Analyses of the usefulness of Software Defined Storage Solutions for Web-based Digital Preservation Applications

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Practical preservation with Arkivum & Eprints

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Influence of surface functionalization on the behavior of silica nanoparticles in biological systems

Personalized nanomedicine has been shown to provide advantages over traditional clinical imaging, diagnosis, and conventional medical treatment. Using nanoparticles can enhance and clarify the clinical targeting and imaging, and lead them exactly to the place in the body that is the goal of treatment. At the same time, one can reduce the side effects that usually occur in the parts of the body that are not targets for treatment. Nanoparticles are of a size that can penetrate into cells. Their surface functionalization offers a way to increase their sensitivity when detecting target molecules. In addition, it increases the potential for flexibility in particle design, their therapeutic function, and variation possibilities in diagnostics. Mesoporous nanoparticles of amorphous silica have attractive physical and chemical characteristics such as particle morphology, controllable pore size, and high surface area and pore volume. Additionally, the surface functionalization of silica nanoparticles is relatively straightforward, which enables optimization of the interaction between the particles and the biological system. The main goal of this study was to prepare traceable and targetable silica nanoparticles for medical applications with a special focus on particle dispersion stability, biocompatibility, and targeting capabilities. Nanoparticle properties are highly particle-size dependent and a good dispersion stability is a prerequisite for active therapeutic and diagnostic agents. In the study it was shown that traceable streptavidin-conjugated silica nanoparticles which exhibit a good dispersibility could be obtained by the suitable choice of a proper surface functionalization route. Theranostic nanoparticles should exhibit sufficient hydrolytic stability to effectively carry the medicine to the target cells after which they should disintegrate and dissolve. Furthermore, the surface groups should stay at the particle surface until the particle has been internalized by the cell in order to optimize cell specificity. Model particles with fluorescently-labeled regions were tested in vitro using light microscopy and image processing technology, which allowed a detailed study of the disintegration and dissolution process. The study showed that nanoparticles degrade more slowly outside, as compared to inside the cell. The main advantage of theranostic agents is their successful targeting in vitro and in vivo. Non-porous nanoparticles using monoclonal antibodies as guiding ligands were tested in vitro in order to follow their targeting ability and internalization. In addition to the targeting that was found successful, a specific internalization route for the particles could be detected. In the last part of the study, the objective was to clarify the feasibility of traceable mesoporous silica nanoparticles, loaded with a hydrophobic cancer drug, being applied for targeted drug delivery in vitro and in vivo. Particles were provided with a small molecular targeting ligand. In the study a significantly higher therapeutic effect could be achieved with nanoparticles compared to free drug. The nanoparticles were biocompatible and stayed in the tumor for a longer time than a free medicine did, before being eliminated by renal excretion. Overall, the results showed that mesoporous silica nanoparticles are biocompatible, biodegradable drug carriers and that cell specificity can be achieved both in vitro and in vivo.

New [18F]Tracers for Alzheimer's Disease Imaging. Labeling Synthesis And Biological Testing

Alzheimer’s disease (AD) is the most common form of dementia. Characteristic changes in an AD brain are the formation of β-amyloid protein (Aβ) plaques and neurofibrillary tangles, though other alterations in the brain have also been connected to AD. No cure is available for AD and it is one of the leading causes of death among the elderly in developed countries. Liposomes are biocompatible and biodegradable spherical phospholipid bilayer vesicles that can enclose various compounds. Several functional groups can be attached on the surface of liposomes in order to achieve long-circulating target-specific liposomes. Liposomes can be utilized as drug carriers and vehicles for imaging agents. Positron emission tomography (PET) is a non-invasive imaging method to study biological processes in living organisms. In this study using nucleophilic 18F-labeling synthesis, various synthesis approaches and leaving groups for novel PET imaging tracers have been developed to target AD pathology in the brain. The tracers were the thioflavin derivative [18F]flutemetamol, curcumin derivative [18F]treg-curcumin, and functionalized [18F]nanoliposomes, which all target Aβ in the AD brain. These tracers were evaluated using transgenic AD mouse models. In addition, 18F-labeling synthesis was developed for a tracer targeting the S1P3 receptor. The chosen 18F-fluorination strategy had an effect on the radiochemical yield and specific activity of the tracers. [18F]Treg-curcumin and functionalized [18F]nanoliposomes had low uptake in AD mouse brain, whereas [18F]flutemetamol exhibited the appropriate properties for preclinical Aβ-imaging. All of these tracers can be utilized in studies of the pathology and treatment of AD and related diseases.

Implementation of Quantitative Reaction-based Model Refinement

Building a computational model for complex biological systems is an iterative process. It starts from an abstraction of the process and then incorporates more details regarding the specific biochemical reactions which results in the change of the model fit. Meanwhile, the model’s numerical properties such as its numerical fit and validation should be preserved. However, refitting the model after each refinement iteration is computationally expensive resource-wise. There is an alternative approach which ensures the model fit preservation without the need to refit the model after each refinement iteration. And this approach is known as quantitative model refinement. The aim of this thesis is to develop and implement a tool called ModelRef which does the quantitative model refinement automatically. It is both implemented as a stand-alone Java application and as one of Anduril framework components. ModelRef performs data refinement of a model and generates the results in two different well known formats (SBML and CPS formats). The development of this tool successfully reduces the time and resource needed and the errors generated as well by traditional reiteration of the whole model to perform the fitting procedure.

Modelling the exothermic heat and the demand of cooling in paper and pulp industry biological wastewater treatment

This master thesis presents a study on the requisite cooling of an activated sludge process in paper and pulp industry. The energy consumption of paper and pulp industry and it’s wastewater treatment plant in particular is relatively high. It is therefore useful to understand the wastewater treatment process of such industries. The activated sludge process is a biological mechanism which degrades carbonaceous compounds that are present in waste. The modified activated sludge model constructed here aims to imitate the bio-kinetics of an activated sludge process. However, due to the complicated non-linear behavior of the biological process, modelling this system is laborious and intriguing. We attempt to find a system solution first using steady-state modelling of Activated Sludge Model number 1 (ASM1), approached by Euler’s method and an ordinary differential equation solver. Furthermore, an enthalpy study of paper and pulp industry’s vital pollutants was carried out and applied to revise the temperature shift over a period of time to formulate the operation of cooling water. This finding will lead to a forecast of the plant process execution in a cost-effective manner and management of effluent efficiency. The final stage of the thesis was achieved by optimizing the steady state of ASM1.