Thesis advisor: Peter Kreeft / Thomas Aquinas is generally viewed as the chief proponent of the theory of delayed animation, the view that the human embryo does not at first have the rational soul proper to human beings. Thomas follows Aristotle's embryology, in which an embryo is animated by a succession of souls. The first is a nutritive soul, having the powers of growth, nutrition, and generation. The second is a sensitive soul, having the additional powers of locomotion and sensing. The third and final soul is the human, or rational soul, which virtually includes the nutritive and sensitive souls. Because Thomas holds that there is only one substantial form of a composite, none of these forms overlap to provide continuity. It is therefore exceedingly difficult to speak of the embryo as one enduring subject through the succession of souls. Moreover, because of the way that the nutritive soul is associated with plants, and the sensitive soul is associated with animals, interpreters generally hold that for Thomas the embryo is first a plant, then an animal, and with the advent of the rational soul, finally a human being. Those who write about the ontological status of the embryo assume that delayed animation necessarily entails delayed hominization, that is, that the embryo only becomes human at a later stage of its development, when it receives the rational soul. Those who hold a delayed animation view of the embryo often invoke Thomas' schedule of successive souls in the embryo as a model for viewing it as not yet human in early stages of development, linking hominization to the ability to perform intellectual operations. That Thomas specifies that a body must be sufficiently organized before the advent of the rational soul seems to them to solidify their view of the embryo as not sufficiently organized to be truly human. Additionally, even outside of an explicitly Thomist framework, Thomist metaphysical principles are often invoked in arguments that center on twinning and totipotency of blastomeres in the early embryo, and whether that early embryo is one individual if it is potentially many. Those who hold immediate animation views (i.e., the embryo receives the rational soul at once, with no mediate states) often adopt the strategy of importing modern data on the internal organization and self-directed development of the embryo, and argue that if only Thomas had known that the zygote was not unformed and undifferentiated, that it has within itself all it needs to become a mature adult human, he would have held that the embryo is immediately suited to receive the rational soul, and thus is human from conception. In this way they attempt to employ a change in scientific data to negate the need for a succession of forms in the embryo. The author identifies the being of the human embryo as a prior metaphysical problem within Thomas' work, and advances a different interpretation of his views: that the embryo, even before the advent of the rational soul, is human. To establish this claim, she traces the problems which emerge in the current debate about when the embryo becomes human, and argues that contrary to expectation, it is not necessary to equate immediate rational animation with immediate hominization, demonstrating that all other approaches yield results entirely untenable for Thomas. A survey of texts reveals that Thomas did in fact view the embryo as human before the rational soul, though he does not methodically work out the implications of that view in a number of areas. Moreover, a distinction based on a passage in Aristotle's Generation of Animals with regard to an additional meaning of generation may resolve the ambivalence in Thomas' account of the embryo as passive under the formative power of the father's semen. Finally, a third meaning of generation is offered to show that Thomas recognized and wished to resolve the difficulty of explaining the continuity and identify of the embryo in the succession of souls. What results is an immediate hominization view of the embryo that, because it accommodates Thomas' succession of souls and does not depend upon importing modern biological data on the embryo, is consistent with Thomas' account, and is thoroughly cognizant of the way Thomas viewed human nature and the final end of human being. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Philosophy.

