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1
Gabbott, Ian. "Designer granules : beating the trade-off between granule strength and dissolution time." Thesis, University of Sheffield, 2007. http://etheses.whiterose.ac.uk/3605/.
Повний текст джерелаАнотація:
The work described in this part of the thesis is involved mainly with uprating a 55W air-turbine driven permanent magnet generator to 250W. It is shown that the electrical performance of the generator can be predicted from a simple equivalent circuit comprising an, induced emf source with a series inductance and resistance. When matching the generator and turbine characteristics iron losses are included as an additional torque requirement. Analysis has identified that the most important parameters which determine the rating-of the generator are the stator flux, linkage, stator inductance, and number of pole pairs. Investigations have therefore centred around the calculation of these quantities. Previous design methods for calculating the parameters have been dependent on experimental data for particular magnet geometries. They are not sufficiently general to permit design calculations for magnets having radically different shapes or properties. Therefore the finite element method is used to predict the magnetic field distribution, from which the stator winding flux linkages and inductance, and the saliency torque, are predicted, an important parameter when matching the turbine and generator at starting. The finite element method offers significant advantages over analytical methods because it can account accurately for leakage flux, it can handle complex configurations of magnetic circuit and the directional properties of the magnet, and it allows different parts of the magnet to operate at different flux density levels. The performance of the generator is predicted with reasonable accuracy. Alternative rotors for the 250W generator have been designed and tested. Results have shown that the existing generator can be adapted to the 250W design simply by using a rare-earth magnet rotor, and selecting a suitable stator winding turns factor for matching the generator and bulb. Two methods of matching the load characteristics of the turbine, generator and bulb, to produce an acceptable system have been developed. A simple electronic protection circuit has been designed to prevent the 250W generator from overspeeding in the event of bulb failure. Additionally it can limit over-voltages, caused by variations in the pressure of the air supply, which would otherwise decrease the life of the bulb.
2
Kilpatrick, Lynn Agnes. "Biogenesis of chromaffin granules." Thesis, University of Edinburgh, 1985. http://hdl.handle.net/1842/18345.
Повний текст джерелаАнотація:
Bovine adrenal medullary messenger RNA was isolated and translated in optimised reticulocyte lysate and wheatgerm cell-free translation systems. Reticulocyte lysate was found to be the superior translation system. An attempt was made to characterize the primary polypeptide precursors to the major chromaffin granule secretory protein, chromogranin A, and to the two major chromaffin granule membrane proteins, dopamine β-hydroxylase and cytochrome b561 using previously prepared and well-characterized antisera raised against these proteins. Two similar polypeptides of 70,000 and pI of about 5.2 were immunoprecipitated from the translation products by the antiserum against chromogranin A. When reticulocyte lysate was supplemented with dog pancreas microsomes, one polypeptide of slightly lower which was translocated into the lumen of the microsomal vesicles as determined by alkaline washing, was immunoprecipitated by this antiserum. Precursors to chromogranin A were subsequently identified from the polypeptide products when reticulocyte lysate was supplemented with adrenal medullary bound polysomes or rough microsomes. The effects of post-translational processing on chromogranin A were observed during the cellular synthesis of chromogranin A, during which chromogranin A becomes more heterogeneous with respect to pi and it is concluded that the smaller members of the chromogranin A family result from the action of intragranular proteolysis on chromogranin A during the maturation and storage of the granules. Two polypeptides of 72,000 and 46,000, were immunoprecipitated from translation products by the antiserum raised against the soluble form of dopamine β-hydroxylase. The 46,000 dalton polypeptide is most likely a breakdown product of the 72,000 dalton polypeptide. When reticulocyte lysate was supplemented with dog pancreas microsomes, a polypeptide of 67,000 daltons was immunoprecipitated by the antiserum to dopamine β-hydroxylase. This polypeptide was translocated into the lumen of the microsomal vesicles as determined by phase separation of the microsomes with Triton X—114. Thus, the soluble form of dopamine β-hydroxylase would appear to be synthesized as a precursor of 72,000 daltons which, on removal of its signal sequence, is reduced to a 67,000 dalton polypeptide. Antisera were prepared against various chemically and enzvmatically modified forms of cytochrome b561 in an attempt to immunoprecipitate the polypeptide precursor to this protein from translation products. However, all attempts to identify the precursor to this protein were unsuccessful. An extensively-labelled small acidic translation product was tentatively identified as calmodulin.
3
Miller, Linda. "Characterization of ribonucleic acid granules." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:8881/R/?func=dbin-jump-full&object_id=92296.
Повний текст джерела
4
Boren, Mats. "Proteomics of barley starch granules /." Uppsala : Dept. of Plantbiology and Forest Genetics, Swedish University of Agricultural Sciences, 2005. http://epsilon.slu.se/2005107.pdf.
Повний текст джерела
5
Van, Eeden Alida Elizabeth. "Extracellular polymer extraction and analysis from UASB granules and batch produced anaerobic granular sludge." Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/52841.
Повний текст джерелаАнотація:
Thesis (MSc Food Sc)--Stellenbosch University, 2002.ENGLISH ABSTRACT: The start-up period of Upflow Anaerobic Sludge Bed (UASB) reactors can significantly be reduced by enhancing the time-consuming granulation process through the batch cultivation of anaerobic granular sludge and thus seeding the reactor with this cultivated granular sludge, instead of raw anaerobic sludge. The precise mechanism for granule formation is not well known, but it is believed that extracellular polymers (ECP) play a critical role in the granulation process. Information on the precise role of ECP is also limited and no universal standardised method for ECP extraction is used at present. Therefore, comparison of results from different researchers has to be made with great caution. The objectives of this study were to evaluate an ECP extraction methód so as to optimise the extraction time, and then to correlate ECP composition of UASB granules with granule metabolic activity. The impact of changes in the environmental conditions, such as sludge sources (Paarl and Kraaifontein-sludge), carbon growth substrates (yeast extract lactate, glucose medium and fruit cocktail effluent) and batch cultivation techniques (roller-table and shake-waterbath), on batch cultivation studies was also evaluated in terms of granule activity, ECP composition and granule formation. A physical extraction method was used to quantify the ECP content of UASB granules from six different sources. The optimal extraction time was taken as the time needed before cell lysis took place, and before intracellular material started contributing to the ECP content of the granules. It was concluded that the ECP composition was affected by the wastewater composition fed to the original UASB reactors, It was also found that the activity test results could be used to indirectly predict the activity of the different trophic groups present in the UASB granules. A correlation was found between the activity test results and the total ECP content, and this showed that the granules with the higher ECP yields exhibited greater biogas (SB) and methanogenic (SM) activities. However, based on the activity data and total ECP content, it appeared that a protein:carbohydrate ratio < 1 affected the activity of the granules, The sludge source used as inoculum for batch cultivation of anaerobic granular sludge had a significant effect on granule formation. The use of a pre- granulated raw anaerobic sludge, such as the Paarl-sludge, resulted in a greater increase in granule numbers at the end of the cultivation period. The acetic acid activity profiles showed that the acetoclastic methanogens that are involved in initiation of granulation by nucleus formation, were inactive or absent in the different batch systems, with the exception of the roller-table glucose cultivated Kraaifontein-sludge (RKG) batch system. The addition of glucose as carbon growth substrate for batch cultivation not only enhanced the activity of the acidogenic population, but also led to the establishment to a greater variety of granule trophic groups within all the glucose cultivated batch systems. The addition of fruit cocktail effluent as carbon substrate enhanced ECP production in the Paarl-sludge cultivated batch systems. However, the addition of carbon substrates showed no discernible trend on granule formation itself. The roller-table cultivation technique resulted in the higher increase in granule numbers, and it was speculated that the more vigorous shake-waterbath technique probably shortened the contact time between biomass and substrate. Large variations in the ECP composition of the different batch systems were found, and these were ascribed to the composition heterogeneity of different sludges. For future studies, it is advisable to characterise sludge, both chemically and microbiologically before using as inoculum. The selection of an appropriate sludge inoculum should then lead to optimisation of the granulation process.
AFRIKAANSE OPSOMMING: Die aanvangsperiode van "Upflow Anaerobic Sludge Bed" (UASB) bioreaktors kan noemenswaardig verminder word deur die tydsame granulasie proses te versnel deur die vooraf lot-kweking van anaërobe granulêre slyk waarmee 'n reaktor dus geïnokuleer kan word in plaas van rou anaërobe slyk. Die presiese meganisme van granulevorming is nog nie welbekend nie, maar daar word beweer dat ekstrasellulêre polimere (ECP) wel 'n kritiese rol speel in die granulasie proses. Inligting; oor die presiese rol van ECP is ook nog beperk, en tans word daar nog , geen universele standaard metode vir ECP-ekstraksie gebruik nie. Gevolglik moet resultate vanaf verskeie navorsers met groot omsigtigheid vergelyk word. Die doelwitte van hierdie studie was om 'n ECP ekstraksiemetode te evalueer deur die ekstraksietyd te optimiseer, en dan te korreleer met die ECP samestelling en metaboliese aktiwiteit van die UASB granules. Die inwerking van veranderinge in omgewingskondisies, soos slykbronne (Paarl- en Kraaifontein-slyk), koolstofbronne (gisekstrak-Iaktaat-, glukose-medium en vrugtekelkie-uitvloeisel) en lot-kwekingstegnieke (rol-tafel en skud-waterbad) op lot-kweking studies in terme van granule aktiwiteit, ECP-samestelling en granulevorming is ook ondersoek. 'n Fisiese ekstraksie metode is gebruik om die ECP-inhoud van UASB granules vanaf ses verskillende bronne te bepaal. Die optimale ekstraksietyd is geneem as die tyd benodig voordat sellise sal plaasvind en die intrasellulêre materiaal 'n bydrae sal lewer tot die ECP-inhoud van granules. Dit is afgelei dat die ECP-samestelling beïnvloed word deur die samestelling van die afvalwater wat vir die oorspronklike UASB bioreaktors gevoer is. Voorts is gevind dat die aktiwiteitstoets resultate indirek gebruik kan word vir die voorspelling van aktiwiteit van die verskillende trofiese groepe wat in die UASB granules teenwoordig is. 'n Korrelasie is gevind tussen die aktiwiteitstoets resultate en die totale ECP-inhoud wat aangedui het dat granules met hoër ECP opbrengste, beter biogas (SB) en metanogeniese (SM) aktiwiteit getoon het. Volgens die aktiwiteitsdata en totale ECP-inhoud het dit egter geblyk dat 'n proteïen:koolhidraat verhouding < 1 die aktiwiteit van granules beïnvloed het. Die slykbron wat as inokulum gebruik is vir lot-kweking van' anaërobiese granulêre slyk het 'n noemenswaardige invloed gehad op granulevorming. Die gebruik van 'n rou anaërobe slyk wat reeds 'n mate van granulasie getoon het, soos die Paarl-slyk, het 'n hoër toename in granule getalle aan die einde van die kwekingsperiode teweeg gebring. Die asynsuur aktiwiteitsprofiele het aangedui dat die asetoklastiese metanogene, wat hoofsaaklik betrokke is by inisiëring van granulasie deur kernvorming, onaktief of afwesig was in al die verskillende lotsisteme, met die uitsondering van die roltafel glukose-gekultiveerde Kraaifonteinslyk (RKG) lot-sisteem. Die toevoeging van glukose as koolstofbron vir lot-kweking het nie alleenlik die aktiwiteit van die asidogene populasie verhoog nie, maar het ook bygedra tot die vestiging van 'n groter verskeidenheid van granule trofiese groepe. Die toevoeging van vrugtekelkie-uitvloeisel as koolstofbron het die produksie van ECP verhoog in die Paarl-slyk gekweekte lot-sisteme. Die toevoeging van koolstofsubstrate het egter geen merkbare verandering getoon in granulasie opsigself nie. Die rol-tafel kwekingstegniek het 'n hoër toename in granule getalle tot gevolg gehad, en dit is gespekuleer dat die meer kragtige skud-waterbad tegniek waarskynlik die kontaktyd tussen die substraat en biomassa verkort het. Groot variasies is gevind in die ECP-samestelling van die verskillende lotsisteme, en dit is toegeskryf aan die heterogene samestelling van die verskillende slyke. Vir toekomstige navorsing is dit raadsaam om slyk voor gebruik as inokulum beide chemies en mikrobiologies te karakteriseer. Die keuse van 'n geskikte slyk-inokulum sal bydra tot die optimisering van die granulasie proses.
