Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models.

The present study was performed in an attempt to develop an in vitro integrated testing strategy (ITS) to evaluate drug-induced neurotoxicity. A number of endpoints were analyzed using two complementary brain cell culture models and an in vitro blood-brain barrier (BBB) model after single and repeated exposure treatments with selected drugs that covered the major biological, pharmacological and neuro-toxicological responses. Furthermore, four drugs (diazepam, cyclosporine A, chlorpromazine and amiodarone) were tested more in depth as representatives of different classes of neurotoxicants, inducing toxicity through different pathways of toxicity. The developed in vitro BBB model allowed detection of toxic effects at the level of BBB and evaluation of drug transport through the barrier for predicting free brain concentrations of the studied drugs. The measurement of neuronal electrical activity was found to be a sensitive tool to predict the neuroactivity and neurotoxicity of drugs after acute exposure. The histotypic 3D re-aggregating brain cell cultures, containing all brain cell types, were found to be well suited for OMICs analyses after both acute and long term treatment. The obtained data suggest that an in vitro ITS based on the information obtained from BBB studies and combined with metabolomics, proteomics and neuronal electrical activity measurements performed in stable in vitro neuronal cell culture systems, has high potential to improve current in vitro drug-induced neurotoxicity evaluation.

Nanoantenna enhanced emission of lightharvesting complex 2: the role of resonance, polarization, and radiative and non-radiative rates

Nanoantennae show potential for photosynthesis research for two reasons; first by spatially confining light for experiments which require high spatial resolution, and second by enhancing the photon emission of single light-harvesting complexes. For effective use of nanoantennae a detailed understanding of the interaction between the nanoantenna and the light-harvesting complex is required. Here we report how the excitation and emission of multiple purple bacterial LH2s (light-harvesting complex 2) are controlled by single gold nanorod antennae. LH2 complexes were chemically attached to such antennae, and the antenna length was systematically varied to tune the resonance with respect to the LH2 absorption and emission. There are three main findings. (i) The polarization of the LH2 emission is fully controlled by the resonant nanoantenna. (ii) The largest fluorescence enhancement, of 23 times, is reached for excitation with light at λ = 850 nm, polarized along the long antenna-axis of the resonant antenna. The excitation enhancement is found to be 6 times, while the emission efficiency is increased 3.6 times. (iii) The fluorescence lifetime of LH2 depends strongly on the antenna length, with shortest lifetimes of [similar]40 ps for the resonant antenna. The lifetime shortening arises from an 11 times resonant enhancement of the radiative rate, together with a 2–3 times increase of the non-radiative rate, compared to the off-resonant antenna. The observed length dependence of radiative and non-radiative rate enhancement is in good agreement with simulations. Overall this work gives a complete picture of how the excitation and emission of multi-pigment light-harvesting complexes are influenced by a dipole nanoantenna.

Imprecise measurements in quantum mechanics

In this thesis the structure and properties of imprecise quantum measurements are investigated. The starting point for this investigation is the representation of a quantum observable as a normalized positive operator measure. A general framework to describe measurement inaccuracy is presented. Requirements for accurate measurements are discussed, and the relation of inaccuracy to some optimality criteria is studied. A characterization of covariant observables is given in the case when they are imprecise versions of a sharp observable. Also the properties of such observables are studied. The case of position and momentum observables is studied. All position and momentum observables are characterized, and the joint positionmomentum measurements are discussed.

Validation of plant dynamic model by online and laboratory measurements – a tool to predict online COD loads out of production of mechanical printing papers

COD discharges out of processes have increased in line with elevating brightness demands for mechanical pulp and papers. The share of lignin-like substances in COD discharges is on average 75%. In this thesis, a plant dynamic model was created and validated as a means to predict COD loading and discharges out of a mill. The assays were carried out in one paper mill integrate producing mechanical printing papers. The objective in the modeling of plant dynamics was to predict day averages of COD load and discharges out of mills. This means that online data, like 1) the level of large storage towers of pulp and white water 2) pulp dosages, 3) production rates and 4) internal white water flows and discharges were used to create transients into the balances of solids and white water, referred to as “plant dynamics”. A conversion coefficient was verified between TOC and COD. The conversion coefficient was used for predicting the flows from TOC to COD to the waste water treatment plant. The COD load was modeled with similar uncertainty as in reference TOC sampling. The water balance of waste water treatment was validated by the reference concentration of COD. The difference of COD predictions against references was within the same deviation of TOC-predictions. The modeled yield losses and retention values of TOC in pulping and bleaching processes and the modeled fixing of colloidal TOC to solids between the pulping plant and the aeration basin in the waste water treatment plant were similar to references presented in literature. The valid water balances of the waste water treatment plant and the reduction model of lignin-like substances produced a valid prediction of COD discharges out of the mill. A 30% increase in the release of lignin-like substances in the form of production problems was observed in pulping and bleaching processes. The same increase was observed in COD discharges out of waste water treatment. In the prediction of annual COD discharge, it was noticed that the reduction of lignin has a wide deviation from year to year and from one mill to another. This made it difficult to compare the parameters of COD discharges validated in plant dynamic simulation with another mill producing mechanical printing papers. However, a trend of moving from unbleached towards high-brightness TMP in COD discharges was valid.