O objetivo deste trabalho foi avaliar a taxa de sucesso, a quantidade de perda óssea em altura e a interação osso/implante para três diferentes protocolos: 1) implantes osseointegráveis mantidos sem carga durante período de reparo de 120 dias; 2) implantes submetidos a interferências oclusais; e 3) implantes que receberam carga imediata para ancoragem ortodôntica. Foram utilizados doze minipigs BR-1, nos quais foram instalados 70 implantes osseointegráveis de titânio (3,75mm diâmetro x 8,50mm comprimento), divididos em 5 grupos: Grupo 1 (n=12), implantes sem carga sepultados na mesial de caninos; Grupo 2 (n=6), implantes sem carga em áreas de extração; Grupo 3 (n=12), implantes expostos a interferências oclusais; Grupo 4 (n=20), implantes submetidos à carga ortodôntica imediata; Grupo 5 (n=20), implantes instalados em áreas de extração e submetidos à carga ortodôntica imediata. Ao término do período experimental, os animais foram eutanasiados e biópsias da região de interesse coletadas. Realizou-se avaliação clínica para estabelecer a porcentagem de sucesso (Teste Exato de Fisher), análise radiográfica para quantificar a perda óssea em altura (programa de análise de imagens KS300-Zeiss®, ANOVA) e análise histológica para descrever as características da interface osso/implante. A análise dos dados demonstrou: 1) Grupos 1, 2, 4 e 5 - taxa de sucesso, quantidade de perda óssea em altura e interação osso/implante semelhantes; 2) Grupo 3 - taxa de insucesso e quantidade de perda óssea significantemente maiores que os demais grupos, além de apresentar ausência de interação osso/implante. Os resultados clínicos, radiográficos e histológicos revelados nos grupos submetidos à carga ortodôntica imediata em relação aos grupos sem carga demonstraram que a perda óssea na região da crista óssea periimplantar é aceitável e não compromete a estabilidade clínica dos implantes. Desta forma, a utilização de carga imediata para ancoragem em Ortodontia não prejudica a posterior utilização desses implantes para a reabilitação protética, objetivo primário da indicação deste protocolo. Estudos clínicos prospectivos são necessários para comprovar estes dados. / This research aimed at evaluating the success rate, the bone height loss, and the bone/implant interface in three different protocols: 1) osseointegrated implants maintained without load during a repair period of 120 days; 2) osseointegrated implants submitted to occlusal interferences; and 3) immediately loaded osseointegrated implants for orthodontic anchorage. Twelve BR-1 minipigs were used, in which 70 osseointegrated titanium implants were inserted (3.75mm diameter x 8.50mm length), divided into 5 groups: Group 1 (n=12), submerged implants without load; Group 2 (n=6), implants without load in extraction sites; Group 3 (n=12), implants exposed to occlusal interferences; Group 4 (n=20), exposed implants submitted to immediate orthodontic load; Group 5 (n=20), exposed implants inserted in extraction sites and submitted to immediate orthodontic load. At the end of the experimental period, the animals were euthanized and biopsies of the areas of interest were harvested. The clinical analysis (Exact Fisher Test) revealed the success rate of the inserted implants, the radiographic analysis quantified the bone height loss (image analysis program KS300-Zeiss®, ANOVA), and the histological analysis showed the bone/implant interface characteristics. The data analysis revealed: 1) Groups 1, 2, 4 and 5 - similar success rate, bone height loss and bone/implant interface characteristics; 2) Group 3 - statistically greater fail rate and bone height loss, and absence of bone/implant interaction characteristics. Clinical, radiographic and histological results presented in the groups submitted to immediate orthodontic load compared with the other without load demonstrated that the bone loss in the bone crest area is acceptable, and does not compromise the clinical stability of the implants. Therefore, the use of immediate load for orthodontic anchorage did not jeopardize the subsequent use of the implants for oral prosthetic rehabilitation, the main objective of this protocol. Further clinical studies are necessary to confirm these data.

O objetivo deste trabalho foi avaliar a taxa de sucesso, a quantidade de perda óssea em altura e a interação osso/implante para três diferentes protocolos: 1) implantes osseointegráveis mantidos sem carga durante período de reparo de 120 dias; 2) implantes submetidos a interferências oclusais; e 3) implantes que receberam carga imediata para ancoragem ortodôntica. Foram utilizados doze minipigs BR-1, nos quais foram instalados 70 implantes osseointegráveis de titânio (3,75mm diâmetro x 8,50mm comprimento), divididos em 5 grupos: Grupo 1 (n=12), implantes sem carga sepultados na mesial de caninos; Grupo 2 (n=6), implantes sem carga em áreas de extração; Grupo 3 (n=12), implantes expostos a interferências oclusais; Grupo 4 (n=20), implantes submetidos à carga ortodôntica imediata; Grupo 5 (n=20), implantes instalados em áreas de extração e submetidos à carga ortodôntica imediata. Ao término do período experimental, os animais foram eutanasiados e biópsias da região de interesse coletadas. Realizou-se avaliação clínica para estabelecer a porcentagem de sucesso (Teste Exato de Fisher), análise radiográfica para quantificar a perda óssea em altura (programa de análise de imagens KS300-Zeiss®, ANOVA) e análise histológica para descrever as características da interface osso/implante. A análise dos dados demonstrou: 1) Grupos 1, 2, 4 e 5 - taxa de sucesso, quantidade