Linguistic and perceptual processing of communicative cues in Asperger Syndrome

Asperger Syndrome (AS) belongs to autism spectrum disorders where both verbal and non-verbal communication difficulties are at the core of the impairment. Social communication requires a complex use of affective, linguistic-cognitive and perceptual processes. In the four studies included in the current thesis, some of the linguistic and perceptual factors that are important for face-to-face communication were studied using behavioural methods. In all four studies the results obtained from individuals with AS were compared with typically developed age, gender and IQ matched controls. First, the language skills of school-aged children were characterized in detail with standardized tests that measured different aspects of receptive and expressive language (Study I). The children with AS were found to be worse than the controls in following complex verbal instructions. Next, the visual perception of facial expressions of emotion with varying degrees of visual detail was examined (Study II). Adults with AS were found to have impaired recognition of facial expressions on the basis of very low spatial frequencies which are important for processing global information. Following that, multisensory perception was investigated by looking at audiovisual speech perception (Studies III and IV). Adults with AS were found to perceive audiovisual speech qualitatively differently from typically developed adults, although both groups were equally accurate in recognizing auditory and visual speech presented alone. Finally, the effect of attention on audiovisual speech perception was studied by registering eye gaze behaviour (Study III) and by studying the voluntary control of visual attention (Study IV). The groups did not differ in eye gaze behaviour or in the voluntary control of visual attention. The results of the study series demonstrate that many factors underpinning face-to-face social communication are atypical in AS. In contrast with previous assumptions about intact language abilities, the current results show that children with AS have difficulties in understanding complex verbal instructions. Furthermore, the study makes clear that deviations in the perception of global features in faces expressing emotions as well as in the multisensory perception of speech are likely to harm face-to-face social communication.

Atomic Layer Deposition of Multicomponent Oxide Materials

Atomic layer deposition (ALD) is a method for thin film deposition which has been extensively studied for binary oxide thin film growth. Studies on multicomponent oxide growth by ALD remain relatively few owing to the increased number of factors that come into play when more than one metal is employed. More metal precursors are required, and the surface may change significantly during successive stages of the growth. Multicomponent oxide thin films can be prepared in a well-controlled way as long as the same principle that makes binary oxide ALD work so well is followed for each constituent element: in short, the film growth has to be self-limiting. ALD of various multicomponent oxides was studied. SrTiO3, BaTiO3, Ba(1-x)SrxTiO3 (BST), SrTa2O6, Bi4Ti3O12, BiTaO4 and SrBi2Ta2O9 (SBT) thin films were prepared, many of them for the first time by ALD. Chemistries of the binary oxides are shown to influence the processing of their multicomponent counterparts. The compatibility of precursor volatilities, thermal stabilities and reactivities is essential for multicomponent oxide ALD, but it should be noted that the main reactive species, the growing film itself, must also be compatible with self-limiting growth chemistry. In the cases of BaO and Bi2O3 the growth of the binary oxide was very difficult, but the presence of Ti or Ta in the growing film made self-limiting growth possible. The application of the deposited films as dielectric and ferroelectric materials was studied. Post-deposition annealing treatments in different atmospheres were used to achieve the desired crystalline phase or, more generally, to improve electrical properties. Electrode materials strongly influenced the leakage current densities in the prepared metal insulator metal (MIM) capacitors. Film permittivities above 100 and leakage current densities below 110-7 A/cm2 were achieved with several of the materials.

