21 research outputs found
Immune consequences and therapeutic targeting of disrupted RNA splicing in cancer
No full textThesis (Ph.D.)--University of Washington, 2022Immunotherapies, such as checkpoint blockade, CAR-T cells, and vaccines, have proven to be a valuable tool to treat various types of cancer. This class of therapy capitalizes on the immune system’s natural ability to recognize foreign antigens and kill cancer cells. Typically, many of these therapies have focused on the changes to DNA, particularly point mutations, that mark cancer cells. However, RNA dysregulation is also a frequent characteristic of cancer, and these transcriptomic changes may provide a large repertoire of new targets that previously has not been well studied. In this thesis, I address the question of whether RNA splicing changes can be immunogenic by studying disrupted splicing arising from 1) pharmacologic manipulation and 2) recurrent driver mutations in splicing factors. I demonstrate that drugs targeting splicing machinery can elicit anti-tumor immune responses dependent on splicing-derived neoantigens, and that checkpoint blockade can be used in combination with these drugs to further improve immune response and tumor clearance. I further provide a framework for identifying splicing-derived neoepitopes and use this framework to identify potential immune targets in splicing factor-mutant cancers. I then use mass cytometry-based approaches with leukemic SF3B1-mutant patient samples to characterize the immune environment in SF3B1-mutant cancers and search for antigen-specific T cells that recognize and respond to splicing-derived neoantigens
Emma Blake: Social Networks and Regional Identity in Bronze Age Italy. Cambridge University Press, Cambridge, 2014. ISBN 978-11-070-6320-4
No full textEmma Blake: Social Networks and Regional Identity in Bronze Age Italy. Cambridge University Press, Cambridge, 2014. ISBN 978-11-070-6320-4
No full textEmma Blake: Social Networks and Regional Identity in Bronze Age Italy. Cambridge University Press, Cambridge, 2014. ISBN 978-11-070-6320-4
No full text
Water consumption patterns in Australian Aboriginal communities
No full textAboriginal Australians have a significantly lower health status than their non-Aboriginal counterparts. To facilitate healthy living practices necessary for good health, a high level investment is currently made in water services, on the assumption that there is a relationship between the volume and quality of water supplied with health outcomes, despite the high economic and environmental cost. This thesis investigates whether the current design supply criteria of 1000-1200 litres per person per day of water, meeting the Australian Drinking Water Quality Guidelines, is both sufficient and necessary to improve the health of Aboriginal Australians. The scope of the thesis is limited to the sufficiency of design guidelines although it necessarily also touches on the broader issues of Aboriginal health.
Both qualitative and quantitative methods were used to explore current water consumption patterns of consumers at multiple hierarchical levels (community, household and individual) and hence the requirements of physical infrastructure on which consumers depend. Multiple linear regression was used to consider factors correlated with supply volume, while metering was used at both the domestic and appliance level to determine where and how water was used. Meters were installed on fixtures in two houses in a community near Alice Springs. This was then complemented by qualitative information obtained through focus group discussions, key informant interviews and observation in the field. The appropriateness of the supply of high quality water for all uses was addressed by considering the volume of drinking water intake and its impact on the derivation of water quality guidelines. This was achieved by a face-to-face survey involving 57 volunteers. Fieldwork was conducted predominantly in three communities near Alice Springs although some additional data was collected in other communities in Western Australia and the Northern Territory.
The results showed that the factors influencing water consumption were highly complex and variable between communities and individuals. However, there were some culturally specific needs identified in Aboriginal communities, such as the need for temperature and dust control, as well as the reduction of losses. The unique characteristics of each community made it difficult to provide a more precise estimate for design supply. As a result, overly conservative guidelines such as those already used are necessary in the short term despite there being no guarantee of improved health. In the long term, issues of community governance and capacity building will start to be addressed, and the realisation that social systems are both complex and dynamic will need to be reflected in policy. These issues were represented in a systemic conceptual model at the end of the thesis, which also highlighted inadequacies of reductionist approaches such as design supply guidelines. The thesis concluded that complex problem situations such as that of health, require a systems approach
Altered FC and FAB glycosylation status in patients with IGG4-related sclerosing cholangitis and autoimmune pancreatitis
No full textPlaying for the planet : a video game about deforestation.
No full textLa investigación se realizó bajo un enfoque cualitativo que pretende evidenciar las percepciones generadas al aplicar un videojuego en la enseñanza sobre el medio ambiente y en concreto sobre la deforestación como problemática socio ambiental realizado con dos grupos de estudiantes; considerando que los videojuegos son una herramienta que atrae positivamente al público para entretener, compartir y divertirse, empleándose con una mirada educativa apreciando la viabilidad que tiene usar estos recursos digitales en un contexto educativo que presenta nuevas exigencias en el que es pertinente seguir sumando iniciativas para recrear los procesos de formación y garantizar una educación de calidad comprometida con los avances y necesidades que se presentan en la sociedad y como tal en el sistema educativo. Se espera con este trabajo aportar al desarrollo de propuestas innovadoras que aborden problemáticas ambientales e incentivar a la aplicación y buen uso de los videojuegos en espacios de formación y concientización frente al cambio climático.Licenciado en Recreación y TurismoPregrad
Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis
No full textProteomic
Unique patterns of glycosylation in immunoglobulin subclass G4‐related disease and primary sclerosing cholangitis
No full textBackground:
Immunoglobulin subclass G4‐related disease (IgG4‐RD) is characterized by an abundance of IgG4 antibodies in the serum and tissue. Glycosylation status of antibodies can impact on immune effector functions and disease pathophysiology. We sought to establish glycosylation patterns in a prospective cohort of patients with IgG4‐RD and the relationship with disease activity and response to treatment.
Methods:
We assessed IgG Fc‐tail and Fab‐arm glycosylation status in patients with IgG4‐RD (n = 22), disease controls with primary sclerosing cholangitis (PSC) (n = 22), and healthy controls (n = 22). Serum IgG and subclasses were quantified using ELISA. Fc and Fab glycosylation were analyzed by mass spectrometry and lectin affinity chromatography, respectively. Disease activity, organ damage, and response to treatment were assessed using the IgG4 Responder Index.
Results:
Immunoglobulin G Fab sialylation was increased in IgG4‐RD compared with PSC and healthy control (P = 0.01), with a preferential increase in IgG4‐specific Fab sialylation, which was independent of IgG4 Fab‐arm exchange. There was a reduction in IgG1‐specific Fc bisection and hybrid structures in IgG4‐RD (P
Conclusion:
We report the first study showing unique antibody glycosylation status in a prospective cohort of IgG4‐RD and PSC patients, which may determine modulation of the immune system and contribute to disease pathophysiology.</p
