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1
Saba, Yasaman. "Déterminants génétiques des marqueurs IRM du vieillissement vasculaire cérébral." Electronic Thesis or Diss., Bordeaux, 2024. http://www.theses.fr/2024BORD0466.
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Au cours des dernières années l’espérance de vie accrue a conduit à une augmentation majeure du nombre de nouveaux patients atteints de maladies neurologiques communes, notamment AVC et démence. Des preuves croissantes suggèrent que des déterminants précoces tout au long de la vie, y compris des facteurs génétiques, jouent un rôle crucial dans l'apparition de ces maladies. La maladie des petits vaisseaux cérébraux (MPVC) est une cause majeure d'AVC, de déclin cognitif et de démence. La MPVC est le plus souvent « occulte », détectable en imagerie cérébrale en l'absence de manifestations cliniques. Les marqueurs en IRM cérébrale de la MPVC, qui peuvent être mesurés de manière non invasive dans de grandes cohortes, peuvent fournir des informations cruciales sur les mécanismes physiopathologiques sous-tendant AVC et démences. Les hypersignaux de la substance blanche (HSB), les lacunes, les microhémorragies cérébrales et les espaces périvasculaires sont les marqueurs de MPVC les plus souvent étudiés en IRM, tandis que l'imagerie par tenseur de diffusion (DTI) offre de nouvelles opportunités pour explorer la susceptibilité à la MPVC tout au long de la vie. Déchiffrer ces facteurs de risque génétiques de la MPVC, y compris à des stades précoces de la vie, est un outil puissant pour comprendre les mécanismes moléculaires menant à cette maladie. Dans cette thèse, nous avons exploré les déterminants génétiques des marqueurs d'IRM de la MPVC dans la population générale tout au long de la vie, en réalisant de grandes métaanalyses collaboratives d'études d'association génétiques pangénomiques (GWAS), incluant jusqu'à 58,403 participants de la population générale. Tout d'abord, nous avons réalisé une GWAS des HSB stratifiée sur la présence ou absence d'hypertension artérielle. Nos résultats apportent un nouvel éclairage sur les effets modificateurs de l'hypertension artérielle sur la susceptibilité génétique aux HSB. Deuxièmement, nous avons examiné les déterminants génétiques d'un nouveau marqueur en DTI, la « peak width of skeletonized mean diffusivity » (PSMD), en réalisant une première GWAS de PSMD, tout au long de la vie. Nous avons identifié 25 nouveaux loci associés à un PSMD plus élevé, avec une bonne corrélation de la taille d’effets entre des populations européennes et asiatiques. De plus, dans une étude d'association sur l'exome entier à partir de données de séquençage panexomique, des variants rares et la combinaison de variants rares avec perte de fonction ou de variants « singleton » dans 4 gènes différents étaient associés au PSMD. Un volume d’HSB déterminé génétiquement était associé significativement à un PSMD plus élevé non seulement à tous les âges de la vie adulte mais également chez l’enfant. Par ailleurs, les variants communs associés à un PSMD élevé étaient enrichis en gènes exprimés dans les cellules endothéliales cérébrales foetales, suggérant des effets développementaux. En conclusion, ce travail fournit de nouvelles informations sur la génomique des formes complexes de MPVC, tout au long de la vie, dans différents groupes ethniques, et en tenant compte de la présence d'hypertension artérielle, le facteur de risque le plus courant de MPVC. Ces résultats sont informatifs pour le développement de stratégies préventives et thérapeutiques pour la MPVC et ses complications, un enjeu majeur de santé publiqueOver the last century, life expectancy has increased dramatically, contributing to a sharp increase in the number of patients with common neurological disease, especially stroke and dementia. Mounting evidence suggests that early life factors, including genetic factors, play a crucial role in the occurrence of such diseases. Cerebral small vessel disease (cSVD) is a major cause of stroke, cognitive decline and dementia. cSVD is most often covert, detectable on brain images in the absence of clinical manifestations. Brain magnetic resonance imaging (MRI) markers of cSVD, which can be measured non-invasively in large population, can provide crucial insights into the cause of late-life neurological diseases. White matter hyperintensities (WMH), lacunes, cerebral microbleeds, and perivascular spaces are the most commonly studied MRI-markers of cSVD, while diffusion tensor imaging (DTI) offers new opportunity to explore susceptibility to cSVD across the lifespan. Deciphering these genetic risk factors of cSVD, including in early life, is a powerful tool to decipher molecular mechanisms leading to this disease. In this thesis, we explored the genetic determinants of MRI-markers of cSVD in the general population across the lifespan, by conducting large collaborative meta-analyses of genome-wide association studies (GWAS) in up to 58,403 participants from the general population. First, we conducted a GWAS of WMH stratified on hypertension status. Our results shed new light into modifying effects of high blood pressure on genetic susceptibility to WMH. Second, we examined the genetic underpinnings of an emerging DTI marker, peak width of skeletonized mean diffusivity (PSMD), by conducting the first GWAS of PSMD, across the lifespan. We identified up to 25 novel genetic risk loci for PSMD, with good effect size correlation across European and East-Asian ancestries. Additionally, in a whole-exome association study (derived from whole exome sequencing), rare variants and burden of rare loss-of-function or singleton variants in 4 different genes were associated with PSMD. Genetically determined larger volume of WMH was associated with higher PSMD from early childhood to older age. Moreover, common PSMD risk loci were enriched in genes expressed in fetal brain endothelial cells. In conclusion, this work provides new insights into complex genomics of cSVD across the lifespan, across ancestries, and in interaction with hypertension, the most common risk factor of cSVD. These results are informative for the development of efficient preventive and therapeutic strategies for cSVD and its complications, a major public health challenge
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Nakahira, Yoichi. "Circadian Clock-Regulated Transcription of the psbD Light-Responsive Promoter (psbD LRP) in Wheat Chloroplasts." Kyoto University, 1998. http://hdl.handle.net/2433/182388.
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Kyoto University (京都大学)0048
新制・課程博士
博士(人間・環境学)
甲第7534号
人博第48号
10||158(吉田南総合図書館)
新制||人||11(附属図書館)
UT51-98-W278
京都大学大学院人間・環境学研究科人間・環境学専攻
(主査)教授 豊島 喜則, 教授 丸山 圭蔵, 教授 竹安 邦夫, 教授 藤堂 剛
学位規則第4条第1項該当
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Pelikán, Leoš. "Průmyslový PSD regulátor." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2012. http://www.nusl.cz/ntk/nusl-219666.
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This master’s thesis deal with principles temperature measurement using resistive temperature sensor PT100 and algorithm design PSD controler. In Work is includ description problems temperature measurement and way evaluation by means of mikrokontroler, which by PWM output controls supplied heat power. Next is here described method realization controls device for heating electric furnace with setup via Ethernet.
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Arabgol, Raheleh. "MBBR Produced Solids: Particle Characteristics, Settling Behaviour and Investigation of Influencing Factors." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/41919.
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The separation of solids from biological wastewater treatment is an important step in the treatment process, as it has a significant impact on effluent water quality. The moving bed biofilm reactor (MBBR) technology is a proven upgrade or replacement wastewater treatment system for carbon and nitrogen removal. However, a challenge of this technology is the characteristics of the effluent solids that results in their poor settlement; with settling being the common method of solids removal. The main objective of this research is to understand and expand the current knowledge on the settling characteristics of MBBR produced solids and the parameters that influence them. In particular, in this dissertation, the impacts are studied of carrier types, biofilm thickness restraint design of carriers, and varying carbonaceous loading rates on MBBR performance, biofilm morphology, biofilm thickness, biofilm mass, biofilm density, biofilm detachment rate, solids production, particle size distribution (PSD) and particle settling velocity distribution (PSVD).
With this aim, three MBBR reactors housing three different carrier types were operated with varying loading rates. In order to investigate the effect of carrier geometrical properties on the MBBR system, the conventional, cylindrically-shaped, flat AnoxK™ K5 carrier with protected voids was compared to two newly-designed, saddle-shaped Z-carriers with the fully exposed surface area. Moreover, the AnoxK™ Z-200 carrier was compared to the AnoxK™ Z-400 carrier to evaluate the biofilm thickness restraint design of these carriers, where the Z-200 carrier is designed for greater biofilm thickness-restraint. The Z-200 carrier is designed to limit the biofilm thickness to the level of 200 µm as opposed to 400 µm for the Z-400 carrier. Finally, to investigate the effects of varying carbonaceous loading rates on system removal performance, biofilm characteristics and solids characteristics, further analyses were performed at three different loading rates of 1.5 to 2.5 and 6.0 g-sBOD/m2·d in steady-state conditions. The PSD and the PSVD analyses were combined to relate these two properties. A settling velocity distribution analytical method, the ViCAs, was applied in combination with microscopy imaging and micro-flow imaging to investigate the relation of PSD and settling behaviour of MBBR produced particles.
The obtained results have indicated that the carrier type significantly impacted the MBBR performance, biofilm, and particle characteristics. As such, the K5 carrier MBBR system demonstrated a statistically significantly higher carbonaceous removal rate and efficiency (3.8 ± 0.3 g-sBOD/m2·d and 59.9 ± 3.0% sBOD removal), higher biofilm thickness (281.1 ± 8.7 μm), higher biofilm mass per carrier (43.9 ± 1.0 mg), lower biofilm density (65.0 ± 1.5 kg/m3), lower biofilm detachment rate (1.7 ± 0.7 g-TSS/ m2·d) and hence lower solids production (0.7 ± 0.3 g-TSS/d) compared to the two Z-carriers. The Z-carriers' different shape exposes the biofilm to additional shear stress, which could explain why the Z-carriers have thinner and denser biofilm, resulting in higher solids production and lower system performance in comparison with K5. Moreover, the carrier type was also observed to impact the particle characteristics significantly. PSD analysis demonstrated a higher percentage of small particles in the Z-carrier system effluent and hence a significantly lower solids settling efficiency. Therefore, the solids produced in the K5 reactor have shown enhanced settling behaviour, consisting of larger particles with faster settling velocities compared to Z-carriers.
This dissertation also investigated the effects of restraint biofilm thickness on MBBR performance by comparing the Z-200 biofilm thickness-restraint carrier to the Z-400 carrier. No significant difference was observed in removal efficiency, biofilm morphology, biofilm density, biofilm detachment rate, and solids production between the Z-200 to the Z-400 carriers. The PSD and the PSVD analyses did not illustrate any significant difference in the particles’ settling behaviour for these two biofilm thickness restraint carriers, indicating that the biofilm thickness-restraint carrier design was not a controlling factor in the settling potential of MBBR produced solids.
