Detection of the Vulnerable Atherosclerotic Plaque. Pre-Clinical Evaluation of Novel PET Imaging Probes With Experimental Models

Atherosclerosis is a life-long vascular inflammatory disease and the leading cause of death in Finland and in other western societies. The development of atherosclerotic plaques is progressive and they form when lipids begin to accumulate in the vessel wall. This accumulation triggers the migration of inflammatory cells that is a hallmark of vascular inflammation. Often, this plaque will become unstable and form vulnerable plaque which may rupture causing thrombosis and in the worst case, causing myocardial infarction or stroke. Identification of these vulnerable plaques before they rupture could save lives. At present, in the clinic, there exists no appropriated, non-invasive method for their identification. The aim of this thesis was to evaluate novel positron emission tomography (PET) probes for the detection of vulnerable atherosclerotic plaques and to characterize, two mouse models of atherosclerosis. These studies were performed by using ex vivo and in vivo imaging modalities. The vulnerability of atherosclerotic plaques was evaluated as expression of active inflammatory cells, namely macrophages. Age and the duration of high-fat diet had a drastic impact on the development of atherosclerotic plaques in mice. In imaging of atherosclerosis, 6-month-old mice, kept on high-fat diet for 4 months, showed matured, metabolically active, atherosclerotic plaques. [18F]FDG and 68Ga were accumulated in the areas representative of vulnerable plaques. However, the slow clearance of 68Ga limits its use for the plaque imaging. The novel synthesized [68Ga]DOTA-RGD and [18F]EF5 tracers demonstrated efficient uptake in plaques as compared to the healthy vessel wall, but the pharmacokinetic properties of these tracers were not optimal in used models. In conclusion, these studies resulted in the identification of new strategies for the assessment of plaque stability and mouse models of atherosclerosis which could be used for plaque imaging. In the used probe panel, [18F]FDG was the best tracer for plaque imaging. However, further studies are warranted to clarify the applicability of [18F]EF5 and [68Ga]DOTA-RGD for imaging of atherosclerosis with other experimental models.

Software Development Process Modeling. Developers Perspective to Contemporary Modeling Techniques

Formal software development processes and well-defined development methodologies are nowadays seen as the definite way to produce high-quality software within time-limits and budgets. The variety of such high-level methodologies is huge ranging from rigorous process frameworks like CMMI and RUP to more lightweight agile methodologies. The need for managing this variety and the fact that practically every software development organization has its own unique set of development processes and methods have created a profession of software process engineers. Different kinds of informal and formal software process modeling languages are essential tools for process engineers. These are used to define processes in a way which allows easy management of processes, for example process dissemination, process tailoring and process enactment. The process modeling languages are usually used as a tool for process engineering where the main focus is on the processes themselves. This dissertation has a different emphasis. The dissertation analyses modern software development process modeling from the software developers’ point of view. The goal of the dissertation is to investigate whether the software process modeling and the software process models aid software developers in their day-to-day work and what are the main mechanisms for this. The focus of the work is on the Software Process Engineering Metamodel (SPEM) framework which is currently one of the most influential process modeling notations in software engineering. The research theme is elaborated through six scientific articles which represent the dissertation research done with process modeling during an approximately five year period. The research follows the classical engineering research discipline where the current situation is analyzed, a potentially better solution is developed and finally its implications are analyzed. The research applies a variety of different research techniques ranging from literature surveys to qualitative studies done amongst software practitioners. The key finding of the dissertation is that software process modeling notations and techniques are usually developed in process engineering terms. As a consequence the connection between the process models and actual development work is loose. In addition, the modeling standards like SPEM are partially incomplete when it comes to pragmatic process modeling needs, like light-weight modeling and combining pre-defined process components. This leads to a situation, where the full potential of process modeling techniques for aiding the daily development activities can not be achieved. Despite these difficulties the dissertation shows that it is possible to use modeling standards like SPEM to aid software developers in their work. The dissertation presents a light-weight modeling technique, which software development teams can use to quickly analyze their work practices in a more objective manner. The dissertation also shows how process modeling can be used to more easily compare different software development situations and to analyze their differences in a systematic way. Models also help to share this knowledge with others. A qualitative study done amongst Finnish software practitioners verifies the conclusions of other studies in the dissertation. Although processes and development methodologies are seen as an essential part of software development, the process modeling techniques are rarely used during the daily development work. However, the potential of these techniques intrigues the practitioners. As a conclusion the dissertation shows that process modeling techniques, most commonly used as tools for process engineers, can also be used as tools for organizing the daily software development work. This work presents theoretical solutions for bringing the process modeling closer to the ground-level software development activities. These theories are proven feasible by presenting several case studies where the modeling techniques are used e.g. to find differences in the work methods of the members of a software team and to share the process knowledge to a wider audience.

