Imaging of Dopamine and Serotonin Transporters. Pre-clinical Studies with Radiotracers for Positron Emission Tomography

The action of the neurotransmitters dopamine (DA) and serotonin (5-HT) at synapses is terminated by their rapid reuptake into presynaptic nerve endings via plasma membrane dopamine (DAT) and serotonin (SERT) transporters. Alterations in the function of these transporters have been suggested as a feature of several neurological and neuropsychiatric diseases, such as Parkinson’s disease (PD), depression, and anxiety. A suitable clinical method for studying these transporters non-invasively in vivo is positron emission tomography (PET) utilizing radiopharmaceuticals (tracers) labelled with short-lived positron-emitting radionuclides. The aim of this study was to evaluate in rats two novel radiotracers, [¹⁸F]beta -CFT-FP and ¹⁸FFMe-McN, for imaging DAT and SERT, respectively, using in vitro, ex vivo and in vivo methods. Substituting an N-methyl in [¹⁸F]beta-CFT, a well known DAT tracer, with a ¹⁸Ffluoropropyl group significantly changed the properties of the tracer. [¹⁸F]beta- CFT showed slow kinetics and metabolism, and a high specific uptake in the striatum, whereas [¹⁸F]beta-CFT-FP showed fast kinetics and metabolism, and a moderate specific uptake in the striatum. [¹⁸F]betaCFT-FP was selective for DAT; but [¹⁸F]beta-CFT also bound to the noradrenaline transporter. [¹⁸F]beta-CFT-FP may be a suitable PET tracer for imaging the striatal DAT sites, but a tracer with a higher affinity is needed for imaging extrastriatal DAT sites. In rats, ¹⁸FFMe-McN showed high target-to-non-target ratios, specificity and selectivity for SERT, but slow kinetics. However, ¹⁸FFMe-McN reveals potential for imaging SERT, at least in pre-clinical studies. In addition, the sensitivities of [¹⁸F]beta CFT and [¹⁸ F]FDOPA (a precursor of DA) for detecting mild nigrostriatal hypofunction were compared in an animal model of PD. The uptake of [¹⁸F]FDOPA was significantly affected by compensatory effects in dopaminergic cells, whereas [¹⁸F]beta-CFT was more sensitive and therefore more suitable for PET studies of mild dopaminergic symptoms. In conclusion, both novel tracers, [¹⁸F]-CFT-FP and ¹⁸FFMe-McN, have potential, but are not optimal PET tracers for DAT and SERT imaging in rats, respectively. [¹⁸F]beta-CFT is superior to [18F]FDOPA for imaging mild nigral lesions in rat brains.

Mild Cognitive Impairment and Early Detection of Alzheimer`s Disease. A Positron Emission Tomography Study

Alzheimer`s disease (AD) is characterised neuropathologically by the presence of extracellular amyloid plaques, intraneuronal neurofibrillary tangles, and cerebral neuronal loss. The pathological changes in AD are believed to start even decades before clinical symptoms are detectable. AD gradually affects episodic memory, cognition, behaviour and the ability to perform everyday activities. Mild cognitive impairment (MCI) represents a transitional state between normal aging and dementia disorders, especially AD. The predictive accuracy of the current and commonly used MCI criteria devide this disorder into amnestic (aMCI) and non-amnestic (naMCI) MCI. It seems that many individuals with aMCI tend to convert to AD. However many MCI individuals will remain stable and some may even recover. At present, the principal drugs for the treatment of AD provide only symptomatic and palliative benefits. Safe and effective mechanism-based therapies are needed for this devastating neurodegenerative disease of later life. In conjunction with the development of new therapeutic drugs, tools for early detection of AD would be important. In future one of the challenges will be to detect at an early stage these MCI individuals who will convert to AD. Methods which can predict which MCI subjects will convert to AD will be much more important if the new drug candidates prove to have disease-arresting or even disease–slowing effects. These types of drugs are likely to have the best efficacy if administered in the early or even in the presymptomatic phase of the disease when the synaptic and neuronal loss has not become too widespread. There is no clinical method to determine with certainly which MCI individuals will progress to AD. However there are several methods which have been suggested as predictors of conversion to AD, e.g. increased [11C] PIB uptake, hippocampal atrophy in MRI, low CSF A beta 42 level, high CSF tau-protein level, apolipoprotein E (APOE) ε4 allele and impairment in episodic memory and executive functions. In the present study subjects with MCI appear to have significantly higher [¹¹C] PIB uptake vs healthy elderly in several brain areas including frontal cortex, the posterior cingulate, the parietal and lateral temporal cortices, putamen and caudate. Also results from this PET study indicate that over time, MCI subjects who display increased [¹¹C] PIB uptake appear to be significantly more likely to convert to AD than MCI subjects with negative [¹¹C] PIB retention. Also hippocampal atrophy seems to increase in MCI individuals clearly during the conversion to AD. In this study [¹¹C] PIB uptake increases early and changes relatively little during the AD process whereas there is progressive hippocampal atrophy during the disease. In addition to increased [¹¹C] PIB retention and hippocampal atrophy, the status of APOE ε4 allele might contribute to the conversion from MCI to AD.