Finally, this research studied the effect of varying loading rates and demonstrated a positive, strong linear correlation between the measured sBOD loading rate and the removal rate, indicating first-order BOD removal kinetics. The biofilm thickness, biofilm density and biofilm mass decreased when the surface area loading rate (SALR) was increased from 2.5 to 6.0 g-sBOD/m2·d. The solids retention time (SRT) was also shown to decrease by increasing the SALR, where the lowest SRT (1.7 ± 0.1 days) was observed at the highest SALR, with the highest cell viability (81.8 ± 1.7%). Significantly higher biofilm detachment rate and yield were observed at SALR 2.5, with the thickest biofilm and a higher percentage of dead cells. Consequently, a higher fraction of larger and rapidly settling particles was observed at SALR of 2.5 g-sBOD/m2·d, which leads to a significantly better settling behaviour of the MBBR effluent solids.
This study expands the current knowledge of MBBR-produced particle characteristics and settling behaviour. A comprehensive understanding of the MBBR system performance and the potential influencing factors on the MBBR produced solids, particle characteristics, and their settleability will lead to optimized MBBR design for future pilot- and full-scale applications of the MBBR.
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Grosof, Isaac (Isaac B. ). "Secure communication : CDS, PIR, PSM." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/113150.
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Thesis: M. Eng., Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2017.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Cataloged from student-submitted PDF version of thesis.
Includes bibliographical references (pages 52-53).
Private Information Retrieval is the problem of querying two servers to nd a value in a database, while keeping the index private. We extend this problem to Generalized Wildcard PIR, where we instead query an aggregate of the entries whose indices match a pattern, called a generalized wildcard, which species what values each segment of the indices may take. We give a construction for this variant with similar communication to that of the best PIR protocols known. We study information theoretic models in cryptography, namely Private Information Retrieval, Conditional Disclosure of Secrets, and Private Simultaneous Messages. We give extensions of PIR and CDS in the area of generalized wildcards, and give constructions for those extensions. We discuss directions towards more ecient protocols, and raise open questions.
by Isaac Grosof.
M. Eng.
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Ribeiro, Ricardo Luiz Mendes. "PFL: do PDS ao PSD." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/8/8131/tde-09092016-130237/.
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Este trabalho aborda a trajetória do PFL (Partido da Frente Liberal), desde a sua fundação em 1985 até 2010, quando já sob nova denominação DEM deixou de contar com seus três principais líderes: Jorge Bornhausen, Marco Maciel e Antônio Carlos Magalhães. A tese busca explicar as razões do sucesso do partido, até 2002, e de sua decadência a partir de então. Como principal hipótese, argumenta-se que a conexão com o governo federal foi a causa principal tanto do sucesso quanto da decadência da legenda, desencadeada pela passagem do PFL para a oposição após a vitória do Partido dos Trabalhadores na eleição presidencial de 2002. A análise da inserção do PFL no presidencialismo de coalizão e a narrativa da atuação dos três principais líderes do partido junto às altas esferas do governo federal foram os principais subsídios para a construção indutiva da comprovação da hipótese acima formulada.This work addresses the path of the PFL (Partido da Frente Liberal), since its foundation in 1985 until 2010, when already under the new name - DEM - no longer count on its three main leaders: Jorge Bornhausen, Marco Maciel and Antonio Carlos Magalhães. The thesis seeks to explain the reasons for the party\'s success, until 2002, and its decline from then on. As the main hypothesis it is claimed that the connection to the federal government was the main cause of both, the success and the decline, triggered by the passage of the PFL to the opposition after the Workers Party (PT) victory in the presidential election of 2002. The analysis of PFL in the Brazilian coalitional presidentialism and the narrative of the three main important party leaders connections with high ranks of federal government provide the inductive proof of the above hypothesis.
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Woythal, Nadine [Verfasser]. "In vitro Validierung der in vivo PSMA-Expression in der 68Ga-PSMA-PET/CT beim primären Prostatakarzinom durch die Immunohistochemie / Nadine Woythal." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1179778480/34.
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Calais, Jérémie. "PSMA-targeted theranostics : from research to standard-of-care." Electronic Thesis or Diss., université Paris-Saclay, 2023. http://www.theses.fr/2023UPAST192.
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L'objectif de ce manuscrit de thèse Thèse de doctorat par Validation des Acquis de l'Expérience (VAE) est de mettre en évidence les principales études de recherche menées à UCLA qui ont conduit à l'implémentation clinique des technique théranostique ciblant le PSMA aux États-Unis. Le manuscrit est divisé en 2 parties : l'imagerie et la thérapie.Dans la première partie sont fournis les essais pivots d'efficacité diagnostique utilisés pour l'autorisation par la FDA du 68Ga-PSMA-11 (Article #1: Performance diagnostique de la TEP-PSMA pour la localisation de la récidive du cancer de la prostate: un essai clinique d'imagerie prospective multicentrique de phase 3 (n=635), PMID 30920593; Article #2: Performance diagnostique de la TEP-PSMA pour la détection des métastases ganglionnaires pelviennes avant prostatectomie radicale et curage ganglionnaire pelvien: un essai clinique d'imagerie prospective multicentrique de phase 3 (n=764), PMID 34529005), des études comparatives comparant la TEP-PSMA aux techniques d'imagerie standard (Article #3: TEP/TDM a la 18F-Fluciclovine et au 68Ga-PSMA-11 chez les patients présentant une récidive biochimique après prostatectomie avec un taux de PSA ≤2,0 ng/ml: un essai d'imagerie comparative prospectif monocentrique (n=50), PMID 31375469; Article #4: Comparaison de la TEP/TDM-PSMA et de l'IRMmp avec référence par histopathologie dans la détection, la localisation intra-prostatique et la détermination de l'extension locale du cancer primitif de la prostate: résultats dans une cohorte monocentrique d'un essai prospectif (n=74), PMID 34649942) et une étude montrant un impact significatif sur la prise en charge (Article #5: Cartographie par TEP/TDM-PSMA de la récidive biochimique du cancer de la prostate après prostatectomie radicale chez 270 patients avec un taux de PSA<1,0 ng/ml : Impact sur la planification de la radiothérapie de rattrapage (n=270), PMID 29123013) qui a conduit à un essai randomisé visant à montrer une amélioration des résultats cliniques grâce à la TEP-PSMA (Article #6: Essai randomisé prospectif de phase 3 de radiothérapie de rattrapage du cancer de la prostate guidée par TEP-PSMA [PSMA-SRT] (n=193), PMID 30616601; Article #7: Mise à jour de l'essai PSMA-SRT NCT03582774: un Essai randomisé prospectif de phase 3 de radiothérapie de rattrapage du cancer de la prostate guidée par TEP-PSMA (n=193), PMID 33386288).Dans la deuxième partie sont présentés les résultats du premier essai de phase 2 de la thérapie au 177Lu-PSMA aux USA qui a précédé l'essai VISION (Article #8 : Essai prospectif de phase 2 de radiothérapie moléculaire au 177Lu-PSMA-617 pour cancer de la prostate métastatique résistant à la castration (RESIST-PC): Résultats d'efficacité de la cohorte UCLA (n=43), PMID 34016732; Article #9: Tolérance et sécurité de la radiothérapie moléculaire au 177Lu-PSMA-617: résultats de l'essai prospectif multicentrique de phase 2 RESIST-PC NCT03042312 (n=64), PMID 34272322), des études rétrospectives multicentriques visant à affiner les critères de sélection TEP-PSMA (Article #10: Suivi des patients négatifs au PSMA par critères TEP-PSMA de l'essai VISION traités par 177Lu-PSMA: une analyse rétrospective multicentrique (n=301), PMID 35273096; Article #11: Ratio tumeur/glande salivaire par TEP-PSMA pour prédire la réponse à la thérapie par 177Lu-PSMA: une étude rétrospective multicentrique internationale (n=237), PMID 36997329; Article #12: Nomogrammes pour prédire les résultats après traitement au 177Lu-PSMA chez les patients atteints d'un cancer de la prostate métastatique résistant à la castration: une étude rétrospective internationale multicentrique (n=270), PMID 34246328) et une revue narrative des mécanismes de résistance à la thérapie au 177Lu-PSMA (Article #13: Prédicteurs de réponse et utilisation dans le monde réel de la radiothérapie moléculaire ciblée du cancer de la prostate: PSMA et au-delà. PMID 35609224)The aim of this manuscript for PhD by Accreditation of Prior Learning is to highlight the key research studies conducted at UCLA which lead to the clinical implementation of PSMA-theranostics in the US. The manuscript is divided in 2 parts: imaging and Therapy.In the first part are provided the pivotal trials of diagnostic efficacy used for the FDA approval of 68Ga-PSMA-11 (Article #1: Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Multicenter Single-Arm Phase 3 Clinical Trial (n=635), WP Fendler at al. JAMA Oncol 2019 PMID 30920593; Article #2: Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial (n=764), TA Hope et al. JAMA Oncol 2021 PMID 34529005), head-to-head comparison trials comparing PSMA PET to standard of care imaging techniques (Article #3: 18F-Fluciclovine and 68Ga-PSMA-11 PET/CT in patients with biochemical recurrence after prostatectomy at PSA levels of ≤2.0ng/ml: a prospective single-center single-arm comparative imaging trial (n=50), J Calais et al. Lancet Oncol 2019 PMID 31375469; Article #4: Head-to-head comparison of 68Ga-PSMA-11 PET/CT and mpMRI with histopathology gold-standard in the detection, intra-prostatic localization and local extension of primary prostate cancer: results from a prospective single-center imaging trial (n=74), I Sonni et al. J Nucl Med 2022 PMID 34649942) and a study showing significant impact on management (Article #5: 68Ga-PSMA-11 PET/CT mapping of prostate cancer biochemical recurrence following radical prostatectomy in 270 patients with PSA<1.0ng/ml: Impact on Salvage Radiotherapy Planning (n=270), J Calais et al. J Nucl Med 2018 PMID 29123013) that lead to a randomized imaging trial powered for clinical outcome (Article #6: Randomized prospective phase 3 trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT] (n=193), J Calais et al. BMC cancer 2019 PMID 30616601; Article #7: Update from PSMA-SRT Trial NCT03582774: A Randomized Phase 3 Imaging Trial of Prostate-specific Membrane Antigen Positron Emission Tomography for Salvage Radiation Therapy for Prostate Cancer Recurrence Powered for Clinical Outcome (n=193), J Calais et al. Eur Urol Focus PMID 33386288).In the second part are provided the results of the first phase 2 trial of 177Lu-PSMA therapy in the US that preceded the VISION trial (Article #8: Prospective phase 2 trial of PSMA-targeted molecular RadiothErapy with 177Lu-PSMA-617 for metastatic Castration-reSISTant Prostate Cancer (RESIST-PC): Efficacy results of the UCLA cohort (n=43), J Calais et al. J Nucl Med 2021 PMID 34016732; Article #9: Safety of PSMA-targeted molecular radioligand therapy with 177Lu-PSMA-617: results from the prospective multicenter phase 2 trial RESIST-PC NCT03042312 (n=64), J Calais et al. J Nucl Med 2021 PMID 34272322), multicenter retrospective studies aiming at refining the PSMA-PET selection criteria (Article #10: Outcome of patients with PSMA-PET/CT screen failure by VISION criteria and treated with 177Lu-PSMA therapy: a multicenter retrospective analysis (n=301), M Hotta et al. J Nucl Med 2022 PMID 35273096; Article #11: PSMA PET Tumor-to-Salivary Gland Ratio to Predict Response to 177Lu-PSMA Radioligand Therapy: An International Multicenter Retrospective Study (n=237), M Hotta et al. J Nucl Med 2023 PMID 36997329; Article #12: Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicenter, retrospective study (n=270), A Gafita et al. Lancet Oncol 2021 PMID 34246328) and a narrative review of the mechanisms of resistance to 177Lu-PSMA therapy (Article #13: Predictors and Real-World Use of Prostate-Specific Radioligand Therapy: PSMA and Beyond. A Gafita et al. Am Soc Clin Oncol Educ Book 2022 PMID 35609224)
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Zrůst, Vojtěch. "Implementation of Case Tool for PSD." Master's thesis, Vysoká škola ekonomická v Praze, 2016. http://www.nusl.cz/ntk/nusl-203866.
