The half-lives of Sr90 and Cs137 were measured by the method of observing the disintegration rate rate of a known number of atoms. A 4(pi) proportional counter was designed and constructed to measure the absolute disintegration rates of the samples used. The efficiency of the counter was tested with calibrated radioactive solutions from the National Bureau of Standards. The submicrogram quantities of the carrier-free radioisotopes used for counting were determined with the mass spectrometer along with isotope dilution techniques. Independent evidence is given to support the half-lives found in this investigation. / Thesis / Master of Science (MS)

The present investigation was prompted by several considerations. In previous studies there was considerable variance with regard to the reported values for the half-lives of the isomeric and ground states in 164 Ho. There was also considerable variance with regard to the values reported for the branching ratios and the relative intensities of the transitions. Thus a further study of the problem was needed.

<p> The performance of a relative decay rate measurement technique was investigated. Determinations of the half-lives of the isotopes copper-64 and ruthenium-97 in various chemical states were attempted as illustrations of the use of the method. Applications of the technique are suggested.</p> / Thesis / Master of Science (MSc)

A series of studies from our lab have investigated the threading polyintercalator approach to sequence specific DNA binding using a 1,4,5,8-naphthalene tetracarboxylic diimide (NDI) intercalating unit connected by flexible peptide linkers. Herein is a report of the sequence specificity, as well as a detailed kinetic analysis, of a threading NDI tetraintercalator. DNase I footprinting using two ~500 base pair DNA fragments containing one designed binding site for the tetraintercalator confirmed highly sequence specific binding. Kinetic analyses include 1H NMR, gel mobility-shift assays, and stopped-flow UV measurements to reveal a polyintercalation binding mode that demonstrates significant similarities between association rate profiles and rate constants for the tetraintercalator binding to its preferred versus a random oligonucleotide sequence. Sequence specificity was found to derive almost entirely from large differences in dissociation rates from the preferred versus random oligonucleotide sequences. Interestingly, the dissociation rate constant of the tetraintercalator complex dissociating from its preferred binding site was extremely slow, corresponding to a 16 day half-life at a benchmark 100 mM [Na+]. This dissociation result for the tetraintercalator is one of the longest bound half-lives yet measured, and to the best of our knowledge, the longest for a DNA binding small molecule. Such a long-lived complex raises the possibility of using threading polyintercalators to disrupt biological processes for extended periods. Current focus is given to deciphering a mechanism for the molecular recognition of the tetraintercalator preferred binding site within a long sequence of DNA. Initial DNase I footprinting results on an approximate 500mer DNA sequence containing three sequential preferred binding sites reveal that the tetraintercalator likely locates its designed binding site by a macro- or microscopic dissociation/re-association type of mechanism. Cooperativity is a possible ally to binding, leaving future studies to distinguish the mechanism for molecular recognition in a manner that is capable of circumventing cooperative binding. Taken together, the threading polyintercalation binding mode presents an interesting topology to sequence specific DNA binding. Extraordinarily long dissociation rates from preferred binding sites offers many future possibilities to disrupt biological processes in vivo. / text

Persistence is one of the core criteria in chemical exposure and hazard assessment. It is often defined as the half-life for the removal of a chemical from a specified environment by transformation. Chemicals with long transformation half-lives may pose high risks for wildlife or humans and be subject to long-range transport to remote areas. It is challenging to measure persistence directly in the field in view of the complexity of the natural environment and spatial and temporal variability in environmental conditions that may affect degradation. The mass balance approach is the most commonly used method for field measurement of persistence. In this thesis an alternative to the traditional mass balance approach that uses benchmarking is proposed and evaluated using models and field application. The benchmarking approach compares the relative behavior of chemicals, rather than measuring the absolute value of a property. The unknown property (persistence in this thesis) of test chemicals can be estimated by comparison against another chemical for which this property is known. In Paper I, the potential of benchmarking to measure persistence in the field was evaluated by modeling. A framework for applying benchmarking to measure persistence in the field was developed. Lake systems with hydraulic residence times of the order of months were identified as appropriate field sites to measure the persistence of chemicals that are close to the regulatory thresholds, which are also on the scale of months. Field studies in two Swedish lakes were conducted. Both are shallow lakes, whereas Norra Bergundasjön (Paper II) has a longer residence time (four months) than Boren (one to two months; Paper III). In Paper II the benchmarking approach was tested to measure the persistence of a group of chemicals that were expected to stay in the water phase. Acesulfame K (artificial sweetener) without observable degradation in the lake was used as the benchmark chemical. The persistence of 9 pharmaceuticals and one X-ray contrast agent was measured to range from &lt;1-2 days (ketoprofen) to 580-5700 days (carbamazepine). The results obtained using the benchmarking approach agreed well with the mass balance approach, indicating that the benchmarking approach can be a valid and useful method to measure persistence in the field. In Paper III the seasonality in chemical persistence was investigated by benchmarking. The seasonal difference in chemical persistence was found to be largest between spring and autumn. The persistence of 5 chemicals in spring were lower than in autumn, mainly attributed to lower temperature and less sunlight in autumn. The spatial variation of the persistence of chemicals was observed by comparing the persistence of chemicals in spring in the two lakes. Thus benchmarking is a useful tool to study the temporal and spatial variation of persistence in the real environment.   Paper IV explores the potential of benchmarking thoroughly and the application of benchmarking in a regulatory context. Benchmarking could facilitate more field measurements of persistence, leading to a better understanding of the temporal and spatial variability of persistence in various environments and a basis for lab-to-field extrapolation. Besides quantitative estimation of persistence in the field, benchmarking can be applied to determine the relative magnitude of persistence, called threshold benchmarking which could be a valuable tool in regulatory processes. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 4: Manuscript.</p>

