The various concepts of the fission process, mass and charge distribution, and fine structure in fission yields are reviewed. Details and results of mass spectrometric analyses of fission-product samples of cesium, rubidium, and strontium are reported. Absolute yield values have been assigned to the mass 87, 135, and 137 chains. Relative yields of the mass 88 and 90 chains have been determined. A mechanism is postulated to account tor anomalies in fission fine structure. The Glendenin mechanism of instantaneous neutron emission is found to require modification. / Thesis / Master of Science (MS)

The general fission process is well known and is applied in nuclear power plants all over the world. However many properties of fission fragments are still not well understood. The angular momentum distribution of fission fragments is an important property to gain a better understanding of the fission process, and that can be derived indirectly from isomeric yield ratios. The goal of this project has been to develop a script in Python that runs the nuclear reaction code TALYS with the Total Monte Carlo method to calculate the isomeric yield ratio. The script generates a matrix consisting of excitation energies and angular momenta that is provided to TALYS. One matrix corresponds to one calculation of the isomeric ratio. Thus, the dependency of the isomeric yield ratio on these matrices can be observed. After looking into the matrices, the dependencies of the isomeric yield ratios on the excitation energies and the angular momentum distribution are observed. In this project, the calculated isomeric yield ratios are compared with the experimental value obtained from an experiment conducted in August of 2019 at the IGISOL-JYFLTRAP facility in Jyväskylä, Finland. It is worth mentioning that, fission system is of Uranium-238 which was induced by a proton beam at an energy of 25 MeV. The dependency of the isomeric yield ratio (IYR) on the angular momentum and the excitation energy has been investigated. However, it has proved more difficult than expected, to deduce an estimation for the angular momentum distribution. Another finding of this project is that the two codes used, GEF and TALYS sometimes produce inconstant results.

Il est bien connu que des cofacteurs comme le zinc et le cuivre sont essentiels pour la progres-sion de la méiose qui permet la formation de gamètes haploïdes à partir d’une cellule diploïde. Au laboratoire, de graves défauts dans la méiose chez la levure à fission Schizosaccharomyces pombe ont été observés en carence de cuivre, mais peu est connu sur son acquisition durant la différentiation méiotique. Trois transporteurs de cuivre sont connus chez S. pombe, soient Ctr4, Ctr5 et Ctr6. Ils ont été largement caractérisés dans un contexte mitotique, mais nous en connaissons peu sur leur contribution à l’homéostasie du cuivre en méiose. Mes travaux avaient pour objectif de dresser un portrait global des transporteurs de cuivre au cours de la méiose. D'abord, j’ai entrepris d’évaluer le profil d’expression de ces gènes. J’ai mis en évidence des patrons différents d’expression selon les transporteurs. L’expression de ctr4+ et ctr5+ a lieu principalement durant les premières heures de la méiose en carence de cuivre alors que ctr6+ a une expression plus étendue avec un pic durant la phase médiane de la méiose. L’expression de ctr4+ et ctr5+ est dépendante uniquement de Cuf1 alors que l’expression de ctr6+ repose sur les facteurs Cuf1 et Mei4. Les deux protéines Ctr4 et Ctr5 co-localisent à la membrane plasmique rapidement durant les premières heures de la méiose en carence de cuivre. À ce moment, Ctr6 apparaît à la membrane vacuolaire. Après la première division méiotique, Ctr4 et Ctr5 disparaissent alors que Ctr6 transite de la membrane vacuolaire vers la membrane des spores où elle se localise même après la libération des spores. Une délétion des gènes ctr4 et ctr6 affecte grandement l’activité d’enzymes cuivre dépendantes. Notons que dans ce mutant, l’activité superoxide dismutase est abolie et l’activité amine oxydase cuivre est grandement diminuée uniquement dans les premières étapes de la méiose. Mes travaux ont permis de mettre en évidence des profils différents d’expression, de localisation et de contribution à l’activité d’enzymes cuivre-dépendantes. Ces observations suggèrent qu’en cours de méiose la levure à fission voit ses besoins en ion de cuivre modulés et doit adapter ses systèmes d’acquisition et de gestion de cuivre intracellulaire.