Modern vulkanisering & reparation av automobilringar

kuv., 14 x 22 cm

Formal development and quantitative verification of dependable systems

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Pre-and post-puberty physiological plasma oxytocin concentrations in male domestic cats (Felis silvestris catus)

The hormone oxytocin is released by the neuropituitary gland through stimulation of the neurons of the supraoptic and paraventricular nuclei of the hypothalamus. In order to determine the physiological concentrations of this hormone in domestic cats, blood samples were collected from 15 male animals (Felis silvestris catus) during the pre- and post-puberty periods (at four and eight months of age, respectively). Oxytocin determination was accomplished by radioimmunoassay. The average oxytocin concentrations measured in the pre- and post-puberty periods were 2.54±0.24 (μg/dL) and 2.53±0.28 (μg/dL), respectively, and there were no statistical differences between these measurements. Because there are few literature on the analysis of this hormone, especially in the case of male Felis silvestris catus, more studies on the influence of oxytocin on the physiology and reproduction of this species should be conducted under maintenance and situations of stress (such as transportation), and other routine events.

Comparative anatomical study of the leg's nerves of Cebus (barbed capuchins) with baboons, chimpanzees and modern humans

The anatomical comparative studies among the primates are important for the investigation of ethology, evolution, taxonomy, and comprehension of tools by hominoids. Especially the anatomical knowledge of Cebus contributes to conservation of the species, and to development of surgical procedures and clinical treatments of these animals, as they frequently are victims of automobile accidents. Recent anatomical studies came to a wrong conclusion regarding behavioral traits of Cebus, ascribed to few data available in previous literature. Therefore, to provide anatomical data and to support the other sciences related to anatomy, and to develop surgical and/or clinical procedures, we described the nerves of the legs of Cebus foccusing on their position and trajectory, as wll as innerved muscles, and compared these results with those of humans and other primates. Eight adult capuchin specimens were used for this study. The anatomical comparative study of the leg's nerves of Cebus demonstrated that, in general, structural organization of the nerves is similar among the four primates analyzed here (Cebus, chimpanzees, baboons and humans), which might be attributed to the fact that the all four primates have similar body structures. However, nerve trajectory and muscles innervation in Cebus was more similar to baboons.

Clinical, hematological, total plasma protein and fibrinogen parameters of magellanic penguins ( Spheniscus magellanicus ) pre- and post-rehabilitation

Abstract: Magellanic penguins (Spheniscus magellanicus) usually arrive in poor body conditions at Brazilian beaches during the winter. Hematology provides valuable information about clinical and immunity status of the animals. The aims of this study were to determine the hematologic, total plasma protein (TPP) and fibrinogen profiles of young and adult magellanic penguins in PROAMAR and CETAS-SC, relating these results with the state of health and survival possibility of the animals. In Paraná 14 animals were evaluated in pre and eight in post-rehabilitation and 29 animals were evaluated in Santa Catarina after rehabilitation. Before rehabilitation, all animals showed weakness. In hematological exams of these animals, we found that anemia was present in 83% of the penguins that died and 50% of those which survived. The heterophils/lymphocytes (H/L) ratio was 3.87±0.57 in animals that died, significantly higher than the average of 2.20±0.30 for animals that survived. These two parameters are useful to assess the survival possibility of animals to rehabilitation. The body condition score was positively correlated with hematocrit and TPP, and negatively correlated with H/L ratio. After rehabilitation, the values were similar to other animals of the family Spheniscidae, with averages ranging from 1.64 to 1.90x106 erythrocytes/μL; 43.38 to 48.80% of hematocrit; 12.45 to 13.52g/dL of hemoglobin; 8,684 to 14,011 leukocytes/μL; 4,767 to 8,041 heterophils/μL; 3,215 to 4,951 lymphocytes/μL; 95 to 655 eosinophils/μl; 179.8 to 277.9 monocytes/μL; 141 to 184.9 basophils/μL; and 1.26 to 1.74 of H/L ratio. These parameters can therefore be used as reference values and release parameters for young and adult Magellanic penguins in captivity on the rehabilitation centers.

