DNA repair pathways in radiation induced cellular damage: a molecular approach

__Abstract__ DNA damage, especially double-strand breaks, can be induced by endogenous or exogenous darnaging agents, such as ionizing radiation. Repair of DNA damage is very important in maintaining genomic stability. Incorrect repair may lead to chromosomal aberrations, translocations and deletions. Consequently, incorrect repair might result in oncogenic transformation of cells, which can lead to the development of cancer. Thus, unreaveling the pathways of double-strand break repair is essential in understanding the genetic interactions that lead to ancogen ie changes. Biochemica I studies have provided insight into the molecular mechanisms by which various proteins involved in repair of double-strand breaks perfarm these essential tasks. The next step ahead is analyzing the relationship between the individual biochemical activities of doublestrand break repair proteins and their coordinated action in the context of the living cell. This thesis describes the cellular behaviour and cooperation of the mammalian double-strand break repair genes Rad51, Rad52, Rad54 and Mre11 after induction of DNA damage by ionizing radiation. Furthermore, the possible use for a predictive assay that measures individual radiosensitivity in humans, ba

Molecular Imaging of Central Dopamine in Obesity : A Qualitative Review across Substrates and Radiotracers

Dopamine is a neurotransmitter that plays a crucial role in adaptive behavior. A wealth of studies suggests obesity-related alterations in the central dopamine system. The most direct evidence for such differences in humans comes from molecular neuroimaging studies using positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of the current review is to give a comprehensive overview of molecular neuroimaging studies that investigated the relation between BMI or weight status and any dopamine target in the striatal and midbrain regions of the human brain. A structured literature search was performed and a summary of the extracted findings are presented for each of the four available domains: (1) D2/D3 receptors, (2) dopamine release, (3) dopamine synthesis, and (4) dopamine transporters. Recent proposals of a nonlinear relationship between severity of obesity and dopamine imbalances are described while integrating findings within and across domains, after which limitations of the review are discussed. We conclude that despite many observed associations between obesity and substrates of the dopamine system in humans, it is unlikely that obesity can be traced back to a single dopaminergic cause or consequence. For effective personalized prevention and treatment of obesity, it will be crucial to identify possible dopamine (and non-dopamine) profiles and their functional characteristics.Peer reviewe

Multiple observations for secret-key binding with SRAM PUFs

We present a new Multiple-Observations (MO) helper data scheme for secret-key binding to an SRAM-PUF. This MO scheme binds a single key to multiple enrollment observations of the SRAM-PUF. Performance is improved in comparison to classic schemes which generate helper data based on a single enrollment observation. The performance increase can be explained by the fact that the reliabilities of the different SRAM cells are modeled (implicitly) in the helper data. We prove that the scheme achieves secret-key capacity for any number of enrollment observations, and, therefore, it is optimal. We evaluate performance of the scheme using Monte Carlo simulations, where an off-the-shelf LDPC code is used to implement the linear error-correcting code. Another scheme that models the reliabilities of the SRAM cells is the so-called Soft-Decision (SD) helper data scheme. The SD scheme considers the one-probabilities of the SRAM cells as an input, which in practice are not observable. We present a new strategy for the SD scheme that considers the binary SRAM-PUF observations as an input instead and show that the new strategy is optimal and achieves the same reconstruction performance as the MO scheme. Finally, we present a variation on the MO helper data scheme that updates the helper data sequentially after each successful reconstruction of the key. As a result, the error-correcting performance of the scheme is improved over time

Over de rechtsstaat en het ‘aso-azc’

Sinds 2017 worden asielzoekers die overlast veroorzaken in reguliere opvangcentra niet langer meer op straat gezet, maar overgeplaatst naar speciale toezichtlocaties waar hun vrijheid in verregaande mate wordt beperkt. In deze bijdrage wordt deze overplaatsing van asielzoekers onderzocht vanuit het perspectief van de rechtsstaat. De rechtsstaat is een veelgebruikt toetsingskader voor overheidshandelen. De vraag waarom de rechtsstaat van zo fundamenteel belang is, wordt echter vaak niet expliciet beantwoord. Deze bijdrage neemt als uitgangspunt dat de rechtsstaat noodzakelijk is voor het waarborgen van een fundamentele vorm van vrijheid: vrijheid als non dominantie. Om deze vorm van vrijheid te kunnen waarborgen is het van belang dat de machtsuitoefening door de staat voldoende wordt gecontroleerd door het recht, waarvoor legaliteit, een verantwoordingsplicht en het respecteren van de dualiteit in het recht noodzakelijke elementen zijn. Bij de aanpak van overlastgevende asielzoekers wordt hier niet altijd aan voldaan. Deze conclusie is niet alleen relevant voor de verdere ontwikkeling van regelgeving en rechtspraak over overlastgevende asielzoekers, maar laat ook het belang zien van het hier ontwikkelde toetsingskader voor de evaluatie van regelgeving en rechtspraak op andere terreinen van machtsuitoefening door de overheid

Stochastic target hitting time and the problem of early retirement

We consider a problem of optimal control of a “retirement investment fund” over a finite time horizon with a target hitting time criteria. That is, we wish to decide, at each stage, what percentage of the current retirement fund to allocate into the limited number of investment options so that a decision maker can maximize the probability that his or her wealth exceeds a target prior to his or her retirement. We use Markov decision processes with probability criteria to model this problem and give an example based on data from certain options available in an Australian retirement fund