6
Cid, Samper Fernando 1991. "Computational approaches to characterize RNP granules." Doctoral thesis, Universitat Pompeu Fabra, 2020. http://hdl.handle.net/10803/668449.
Повний текст джерелаАнотація:
Ribonucleoprotein granules (RNP granules) are liquid-liquid phase separated
complexes composed mainly by proteins and RNA. They are responsible of many
processes involved in RNA regulation. Alterations in the dynamics of these proteinRNA complexes are associated with the appearance of several neurodegenerative
disorders such as Amyotrophic Lateral Sclerosis ALS or Fragile X Tremor Ataxia
Syndrome FXTAS. Yet, many aspects of their organization as well as the specific
roles of the RNA on the formation and function of these complexes are still unknown.
In order to study RNP granules structure and formation, we integrated several state of
the art high-throughput datasets. This includes protein and RNA composition obtained
from RNP pull-downs, protein-RNA interaction data from eCLIP experiments and
transcriptome-wide secondary structure information (produced by PARS). We used
network analysis and clustering algorithms to understand the fundamental properties
of granule RNAs. By integrating these properties, we produced a model to identify
scaffolding RNA. Scaffolding RNAs are able to recruit many protein components into
RNP granules. We found that the main protein components of stress granules (a kind
of RNP granules) are connected through protein-RNA interactions. We also analyzed
the contribution of RNA-RNA interactions and RNA post-transcriptional
modifications on the granule internal organization.
We applied these findings to understand the biochemical pathophysiology of FXTAS
disease, employing as well some novel experimental data. In FXTAS, a mutation on
the FMR1 gene produces a 5´microsatellite repetition that enhances its scaffolding
ability. This mutated mRNA is able to sequester some important proteins into nuclear
RNP granules, such as TRA2A (i.e. a splicing factor), impeding their normal function
and therefore producing some symptoms associated with the progress of the disease.
The better understanding of the principles governing granules formation and structure
will enable to develop novel therapies (e.g. aptamers) to mitigate the development of
several neurodegenerative diseases.Los gránulos ribonucleoproteicos (gránulos RNP, por sus siglas en inglés) son complejos producidos mediante separación líquido-líquido y están constituidos principalmente por proteínas y ARN. Son responsables de numerosos procesos involucrados con la regulación del ARN. Alteraciones en la dinámica de estos complejos de proteínas y ARN están asociadas con la aparición de diversas enfermedades neurodegenerativas como el ELA o FXTAS. Sin embargo, todavía se desconocen muchos aspectos relativos a su organización interna así como las contribuciones específicas del RNA en la formación y funcionamiento de estos complejos. A fin de estudiar la estructura y formación de los gránulos RNP, hemos integrado varias bases de datos de alto rendimiento de reciente aparición. Esto incluye datos sobre la composición proteica y en ARN de los RNP, sobre la interacción de proteínas y ARN extraída de experimentos de eCLIP y sobre la estructura secundaria del transcriptoma (producida mediante PARS). Todos estos datos han sido procesados para comprender las propiedades fundamentales de los ARNs que integran los gránulos, mediante el empleo de métodos computacionales como el análisis de redes o algoritmos de agrupamiento. De esta manera, hemos producido un modelo que integra varias de estas propiedades e identifica candidatos denominados ARNs de andamiaje. Definimos ARNs de andamiaje como moléculas de ARN con una alta propensión a formar gránulos y reclutar un gran número de componentes proteicos a los gránulos RNP. También hemos encontrado que las interacciones proteína-ARN conectan los principales componentes proteicos de consenso de los gránulos de estrés (un tipo específico de gránulos RNP). También hemos estudiado la contribución de las interacciones ARN-ARN y las modificaciones post-transcriptionales del RNA en la organización interna del gránulo. Hemos aplicado estos resultados para la comprensión de la fisiopatología molecular de FXTAS, empleando también algunos datos experimentales originales. En FXTAS, una mutación en el gen FMR1 produce una repetición de microsatélite en 5´ que incrementa su capacidad como ARN de andamiaje. Este mARN mutado es capaz de secuestrar algunas proteínas importantes como TRA2A (un factor de ayuste alternativo) en gránulos RNP nucleares, impidiendo su normal funcionamiento y por consiguiente produciendo algunos síntomas asociados con el progreso de la enfermedad. Una mejor comprensión de los principios que gobiernan la formación y estructura de los gránulos puede permitir desarrollar nuevas terapias (ej: aptámeros) para mitigar el desarrollo de diversas enfermedades neurodegenerativas.
7
Abou, Chakra Oussama. "Allergénicité des Granules Cytoplasmiques de Pollen." Phd thesis, Université Paris-Diderot - Paris VII, 2009. http://pastel.archives-ouvertes.fr/pastel-00567120.
Повний текст джерелаАнотація:
Le pollen des Graminées est l'un des principaux vecteurs d'allergènes. Il contribue à l'apparition des allergies respiratoires comme l'asthme et la rhinite allergique. En contact avec l'eau de pluie ou des polluants atmosphériques, le pollen peut libérer des microparticules (<5 !m) dites granules cytoplasmiques de pollen. À cause de leur taille, ces granules peuvent pénétrer plus profondément dans l'appareil respiratoire que le pollen entier et induire ainsi des réactions allergiques. L'objectif de ce travail est de caractériser l'allergénicité de ces granules selon 3 volets : épidémiologique, expérimental et analytique. Les résultats de l'étude épidémiologique mettent évidence un effet éventuel des granules dans la survenue des allergies respiratoires, et plus particulièrement de l'asthme. Dans la partie expérimentale, les résultats obtenus permettent de montrer que les granules induisent des réactions allergiques, humorales et cellulaires ainsi que des réponses inflammatoires, comparables au pollen entier, chez le rat Brown Norway, le modèle animal d'allergie ici utilisé. Enfin, la partie analytique permet de conclure que l'allergénicité des granules dépend à la fois de leur contenu en allergènes hydrosolubles et non-hydrosolubles.
8
Mokas, Sophie. "Mécanismes d'assemblage des granules de stress." Thesis, Université Laval, 2012. http://www.theses.ulaval.ca/2012/28583/28583.pdf.
Повний текст джерелаАнотація:
Les granules de stress (GS) sont des sites de régulation de la traduction qui permettent aux cellules cancéreuses de survivre au stress. Elles apparaissent sous différentes conditions de stress et disparaissent une fois remises de celles-ci. Elles se forment selon deux voies, l’une dépendante de la phosphorylation du facteur eIF2α et l’autre indépendante. Les mécanismes d’assemblage des GS par cette dernière voie restent méconnus. Afin de définir ces mécanismes, l’objectif principal de ma maîtrise était de caractériser les étapes critiques de la formation de GS. En utilisant des approches pharmacologiques et d’interférence à l’ARN, nous démontrons que l’inactivation de plusieurs facteurs d’initiation de la traduction provoque la formation de GS indépendamment de la phosphorylation d’eIF2α. Par contre, l’inactivation du facteur eIF4E, ainsi que ceux permettant l’association du 60S à l’ARNm, n’induit pas de GS. De nouvelles stratégies anti-cancer inhibant la traduction et bloquant la formation de GS serait alors possible.
9
Marmuse, Laurence. "Maltooligosaccharides as models for starch granules." Thesis, University of East Anglia, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.410123.
Повний текст джерела
10
Cheong, Yuen Sin. "Mechanical characteristics of model binderless granules." Thesis, University of Sheffield, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434489.
Повний текст джерела
11
Horowitz, Daniel Mark. "Biomimetic, amorphous granules of poly(hydroxyalkanoates)." Thesis, University of Cambridge, 1994. https://www.repository.cam.ac.uk/handle/1810/272774.
Повний текст джерела
12
Abou, Chakra Oussama. "Allergénicité dez Granules Cytoplasmiques de Pollen." Paris 7, 2009. https://pastel.archives-ouvertes.fr/pastel-00567120.
Повний текст джерелаАнотація:
Le pollen des Graminées est l'un des principaux vecteurs d'allergènes. Il contribue à l'apparition des allergies respiratoires comme l'asthme et la rhinite allergique. En contact avec l'eau de pluie ou des polluants atmosphériques, le pollen peut libérer des microparticules (<5 μm) dites granules cytoplasmiques de pollen. À cause de leur taille, ces granules peuvent pénétrer plus profondément dans l'appareil respiratoire que le pollen entier et induire ainsi des réactions allergiques. L'objectif de ce travail est de caractériser l'allergénicité de ces granules selon 3 volets : épidémiologique, expérimental et analytique. Les résultats de l'étude épidémiologique mettent évidence un effet éventuel des granules dans la survenue des allergies respiratoires, et plus particulièrement de l'asthme. Dans la partie expérimentale, les résultats obtenus permettent de montrer que les granules induisent des réactions allergiques, humorales et cellulaires ainsi que des réponses inflammatoires, comparables au pollen entier, chez le rat Brown Norway, le modèle animal d'allergie ici utilisé. Enfin, la partie analytique permet de conclure que l'allergénicité des granules dépend à 1 fois de leur contenu en allergènes hydrosolubles et non-hydrosolublesGrass pollen is one of the most important aeroallergen vectors in Europe. It highly contributes to respiratory allergic diseases such as asthma or allergic rhinitis. In contact to water or airborne pollutants, pollen grains can release microparticles or pollen cytoplasmic granules. Because of their size (<5 μm), granules may penetrate deeper into the lungs than pollen grains and so, can induce stronger allergie responses. The aim of this study was to characterized allergic potential of pollen cytoplasmic granules along 3 axes: epidemiological, experimental and analytical. Results of the epidemiological study involve a possible effect of granules in the onset of allergic reparatory diseases, in particular asthma. In experimental part, the results show that granules induced allergic - both humoral and cellular - and inflammatory responses. These results are compared with whole pollen, on a good animal model of allergy, the Brown Norway rat. Finally, according to the results of the analytical study, both water-soluble and water-insoluble allergens of granules contribute to the allergenicity of these microparticules
13
Myllärinen, Päivi. "Starches : from granules to novel applications /." Espoo [Finland] : Technical Research Centre of Finland, 2002. http://www.vtt.fi/inf/pdf/publications/2002/P473.pdf.