Ramos colaterais do Arco aórtico do preá (Galea spixii Wagler, 1831)

Resumo: O preá é um roedor típico da caatinga pertencente à família Caviidae. Considerando a inexistência de dados sobre o arco aórtico do preá, foi realizado este estudo tendo como objetivo descrever os ramos colaterais do arco aórtico neste cavídeo, e dessa forma, contribuir com dados para biologia da espécie. Foram utilizados vinte preás machos provenientes de estudos anteriores e encontravam-se armazenados em freezer no Centro de Multiplicação de Animais Silvestres (CEMAS/UFERSA). Os animais foram descongelados, a cavidade torácica foi aberta, a aorta canulada e o sistema vascular lavado com solução salina e em seguida, injetado látex Neoprene corado com pigmento vermelho, amarelo ou branco. Posteriormente, os animais foram fixados em formol e depois de 72 horas, dissecados e analisados, sendo obtidos desenhos esquemáticos e os exemplares mais representativos fotografados. O arco aórtico do preá emitiu como ramos colaterais, o tronco braquiocefálico e a artéria subclávia esquerda. O tronco braquiocefálico originou na maioria das peças estudadas, a artéria carótida comum esquerda e o tronco braquiocarotídeo, do qual surgem as artérias subclávia direita e carótida comum direita. As artérias subclávias direita e esquerda em todos os animais estudados emitiram a artéria vertebral, a artéria torácica interna, a artéria cervical superficial, o tronco costocervical e a artéria axilar. O padrão da formação do arco aórtico do preá assemelhou-se ao observado em outros roedores, tais como no mocó, no porquinho-da-índia e na chinchila.

Retrospective study of pre-anesthetic electrocardiogram examination of 700 dogs conducted at the Veterinary Hospital of UFMG (2013-2014)

Abstract: Pre-operative electrocardiograms performed in 700 dogs were analyzed in order to establish correlation between sex, age, indication for surgery, body condition score, breed and weight. Initially a clinical questionnaire was filled out from each owner, including age, breed, sex, weight, clinical history and surgical indication. Dogs above 6 years of age or those showing any kind of cardiac auscultation disturbances were referred to electrocardiogram (ECG) evaluation. All ECG were performed and analyzed by the same veterinary specialist. Abnormalities at ECG were founnd in 364 of 700 (52%) evaluated dogs, and the most frequent variation was sinus arrhythmia, observed in 293 dogs (25.4%). No significant correlation was found between the electrocardiographic alterations with weight, sex and age of the animals. Therefore ECG should be conducted routinely regardless of age, sex, breed or surgical indication, highlighting its value for determining a safe anesthetic protocol that promotes minimal cardiopulmonary depression and allows rapid post-surgical recovery.

Lithostratigraphy and age of pre-Late Weichselian sediments in the Suupohja area, western Finland

Different types of laterally extensive sand- and gravel-dominated deposits, up to several tens of metres thick, were investigated in the Suupohja area of western Finland. The studied sediments were deposited in glacial, ice-marginal, glaciofluvial, sea or lake, littoral and terrestrial environments during several glacial-non-glacial cycles. Seventeen pre-Late Weichselian and three Late Weichselian/Holocene sedimentary units were identified. These were divided into ten formally and two informally defined formations that were together termed the Suupohja Group. Every unit are nevertheless not detectable throughout the study area. The informally defined “Karhukangas lower deposits” represent the lowest units in the Suupohja Group. The Karhukangas lower deposits with 5 till units, 3 glaciolacustrine/-marine units and 2 sand units, were interpreted as having been deposited during possibly four glacial-non-glacial cycles before the Late Pleistocene Subepoch (MIS 6 or earlier). The Kankalo Sand above the Karhukangas lower deposits comprises glaciofluvial and aeolian sands of Late Saalian, Eemian or Early Weichselian origin (MIS 6–MIS 5c). The Kariluoma Till above the Kankalo Sand was possibly deposited during the Late Saalian glacial advance, although an Early Weichselian origin is also possible. The Harrinkangas Formation, with glaciofluvial and quiet-water sediments, is interpreted as having been deposited during the Late Saalian and Eemian Stages (MIS 6–MIS 5e). The uppermost units in the deposits studied, the Kodesjärvi Formation (shore deposit), Isojoki Sand (aeolian), Rävåsen Formation (glaciofluvial), Vanhakylä Formation (shore line deposit), Dagsmark Till and Kauhajoki Till, were deposited during the Weichselian Stage (MIS 5d–MIS 2). In addition, Early Holocene (MIS 1) eskers without till cover were informally termed the “Holocene esker deposits”. The Lumikangas Formation represents gravelly shore deposits formed in the Holocene Epoch, when these areas last emerged from the sea. The first Weichselian ice expansion possibly reached the western part of Suupohja in the Early Weichselian Substage (MIS 5d?), but it did not expand further to the east. The second Weichselian glaciation of relatively short duration occupied the southern part of Finland in the later part of Middle Weichselian (MIS 3). Thus, the southern half of the country remained ice-free for the majority (~65–75%) of the Weichselian Stage. Instead, both humid temperate and periglacial conditions alternated. In the initial part of Middle Weichselian, this area was partly submerged, which indicates eastward expansion of the Scandinavian ice sheet(s), depressing the lithosphere. The exceptionally thick sediment cover, multiple lithofacies, relict landscape and preserved preglacially weathered bedrock are evidence of weak glacial erosion in the Suupohja area during the latest as well as earlier glaciations, making this area one of the key areas in Quaternary research.

