京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第21709号 / 薬科博第100号 / 新制||薬科||11(附属図書館) / 京都大学大学院薬学研究科薬科学専攻 / (主査)教授 中山 和久, 教授 竹島 浩, 教授 土居 雅夫 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

In today's society, it's becoming increasingly important to find methods which useenergy more efficiently. One established method is night time set-back. When usingnight time set-back the indoor temperature is lowered during the night. This result ina smaller temperature difference between indoors and outdoors, which in turnreduces heat losses. The method requiers that heat can be stored into and emittedfrom the building's frame. This thesis examines the effects of night time set-back on four different building types.The building types are: a concrete building from the 1960s, a concrete building fromthe 1960s with new windows and doors, a concrete building from the 2010s and awooden building from the 2020s. The thesis examines how the night time set-backaffect the heat demand, the heat power demand and the cost of heat. The results show that the night time set-back reduces the heat demand by 5-11 % forall building types that are examined. The daily average power reduces by 1-4 % for allbuilding types, which results in the cost of heating reduces by 3-7 %for all buildingtypes. The maximum power peak increases by 1-12 %. The set-up of the districitheating price model is critical for the economical outcomes. Since night time set-backcontributes to increased power peaks, new calculations for the economics can beneeded in the future if the price model change from daily power to maxiumum power(on hourly basis).

A hallmark of higher-order cortical regions is their functional heterogeneity, but it is not well understood how these areas are able to encode diverse behavioral information. The anterior cingulate cortex (ACC), for example, is known to be important in a large range of behaviors, including, decision making, emotional regulation and social cognition. In support of this, previous work shows activation of the ACC to anxiety-related and social stimuli but does not use cellular resolution or cell-type specific techniques to elucidate the possible heterogeneity of its subcircuits. In this work, I investigate how subpopulations of neurons or microcircuits within the ACC encode these different kinds of stimuli. One type of inhibitory interneuron, which is positive for vasoactive intestinal peptide (VIP), is known to alter the activity of clusters of pyramidal excitatory neurons, often by inhibiting other types of inhibitory cells. Prior to this research, it was unknown whether the activity of VIP cells in the ACC (VIPACC) encodes anxiety-related or social information and whether all VIPACC activate similarly to the same behavioral stimuli. Using in vivo Ca2+ imaging and 3D-printed miniscopes in freely behaving mice to monitor VIPACC activity, I have identified distinct subpopulations of VIPACC that preferentially activate to either anxiogenic, anxiolytic, social, or non-social stimuli. I also demonstrate that these stimulus-selective subpopulations are largely non-overlapping and that clusters of cells may co-activate, improving their encoding. Finally, I used trans-synaptic tracing to map monosynaptic inputs to VIP and other interneuron subtypes in the ACC. I found that VIPACC receive widespread inputs from regions implicated in emotional regulation and social cognition and that some inputs differ between types of ACC interneurons. Overall, these data demonstrate that the ACC is not homogeneous – there is marked functional heterogeneity within one interneuron population in the ACC and connective heterogeneity across ACC cell types. This work contributes to our broader understanding of how the cortex encodes information across diverse contexts and provides insight into the complexity of neural processes involved in anxiety and social behavior.

In this work, an audit of energy use and the indoor climate in anindustrial property has been carried out and measures taken that canimprove these aspects have been investigated. The property that wasstudied in this project is Munters factory in Tobo. Munters is aninternational company working in AirTech and FoodTech and thefactory in Tobo is the only Swedish Munters factory. The factoryproduces aggregates for dehumidifying air and the material used fordehumidification. The facility has office landscapes, assembly workand production. Today, the factory has an indoor climate that varieswith the seasons, with high temperatures in summer and lowtemperatures in winter. A more constant indoor climate is desired. The audit of energy consumption shows that the energy consumptionfor the year 2019 was approximately 8033 MWh, of which electricityconsumption accounts for 77% and gas consumption for 23%. However,the lack of sub-meters in the plant has made it difficult toidentify exactly how much of the electricity and gas consumptiongoes to heating, ventilation and business processes. Consequently,some estimates and observations have been made to map how energy useis distributed. The indoor climate in the office parts of the plant has during mostof the measurement period had an air temperature within 20-25 °Cand a relative humidity within 20-70%. On extremely cold and hotdays, the temperature and relative humidity may fall outside thespecified ranges. In production, high temperatures were measuredabove 30 °C during summer and temperatures down to 15 °C duringwinter.

No description available.

Energy efficiency of buildings is becoming more and more common as a step towards decreasing the amount of climate emissions in the world. In the Swedish city Gothenburg, there are many existing buildings that soon faces extensive renovations due to age and therefore they have a lot of potential to, at the same time, improve the energy efficiency. Some of the buildings uses district heating as heating system and therefore this project has included an investigation of how the energy efficiency of a building affects the delivery of the district heating. The project also included an investigation of how energy efficiency of existing buildings affects the planning of the future needs of district heating.By applying energy saving measures on a reference building that can represent all the buildings in an area can the maximal power use at the DVUT be forecasted. The energy savings impact on the building’s energy- and power signatures is also a part of the study. The result of the energy savings measures is then used in an example of Gothenburg´s urban development by applying the results of the reference building on an area called Heden.The project includes a study, a model in VIP-Energy, an economic analysis of the energy savings and the example of the urban development of Heden. The results shows that the suggested measures reduce the primary energy number by 47 % and that the maximal power use reduced by 50 %. For property owners the economic analysis showed that the measures were not enough profitable. On the other hand, did the result, by the example with Heden also showed that Göteborg Energi can profit by reducing the energy use in existing buildings because it reduces the future additional net power.

Le neuroblastome (NB) est un cancer pédiatrique dérivé de la crête neurale. Les NB à haut risque sont des tumeurs peu différenciées présentant une amplification de MYCN et les plus agressives possèdent en plus une mutation d'ALK. Pour améliorer le traitement de ces tumeurs, les nouvelles thérapies cherchent à induire la différenciation cellulaire, l'inhibition de MYCN et la réduction de la signalisation d'ALK. Les résultats obtenus indiquent que le VIP induit une neuritogenèse dans les cellules de NB à haut risque SK-N-DZ et Kelly, et réduit en plus l'expression de MYCN dans les cellules Kelly, comme précédemment observé pour les cellules IMR-32. En parallèle, le VIP diminue l'invasion des cellules Kelly et IMR-32 et réduit également l'activité d'AKT qui est impliquée dans la signalisation d'ALK, dans les cellules Kelly qui présentent la mutation ALK F1174L. Certains effets du VIP sont dépendants de la PKA. Des analogues du PACAP, un peptide apparenté au VIP, présentent une efficacité supérieure à celle du VIP dans les cellules Kelly. Les effets du VIP sur la neuritogenèse et l'expression de MYCN dans ces cellules sont médiés par le récepteur VPAC2 qui peut avoir une localisation nucléaire dans les lignées cellulaires et les cellules de patients atteints de NB. Une délocalisation de ce récepteur nucléaire par ses propres ligands est observée. De plus, des cellules souches mésenchymateuses humaines dérivées du tissu adipeux induisent la différenciation des cellules de NB via les peptides VIP et/ou PACAP. L'ensemble de ces résultats indiquent que le VIP et des analogues du PACAP agissent sur des processus moléculaires et cellulaires qui pourraient réduire l'agressivité des NB à haut risque, et pourraient donc présenter un intérêt pour une nouvelle thérapie. / Neuroblastoma (NB) is a pediatric cancer derived from neural crest. High-risk NB are poorly differentiated tumors with MYCN amplification and the most aggressive forms in addition have an ALK mutation. To improve the treatment of these tumors, the new therapies aim to induce cell differentiation, inhibition of MYCN and reduction of ALK signaling. The obtained results indicate that the neuropeptide VIP induces neuritogenesis in high-risk SK-N-DZ and Kelly NB cells, and in addition reduces the expression of MYCN in Kelly cells, as previously observed in IMR-32 cells. In parallel, VIP decreases Kelly and IMR-32 cell invasion and also reduces the activity of AKT that is involved in the signaling of ALK, in Kelly cells harboring the mutation ALK F1174L. Most of these VIP effects are PKA-dependent. Analogs of PACAP, a VIP-related peptide, exhibit a higher efficiency than VIP in Kelly cells. VIP effects on neuritogenesis and MYCN expression in these cells are mediated by the VPAC2 receptor which can have a nuclear localization in the NB cell lines and in NB from patients. A relocation of this nuclear receptor by its own ligand is observed. Moreover, human mesenchymal stem cells derived from adipose tissue induce NB cells differentiation via VIP and/or PACAP peptides. Taken together, these results indicate that VIP and PACAP analogs act on molecular and cellular processes that might reduce aggressiveness of high-risk NB, and thus could be of interest for new therapy.

O núcleo hipotalâmico supraquiasmático (SCh), apresenta caracterização neuroquímica com duas subpopulações principais de células, a produtora de polipeptídeo intestinal vasoativo (VIP) e argenina vasopressina (AVP). As fibras IR AVP e VIP oriundas do SCh apresentam características morfológicas específicas que possibilitam o rastreamento a longas distâncias dentro do hipotálamo. No presente estudo buscamos mapear os terminais IR VIP e AVP nas áreas hipotalâmicas do primata Cebus apella utilizando a imuno-histoquímica, e fazer a identificação das áreas hipotalâmicas recipientes do SCh, utilizando o mapeamento da distribuição das fibras IR associado à análise morfológica destas duas substâncias neuroativas. As fibras IR VIP e AVP com características do SCh foram identificadas em porções anteriores como hipotálamo anterior, área pré-óptica, área hipotalâmica lateral, SPZV, até porções mais caudais, porção retroquiasmática, área tuberal. Os resultados indicam um padrão similar de distribuição de fibras IR VIP e AVP nas áreas do hipotálamo e também em áreas descritas como recipientes das projeções do SCh, quando comparado com outras espécies como roedores descritos na literatura. / The suprachiasmatic nucleus (SCN) of the hypothalamus, contains a variety of different neurons that tend to form two major subpopulations within the nucleus, the vasoactive intestinal peptide (VIP) and vasopressin (VP). The immunoreactive (IR) fibers derived from the VIP and VP IR cells of the SCN present morphological characteristics that allow their specific tracking in long distances within the hypothalamus. In the present investigation we aimed map VIP and VP IR terminals in hypothalamic areas of the primate Cebus apella using immunohistochemistry, and to do identification of hypothalamic recipient areas from SCN using the mapping distribution of fibers IR associated with morphological analysis of these two neuroactive substances. VIP and VP IR fibers with characteristics from SCN were identified in the rostral anterior hypothalamic area and medial preoptic area, laterally to the lateral hypothalamic area, and more caudally in SPZV and retrochiasmatic tuberal area. The results indicate that there is a similarity in the pattern of distribution of VIP and VP fibers in the hypothalamic areas and also in areas recipients from SCN projections when compared with nocturnal rodent species described in the literature.