Повний текст джерела
14
Petoukhov, Eugenia. "Activity-mediated secretion of progranulin-containing granules." Thesis, University of British Columbia, 2012. http://hdl.handle.net/2429/43133.
Повний текст джерелаАнотація:
Progranulin (PGRN) is a multi-functional, secreted growth factor expressed in a variety of tissues throughout the body. In the central nervous system (CNS), PGRN is expressed in microglia as well as in a number of neuronal populations and has been shown to promote neuronal survival, enhance neurite outgrowth and regulate inflammation and development. Mutations in the progranulin (GRN) gene have been identified as a major cause of autosomal dominant frontotemporal dementia (FTD) with tau-negative inclusions. The majority of GRN mutations result in the production of a null allele and reduced PGRN expression. However, the normal functions of PGRN in the CNS remain poorly understood. Our study examines the secretion characteristics of PGRN in neurons. To study the secretion of PGRN from axons and dendrites, we have fused a pH-sensitive optical reporter of exocytosis, superecliptic pHluorin, to PGRN (PGRN-SEP). We demonstrate that activity enhances the secretion of PGRN from axons and dendrites with different temporal profiles of secretion. We show, using calcium blockers and calcium-free media, that activity-mediated secretion of PGRN requires Ca²⁺ entry via voltage-gated calcium channels (VGCC). We postulate that activity-dependent secretion of PGRN may enhance the formation and maturation of synapses as treatment of hippocampal neurons with recombinant PGRN results in an increase in synapse density.
15
Lynn, Andrew. "The effect of processing on starch granules." Thesis, Heriot-Watt University, 1992. http://hdl.handle.net/10399/1503.
Повний текст джерела
16
Brind, Alison Mary. "Alpha-1-antitrypsin granules in the liver." Thesis, University of Newcastle Upon Tyne, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309067.
Повний текст джерела
17
Zhuk, Mikalai. "Nanostructured granules for controlled delivery of dexamethasone." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/14181.
Повний текст джерелаАнотація:
Mestrado em Ciência e Engenharia de MateriaisA Drug Delivery System (DDS) may provide the precise transportation of the medical drug inside the patient’s body, directly to the pathological area or alternatively it may be also locally administrated. Once at the site of interest, the ideal DDS is expected to release the drug in a sustained manner according to the specific needs of the patient. As compared to other routes of drug administration, an appropriately designed DDS which active components are conveniently targeted should also ensure the desired in situ treatment without harmful effects of the drug over healthy tissues. The inorganic part of the human bone is mainly composed by hydroxyapatite (Ca10(PO4)6(OH)2) (HAP). Chitosan (CH), a natural polymer, is a linear glucose based polysaccharide. These two compounds are non-toxic, biodegradable and highly biocompatible and hence widely used for various biomedical applications (DDS, tissue engineering, implants, etc.). Moreover, some unique features including the amphiphilicity and good mucoadhesive properties of chitosan together with the ability of HAP to adsorb and then release different chemical species make these compounds challenging materials for DDS design. The present work addresses the combination of HAP and CH with a drug model aimed at engineering a DDS with a controlled drug release. Dexamethasone (DEX) is the drug model here selected. DEX is a corticosteroid with anti-inflammatory, antineoplastic and immunosuppressant effects, which is used for the treatment of various diseases like endocrine, dermatologic and neoplastic disorders and cancer among others. In the present research, composite granules with different ratios of HAP and CH components were produced by spray drying aqueous suspension of HAP, chitosan and DEX. To reduce polymer swelling, Glutaraldehyde (GA) was used to cross-link CH. Granules were also produced by a double spray drying technique, which so far has not been yet reported in the literature. The morphology and crystal phase composition of the produced granules were evaluated by scanning electron microscopy (SEM), N2 adsorption using the BET isotherm (BET), and X-ray diffraction (XRD). The obtained results showed that the variation of (HAP/CH) ratio affected the morphology of the granules as when that ratio increases the granules morphology changes from spherical with rough surface to a shape with concavities and smooth surface. Regarding the granules obtained by double spray drying, their morphological characteristics indicated that a core-shell structure was obtained. The drug release experiments were carried out by immersing the DEX loaded granules into phosphate buffer solution (PBS), kept at 37 °C under constant stirring. Aliquots of PBS were withdrawn after different times and their drug content evaluated by UV-Vis spectroscopy at λ= 241,5 nm. The results showed that granules with different composition could display different drug release patterns: HAP/CH granules cross-linked with GA (0,2 wt %) exhibit a more sustained drug release than granules with the same HAP/CH ratio without modification; as for double spray dried granules, a characteristic profile with a double plateau was observed, in line with a core-shell structure. Attempting to elucidate the mechanisms underlying DEX release, different mathematical models were compared with the measured release profiles. It was found that Peppas-Sahlin and Weibull equations are appropriate models for predicting the drug release from the produced granules. In conclusion, the cross-linking and morphology engineering (core-shell structure) via double spray drying allowed improving DEX release profile of HAP/CH DDSs.
Um sistema de libertação de fármacos (DDS) pode transportar de forma precisa o fármaco para o sítio alvo,,i.e., directamente para a zona patológica ou ser administrado localmente. Uma vez no local de interesse, o DDS deve libertar o fármaco de forma controlada, de acordo com as necessidades específicas do paciente, garantindo in situ o tratamento desejado, sem efeitos nocivos sobre os tecidos saudáveis. A parte inorgânica do osso humano é composta principalmente por hidroxiapatite (Ca10(PO4)6(OH)2) (HAP). O quitosano (CH), um polímero natural e abundante. Para além de altamente biocompatíveis estes dois compostos são biodegradáveis, podendo ser utilizados em várias aplicações biomédicas (DDS, engenharia de tecidos, implantes, etc.). Além disso, as características de anfifilicidade e as boas propriedades mucoadesivas do quitosano, somadas à capacidade da HAP para absorver diferentes espécies químicas fazem destes compostos materiais desafiantes para um projecto de DDS. O presente trabalho aborda a combinação de HAP com CH para produção de um DDS. A dexametasona (DEX), que é um corticosteróide com acção anti-inflamatória, anti-neoplásica e efeitos imunossupressores, foi o fármaco modelo seleccionado. Neste trabalho produziram-se grânulos compósitos, com diferentes proporções de HAP e CH, por atomização de suspensões aquosas de HAP, quitosano e DEX. Utilizou-se glutaraldeído (GA) para reticular o CH e procedeu-se também à dupla atomização dos grânulos, uma técnica ainda não reportada na literatura. Os ensaios de libertação do fármaco foram efectuados por imersão dos grânulos carregadas com DEX em solução de fosfato tampão mantida a 37 ° C e sob agitação constante. Alíquotas de PBS foram retiradas após diferentes períodos de tempo e a sua concentração de fármaco avaliada por UV-Vis a λ = 241,5 nm. As características morfológicas e a composição de fases cristalinas dos grânulos atomizados foram avaliadas por micróscopia eletrónica de varrimento (SEM), por adsorção de N2 usando a isotérmica de BET e por difração de raios-X (XRD). Os resultados obtidos mostraram que a variação da razão (HAP / CH) afectou a morfologia dos grânulos: quando a razão aumenta a morfologia dos grânulos evolui de esférica e rugosa para lisa e com concavidades. Por outro lado as características morfológicas dos grânulos duplamente atomizados indicam uma estrutura core-shell. No que se refere aos resultados de libertação de DEX, verificou-se que grânulos de composição diferente evidenciam perfis de libertação distintos: os grânulos reticulados com GA (0,2 %) apresentam uma curva de libertação mais lenta do que a observada para os grânulos com igual razão HAP/CH mas não modificados; quanto aos grânulos com dupla atomização, estes apresentam um padrão de libertação característico, com duplo patamar, em linha com a referida estrutura core-shell. Na tentativa de elucidar os mecanismos subjacentes à libertação de DEX, compararam-se os perfis medidos com diferentes modelos matemáticos. Verificou-se que o padrão de libertação da DEX pode ser adequadamente descrito pela equação de Peppas-Sahlin e de Weibull. Em conclusão, a reticulação e a engenharia de morfologia (estrutura core-shell) pela via da dupla atomização permitiram melhorar o perfil de libertação de DEX do DDS à base de grânulos compósitos de HAP/CH.
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Al-Sailawi, Majid. "Investigating RNA granules formation during caliciviruses infection." Thesis, University of Surrey, 2015. http://epubs.surrey.ac.uk/809289/.
Повний текст джерелаАнотація:
Human norovirus (HuNV) is a member of the calicivirus family and is a major cause of viral gastroenteritis worldwide. Due to the absence of a suitable cell culture system, HuNoV replication mechanisms are poorly understood, but two animal caliciviruses, Feline calicivirus (FCV) and Murine Norovirus (MNV) provide models to increase our understanding of norovirus biology. Unlike cellular mRNAs, the calicivirus RNA genome does not possess a 5' cap structure but instead has a 13–15 kDa viral protein, genome linked (VPg) directing translation, hijacking the host protein synthesis machinery. The viral life cycle requires separated events occurring at different times since viral transcripts are used as the template both for translation (mRNA) and replication (genomic RNA). Therefore mechanisms are required to control the viral RNA fate. In eukaryotes, during stress conditions, mRNAs can be stored in subcellular compartments such as stress granules to stall their translation or in processing bodies to be degraded. Recent evidence indicates that these compartments also play an important role during the viral life cycle. Therefore, using immunofluorescence microscopy we set out to investigate how FCV and MNV infection regulate the formation of G3BP1- and PABP-1-containing stress granules and DCP-1-containing processing bodies to address whether these cytoplasmic granules could play a role during the viral life cycle. We have now shown that FCV has the ability to prevent stress granules formation during infection and that this is important for replication in CRFK and FEA cells. Using FCV-free supernatant from infected CRFK cells and immunofluorescence microscopy, we have also shown that during infection, the formation of stress granules is induced in a paracrine manner in uninfected cells via a messenger molecule released from infected cells. We hypothesize that this could reflect a new antiviral role for stress granules. Furthermore, MNV and FCV infection also led to the disruption of processing-bodies assembly. Overall, this study revealed that caliciviruses modulate the RNA granules during infection and that this could be part of viral mechanism to counteract the antiviral response.
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Piccinini, Marzio. "Porous calcium phosphate granules for biomedical applications." Doctoral thesis, Università degli studi di Trento, 2012. https://hdl.handle.net/11572/368075.