Development of nano-meter motion control in Japan

Production machines for next generation LSIs such as 4G-DRAMs and for large liquid crystal displays such as 0.5mx0.5m size, and information equipment such as magnetic hard disks and DVDs must have the positioning accuracy of a nano-meter order. To realize such a high degree of the positioning accuracy, not only precision machine elements and mechanisms but also high precision sensors, actuators and controller design techniques becomes crucial. This paper introduces recent topics of precision positioning and motion control technology in Japan.

Käsitteen pre-conflict käsiteanalyysi

Maailmassa on tälläkin hetkellä käynnissä useita sotaan rinnastettavia aseellisia selkkauksia. Käsite sota on kuitenkin menettänyt merkitystään ja sen on korvanneet käsitteet kuten aseellinen selkkaus ja konflikti. Kansainvälisessä ja humanitaarisessa oikeudessa on epäonnistuttu käsitteiden määrittelyssä, mikä on luonut haasteita lakien ja säädösten tulkintaan. Sodankuvan muutoksen ja kansainvälisen oikeuden kehittymisen myötä myös sodan julistus on menettänyt merkityksensä, mikä on johtanut siihen, että aseellisten selkkausten ja konfliktien alkuajankohtaa on hyvin vaikea määritellä. Tässä tutkimuksessa avataan ja selvennetään käsitteen pre-conflict merkitys käsiteanalyysin avulla. Päämääränä ei ole kääntää käsitettä suomeksi, vaan tuottaa lisää tietoa käsitteestä. Tutkimusaineistona käytetään EU:n, YK:n sekä Naton virallisia tiedotteita vuonna 2011 alkaneesta Syyrian tilanteesta. Analyysin avulla saavutetaan ymmärrys EU:n, YK:n sekä Naton käsitteiden käytölle, jonka avulla käsitteen pre-conflict ominaispiirteet, säännönmukaisuudet ja syysuhteet kyetään tunnistamaan. Analyysin ensimmäisessä osassa keskitytään käsitteen osien alkuperän tunnistamiseen ja analyysin tavoitteiden asettamiseen. Seuraavassa osassa Syyrian tilanteelle suoritetaan perusteellinen analyysi, jonka avulla käsitteen ominaispiirteet kyetään tunnistamaan. Pääkäsite erotetaan sen lähikäsitteistä sota, sisällissota sekä kriisi ja sen pohjalta käsitteelle luodaan ennakkoehdot ja seuraukset. Lopuksi pragmaattisuuden tavoittelemiseksi käsitteelle luodaan malliesimerkki Syyrian tilanteeseen sitoen. Tutkielma tiivistyy empiiriseen malliin, josta käsitteen tarkasteleminen yksinkertaistuu. Laajan kirjallisuuskatsauksen tuloksena voidaan käsitteen todeta tarkoittavan aikaa ennen konfliktia. Käsite konflikti on rinnastettavissa kansainvälisessä oikeuden tunnistamaan aseelliseen selkkaukseen. Keskeisimmät tutkimustulokset liittyvät käsitteen pre-conflict ajalliseen rajaukseen. Ajallisesti pre-conflict-ajan alku rajautuu yksittäiseen tapahtumaan, minkä jälkeen tilanne ei tule päättymään ennen kuin aseellinen selkkaus on saavuttanut ratkaisunsa. Pre-conflict-aika rajaa rauhanajan sekä erilaiset yhteiskunnalliset häiriötilanteet ajasta, jolloin häiriötilanteet eskaloituvat aseelliseksi selkkaukseksi sekä aikaan jolloin tilanne on jo eskaloitunut aseelliseksi selkkaukseksi. Kohdistettaessa tutkimusta aikaan ennen aseellisen selkkauksen alkua saadaan tietoa eskaloitumisen syistä, jolloin ennaltaehkäisevät toimenpiteet olisivat hyödynnettävissä alkavissa tilanteissa. Sotilaallisiin kriiseihin tai aseellisiin selkkauksiin liittyy voimakeinojen käyttö, joita säännellään kansallisessa lainsäädännössä. Voimankäyttö perustuu osittain kansainvälisen oikeuteen ja niiden sopimuksiin, joissa säädetään muun muassa suhteellisen voimankäytön periaate. Siinä missä rauhanaikana varaudutaan erinäisiin uhkatilanteisiin ja laaditaan suunnitelmia häiriötiloja ja poikkeusoloja varten, tulisi myös varautua poistamalla käsitteisiin liittyvät epäselvyydet. Laatimalla malleja, joiden avulla alkavat tilanteet tai aseelliset selkkaukset tunnistetaan ajoissa, mahdollistetaan oikeanaikainen päätöksenteko ja ennaltaehkäisevät toimenpiteet.