Photoelectric Measurements and Modeling of Bacteriorhodopsin

Recent technology has provided us with new information about the internal structures and properties of biomolecules. This has lead to the design of applications based on underlying biological processes. Applications proposed for biomolecules are, for example, the future computers and different types of sensors. One potential biomolecule to be incorporated in the applications is bacteriorhodopsin. Bacteriorhodopsin is a light-sensitive biomolecule, which works in a similar way as the light sensitive cells of the human eye. Bacteriorhodopsin reacts to light by undergoing a complicated series of chemical and thermal transitions. During these transitions, a proton translocation occurs inside the molecule. It is possible to measure the photovoltage caused by the proton translocations when a vast number of molecules is immobilized in a thin film. Also the changes in the light absorption of the film can be measured. This work aimed to develop the electronics needed for the voltage measurements of the bacteriorhodopsin-based optoelectronic sensors. The development of the electronics aimed to get more accurate information about the structure and functionality of these sensors. The sensors used in this work contain a thick film of bacteriorhodopsin immobilized in polyvinylalcohol. This film is placed between two transparent electrodes. The result of this work is an instrumentation amplifier which can be placed in a small space very close to the sensor. By using this amplifier, the original photovoltage can be measured in more detail. The response measured using this amplifier revealed two different components, which could not be distinguished earlier. Another result of this work is the model for the photoelectric response in dry polymer films.

Ilmaan johdettavien päästöjen tarkkailun luotettavuus sellutehtaalla

Suomen ympäristönsuojelulaki (86/200) velvoittaa toiminnanharjoittajia olemaan selvillä päästöistään ja hakemaan ympäristöluvan ympäristön pilaantumisen vaaraa aiheuttavalle toiminnalle. Sellutehtaat tuottavat tietoa merkittävimmistä ilmaan johdettavista päästöistään mittaamalla niitä jatkuvatoimisesti. Tuloksia käytetään tiedottamisessa ja päätöksenteossa. Yksi tärkeimmistä käyttökohteista on ympäristöluvan ehtojen täyttymisen seuranta. Mittaustulosten on oltava luotettavia. Luotettavuutta voidaan arvioida vertailumittauksien ja mittausepävarmuustarkastelujen avulla. Tässä työssä määritettiin mittausepävarmuudet Imatran tehtaiden kuorikattilan (LCP-kattila) NOX-mittaukselle sekä sellutehtaan meesauunien ja soodakattiloiden mittauksille. Tämän jälkeen tarkasteltiin, kuinka mittausepävarmuus huomioidaan ympäristö¬luparajaseurannassa. Lopuksi arviointiin, kuinka jatkuvatoimisten mittalaitteiden laadunvarmistusstandardia SFS-EN 141481 voidaan soveltaa Imatran tehtailla. Tarkastellut jatkuvatoimiset mittaukset todettiin varsin luotettaviksi. Etenkin NOx¬mittaukset ovat luotettavia. Kuorikattila 2:lla luotettavuutta heikentää mittauspaikan epä¬edustavuus. Rikin yhdisteiden (SO2 ja TRS) mittausten luotettavuus on alhaisempi, koska mitattavat pitoisuudet ovat pieniä. Mittausten luotettavuus on kuin vertailumittausten. Kuorikattila 2:lla Mittausepävarmuus huomioidaan NOX-pitoisuuden lupaseurannassa LCP-asetuksen mukaisesti. Sellutehtaan TRS-päästöillä mittausepävarmuus voidaan huomioida joko LCP-asetuksen mukaisesti tai tilastomatemaattisesti. Kummallakin tavalla saadaan negatiivisia luparajaan verrattavia keskiarvoja. Standardia SFS-EN 141481 voidaan soveltaa kuorikattilalla mutta sellutehtaalla se voi olla epäkäytännöllistä, eikä välittömästi paranna mittausten luotettavuutta