Повний текст джерелаАнотація:
The repair or replacement of damaged or diseased hard tissue is a biomedical field that has been the subject of more and more interest in many areas of research and especially in the development of new biomaterials. The rise in the average age of the world population, increasing osteoporosis treatments and the spread of cancer and genetic bone diseases, has brought about the need to find solutions for patient care. To achieve this target/objective, biomaterials must simulate the body environment as much as possible and favour tissue repair by integrating them into the host site.
Calcium phosphates are used as medical implants because they have a chemical composition similar to the mineral of human bones, i.e. apatite. For this reason they are biocompatible and they can interact in a bioactive way with bone tissue.
In the present work a specific form of bone graft, in the form of calcium phosphate granules, has been developed by using the droplet extrusion technique. The granules were characterized chemically and physically, with specific attention to in vivo and in vitro analyses. The proposed method has allowed us to obtain spherical granules in very narrow micrometric size distribution (300-1200 μm) without the use of solvents or oils thus avoiding time consuming washing processes. Granules were produced with several controlled mineralogical compositions including: pure Hydroxyapatite (HA) and β-Tricalcium Phosphate (βTCP), mixtures of HA/βTCP and Hydroxyapatite/Tetracalcium phosphate (HA/TTCP), and compositions doped with zinc (for antibacterial purposes) and strontium (for anti-osteoporosis purposes). Of several interesting features, the produced granules show high interconnected microporosity (0.1-10 μm) and surface roughness, properties necessary for osteoconductivity.
The solubility behavior of granules was studied and demonstrated that the morphology and microporosity are more important in dissolution processes than chemical or mineralogical composition. Products were tested in simulated body fluid (SBF), and among the different compositions, HA/TTCP has been found to be bioactive during in vitro studies. In fact an intense precipitation of a carbonated layer of apatite was observed, associated with the high dissolution of a TTCP phase. All pure granules were demonstrated to not be cytotoxic. Bone implantations in different animal models (rabbits and primates) showed good performance of granules in the repairing of bone. The granules stimulated the bone growth without any inflammatory reactions. In particular, HA/TTCP granules exhibited excellent biomechanical properties by increasing the stability of neo-formed bone. These preliminary investigations were sufficient to show that the developed granules can be used for bone repair or replacement. However, more studies, especially for doped products, such as in vitro cells experiments, have to be performed to assure the biocompatibility and the effective stimulation of bone growth.
This work was performed in collaboration with Eurocoating S.p.A. (Trento, Italy), a company expert in biomedical coatings for prostheses and implants, and it is a part of “CaP project†co-sponsored by Provincia Autonoma di Trento (Italy).
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Piccinini, Marzio. "Porous calcium phosphate granules for biomedical applications." Doctoral thesis, University of Trento, 2012. http://eprints-phd.biblio.unitn.it/794/1/PhD%2BThesis_Piccinini_Definitiva_Aprile%2B2012.pdf.
Повний текст джерелаАнотація:
The repair or replacement of damaged or diseased hard tissue is a biomedical field that has been the subject of more and more interest in many areas of research and especially in the development of new biomaterials. The rise in the average age of the world population, increasing osteoporosis treatments and the spread of cancer and genetic bone diseases, has brought about the need to find solutions for patient care. To achieve this target/objective, biomaterials must simulate the body environment as much as possible and favour tissue repair by integrating them into the host site.
Calcium phosphates are used as medical implants because they have a chemical composition similar to the mineral of human bones, i.e. apatite. For this reason they are biocompatible and they can interact in a bioactive way with bone tissue.
In the present work a specific form of bone graft, in the form of calcium phosphate granules, has been developed by using the droplet extrusion technique. The granules were characterized chemically and physically, with specific attention to in vivo and in vitro analyses. The proposed method has allowed us to obtain spherical granules in very narrow micrometric size distribution (300-1200 μm) without the use of solvents or oils thus avoiding time consuming washing processes. Granules were produced with several controlled mineralogical compositions including: pure Hydroxyapatite (HA) and β-Tricalcium Phosphate (βTCP), mixtures of HA/βTCP and Hydroxyapatite/Tetracalcium phosphate (HA/TTCP), and compositions doped with zinc (for antibacterial purposes) and strontium (for anti-osteoporosis purposes). Of several interesting features, the produced granules show high interconnected microporosity (0.1-10 μm) and surface roughness, properties necessary for osteoconductivity.
The solubility behavior of granules was studied and demonstrated that the morphology and microporosity are more important in dissolution processes than chemical or mineralogical composition. Products were tested in simulated body fluid (SBF), and among the different compositions, HA/TTCP has been found to be bioactive during in vitro studies. In fact an intense precipitation of a carbonated layer of apatite was observed, associated with the high dissolution of a TTCP phase. All pure granules were demonstrated to not be cytotoxic. Bone implantations in different animal models (rabbits and primates) showed good performance of granules in the repairing of bone. The granules stimulated the bone growth without any inflammatory reactions. In particular, HA/TTCP granules exhibited excellent biomechanical properties by increasing the stability of neo-formed bone. These preliminary investigations were sufficient to show that the developed granules can be used for bone repair or replacement. However, more studies, especially for doped products, such as in vitro cells experiments, have to be performed to assure the biocompatibility and the effective stimulation of bone growth.
This work was performed in collaboration with Eurocoating S.p.A. (Trento, Italy), a company expert in biomedical coatings for prostheses and implants, and it is a part of “CaP project” co-sponsored by Provincia Autonoma di Trento (Italy).
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Jayakody, J. A. Luckshman Priyadharshana. "The effect of acid hydrolysis on granular morphology and physicochemical properties of native cereal starch granules." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ62392.pdf.
Повний текст джерела
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Agniel, Yvan. "Rôle des propriétés des granules pour la fabrication de pièces de poudres céramiques granulées sans défaut de compaction." Lyon, INSA, 1992. http://www.theses.fr/1992ISAL0072.
Повний текст джерелаАнотація:
La granulation d'une poudre fine de céramique permet d'améliorer considérablement ses propriétés de compaction et donc de frittage à condition d'obtenir une destruction totale des granules lors de la mise en forme. Des granules modèles ont pour ce faire été testées de façon unitaire (compression uni axiale) et dans un lit de granules (compaction bilatérale dans une presse instrumentée construite par nos soins). Les résultats ont ensuite été comparés sur la base de modèles de compaction de la littérature scientifique après leur modification, et une corrélation empirique a été trouvée entre les propriétés d'une granule et son comportement en compaction. Des moyens céramographiques et porosimétriques ont permis de conclure sur la création et le développement des défauts lors de la compaction et du frittageThe granulation of fine ceramic powders improves considerably its compaction and thus sintering properties, provided that a full destruction of the granules is obtained by the shaping of the part. Model granules were tested as single ones (uniaxial compression ) and in a packing (double-action-compaction in an instrumented pressing tool developed during this work). Both results were then compared on the basis of modified compaction models from the literature , and an empirical correlation between single granule properties and compaction behaviour of the granulated powder was found. Ceramographical and porosimetrical methods helped to conclude about the formation and development of flaws during compaction and sintering
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Perry, Paul Anthony. "Plasticisation and thermal modification of starch." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340970.
Повний текст джерела
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Stewart, James Alexander. "Engineering the properties of spray-dried detergent granules." Thesis, University of Manchester, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.548673.
Повний текст джерела
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Griffith, J. D. "The drying and absorption properties of surfactant granules." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.599715.
Повний текст джерелаАнотація:
The work in this thesis contributes to an understanding of the evolution of the drying kinetics and internal microstructure of a model detergent paste (called a crutcher mix) during the spray drying stage in the manufacture of washing powders in order that the physical and cleaning properties of the final dried detergent powder can ultimately be more easily controlled and manipulated. Regularisation algorithms were developed and employed in conjunction with nuclear magnetic resonance (NMR) spectroscopy and relaxometry techniques to characterise both the bulk and individual constituent components of crutcher mix. In addition, novel 2-D relaxation methods were applied and used to characterise the sizes of the different phase domains within crutcher mix. The in-situ drying of crutcher mix has been investigated using NMR. Large samples have been studied to identify the changes in bulk properties, whilst studies on individual 10 µl droplets mimic the material geometry in an industrial spray dryer. Quantitative imaging and relaxometry experiments have been used to show that the drying is in the failing rate regime throughout and to deduce that there is preferential drying of the water-rich phase over the surfactant-rich phase. Novel rapid pulsed field gradient (PFG) experiments have been destroyed and then used to probe the dynamic evolution of the internal microstructure during drying. A parameter free model describing the drying of single detergent pate droplets has been established and compared favourably to experimental data. The model has been expanded to provide very preliminary simulations of the drying conditions within industrial spray dryers. A feasibility study looking into the use of NMR to study the absorption properties of the dried granular detergent product was also conducted. The ingress of water into a compacted detergent tablet has been monitored through the acquisition of 1-D image profiles of the water content and shown to exhibit Case II diffusion characteristics.
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Pilling, Emma. "The origins of growth ring in starch granules." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365027.
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Rinn, Cornelia. "Pancreatic zymogen granules: new proteins in unexpected places." Doctoral thesis, Universidade de Aveiro, 2011. http://hdl.handle.net/10773/7309.
Повний текст джерелаАнотація:
Doutoramento em BiologiaOs mecanismos de biogénese, distribuição apical e secreção regulada de enzimas digestivas dos grânulos de zimogénio são, atualmente, pouco conhecidos. De modo a esclarecer e descrever estes processos de elevada importância biológica e clínica, é necessária uma melhor compreensão dos componentes da membrana granular e as funções e interações destes. Neste trabalho, através de uma abordagem proteómica, foi possível identificar novas proteínas granulares previamente associadas ao transporte vesicular sináptico. Para estudar as funções destas proteínas na génese e secreção de grânulos, foram realizados estudos de sobre-expressão, assim como estudos bioquímicos (1D, 2D, and LC-MS/MS) e morfológicos, utilizando céluas de mamífero. Entre as proteínas descobertas, cinco foram selecionadas e analisadas: RMCP-1, Piccolo, Synaptojanin-1, APP e ZG16p. Destas proteínas, confirmou-se a presença da RMCP-1 e APP nos grânulos de zimogénio. Interessantamente, o lectin ZG16p da secreção pâncreatico, encontra-se expressa no cérebro de rato, estando localizada nos terminais pós-sinápticos e em grânulos de RNA, indicando uma possível função desta proteína na formação das vesículas sinápticas. Finalmente, demonstrei que a formação de grânulos de zimogénio pode ser modulada, no modelo de células pancreáticas AR42J, pelas condições de cultura. Em contraste com as proteínas de carga neuroendocrinas, a sobreexpressão de proteínas de carga ou da membrana dos grânulos de zimogénio não foi suficiente para induzir a formação de grânulos ou de estruturas granulares em células constitutivamente secretoras, indicando diferenças na biogénese de grânulos neuroendócrinos e exócrinos.