Ultrasound-assisted surface engineering of pharmaceutical powders

Effective processing of powdered particles can facilitate powder handling and result in better drug product performance, which is of great importance in the pharmaceutical industry where the majority of active pharmaceutical ingredients (APIs) are delivered as solid dosage forms. The purpose of this work was to develop a new ultrasound-assisted method for particle surface modification and thin-coating of pharmaceutical powders. The ultrasound was used to produce an aqueous mist with or without a coating agent. By using the proposed technique, it was possible to decrease the interparticular interactions and improve rheological properties of poorly-flowing water-soluble powders by aqueous smoothing of the rough surfaces of irregular particles. In turn, hydrophilic polymer thin-coating of a hydrophobic substance diminished the triboelectrostatic charge transfer and improved the flowability of highly cohesive powder. To determine the coating efficiency of the technique, the bioactive molecule β-galactosidase was layered onto the surface of powdered lactose particles. Enzyme-treated materials were analysed by assaying the quantity of the reaction product generated during enzymatic cleavage of the milk sugar. A near-linear increase in the thickness of the drug layer was obtained during progressive treatment. Using the enzyme coating procedure, it was confirmed that the ultrasound-assisted technique is suitable for processing labile protein materials. In addition, this pre-treatment of milk sugar could be used to improve utilization of lactose-containing formulations for populations suffering from severe lactose intolerance. Furthermore, the applicability of the thin-coating technique for improving homogeneity of low-dose solid dosage forms was shown. The carrier particles coated with API gave rise to uniform distribution of the drug within the powder. The mixture remained homogeneous during further tabletting, whereas the reference physical powder mixture was subject to segregation. In conclusion, ultrasound-assisted surface engineering of pharmaceutical powders can be effective technology for improving formulation and performance of solid dosage forms such as dry powder inhalers (DPI) and direct compression products.

Neurochemical regulation of auditory information processing studied with EEG/MEG: application to schizophrenia

Cognitive impairments of attention, memory and executive functions are a fundamental feature of the pathophysiology of schizophrenia. The neurophysiological and neurochemical changes in the auditory cortex are shown to underlie cognitive impairmentsin schizophrenia patients. Functional state of the neural substrate of auditory information processing could be objectively and non-invasively probed with auditory event-related potentials (ERPs) and event- related fields (ERFs). In the current work, we explored the neurochemical effect on the neural origins of auditory information processing in relation to schizophrenia. By means of ERPs/ERFs we aimed to determine how neural substrates of auditory information processing are modulated by antipsychotic medication in schizophrenia spectrum patients (Studies I, II) and by neuropharmacological challenges in healthy human subjects (Studies III, IV). First, with auditory ERPs we investigated the effects of olanzapine (Study I) and risperidone (Study II) in a group of patients with schizophrenia spectrum disorders. After 2 and 4 weeks of treatment, olanzapine has no significant effects on mismatch negativity(MMN) and P300, which, as it has been suggested, respectively reflect preattentive and attention-dependent information processing. After 2 weeks of treatment, risperidone has no significant effect on P300, however risperidone reduces P200 amplitude. This latter effect of risperidone on neural resources responsible for P200 generation could be partly explained through the action of dopamine. Subsequently, we used simultaneous EEG/MEG to investigate the effects of memantine (Study III) and methylphenidate (Study IV) in healthy subjects. We found that memantine modulates MMN response without changing other ERP components. This could be interpreted as being due to the possible influence of memantine through the NMDA receptors on auditory change- detection mechanism, with processing of auditory stimuli remaining otherwise unchanged. Further, we found that methylphenidate does not modulate the MMN response. This finding could indicate no association between catecholaminergic activities and electrophysiological measures of preattentive auditory discrimination processes reflected in the MMN. However, methylphenidate decreases the P200 amplitudes. This could be interpreted as a modulation of auditory information processing reflected in P200 by dopaminergic and noradrenergic systems. Taken together, our set of studies indicates a complex pattern of neurochemical influences produced by the antipsychotic drugs in the neural substrate of auditory information processing in patients with schizophrenia spectrum disorders and by the pharmacological challenges in healthy subjects studied with ERPs and ERFs.

