1,096 research outputs found
Parga, and the Ionian islands; comprehending a refutation of the mis-statements of the Quarterly Review and of Lieut.- Gen. Sir Thomas Maitland, on the subject; with a report of the trial between that officer and the author.
No full textPreface: Bosset, C.P.(de)Appendix.Dedication:Content description: TitleIllustration: (Maps ,)Pagination: PP26+530PVolumes: 1Text Genre:ProseIllustration: (χάρτες ,
Improving bladder cancer immunotherapy by tailoring protein secretion in mycobacteria
No full textBladder cancer is the 4th to 10th most common cancer worldwide, with non-muscle invasive bladder cancer (NMIBC) counting for 70-75% of cases. Standard treatment of NMIBC includes resection of the tumor followed by intravesical treatment with Mycobacterium bovis BCG (BCG). BCG is a live but attenuated vaccine strain well-known for its use against tuberculosis, an infectious disease caused by Mycobacterium tuberculosis. BCG bacteria induce a local inflammatory response that not only clears the bacterium but also eradicates the remaining tumor cells. Although effective, BCG treatment may still show up to 30% recurrences. The research described in this thesis aims for improvement of bladder cancer treatment. First, since secretion and surface display of (tumor) antigens might improve BCG anti-tumor efficacy, the aim was to enable heterologous secretion in mycobacteria. Mycobacteria use specialized secretion systems to secrete proteins over their unique cell envelope, known as Type VII secretion systems. For heterologous secretion we focused on one of these systems, the ESX-5 system. Model protein OVA was fused to the PE and linker domain of ESX-5 substrate LipY. Screening of an M. marinum error-prone PCR mutant library showed that two mutations in OVA or deletion of the linker domain lead to increased secretion. Thus, the ESX-5 secretion system is suitable for heterologous secretion in mycobacteria but optimization is required for each desired heterologous protein. Second, we focused on the function of ESX-5. Studying the processing of LipY in more detail lead to the discovery of PecA, an ESX-5 dependent secreted aspartic protease that cleaves the PE domain of LipY, other PE_PGRS proteins and itself. Furthermore, deletion of pecA resulted in an attenuated phenotype in zebrafish larvae. Next, we studied the role of ESX-5 in fatty acid uptake. In tuberculosis mycobacteria reside in the lungs inside structures known as granulomas, in which lipids form the main energy source. By screening for transposon mutants showing increased growth on Tween 80 as sole carbon source, two PE proteins, MMAR_0369 and MMAR_4321, were identified to be able to cleave fatty acids. These cutinase-like proteins harbor an α/β hydrolase domain, a domain also predicted for multiple other proteins in M. tuberculosis and M. marinum. Together, these findings demonstrated that PE proteins can have distinctive functions depicted by their C-terminal domains and not by the PE domain by which they are usually categorized. The main aim was to improve bladder cancer immunotherapy. To study anti-tumor activity in vivo we used an orthotopic bladder cancer mouse model. We showed that combining multimodal imaging techniques, e.g. high ultrasound imaging, photoacoustic imaging and bioluminescent imaging, enables longitudinal studies on tumor development in the bladder. The integration of individual strengths enabled sensitive and improved quantification and understanding of tumor biology and ultimately can aid in the discovery and development of new therapeutics. Finally, we tested the hypothesis that anti-tumor activity can be improved by enhancing bacterial binding to the bladder wall. Recently, Salmonella enterica Typhi Ty21a (Ty21a), an oral vaccine strain against typhoid fever, has been shown to be potentially more effective against bladder cancer than BCG. Labeling of Ty21a with adhesion protein FimH resulted in a ~5 fold increased binding to the mouse bladder in vivo. Furthermore, a single bladder cancer mouse study showed a modest increase in median survival for mice treated with FimH-labeled Ty21a. In conclusion, this thesis presents a study on mycobacterial protein secretion in order to improve bladder cancer immunotherapy. We identified novel functions for 3 PE proteins providing more insight into the function of ESX- 5 and its role in virulence. Furthermore, we showed that labeling Ty21a with FimH shows promise for improving bladder cancer treatment
Regulation of endosomal and phagosomal transport
No full textEndocytosis can be conceptually broken down into two stages: The formation of the nascent vesicle containing the ingested proteins and lipids, and its subsequent maturation into a degradative compartment. During this maturation process proteins can be recycled back to the plasma membrane to prevent degradation. The vesicular membrane and the luminal contents undergo considerable remodeling to transform this compartment into a degradative one. This stops signal transduction by degrading the receptors within the vesicle and also generates antigens for presentation on MHC class II molecules in order to elicit an adaptive immune response. The engulfment of large particles and microorganisms (e.g. pathogens) is referred to as phagocytosis. The vesicle created by phagocytosis is called the phagosome. Phagosome maturation is considered to involve a complex sequence of fusion and fission events with the sub compartments of the endocytic pathway. In many ways, phagosome maturation recapitulates the progression of cargo along the endocytic pathway. In this thesis we have described molecular mechanisms that regulate the endocytic route and how pathogens explore this endocytic route to ensure survival.Nederlands Kanker Instituut Nederlandse Vereniging voor Microscopie Koningin Wilhelmina FondsUBL - phd migration 201
La Cassazione si pronuncia sull'esatta portata della fattispecie di "denuncia di un sinistro non accaduto" di cui all'art. 642 c.p.
