Coming dissertations at Uppsala university
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PET imaging of inflammation and fibrosis
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-543028
When the body faces an injury, the immune system triggers inflammation to initiate tissue repair. However, dysregulation of this process can lead to chronic inflammation, driving persistent scar formation and resulting in fibrosis. Fibrosis, characterised by pathological scar tissue accumulation, impairs organ function which could ultimately lead to death. Despite its clinical significance, treatment options remain limited. Positron Emission Tomography (PET) imaging, a highly sensitive and quantitative technique, offers significant potential for the non-invasive assessment of inflammatory and fibrotic processes.
Papers I and II investigate the Affibody molecule Z09591, which targets platelet-derived growth factor receptor β (PDGFR β), as a PET tracer for assessing liver fibrogenesis in a murine model of toxin-induced fibrosis (the CCl4 model). PDGFRβ, expressed on fibrogenic cells such as activated hepatic stellate cells, is absent in quiescent cells. Two radiolabeling techniques were compared: the TCO-TZ conjugation method ([18F]TZ-Z09591, Paper I) and the Al18F-RESCA method ([18F]AlF-RESCA-Z09591, Paper II). Both tracers demonstrated specific uptake in fibrotic regions with low liver background, highlighting their potential for non-invasive assessment of fibrogenic activity. These findings have supported the initiation of a first-in-human clinical trial evaluating a Z09591-based PET tracer.
Papers III and IV focus on two PET tracers, [¹¹C]NES and [68Ga]Ga-FAPI-46, targeting neutrophil elastase (NE) and fibroblast activation protein (FAP), respectively, in pulmonary fibrosis. NE is a protease released by activated neutrophils, while FAP is expressed on activated fibroblasts. Sequential PET scans were performed in patients with long COVID-19 (Paper III) and interstitial lung disease (Paper IV), with [¹¹C]NES assessing neutrophil-mediated inflammation and [68Ga]Ga-FAPI-46 imaging tissue remodeling activity. Tracer uptake correlated with lung abnormalities seen on computed tomography scans, underscoring their potential in imaging inflammation and tissue remodeling activity processes.
Given the complex pathogenesis of fibrosis and the lack of curative treatments, PET tracers that enable earlier diagnosis and disease monitoring may improve patient management and support the development of anti-fibrotic therapies.
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Eating alone or eating in loneliness : Food routines, health, and social relations in later life
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-543636
The overall aim of this thesis was to study eating alone or together with others among community-living older adults, focusing on how eating alone is experienced and how it is associated with aspects related to food routines, health, and social relations in Sweden. In Paper I, a scoping review was used to map and summarize existing scientific articles, while Paper II explored experiences and perceptions of eating alone through qualitative interviews. Papers III and IV are based on a national cross-sectional survey of 70- to 75-year-old adults, examining both the objective frequency and subjective experience of eating alone, and their associations with food-related outcomes, loneliness, and self-rated health.
Research across various research fields has examined eating alone as a potential risk factor for different food- and health-related outcomes, often using cross-sectional designs to assess the frequency, but not the subjective experience, of eating alone or with others (Paper I). Perceptions of eating alone ranged from being a symbol of loss to an unproblematic routine or a sign of independence (Paper II). One-quarter of the 695 survey participants were categorised as eating alone, while three-quarters were eating together with someone daily. Eating alone seemed to be related to the organisation of food routines (e.g., lower number of main meals per day, and more frequent consumption of ready-made meals) but not to the healthiness of food intake (food index scores) or BMI (Paper III). A small share reported being bothered when eating alone; however, one-third of those eating alone reported not having the opportunity to eat together with someone if desired. Both eating alone and lower engagement in social activities were associated with loneliness. Lower engagement in social activities was also associated with lower self-rated health, though eating alone was not (Paper IV).
In conclusion, eating alone, in the early phase of retirement age, is experienced in various ways and appears to be more closely related to food routines and social relations than to aspects of health. This thesis provides valuable insights for the development of future health policies and research on the implications of eating alone among older adults.
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Design and Implementation of Temperature-Aware Garbage Collectors
Link: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-543568
Garbage collectors (GCs) were invented as a technique to free programmers from the tedious and error-prone task of manual memory management. Traditionally, tracing collectors start with roots (such as global variables and active stack frames),traverse the entire heap to identify live (reachable) and dead (unreachable) objects, and reclaim memory occupied by dead objects. This simple binary classification of live versus dead objects is sufficient for memory reclamation.
In modern hardware, the use of cache memory is widely adopted to bridge the significant latency gap between CPUs and main memory,by leveraging spatial and temporal locality. Since the majority of applications indeed exhibit spatial and/or temporal locality,this memory hierarchy works very well in practice, effectively hiding the large latency of main memory accesses. Inspired by this observation of heterogeneous access patterns, we extend the binary classification of objects by further dividing live objects into two categories: hot (recently accessed by application threads) and cold (the inverse). We explore how to make GCs temperature-aware, taking advantage of this refinement to improve cache efficiency and achieve better application throughput.
This work is conducted with ZGC, a modern garbage collector in OpenJDK. The main body of this work consists of three components. First, we provide a thorough description of ZGC, the base collector upon which our implementations are built. Additionally, we build a SPIN model to capture the key aspects of of ZGC's design and study various concurrency behaviors in its low-level implementation. We believe this documentation and the SPIN model will be valuable for future research building on ZGC. The second component is a temperature-aware collector that relocates hot objects to improve cache locality and application performance. Our evaluation demonstrates significant performance improvements in applications with stable and recurring access patterns. The third component involves studying the behavior of cold objects and designing a temperature-aware collector that separates hot and cold objects into two subheaps, similar to the partitioning used in generational collectors. The evaluation reveals that many applications exhibit stable cold-hot clustering, allowing each cluster to be confined to its own subheap with only marginal overhead.
In summary, we believe that by treating hot and cold objects non-uniformly, temperature-aware collectors can unlock additional optimization opportunities and warrant further exploration.