Computer simulation of H and He effects in fusion reactor materials

Fusion power is an appealing source of clean and abundant energy. The radiation resistance of reactor materials is one of the greatest obstacles on the path towards commercial fusion power. These materials are subject to a harsh radiation environment, and cannot fail mechanically or contaminate the fusion plasma. Moreover, for a power plant to be economically viable, the reactor materials must withstand long operation times, with little maintenance. The fusion reactor materials will contain hydrogen and helium, due to deposition from the plasma and nuclear reactions because of energetic neutron irradiation. The first wall divertor materials, carbon and tungsten in existing and planned test reactors, will be subject to intense bombardment of low energy deuterium and helium, which erodes and modifies the surface. All reactor materials, including the structural steel, will suffer irradiation of high energy neutrons, causing displacement cascade damage. Molecular dynamics simulation is a valuable tool for studying irradiation phenomena, such as surface bombardment and the onset of primary damage due to displacement cascades. The governing mechanisms are on the atomic level, and hence not easily studied experimentally. In order to model materials, interatomic potentials are needed to describe the interaction between the atoms. In this thesis, new interatomic potentials were developed for the tungsten-carbon-hydrogen system and for iron-helium and chromium-helium. Thus, the study of previously inaccessible systems was made possible, in particular the effect of H and He on radiation damage. The potentials were based on experimental and ab initio data from the literature, as well as density-functional theory calculations performed in this work. As a model for ferritic steel, iron-chromium with 10% Cr was studied. The difference between Fe and FeCr was shown to be negligible for threshold displacement energies. The properties of small He and He-vacancy clusters in Fe and FeCr were also investigated. The clusters were found to be more mobile and dissociate more rapidly than previously assumed, and the effect of Cr was small. The primary damage formed by displacement cascades was found to be heavily influenced by the presence of He, both in FeCr and W. Many important issues with fusion reactor materials remain poorly understood, and will require a huge effort by the international community. The development of potential models for new materials and the simulations performed in this thesis reveal many interesting features, but also serve as a platform for further studies.

Modeling of Surface UV Radiation Using Satellite Data

Solar UV radiation is harmful for life on planet Earth, but fortunately the atmospheric oxygen and ozone absorb almost entirely the most energetic UVC radiation photons. However, part of the UVB radiation and much of the UVA radiation reaches the surface of the Earth, and affect human health, environment, materials and drive atmospheric and aquatic photochemical processes. In order to quantify these effects and processes there is a need for ground-based UV measurements and radiative transfer modeling to estimate the amounts of UV radiation reaching the biosphere. Satellite measurements with their near-global spatial coverage and long-term data conti-nuity offer an attractive option for estimation of the surface UV radiation. This work focuses on radiative transfer theory based methods used for estimation of the UV radiation reaching the surface of the Earth. The objectives of the thesis were to implement the surface UV algorithm originally developed at NASA Goddard Space Flight Center for estimation of the surface UV irradiance from the meas-urements of the Dutch-Finnish built Ozone Monitoring Instrument (OMI), to improve the original surface UV algorithm especially in relation with snow cover, to validate the OMI-derived daily surface UV doses against ground-based measurements, and to demonstrate how the satellite-derived surface UV data can be used to study the effects of the UV radiation. The thesis consists of seven original papers and a summary. The summary includes an introduction of the OMI instrument, a review of the methods used for modeling of the surface UV using satellite data as well as the con-clusions of the main results of the original papers. The first two papers describe the algorithm used for estimation of the surface UV amounts from the OMI measurements as well as the unique Very Fast Delivery processing system developed for processing of the OMI data received at the Sodankylä satellite data centre. The third and the fourth papers present algorithm improvements related to the surface UV albedo of the snow-covered land. Fifth paper presents the results of the comparison of the OMI-derived daily erythemal doses with those calculated from the ground-based measurement data. It gives an estimate of the expected accuracy of the OMI-derived sur-face UV doses for various atmospheric and other conditions, and discusses the causes of the differences between the satellite-derived and ground-based data. The last two papers demonstrate the use of the satellite-derived sur-face UV data. Sixth paper presents an assessment of the photochemical decomposition rates in aquatic environment. Seventh paper presents use of satellite-derived daily surface UV doses for planning of the outdoor material weathering tests.