No full textNella prima parte della nota, l’Autore analizza la fattispecie di «denuncia di un sinistro non accaduto» di cui all’art. 642, comma 2, c.p., introdotta nel 2002 nell’ambito della riforma delle assicurazioni R.C. Auto, per, poi, affrontare la questione su cui si è pronunciata la Corte di cassazione, relativa al significato da attribuire al concetto di “sinistro”. Infine, l’Autore offre le proprie riflessioni sui rapporti intercorrenti tra la fattispecie esaminata e le altre ipotesi delittuose previste dall’art. 642 c.p. e sulla compatibilità di tali reati con il principio di offensività.In the first part of the note, the Author analyzes the crime of “denunciation of a false accident” that was introduced into the art. 642 c.p. in 2002, and, then, the question about the meaning of “sinistro” (accident) on which the Supreme Court stated. Finally, the Author offers his own reflections on the connection between the examinated crime and other felonies provided under art. 642 c.p., and, also, on compatibility of those crimes with the principle of seriousness of the offense
Book Review: Jesus in an age of enlightenment: Radical gospels from Thomas Hobbes to Thomas Jefferson. By Jonathan C.P Birch
No full textThis is a pre-copyedited, author-produced PDF of an article accepted for publication in [Literature and Theology] following peer review. The version of record [Greenaway, J. (2021). Jesus in an Age of Enlightenment: Radical gospels from Thomas Hobbes to Thomas Jefferson. By Jonathan C.P Birch. Literature and Theology, 35(1), 100–102] is available online at: [https://academic.oup.com/litthe/article/35/1/100/6130117?guestAccessKey=0523008b-46e6-4ed2-ab5d-001d93207bed].A review of Jesus in an Age of Enlightenment: Radical Gospels from Thomas Hobbes to Thomas Jefferson by Jonathan C.P Birc
On morphology, molecular composition and breakdown behaviour in semi-crystalline polymers
No full textA Review on Automatic Generation of Architectural Space Layouts with Energy Performance Optimization
No full textGreen Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Climate Design and SustainabilityDesign InformaticsBuilding ServicesArchitectural Engineering +Technolog
Suspended graphene beams with tunable gap for squeeze-film pressure sensing
No full textWe present suspended graphene pressure sensors fabricated using an innovative surface micro-machining process. The great advantage of this process is that the molybdenum (Mo) catalyst layer for multi-layer graphene chemical vapor deposition (CVD) is also used as a sacrificial layer to suspend the graphene. This method allows for accurate control of the gap size under the beam by simply varying the catalyst thickness. Furthermore, the need for transfer of the graphene layer is eliminated. Using this method, wafer-scale graphene squeeze-film pressure sensors are fabricated and characterized.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Electronic Components, Technology and MaterialsQN/Steeneken LabQN/van der Zant LabDynamics of Micro and Nano System
2021 butterfly inventories within Boulder County open spaces, Boulder, Colorado
No full textApril 4, 2022.Includes bibliographical references.The butterfly inventories continued for the 18th year in a few of the Boulder County Open Space properties. However, because of the Calwood Fire during October 17, 2020, two of the survey areas were inaccessible; Plumely Canyon and the work road through the streamlet near the Lichen Trail. Geer Watershed had been burned, but the meadows above the Resident Ranger's Cabin and associated streamlets were made accessible with our 2021 permit. Cabbage Whites (Pieris rapae), Orange Sulphurs (Colias eurytheme) and Common Wood-nymphs (Cercyonis pegala) were more numerous when compared to 2015-2020 populations before the burn. In 2021 within other Open Spaces, Anne U. White and Caribou, the resident species produced noticeably large populations: Julia Orangetips (Anthocharis julia), Pine Whites (Neophasia menapia), Northern Checkerspots (Chlosyne palla), Common Wood-nymphs, Small Wood-nymphs (C. oetus), Common Checkered-skippers (Burnsius communis). On the other hand, the well adapted non- native Cabbage Whites were again the most common during the long season; Variegated Fritillaries (Euptoieta claudia) and Dainty Sulphurs (Nathalis iole) were numerous flying in from colonies in the eastern plains and low foothills where their host plants were plentiful. 95 species were seen in 2021: 129 species between 2004 and 2021 in the county Open Spaces. 203 species are on the record for Boulder County (Butterflies and Moths of America 2021) website. The average number of species per year observed within the Open Spaces by this team is 88
Riflessioni sull’eutanasia. A margine della sentenza della Corte Costituzionale sull’art. 580 c.p
No full textOn September 25th the Supreme Court recognized, under certain conditions, the constitutional illegitimacy of article 580 c.p., the rule that punishes the conduct of those who facilitate suicide. By means of this judgment, the Court lays the foundations for a legislative recognition of active euthanasia. Starting from Seneca’s observations about suicide, the Author will question whether the right to die can be regulated by law and whether the recognition of individual freedom to decide to end one’s life really makes it necessary to recognize the lawfulness of medically assisted suicide
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