de perda óssea em altura e interação osso/implante semelhantes; 2) Grupo 3 - taxa de insucesso e quantidade de perda óssea significantemente maiores que os demais grupos, além de apresentar ausência de interação osso/implante. Os resultados clínicos, radiográficos e histológicos revelados nos grupos submetidos à carga ortodôntica imediata em relação aos grupos sem carga demonstraram que a perda óssea na região da crista óssea periimplantar é aceitável e não compromete a estabilidade clínica dos implantes. Desta forma, a utilização de carga imediata para ancoragem em Ortodontia não prejudica a posterior utilização desses implantes para a reabilitação protética, objetivo primário da indicação deste protocolo. Estudos clínicos prospectivos são necessários para comprovar estes dados. / This research aimed at evaluating the success rate, the bone height loss, and the bone/implant interface in three different protocols: 1) osseointegrated implants maintained without load during a repair period of 120 days; 2) osseointegrated implants submitted to occlusal interferences; and 3) immediately loaded osseointegrated implants for orthodontic anchorage. Twelve BR-1 minipigs were used, in which 70 osseointegrated titanium implants were inserted (3.75mm diameter x 8.50mm length), divided into 5 groups: Group 1 (n=12), submerged implants without load; Group 2 (n=6), implants without load in extraction sites; Group 3 (n=12), implants exposed to occlusal interferences; Group 4 (n=20), exposed implants submitted to immediate orthodontic load; Group 5 (n=20), exposed implants inserted in extraction sites and submitted to immediate orthodontic load. At the end of the experimental period, the animals were euthanized and biopsies of the areas of interest were harvested. The clinical analysis (Exact Fisher Test) revealed the success rate of the inserted implants, the radiographic analysis quantified the bone height loss (image analysis program KS300-Zeiss®, ANOVA), and the histological analysis showed the bone/implant interface characteristics. The data analysis revealed: 1) Groups 1, 2, 4 and 5 - similar success rate, bone height loss and bone/implant interface characteristics; 2) Group 3 - statistically greater fail rate and bone height loss, and absence of bone/implant interaction characteristics. Clinical, radiographic and histological results presented in the groups submitted to immediate orthodontic load compared with the other without load demonstrated that the bone loss in the bone crest area is acceptable, and does not compromise the clinical stability of the implants. Therefore, the use of immediate load for orthodontic anchorage did not jeopardize the subsequent use of the implants for oral prosthetic rehabilitation, the main objective of this protocol. Further clinical studies are necessary to confirm these data.

Parkinson’s disease is a neurodegenerative disease caused by a loss of dopamine-producing neurons in the basal ganglia. Primary motor deficits include resting tremor, bradykinesia, muscular rigidity, and postural instability. Most importantly, patients have difficulty both initiating movements and performing well-timed movements. This study explored the effect of rhythm on the timing of upper extremity movements in patients with Parkinson’s disease. Comparisons were made between an external rhythmic cue, an external rhythmic cue in combination with auditory feedback, and no cue. Fifteen participants performed a simple reaching task in each of the four cueing conditions with the use of an interactive touch table. Condition 1 consisted of no cue. Condition 2 included a metronome set to the participant’s baseline tempo. Condition 3 included a metronome set to the participant’s baseline tempo, and a synthesized tone that occurred as a result of contact with the table. Finally, Condition 4 included no cue, similar to Condition 1. Participants were placed into either a mild/moderate level of impairment group, or a severe level of impairment group. Data were collected for total movement time, initiation time, and delta time for each participant in all four conditions. Results of the study did not reveal a main effect of condition on total movement time, initiation time or delta time. However, post-hoc pair-wise comparisons revealed significant decreases between Condition 1 and Condition 4, which were both uncued conditions, for both total movement time and delta time. In addition, for total movement time, a significant decrease was found between Condition 2 (external rhythmic cue) and Condition 4 (no cue). An immediate effect of cueing was found for initiation time and delta time, but did not reach a level of significance. An immediate effect of cueing on total movement time was not evident. Overall, from Condition 1 to Condition 2 as well as Condition 1 to Condition 3, initiation time and delta time decreased, but total movement time did not. Further analysis of level of impairment could not be conducted because of the small number of participants in the severe level of impairment group. The results suggest that one auditory cue was not more beneficial than the other for improving total movement time, initiation time, or delta time. In addition, the improvement from Condition 1 to Condition 4 for total movement time and delta time suggests that a practice effect was evident for the participants. The results of the study suggest that long-term training of either auditory cue can be an effective rehabilitation technique for patients with Parkinson’s disease to improve the timing of upper extremity movements.