Temporal variability of soil CO2 emission after conventional and reduced tillage described by an exponential decay in time model

To study Assessing the impact of tillage practices on soil carbon losses dependents it is necessary to describe the temporal variability of soil CO2 emission after tillage. It has been argued that large amounts of CO2 emitted after tillage may serve as an indicator for longer-term changes in soil carbon stocks. Here we present a two-step function model based on soil temperature and soil moisture including an exponential decay in time component that is efficient in fitting intermediate-term emission after disk plow followed by a leveling harrow (conventional), and chisel plow coupled with a roller for clod breaking (reduced) tillage. Emission after reduced tillage was described using a non-linear estimator with determination coefficient (R²) as high as 0.98. Results indicate that when emission after tillage is addressed it is important to consider an exponential decay in time in order to predict the impact of tillage in short-term emissions.

In vivo imaging of vascular adhesion protein 1 - preclinical studies with positron emission tomography

The golden standard in nuclear medicine imaging of inflammation is the use of radiolabeled leukocytes. Although their diagnostic accuracy is good, the preparation of the leukocytes is both laborious and potentially hazardous for laboratory personnel. Molecules involved in leukocyte migration could serve as targets for the development of inflammation imaging agents. An excellent target would be a molecule that is absent or expressed at low level in normal tissues, but is induced or up-regulated at the site of inflammation. Vascular adhesion protein-1 (VAP-1) is a very promising target for in vivo imaging, since it is translocated to the endothelial cell surface when inflammation occurs. VAP-1 functions as an endothelial adhesion molecule that participates in leukocyte recruitment to inflamed tissues. Besides being an adhesion molecule, VAP-1 also has enzymatic activity. In this thesis, the targeting of VAP-1 was studied by using Gallium-68 (68Ga) labeled peptides and an Iodine-124 (124I) labeled antibody. The peptides were designed based on molecular modelling and phage display library searches. The new imaging agents were preclinically tested in vitro, as well as in vivo in animal models. The most promising imaging agent appeared to be a peptide belonging to the VAP-1 leukocyte ligand, Siglec-9 peptide. The 68Ga-labeled Siglec-9 peptide was able to detect VAP-1 positive vasculature in rodent models of sterile skin inflammation and melanoma by positron emission tomography. In addition to peptides, the 124I-labeled antibody showed VAP-1 specific binding both in vitro and in vivo. However, the estimated human radiation dose was rather high, and thus further preclinical studies in disease models are needed to clarify the value of this imaging agent. Detection of VAP-1 on endothelium was demonstrated in these studies and this imaging approach could be used in the diagnosis of inflammatory conditions as well as melanoma. These studies provide a proof-of-concept for PET imaging of VAP-1 and further studies are warranted.

Soil CO2 emission as related to incorporation of sugarcane crop residues and aggregate breaking after rotary tiller

Soil tillage is a process that accelerates soil organic matter decomposition transferring carbon to atmosphere, mainly in the CO2 form. In this study, the effect of rotary tillage on soil CO2 emission was investigated, including the presence of crop residues on the surface.Emissions were evaluated during 15 days after tillage in 3 plots: 1) non-tilled and without crop residues on soil surface (NTwo), 2) rotary tiller without the presence of crop residues on soil surface (RTwo), and 3) rotary tiller with the presence of crop residues in soil surface (RTw). Emissions from the RTw plot were higher than the other plots, (0.777 g CO2 m-2 h-1), with the lowest emissions recorded in the NTwo plot (0.414 g CO2 m-2 h-1). Total emission indicates that the difference of C-CO2 emitted to atmosphere corresponds to 3% of the total additional carbon in the crop residues in the RTw plot compared to RTwo. The increase in the RTwo emission in comparison to NTwo was followed by changes in the aggregate size distribution, especially those with average diameter lower than 2 mm. The increase in emission from the RTw plot in relation to RTwo was related to a decrease in crop residue mass on the surface, and its higher fragmentation and incorporation in soil. When the linear correlation between soil CO2 emission, and soil temperature and soil moisture is considered, only the RTw treatment showed significant correlation (p<0.05) with soil moisture.