The mechanisms of secretory granule biogenesis, apical sorting and regulated secretion of digestive enzymes in pancreatic acinar cells are not yet well understood. In order to shed light on these biologically and clinically important processes, a better molecular understanding of the components of the granule membrane, their functions and interactions is required. Using a proteomicsbased approach, novel granule proteins were identified, which have been previously described to be involved in synaptic vesicle biogenesis and trafficking. To elucidate the yet unknown functions of these proteins in zymogen granule biogenesis and secretion, overexpression studies as well as biochemical (1D, 2D, and LC-MS/MS) and morphological methods were applied to mammalian cells. Five proteins identified were selected for further evaluation: RMCP-1, Piccolo, Synaptojanin-1, APP and ZG16p. While RMCP-1 and APP were confirmed to be new zymogen granule proteins, the existence of Synaptojanin-1 and Piccolo in ZGs could not be verified. Interestingly, the pancreatic secretory lectin ZG16p was demonstrated to be expressed in rat brain, localizing to post-synapses and RNA granules suggesting a potential function in synaptic vesicle formation. I also demonstrated that ZG formation in AR42J cells, a pancreatic model system, can be modulated by altering the growth conditions in cell culture. In contrast to neuroendocrine cargo proteins, overexpression of ZG cargo and membrane proteins was not sufficient to induce ZG formation or granule-like structures in constitutively secreting cells pointing to differences in neuroendocrine and exocrine granule biogenesis.
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Mansour, Rana. "Rôle du Ptdlns5P et de PIKfyve dans le contrôle de l'intégrité des granules plaquettaires." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30089/document.
Повний текст джерелаАнотація:
Les plaquettes jouent un rôle primordial dans le processus d'hémostase. Elles sont générées à partir des mégacaryocytes (MK) présents dans la moelle osseuse. En plus des compartiments vésiculaires classiques de la voie d'endocytose et de dégradation vers les lysosomes, les plaquettes possèdent deux compartiments sécrétoires additionnels, les granules alpha et denses. Ces granules sont générés au cours de la maturation des MK à partir des corps multivésiculaires (MVB) et contiennent des molécules essentielles aux fonctions plaquettaires. Un défaut dans la production ou le remplissage de ces granules est à l'origine de symdromes hémorragiques. Malgré des études montrant l'implication de certaines protéines du trafic vésiculaire, les mécanismes moléculaires qui contrôlent la biogenèse et la maintenance des granules plaquettaires dans les MK ainsi que les mécanismes de tri des cargos qu'ils contiennent, ne sont pas complètement élucidés. Au cours de ces dernières années les phosphoinositides (PI) sont apparus comme des acteurs majeurs du trafic vésiculaire en régulant de la localisation de certaines protéines. Cependant, peu de choses sont connues à ce jour quant au rôle de ces lipides dans la biogenèse et le trafic des granules plaquettaires dans les MK. Au cours de ma thèse, j'ai étudié le rôle d'un des membres de la famille des PI, le phosphatidylinositol 5-phosphate (PtdIns5P), ainsi que deux enzymes responsables de sa synthèse : la 3-phosphatase MTM1 (mutée dans la myopathie centronucléaire, CNM) et la lipide kinase PIKfyve, dans le contrôle de la dynamique des granules. Mes résultats montrent que MTM1 est présente dans les MK et les plaquettes et est localisée en partie sur les granules denses. Cependant, cette phosphatase n'est pas essentielle pour la production et l'activation plaquettaire. En effet, les souris MTM1 KO ne présentent pas de défaut du nombre plaquettaire, ni d'agrégation et de sécrétion suite à une stimulation par la thrombine ou le collagène. Nous montrons la présence d'autres membres de la famille des myotubularines dans les plaquettes et les MK différenciés, ce qui pourrait expliquer une redondance de fonction. De façon intéressante, nous montrons que la détection de MTM1 à partir de faible quantité de sang (<100 ?l) pourrait déboucher sur la mise au point d'un test diagnostic rapide pour la détection de la CNM. Mes travaux ont été focalisés par la suite sur PIKfyve. En utilisant la lignée leucémique mégacaryoblastique MEG-01 différenciée, je montre pour la première fois que le PtdIns5P est localisé dans les compartiments endosomes tardifs ainsi que dans les granules alpha et denses. Dans ces cellules, PIKfyve contrôle plus de 50% du PtdIns5P. De façon remarquable, l'inhibition pharmacologique de PIKfyve ou son invalidation par siRNA entraine une perte d'identité des granules avec la formation de granules élargis qui présentent à la fois des marqueurs de granules denses et alpha et bloque totalement leur mobilité. Ces données ont été confirmées dans des MK primaires de souris. L'addition de PtdIns5P exogène sur les MEG-01 restaure le phénotype normal des granules démontrant que PIKfyve, par l'intermédiaire du PtdIns5P, contrôle l'intégrité des granules qui est donc un phénomène actif et les mécanismes de fusion/fission des vésicules affectant le tri des cargos. De plus, l'inhibition de PIKfyve dans les plaquettes isolées affecte leur agrégation et leur sécrétion, montrant que PIKfyve et le PtdIns5P peuvent agir d'une part lors de la biogénèse des plaquettes dans les MK et d'autre part sur le fonctionnement des plaquettes. Dans leur ensemble, mes travaux placent PIKfyve et son produit lipidique, le PtdIns5P, comme des acteurs majeurs de la maintenance et l'identité des granules plaquettairesPlatelets play a major role in homeostasis processes. They are generated from megakaryocytes (MKs) in the bone marrow. In addition to the classic vesicular compartments of the endocytic and degradation pathway toward lysosomes, platelets have two additional specialized secretory compartments, the dense and alpha granules. These granules are made during MK maturation from multivesicular bodies (MVB) and contain molecules that are essential to platelet functions. Defect in the production of these granules or absence of their cargos is the cause of hemorrhagic syndromes. Despite many studies showing the implication of vesicle trafficking proteins, the molecular mechanisms controlling the biogenesis and maintenance of the granules and cargo sorting are not completely understood. In recent years, phosphoinositides (PIs) have emerged as key actors in vesicular trafficking playing a role of important spatial regulators of many proteins. However, little is known about the role of these lipids in the biogenesis and the trafficking of platelet granules in the MK.During my thesis, I have studied the role of one the member of the PI family, the phosphatidylinositol 5-phosphate (PtdIns5P), and of two enzymes responsible of its synthesis : the 3-phosphatase MTM1(mutated in the Centronuclear myopathy, CNM) and the lipid kinase PIKfyve, in the control of granules dynamic. My results show that MTM1 is present in MK and platelet and that platelet MTM1 localizes in part on dense granules. However, the phosphatase is not mandatory for platelet production and activation. Indeed, the knock-out of MTM1 in mice has no effect on platelet count, aggregation and secretion following thrombin or collagen stimulation. We show the presence of other members of the myotubularins family in platelet and differentiated MK, which can explain a redundancy in functions. Interestingly, we show that MTM1 detection from small amount of blood (<100 ?l) could lead to the development of a rapid diagnostic test for the detection of the CNM. My work was next focalized on PIKfyve. Using the differentiated leukemic megakaryoblastic cell line MEG-01 as a cell model, I showed for the first time that PtdIns5P is localized on late endosome and on alpha and dense granules. In these cells, PIKfyve controls more than 50% of cellular PtdIns5P. Remarkably, pharmacological inhibition of PIKfyve or its invalidation by siRNA leads to a loss of granules identity with the formation of enlarged granules containing both alpha and dense granules markers, and totally blocks their mobility. These data were also confirmed on primary mice MK. Addition of exogenous PtdIns5P on MEG-01 cells restores the normal phenotype of granules showing that PIKfyve, via PtdIns5P, controls granules integrity, an active phenomenon, and the fusion/fission mechanisms that affect cargos sorting. Furthermore, PIKfyve inhibition in isolated platelet affects their aggregation and secretion, showing that PIKfyve and the PtdIns5P may act on the biogenesis of platelets in MK and also on the function of mature platelets. In conclusion, my Ph.D. work shows that PIKfyve and its product PtdIns5P are major actors in platelet granules maintenance and integrity
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Heinze, Karsta. "From grain to granule : the biomechanics of wheat grain fractionation with a focus on the role of starch granules." Thesis, Montpellier, 2017. http://www.theses.fr/2017MONTS072/document.