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The objective of this thesis is analysis, design and development of an application used for the Process-State Diagram (PSD). Purpose of this thesis is to make PSD tool available for as many users as possible in order to make it a standard tool for managers and analysts. The theoretical part analyzes the basic functionality that should be included in the first version of this app and the strategy and the method of implementation. An important part of the analysis is to compare the three types of applications: desktop, web and mobile; and their relevance to a given problem. The practical part includes the actual implementation and the necessary steps to deploy the application.
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Walker, Natalie. "PSMA-1-Doxorubicin Conjugates for Targeted Therapy of Prostate Cancer." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554496393458066.
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Frigerio, B. "PSMA-SPECIFIC ANTIBODY FRAGMENTS FOR PROSTATE CANCER IMAGING AND THERAPY." Doctoral thesis, Università degli Studi di Milano, 2013. http://hdl.handle.net/2434/221052.
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In this study we want to evaluate the potentiality of the use of a single chain Fv (scFv) for molecular imaging and therapy of Prostate Cancer. The target of this scFv is the Prostate Specific Membrane Antigen (PSMA), a type II transmembrane protein overexpressed in advances stages of this disease. In the past we have generated the murine antibody D2B recognizing hPSMA, whose diagnostic specificity has been investigated in xenograft murine models by imaging.
In order to obtain a smaller protein able to better penetrate the tissues we decided to convert the murine monoclonal antibody D2B into a format like scFv. This format, due to its smaller size, have also the advantage, compare to the entire antibody, to have a faster clearance from the blood.
The scFv has been constructed and its functionality has been tested with success on LNCaP cells. Using BIAcore (a technology able to measure the kinetic interaction between two molecules) we showed that the affinity of our scFv is still remarkable despite its monovalent binding.
One goal of the present study is the assessment of potential role of this antibody fragment as diagnostic reagent for the development of radiopharmaceuticals for tumor characterization and molecular imaging. A second goal of the project is the production of a completely human antibody fragment against hPSMA in order to develop a reagent more suitable for therapy. We used phage display technology to convert the murine antibody in a human antibody applying guided selection technology which permits to generate an antibody with the specificity and functionality of the starting rodent mAb.
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二コール, コマファイ, and Nicolle Comafay. "The sociology of people with special needs in times of disaster(PSND): assessing the special needs of PSND using person-in-environment model of vulnerability." Thesis, https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB12416080/?lang=0, 2011. https://doors.doshisha.ac.jp/opac/opac_link/bibid/BB12416080/?lang=0.
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Marchner, Bartholomäus [Verfasser], and Dirk [Akademischer Betreuer] Hellwig. "Korrelationsanalyse von PSMA-Expression und Mineralisation in Knochenmetastasen von Prostatakarzinomen in vivo gemessen mit Ga-68-HBED-CC-PSMA-PET/CT / Bartholomäus Marchner ; Betreuer: Dirk Hellwig." Regensburg : Universitätsbibliothek Regensburg, 2021. http://d-nb.info/1227039654/34.
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Escudero, Castellanos Alondra. "Radiofármacos oncoteranósticos inhibidores de PSMA dirigidos a la medicina nuclear traslacional." Tesis de doctorado, Universidad Autónoma del Estado de México, 2020. http://hdl.handle.net/20.500.11799/109500.
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El antígeno prostático específico de membrana (PSMA) se expresa normalmente en células epiteliales de la próstata, pero se sobreexpresa en el 95% de los cánceres de próstata metastásicos (mPCa). Es por eso que PSMA es un apropiado objetivo molecular para la obtención de imágenes y radioterapia de mPCa utilizando radiofármacos específicos.
Por otro lado, los radiopéptidos basados en la secuencia Arg-Gly-Asp (RGD) muestran una alta afinidad y selectividad por las integrinas α(v)β(3). Como resultado, estos péptidos son útiles para unirse a tumores debido a la sobreexpresión de integrinas en la neovasculatura tumoral. De forma similar, el péptido bombesina (BN) posee alta expresión en etapas tempranas del cáncer prostático (PCa), el cual se une específicamente al receptor de péptido liberador de gastrina (GRPr), que es sobreexpresado en el 84% del PCa humano. GRPr es clínicamente relevante debido a su alta expresión en etapas de PCa temprano.
Los tumores humanos muestran heterogeneidad intrínseca y cambios en el fenotipo durante la progresión de la enfermedad, lo que implica diferentes niveles de expresión de los receptores de la superficie celular. La investigación sobre nuevos productos farmacéuticos heterodiméricos radiomarcados con Lu-177 que interactúen con dos blancos moleculares diferentes en células tumorales es una estrategia para mejorar el rendimiento radioterapéutico.
Este estudio tuvo como objetivo sintetizar y caracterizar dos nuevos radiofármacos heterobivalentes, el 177Lu-iPSMA-RGD y el 177Lu-iPSMA-BN, así como evaluar su potencial para enlazarse a células cancerosas que sobreexpresan PSMA, integrinas α(v)β(3) y GRPr, respectivamente. Los radiofármacos fueron preparados con una pureza radioquímica >98%, demostrando alta estabilidad en suero humano, reconocimiento específico con afinidad adecuada hacia los receptores correspondientes, así como capacidad para inhibir la proliferación de células cancerosas. En el caso de la presencia del péptido RGD, se demostró la capacidad para inhibir la señalización de VEGF (efecto antiangiogénico). En el caso de 177Lu-iPSMA-BN se observó una alta captación tumoral in vivo por las células LNCaP y PC3. Las imágenes de micro-SPECT/CT demostraron la capacidad del heterodímero para dirigirse a los tumores, sin aumentar la captación de forma significativa, comparado con sus monómeros, pero siendo captado por los distintos fenotipos de tumores y por lo tanto en las diferentes etapas del cáncer. Los resultados obtenidos justifican realizar estudios preclínicos adicionales para establecer la eficacia terapéutica de los radiofármacos heterodiméricos.El presente trabajo de tesis de doctorado se realizó en el Laboratorio Nacional de Investigación y Desarrollo de Radiofármacos (LANIDER) adscrito a la Gerencia de Aplicaciones Nucleares en la Salud del Departamento de Materiales Radiactivos en el Instituto Nacional de Investigaciones Nucleares (ININ), México. Se realizó con financiamiento del proyecto CONACyT-A1-S-38087.
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Bradbury, Robyn. "The interplay between MDM2 and PSMA in metastatic breast cancer cells." Thesis, Cardiff University, 2016. http://orca.cf.ac.uk/100068/.
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Both mouse double minute (MDM2) and prostate-specific membrane antigen (PSMA) are known to be associated with the progressive properties of cancer. Moreover, overexpression of both molecules has been implicated in an increase in the proliferation, migration and invasion of tumour cells. MDM2 is a negative regulator of tumour suppressor of p53 but also is known to play multiple p53-independent roles in many cancer types. PSMA was originally thought to be solely expressed in prostate tissues and overexpression prostatic cancers; however, recently its expression was reported in various other solid tumours, including those of the breast. Our work showed a possible link between these proteins following knockdown of each molecule in breast cancer cell lines, ZR-75.1 and MDA-MB-231, with targeted siRNA molecules. A decrease of MDM2 and PSMA led to a decrease in the proliferative, adhesive, migratory and invasive capacities of the cell lines. Additionally, knockdown of MDM2 and PSMA led to similar changes in secretion of matrix metalloproteinases (MMPs), with decreases in MMP2 and MMP8 being seen from both breast cell lines investigated. It was then seen that a link between the two protein could be mediated through the phosphorylation status of serine 473 on protein kinase B (AKT). PSMA knockdown in both breast cancer cell lines led to a decrease of AKT phosphorylation and thus a decrease in MDM2 serine 188. Additionally, it was found that MDM2 siRNA leads to an increase in c-JUN serine 63 phosphorylation, and that PSMA siRNA can lead to an increase at the same site, depending on the cell line. These results indicate that MDM2, AKT and PSMA may represent a new pathway which could be targeted for therapy for breast tumours and perhaps other types of cancer.
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Abbas, Atheir Ibrahim. "PSD-95 Regulates Serotonin Receptor Function in vivo." Case Western Reserve University School of Graduate Studies / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=case1237990096.
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Stodieck, Sophia Katharina [Verfasser], Siegrid [Akademischer Betreuer] [Gutachter] Loewel, Tim [Gutachter] Gollisch, and Oliver M. [Gutachter] Schlueter. "The role of postsynaptic density (PSD) proteins PSD-95 and PSD-93 for mouse visual cortical plasticity and vision / Sophia Katharina Stodieck ; Gutachter: Siegrid Loewel, Tim Gollisch, Oliver M. Schlueter ; Betreuer: Siegrid Loewel." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2017. http://d-nb.info/1140641999/34.
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Wilson, Jonathan Robert. "Copper and zinc ligands of Pisum sativum and expression of psMT(_A)." Thesis, Durham University, 1995. http://etheses.dur.ac.uk/5320/.