Clinically occult metastases in patients with cutaneous melanoma. Detection with sentinel lymph node biopsy and whole body positron emission tomography

Objective: The aim of this study was to investigate the use of sentinel lymph node biopsy (SLNB) and whole body positron emission tomography (PET), with emphasis on surgical treatment and prognosis, in the detection of clinically occult metastases in patients with clinically localized cutaneous melanoma. Patients and methods: The study population consisted of 1255 patients with clinical stage I–II cutaneous melanoma, operated at Turku University Hospital between 1983 and 2007. 334 patients underwent SLNB and they were compared to 921 retrospective patients. A subgroup of 30 symptom-free patients with high risk melanoma underwent prospectively whole body PET 6–24 months postoperatively. Results: Overall, the disease-specific survival rate was 84.4 % at five years. Sex, Breslow thickness, age and nodal status were independent prognostic factors for survival. SLNB revealed occult nodal metastases in 17 % of the patients. There was no significant difference in disease-specific overall survival between SLNB patients and controls, but the nodal disease-free time was significantly longer suggesting better local control after SLNB and subsequent completion lymph node dissection. The followup time was different between the study cohorts and initial surgery was performed during different time periods. SLNB detected micrometastases in seven of 155 patients (4.5 %) with thin T1 primary melanoma and in four of 25 patients (16 %) with head and neck melanoma. In six of 30 asymptomatic patients with high risk melanoma (20 %), whole body PET detected occult distant metastases. Conclusion: Both SLNB and whole body PET were reliable methods to detect clinically occult metastases in patients with cutaneous melanoma. This upstaging altered the treatment in each case.

Monte Carlo simulation of x-ray spectra generated by kilo-electron-volt electrons

We present a general algorithm for the simulation of x-ray spectra emitted from targets of arbitrary composition bombarded with kilovolt electron beams. Electron and photon transport is simulated by means of the general-purpose Monte Carlo code PENELOPE, using the standard, detailed simulation scheme. Bremsstrahlung emission is described by using a recently proposed algorithm, in which the energy of emitted photons is sampled from numerical cross-section tables, while the angular distribution of the photons is represented by an analytical expression with parameters determined by fitting benchmark shape functions obtained from partial-wave calculations. Ionization of K and L shells by electron impact is accounted for by means of ionization cross sections calculated from the distorted-wave Born approximation. The relaxation of the excited atoms following the ionization of an inner shell, which proceeds through emission of characteristic x rays and Auger electrons, is simulated until all vacancies have migrated to M and outer shells. For comparison, measurements of x-ray emission spectra generated by 20 keV electrons impinging normally on multiple bulk targets of pure elements, which span the periodic system, have been performed using an electron microprobe. Simulation results are shown to be in close agreement with these measurements.

Gamma spectrometry and gamma and X-ray tomography of nuclear fuel

The purpose of gamma spectrometry and gamma and X-ray tomography of nuclear fuel is to determine both radionuclide concentration and integrity and deformation of nuclear fuel. The aims of this thesis have been to find out the basics of gamma spectrometry and tomography of nuclear fuel, to find out the operational mechanisms of gamma spectrometry and tomography equipment of nuclear fuel, and to identify problems that relate to these measurement techniques. In gamma spectrometry of nuclear fuel the gamma-ray flux emitted from unstable isotopes is measured using high-resolution gamma-ray spectroscopy. The production of unstable isotopes correlates with various physical fuel parameters. In gamma emission tomography the gamma-ray spectrum of irradiated nuclear fuel is recorded for several projections. In X-ray transmission tomography of nuclear fuel a radiation source emits a beam and the intensity, attenuated by the nuclear fuel, is registered by the detectors placed opposite. When gamma emission or X-ray transmission measurements are combined with tomographic image reconstruction methods, it is possible to create sectional images of the interior of nuclear fuel. MODHERATO is a computer code that simulates the operation of radioscopic or tomographic devices and it is used to predict and optimise the performance of imaging systems. Related to the X-ray tomography, MODHERATO simulations have been performed by the author. Gamma spectrometry and gamma and X-ray tomography are promising non-destructive examination methods for understanding fuel behaviour under normal, transient and accident conditions.