Повний текст джерелаАнотація:
La culture du blé est l’une des plus importantes au monde. Le grain de blé est un matériau composite naturel dont la majeure partie est constituée d’albumen amylacé formé d’un assemblage compact de granules d’amidons (glucides) enchâssés dans une matrice protéique (gluten). Pour obtenir des produits comme la farine, la structure de l'albumen doit être fragmentée en broyant les grains sous des fortes contraintes. La quantité et la qualité des produits obtenus dépendent du comportement de l’albumen à la fragmentation. En raison de sa nature composite, le comportement rhéologique du grain est tributaires des propriétés mécaniques des phases qui le composent (granules, gluten, pores), de leurs interactions, ainsi que de leur distribution spatiale. Les granules d’amidons sont de formes relativement sphériques et de tailles micrométriques, tandis que les protéines sont organisées en un réseau entourant les granules. L'interaction entre l'amidon et ce réseau protéique est influencée par certaines protéines, les puroindolines, dont la présence et le type d’allèle sont contrôlées génétiquement. Si les gènes codant pour les puroindolines sont présents sous forme sauvages, la dureté meunière, c’est à dire l’aptitude à la fragmentation du grain est faible. L’origine de ce comportement est liée à une adhérence limitée entre matrice protéique et amidon. L'absence totale de puroindolines chez le blé dur conduit au contraire à une dureté très élevée des grains et à une forte adhérence. L'objectif de cette thèse est d'étudier, à partir d’une approche multidisciplinaire, la biomécanique du fractionnement du grain de blé en mettant l'accent sur le rôle des granules d'amidon. Des échelles de taille différentes sont considérées : échelle micrométrique du granule et de la matrice protéique; agencement complexe de ces composants dans l'albumen et échelle millimétrique du grain. Ainsi, des expériences de broyage à l'échelle du grain ont été combinées avec des mesures nano-mécaniques par microscopie à force atomique (AFM) et des simulations numériques.Le comportement au broyage a été étudié en utilisant un micro-moulin instrumenté. Une comparaison a été effectuée entre des essais réalisés sur une variété de blé dur et sur la même variété dans laquelle ont été introduits les gènes codant pour les puroindolines. Un changement significatif du comportement mécanique des grains transformés, attribuable uniquement à la présence de puroindolines, a été observé - en termes d'énergie consommée, - de productivité en farine et - de taux d'amidon endommagé. Ces changements sont compatibles avec l'hypothèse d'une faible adhérence, entre granules d'amidon et matrice protéique, induite par la présence des puroindolines et montrent l'effet significatif de celles-ci sur le comportement à la fragmentation. Ces modifications de comportement mécanique peuvent être étudiées par des mesures AFM nano-mécaniques. Pour compléter des travaux antérieurs ayant permis la mesure des propriétés de l'amidon et du gluten, une méthode basée sur des mesures AFM en mode résonance de contact (CR-AFM) a été développée. Celle-ci permet de cartographier les propriétés directement à l'intérieur des granules d’amidon et prend en compte à travers un modèle théorique les variations importantes de topographie observées dans les sections de grains. Ces études CR-AFM de l'albumen ont ensuite porté sur les propriétés mécaniques des granules d'amidon d'origines botaniques différentes (céréales et légumineuses).Enfin, le rôle de la distribution bimodale en taille des granules d'amidon sur la fragmentation de l'albumen a été précisé à partir d’une étude numérique paramétrique détaillée. Les propriétés mécaniques élastiques et à la rupture ont été analysées en détail, ainsi que le rôle dominant de la ténacité des granules et de l'adhérence à l'interface sur l’endommagement de l’amidonThe wheat grain is a natural composite material of worldwide importance. The major part of the grain is the starchy endosperm. To obtain food products, such as flour, the endosperm’s compact structure needs to be disintegrated, which is achieved by milling the grains under high forces. The quantity and quality of the milling products notably depend on the fragmentation behaviour of the endosperm.Due to the endosperm’s composite nature, this behaviour depends strongly on the mechanical properties of its components and their interaction. The main components of the endosperm are carbohydrates and proteins. The carbohydrates are deposited as starch in the form of granules of micro-meter size, whereas proteins form a network (gluten), which surrounds the starch granules. The interactions between starch and proteins is believed to be influenced by certain non-gluten proteins (puroindolines), whose presence and allelic state are genetically controlled. If puroindoline genes are present in the wild-type form, grain hardness is low, which have been related to low starch-protein adhesion. The complete absence of puroindolines in the durum wheat species leads to very high grain hardness and indicates a strong adhesion.The aim of this thesis was to investigate the biomechanics of wheat grain fractionation with a focus on the role of the starch granules therein, which was pursued with a multi-disciplinary approach. Different size scales were considered, from the micro meter-sized structures of starch and protein, the complexity of their arrangement in the endosperm, up to the millimeter-sized grains. In this work, grain-scale milling experiments were combined with nano-mechanical measurements by atomic force microscopy (AFM) and numerical simulations.The milling behaviour of a transgenic durum wheat line, which contained puroindoline genes, was determined by grain scale milling experiments and compared to the milling behavior of non-modified durum wheat. A significant change of milling behavior of the transformed durum wheat grains was observed in terms of milling energy, flour yield and starch damage, which was solely attributable to the presence of puroindolines. The observed changes were consistent with the hypothesis of a lower adhesion between starch granules and protein matrix due to the presence of puroindolines and confirmed the significant effect of puroindolines on the fragmentation behaviour, independent of the grain’s genetic background.The change of fragmentation behaviour is a result of modifications of the mechanical properties of the endosperm’s components and/ or their interaction. Such modifications can be investigated by AFM nano-mechanical measurements. Based on previous work illuminating the global nano-mechanical properties of starch and gluten, contact-resonance AFM (CR-AFM) was applied to obtain maps of the nano-mechanical properties inside the grains. Due to the high topography variations of grain section surfaces and the non-trivial correlation between surface slope and contact resonance-frequency, which hindered a straight-forward interpretation of CR-AFM measurements, a practical method based on existing analytical models of the cantilever vibration was developed to correct the measurements. CR-AFM studies of the endosperm were then focused specifically on the mechanical properties of starch granules and the link to starch structure, and applied to the study of starches from wheat in comparison to plants from different botanical origin (other cereals and legumes).Finally, the role of starch granules, their size distribution, and mechanical properties on endosperm fragmentation was analysed by parametric numerical studies. The influence of the bi-modal size distribution of granules on the mesoscale mechanical properties was shown, as well as the governing role of granule toughness and interface adhesion on the granule damage
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KANEDA, TOSHIO, TAKESHI HOSHINO, MINORU UEDA, HIDEKI MIZUTANI, and MICHIO KAWAI. "Cervicofacial Actinomycosis: Report of Two Cases." Nagoya University School of Medicine, 1993. http://hdl.handle.net/2237/17537.
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Verhoeven, Tamara M. O. "Determination of the morphology of starch granules in cereal endosperm." Thesis, University of East Anglia, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268549.
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Pryde, James Grant. "Biogenesis of secretory granules in the bovine adrenal medulla." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/24238.
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Fanous, Alaa. "Elucidating the Functional Role of TDRD3 in Stress Granules." Thèse, Université d'Ottawa / University of Ottawa, 2014. http://hdl.handle.net/10393/31019.
Повний текст джерелаАнотація:
Tudor domain-containing protein 3, TDRD3, was first identified in a proteomic survey of the spliceosome machinery. Although its function remains elusive, elevated TDRD3 gene expression is associated with poor prognosis of estrogen receptor-negative breast cancer. The Tudor domain of TDRD3 is highly similar to the Tudor domain of the survival of motor neuron (SMN) and accordingly, it has been shown to bind dimethylated arginine residues. Our lab has previously demonstrated the association of TDRD3 with the translation machinery and most importantly, its localization to stress granules (SG) upon various cellular stresses. In this study, it was revealed that TDRD3 knockdown facilitates and accelerates SG assembly and consequently accelerates SG disassembly. Moreover, we showed that wildtype TDRD3 rescued this defect while a mutation in the Tudor domain of TDRD3, E691K, was not able to do so. Taken together, these findings allude to a prominent role for TDRD3, via its Tudor domain, in the proper formation of SGs.
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Arden, Catherine. "Compartmentation and function of glucokinase in insulin secretory granules." Thesis, University of Newcastle Upon Tyne, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.407841.
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Maxim, Robert E. "Designing granules for abrasive cleaning (using high-shear granulation)." Thesis, University of Sheffield, 2006. http://etheses.whiterose.ac.uk/14898/.
Повний текст джерелаАнотація:
This work investigates the granulation of fine calcium carbonate powder to form microgranules (less than lOOf.lll1). The influence offormulation and operating conditions on granule properties was investigated. This work analyses experimental data using a database approach to relate granulation conditions to granule properties, to fmd propertyto-property relationships and to investigate the influence on the abrasion of Perspex. It was found that the granulation was undertaken in an unstable regime dictated by the need to produce small granules. As a result, it was not possible to achieve reproducibility in making the granules. For the range of granules produced it was difficult to determine variation in abrasiveness within the experimental errors, a detailed error analysis was carried out. A theoretical relationship between strength and porosity is developed and the factors influencing abrasive wear are investigated. Two theoretical models are presented: 1) Impact Failure model and 2) Granule Consolidation model. The impact failure model relates dynamic impact strength to static strength, which enables the prediction of a failure distribution curve (how many particles will fail per hundred impacts as a function of velocity). This is done using a "critical normal impact velocity" determined from the properties of the granule, properties of the impact surface and experimentally measured granule static strength. The granule consolidation model allows the qualitative prediction of the rate and extent of consolidation from granulation conditions. It models the compaction of a granule by descnbing the packing of its primary particles within an imaginary internal granule. Sphere packing is discussed with implications for determining the maximum packing of a primary particle size distribution.
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Formicola, Nadia. "Remodelage des granules ARN en réponse à l’activité neuronale." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://theses.univ-cotedazur.fr/2019AZUR6008.
Повний текст джерелаАнотація:
Une des questions les plus fascinantes – et les plus ouvertes – en neuroscience est de comprendre comment les cellules neuronales contribuent à la formation, le maintien puis le rappel des souvenirs. Des travaux antérieurs ont montré que la formation de la mémoire à long-terme (MLT) requiert la synthèse de novo de protéines, impliquant non seulement la traduction d’ARNs nouvellement transcrits, mais aussi la traduction locale, induite par l’expérience, d’ARNms latents transportés et stockés dans les synapses. En vue de leur transport et du contrôle de leur traduction, les ARNms sont empaquetés avec des protéines de liaison aux ARNs (RBP), qui sont majoritairement des répresseurs de traduction, dans des granules ribonucléoprotéiques (RNP). La manière dont les granules RNP neuronaux sont remodelés en réponse à l’activité neuronale pour lever la répression traductionelle des ARNms est pour l’instant peu claire. En outre, l’impact fonctionnel d’un tel remodelage sur l’établissement de la MLT reste à démontrer in vivo. L’objectif de mon doctorat était 1) d’étudier les mécanismes in vivo qui sous-tendent le remodelage des granules RNP neuronaux ; 2) de tester l’hypothèse que les granules RNP pourraient être impliqués dans les mécanismes de renforcement de la MLT en régulant l’expression génétique. Dans cette optique, j’ai utilisé comme modèle des granules RNP contenant la RBP conservée Imp chez la drosophile. Tout d’abord, j’ai étudié l’impact de l’activité neuronale sur les propriétés des granules RNP Imp, en traitant des explants de cerveau soit avec du KCl, soit avec le neuromodulateur Tyramine. Dans les deux cas, un désassemblage des granules RNP Imp - caractérisé par une dé-granulation à la fois de Imp et d’autres composants – est observé. Le désassemblage des granules RNP est réversible après retrait de la tyramine, et n’a pas été observé dans les neurones hyperpolarisés. Il ne dépend pas strictement du domaine de type prion qui se trouve à l’extrémité carboxy-terminale de Imp, un domaine connu pour être impliqué dans l’homéostasie des granules RNP. De plus, mes données suggèrent que ce désassemblage soit lié à une augmentation de la traduction des ARNms associés, ce qui est cohérent avec un modèle dans lequel le remodelage des granules RNP induit par l’activité des neurones induit une dé-répression de la traduction. Ensuite, j’ai recherché les mécanismes contrôlant le remodelage des granules RNP. Un candidat pour cette régulation était CamkII, une kinase conservée activée par le calcium, et identifiée comme partenaire de Imp dans une analyse d’immunoprécipitation-spectrométrie de masse. Au cours de mon doctorat, j’ai pu valider l’intéraction Imp-CamkII et montrer qu’elle n’est pas médiée par l’ARN, mais dépend de l’activité de CamkII. De plus, j’ai montré qu’inhiber l’activité de CamkII empêche le désassemblage des granules RNP Imp observé lors de l’activation neuronale, suggérant que CamkII pourrait être impliquée dans le remodelage des granules RNP Imp induit par l’activité neuronale. Ces résutats sont particulièrement intéressants dans le contexte de l’établissement de la MLT, car CamkII est depuis longtemps reconnue comme y étant essentielle. Plus encore, nous avons récemment démontré chez la drosophile qu’inactiver la fonction de Imp dans une population de neurones du cerveau central impliquée dans l’apprentissage et la mémoire – les neurones du Mushroom Body – altère radicalement la MLT. En conclusion, mes résultats sont cohérents avec un modèle où le remodelage des granules RNP Imp en réponse à l’activation neuronale dépend de CamkII, et pourrait contribuer à la formation de la MLT in vivoOne of the most fascinating – and still open – questions in neuroscience is how neuronal cells can form, store and then recall memories. Previous work has shown that Long-term memory (LTM) formation requires de novo protein synthesis, involving not only translation of newly transcribed RNAs, but also local, experience-induced translation of quiescent mRNAs carried and stored at synapses. For their transport and translational control, mRNAs are packaged with regulatory RNA binding proteins (RBPs), mainly translational repressors, into ribonucleoprotein (RNP) granules. To date, how neuronal RNP granules are remodelled in response to neuronal activity to relieve translation repression of mRNAs is unclear. Furthermore, the functional impact of such a remodelling in the establishment of long-term memories remains to be demonstrated in vivo. The objective of my PhD was to 1) investigate the in vivo mechanisms underlying activity-dependent remodelling of neuronal RNP granules; 2) test the hypothesis that RNPs could be involved in LTM-underlying mechanisms by regulating gene expression. To this end, I used as paradigm RNPs containing the conserved RBP Imp in Drosophila. First, I studied the impact of neuronal activity on Imp RNP properties by treating Drosophila brain explants with either KCl or the tyramine neuropeptide. In both cases, a disassembly of Imp RNPs was observed, characterized by a loss of both Imp and other RNP-component granular patterns, and a de-clustering of RNP-associated mRNA molecules. RNP disassembly could be reverted upon Tyramine withdrawal and was not observed in hyperpolarized neurons. Furthermore, my data suggest that RNP-disassembly is linked to increased translation of associated mRNAs, consistent with a model in which activity-induced RNP remodelling would lead to translational de-repression. Second, I investigated the mechanisms controlling RNP remodelling. A candidate regulator was CamkII, a conserved Ca2+ -activated kinase identified as a partner of Imp in an IP-Mass Spectrometry analysis. During my PhD, I could validate the Imp-CamkII interaction and showed that it is not mediated by RNA but depends on CamkII activity. Furthermore, I showed that inactivating CamkII function prevents the disassembly of Imp RNPs observed upon neuronal activation of brain explants, suggesting that CamkII may be involved in the activity-dependent remodelling of Imp RNP granules. These results are particularly interesting in the context of establishment of LTM, as CamkII has long been recognized as essential for LTM. Moreover, we recently showed in Drosophila that interfering with Imp function in a population of CNS neurons involved in learning and memory – the Mushroom Body γ neurons -, dramatically impairs LTM and that this effect relies on Imp C-terminal Prion-like domain, a domain known to be involved in RNP homeostasis. Altogether, my thesis work suggests a model where CamkII-dependent remodelling of Imp RNPs in response to neuronal activation might underlie LTM formation in vivo
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Langford, Harry. "The microstructure, biogeochemistry and aggregation of Arctic cryoconite granules." Thesis, University of Sheffield, 2012. http://etheses.whiterose.ac.uk/2931/.