The first wave of the inducible gene network up-regulated by pathogen-stimulated mononuclear cells encodes a variety of effector proteins with pleitropic biological activities. This class of primary immediate early (IE) genes codes for potent pro-inflammatory cytokines and chemokines that play a prominent role during the manifestation of inflammatory response. In an attempt to better understand induction mechanisms for such genes, I have focused on those coding for human interleukin-1β (IL1B) and tumor necrosis factor α (TNF), which exhibit both transient IE induction as well as cell-type restriction. Employing a combined approach using cell lines and primary cells, reporter transient transfection, chromatin conformational capture and immunoprecipitation, evaluation of transcript integrity, ectopic expression in a non-competent cell type, and comparison to mouse orthologs, I have determined that a complex array of mechanisms interplay in order to distinctly regulate the Toll-like receptor (TLR) signaling-dependent induction of these two important pro-inflammatory genes whose deregulation provides the etiology for numerous diseases. Prior to induction, TNF exhibited pre-bound TATA Binding Protein (TBP) and paused RNA Polymerase II (Pol II), which are the hallmarks of poised IE genes. In contrast, IL1B is stringently regulated by long-distance chromosome gyrations, multistep activation through a unique doubly-paused Pol II which, in association with the monocyte lineage factor Spi1/PU.1 (Spi1), maintains a low TBP and Pol II occupancy prior to activation. Activation and DNA binding of the transcription factors C/EBPβ and NF-κB resulted in de novo recruitment of TBP and Pol II to IL1B in concert with a permissive state for elongation mediated by the recruitment of the positive elongation factor b (P-TEFb). This Spi1-dependent mechanism for IL1B transcription, which is unique for a rapidly-induced/poised IE gene, was more dependent upon P-TEFb than was the case for the TNF gene. Nucleosome occupancy and chromatin modification analyses of the IL1B and TNF promoters, revealed activation-specific changes in chromatin marks that are supportive for nucleosome clearance and formation of nucleosome free regions (NFR). Furthermore, ectopic expression of Spi1, along with a TLR surrogate (over-expressed TNF receptor associated factor 6, TRAF6), in a cell line incompetent for IL1B transcription, is observed to prime the cell's endogenous genome for IL1B induction by appropriately phasing promoter nucleosomes and recruiting paused Pol II in a manner reminiscent of that observed in competent monocytes. Here I report a novel connection between the metabolic state of cells and HIF-1α in regulating murine Il1b gene expression. With regard to the lipopolysaccharide (LPS) unresponsive state known as endotoxin tolerance, my data revealed that following transient induction, IL1B and TNF remained marked with paused Pol II complexes for up to 24 hours post-stimulation. Upon subsequent LPS exposure, tolerized TNF remained in an unresponsive paused state, while IL1B resumed transcription due to recruitment of positive elongation kinase P-TEFb. Emerging evidence suggests that inflammatory responses of LPS/TLR4 activated macrophages are interconnected with metabolic pathways, resulting in the shift of energy utilization by the cells. Here I report that inhibition of either phosphoinositide 3-kinase (PI3K) or glucose metabolism had a greater affect on the transcriptional response of Il1b than of Tnf. The differences between these two genes, especially for endotoxin tolerance, suggest that il1b may play a distinct role from tnf in chronic inflammation. / Bayer School of Natural and Environmental Sciences; / Biological Sciences / PhD; / Dissertation;

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

In the last decade we have witnessed the strengthening of an international network of higher education all over the world. The need to educate and develop our contemporary society is a machine in continuous work and progress. Being a student is a condition that makes individuals, enriches culture and often crosses boundaries. Students are a necessary piece in the capitalist economy, which makes them a valuable and essential resource in order to sustain its markets. Therefore, countries and institutions compete to hold more and more students within their society but what are the consequences of the internationalisation of higher education (and its market(s) that is taking place on a global scale? The globalisation and internationalisation of education promote a migration of students always on the rise. In some cities such as Umeå, it implies consequent urban growth, the need to develop facilities, services and accommodations. Such patterns of immigration make students actors in the real estate market of the country they move to but they do not always find adequate conditions for their integration. The current economic crisis has debilitated many markets including that of real estate, and in that context, the thesis explores alternative ways of approaching affordable accommodation for students, as well as a different understanding of urban planning that aims at enabling diverse coexistences of students and other inhabitants and the progressive transformation and hybridisation of otherwise very homogenous areas of the city.