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The gene, PsMT(_A) is highly expressed in the roots of the garden pea, Pisum sativum. The predicted primary structures of homologues of the PsMT(_A) gene from a range of plant species were compared. Common features are amino and carboxyl terminal domains of approximately 20 residues which are rich in cysteine residues many of which are arranged in the cysteine-Xaa-cysteine (Xaa is not a cysteine) motifs characteristic of metallothionein. The greatest degree of sequence conservation between these predicted gene products occurs within the cysteine rich domains. Two principal (most highly represented in the available sample) categories of sequence were identified on the basis of the arrangement of the cysteine residues within the amino termina domain. A secondary structure motif (β-strand) was predicted (using a computer algorithm) to occur in a conserved position in the central domain linking the two cysteine rich domains of these predicted proteins. This feature is not apparent in the structure of metallothioneins from other species. A recombinant GST-PsMT(_A) fusion protein was isolated from crude lysates of Escherichia coli. containing the plasmid pGEX3X with PsMT(_A) coding sequence. When isolated from Escherichia coli cells grown in zinc supplemented media it was demonstrated that zinc was associated with the PsMT(_A) moiety of the fusion protein. In aqueous solution the PsMT(_A) moiety of the fusion protein formed discreet degradation products. The fusion protein was insoluble at concentrations greater than 20 mg ml(^-1) which rendered it unsuitable for a structural study of the putative metal binding site(s) by (^113)Cd NMR. An antibody to the GST- PsMT(_A) fusion protein was characterised and the epitope was found to lie within the GST moiety. Comparison of the arrangement of cysteines in the amino terminal domains with the different domains of mammalian metallothionein suggested that the two principal categories of predicted plant metallothionein- like gene products may have different affinities for zinc. The predicted products of the metallothionein-like gene highly expressed in the leaves of Arabidopsis thali ana (AtMT-t2) and the PsMT(_A) gene are representative of the two principal categories identified by sequence analysis. The AtMT-t2 coding sequence was amplified from an Arabidopsis thaliana leaf cDNA library and cloned into the pGEX3X plasmid to allow expression of the protein as a fusion to GST in Escherichia coli. Zinc was associated with the AtMT-t2 moiety of the fusion protein. The pH of 50 % displacement for the GST-AtMT-t2 fusion protein with respect to zinc was 0.25 pH units lower than that for the GST-PsMT(_A) fusion protein indicating that putative metallothionein-like protein from Arabidopsis thaliana may have a higher affinity for zinc. It is feasible that this difference allows AtMT-t2 to compete with endogenous ligands of zinc more effectively than PsMT(_A). Expression of the AtMT-t2 gene in a zinc metallothionein deficient strain of Synechococcus (in collaboration with Dr. J.S. Turner) partially restored zinc tolerance to the transformed cells. The similarity of the cysteine rich domains of the predicted metallothionein-like proteins with metallothionein and the demonstration of metal binding in vitro suggested that these genes may be metal regulated. The effect of variations in the exogenous concentration of the trace metals copper zinc and iron on the expression of the PsMT(_A) gene in the roots of Pisum sativum seedlings was investigated by northern analysis. Induction of PsMT(_A) expression was seen with increasing iron concentrations up to 2.0 µM iron chelate. At this concentration of iron chelate, and above, expression of PsMT(_A), decreased. At concentrations of copper above 100 nM induction of PsMT(_A) expression was seen. Below 100 nM copper PsMT(_A) expression increased with decreasing copper concentrations. This response has not been reported for metallothioneins from other species and may be significant for the role of PsMT(_A) in root tissue. In the presence of 2.0 µM iron zinc concentrations above 5.0 µM induced expression of PsMT(_A). The response to changes in exogenous metal concentrations was rapid. Complete repression of PsMT(_A) transcription occurred within 1 h of transfer to media supplemented with 2.0 µM iron. To date no translational products of plant metallothionein-like genes (excluding the E(_c) protein from Tritticum aestivum) have been identified in plant tissue. Two copper and one zinc complex were identified following ion exchange chromatography of soluble extracts from roots of Pisum sativum. The quantity' of the zinc complex eluted from the matrix was reduced by the addition of iron chelate to the growth media. There was no consistent change in the quantity of copper complex recovered in response to iron. Two copper and one zinc component of low molecular weight were identified following gel filtration chromatography of the above complexes. Following polyacrylamide gel electrophoresis of extracts from roots of Pisum sativum, labelled in vivo with (^35)S cysteine, a band was identified with the characteristics predicted for the product of the PsMT(_A) gene. On two dimensional polyacrylamide gels a doublet of spots was identified (migrating to a low pH as predicted for PsMT(_A)) in an extract from roots of seedlings grown in media not supplemented with iron which were not observed on gels of extracts from seedlings grown in media supplemented with iron. The identity of these polypeptides was not established by sequence analysis.
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Nixon, Peter Julian. "An investigation of the psbA and psbD gene products from higher plants." Thesis, Imperial College London, 1988. http://hdl.handle.net/10044/1/47203.
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Broadhead, Matthew James. "The nanostructural organisation of PSD-95 at the synapse." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/28711.
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Synapses are the communication junctions of the nervous system and contain protein machinery necessary for cognitive functions such as learning and memory. Postsynaptic density protein-95 (PSD-95) is a key scaffolding molecule at the PSD of synapses, yet its sub-synaptic organisation in the mammalian brain remains poorly understood. This thesis presents the use of genetically labelled PSD-95 with super-resolution imaging to resolve its nano-architecture in the mouse brain. To visualize PSD-95, two knock-in mouse lines were generated where the fluorescent proteins eGFP or mEos2 was fused to the carboxyl terminus of the endogenous PSD- 95 protein (PSD-95-eGFP or PSD-95-mEos2). Methods were developed by which fixed tissue sections of PSD-95-eGFP mice were examined using gated-stimulated emission depletion (g-STED) microscopy and PSD-95-mEos2 sections were examined with photoactivatable localisation microscopy (PALM) and quantitative image analysis was developed for both methods. From these platforms it was demonstrated that PSD-95 has a two tiered organisation: it is assembled into nanoclusters (NCs) approximately 140 nm diameter, which form part of the greater envelope of the PSD within synapses. Synapse subtypes were observed as characterised by the number of NCs per PSD. Using double colour g- STED microscopy. It was then asked whether PSD-95 nano-architecture remained the same across different sub-regions of the brain. A survey of PSD-95 was performed from seven different sub-regions of the hippocampus, quantifying ~110,000 NCs within ~70,000 PSDs from across the two super-resolution platforms. It was found that synapses displayed structural diversity both within and between different brain subregions as a function of the number of NCs per PSD. PSD-95 NCs were structurally conserved across the hippocampus, but showed molecular diversity in the abundance of PSD-95 molecules within. The findings of this thesis are: 1) genetic labelling of endogenous proteins combined with super-resolution microscopy is a powerful tool to study synaptic protein organisation in tissue. 2) Synaptic structural diversity in the brain is underlined by the number of PSD-95 NC units per synapse 3) PSD-95 NCs are structurally conserved but molecularly diverse synaptic units of synapses throughout the brain. These findings suggest that cognitive processing at the synapse is based upon a conserved, fundamental, molecular architecture.
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Nzatsi, Nzatsi Max Célio. "Optimisation des procédures d’imagerie à visée dosimétrique en radiothérapie interne vectorisée." Electronic Thesis or Diss., Nantes Université, 2024. http://www.theses.fr/2024NANU1009.
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La radiothérapie interne vectorisée (RIV) connait une croissance significative depuis la dernière décennie, en particulier pour le traitement des stades métastatiques des cancers de la prostate et des tumeurs neuroendocrines en utilisant un vecteur lié au ¹⁷⁷Lu. La posologie thérapeutique consiste actuellement en l'administration d’une activité unique à chaque cure sur plusieurs cycles. Cette méthode uniformisée limite potentiellement une approche personnalisée de leur traitement. En dehors de la surveillance post-thérapie, une voie d'optimisation envisagée pour adapter le traitement au patient serait d'utiliser la dosimétrie pour moduler ces thérapies si tant est qu'une relation dose absorbée-effets cliniques ait été démontrée. La dosimétrie peine à être acceptée en pratique clinique car la démonstration de cette relation n'a pas encore été clairement établie. En effet, les procédures nécessaires à cette dosimétrie sont chronophages et les ressources matérielles et humaines sont limitées ne favorisant donc pas son déploiement et par conséquence la mise en évidence de la relation cherchée. Afin de lever ce verrou, nous avons développé et évalué un réseau antagoniste génératif pour réduire l’empreinte temporelle des imageries nécessaires à la dosimétrie en réduisant, dans un premier temps la durée d’acquisition des projections, puis leur nombre et enfin la combinaison de ces 2 approches. Également, nous avons évalué l'effet de la réduction du nombre de temps-points (venues du patient) au cours d’une cure, sur l’estimation des doses absorbées aux organes à risque et aux tumeurs de patients traités par [¹⁷⁷Lu]Lu-PSMA. Nos résultats ont montré qu'il était possible de réduire la durée d'un examen à visée dosimétrique d'un facteur 5 et de réduire le nombre de venues du patient sans dégradation majeure sur l'estimation des doses absorbée à ses OARs et tumeurs. Ce travail devrait permettre de faciliter la mise en œuvre de l'imagerie à visée dosimétrique dans les services de médecine nucléaire afin de mieux cerner la relation doseeffets cliniques de la RIV au ¹⁷⁷LuVectorized internal radiotherapy (VIR) has seen significant growth over the last decade, particularly for the treatment of metastatic stages of prostate cancer and neuroendocrine tumors using a vector linked to ¹⁷⁷Lu. The current therapeutic dosage consists of administering a single activity dose per cycle across multiple cycles. This standardized method potentially limits a personalized approach to treatment. Beyond post-therapy monitoring, one potential avenue for optimizing treatment personalization would be to use dosimetry to adjust these therapies, provided that a relationship between absorbed dose and clinical effects has been demonstrated. However, dosimetry has struggled to gain acceptance in clinical practice because this relationship has not yet been clearly established. Indeed, the procedures necessary for dosimetry are time-consuming, and material and human resources are limited, which hinders its deployment and, consequently, the demonstration of the desired relationship. To overcome this barrier, we developed and evaluated a generative adversarial network to reduce the time footprint of the imaging required for dosimetry. Initially, this involved reducing the acquisition time for projections, then reducing their number, and finally combining these two approaches. Additionally, we evaluated the effect of reducing the number of time points (patient visits) during a treatment cycle on the estimation of absorbed doses to organs at risk and tumors in patients treated with [¹⁷⁷Lu]Lu-PSMA. Our results showed that it is possible to reduce the duration of a dosimetric examination by a factor of 5 and to reduce the number of patient visits without significant degradation in the estimation of absorbed doses to their OARs and tumors. This work should facilitate the implementation of dosimetric imaging in nuclear medicine departments to better understand the dose-effect relationship of ¹⁷⁷Lu VIR
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Xu, George Jianzhou. "Influence of PSMC and other mineral admixtures on the properties of cement mortar." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp02/NQ30300.pdf.
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Williams, Tiffany L. Kole Ryszard. "Modulation of PSMA splice variants using splice switching oligonucleotides in prostate cancer cells." Chapel Hill, N.C. : University of North Carolina at Chapel Hill, 2006. http://dc.lib.unc.edu/u?/etd,268.
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Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 2006.Title from electronic title page (viewed Oct. 10, 2007). "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Curriculum in Genetics and Molecular Biology." Discipline: Genetics and Molecular Biology; Department/School: Medicine.