Three Wavelength Optical Probe for Surface Roughness Measurements of Paper Samples

In the present diploma work optical inspection methods were used to investigate surface roughness of paper samples. A special measurement setup, which includes three laser light sources of three different wavelengths, photodetector and goniometer, was used to measure the reflected laser light properties. The intensity of the light reflected in specular direction was measured versus the laser incidence angle for reference metal sample. The value of roughness was estimated and compared to initially known value of metal sample roughness. Thus, the measurement equipment and method were validated. Then the reflected intensity was measured versus reflection angle at constant incidence angle for the same metal sample and paper samples under investigation. The final values of the surface roughness were obtained from the analysis of the reflected intensity dependence. The results are in good correlation with other research groups.

Amônia (NH3) atmosférica: fontes, transformação, sorvedouros e métodos de análise

Ammonia is the most common alkaline gas of the atmosphere, being important in the neutralization of various processes that occur in the atmosphere. Its main sources of emission are the decomposition of organic matter and dejections of animals. Ammonia is used by man in diverse activities of production, therefore it is a gas that can contaminate work environments. Measurements of ammonia concentration in some parts of the world have shown great spatial and weather variation. This large variability makes it difficult to estimate the input of reduced nitrogen to different ecosystems from measurements.

Ultra-trace monitoring of copper in environmental and biological samples by inductively coupled plasma atomic emission spectrometry after separation and preconcentration by using octadecyl silica membrane disks modified by a new schiff's base

Ultra-trace amounts of Cu(II) were separated and preconcentrated by solid phase extraction on octadecyl-bonded silica membrane disks modified with a new Schiff,s base (Bis- (2-Hydroxyacetophenone) -2,2-dimethyl-1,3-propanediimine) (SBTD) followed by elution and inductively coupled plasma atomic emission spectrometric detection. The method was applied as a separation and detection method for copper(II) in environmental and biological samples. Extraction efficiency and the influence of sample matrix, flow rate, pH, and type and minimum amount of stripping acid were investigated. The concentration factor and detection limit of the proposed method are 500 and 12.5 pg mL-1, respectively.

Avaliação da padronização interna em espectrometria de absorção atômica utilizando gráficos de correlação

The use of an internal standard (IS) in ET AAS can be considered a new trend after the commercial introduction of a simultaneous spectrometer. The evaluation of experimental data to choose the most appropriate IS can be done by comparing correlation graphs. They were used to verify the resemblance among the simultaneous measurements obtained for the analyte(s) and the IS by inductively coupled plasma optical emission spectrometry (ICPOES). The judicious selection of IS by using correlation graphs for determinations by ET AAS can be exploited to improve the precision and accuracy of the analytical results. Therefore, a new approach for studying the use of IS in ET AAS is presented.

Estudo do nitrogênio na combustão do gás natural

Nitrogen content in natural gas was studied in experimental and computational investigations to identify its influence on the emission level of exhaust gases from combustion facilities. Changes in natural gas composition with different N2 concentrations may result from introducing a new source gas into the system. An industrial burner fired at 75 kW, housed in a laboratory-scale furnace, was employed for runs where the natural gas/N2 proportion was varied. The exhaust and in-furnace measurements of temperature and gas concentrations were performed for different combustion scenarios, varying N2 content from 1-10 %v. Results have shown that the contamination of natural gas with nitrogen reduced the peak flame temperature, the concentration of unstable species, the NO X emission level and the heat transfer rate to the furnace walls, resulting from the recombination reactions.

Small scale energy production in Helsinki Metropolitan area in emission trading point of view

Emission trading with greenhouse gases and green certificates are part if the climate policy the main target of which is reduce greenhouse gas emissions. The carbon dioxide and fine particle emissions of energy production in Helsinki Metropolitan area are calculated in this study. The analysis is made mainly by district heating point of view and the changes of the district heating network are assessed. Carbon dioxide emissions would be a bit higher, if the district heating network is expanded, but then the fine particle emissions would be much lower. Carbon dioxide emissions are roughly 10 % higher, if the district heating network is expanded at same rate as it has in past five years in the year 2030. The expansion of district heating network would decrease the fine particle emissions about 40 %. The cost of the expansion is allocated to be reduction cost of the fine particle emissions, which is considerably higher than the traditional reduction methods costs. The possible new nuclear plant would reduce the emissions considerably and the costs of the nuclear plant would be relatively low comparing the other energy production methods.