The use of fission product yield data is pervasive among nuclear calculations, particularly in the realm of nuclear forensics and active interrogation for special nuclear material. The capital source of fission product yield data is the work of T.R. England and B.F. Rider, of Los Alamos National Laboratory, in the early 1990s. Though their work was certainly substantial, a great deal of data was generated computationally, in lieu of done empirically—particularly with low-yield, short-lived progeny. Due to this, relative uncertainties in the measurements can be as high as 64%, and vary wildly from database to database (oft times not even within one standard deviation of one another). The purpose of this work is to build a pneumatic system capable of cyclic irradiation coupled to a D-T neutron source, in order to cumulate proper counting statistics, by which one can backcalculate independent and cumulative fission yields. Beyond the design and control parameters of the pneumatic system, a precise flux characterization of the facility is presented, and finally, proof-of-concept is demonstrated by causing 14 MeV neutron-induced fission and identifying every observed fission product photopeak. / text

In Schizosaccharomyces pombe mitosis is initiated when Cdc25 tyrosine phosphatase dephosphorylates Cdc2 (Cdk1) and in turn Cdc2 kinase phosphorylates mitotic targets. Cdc2 is thought to phosphorylate and further activate Cdc25, forming a positive feedback loop between the two for robust entry into mitosis. Pyp3 tyrosine phosphatase is essential in the absence of Cdc25. Its role is thought to be in directly dephosphorylating Cdc2 under these conditions. Pyp3 also presents a link between cell division and growth. It interacts physically and genetically with the mRNA cap-binding protein eIF4E and is thought to play the same role as mammalian 4E-binding proteins. Pyp3 has a consensus TOS motif potentially enabling nutritional input from the TOR pathway into translation regulation. Since known 4E-BPs are not phosphatases, Pyp3 may act as a 4E-binding protein independently of its phosphatase activity. Evolutionarily conserved Cdc2 phosphorylation sites in Cdc25 were substituted to non-phosphorylatable Ala, or to Glu as a phosphomimic. The T89E phosphomimic mutation creates an activated allele of Cdc25, cdc25-89w. It has a dominant semi-wee phenotype due to accelerated entry into mitosis. Pyp3 was mutagenized to remove the function of the phosphatase active site and also the putative TOS motif. The Pyp3 active site is essential for its role in cell cycle initiation. It is also essential for the genetic interaction with eIF4E, tif1. Removal of a putative Pyp3 TOS motif affects the Pyp3 localization to cytoplasmic foci following co-overexpression of eIF4E. Similar localization occurs in response to heat stress. These results make important contributions to the understanding of mitotic initiation, and link between cell growth and division. / Thesis (Master, Biology) -- Queen's University, 2013-09-12 14:40:40.384

Microtubules (MTs) are important components of the eukaryotic cytoskeleton, with critical functions in intracellular trafficking, establishing and maintaining cell morphology, and segregating chromosomes during mitosis. MTs are hollow, cylindrical polymers composed of αβ-tubulin heterodimers. The longitudinal assembly of αβ-tubulin subunits generates protofilaments, and multiple protofilaments (typically 13 in vivo) interact laterally to form the wall of the MT. In vitro, the polymerization of MTs proceeds in two steps: nucleation and elongation. During the nucleation phase, several αβ-tubulin subunits associate to form a seed, from which further MT elongation then occurs. However, at the relatively low αβ-tubulin concentrations found in vivo, the spontaneous assembly of MTs is not favoured, due largely to the slow kinetics of MT nucleation. The nucleation of MTs in vivo requires the γ-tubulin complex (γ-TuC), a ring-like complex composed of γ-tubulin and γ-tubulin complex proteins (GCPs). Two copies of γ- tubulin associate with one copy each of GCP2 and GCP3 to produce the γ-tubulin small complex (γ-TuSC). Multiple γ-TuSCs, along with the additional GCPs 4,5, and 6, assemble to form the larger γ-tubulin ring complex (γ-TuRC). The γ-TuRC contains a ring of 13 γ-tubulins, which acts as a template for the nucleation of MTs. Typically, the γ-TuC nucleates MTs only when localized to specific subcellular sites, referred to as microtubule organizing centres (MTOCs). However, the precise mechanism by which the γ-TuC is activated at MTOCs remains unknown. In fission yeast, the proteins Mto1 and Mto2 form a complex (Mto1/2) required for the nucleation and organization of cytoplasmic MTs. Mto1/2 determines sites of MT nucleation by recruiting the γ-TuC to several different MTOCs. Different sequences in the Mto1 C-terminus independently confer γ-TuC localization to spindle pole bodies, MTs, and the cell equator. Here, I show that the Mto1 N-terminus is necessary for localization to the nuclear envelope (NE). By simultaneously removing the N- and C-terminal localization domains, I generated the "Mto1-bonsai" mutant, which fails to localize to any conventional MTOCs. In mto1-bonsai cells, MTs are still nucleated in the cytoplasm in an Mto1- dependent manner, but nucleation is spatially random. This reveals that targeting of the γ- TuC to conventional MTOCs is not necessary for MT nucleation, and suggests that Mto1/2 has a direct role in activating MT nucleation by the γ-TuC. Live-cell confocal microscopy allows us to detect individual MT nucleation events, in which newly nucleated MTs are associated with single γ-TuCs as well as Mto1/2-bonsai complexes. Fluorescence quantification reveals that these nucleating complexes contain approximately 13 molecules of both Mto1-bonsai and Mto2, matching the 13 copies of γ-tubulin anticipated for a single γ-TuC. We propose that Mto1/2 may contribute to γ-TuC activation by promoting γ-TuSC assembly and/or inducing conformational changes in the γ-TuC upon binding. I also expressed and purified recombinant Mto1/2-bonsai complex, using a baculovirus/insect cell system. This recombinant Mto1/2-bonsai self-assembles into higher-order complexes, comparable in size to the complexes analyzed in vivo by fluorescence microscopy.

Thesis advisor: Charles Hoffman / Cyclic adenosine monophosphate (cAMP) and the second messengers that modulate several biological processes are regulated by adenylyl cyclase (AC) and cyclic nucleotide phosphodiesterases (PDEs). ACs and PDEs are comprised of superfamilies of enzymes that are viewed as druggable targets due to their many distinct biological roles and tissue-specific distribution. As such, small molecule regulators of ACs and PDEs are important as chemical probes to study the roles of individual ACs or PDEs and as potential therapeutics. In the past, our lab has expressed 15 mammalian PDE genes in S. pombe, replacing the endogenous Cgs2 PDE. High throughput screens for PDE inhibitors identified novel compounds that show relevant biological activity in mammalian cell culture assays. The aim of this thesis is to develop tools to understand the mechanism of interaction between key regulators of the cAMP pathway and small molecules. The current study is comprised of two parts. In the first part of this thesis, I developed a genetic screen that detected alleles whose proteins remain active in the presence of BC54 and was to confirm the effect of the PDE4BT407A mutation using cell-based assays and in vitro enzyme assays. In the second part of this thesis, I developed and carried out HTSs using a PKA-repressed GFP reporter that can identify compounds that reduce PKA activity, which would include PDE activators and AC or GNAS1 inhibitors. To date, I have identified three AC inhibitors that appear to act on several of the ten different mammalian ACs. To our knowledge, this is the first time a large HTS has identified AC inhibitors, where inhibition was assessed inside the cells. The findings in this thesis will be useful in the design of more effective PDE inhibitors and in the development of novel chemical probes for studying cAMP signaling in mammalian cells. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