Ortho-Fluorazobenzole stellen eine der interessantesten Familien von Azobenzolen dar, die mit sichtbarem Licht geschaltet werden können. Seit ihrer ersten Erwähnung durch unsere Gruppe im Jahr 2012 wurden sie aufgrund ihrer hervorragenden photo/elektrochemischen Eigenschaften intensiv auf molekularer Ebene, für biologische Anwendungen und in Volumenmaterialien untersucht. Typischerweise können ortho-fluorierte Azobenzole in beide Richtungen mit sichtbarem Licht und hohem Photoumsatz geschaltet werden. Außerdem weisen die Z-Isomere überlegene thermische Halbwertszeiten (bis zu 2 Jahre) auf. In dieser Arbeit werden zwei Projekte vorgestellt, die auf unseren kürzlich erworbenen Kenntnissen über fluorierte Azobenzole basieren. Zunächst wurde ein gemischtes Azobenzoldimer dargestellt, welches komplementäre Absorptionsprofile sowie die leichte elektrochemische Isomerisierung ausnutzt und dadurch dessen vier Schaltzustände orthogonal adressiert werden können. Dieses wurde bezüglich seiner Photoisomerisierung, thermischen Relaxation und seines elektrochemischen Schaltverhaltens untersucht. Anschließend haben wir ein 3D-Polymernetzwerk durch kovalente Vernetzung einer polyethylenglykol(PEG)-basierten Vorstufe mit einem fluorierten Azobenzol hergestellt, was zur Bildung eines photoempfindlichen Hydrogels führte. Als Folge davon konnten die mechanischen Eigenschaften des Gels durch Bestrahlung mit sichtbarem Licht und der dadurch ausgelösten Azobenzol-Isomerisierung reversibel beeinflusst werden. / Ortho-fluoroazobenzenes represent one of the most interesting family of visible-light-responsive azobenzenes. Since the first report by our group in 2012, they have been intensively studied at the molecular level, for biological applications, and in bulk materials, due to their outstanding photo/electrochemical properties. Typically, ortho-fluorinated azobenzenes can isomerize in both directions using visible light with high photo-conversions, and the Z-isomers exhibit superior thermal half-lives (up to 2 years). In this work, two projects based on our recently acquired knowledge of fluorinated azobenzenes are presented. First, exploiting complementary absorption profiles and ease of electrochemical isomerization, a mixed azobenzene dimer, whose four isomers can be orthogonally addressed was prepared. It was investigated from its photo-isomerization, thermal relaxation, and electrochemical isomerization aspects. Second, we prepared a photo-responsive hydrogel via covalently cross-linking a poly(ethylene glycol) (PEG)-based precursor with a fluorinated azobenzene forming a 3D polymer network. As a result, the gel’s mechanical properties could be tuned reversibly due to the azobenzenes’ isomerization triggered by visible light irradiation.

The existence of highest proton numbers at which the nuclear landscape cease to ex- ist, the end of the periodic table of elements and the limits of the existence of the nu- clei are some of the difficult questions to answer. To explore those questions, we in- vestigated hyperheavy nuclei (Z ≥ 126) using covariant density functional theory. We demonstrate the existence of three regions of spherical hyperheavy nuclei centered around (Z ∼ 138, N ∼ 230), (Z ∼ 156, N ∼ 310) and (Z ∼ 174, N ∼ 410). Also, we explored other properties of hyperheavy nuclei such as octupole deformation, alpha decay half lives, chemical potential, etc.