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Alcarde, Lais Fernanda. "Estudo de radiomarcação com gálio-68 do inibidor de PSMA baseado em ureia - avaliação comparativa de método automatizado e não automatizado." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/85/85131/tde-30112016-103604/.
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Os métodos para o diagnóstico clínico de câncer de próstata incluem o toque retal e a dosagem do antígeno prostático específico (PSA). Entretanto, o nível de PSA encontra-se elevado em cerca de 20 a 30% dos casos relacionados a patologias benignas, o que resulta em falsos positivos e leva os pacientes a realização de biópsias desnecessárias. O antígeno de membrana prostático específico (PSMA), ao contrário, é sobre expresso no câncer de próstata e encontrado em baixos níveis em órgãos saudáveis. Em razão disso, estimulou-se o desenvolvimento de pequenas moléculas inibidoras do receptor de PSMA, que carreguem agentes de imagem ao tumor e que não sejam prejudicadas pela microvasculatura deste. Estudos recentes sugerem que o quelante HBED-CC contribui intrinsicamente para a ligação do peptídeo inibidor de PSMA baseado em ureia (Glu-ureia-Lys) ao grupo farmacofórico. Este trabalho descreve os estudos de otimização das condições de radiomarcação do PSMA-HBED-CC com 68Ga, utilizando sistema automatizado (módulo de síntese) e método não automatizado, buscando estabelecer uma condição adequada de preparação deste novo radiofármaco, com ênfase no rendimento da marcação e na pureza radioquímica do produto. Também objetivou avaliar a estabilidade do peptídeo radiomarcado em condições de transporte e estudar a distribuição biológica do radiofármaco em camundongos sadios. O estudo dos parâmetros de radiomarcação possibilitou definir um método não automatizado que resultou em alta pureza radioquímica (> 95%), sem a necessidade de purificação do radiomarcado. Já o método de marcação automatizado foi adaptado para utilizar módulo de síntese e software já disponíveis no IPEN, e também resultou em rendimento de síntese elevado (≥ 90%) e superior aos descritos em literatura, com a vantagem associada de maior controle do processo produtivo em atendimento aos requisitos de Boas Práticas de Fabricação. O estudo dos parâmetros de radiomarcação permitiu a obtenção do PSMA-HBED-CC-68Ga com atividade específica superior à utilizada em estudos clínicos publicados (≥ 140,0 GBq/μmol), com estabilidade suficientemente longa, que permitirá o transporte às clínicas para aplicação na obtenção de imagens diagnósticas. Os perfis de biodistribuição e farmacocinético do peptídeo radiomarcado foram compatíveis com os encontrados na literatura. Conclui-se que o PSMA-HBED-CC-68Ga, é uma importante ferramenta de diagnóstico do câncer de próstata por imagem PET, pode ser produzido tanto por método automatizado ou não automatizado, com alta pureza radioquímica, alto rendimento de síntese e estabilidade do radiofármaco.The methods for clinical diagnosis of prostate cancer include rectal examination and the dosage of the prostatic specific antigen (PSA). However, the PSA level is elevated in about 20 to 30% of cases related to benign pathologies, resulting in false positives and leading patients to unnecessary biopsies. The prostate specific membrane antigen (PSMA), in contrast, is over expressed in prostate cancer and founded at low levels in healthy organs. As a result, it stimulated the development of small molecule inhibitors of PSMA, which carry imaging agents to the tumor and are not affected by their microvasculature. Recent studies suggest that the HBED-CC chelator intrinsically contributes to the binding of the PSMA inhibitor peptide based on urea (Glu-urea-Lys) to the pharmacophore group. This work describes the optimization of radiolabeling conditions of PSMA-HBED-CC with 68Ga, using automated system (synthesis module) and no automated method, seeking to establish an appropriate condition to prepare this new radiopharmaceutical, with emphasis on the labeling yield and radiochemical purity of the product. It also aimed to evaluate the stability of the radiolabeled peptide in transport conditions and study the biological distribution of the radiopharmaceutical in healthy mice. The study of radiolabeling parameters enabled to define a non-automated method which resulted in high radiochemical purity (> 95 %) without the need for purification of the labeled peptide. The automated method has been adapted, using a module of synthesis and software already available at IPEN, and also resulted in high synthetic yield (≥ 90%) specially when compared with those described in the literature, with the associated benefit of greater control of the production process in compliance with Good Manufacturing Practices. The study of radiolabeling parameters afforded the PSMA-HBED-CC-68Ga with higher specific activity than observed in published clinical studies (≥ 140,0 GBq/μmol), with a sufficiently long stability, which will enable transport to clinics for use in diagnostic imaging. Biodistribution and pharmacokinetic profiles of the radiolabeled peptide were consistent with those founded in the literature. We concluded that PSMA-HBED-CC-68Ga, important diagnostic tool for prostate cancer imaging with PET, can be produced by either automated or not automated method with high radiochemical purity, high synthetic yield and stability of the radiopharmaceutical.
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Chipperfield, John. "A structural investigation of the postsynaptic density protein, PSD-95." Thesis, University of Manchester, 2012. https://www.research.manchester.ac.uk/portal/en/theses/a-structural-investigation-of-the-postsynaptic-density-protein-psd95(b69becc3-d2a1-4e35-a4da-94b6667c0a4b).html.
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The mechanism known as Long-Term Potentiation (LTP), which is perhaps the most established mechanism associated with memory and learning, describes the Hebbian postulate that “neurons that fire together, wire together”. LTP refers to the upregulation of synaptic strength in response to high activity and can be subdivided into distinct phases. Early-LTP involves the phosphorylation of neurotransmitter receptors while Late-LTP involves the increase in expression of receptors at the postsynaptic membrane. These are long-term, stable perturbations of synaptic activity, lasting from hours to weeks. However, more subtle mechanisms controlling shorter-term plastic changes in synaptic function lie in the spatial distribution of postsynaptic receptors. In glutamatergic synapses within the mammalian CNS the distribution of neurotransmitter receptors is controlled by a scaffold of proteins under the postsynaptic membrane known as the PostSynaptic Density (PSD). This complex has been observed to change shape on a rapid scale, however little is understood about its macromolecular structure. The PSD anchors glutamate receptors within the postsynaptic membrane along with metabotropic receptors and cytoplasmic enzymes that modulate synaptic function and PSD and dendritic spine morphology. Much of what is understood on the macro-molecular structure of the PSD is based on knowledge of known binding partners. A recent paper within the group presented the PSD-95-Kir2.1 sub-complex of the PSD using a multi-disciplinary structural approach, blending Transmission Electron Microscopy (TEM) and solution scattering models with high-resolution X-ray and NMR structures for individual folded domains. In this thesis the solution state structure of PSD-95 is examined more closely. Deletion constructs of PSD-95 have been obtained by expressing subcloned fragments of the gene from Homo sapiens in an E. coli expression system and purifying them through a combination of IMAC, ion exchange chromatography and gel filtration. The PDZ region is rigorously described using Small Angle X-ray Scattering and is orthogonally validated by comparing the models against hydrodynamic data for the constructs. The PDZ12 region was crystallized and subjected to extensive optimisation to improve the resulting diffraction, falling just short of a molecular replacement structure. Attempts were made to crystallize the PDZ3 domain with the K¬ir¬2.1 C-terminus. PSD-95 dynamics was also investigated using Deuterium Exchange Mass Spectrometry (DXMS) to test a hypothesis for an internal binding interaction but was found not to be present using the methods developed.
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Barauskas, Tadas, and Raimundas Balčiūnas. "Automatizuotas grafinio internetinio interfeiso sudarymas." Master's thesis, Lithuanian Academic Libraries Network (LABT), 2013. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2013~D_20130826_110947-55765.
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Tiek tinklapio projektuotojui, tiek programuotojui apdoroti ir pritaikyti sukurtą grafinį dizainą internetiniams tinklapiams yra sudėtingas bei laiko sąnaudas suvartojantis procesas. Darbo tikslas palengvinti šį procesą sutaupant tiek darbo, tiek laiko kaštų vartotojams susijusiems su tiriama sritimi. Tikslui įgyvendinti sukurta internetinėje aplinkoje veikiančią programinę įrangą, kuri supaprastina ir palengvina internetinių grafinių šablonų kūrimą. Programinė įranga kurta pasitelkus PHP, CSS ir JAVA programavimo kalbas. Galutinis darbo produktas iš Photoshop įrankiu sukurto grafinio tinklapio eskizo generuoja tiek statinį tinklapio šabloną, tiek pritaiko šio šablono grafinius elementus turinio valdymo sistemos grafiniam atvaizdavimui. Nors jau egzistavo panašių įrankių (atliekančių panašias funkcijas), tokių kaip Adobe Fireworks ir Psd2CssOnline, tačiau šie įrankiai nusileido atpažįstamų elementų kiekiu ir kokybe. Tai patvirtino darbe atliktas tyrimas.To process and adjust a graphical design for web pages is a difficult and time consuming task for both: designer and developer. The main goal of this work was to make this task less time and effort consuming. To achieve this goal a web accessible software tool was created in our work. This automated tool can analyze graphical project files (made with Adobe Photoshop) and output desired end result, thus preserving time and effort. The developed tool analyzes initial file layer by layer and automatically assigns appropriate parameters to CSS and html patterns. These patterns then can be extracted as static web pages or with a next step these patterns can be adjusted to fit a chosen content managing system. Although there already are some similar products with the same functionality (such as Adobe Fireworks or Psd2CssOnline), the developed tool was greater in quality and quantity of recognizable web elements. This was proven by the research provided in this work.
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Page, N. L. "Development of a Novel PSMA - Driven Gene Therapy for the Treatment of Prostate Cancer." Thesis, Queen's University Belfast, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.517530.
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Waschan, Julia [Verfasser]. "Wertigkeit der 68Ga-PSMA-PET/CT als Nachsorgeuntersuchung des metastasierten kastrationssensitiven Prostatakarzinoms / Julia Waschan." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2021. http://d-nb.info/1241540152/34.
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Thibaut, Annika Leonie [Verfasser]. "PSMA im klarzelligen Nierenzellkarzinom : eine neue Option zur Detektion von Metastasen / Annika Leonie Thibaut." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2020. http://d-nb.info/1234451190/34.
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Joshi, Andre. "Precision medicine in early recurrent prostate cancer: identification of metastases by PSMA PET MRI." Thesis, Queensland University of Technology, 2018. https://eprints.qut.edu.au/122472/1/Andre_Joshi_Thesis.pdf.
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Through a prospective clinical trial exploring PSMA PET/MRI, we aimed to address the current clinical need for more sensitive and specific imaging in biochemically recurrent prostate cancer. This imaging technology has the potential to detect micro-metastatic and low volume recurrent disease, potentially altering standard of care treatment options for patients. Additionally, as a proof of principle we aimed to apply novel organoid culture technology to develop patient derived cell models to allow drug testing and next generation sequencing as part of a precision medicine approach in early recurrent prostate cancer.