Повний текст джерелаАнотація:
Cryoconite granules are hydrous microaggregates, principally composed of microorganisms, organic matter and mineral particles, that reside upon glacier surfaces. Whilst recent research has highlighted the diverse microbial community within cryoconite granules and their role as biogeochemical reactors, little is known about their microstructure, the cell–mineral interaction within them, or their aggregation mechanisms. Knowledge of these is crucial for the understanding of autotrophic organic matter production and cycling, the entrainment of particulate matter and its consequential effect on glacier melt, and the life cycle of cryoconite granules and its impact on proglacial soil development. These studies find that cryoconite granules are heterogeneous, demonstrating spatially variable microorganism and organic matter contents, containing significant quantities of filamentous cyanobacteria and exhibiting a fine groundmass of clay-sized particles enmeshed within various extracellular polymeric substances (EPS). The importance of photoautotrophy, EPS production and cation-bridged EPS–mineral interactions as biological ‘forming factors’ is demonstrated. The cyanobacterial filament and carbohydrate contents of cryoconite material explain 83% of the measured variability in aggregate size and stability upon Longyearbreen glacier. Geospatial investigations of these ‘forming factors’ reveal spatial patterns, with a zone of excess EPS production evident towards the snowline and increased pigment production evident in stable, down-glacier locations. A variety of mineral particles can co-aggregate with EPS-producing cyanobacteria, with ionic strength, temperature and growth phase all affecting efficiency. Spectroscopic studies reveal evidence for chiefly polymer-based modes of attachment within cyanobacteria–EPS–mineral aggregates, with complex EPS able to overcome surface charge and interact with mineral surfaces in a variety of ways. This thesis presents the first detailed study of cryoconite granule microstructure and aggregation, finding that photoautotrophy and EPS production are vital to the development of stable aggregates, providing a matrix that attracts aeolian particulates, stabilises granules and promotes biogeochemical interaction and the development of microenvironments.
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Riemschoß, Katrin [Verfasser]. "Similarities of stress granules and cytosolic prions / Katrin Riemschoß." Bonn : Universitäts- und Landesbibliothek Bonn, 2019. http://d-nb.info/1206246170/34.
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Ikeda, Noboru. "Quantitative comparison of osteoconduction of porous, dense A-W glass-ceramic and hydroxyapatite granules (effects of granule and pore size)." Kyoto University, 2000. http://hdl.handle.net/2433/180891.
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Tahir, Muhammad Javaid. "Isolation and characterization of dense granules of Eimeria tenella sporozoites." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ35939.pdf.
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Lauzier, Christian. "Morphology and crystallization behavior of nascent poly(3-hydroxybutyrate) granules." Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41136.
Повний текст джерелаАнотація:
The structure of poly(3-hydroxybutyrate) (PHB) granules was examined by transmission and scanning electron microscopy (TEM and SEM). They are made of two distinct components: a solid shell (overlapping lamellar crystals) and a non-crystalline core.TEM examination of sections of PHB granules revealed that, upon annealing, the core molecules transform into stacks of lamellar crystals of $ sim$50-70A in thickness. Fourier transform infrared results revealed the presence of bound water in a sample of freeze dried granules. Solid state $ sp{13}$C NMR results showed that the mobility of the granule core molecules was partly retained upon drying. A model for biosynthesis where emerging PHB chains in an extended conformation are simultaneously hydrogen bonded to water molecules is proposed.
Hydrolytic degradation of PHB granules in hot HCl proceeds through random scission of the molecules of both the crystalline shell and the non-crystalline core indiscriminately.
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Boutell, Suzanne Louise. "Factors influencing the preparation of spherical granules by extrusion/spheronisation." Thesis, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.481206.
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Chapman, Stephen Robert. "Influence of process variables on the preparation of spherical granules." Thesis, King's College London (University of London), 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282983.
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Gasparinho, Goncalves A. C. "Understanding the role of stress granules in the inner ear." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1553331/.
Повний текст джерелаАнотація:
The human ear undergoes stress constantly. Exposure to noise, drugs or ageing contribute to the irreversible loss of hair cells, resulting in hearing loss. To understand why we go deaf, it is important to understand how the ear responds to stress. Stress granules (SGs) are aggregates of mRNA and proteins that are formed during stress. The SG-pathway has been implicated in the cochlea’s response to aminoglycoside antibiotics, suggesting that SGs play an important role during ototoxicity. Dysregulation of SG-formation has also been linked to neurodegeneration, supporting the hypothesis that SGs play a critical role in cell survival. Here, the formation and regulation of SGs have been investigated in an inner ear context using a combination of inner ear-derived UB/OC-2 cells, cochlear explants and the in-vivo mouse cochlea. Cells were labelled for two SG-proteins, TIA-1 and Caprin-1, and polyA+ mRNA was detected within SGs using RNA-immuno-FISH. A novel quantification method was developed to characterise in detail the number and size of SGs upon two stress paradigms, heat shock and arsenite. PolyA+ mRNA was observed to aggregate within SGs following different types of stress, suggesting that SGs are involved in post transcriptional regulation of gene expression in the cochlea. Experiments in cochlear explants suggest that pharmacological induction of SGs promotes outer hair cell survival during aminoglycoside exposure. In addition, SG formation was observed in the in-vivo C57BL/6 cochlea during ageing, suggesting that SGs may be related to cochlear degeneration. Hsp70, previously shown to promote hair cell survival following ototoxicity has been associated with SGs in other systems. Here, Hsp70 expression was evaluated in OC 2 cells following different stressors and evidence suggests it to be a key regulator of SGs. Taken together, these data implicate the SG pathway with maintenance of auditory function as a potential therapeutic target for further investigation.
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Острога, Руслан Олексійович, Руслан Алексеевич Острога, Ruslan Oleksiiovych Ostroha, and S. P. Shevets. "The mineral fertilizer granules encapsulating in a multistage shelf apparatus." Thesis, Sumy State University, 2016. http://essuir.sumdu.edu.ua/handle/123456789/52135.
Повний текст джерелаАнотація:
Currently the production and rational use of fertilizers is extremely important for agriculture, and before science there is a task to develop environmental friendly technologies of manufacturing and use of fertilizers. Nitrogen fertilizers (ammonium nitrate, urea) and phosphorus ones (superphosphate, ammophos) dominate in the range of mineral fertilizers used in all edaphic-climatic zones all over the world. They are transformed in the system soil - plant and provide the needs of growing plants in nutrient components. But along with the well-known advantages these fertilizers have significant drawbacks. They are highly soluble and they are quickly washed out from the arable layer, which leads to surface and groundwater contamination. Also, due to inefficient plant nutrition at different stages of growth, nitrite and nitrate accumulate in the main agricultural products.
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Albaraki, Saeed Mohammed A. "Micromechanical analysis of pharmaceutical granules using advanced experimental imaging methodologies." Thesis, University of Leeds, 2015. http://etheses.whiterose.ac.uk/12207/.
Повний текст джерелаАнотація:
Fundamental level understandings on the processing behaviours of materials in granular and powder form is of high interest to number of engineering industries for example, mining, mineral, pharmaceutical, geotechnical and for advanced material processing applications. Handling and processing of pharmaceutical powders through confined geometries have very important role in pharmaceutical industry and many related powder process engineering sectors. Smooth flow of powders and granules mixtures from the feeding hopper to the compression chamber plays a very crucial role to achieve the integrity and quality of the final product. In this context, establishing clear understandings on the flow and compaction characteristics of particulates is vital. The mechanical behaviour of particulate materials such as powders and grains are different from the conventional states of matter. Depending on the loading levels and geometrical conditions, often they display combined features of solid, liquid and gaseous states. Though an extensive amount of studies are reported in the existing literatures on their mechanical response to loading, there are still a number of challenges to address: (i) Sensing stress distribution in particulate systems is not yet established especially when the size of the particulates are less than a millimetre (ii) Understanding is lacking on whether the stress distribution in initial static filling would influence the dynamic flow trajectories of the particulates when they are allowed to flow from the static state (iii) Micromechanical behaviour of particulates under low levels of external loading is still lacking and (iv) Interaction characteristics of stress and velocity distributions in particulate systems as a function of grain-scale properties and geometrical arrangements are still lacking. The present thesis addresses all of these important challenges in a systematic manner. The research is primarily based on the application of sensing stresses and displacements in particulates using advanced photo stress analysis tomography (PSAT), qualitative velocimetry using colour coding technique (CCT) and quantitative digital particle image velocimetry (DPIV). The required grain-scale properties are characterised comprehensively using a number of standard experimental methods. Where possible, experimental results on the stress and velocity distribution for particulate systems are compared with simulations using discrete element method (DEM) and analytical equations respectively, though the primary focus is on the experimental approaches. A number of outcomes from this research shed new lights and provide fundamental level understandings on the micromechanical properties of particulate systems with relevance to pharmaceutical granules processes.