Diffusion of Be, Co and Mn impurities in compound semiconductors and glassy carbon studied by the modified radiotracer technique

The main method of modifying properties of semiconductors is to introduce small amount of impurities inside the material. This is used to control magnetic and optical properties of materials and to realize p- and n-type semiconductors out of intrinsic material in order to manufacture fundamental components such as diodes. As diffusion can be described as random mixing of material due to thermal movement of atoms, it is essential to know the diffusion behavior of the impurities in order to manufacture working components. In modified radiotracer technique diffusion is studied using radioactive isotopes of elements as tracers. The technique is called modified as atoms are deployed inside the material by ion beam implantation. With ion implantation, a distinct distribution of impurities can be deployed inside the sample surface with good con- trol over the amount of implanted atoms. As electromagnetic radiation and other nuclear decay products emitted by radioactive materials can be easily detected, only very low amount of impurities can be used. This makes it possible to study diffusion in pure materials without essentially modifying the initial properties by doping. In this thesis a modified radiotracer technique is used to study the diffusion of beryllium in GaN, ZnO, SiGe and glassy carbon. GaN, ZnO and SiGe are of great interest to the semiconductor industry and beryllium as a small and possibly rapid dopant hasn t been studied previously using the technique. Glassy carbon has been added to demonstrate the feasibility of the technique. In addition, the diffusion of magnetic impurities, Mn and Co, has been studied in GaAs and ZnO (respectively) with spintronic applications in mind.

Local systems, global impacts : Using life cycle assessment to analyse the potential and constraints of industrial symbioses

Human activities extract and displace different substances and materials from the earth s crust, thus causing various environmental problems, such as climate change, acidification and eutrophication. As problems have become more complicated, more holistic measures that consider the origins and sources of pollutants have been called for. Industrial ecology is a field of science that forms a comprehensive framework for studying the interactions between the modern technological society and the environment. Industrial ecology considers humans and their technologies to be part of the natural environment, not separate from it. Industrial operations form natural systems that must also function as such within the constraints set by the biosphere. Industrial symbiosis (IS) is a central concept of industrial ecology. Industrial symbiosis studies look at the physical flows of materials and energy in local industrial systems. In an ideal IS, waste material and energy are exchanged by the actors of the system, thereby reducing the consumption of virgin material and energy inputs and the generation of waste and emissions. Companies are seen as part of the chains of suppliers and consumers that resemble those of natural ecosystems. The aim of this study was to analyse the environmental performance of an industrial symbiosis based on pulp and paper production, taking into account life cycle impacts as well. Life Cycle Assessment (LCA) is a tool for quantitatively and systematically evaluating the environmental aspects of a product, technology or service throughout its whole life cycle. Moreover, the Natural Step Sustainability Principles formed a conceptual framework for assessing the environmental performance of the case study symbiosis (Paper I). The environmental performance of the case study symbiosis was compared to four counterfactual reference scenarios in which the actors of the symbiosis operated on their own. The research methods used were process-based life cycle assessment (LCA) (Papers II and III) and hybrid LCA, which combines both process and input-output LCA (Paper IV). The results showed that the environmental impacts caused by the extraction and processing of the materials and the energy used by the symbiosis were considerable. If only the direct emissions and resource use of the symbiosis had been considered, less than half of the total environmental impacts of the system would have been taken into account. When the results were compared with the counterfactual reference scenarios, the net environmental impacts of the symbiosis were smaller than those of the reference scenarios. The reduction in environmental impacts was mainly due to changes in the way energy was produced. However, the results are sensitive to the way the reference scenarios are defined. LCA is a useful tool for assessing the overall environmental performance of industrial symbioses. It is recommended that in addition to the direct effects, the upstream impacts should be taken into account as well when assessing the environmental performance of industrial symbioses. Industrial symbiosis should be seen as part of the process of improving the environmental performance of a system. In some cases, it may be more efficient, from an environmental point of view, to focus on supply chain management instead.  

Molecular Characterization of Viruses Causing the Cassava Brown Streak Disease Epidemic in Eastern Africa

Cassava brown streak disease (CBSD) was described for the first time in Tanganyika (now Tanzania) about seven decades ago. Tanganyika (now Tanzania) about seven decades ago. It was endemic in the lowland areas of East Africa and inland parts of Malawi and caused by Cassava brown streak virus (CBSV; genus Ipomovirus; Potyviridae). However, in 1990s CBSD was observed at high altitude areas in Uganda. The causes for spread to new locations were not known.The present work was thus initiated to generate information on genetic variability, clarify the taxonomy of the virus or viruses associated with CBSD in Eastern Africa as well as to understand the evolutionary forces acting on their genes. It also sought to develop a molecular based diagnostic tool for detection of CBSD-associated virus isolates. Comparison of the CP-encoding sequences of CBSD-associated virus isolates collected from Uganda and north-western Tanzania in 2007 and the partial sequences available in Genbank revealed occurrence of two genetically distinct groups of isolates. Two isolates were selected to represent the two groups. The complete genomes of isolates MLB3 (TZ:Mlb3:07) and Kor6 (TZ:Kor6:08) obtained from North-Western (Kagera) and North-Eastern (Tanga) Tanzania, respectively, were sequenced. The genomes were 9069 and 8995 nucleotides (nt), respectively. They translated into polyproteins that were predicted to yield ten mature proteins after cleavage. Nine proteins were typical in the family Potyviridae, namely P1, P3, 6K1, CI, 6K2, VPg, NIa-Pro, NIb and CP, but the viruses did not contain HC-Pro. Interestingly, genomes of both isolates contained a Maf/HAM1-like sequence (HAM1h; 678 nucleotides, 25 kDa) recombined between the NIb and CP domains in the 3’-proximal part of the genomes. HAM1h was also identified in Euphorbia ringspot virus (EuRSV) whose sequence was in GenBank. The HAM1 gene is widely spread in both prokaryotes and eukaryotes. In yeast (Saccharomyces cerevisiae) it is known to be a nucleoside triphosphate (NTP) pyrophosphatase. Novel information was obtained on the structural variation at the N-termini of polyproteins of viruses in the genus Ipomovirus. Cucumber vein yellowing virus (CVYV) and Squash vein yellowing virus (SqVYV) contain a duplicated P1 (P1a and P1b) but lack the HC-Pro. On the other hand, Sweet potato mild mottle virus (SPMMV), has a single but large P1 and has HC-Pro. Both virus isolates (TZ:Mlb3:07 & TZ:Kor6:08) characterized in this study contained a single P1 and lacked the HC-Pro which indicates unique evolution in the family Potyviridae. Comparison of 12 complete genomes of CBSD-associated viruses which included two genomes characterized in this study, revealed genetic identity of 69.0–70.3% (nt) and amino acid (aa) identities of 73.6–74.4% at polyprotein level. Comparison was also made among 68 complete CP sequences, which indicated 69.0-70.3 and 73.6-74.4 % identity at nt and aa levels, respectively. The genetic variation was large enough for dermacation of CBSD-associated virus isolates into two distinct species. The name CBSV was retained for isolates that were related to CBSV isolates available in database whereas the new virus described for the first time in this study was named Ugandan cassava brown streak virus (UCBSV) by the International Committee on Virus Taxonomy (ICTV). The isolates TZ:Mlb3:07 and TZ:Kor6:08 belong to UCBSV and CBSV, respectively. The isolates of CBSV and UCBSV were 79.3-95.5% and 86.3-99.3 % identitical at nt level, respectively, suggesting more variation amongst CBSV isolates. The main sources of variation in plant viruses are mutations and recombination. Signals for recombination events were detected in 50% of isolates of each virus. Recombination events were detected in coding and non-coding (3’-UTR) sequences except in the 5’UTR and P3. There was no evidence for recombination between isolates of CBSV and UCBSV. The non-synonomous (dN) to synonomous (dS) nucleotide substitution ratio (ω) for the HAM1h and CP domains of both viruses were ≤ 0.184 suggesting that most sites of these proteins were evolving under strong purifying selection. However, there were individual amino acid sites that were submitted to adaptive evolution. For instance, adaptive evolution was detected in the HAM1h of UCBSV (n=15) where 12 aa sites were under positive selection (P< 0.05) but not in CBSV (n=12). The CP of CBSV (n=23) contained 12 aa sites (p<0.01) while only 5 aa sites in the CP gene of UCBSV were predicted to be submitted to positive selection pressure (p<0.01). The advantages offered by the aa sites under positive selection could not be established but occurrence of such sites in the terminal ends of UCBSV-HAMIh, for example, was interpreted as a requirement for proteolysis during polyprotein processing. Two different primer pairs that simultaneously detect UCBSV and CBSV isolates were developed in this study. They were used successfully to study distribution of CBSV, UCBSV and their mixed infections in Tanzania and Uganda. It was established that the two viruses co-infect cassava and that incidences of co-infection could be as high as 50% around Lake Victoria on the Tanzanian side. Furthermore, it was revealed for the first time that both UCBSV and CBSV were widely distributed in Eastern Africa. The primer pair was also used to confirm infection in a close relative of cassava, Manihot glaziovii (Müller Arg.) with CBSV. DNA barcoding of M. glaziovii was done by sequencing the matK gene. Two out of seven M. glaziovii from the coastal areas of Korogwe and Kibaha in north eastern Tanzania were shown to be infected by CBSV but not UCBSV isolates. Detection in M. glaziovii has an implication in control and management of CBSD as it is likely to serve as virus reservoir. This study has contributed to the understanding of evolution of CBSV and UCBSV, which cause CBSD epidemic in Eastern Africa. The detection tools developed in this work will be useful in plant breeding, verification of the phytosanitary status of materials in regional and international movement of germplasm, and in all diagnostic activities related to management of CBSD. Whereas there are still many issues to be resolved such as the function and biological significance of HAM1h and its origin, this work has laid a foundation upon which the studies on these aspects can be based.