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Ranc, Anne-Gaëlle. "Phenol Soluble Modulins et lipopolysaccharide de Legionella pneumophila : rôle dans la réponse immunitaire innée." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1010/document.
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Legionella pneumophila (Lp) est une bactérie ubiquitaire dans les environnements aqueux et responsable d’une pneumopathie potentiellement sévère : la légionellose. La majorité des souches impliquées appartiennent au sérogroupe 1 (Lp1) et à un sous- groupe spécifique de souches portant un épitope particulier dites mAb3/1+. Cependant, la différence de distribution entre les souches retrouvées dans l’environnement et celles impliquées en clinique n’est pas clairement élucidée. Notre travail a porté sur la détection de deux facteurs de virulence de Lp. Nous avons voulu mettre en évidence l’existence de Phenols Soluble Modulines (PSMs), peptides uniquement décrit chez Staphylocoques et avons ainsi pu démontrer l’activité de peptides prédits par analyse in silico chez Lp capables d’activer la réponse inflammatoire par la voie du NF-?B et sont dotés d’une action cytotoxique. Notre deuxième axe d’étude a porté sur le lipopolysaccharide (LPS) de Lp. Afin de vérifier si la prédominance de certaines souches était liée à un biais diagnostique, nous avons voulu tout d’abord vérifier la sensibilité de 3 tests urinaires diagnostiques envers le LPS extrait de souches de différents sous- groupes de Lp1 et sérogroupes de Lp et avons ainsi pu montrer que ces tests sont capables de détecter tous les LPS de Lp1. La sensibilité envers le LPS des autres sérogroupes est très variable mais reste insuffisante pour permettre leur détection. Nous avons ensuite utilisé ces LPS extraits pour vérifier la réponse immunitaire innée en fonction des souches de Lp1. Ainsi les souches mAb3/1+ activent moins le système immunitaire que les souches mAb3/1-, ce qui pourrait expliquer alors une moins bonne clairance de ces souches permettant leur multiplication à l’origine d’une infection. Au final, notre travail a permis d’étudier deux facteurs de virulence potentiels au sein de Lp, pouvant expliquer partiellement la prédominance de certaines souches en pathologie humaineLegionella pneumophila (Lp) is a ubiquitous intracellular bacterium found widely in the environment and is the cause of an opportunistic infection named legionellosis. The majority of the strains involved belong to serogroup 1 (Lp1) and to a specific subgroup named mAb3/1+, linked to a specific epitope expressed at the cell membrane. However the distribution difference between the strains found in the environment and the ones involved in pathology is not fully understood. We here studied two virulence factors of Lp. We first demonstrated the existence of Phenols Soluble Modulines (PSMs), smalls peptides that only have been described for Staphylococcus and found that the peptides that were predicted for Lp by in silico analysis were able to activate the innate immune response by NF-?B pathway and were able to have a cytotoxic activity. We also studied the lipopolysaccharide (LPS) of Lp. To found out if the predominance of some strains was linked to a diagnosis biais, we first evaluated the sensitivity of 3 urinary antigens tests against extracted LPS of strains belonging to all the sous-groups of Lp1 and serogroups of Lp. We then demonstrated that those tests are able to detect all LPS of Lp1, independently of mAb3/1 character. The sensitivities of the 3 tests were very variable for the other serogroups of Lp, but were too low to be able to detect those LPS in practice. We then used these extracted LPS to evaluate the innate immune response for different strains of Lp1. We demonstrated that mAb3/1- strains needed lower dose of LPS to activate the innate immune response than mAb3/1+ strains, which could be linked to a better clearance of the bacteria from the host, which doesn’t develop an infection. This work has studied two potentially virulent factors of Lp, which could partially explain the predominance of some strains of Lp in human pathology
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Paiva, Hélder Filipe Cardoso. "A qualidade das relações e o ajustamento Pessoa-Organização: o papel mediador da motivação para o serviço público." Master's thesis, Instituto Superior de Ciências Sociais e Políticas, 2020. http://hdl.handle.net/10400.5/20556.
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Dissertação de Mestrado em Gestão e Políticas PúblicasPortugal tornou-se num exemplo recente no contexto Europeu pelas políticas de austeridade que implementou em consequência da crise financeira de 2008 e também pelo impacto que essas políticas tiveram nas condições de trabalho e nos trabalhadores em funções públicas. Algumas das consequências dessa crise ainda se refletem atualmente nas condições de trabalho em funções públicas, pelo que, o presente estudo procura saber como podem os gestores públicos manter o ajustamento dos trabalhadores com a organização, através da qualidade das relações desenvolvidas nos seus contextos de trabalho. O objetivo geral deste estudo foi investigar a influência que a qualidade da relação com a liderança e com os colegas de trabalho exercem na perceção de ajustamento pessoa-organização. Pretendeu-se ainda testar se a influência da liderança e dos colegas é mediada pela motivação do trabalhador para o serviço público. Com a aplicação de um questionário online foram recolhidas 263 respostas de trabalhadores que desempenham funções públicas na administração pública portuguesa. Os resultados deste estudo demonstraram que, as trocas Líder-Membro (LMX) e as trocas Membro-Membro (MMX), estão positivamente correlacionadas com a perceção de ajustamento pessoa-organização (POFIT). No entanto, a motivação para o serviço público (PSM), operacionalizada com as dimensões de atracão pela realização de políticas publicas (APM) e compromisso com o interesse publico (CPI), não apresentou um efeito mediador, ao contrário do previsto. Conclui-se assim que a perceção de ajustamento com a organização é sensível a fatores do contexto mais próximo: os líderes podem intervir na manutenção do ajustamento dos trabalhadores e os colegas de trabalho também podem influenciar esta perceção de ajustamento. Face aos resultados obtidos, conclui-se ainda que os conceitos de ajustamento pessoaorganização e de motivação para o serviço público carecem de uma dimensão cultural que integre as várias camadas de valores que determinam a perceção e a conduta de atuação dos trabalhadores em funções públicas.
Portugal became a recent example in the european context due to the successful implementation of austerity policies after the 2008 financial crisis and the impact those policies had on public services and public servants work conditions. Some consequences of this crisis are still reflected today in public organizations, especially on workers general conditions, therefore the present study tries to understand if public managers can maintain workers personorganization fit using a social exchange approach. This study investigated the antecedents of person-organization fit (PO Fit) in public organizations using leader-member exchange theory (LMX) and member-member exchange (MMX). One individual variable was also included to test if public service motivation (PSM) mediated the effect of these contextual factors in the perception of fit with public organizations. An online questionnaire was applied to a sample of 263 public servants from several subsectors of the portuguese public administration. Results demonstrated the direct effects of LMX and MMX on PO Fit, however the mediation effect of PSM was not confirmed when using dimensions of attraction to policy making (APM) and commitment to public interest (CPI). Overall, these findings suggest that perceptions of personorganization fit go beyond the initial perception of newcomers, as initially conceived. Organizational context can change and individuals can also reevaluate their initial assessment based on these changes. This study demonstrated that PO Fit can be affected by work environment relationships. Specifically, public managers can influence the perception of core organizational values of their subordinates, but also co-workers can act as examples for individual assessment of value congruence with the organization. Finally, in a broader scope of analysis, the findings in this study also suggest that person-organization fit and public service motivation theories need to integrate a cultural dimension in order to capture the multilayered, and sometimes conflicting values in play, within public organizations.
N/A
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Keenan, Luke. "Post-synthetic modification of metal-organic frameworks." Thesis, University of Bath, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.619226.
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Post-synthetic modification (PSM) of metal-organic frameworks (MOFs) has increased in importance in the last decade, as a pathway to access more complex surfaces in the pores and channels of porous coordination polymers. This thesis will describe new examples of tandem PSM processes leading to new functionalised MOFs that are inaccessible by direct synthesis. Chapter 1 introduces metal-organic frameworks (MOFs) and reviews the literature ranging from the basic building blocks to 3-D infinite networks. Post-synthetic modification (PSM) is introduced and a review of recent literature given. The aims of this report are also detailed at the close of the chapter. Chapter 2 contains an investigation into the conversion of primary amino to secondary amino groups in the pores of MOFs via a tandem PSM reaction. The pendent amino groups of [Zn4O(BDC-NH2)3] (IRMOF-3) and [Cr3O(OH)(OH2)2(BDC)3] (MIL-101(Cr)-NH2) were modified to produce secondary amino functionalised groups protruding into the void space. Several crystal structures are described including two obtained for the products of the PSM reaction on IRMOF-3. Nitrogen and carbon dioxide absorption was carried and high selectivity for CO2 over N2 was observed. Chapter 3 describes a new hydrothermal synthetic method of MIL-101(Cr)-NH2 and the modification, post-synthesis, to form halo- and azo dye-functionalised pore surfaces by a tandem diazotisation reaction. Quantitative yields are reported for the conversion to the halogenated frameworks inaccessible by direct synthesis with the analogous dicarboxylic acid. Gas adsorption studies demonstrated increased selectivity for CO2 over N2. Chapter 4 details the synthesis of new MOFs, with the potential for PSM, and crystallographic information is supplied for each new extended structure. The linkers, based on isophthalic acid, (1,3-benzenedicarboxylic acid) functionalised at the 5- position, were investigated with a range of metal salts and the resulting frameworks exposed to PSM reaction conditions where appropriate. By using a mixed ligand stoichiometry in the MOF synthesis reaction, 4,4’-bipy and BPDC have been incorporated into new extended frameworks. A new, simpler, synthetic route to the amino functionalised honeycomb framework [Zn4(BDC-NH2)3(NO3)2(H2O)2] (PNMOF-3) is also reported.
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Wehofsky, Marco. "Struktureinflüsse auf das Fragmentierungs-Verhalten von Peptiden bei PSD-MALDI-Massenspektrometrie." [S.l. : s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=962819603.
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Sun, Linus Da-Shih 1972. "Impaired and enhanced spatial representation of the PSD-95 knockout mouse." Thesis, Massachusetts Institute of Technology, 2003. http://hdl.handle.net/1721.1/27046.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, June 2004.Includes bibliographical references (p. 175-185).
Postsynaptic density protein-95 (PSD-95) is the second most abundantly expressed synaptic protein in the postnatal forebrain. It is an integral part of the postsynaptic scaffolding complex and helps recruit receptors, channels and associated factors involved with synaptic transmission. A mouse whose wildtype gene was replaced with truncation mutant of PSD-95 preserving two PDZ binding domains causes a spatial learning and memory deficit and a dramatic enhancement of synaptic strengthening. Long Term Potentiation is enhanced at all frequencies of stimulation (1-100Hz), while Long Term Depression is absent in the mutants. This study explores CA1 pyramidal cell spatial representations in the PSD-95 mutant mice. Mutants are not significantly different than controls in running velocity. Nor are its pyramidal cells or interneurons different than controls in: place cell firing rates, sparsity of run active cells, bursting behavior, or theta modulated activity. However, mutants do exhibit significantly larger place fields and wider spike waveforms. Mutants also expressed enhanced directionality of place fields and increased post-run sleep correlation of firing for overlapping place fields. Mutants also exhibited disruption of asymmetrical place fields and phase precession, the first such observation reported in mice. In conclusion, LTP alone is not enough for the active process of encoding experience. Instead, bi-directional synaptic plasticity is necessary for proper place field formation, correlation, directionality, asymmetry, phase precession, and the formation of spatial memories.
by Linus Da-Shih Sun.