Aplicação pre-emergente de misturas de alachlor com diuron e cyanazine para o controle de plantas daninhas em algodão "IAC-17"

Para se conhecer a ação de misturas de alachlor com diuron ou com cyanazine para o controle de monotiledôneas e de dicotiledôneas em cultura de algodão 'IAC-17', foi conduzido um experimento de campo, em 1981/82, em Mogi-Mirim, SP, em solo com textura areno-argilosa, onde alachlor a 2,15 kg, 2,58 kg e 3,01 kg/ha foi aplicado em mistura de tanque com diuron, a 1,00 kg/ha ou com cyanazine a 1,00 kg/ha. Os herbicidas que compuseram as misturas foram empregados isoladamente, naquelas mesmas doses. Constaram do experimento ainda, duas testemunhas mantidas sem mato por meio de capinas e uma testemunha sem capina. Os 14 tratamentos foram distribuídos em blocos ao acaso, com quatro repetições. Foram realizadas observações visuais de infestação de mato aos 14, 31, 45, 75, 82, 94 e 100 dias após a aplicação dos herbicidas. Quando, pelo menos, uma parcela do tratamento atingia 25% de reinfestação, todo o tratamento era capinado e mantido no limpo até a colheita. Foram consideradas também a altura das plantas, sua população e a produção do algodão em caroço. Os resultados obtidos mostram que alachlor a 3,01 kg/ha + diuron a 1,00 kg/ha conseguiram bons resultados de controle das plantas daninhas por período de 100 dias enquanto que alachlor a 2,58 kg/ha + diuron a 1,00 kg/ha, e alachlor a 2,58 kg/ha e a 3,01 kg/ha + cyanazine a 1,00 kg/ha persistiram com sua ação de controle por 94 dias. Os tratamentos com alachlor a 3,01 kg/ha, diuron a 1,00 kg/ha, alachlor a 2,15 kg, 2,58 kg e 3,01 kg/ha em mistura com diuron a 1,00 kg/ha, e ainda alachlor a 3,01 kg/ha + cyanazine a 1,00 kg/ha, apresentaram tendências a reduzir a altura das plantas, segundo resultados de suas análises pelo teste de Tukey a 5%, sendo que a testemunha sem capina apresentou altura significativamente inferior aos demais tratamentos. A população e a produção não foram influenciadas pelos tratamentos com herbicidas, sendo semelhantes à testemunha capinada e superiores à testemunha sem capina.

Commercialization of Modern Renewable Energy

The threat of global warming and its consequences are widely recognized, and the question of how to proceed with the long transition towards fossil fuel -neutral economies concerns many nations and people. At the same time the world’s primary energy use is predicted to increase significantly during the next decades as a result of global population and welfare increase. Improved energy efficiency and increased use of renewable energy sources in the world’s energy mix play important roles in the future energy production and consumption. The objective of this thesis is to study how novel renewable energy technologies, such as distributed small-scale bio-fueled combined heat and power production and wind power technologies could be commercialized efficiently. A wide array of attributes may contribute to the diffusion of new products. In general, the bioenergy and wind power technologies are in emerging phases, and the diffusion stage varies from country to country. The effects of firms’ technology choices, collaboration and alliances are studied in this thesis. Furthermore, the roles of national energy infrastructure and energy support schemes in the commercialization of new renewable energy products are explored. The empirical data is based on energy expert interviews, financial and patent data, and literature reviews of different case studies. The thesis comprises two parts. The first part provides an overview of the study, and the second part includes six research publications. The results reveal that small-scale bio-fueled combined heat and power production and wind power technologies are still in emerging phases in their life cycles, and energy support schemes are crucial in the market diffusion. The study contributes to earlier findings in the literature and industry by confirming that adequate energy policies and energy infrastructure are fundamental in the commercialization of novel renewable energy technologies. Firm-specific issues, including business relationships and new business models, and market-related issues will have a more significant role in the market penetration in the future, when the technologies mature and become competitive without political support schemes.