Suomen metsäteollisuuden päästökehitys vuoteen 2020

Metsäteollisuudessa on käynnissä rakennemuutos, joka tuo haasteita toimialan ympäristöasioiden hallintaan sekä ympäristölupia myöntävän ja valvovan viranomaisen toimintaan. Lähivuosina tulee myös runsaasti voimaan uutta lainsäädäntöä, joka vaikuttaa metsäteollisuuden ympäristöasioiden hallintaan. Tämän työn tarkoituksena oli arvioida Suomen kemiallisen metsäteollisuuden päästökehitystä vuoteen 2020 huomioiden metsäteollisuuden uusi tuotanto sekä lähivuosina voimaan tuleva ympäristölainsäädäntö, erityisesti päivitettävänä oleva massa- ja paperiteollisuuden BREF-asiakirja. Päästökehitystä arvioitiin viiden skenaarion avulla. Vesistöpäästöjen osalta tarkasteltiin COD- ja AOX-päästöjä sekä typpi- ja fosforipäästöjä, ja ilmapäästöjen osalta sellun tuotannon rikki- ja typpioksidi- sekä hiukkaspäästöjä. Massan- ja paperintuotannon oletettiin pysyvän muutaman prosentin nykyistä tasoa korkeammalla tasolla. Uuden tuotannon osalta kahdessa skenaariossa huomioitiin nestemäisten biopolttoaineiden tuotanto kolmella laitoksella, yhteensä 600 000 t/a. Päästölaskennassa käytettiin päivitettävänä olevan massa- ja paperiteollisuuden BREF-asiakirjan BAT-päätelmissä annettuja luonnoksia uusista päästötasoista. Skenaarioiden pohjalta havaittiin, että massa- ja paperiteollisuuden BAT-päätelmien mukaiset päästötasot eivät tuo merkittäviä muutoksia metsäteollisuuden vesistöpäästöihin vuoteen 2020 mennessä. Biojalosteiden tuotannon vaikutus vesistöpäästöihin todettiin myös hyvin vähäiseksi. Sen sijaan ilmaan johdettavat päästöt pienenevät huomattavasti: hiukkaspäästöt vähenivät 42–50 prosenttia uusien päästötasojen myötä. Biojalosteiden tuotannon vaikutus oli myös merkittävämpi kuin ilmapäästöihin kuin vesistöpäästöihin. Prosentuaalisesti eniten biojalostus lisäsi rikkidioksidipäästöjä.

Effects of splenic allograft in lipid profile of non-splenectomized rats: the immune and metabolic role of the "double spleen"

OBJECTIVE: To elucidate the role of the spleen and splenic allograft in lipid control and evaluate its effect on the lipid profile of rats.METHOD: 32 male Wistar rats were randomly assigned into four groups: control group (1), total splenectomy group (2), splenectomy and implantation of allograft group (3) and double spleen group (4). Each group was subdivided into two subgroups: A and B, based on the death of the animals after 30 or 120 days of monitoring. The procedures in groups 2, 3 and 4 were made simultaneously, and splenectomized animals, groups 2 and 3 were donors, respectively, for the animals of groups 3 and 4. In group 4 the spleen was preserved and the animals received implants from the spleens of rats from group 3. The regeneration of splenic tissue was evaluated by macroscopic and microscopic analyzes of the grafts and own spleens, as well as with measurements of VLDL, HDL, LDL, total cholesterol and triglycerides.RESULTS: after 120 days, Group 4 showed levels of total cholesterol and LDL lower than the other groups. Group 1 had higher levels of lipids.CONCLUSION: The technique of double spleen was effective in the control of lipid metabolism, corroborating the function of the spleen as a reserve of lipids.