Ph.D.
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Rosa, Ellysson Fernandes. "O perfil do public service motivation (psm) de servidores públicos inovadores." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/6969.
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This research intended to know the PSM profile of public servants who submitted their innovative projects in the 1st project contest for government managers of Goiás-Brazil in 2012. Considering the importance of motivation in the context of public administration, as well as the pressing need for innovation to respond to the social demands, this research was concerned to understand the relationship of PSM level with the profile of public servants of strategic level considered innovative. Using the t-test, multiple correspondence analysis (MCA) and hierarchical cluster analysis (HCA), it was concluded that the PSM level of innovative public servants is significantly higher than that of public servants in general, compared to a research that is a reference in the subject in Brazil. As for the public servers profile, it was found that most of the results achieved are in agreement with previous studies in the literature that investigated the profile of public servants with high levels of PSM, highlighting the Information Technology Managers to a greater extent.
Esta pesquisa pretendeu conhecer o perfil da motivação do serviço público (PSM) em gestores governamentais goianos que inscreveram seus projetos inovadores no 1º concurso de projetos dos Gestores Governamentais de Goiás em 2012, promovido pelo SINDGESTOR. Considerando a importância da motivação no contexto da administração pública, bem como, a necessidade premente por inovação para dar respostas às demandas sociais, esta pesquisa se ocupou em entender a relação do índice de PSM com o perfil de servidores públicos de nível estratégico considerados inovadores. Utilizando teste t, análise de correspondência múltipla (MCA) e a análise hierárquica de cluster (HCA) concluiu-se que o nível de PSM destes servidores públicos inovadores é significativamente maior do que os servidores públicos em geral em comparação à uma pesquisa que é referência no tema no Brasil. Quanto ao perfil dos servidores descobriu-se que a maior parte dos resultados alcançados está em consonância com estudos anteriores da literatura que pesquisaram sobre o perfil de servidores públicos com alto índice de PSM, destacando os gestores da tecnologia da informação em maior proporção.
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Raupp, Marcelo Coelho. "Pequenos Getúlios: O PSD e as elites políticas catarinenses (1945-1970)." Universidade do Estado de Santa Catarina, 2011. http://tede.udesc.br/handle/handle/1507.
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Previous issue date: 2011-05-23Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
This work aims to discuss some ideas that permeate the understanding of Brazilian politics, in general, and Santa Catarina, Brazil, in particular. "Oligarchy", "patronage," paternalism and populism are discussed in terms from the notion that political processes are affected by the actions of political elites, among them, a portion gradually stood out from the Estado Novo period (1937-1945), by seeking to join to what is thought to be the actions of Getulio Vargas. In this period, appear the "Pequenos Getúlios" of Santa Catarina. Part of they draw a personalistic political culture, essential in their performances in public space. It is the case with the group founder of Partido Social Democrático (PSD). Moreover, the attention turns to the application of elements of personalist political party, as well as the individual actions of its members. Effective party machines are established between the "simple people" and the "professional politicians". And finally, attempts to understand how the elite acting in PSD articulates the relationship with the working classes to a new configuration of the state to society. In 1960, after ten years in opposition, PSD wins the state government and sees a "state machine" in order to achieve "governance" of the entire population and Santa Catarina
O presente trabalho tem por objetivo discutir algumas noções que permeiam a compreensão da política brasileira, em geral, e catarinense, em particular. Oligarquia , clientelismo , assistencialismo e populismo são termos debatidos a partir da noção de que os processos políticos são afetados pela atuação de elites políticas, dentre as quais, uma parcela, aos poucos se destacou, desde o Estado Novo, por procurar associar-se ao que se julgava serem as ações do Estado varguista. Aparecem então os Pequenos Getúlios de Santa Catarina. Parte destas elabora para si uma cultura política personalista, primordial em suas atuações no espaço público, sobretudo na capital do estado. É o caso do grupo fundador do Partido Social Democrático. Além disso, as atenções se voltam para a aplicação dos elementos personalistas deste partido político, bem como das ações individuais de seus membros. Eficientes máquinas partidárias são estabelecidas entre o povo simples e os políticos profissionais . E, por fim, procura perceber como a elite atuante no Partido Social Democrático (PSD) articula as relações com as camadas populares a uma nova configuração do papel do estado perante a sociedade catarinense. A partir de 1960, após dez anos na oposição, o partido conquista o governo estadual e concebe uma máquina estatal com o objetivo de alcançar a governança de todo o território e população catarinenses
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Semeniuk, A. V., L. M. Magas, А. В. Семенюк, and Л. М. Магас. "From .PSD to interactive website: modern instruments for front-end development." Thesis, ВНТУ, 2019. http://ir.lib.vntu.edu.ua//handle/123456789/24780.
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Today, information is the most important instrument in all areas of our life. It`s important to develop tools that can transfer pieces of information one point to another. Moreover, it`s adaptive for every user. Web-application is the best choice.На сьогоднішній день, інформація відіграє ключову роль у всіх сферах нашого життя. Актуальним питанням є розробка швидких та комфортних засобів, завданням яких є доставка цієї інформації з одного вузла до іншого, максимальна простота у користуванні та адаптація під кожного користувача окремо. Одними із найкращих таких застосунків є веб-додатки
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Ugurlu, Ibrahim Olgun. "A New Method of Determining Pore Size Distribution (PSD) in Sandstones." University of Cincinnati / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1447070674.
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Kratschke, Maximilian Moritz. "Investigating PSD-95 turnover at the synapse using the HaloTag technology." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31131.
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PSD-95 is an abundant scaffolding protein found in the postsynaptic densities (PSDs) of excitatory synapses throughout the mammalian brain, and plays a critical role in innate and learned behaviours. PSD-95 assembles with numerous other proteins, including glutamate receptors, adhesion molecules and signalling proteins, into postsynaptic supercomplexes that are then organised into nanoclusters that comprise the postsynaptic density of excitatory synapses. While the subcellular localisation of PSD-95 has been widely studied, much less is known about its turnover. In this thesis, I present novel insights into PSD-95 synthesis and degradation at synapses of cultured primary neurons gained using the HaloTag technology. The HaloTag consists of an engineered bacterial protein domain that covalently binds synthetic ligands labelled with fluorescent and affinity moieties. Hence, cells expressing proteins fused to the HaloTag can be used to study protein levels, complexes and turnover using these different ligands. This project was based upon a knock-in mouse line expressing the HaloTag fused to endogenous PSD-95 using gene targeting. After demonstrating that these mice were phenotypically normal and that PSD95-HaloTag fusion proteins normally assembled into supercomplexes in the PSD, hippocampal primary cultures were grown from this mouse line. Fluorescent HaloTag ligands were then used to label live neurons, allowing for the visualisation of PSD-95 at synapses by confocal microscopy. Next, I established a pulse-chase labelling method, where one ligand is used to label all existing PSD-95 first, before a second ligand can then be used to label any newly synthesised PSD-95. This allows for the identification and characterisation of subpopulations of PSD-95, which can be separately analysed. I find that PSD-95 has a half-life of 36 hours at synapses, consistent with previous literature. I was also able to observe synaptic heterogeneity in PSD-95 turnover, and classify synapses into types according to their PSD-95 expression profile. Finally, a range of chemical compounds known to modulate protein turnover and neuronal activity was applied over a 24-hour period, and their effects on PSD-95 turnover analysed. It was found that inhibiting either the proteasome or protein synthesis led to significant reductions in PSD-95 degradation as well as inhibiting PSD-95 synthesis. Thus, this project established a method offering a unique way of investigating the turnover of a specific, tagged protein, as well as gaining novel insights into the turnover of PSD-95 at individual synapses.
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Oliveira, Dennis [Verfasser], Björn Michael [Akademischer Betreuer] Kampa, Karl-Josef [Akademischer Betreuer] Langen, and Frank [Akademischer Betreuer] Müller. "In vivo imaging of brain tumors using the PSMA-selective PET ligands [68Ga]Ga-PSMA-HBED-CC and [18F]DCFPyL in rat glioma models / Dennis Oliveira ; Björn Michael Kampa, Karl-Josef Langen, Frank Müller." Aachen : Universitätsbibliothek der RWTH Aachen, 2019. http://d-nb.info/1195150741/34.
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Camargo, Filho Altair. "Impacto das atividades de marketing nos primeiros anos do negócio em seu desempenho futuro." Universidade Federal de Goiás, 2015. http://repositorio.bc.ufg.br/tede/handle/tede/5418.
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Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG
This study aimed to analyze how the moment in which the venture starts using marketing activities in its early stages affects its future performance. In order to achieve this goal the Panel Study of Entrepreneurial Dynamics (PSED), which consisted of application of questionnaires, via telephone, to 1,214 new entrepreneurs from the United States between the years 2005 and 2011. The data analysis was done using descriptive statistics and logistic regression analysis in which the dependent variables considered as performance were the survival and profitability of companies. The independent variables, marketing activities, were “effort to talk with potential clients”; “effort to collect competitors information”, and “execution of promotional efforts”. For the analysis, it was related the beginning of realization of marketing activities in the first and second years with the new venture’s performance in the second, third and fourth years. Results show that the first year is the optimal time for entrepreneurs to start talking to consumers, that is, the moment that takes the company to perform better in subsequent years. The execution of promotional efforts in the first year also leads to positive results for business, but results regarding the optimal moment to develop this action and regarding the collection of information about competitors were inconclusive.
O objetivo deste trabalho foi analisar como o momento do início da realização de atividades de marketing nos primeiros anos de uma empresa impacta no seu desempenho futuro. Para atingir o objetivo foi utilizada a base de dados longitudinal do Panel Study of Entrepreneurial Dynamics (PSED), que consistiu na aplicação de questionários, via telefone, a 1214 empreendedores nascentes dos Estados Unidos entre os anos de 2005 e 2011. A análise de dados se deu por estatística descritiva e análise de regressão logística, em que as variáveis dependentes consideradas como desempenho foram a sobrevivência e a rentabilidade das empresas. Como variáveis independentes – atividades de marketing – foram consideradas o “diálogo com clientes”, “coleta de informações dos concorrentes”, e “execução de esforços promocionais”. Para a análise, foram relacionados o início da realização das atividades de marketing no primeiro e no segundo anos da empresa com o desempenho do negócio no segundo, terceiro e quarto anos. Como resultados, esta pesquisa mostra que ao longo do primeiro ano de funcionamento é o momento ótimo para que o empreendedor inicie diálogos com seus clientes, ou seja, que leva a empresa ao melhor desempenho nos anos subsequentes. Constatou-se que a execução de esforços promocionais logo no primeiro ano também leva a resultados positivos para o negócio, mas não foram encontrados resultados conclusivos sobre o momento ótimo para realizar esta ação, bem como para coletar informações dos concorrentes.