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Muckley, Philippa L. "A study of RAB3 GTP-binding proteins in the secretory pathways of a mouse pituitary cell line." Thesis, Oxford Brookes University, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287728.
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Franco, Daiane Gil. "Modulação da produção de óxido nítrico por melatonina em cultura de células de cerebelo." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/41/41135/tde-25082010-110730/.
Повний текст джерелаАнотація:
A melatonina, um derivado da serotonina, é o principal produto da glândula pineal. Pode ser produzida também por diversas células e tecidos extrapineais, como retina, trato gastrointestinal, células do sistema imunológico, entre outros. Nos mamíferos exerce diferentes papéis, sendo que, classicamente, é conhecida por atuar como mediadora química da fase escura. A liberação rítmica desse hormônio para a corrente sanguínea e para o líquido cefalorraquidiano marca o ciclo claro-escuro e as estações do ano para os órgãos internos. Além disso, a melatonina atua como moduladora do sistema imunológico e da inflamação, agente citoprotetora e antioxidante. Os mecanismos de ação também são diversos e variam desde receptores de membrana às interações intracelulares. No presente trabalho mostramos que a melatonina inibe a produção de NO ativado por ACh ou BK em cultura de células granulares de cerebelo. Esses agonistas ativam as NOS constitutivas, que são dependentes do aumento de Ca2+ intracelular. A melatonina também bloqueia o aumento de Ca2+ intracelular induzido por ACh, sugerindo que, o efeito dessa indolamina sobre a produção de NO ativado por ACh é, provavelmente, um efeito sobre o aumento de Ca2+ intracelular. Lipopolissacarídeo da parede de bactéria gram-negativa ativa a transcrição da isoforma induzida NOS. A melatonina inibe a expressão dessa enzima e a produção de NO induzidas pela endotoxina bacteriana. Nossos resultados indicam que esses efeitos são dependentes da inibição da via do fator de transcrição NFKB. Em resumo, o presente trabalho mostra que a melatonina inibe a atividade da NOS constitutiva e a expressão da NOS induzida. Esses efeitos são dependentes de mecanismos específicos e devem estar relacionados às diferentes funções celulares.Melatonin, a serotonin derivative, is the main product of the pineal gland. Can also be produced by various extra¬pineal sites as retina, gastrointestinal tract, immune cells, among others. In mammals it has different roles, and, classically, is known to act as a chemistry mediator of the darkness. The rhythmic release of this hormone into the blood and cerebrospinal fluid marks the light¬dark cycle and the seasons to the internal organs. Moreover, melatonin acts as a modulator of the immune system and inflammation, a cytoprotective agent and reduces free radicals formation. The mechanisms of action are also diverse and vary from membrane receptors to intracellular interactions. Here we show that melatonin inhibits the production of NO activated by ACh or BK in cultured cerebellar granule cells. These agonists activate constitutive NOS, which are dependent on increased intracellular Ca2+. Melatonin also blocks acetylcholine-induced Ca2+ intracellular increase, suggesting that, this indolamine effects on NO production activated by ACh is, probably, an effect on the increase of intracellular Ca2+. Lipopolysaccharide of gram¬negative bacteria wall activates the transcription of inducible NOS isoform. Melatonin inhibits the enzyme expression and NO production in granule cerebellar cells activated with the bacterial endotoxin. Our data shows that these effects are dependent on inhibition of nuclear factor kappa B pathway. In summary, the present work shows that melatonin inhibits constitutive NOS activity and inducible NOS expression. These effects are dependent on specific mechanisms and should be related to different cellular functions.
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Vijayakumar, Jeshlee Cyril. "Rôle du domaine de type prion de Imp dans la régulation des granules RNP neuronaux." Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR4099/document.
Повний текст джерелаАнотація:
Les ARNms des cellules eucaryotes sont liés à des protéines de liaison aux ARNs (RBPs) et empaquetés au sein d’assemblages macro-moléculaires appelés granules RNP. Dans les cellules neuronales, les granules RNP de transport sont impliqués dans le transport d’ARNms spécifiques jusqu’aux axones et dendrites, ainsi que dans leur traduction locale en réponse à des signaux externes. Bien que peu de choses soient connues sur l’assemblage et la régulation de ces granules in vivo, des résultats récents ont indiqué que la présence de domaines de type prion (PLDs) dans les RBPs facilite les interactions protéines-protéines et protéines-ARN, favorisant ainsi la condensation de complexes solubles en granules RNP. La RBP conservée Imp est un composant central de granules RNP qui sont transportés dans les axones lors du remodelage neuronal chez la drosophile. De plus, la fonction de Imp est nécessaire au remodelage des axones lors de la maturation du système nerveux de drosophile. Une analyse de la séquence de la protéine Imp a révélé qu’en plus de quatre domaines de liaison aux ARNs, Imp contient un domaine C-terminal désordonné enrichi en Glutamines et Serines, deux propriétés caractéristiques des domaines PLDs. Lors de ma thèse, j’ai étudié la fonction de ce PLD dans le contexte de l’assemblage et du transport des granules RNP. J’ai observé en culture de cellules que les granules Imp s’assemblent en absence de PLD, bien que leur nombre et leur taille soient augmentés. Des protéines présentant une séquence PLD mélangée, au contraire, s’accumulent dans des granules au nombre et à la taille normale, indiquant que l’état désordonné de ce domaine, et non sa séquence primaire, est essentiel à l’homéostasie des granules. De plus, des expériences de FRAP réalisées en culture de cellule et in vivo ont révélé que le domaine PLD de Imp favorise la dynamique des granules. In vivo, ce domaine est nécessaire et suffisant à l’accumulation axonale de Imp. Comme montré par une analyse en temps réel, l’absence de domaine PLD aboutit également à une diminution du nombre de granules axonaux motiles. Fonctionnellement, le domaine PLD de Imp est essentiel au remodelage neuronal car des protéines sans ce domaine ne sont pas capables de supprimer les défauts de repousse axonale observés après inactivation de imp. Enfin, la génération d’un variant de Imp dans lequel le domaine PLD a été déplacé en N-terminus a montré que les fonctions du PLD dans le transport des granules et dans leur assemblage sont découplées, et que la modulation des propriétés des granules Imp médiée par le domaine PLD n’est pas nécessaire au remodelage neuronal in vivo. En conclusion, mes résultats ont montré que le domaine PLD de Imp n’est pas nécessaire à l’assemblage des granules RNP Imp, mais régule leur nombre et leur dynamique. De plus, mon travail a mis en évidence une fonction inattendue pour un domaine PLD dans le transport axonal et le remodelage des neurones lors de la maturation du système nerveuxEukaryotic mRNAs are bound by RNA Binding Proteins (RBP) and packaged into diverse range of macromolecular assemblies named RNP granules. In neurons, transport RNP granules are implicated in the transport of specific mRNAs to axons or dendrites, and in their local translation in response to external cues. Although little is known about the assembly and regulation of these granules in vivo, growing evidence indicates that the presence of Prion Like domains (PLD) within RBPs favours multivalent protein–protein and protein-RNA interactions, promoting the transition of soluble complexes into RNP granules. The conserved RBP Imp is as a core component of RNP granules that are actively transported to axons upon neuronal remodelling in Drosophila. Furthermore, Imp function was shown to be required for axonal remodelling during Drosophila nervous system maturation. Analyses of the domain architecture of the Imp protein revealed that, in addition to four RNA binding domains (RBD), Imp contains a Cterminal domain showing a striking enrichment in Glutamines and Serines, which is one of the characteristics of a PLD. During my PhD, I explored the function of the PLD in the context of granule assembly and transport. In cultured cells, I observed that Imp granules assembled in the absence of the PLD, however their number and size were increased. Proteins with scrambled PLD sequence accumulated in granules of normal size and number, implying that the degree of disorder of this domain, and not its sequence, is essential for granule homeostasis. Moreover, FRAP experiments, performed on cultured cells and in vivo, revealed that Imp PLD is important to maintain the turnover of these granules. In vivo, this domain is both necessary and sufficient for efficient transport of Imp granules to axons. These defects are associated with a reduction on the number of motile granules in axons. Furthermore, mutant forms lacking the PLD do not rescue the axon remodelling defects observed upon imp loss of function. Finally, a swapping experiment in which I moved Imp PLD from the C-terminus to the N-terminus of the protein revealed that the functions of Imp PLD in granule transport and homeostasis are uncoupled, and that PLD-dependent modulation of Imp granule properties is dispensable in vivo. Together, my results show that Imp PLD of is not required for the assembly of RNP granules, but rather regulates granule number and dynamics. Furthermore, my work uncovered an unexpected in vivo function for a PLD in axonal transport and remodelling during nervous system maturation
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Fung, Gabriel. "Interplay between stress granules, cellular stress response, and coxsackievirus B3 infection." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/58510.
Повний текст джерелаАнотація:
Viral infection affects a multitude of cellular processes to facilitate successful replication. Such responses include the formation of stress granules (SGs) and the activation of autophagy. SGs are stalled translational complexes and function to restore cellular homeostasis after stress. Autophagy is a cellular process that recycles misfolded proteins and damaged organelles and plays an important role in various stress responses. We previously demonstrated that infection with Coxsackievirus B3 (CVB3), a common human pathogen for viral myocarditis, disrupts the autophagic process to support effective viral replication. However, the interplay between CVB3 and SGs, and the ability of SGs to regulate autophagy have not been investigated. Here we showed that SGs are formed early and actively disassembled late during CVB3 infection due to viral protease 3Cpro-mediated cleavage of Ras-GAP SH3 domain binding protein 1 (G3BP1), a key nucleating protein of SGs. Overexpression of G3BP1 inhibits CVB3 replication, indicating an anti-viral function of SGs. We further demonstrated that the C-terminal product of G3BP1 has a toxic gain-of-function that further inhibits SG formation. We also examined the interaction between CVB3 and the transactive response DNA-binding protein-43 (TDP-43), an RNA binding protein that mislocates to SGs under cellular stress. We found that TDP-43 is translocated from the nucleus to SGs upon infection through the activity of viral protease 2Apro, followed by cleavage by protease 3Cpro. The C-terminal product of TDP-43 is quickly degraded by the proteasome, whereas the N-terminal truncate acts as a dominant-negative mutant that inhibits the function of native TDP-43 in alternative RNA splicing. Knockdown of TDP-43 results in an increase in viral titres, suggesting a protective role for TDP-43 in CVB3 infection. Lastly, we explored the possible role of G3BP1-SGs in regulating autophagy. We showed that G3BP1 inhibits autophagic flux, likely by binding to cytoplasmic signal transducer and activator of transcription 3 (STAT3). Taken together, our results reveal that the host SGs and associated proteins, including G3BP1 and TDP-43, are utilized and modified during CVB3 infection to promote efficient viral replication and induce viral pathogenesis. Moreover, we propose a novel mechanism by which G3BP1 binds cytoplasmic STAT3 to inhibit autophagy.Medicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate