京都大学 / 0048 / 新制・課程博士 / 博士(薬科学) / 甲第18919号 / 薬科博第33号 / 新制||薬||4(附属図書館) / 31870 / 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 金子 周司, 教授 竹島 浩 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(生命科学) / 甲第19907号 / 生博第354号 / 新制||生||47(附属図書館) / 32984 / 京都大学大学院生命科学研究科統合生命科学専攻 / (主査)教授 藤田 尚志, 教授 米原 伸, 教授 朝長 啓造 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21668号 / 医博第4474号 / 新制||医||1035(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 松田 道行, 教授 萩原 正敏, 教授 安達 泰治 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

På senare tid har mikroplaster i hav och sjöar uppmärksammats som ett potentiellt stortmiljöproblem. Idag finns mikroplaster spridda över hela världens vatten från polerna till ekvatorn.År 2016 uppmärksammades konstgräsplaner som den nästa största källan till spridning avmikroplaster till sjöar och vattendrag i Sverige [1]. Fotboll är Sveriges nationalsport och är densporten som står för flest aktivitetstimmar i Sverige. Konstgräs har gjort det möjligt för fler barnoch ungdomar att få fler speltimmar och idag spelar 90 % av alla fotbollsspelare på konstgräs [2].De olika spridningsvägarna för mikroplaster från konstgräsplaner undersöktes med fokus påspridningsvägen via dagvatten. Det finns fler olika reningsmetoder för dagvatten innehållandemikroplaster, en av dessa är granulatfällan, en filterpåse som placeras i en dagvattenbrunn för attfånga upp granulat och konstgräsfibrer som sprids från konstgräsplanen till dagvattenbrunnen.Syftet med denna studie var att optimera reningsmetoden granulatfälla utifrån möjligavattenflöden och dess effektivitet i att fånga upp mikroplaster. Detta undersöktes genomframtagandet av en vattenflödesmodell vid konstgräsplaner med variationer i konstruktion ochgenom fältstudier av granulatfällans effektivitet vid två konstgräsplaner i Storstockholm.Det regn som undersöktes i vattenflödesmodellen var extremregn för ett 10 års regn under 10minuter. Detta för att hitta det maximala flöde granulatfällorna kommer behöva klara av. Vilkavattenflöden som nådde dagvattenbrunnarna var beroende på antalet dagvattenbrunnarplacerade runt konstgräsplanen, i vilket område i Sverige som konstgräsplanen var placerad, detvill säga hur mycket regn som kom, och konstgräsplanens infiltrationsförmåga.Vattenflödesmodellen fungerar som en mall för möjliga vattenflöden vid en specifik plats i Sverigeoch en viss konstruktion av konstgräsplan.De konstgräsplaner som var med i fältstudierna var Skytteholms IP i Solna och Spånga IP iStockholm. Vid varje konstgräsplan placerades 6 granulatfällor med två filterpåsar på varje fälla,den inre med större maskor och den yttre med mindre maskor. Kombinationerna var 200 μm med100 μm, 200 μm med 50 μm och 100 μm med 50 μm. Totalt fångades 10,3 kg mikroplast vidSkytteholms IP och 1,5 kg vid Spånga IP under de 49 dygn granulatfällorna var utplacerade. Avden totala mängden mikroplast viktmässigt i varje granulatfälla fanns minst 99 % i den inrefilterpåsen och maximalt 1 % i den yttre filterpåsen, det vill säga i storleksfraktionen mellan denyttre och den inre filterpåsen.Slutsatserna från denna studie är att vattenflödet till dagvattenbrunnarna placerade runtkonstgräsplaner kan variera mycket på grund av hur konstgräsplanen är konstruerad. Det berorframförallt på konstgräsplanens infiltrationsförmåga och antal dagvattenbrunnar runtkonstgräsplanen. Utifrån de teoretiska vattenflödena och fältstudierna rekommenderas att enfilterpåse med maskstorlek 200 μm används i granulatfällan. Detta utifrån att den inre filterpåsenfångade minst 99 % av de mikroplaster som nådde granulatfällorna, som var större än 50 μm, ochökad risk för igensättning och tillväxt av biofilm på filterpåsarna med mindre maskor. Vidarestudier bör genomföras på granulatfällans vattenflöde över tid, mikroplaster mindre än 50 μm,IIandra spridningsvägar för mikroplaster från konstgräsplaner, förbättrade konstruktioner avkonstgräsplaner och förbättrat underhållningsarbete för att minska spridningen av mikroplasterfrån konstgräsplaner. / In the recent years microplastics in the marine environment has been recognized as a potentiallyimportant environmental issue. Today there are microplastics spread in the waterbodies all overthe world, from the equator to the poles in south and north. In 2016 artificial turf was labeled thesecond largest source of microplastics to the marine environment in Sweden [1]. Football is thenational sport of Sweden and accounts for the majority of the activity hours among the youth inSweden. The artificial turf has made it possible for more children to play football and for them toget more hours on the field. Today about 90 % of the football players play on artificial turf [2].The microplastics pathways to the nature and the marine environment were studied andtreatment methods were developed. One of these methods is the so called granule trap, a filterbag which is placed in a stormwater drainage well to catch the rubber granulates and the artificialturf fibers which can be spread from the artificial field to the drainage system. The aim of thisstudy was to optimize the granule trap for possible waterflows to the stormwater drainage welland its efficiency to catch microplastics. This was researched through field studies of the efficiencyof the granule trap at two artificial turfs in Stockholm and the development of a waterflow modelof an artificial turf with varying construction.The rainfall which was used in the waterflow model was the 10-year storm with a duration of 10minutes. This to find the maximum waterflow the granuletraps must manage. The waterflows tothe stormwater drainage well were dependent on the number of wells placed around the artificialturf, in which area of Sweden the football field was placed, in other words the amount of rain thatfell, and the infiltration capacity of the artificial turf. The waterflow model works as a templatefor possible waterflows at an artificial turf with a certain construction and at a certain location inSweden.The artificial turfs which were examined in the field studies were Skytteholms IP in Solna andSpånga IP in Stockholm. At each football field 6 granuletraps were placed, each loaded with twofilter bags, the inner with larger sized mesh and the outer with smaller sized mesh. The mesh sizecombinations were 200 μm with 100 μm, 200 μm with 50 μm and 100 μm with 50 μm. atSkytteholms IP a total amount of 10.3 kg microplastics were caught and at Spånga IP a total of 1.5kg microplastics were caught during the 49 days the granuletraps were placed at the footballfields. Out of the total amount of microplastics in each granuletrap at least 99 % by mass was inthe inner filter bag and maximum 1 % by mass was in the outer filter bag, in the size fractionbetween the outer and the inner filter bag..In conclusion this study shows that the waterflow to the stormwater drainage wells placed aroundthe artificial turfs vary a lot depending on the construction of the artificial turf. Foremost itdepends on the infiltration capacity of the artificial turf and the number of stormwater drainagewells around the field. With regards to the waterflows from the waterflow model and the resultsfrom the field studies the recommended mesh size for the filter bags is 200 μm. This since at least99 % by mass of the microplastics, which were larger than 50 μm, that reached the granule trapsIVwere trapped in the inner filter bag and the elevated risk of clogging and biofilm growth on thefilter bags with smaller mesh size. Further studies should be conducted on the waterflow throughthe granuletraps over time, microplastics smaller than 50 μm, other pathways for themicroplastics away from the artificial turf, improved constructions of artificial turfs and improvedmaintenance on the artificial turfs to reduce the risk of spreading of microplastics from artificialturfs.

No description available.

Continuous wet granulation using a twin-screw extruder has attracted considerable attentions in pharmaceutical industry as it ensures consistent tablet quality at a high production rate. However, challenge still exists in controlling desired granule properties especially when different sized twin-screw granulators are used. This study therefore explored the potential of scalability of two sized twin-screw extruders and the how raw materials affect granules properties in two twin-screw extruders. The first study focuses on aspects of scaling using two twin-screw extruders, 18mm and 27mm. Dimensionless groups including Fr Number, Powder Feed Number and Degree of Fill (<30%) were studied to observe their influences on granule attributes. It was found that these dimensionless groups demonstrated inconsistent effects on granule properties and the effect of Powder Feed Number was highly dependent on Degree of Fill. Different extruder still exerts significant impact on granule properties. A scaling rule was established for median granule size (d50) only, but only moderate degree of fit was found. Although a considerable number of studies have been published on controlled-release and extended-release excipients, little attentions have been given to the influence of microcrystalline cellulose (MCC) grades in twin-screw wet granulation. The second study therefore investigated the processability of five grades MCC from the Avicel® PH family using two twin-screw extruders again, 18mm and 27mm. Granule attributes including particle size, density, moisture, and strength were tested and it was found that MCC inherent density has the most significant impact on granule properties while particle size of MCC has minor positive effect on granule size. This study also concluded that better granule flowability and uniformity can be achieved by using low moisture, larger particle size and high density MCC as excipients. / Thesis / Master of Applied Science (MASc)

The 43 kDa TAR DNA binding protein (TDP-43) has been identified as one of the major proteins that accumulates in the cytoplasm of brain and spinal cord from the patients affected with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Under basal conditions, TDP-43 localizes in nucleus functioning as an RNA binding protein to regulate different aspects of RNA metabolism, such as alternative splicing of messenger RNA. In ALS/FTLD brains and spinal cords, TDP-43 forms well-defined cytoplasmic granules, the behavior very similar to stress granule (SG) proteins, but the mechanisms are poorly understood. To investigate the mechanism of TDP-43 granule formation and to identify potential therapeutic targets by inhibiting the granule formation, our laboratory screened a chemical library of 75,000 compounds using the inducible PC12 cells that express EGFP-tagged wild-type human TDP-43. We used the biological effect of cycloheximide on SGs as a basis for the screen, since it is known to prevent the formation of SGs and TDP-43 granules, pointing to a novel biological pathway that regulates TDP-43 granule formation. One of the candidate compounds, Compound 8 (C8) and its analog C8j dose- dependently decreased the arsenite-induced TDP-43 granules without cytotoxicity, and reduced the protein levels of full-length, truncated, high molecular weight and phosphorylated TDP-43. In addition, we found C8j reduced the phosphorylation at novel, previously unknown Thr103-Ser104 amino acid residues of human TDP-43 under arsenite stress. The phospho-mimetic mutations at these sites induced spontaneous intracellular TDP-43 granules, indicating their regulatory role in TDP-43 granule formation. We also performed a series of gene expression analysis combined with the systems biology algorithm, mode of action by network identification (MNI), to identify the mode of action of C8, and found C8 potentially targets protein metabolism and modification processes to reduce the TDP-43 granules. Our study identified a family of non-cytotoxic chemical compounds that reduces the formation of arsenite-induced TDP-43 granules and their potential mode of action. Furthermore, we identified previously unknown TDP-43 phosphorylation sites Thr103- Ser104 that are involved in the TDP-43 granule formation. We anticipate this study will elucidate the biological pathways regulating TDP-43 aggregation and potential therapeutics for ALS/FTLD-U.

Results of a study on the influence of process parameters such as impeller speed, granulation time and binder viscosity on granule strength and properties are reported. A high shear granulator (Cyclomix manufactured by Hosokawa Micron B.V., The Netherlands) has been used to produce granules. Calcium carbonate (Durcal) was used as feed powder and aqueous polyethylene glycol (PEG) as the binder. The dried granules have been analysed for their strength, density and size distribution. The results show that increasing the granulation time has a great affect on granules strength, until an optimum time has been reached. The underlying cause is an increase in granule density. Granules are consolidated more at higher impeller speeds. Moreover, the granule size distribution seems not to be affected significantly by an increase in impeller speed. Granules produced with high binder viscosity have a considerably lower strength, wide strength distribution due to poor dispersion of binder on the powder bed. Binder addition methods have showed no considerable effect on granule strength or on granule size distribution.

Yes / The effect of screw configuration on granule size distribution (GSD) using gPROMS FormulatedProduct (gFP) software to perform optimization, estimation of complex processes, and analyses is evaluated. Twin-screw granulation modeling was used to investigate the contribution of screw configuration and liquid-to-solid (L/S) ratio on GSD. Lactose and Avicel were the granulating materials. Twelve different configurations were investigated under three feed rates as consistent with literature and at various L/S ratios. Results indicate that kneading elements promote the recovery of 100–1000 µm granules while reducing the production of oversized granules. Higher feed rates support the production of fines and agglomerates, while a low feed rate produces 100–1000 µm granules. / Ghana Scholarship Secretariat