Food is something that we all have in common. We need it to survive and although we don’t always notice it, it has structured our relationships, homes, communities, countryside and cities for as long as humans have been around. The invention of farming led to the first static settlements, thus, enabling the evolution of cities.  In Sweden, the way people live and eat has changed drastically over the last fifty years. A society that was previously made up of clusters of small self-sufficient family-run farms has urbanised rapidly becoming one of the least self-sufficient, supermarket-dominated countries in Europe. Current housing developments such as Tavleliden (described by the municipality as a ‘nature-oriented’ area) on the outskirts of Umeå are designed and marketed in a way that encourages its residents to do little else but drive to the shops and consume.   In order to reach optimistic population and economic growth goals, politicians in Umeå hope that the rapid rate of urbanisation will continue. Many decisions, such as building new roads, covering up valuable agricultural land, subsidising large out-of-town retail centres and cutting down on services in surrounding villages are being justified because of these expectations. The landscape is not only becoming defined by cars and places to shop, but it seems the only people being catered for are those with money to spend.   The favouritism towards large corporations has not only made life almost impossible for independent businesses in the city to survive, (the number of independent food shops in the city centre has gone from thirty-six in 1950 to just one upmarket delicatessen in 20142), but according to Bjorn Forsberg they are also making it difficult for small food shops and farms outside Umeå - and the communities that rely on them to survive. While many middle-class families with jobs in the city are choosing to move to the suburbian developments outof- town, people whose livelihoods may have depended on the land are being forced to move into the town.  Some of us may find the experience of visiting a supermarket bland. Others may find the permanent and predictable choice of products from all over the world thrilling. Whatever our differing opinions, the fact is that, as there is very little else to choose from, whether we want to or not, in Umeå we all rely on them.   If we start trying to imagine the length of roads, train lines, airports, food-distribution centres and ferries that need to work faultlessly day in and day out delivering enough food for almost 300,000 meals a day to Umeå alone, we realise how important, but also how dependent the current food network is. If this system failed in Sweden, unlike many other counties who stock reserves, there would be a food crisis in only two days.   By emphasising the benifits of organic and offering connections to the production process Swedish food businesses such as Minfarm, Älvåkern and phone applications like ‘Bonde På Köpet’ are working to increase the appeal of locally produced food, though still cater for a largely middle-class market. Other producers in Västerbotten such as Hallnås or Baggböle Gård, are either relient on the neo-liberal supermarket system to sell their products or if they do sell directly to clients currently lack the resources to make themselves known.   You may wonder why I think that this matters and why it has any relation to architecture. If there’s food on the shelves, what’s wrong with continuing with business as usual?   If ‘we are what we eat’, I would also argue that the design of our cities, homes (and of course, the hinterland that we rely on!) are also a result of ‘what we eat’. But, as the English architect Carolyn Steel points out in her book Hungry City “No government, including our own, has ever wanted to admit its dependency on others for sustenance.” Arne Lindström, the regional manager for The Federation of Swedish Farmers (LRF) has similar concerns. In a recent article in Västerbotten’s Kuriren he exclaims: “The reason why we have to farm seems to have been lost during an era of abundance. That food is essential is actually no longer obvious, and it is even less obvious that agriculture’s primary task is precisely to produce our food.”   So, it seems that as a city we care very little about our food. We are happy to exchange valuable arable land for a large shop that sells cheap mass-produced furniture. We are happy to drain our hinterlands of the people and expertise that know how to produce food. We are happy to keep building more supermarkets and ordering catalogue houses that require more cars and more oil.  What if instead, there was an architecture that allowed another kind of living? One that was less dependent on cars and imported food. One that encouraged residents to be producers as well as consumers. Maybe an alternative to the secluded suburbs and souless supermarkets that are being planned all around the city. An architecture that allows communities develop that are more connected to the land and the food that it eats. This thesis will explore these ideas.

Diss. (sammanfattning) Uppsala : Univ., 2003. / Härtill 3 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.