Thesis advisor: Charles Hoffman / Cyclic adenosine monophosphate (cAMP) and the second messengers that modulate several biological processes are regulated by adenylyl cyclase (AC) and cyclic nucleotide phosphodiesterases (PDEs). ACs and PDEs are comprised of superfamilies of enzymes that are viewed as druggable targets due to their many distinct biological roles and tissue-specific distribution. As such, small molecule regulators of ACs and PDEs are important as chemical probes to study the roles of individual ACs or PDEs and as potential therapeutics. In the past, our lab has expressed 15 mammalian PDE genes in S. pombe, replacing the endogenous Cgs2 PDE. High throughput screens for PDE inhibitors identified novel compounds that show relevant biological activity in mammalian cell culture assays. The aim of this thesis is to develop tools to understand the mechanism of interaction between key regulators of the cAMP pathway and small molecules. The current study is comprised of two parts. In the first part of this thesis, I developed a genetic screen that detected alleles whose proteins remain active in the presence of BC54 and was to confirm the effect of the PDE4BT407A mutation using cell-based assays and in vitro enzyme assays. In the second part of this thesis, I developed and carried out HTSs using a PKA-repressed GFP reporter that can identify compounds that reduce PKA activity, which would include PDE activators and AC or GNAS1 inhibitors. To date, I have identified three AC inhibitors that appear to act on several of the ten different mammalian ACs. To our knowledge, this is the first time a large HTS has identified AC inhibitors, where inhibition was assessed inside the cells. The findings in this thesis will be useful in the design of more effective PDE inhibitors and in the development of novel chemical probes for studying cAMP signaling in mammalian cells. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Biology.

L'objectif de cette thèse est d'explorer les mécanismes d'émission des neutrons émis lors du processus de la fission. En particulier, la question ouverte de l'existence d'une anisotropie dynamique dans le centre de masse des fragments de fission et/ou de la possibilité d'une émission de neutrons de scission est explorée. La thèse débute par une introduction aux concepts théoriques permettant de décrire les processus de fission et les mécanismes d'émission de neutrons. La nécessité de concevoir une méthode d'analyse appropriée pour caractériser des mécanismes très subtiles est discutée, en insistant sur l'importance de maîtriser les biais expérimentaux. Le travail effectué a exigé un effort important de simulation, à travers le développement d'une procédure Monte Carlo pour décrire la fission spontanée du 252Cf, ainsi qu'une modélisation du dispositif expérimental de l'expérience CORA3.Nous proposons pour la première fois une approche simultanée et indépendante des deux mécanismes, émission de scission et anisotropie dynamique, ainsi que des valeurs quantitatives d'anisotropie et d'émission de scission mesurées expérimentalement. / The subject of this thesis is to explore the neutron emission mechanisms in the fission process. In particular a long standing open question, the existence of a dynamical anisotropy in the centre of mass of the fission fragments and/or a possible scission neutron emission is explored. The thesis starts with an overview of the theoretical concepts on the fission process and on the neutron emission mechanisms. Also the necessity to conceive an appropriate analysis method is stressed when a very subtle mechanism is studied as various approximations and/or experimental biases not completely handled can hide the physical phenomena. In the presented work a huge effort was required to write a Monte Carlo procedure based on a coherent model for the spontaneous fission of 252Cf and to couple it with the devices exploited in the CORA3 experiment.

This study explores an innovative approach to control the droplet size distribution produced by an electrospray with the intention of eventually being able to deliver precisely controlled quantities of precursor materials for nanofabrication. The technique uses a thermionic cathode to charge the droplets in excess of the Rayleigh limit, leading to droplet breakup or fission. The objective of these experiments was to assess whether the proposed technique could be used to produce a new droplet size distribution with a smaller mean droplet diameter without excessively broadening the distribution. An electrospray was produced in a vacuum chamber using a dilute mixture of ionic liquid. During their transit from the capillary source to a diagnostic instrument, the resulting droplets were exposed to an electron stream with controlled flux and kinetic energy. The droplets were sampled in an inductive charge detector to characterize changes in the size distribution. A positively biased anode electrode was used to collect electron current during droplet exposure. This collected current was used as the primary control variable and used as a measure of the electron flux. The anode bias voltage was a secondary control variable and used as a measure of the electron energy. In a series of seven tests, two sets showed evidence of fission having occurred resulting in the formation of two droplet populations after electron bombardment. Three sets of results showed evidence of a single droplet population after electron bombardment, but shifted to a smaller mean diameter, and one set of results was inconclusive. Because of the large standard deviation in the droplet diameter distributions, the two cases in which a second population was evident were the strongest indication that droplet fission had occurred.