Computer simulation of multi-elemental fusion reactor materials

Thermonuclear fusion is a sustainable energy solution, in which energy is produced using similar processes as in the sun. In this technology hydrogen isotopes are fused to gain energy and consequently to produce electricity. In a fusion reactor hydrogen isotopes are confined by magnetic fields as ionized gas, the plasma. Since the core plasma is millions of degrees hot, there are special needs for the plasma-facing materials. Moreover, in the plasma the fusion of hydrogen isotopes leads to the production of high energetic neutrons which sets demanding abilities for the structural materials of the reactor. This thesis investigates the irradiation response of materials to be used in future fusion reactors. Interactions of the plasma with the reactor wall leads to the removal of surface atoms, migration of them, and formation of co-deposited layers such as tungsten carbide. Sputtering of tungsten carbide and deuterium trapping in tungsten carbide was investigated in this thesis. As the second topic the primary interaction of the neutrons in the structural material steel was examined. As model materials for steel iron chromium and iron nickel were used. This study was performed theoretically by the means of computer simulations on the atomic level. In contrast to previous studies in the field, in which simulations were limited to pure elements, in this work more complex materials were used, i.e. they were multi-elemental including two or more atom species. The results of this thesis are in the microscale. One of the results is a catalogue of atom species, which were removed from tungsten carbide by the plasma. Another result is e.g. the atomic distributions of defects in iron chromium caused by the energetic neutrons. These microscopic results are used in data bases for multiscale modelling of fusion reactor materials, which has the aim to explain the macroscopic degradation in the materials. This thesis is therefore a relevant contribution to investigate the connection of microscopic and macroscopic radiation effects, which is one objective in fusion reactor materials research.