Ces travaux de recherche visaient à développer un système d'aide à la mobilité pour les personnes ayant une déficience visuelle (VIP ‘Visually Impaired Person’) appelé ‘Smart Environment Explorer Stick (SEES)’. Le but particulier de cette recherche était de développer de nouveaux algorithmes pour améliorer la précision de la détection de la présence de poteaux de la canne SEE-stick en utilisant la méthode de calcul de distance et la recherche de paires de lignes verticales basées sur l'optimisation de la technique de détection de contour de Canny. Désormais, l'algorithme de détection des poteaux est appelé l’algorithme YuRHoS. Le SEES développé comme système de support d'aide à la mobilité VIP a été intégré avec succès à plusieurs dispositifs tels que le serveur distant dénommé iSEE, le serveur local embarqué dénommé SEE-phone et la canne intelligente dénommée SEE-stick. Les performances de SEE-stick ont été améliorées grâce à l'algorithme YuRHoS qui permet de discriminer avec précision les objets (obstacles) en forme de poteau parmi les objets détectés. La comparaison des résultats de détection des poteaux avec ceux des autres algorithmes a conclu que l'algorithme YuRHoS était plus efficace et précis. Le lieu et la couleur des poteaux de test d’évaluation étaient deux des facteurs les plus importants qui influaient sur la capacité du SEE-stick à détecter leur présence. Le niveau de précision de SEE-stick est optimal lorsque le test d’évaluation est effectué à l'extérieur et que les poteaux sont de couleur argentée. Les statistiques montrent que la performance de l'algorithme YuRHoS à l'intérieur était 0,085 fois moins bonne qu'à l'extérieur. De plus, la détection de la présence de poteaux de couleur argentée est 11 fois meilleure que celle de poteaux de couleur noir. / This research aimed to develop a technology system of mobility aid for Visually Impaired Person (VIP) called Smart Environment Explorer Stick (SEES).Particular purpose of this research was developing new algorithm in improving accuracy of SEE-stick for pole detection using distance calculation method and vertical line pair search based on Canny edge detection optimization and Hough transform. Henceforth, the pole detection algorithm was named as YuRHoS algorithm.The developed SEES as supporting system of VIP mobility aid had been successfully integrated several devices such as global remote server (iSEE), embedded local server (SEE-phone) and smart stick (SEE-stick). Performance of SEE-stick could be improved through YuRHoS algorithm, which was able to fix the accuracy of SEE-stick in detecting pole. Test comparison of pole detection results among others algorithm concluded that YuRHoS algorithm had better accuracy in pole detection.Two most significant factors affecting SEE-stick ability in detecting pole was test location and pole color. Level of accuracy of SEE-stick would be optimum once the test location was performed outdoor and pole color was silver. Statistics result shown that YuRHoS algorithm performance indoor was 0.085 times worse than outdoor. Meanwhile, silver-pole-color as object detection could increase YuRHoS algorithm performance as much as 11 times better compare to black-pole-color.

Senast år 2045 ska utsläpp av växthusgaser reduceras till en nollnivå enligt Sveriges riksdag. I Sverige står bostads- och servicesektorn för 40 % av den sammanlagda energiförbrukningen. Studien baseras på en energianalys av ett flerbostadshus beläget i Ronneby, av typen trygghetsboende vilket leder till en unik boendesituation i byggnaden. Byggnaden förbrukar cirka 25 % mer energi än den beräknade samt avtalade energiförbrukningen. Syftet är att i framtida projekt kunna få energiberäkningar att stämma bättre överens med verklig specifik energiförbrukning. Studien bygger på energisimuleringar, termografering samt undersökningar av vädringsvanor. Simuleringarna som är baserade på den verkliga datan, visar en förväntad energiförbrukning i liknande storleksordning som den uppmätta förbrukningen. Skillnaden mellan resultaten i studiens olika beräkningar beror på den unika boendesituationen i byggnaden, indatan för installationer samt byggnadens klimatskal. Studien påvisar att aktuella boendesituationer i byggnader och hur byggnader nyttjas påverkar den specifika energiförbrukningen i stor grad. / After 2045, greenhouse gases should be reduced to a zero level according to the Swedish parliament. Energy use in Sweden from residential and service sector is 40 % of the country´s total energy use. The study is based on an energy analysis of a multi-family building in Ronneby. The building is a trygghetsboende, which means unique living conditions for the residens. Actual energy use in the building is about 25 % higher than projected energy use. The main purpose of the study is to make energy calculations to match better with real specific energy use. The study is based on energy simulations, thermography and interviews of residents´ airing habits. Results from the simulations based on actual data, show an expected energy use similar to the measured values. Differences between the simulations depend on the unique conditions in the building, input data for ventilation and the building envelope elements. The conclusion is that living habits of residents in buildings have a decisive role in the buildings energy use.