Enhanced muscle strength with carbohydrate supplement two hours before open cholecystectomy: a randomized, double-blind study

Objective: to investigate the effects of preoperative fasting abbreviation with oral supplementation with carbohydrate in the evolution of grip strength in patients undergoing cholecystectomy by laparotomy. Methods : we conducted a clinical, randomizeddouble blind study with adult female patients, aged 18-60 years. Patients were divided into two groups: Control Group, with fasting prescription 6-8h until the time of operation; and Intervention Group, which received prescription of fasting for solids 6-8h before surgery, but ingested an oral supplement containing 12.5% carbohydrate, six (400ml) and two (200ml) hours before theprocedure. The handgrip strength was measured in both hands in both groups, at patient's admission (6h before surgery), the immediate pre-operative time (1h before surgery) and 12-18h postoperatively. Results : we analyzed 27 patients, 14 in the intervention group and 13 in the control group. There was no mortality. The handgrip strength (mean [standard deviation]) was significantly higher in the intervention group in the three periods studied, in at least one hand: preoperatively in the dominant hand (27.8 [2.6] vs 24.1 [3.7] kg; p=0.04), in the immediate preoperative in both hands, and postoperatively in the non-dominant hand (28.5 [3.0] vs 21.3 [5.9] kg; p=0.01). Conclusion : the abbreviation of preoperative fasting to two hours with drink containing carbohydrate improves muscle function in the perioperative period.

Imaging of Tumour Microenvironment for the Planning of Oncological Therapies Using Positron Emission Tomography

Tumour cells differ from normal tissue cells in several important ways. These differences, like for example changed energy metabolism, result in altered microenvironment of malignant tumours. Non-invasive imaging of tumour microenvironment has been at the centre of intense research recently due to the important role that this changed environement plays in the development of malignant tumours and due to the role it plays in the treatment of these tumours. In this respect, perhaps the most important characteristics of the tumour microenvironment from this point of view are the lack of oxygen or hypoxia and changes in blood flow (BF). The purpose of this thesis was to investigate the processes of energy metabolism, BF and oxygenation in head and neck cancer and pancreatic tumours and to explore the possibilities of improving the methods for their quantification using positron emission tomography (PET). To this end [18F]EF5, a new PET tracer for detection of tumour hypoxia was investigated. Favourable uptake properties of the tracer were observed. In addition, it was established that the uptake of this tracer does not correlate with the uptake of existing tracers for the imaging of energy metabolism and BF, so the information about the presence of tissue hypoxia cannot therefore be obtained using tracers such as [18F]FDG or [15O]H2O. These results were complemented by the results of the follow-up study in which it was shown that the uptake of [18F]EF5 in head and neck tumours prior to treatment is also associated with the overall survival of the patients, indicating that tumour hypoxia is a negative prognostic factor and might be associated with therapeutic resistance. The influences of energy metabolism and BF on the survival of patients with pancreatic cancer were investigated in the second study. The results indicate that the best predictor of survival of patients with pancreatic cancer is the relationship between energy metabolism and BF. These results suggest that the cells with high metabolic activity in a hypoperfused tissue have the most aggressive phenotype.

Fracture modes and acoustic emission characteristics of hydrogen-assisted cracking in high-strength low-alloy steel weldment

The aim of the present paper is to study the relationship between the fracture modes in hydrogen-assisted cracking (HAC) in microalloied steel and the emission of acoustic signals during the fracturing process. For this reason, a flux-cored arc weld (FCAW) was used in a high-strength low-alloy steel. The consumable used were the commercially available AWS E120T5-K4 and had a diameter of 1.6 mm. Two different shielding gases were used (CO2 and CO2+5% H2) to obtain complete phenomenon characterization. The implant test was applied with three levels of restriction stresses. An acoustic emission measurement system (AEMS) was coupled to the implant test apparatus. The output signal from the acoustic emission sensor was passed through an electronic amplifier and processed by a root mean square (RMS) voltage converter. Fracture surfaces were examined by scanning electron microscopy (SEM) and image analysis. Fracture modes were related with the intensity, the energy and the number of the peaks of the acoustic emission signal. The shielding gas CO2+5% H2 proved to be very useful in the experiments. Basically, three different fracture modes were identified in terms of fracture appearance: microvoid coalescence (MVC), intergranular (IG) and quasi-cleavage (QC). The results show that each mode of fracture presents a characteristic acoustic signal.

Best Practices of International Double Master's Degree Programmes: Comparative Study on Finnish and Russian Universities

The purpose of this report is to disseminate the best practices of double degree programmes’ organization, implementation and development between Russian and European universities. The findings reveal good developments in the field of double degree cooperation between Russian and European universities and a high motivation from both parties. The report depicts different models of building a joint curriculum and organizing academic mobility. Foreign language skills improvement for students and university staff, involvement of international companies, and joint strategy and actions in marketing and quality assurance are some redevelopments points recommended in the report.

