Mechanisms by Which MnTE-2-PyP Suppresses Prostate Cancer Cell Growth

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial membrane potential was unaffected. In addition, MnTE-2-PyP significantly increased NAD(P)+/NAD(P)H ratios in PC3 and LNCaP cells in a dose-dependent manner, which was mainly due to a reduction of cellular NAD(P)H pool. Correspondingly, we observed a significant decrease of activity in glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD), which are major cellular NADPH producing enzymes in pentose phosphate pathway. A decrease of GSH/GSSG ratios were confirmed in MnTE-2-PyP-treated prostate cancer cells, which may result from the decreased glutathione reductase (GR) activity due to NADPH depletion. We also identified the oxidation of Ser/Thr protein phosphatase 1 beta catalytic subunit (PP1CB), and a decrease of PP1CB activity in MnTE-2-PyP-treated prostate cancer cells. One key protein, pRB, regulates cell cycle progression that is downstream target of PP1CB was hypophosphorylated in MnTE-2-PyP-treated prostate cancer cells. Significant increase of Ki67-negative populations were observed in both PC3 and LNCaP cells but overall cell cycle progression was not altered, which indicates v interfering cell cycle progression is not the major mechanism of MnTE-2-PyP-induced cell growth inhibition. Besides protein oxidation, MnTE-2-PyP also caused nuclear abnormalities in prostate cancer cells. High H2O2 levels by MnTE-2-PyP treatment induced nuclear fragmentation in PC3 cells, which could be synergistically enhanced with radiotherapy both in vitro and in vivo. In LNCaP cells, disturbing H2O2 balance may contribute to the bi-nucleation phenomenon. The increased H2O2 levels, protein oxidative modifications, mitotic catastrophe, cellular energy metabolism alterations, and NAD(P)H depletion caused by MnTE-2-PyP are all likely factors contributing to prostate cancer cell growth inhibition

Hunter gatherer: within-web-page collection making

Hunter Gatherer is a tool that lets Web users carry out three main tasks: (1) collect components from within Web pages; (2) represent those components in a collection; and (3) edit those collections. We report on the design and evaluation of the tool and contextualize tool use in terms of our research goals to investigate possible shifts in information interaction practices resulting from tool use

Spatial Dislocation Analysis of Tourism Economy and Its Influencing Factors in Jiangsu Province

Taking 13 prefecture-level cities in Jiangsu Province as the research object, based on the theory of spatial dislocation, the gravity model and two-dimensional composite matrix method are used to analyze the spatial dislocation between tourism resources, permanent population and other factors in Jiangsu Province and tourism revenue. The results show that the population center, the center of tourism resources, the center of tourist numbers, the center of economic development, and the center of tourism revenue of Jiangsu Province are all biased toward the southern part of Jiangsu Province. From the analysis of four sets of two-dimensional composite matrixes, 13 prefecture-level cities have synchronized coordination and also have positive and negative dislocation types. Southern Jiangsu has the best synchronization and coordination, and northern Jiangsu has a strong negative dislocation trend; the combination of tourist numbers and tourism revenue is the strongest, but the dislocation is weak; population and tourism revenue have a strong positive dislocation trend; there is a strong negative dislocation trend between economic development and tourism revenue; the matrix combination of Nanjing, Wuxi and Suzhou has good synchronization; the city of Xuzhou in northern Jiangsu has a strong negative dislocation. In view of the results of spatial dislocation analysis, suggestions for improvement and optimization are put forward to promote the high-quality development of tourism in Jiangsu Province

UNDERSTANDING POST ADOPTION SWITCHING BEHAVIOR FOR MOBILE INSTANT MESSAGING APPLICATION IN CHINA: BASED ON MIGRATION THEORY

Post adoptive IT use is a hot research stream in information systems field, including continuance behaviours and switching behaviours. While there are a great number of studies on users’ intentions or behaviors for diversified information systems, previous post adoptive IT studies pay relatively less attention on users’ switching behaviors. Hence, we know little about this phenomenon and triggers on users’ switching behaviors. This research identifies the features of users IT switching behaviors and examines what trigger their switching intentions and actual behaviors in the context of mobile instant messaging (MIM) application in China. A model of MIM switching behaviors is developed based on Curran and Saguy’s (2001) research on how networks of obligation, trust and relative deprivation affect human’s migration decision and process. Besides these three triggers, we also introduce dissatisfaction and curiosity into our model according to prior IS studies on switching behaviors. A survey research method will be adopted to test this model. Overall, our study may theoretically contribute to further understand users’ IT switching behaviors and yield some practical implications for designers and managers in MIM providers and their products propaganda

Federated Two Stage Decoupling With Adaptive Personalization Layers

Federated learning has gained significant attention due to its groundbreaking ability to enable distributed learning while maintaining privacy constraints. However, as a consequence of data heterogeneity among decentralized devices, it inherently experiences significant learning degradation and slow convergence speed. Therefore, it is natural to employ the concept of clustering homogeneous clients into the same group, allowing only the model weights within each group to be aggregated. While most existing clustered federated learning methods employ either model gradients or inference outputs as metrics for client partitioning, with the goal of grouping similar devices together, may still have heterogeneity within each cluster. Moreover, there is a scarcity of research exploring the underlying reasons for determining the appropriate timing for clustering, resulting in the common practice of assigning each client to its own individual cluster, particularly in the context of highly non independent and identically distributed (Non-IID) data. In this paper, we introduce a two-stage decoupling federated learning algorithm with adaptive personalization layers named FedTSDP, where client clustering is performed twice according to inference outputs and model weights, respectively. Hopkins amended sampling is adopted to determine the appropriate timing for clustering and the sampling weight of public unlabeled data. In addition, a simple yet effective approach is developed to adaptively adjust the personalization layers based on varying degrees of data skew. Experimental results show that our proposed method has reliable performance on both IID and non-IID scenarios

The impact of evidence type and message framing on promoting HPV vaccination in online health communities

Message features and type are crucial in health-related communication, especially due to the potential impact these messages can have on an individual's health. This study uses a 2 ' 2 experimental design (evidence type: statistical evidence vs. narrative evidence; message framing: gain-framed message vs. loss-framed message), to investigate how evidence type and message framing affect the attitudes, health beliefs, and intentions of college students in online health communities, regarding getting the HPV vaccination. Preliminary results (N=300) indicated that; (1) evidence type and message framing both influence attitudes and intentions significantly; Statistical evidence will lead to more favorable views than narrative evidence, and loss-framed messages will lead to more favorable views than gain-framed messages. (2) Concerning the interactions, we used construal level theory and found that, for gain-framed message, narrative evidence will lead to more favorable attitudes, free intentions, perceived benefits and barriers of HPV vaccination than statistical evidence; for loss-framed message, statistical evidence will lead to more favorable attitudes, intentions, perceived seriousness, benefits and barriers of HPV vaccination than narrative evidence