The GERDA experiment is searching for the neutrinoless double beta (0vbb) decay of Ge-76. By that, it tries to answer two long standing questions about the neutrino: 'How large is the neutrino mass?' and 'Is the neutrino either Dirac or Majorana particle?'. Additionally, an observation would imply that lepton number is not conserved, which is an important puzzle piece for theories explaining the asymmetry between matter and anti-matter in the universe. The effective Majorana electron neutrino mass can be extracted from the half-life of the 0vbb -decay. However, during that conversion large uncertainties are added through nuclear matrix elements, that are calculated by a variety of theoretical models. Experimental input is required to constrain such models and their parameters to improve the reliability of the calculations. Additional input can be obtained by comparing the model predictions for the two neutrino double beta (2vbb) decay to the ground state, but also for decay modes to excited states of the daughter nuclide with measurements. The latter decay modes have not yet been observed in the case of Ge-76. The event signature of transitions to excited states is enhanced by de-excitation gamma-rays. The GERDA experiment employs an array of bare germanium semi-conductor detectors in a liquid argon cryostat. This array is suited to search for excited state transition in the 2vbb and 0vbb -decay modes using data with coincident energy depositions in multiple detectors. This work presents the preparation and characterisation of this data set, which includes the evaluation and correction of crosstalk between detector channels, the determination of the energy resolution of the detectors and the modelling of background. In an analysis combining 22 kgyr of Phase I data with the first 35 kgyr of Phase II data of GERDA, no signal has been observed for 2/0vbb -decays of Ge-76 to the energetically lowest three excited states in Se-76. New limits have been set for the two neutrino decay modes at T1/2(2v)(0+g.s. to 0+1) > 3.1x10^23 yr, T1/2(2v)(0+g.s. to 2+1) > 3.4x10^23 yr T1/2(2v)(0+g.s. to 2+2) > 2.5x10^23 yr with 90% credibility using a Bayesian approach, improving upon the limits obtained in Phase I. The corresponding sensitivities are 3.6x10^23 yr, 6.7x10^23 yr and 3.7x10^23 yr, respectively. First limits are set for the neutrinoless decay modes in the order of (10^24-10^25) yr. Reaching the desired Phase II exposure of 100 kgyr, the sensitivities will increase by up to 50%.

Der erste Teil der Arbeit beschreibt die Etablierung einer modifizierten Form des klassichen SILAC-Verfahrens, das in der quantitativen Massenspektrometrie zur Bestimmung von relativen Änderungen in Proteinmengen benutzt wird. Im sog. „pulsed SILAC (pSILAC)“ Verfahren werden Zellen im Zuge einer differentiellen Behandlung in Kulturmedien transferiert, die unterschiedlich Isotop-markierte Aminosäuren enthalten. Da hier die Quantifizierung auf dem Verhältnis der neusynthetisierten Proteinmengen beruht, können gezielt Unterschiede in der Proteinproduktion bestimmt werden. Mit Hilfe von pSILAC konnte im zweiten Teil der Arbeit erstmals quantitativ erfasst werden, welchen Einfluss microRNAs auf die Proteinsynthese ausüben. So konnte gezeigt werden, dass sowohl die Überexpression als auch die Repression einzelner microRNAs die Produktion hunderter Proteine beeinflussen kann. Außerdem konnten Genprodukte identifiziert werden, die ausschließlich translational reguliert werden. Die Messung von Proteinneusynthese ermöglichte auch die Bestimmung von Proteinumsatzraten, dargestellt im dritten Teil der Arbeit. Zusammen mit mRNA-Umsatzraten sowie Protein- und mRNA-Mengen bilden sie die Grundlage für eine dynamische Beschreibung zelluärer Genexpression. Durch den gleichzeitigen Einsatz des Nukleosidanalogons 4-Thiouridin (4sU) und von schweren Aminosäuren (SILAC) konnte eine metabolische Markierung neusynthetiserter mRNAs und Proteine in murinen Fibroblasten erreicht und damit eine Berechnung von Protein- und mRNA-Halbwertszeiten und absoluten Mengen für ca. 5,000 Gene ermöglicht werden. Während mRNA- und Proteinenmengen deutlich korrelierten, war zwischen mRNA- und Proteinhalbwertszeiten nur eine äußerste schwache Korrelation zu erkennen. Dennoch stehen mRNA- und Proteinumsatzraten nicht einem willkürlichen Zusammhang zu einander, da bestimmte Kombinationen von mRNA- und Proteinhalbwertszeiten eine Optimierung von Genen hinsichtlich ihrer biologischen Funktionen erkennen ließen. / The first part of the thesis describes the establishment of a modified version of the classic SILAC approach routinely used in quantitative mass spectrometry (MS) to assay relative changes in protein levels. In the newly-devised approach termed pulsed SILAC (pSILAC) differentially treated cells are transferred to culture medium supplemented with different versions of stable-isotope labeled heavy amino acids. As MS-based relative quantification is exclusively based on the newly-synthesized heavy protein amounts the method enables the detection of differences in protein production resulting from the treatment. The second part of the thesis shows the use of pSILAC to globally quantify the impact of microRNAs onto the proteome. Ectopic over-expression or knock-down of a single microRNA both affected protein production of hundreds of proteins. pSILAC identified several target genes as exclusively translationally regulated as changes in corresponding transcript levels were virtually absent. Measuring newly-synthesized protein amounts with heavy amino acids in a pulsed-labeling fashion has also been used to determine turnover rates of individual proteins, described in the third part of the present work. Along with transcript turnover as well as mRNA and protein levels they are essential for a dynamic description of gene expression. Simultaneous application of the nucleoside analogue 4-thiouridine (4sU) and heavy amino acids (SILAC) to metabolically label newly-produced mRNAs and proteins in mouse fibroblasts resulted in the calculation of mRNA and protein lifetimes and absolute levels for approximately 5,000 genes. While mRNA and protein levels were overall well correlated, a correlation between mRNA and protein half-lives was virtually absent. Yet this seemingly chaotic distribution of mRNA and protein half-lives was highly instructive since specific gene subsets have obviously evolved distinct combinations of half-lives that relate to their biological functions.

