Spaces for Economic Diversity

The discipline of architecture operates within the organizing structure of the economy and is directly influenced by its flows and cycles. The fabric of the city is often a product of profit-pursuing goals, resulting in spaces prioritizing exchanges comprised only of monetary values. These spaces, however, are not built for exchanges based in other values that are meaningful to the lives of the occupants. Currently, these diverse and enriching exchanges are limited to private spaces such as homes, resulting in a built environment that spatially contributes to the separation of peoples’ everyday lives and the capitalist economy. Utilizing J.K Gibson-Graham’s theoretical framework of economic diversity, which asserts that non-capitalist and alternative forms of exchanges underpin the capitalist economy, this thesis explores Toronto’s employment and residential land use zoning designations as a physical manifestation of the divide between the understanding of value and peoples’ lives. By investigating the conditions resulting from current zoning by-laws within the city of Toronto through this lens, architecture can be expanded beyond a capitolocentric view and instead, examined as both a participator and a container for a more diverse economy. The thesis is located within the suburbs of Toronto that are often made of segregated and homogenous built fabric. By examining currently existing adjacency typologies between these spaces of work and home, as well as nearby suburban residential lots, the thesis conceives of a zoning overlay that amends the land use categories of employment and residential. The design proposes a network fostering economic diversity that is comprised of a new right-of-way mediating the space between employment lands and residential lots, interlinked with additions or renovations to existing warehouses and homes. Rethought processes of making, land ownership, and spatial qualities generate a heterogeneous built environment in the suburbs that can host the currently undervalued diverse exchanges beyond the private realm. These spaces of economic diversity will act as catalysts for restructuring the social relationships of work and value production, progressing towards increasingly interdependent, interconnected communities

SugarMate: Non-intrusive blood glucose monitoring with smartphones

Inferring abnormal glucose events such as hyperglycemia and hypoglycemia is crucial for the health of both diabetic patients and non-diabetic people. However, regular blood glucose monitoring can be invasive and inconvenient in everyday life. We present SugarMate, a first smartphone-based blood glucose inference system as a temporary alternative to continuous blood glucose monitors (CGM) when they are uncomfortable or inconvenient to wear. In addition to the records of food, drug and insulin intake, it leverages smartphone sensors to measure physical activities and sleep quality automatically. Provided with the imbalanced and often limited measurements, a challenge of SugarMate is the inference of blood glucose levels at a fine-grained time resolution. We propose Md3RNN, an efficient learning paradigm to make full use of the available blood glucose information. Specifically, the newly designed grouped input layers, together with the adoption of a deep RNN model, offer an opportunity to build blood glucose models for the general public based on limited personal measurements from single-user and grouped-users perspectives. Evaluations on 112 users demonstrate that Md3RNN yields an average accuracy of 82.14%, significantly outperforming previous learning methods those are either shallow, generically structured, or oblivious to grouped behaviors. Also, a user study with the 112 participants shows that SugarMate is acceptable for practical usage.</jats:p

Association between pregnancy and pregnancy loss with COPD in Chinese women: The China Kadoorie Biobank study

Background Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by airflow blockage. Pregnancy and pregnancy loss may be related to an elevated risk of COPD, although studies have yet to report on this association. Hence, this study aims to investigate the association between pregnancy and pregnancy loss with the risk of COPD among Chinese women. Methods Data on 302,510 female participants from the China Kadoorie Biobank were utilized for this study. Multivariable logistic regression, stratified by sociodemographic and lifestyle factors, was employed to obtain the odds ratio (ORs) and 95% confidence intervals (CIs) for the association between pregnancy and pregnancy loss with COPD. Results Pregnancy loss was significantly associated with increased risk of COPD (OR 1.19, 95% CI 1.13–1.25), specifically, spontaneous (OR 1.19, 95% CI 1.11–1.29) and induced abortion (OR 1.18, 95% CI 1.12–1.25). Stillbirth, however, was not significantly associated with the risk of COPD (OR 1.09, 95% CI 0.99–1.20). Increasing number of pregnancy losses was associated with increasing risk of COPD (one pregnancy loss: OR 1.14, 95% CI 1.07–1.21, two or more pregnancy loss: OR 1.25, 95% CI 1.17–1.32, and each additional pregnancy loss: OR 1.06, 95% CI 1.03–1.09). A single pregnancy was significantly associated with reduced risk of COPD (OR 0.75, 95% CI 0.59–0.97), although each additional pregnancy was significantly associated with increased risk of COPD (OR 1.03, 95% CI 1.01–1.04). Conclusion Pregnancy loss, in particular, spontaneous and induced abortions are associated with increased risk of COPD among Chinese women. A single pregnancy, however, demonstrated protective effects

Complex I assembly function and fatty acid oxidation enzyme activity of ACAD9 both contribute to disease severity in ACAD9 deficiency

Acyl-CoA dehydrogenase 9 (ACAD9) is an assembly factor for mitochondrial respiratory chain Complex I (CI), and ACAD9 mutations are recognized as a frequent cause of CI deficiency. ACAD9 also retains enzyme ACAD activity for long-chain fatty acids in vitro, but the biological relevance of this function remains controversial partly because of the tissue specificity of ACAD9 expression: high in liver and neurons and minimal in skin fibroblasts. In this study, we hypothesized that this enzymatic ACAD activity is required for full fatty acid oxidation capacity in cells expressing high levels of ACAD9 and that loss of this function is important in determining phenotype in ACAD9-deficient patients. First, we confirmed that HEK293 cells express ACAD9 abundantly. Then, we showed that ACAD9 knockout in HEK293 cells affected long-chain fatty acid oxidation along with Cl, both of which were rescued by wild type ACAD9. Further, we evaluated whether the loss of ACAD9 enzymatic fatty acid oxidation affects clinical severity in patients with ACAD9 mutations. The effects on ACAD activity of 16 ACAD9 mutations identified in 24 patients were evaluated using a prokaryotic expression system. We showed that there was a significant inverse correlation between residual enzyme ACAD activity and phenotypic severity of ACAD9-deficient patients. These results provide evidence that in cells where it is strongly expressed, ACAD9 plays a physiological role in fatty acid oxidation, which contributes to the severity of the phenotype in ACAD9-deficient patients. Accordingly, treatment of ACAD9 patients should aim at counteracting both CI and fatty acid oxidation dysfunction

Efficacious Intermittent Dosing of a Novel JAK2 Inhibitor in Mouse Models of Polycythemia Vera

A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617→Phe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617F-expressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients