en vinylidène cationique ainsi que le contrôle cohérent de la localisation électronique lors de la photodissociation de H2+. La simplicité de ces systèmes moléculaires a permis la comparaison des résultats expérimentaux avec des calculs théoriques de pointe,révélant l'importance du couplage entre les degrés de liberté nucléaires et électroniques lors de dynamiques moléculaires photoinduites.Un autre pilier majeur de cette thèse est l'étude de l'ionisation de molécules chirales avec des impulsions chirales. On sait depuis les années 70 que l'ionisation d'un ensemble de molécules chirales aléatoirement orientées, en utilisant une impulsion polarisée circulairement, conduit à une forte asymétrie avant-arrière dans le nombre de photoélectrons émis, selon l'axe de propagation de la lumière (DichroismeCirculaire de Photoélectron, DCPE). Avant cette thèse, le DCPE a été largement étudié à l’aide du rayonnement synchrotron (ionisation à un photon) et a récemment été démontré avec des lasers femtoseconde, via des schémas d'ionisation multiphotonique. Dans cette thèse, nous avons montré que le DCPE est un effet universel, c'est-à-dire qu'il émerge dans tous les régimes d'ionisation: l'ionisation àun photon, l'ionisation à multiphonique, l'ionisation au-dessus du seuil ainsi que l’ionisation par effet tunnel. Ensuite, nous avons démontré que la combinaison d’approches standard de femtochimie et du DCPE peuvent être utilisées pour suivre des dynamique de molécules chirales photoexcitées. En utilisant des approches expérimentales similaires, avec des séquences d'impulsions ayant des états de polarisation contre-intuitifs, nous avons démontré un nouvel effet chiroptique, appelé Dichroïsme Circulaire de Photoexcitation (DCPX), qui est décrit par un courant électronique directionnel et chirosensible, lorsque plusieurs niveaux sont peuplés de manière cohérente avec de la lumière chirale. Enfin, nous avons introduit une perspective temporelle à la photoionisation chirale en mesurant l'asymétrie avant arrièredes retards de photoionisation dans les molécules chirales photoionisées par des impulsions lumineuses chiralesThis thesis manuscript is articulated around the investigation of the interaction between ultrashort light pulses and gas-phase atoms, polyatomic and chiral molecules. Using the toolboxes developed in attosecond and strong-field physics as well as in femtochemistry, our general goal is to reach a better understanding of subtle effects underlying ultrafast light-induced dynamics in matter.To do so, we developed cutting-edge near-infrared and mid-infrared few-cycle light sources, which were used to build a water-window soft-X-ray source based on high order harmonic generation (HHG), as well as to study new HHG channels involving highly-excited (Rydberg) states. The latter study revealed a delayed HHG emission from the ionization of Rydberg states and radiative recombination onto the electronicground state, triggering our interest in the role of Rydberg states in strong-field physics. This led us to investigate the laser-induced XUV Free Induced Decay from electronic wave packets as a new background-free 2D spectroscopic technique.More over, we have found out that strong-field interaction with a well prepared coherent superposition of electronic states led to the generation of hyper-Ramanlines concomitant with standard high-order harmonics. These spectral features were predicted in the early-days theoretical calculations of HHG but had never been reported experimentally.After these experiments in rare gas atoms, we moved to molecular targets, in whichlight-induced electronic excitation can trigger nuclear dynamics. Using simple benchmark molecules, we have studied dynamics involving the participation of both nuclear and electronic degrees of freedom: first, we studied the ultrafast non adiabatic photoisomerization of the acetylene cation into vinylidene cation, andsecond, we investigated the coherent control of electron localization during molecular photodissociation of H2+. The simplicity of these molecular targets enabled the comparison of the experimental results with state-of-the-art theoretical calculations,revealing the importance of the coupling between nuclear and electronic degrees of freedom in photoinduced molecular dynamics.The other major pillar of this thesis is the study of ionization of chiral molecules usingchiral light pulses. It has been known since the 70s that the ionization from an ensemble of randomly oriented chiral molecules, using circularly polarized light pulse,leads to a strong forward-backward asymmetry in the number of emitted photoelectrons, along the light propagation axis (Photoelectron Circular Dichroism,PECD). Prior to this thesis, PECD was widely studied at synchrotron facilities (single photonionization) and had recently been demonstrated using table-top lasers in resonant-enhanced multiphoton ionization schemes. In this thesis, we have shownthat PECD is a universal effect, i.e. that it emerges in all ionization regimes, from single photon ionization, to few-photon ionization, to above-threshold ionization, up to the tunneling ionization regime. This bridges the gap between chiral photoionizationand strong-field physics. Next, we have shown how the combination of standard femtochemistry approaches and PECD can be used to follow the dynamics of photoexcited chiral molecules using time-resolved PECD. Using similar experimental approaches, but by using pulse sequences with counter-intuitive polarization states,we have demonstrated a novel electric dipolar chiroptical effect, called Photoexcitation Circular Dichroism (PXCD), which emerges as a directional and chirosensitive electron current when multiple excited bound states of chiral molecules are coherently populated with chiral light. Last, we introduced a time-domain perspective on chiral photoionization by measuring the forward-backward asymmetry of photoionization delays in chiral molecules photoionized by chiral light pulses. Our work thus carried chiral-sensitive studies down to the femtosecond and attosecond ranges