L’étude de la décroissance β est un outil fantastique pour approfondir notreconnaissance de l’interaction faible décrite par le Modèle Standard. Ce modèle et laphysique au-delà peuvent être testés par des mesures précises de paramètres caractérisantces décroissances. Parmi ces tests, la vérification de l’hypothèse de la conservation ducourant vectoriel (CVC) et de l’unitarité de la matrice de mélange des quarks de Cabibbo-Kobayashi-Maskawa (CKM) sont d’un grand intérêt. Pour cela, les paramètres caractérisantles transitions β doivent être déterminés très précisément. Les meilleures précisions ont étéobtenues pour les transitions super-permises de Fermi de type 0+ → 0+. Cependant, il existed’autres types de décroissances pour réaliser ces tests, par exemple, les décroissances βmiroir. À ce jour, elles ne permettent pas d’atteindre les précisions obtenues avec lestransitions de type 0+ → 0+. Pour améliorer cela, de nouvelles mesures très précises desparamètres expérimentaux caractérisant ces transitions, comme la demi-vie et le rapportd’embranchement, sont nécessaires. C’est pourquoi une expérience a été réalisée àl’université de Jyväskylä en Finlande, afin d’étudier la décroissance β des noyaux miroir 23Mget 27Si et de mesurer ces paramètres. Les valeurs des demi-vies obtenues pour ces deuxnoyaux sont respectivement dix fois et sept fois plus précises que les moyennes de lalittérature. La valeur obtenue pour le rapport d’embranchement de 23Mg est trois fois plusprécise que la moyenne de la littérature, celui de 27Si étant déjà connu avec une très grandeprécision (0,02%), n’a pas été déterminé avec une meilleure précision. / Beta decays are a fantastic tool to study the weak interaction described by theStandard Model. This model and the physics beyond can be tested by precisemeasurements of nuclear β decays. Among these tests, the conserved vector current (CVC)hypothesis and the unitarity of the Cabibbo-Kobayashi-Maskawa (CKM) quark-mixing matrixare of great interest. For these, the parameters of β transitions must be precisely determined.The highest precisions have been obtained with superallowed 0+ → 0+ Fermi β decays.However, there are other possibilities to make these tests, for example mirror β decays. Fornow, they do not allow to achieve the precision of the 0+ → 0+ transitions. To improve this,new accurate measurements of experimental parameters characterizing these transitions,such as the half-life and the branching ratio, are needed. For this purpose, an experimenthas been carried out at the University of Jyväskylä to study the mirror β decays of 23Mg and27Si and to measure these parameters. The half-life values obtained for these two nuclei are,respectively, ten times and seven times more precise than the literature averages. The valueof the branching ratio obtained for 23Mg is three times more precise than the literatureaverage; the one of 27Si has not been improved as it is already precisely known (0.02%).