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Unger, Clara [Verfasser], and Ingolf [Akademischer Betreuer] Juhasz-Böss. "Die Expression des prostataspezifischen Membranantigens (PSMA) beim Mammakarzinom / Clara Marie Unger ; Betreuer: Ingolf Juhasz-Böss." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2020. http://d-nb.info/1213724023/34.
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Unger, Clara Marie [Verfasser], and Ingolf [Akademischer Betreuer] Juhasz-Böss. "Die Expression des prostataspezifischen Membranantigens (PSMA) beim Mammakarzinom / Clara Marie Unger ; Betreuer: Ingolf Juhasz-Böss." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2020. http://d-nb.info/1213724023/34.
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Rust, Arne Francois. "The impact of following a causation versus an effectuation approach on the survival of nascent entrepreneurial ventures in dynamic industries." Diss., University of Pretoria, 2010. http://hdl.handle.net/2263/26036.
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This study determines the influence of causation versus effectuation on entrepreneurial firm survival in high and low dynamism industries. Causation approaches a problem with the end in mind while effectuation’s point of departure is the means. Causal logic predicts a best case future scenario and then gathers the necessary resources to realize that scenario. This is contrasted by effectual logic that attempts to “control” the future by making use of the resources in hand (and those that can be borrowed) while trying to achieve the best possible result. The study consists of a means analysis testing for firm survival in highly dynamic industries per “pure” causal or effectual approach and of a variance analysis, testing for survival as a function of the mixed use of causation and effectuation in both high and low dynamism industries. The product of the means analysis indicates that only two entrepreneurs out of a cohort of 1771 follow a “pure” causal or “pure” effectual approach. As a result of this finding the incidence of “pure” causal or effectual approaches in either high or low dynamism industries is negligible. The output from the variance analysis indicates that causation is a significantly better predictor of entrepreneurial survival than effectuation in both high and low dynamism industries at a 99% confidence level. Below is a summary of the survival probabilities for both high and low dynamism industries across the causal/effectual decision spectrum.This study determines the influence of causation versus effectuation on entrepreneurial firm survival in high and low dynamism industries. Causation approaches a problem with the end in mind while effectuation’s point of departure is the means. Causal logic predicts a best case future scenario and then gathers the necessary resources to realize that scenario. This is contrasted by effectual logic that attempts to “control” the future by making use of the resources in hand (and those that can be borrowed) while trying to achieve the best possible result. The study consists of a means analysis testing for firm survival in highly dynamic industries per “pure” causal or effectual approach and of a variance analysis, testing for survival as a function of the mixed use of causation and effectuation in both high and low dynamism industries. The product of the means analysis indicates that only two entrepreneurs out of a cohort of 1771 follow a “pure” causal or “pure” effectual approach. As a result of this finding the incidence of “pure” causal or effectual approaches in either high or low dynamism industries is negligible. The output from the variance analysis indicates that causation is a significantly better predictor of entrepreneurial survival than effectuation in both high and low dynamism industries at a 99% confidence level. Below is a summary of the survival probabilities for both high and low dynamism industries across the causal/effectual decision spectrum. CopyrightDissertation (MBA)--University of Pretoria, 2010
Gordon Institute of Business Science (GIBS)
unrestricted
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Vickers, Catherine. "The role of postsynaptic density protein 95 (PSD-95) in excitatory signalling." Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/27580.
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The major receptor for excitatory neurotransmission in the central nervous system is the n-methyl-D-aspartate (NMDA) receptor. Recent study has shown that this receptor can be linked to networks of signalling proteins through binding to a scaffolding protein. Postsynaptic Density Protein 95 (PSD-95). This complex of proteins is termed the NMDA receptor complex (NRC). This thesis examined the role of PSD-95 in excitatory signalling and synaptic plasticity throughout the brain, with particular focus on the corticostriatal system. A proteomic approach was used to assess the expression levels of proteins in the NRC throughout specific regions of the mouse brain in wild type and PSD-95 mutants. Analysis revealed there to be no difference in expression levels of associated proteins within the forebrain (striatum, hippocampus and context) of wild type animals, but that the cerebellum showed expression levels that differed to the other areas. However, analysis of mice with a mutation in PSD-95 revealed there to be alterations in the expression levels and phosphorylation states of NRC associated proteins. These proteins were altered throughout the forebrain regions analysed, along with the cerebellum. They included proteins known to be important in NMDA receptor dependant signalling and synaptic plasticity. Moreover, analysis of expression levels of specific NRC associated proteins believed to have roles in focal ischaemia, revealed further alterations in PSD-95 mutant mice that had been subjected to focal ischaemia. The final set of experiments addressed the role of PSD-95 in corticostriatal synaptic plasticity. Electrophysiological recordings from striatal spiny cells revealed no strong phenotype in the PSD-95 mutant mouse with regard to alterations in excitatory postsynaptic potential (EPSP) amplitude post trains of cortical stimulation. The data reveal that PSD-95 is important in several aspects of neuronal connectivity, but that its effects can be specific to different areas of the brain. Moreover, the data suggest that the removal of an important protein from a signalling network can affect other signalling molecules within the same network.
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Bertoco, Juliana. "Solução numérica do modelo constitutivo KBKZ-PSM para escoamentos com superfícies livres." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/55/55134/tde-16012017-162912/.
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Escoamentos viscoelásticos não estacionários com superfícies livres são comuns em muitos processos industriais e diversas técnicas numéricas têm sido empregadas para reproduzir computacionalmente estes processos. A maioria dos modelos empregados utiliza equações diferenciais na definição do tensor de tensões. Porém, para alguns grupos de fluidos complexos, por exemplo, fluidos de Boger, os modelos integrais mostram-se mais capacitados em fornecer uma boa aproximação para os comportamentos não lineares desses fluidos. Este trabalho trata da solução numérica do modelo constitutivo integral KBKZ-PSM para escoamentos transientes bidimensionais com superfícies livres. O método numérico proposto é uma técnica numérica que utiliza diferenças finitas para simular escoamentos com superfícies livres na presença de paredes sólidas. As principais características do método numérico proposto são: solução das equações de conservação de quantidade de movimento e massa utilizando um método semi-implícito; a condição de contorno na superfície livre é acoplada à equação de Poisson, o que garante conservação de massa; a discretização do tempo t é realizada por uma nova técnica numérica; o tensor de Finger é calculado pelo método dos campos de deformação e avançado no tempo pelo método de Euler modificado. Essa nova técnica é verificada em escoamentos cisalhantes e elongacionais. Adicionalmente, uma solução analítica desenvolvida para escoamentos em canais bidimensionais é empregada para verificar e analisar a convergência do método proposto. Com relação a escoamentos com superfícies livres, a convergência é verificada por meio de refinamento de malha nas simulações de um jato incidindo sobre placa rígida e no problema do inchamento do extrudado. Finalmente, o método é aplicado para investigar os problemas jet buckling e inchamento do extrudado de fluidos KBKZ-PSM.Unsteady viscoelastic free surface flows are common in many industrial processes and a variety of numerical techniques have been employed to simulate these flows. The majority of constitutive models employed are based on differential equations to define the extra stress tensor. However, for some complex fluids, for instance, Boger fluids, integral models are more adequate to approximate the nonlinear behaviour of these fluids. This work deals with the numerical solution of the integral constitutive model KBKZ-PSM for two-dimensional unsteady free surface flows. The proposed numerical method is a numerical technique that employs finite differences to simulate moving free surface flows that interact with solid walls. The main features of the method are: numerical solution of the momentum and mass equations by an implicit method; the pressure condition on the free surface is implicitly coupled with the Poisson equation for obtaining the pressure field from mass conservation; a novel scheme for defining the past times t is employed; the Finger tensor is calculated by the deformation fields method and is advanced in time by the modified Euler method. This new technique is verified by solving shear and uniaxial elongational flows. Moreover, an analytic solution for channel flows is obtained that is used in the verification and convergence analysis of the proposed methodology. For free surface flows, the assessment of convergence lies on the mesh refinement on the simulation of a jet impinging on a flat surface and the extrudade swell problem. Finally, the new method is applied to investigate the jet buckling phenomenon and extrudate swell of KBKZ-PSM fluids.
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Gericke, Maximilian [Verfasser]. "Einfluss der 68Ga-HBED-CC PSMA PET/CT auf Diagnostik und Therapiemanagement des Prostatakarzinoms / Maximilian Gericke." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2019. http://d-nb.info/1194949231/34.
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Reinhardt, Svenja [Verfasser], and Andrei [Akademischer Betreuer] Todica. "Nebenwirkungen und Ansprechen nach einer Radioligandentherapie mit 177Lu-DKFZ-PSMA-617 / Svenja Reinhardt ; Betreuer: Andrei Todica." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1222909065/34.
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Stockgard, Rebecka. "Generation of affinity maturation libraries of PSMA targeting affibody molecules and selections to find improved binders." Thesis, KTH, Skolan för kemi, bioteknologi och hälsa (CBH), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-234955.
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Prostate specific membrane antigen (PSMA) is a membrane protein expressed in both prostate cancer cells and in the neovasculature of many other solid tumors. It can act as a therapeutic target and as a target for an imaging agent for various cancers. Earlier, three different PSMA targeting affinity molecules, called Affibody molecules, were generated through phage selection. The aim of this thesis was to produce three corresponding affinity maturation libraries based on the three potential PSMA binders and select for improved binders through phage display. The affinity maturation libraries were produced, and two to four selection cycles were performed with yet insufficient enrichment. Therefore, more cycles must be performed in order to discover potential PSMA-binders with sufficient affinity.Prostataspecifikt membranantigen (PSMA) är ett membranprotein som uttrycks i både prostatacancerceller såväl som i nybildade blodkärl kring en tumör. Cancercellers uttryck av PSMA kan användas för att både behandla och upptäcka tumörer i kroppen. Tidigare har tre PSMA-sökande affinitetsmolekyler tagits fram, kallade Affibodymolekyler, genom fagdisplay. Syftet med detta examensarbete var att producera tre korresponderande affinitetsmatureringsbibliotek baserat på de tidigare potentiella PSMA-bindarna, och att selektera via fagdisplay för att hitta bindare med högre affinitet. De tre affinitetsmatureringsbiblioteken producerades och två till fyra selektionscykler har genomförts utan att se tillräcklig anrikning av bindare. Därför måste fler cykler genomföras i syfte att hitta potentiella PSMA-bindare med tillräckligt god affinitet.