Differentiation of Metabolically Distinct Areas within Head and Neck Region using Dynamic 18F-FDG Positron Emission Tomography Imaging

Positron Emission Tomography (PET) using ¹⁸F-FDG is playing a vital role in the diagnosis and treatment planning of cancer. However, the most widely used radiotracer, ¹⁸F-FDG, is not specific for tumours and can also accumulate in inflammatory lesions as well as normal physiologically active tissues making diagnosis and treatment planning complicated for the physicians. Malignant, inflammatory and normal tissues are known to have different pathways for glucose metabolism which could possibly be evident from different characteristics of the time activity curves from a dynamic PET acquisition protocol. Therefore, we aimed to develop new image analysis methods, for PET scans of the head and neck region, which could differentiate between inflammation, tumour and normal tissues using this functional information within these radiotracer uptake areas. We developed different dynamic features from the time activity curves of voxels in these areas and compared them with the widely used static parameter, SUV, using Gaussian Mixture Model algorithm as well as K-means algorithm in order to assess their effectiveness in discriminating metabolically different areas. Moreover, we also correlated dynamic features with other clinical metrics obtained independently of PET imaging. The results show that some of the developed features can prove to be useful in differentiating tumour tissues from inflammatory regions and some dynamic features also provide positive correlations with clinical metrics. If these proposed methods are further explored then they can prove to be useful in reducing false positive tumour detections and developing real world applications for tumour diagnosis and contouring.

Modeling and Parameter Estimation of Double-Star Permanent Magnet Synchronous Machines

The power rating of wind turbines is constantly increasing; however, keeping the voltage rating at the low-voltage level results in high kilo-ampere currents. An alternative for increasing the power levels without raising the voltage level is provided by multiphase machines. Multiphase machines are used for instance in ship propulsion systems, aerospace applications, electric vehicles, and in other high-power applications including wind energy conversion systems. A machine model in an appropriate reference frame is required in order to design an efficient control for the electric drive. Modeling of multiphase machines poses a challenge because of the mutual couplings between the phases. Mutual couplings degrade the drive performance unless they are properly considered. In certain multiphase machines there is also a problem of high current harmonics, which are easily generated because of the small current path impedance of the harmonic components. However, multiphase machines provide special characteristics compared with the three-phase counterparts: Multiphase machines have a better fault tolerance, and are thus more robust. In addition, the controlled power can be divided among more inverter legs by increasing the number of phases. Moreover, the torque pulsation can be decreased and the harmonic frequency of the torque ripple increased by an appropriate multiphase configuration. By increasing the number of phases it is also possible to obtain more torque per RMS ampere for the same volume, and thus, increase the power density. In this doctoral thesis, a decoupled d–q model of double-star permanent-magnet (PM) synchronous machines is derived based on the inductance matrix diagonalization. The double-star machine is a special type of multiphase machines. Its armature consists of two three-phase winding sets, which are commonly displaced by 30 electrical degrees. In this study, the displacement angle between the sets is considered a parameter. The diagonalization of the inductance matrix results in a simplified model structure, in which the mutual couplings between the reference frames are eliminated. Moreover, the current harmonics are mapped into a reference frame, in which they can be easily controlled. The work also presents methods to determine the machine inductances by a finite-element analysis and by voltage-source inverters on-site. The derived model is validated by experimental results obtained with an example double-star interior PM (IPM) synchronous machine having the sets displaced by 30 electrical degrees. The derived transformation, and consequently, the decoupled d–q machine model, are shown to model the behavior of an actual machine with an acceptable accuracy. Thus, the proposed model is suitable to be used for the model-based control design of electric drives consisting of double-star IPM synchronous machines.

Best practices of international double degree programmes. Case of Russian and European universities

The purpose of the Master’s thesis research is to study and disseminate the best practices of international double Master’s degree programmes organization, implementation and development. The given research is focused on two main areas: motivation of higher education institutions to start double degree programmes and best practices of double degree programme design and implementation from the perspective of building joint curriculum and organizing balanced mobility and development of existing programmes in terms of increasing their quality and attractiveness. This is a case study of the double degree programmes between Russian and European universities. The study findings reveal good developments in the field of double degree cooperation between Russian and European universities and a high motivation from both parties. The research depicts different models of building a joint curriculum and organizing academic mobility. The following areas could be outlined as development points for double degree programmes: - Personal interest and commitment of organizers of double degree programmes; - Comprehensive agreement between partners on different aspects and practicalities of the double degree programme implementation; - Promotion towards more balanced student participation and two-way mobility; - Foreign language skills improvement for students and university staff; - Joint strategy and actions in marketing and quality assurance; - Involvement of international companies; - Wider usage of e-learning technology.