Essays on risk and uncertainty in financial decision making: Bayesian inference of multi-factor affine term structure models and dynamic optimal portfolio choices for robust preferences

Thesis (Ph.D.)--Boston UniversityThis thesis studies model inference about risk and decision making under model uncertainty in two specific settings. The first part of the thesis develops a Bayesian Markov Chain Monte Carlo (MCMC) estimation method for multi-factor affine term structure models. Affine term structure models are popular because they provide closed-form solutions for the valuation of fixed income securities. Efficient estimation methods for parameters of these models, however, are not readily available. The MCMC algorithms developed provide more accurate estimates, compared with alternative estimation methods. The superior performance of the MCMC algorithms is first documented in a simulation study. Convergence of the algorithm used to sample posterior distributions is documented in numerical experiments. The Bayesian MCMC methodology is then applied to yield data. The in-sample pricing errors obtained are significantly smaller than those of alternative methods. A Bayesian forecast analysis documents the significant superior predictive power of the MCMC approach. Finally, Bayesian model selection criteria are discussed. Incorporating aspects of model uncertainty for the optimal allocation of risk has become an important topic in finance. The second part of the thesis considers an optimal dynamic portfolio choice problem for an ambiguity-averse investor. It introduces new preferences that allow the separation of risk and ambiguity aversion. The novel representation is based on generalized divergence measures that capture richer forms of model uncertainty than traditional relative entropy measures. The novel preferences are shown to have a homothetic stochastic differential utility representation. Based on this representation, optimal portfolio policies are derived using numerical schemes for forward-backward stochastic differential equations. The optimal portfolio policy is shown to contain new hedging motives induced by the investor's attitude toward model uncertainty. Ambiguity concerns introduce additional horizon effects, boost effective risk aversion, and overall reduce optimal investment in risky assets. These findings have important implications for the design of optimal portfolios in the presence of model uncertainty

Mechanism of liver regeneration: 20-year bibliometric analyses

Objectives: The study aims to explore the most influential countries, institutions, journals, authors, “research hotspots,” and trends in the study of the mechanism of liver regeneration (MoLR) in the last 20 years using bibliometric analyses.Methods: The literature associated with the MoLR was retrieved from the Web of Science Core Collection on 11 October 2022. CiteSpace 6.1.R6 (64-bit) and VOSviewer 1.6.18 were used for bibliometric analyses.Results: A total of 18,956 authors from 2,900 institutions in 71 countries/regions published 3,563 studies in different academic journals on the MoLR. The United States was the most influential country. The University of Pittsburgh was the institution from which most articles on the MoLR were published. Cunshuan Xu published the most articles on the MoLR, and George K. Michalopoulos was the most frequently co-cited author. Hepatology was the journal in which most articles on the MoLR were published and the most frequently co-cited journal in this field. The research hotspots for the MoLR were origin and subsets of hepatocytes during LR; new factors and pathways in LR regulation; cell therapy for LR; interactions between liver cells in LR; mechanism of the proliferation of residual hepatocytes and trans-differentiation between cells; and prognosis of LR. The emerging topic was the mechanism of regeneration of a severely injured liver.Conclusion: Our bibliometric analyses provide (i) a comprehensive overview of the MoLR; (ii) important clues and ideas for scholars in this field

Design and research of intelligent QA system for flight crew operating manual

Aviation flight crews rely on a large number of complex standard documents and operation manuals when performing flight tasks. In order to relieve the pressure of manual retrieval of documents, intelligent question-answering technology based on reading comprehension is gradually applied. In this paper, the flight crew operation manual SQuAD dataset is studied and built, based on which the reader-retriever framework of text content-based reading question answering system (TCQA) is analyzed and established. Experiments are conducted to compare the relevant indexes of the QA system with different combinations of reader and retriever models under the open-source tool haystack. Based on the comparison of response speed and retrieval capability, the best model combination is obtained for the flight crew operation manual dataset, and suggestions are made for the model-related performance improvement

Ku80 cooperates with CBP to promote COX-2 expression and tumor growth.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation

BACKGROUND: Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. METHODS: Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment. Cardiac function was analyzed in isolated-perfused working hearts, and myocardial total copper content measured by particle-induced x-ray emission spectroscopy (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative expression (mRNA and protein) and/or activity of key proteins that mediate LV-tissue-copper binding and transport, were analyzed by combined RT-qPCR, western blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical analysis was performed using Student’s t-tests or ANOVA and p-values of < 0.05 have been considered significant. RESULTS: Left-ventricular (LV) copper levels and function were severely depressed in rats following 16-weeks’ diabetes, but both were unexpectedly normalized 8-weeks after treatment with TETA was instituted. Localized myocardial copper deficiency was accompanied by decreased expression and increased polymerization of the copper-responsive transition-metal-binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant defences and elevated susceptibility to pro-oxidant stress. Levels of the high-affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with impaired membrane copper uptake, and were not modified by TETA which, contrastingly, renormalized myocardial copper and increased levels and cell-membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes also lowered indexes of intracellular (IC) copper delivery via the copper chaperone for superoxide dismutase (CCS) to its target cuproenzyme, superoxide dismutase-1 (SOD1): this pathway was rectified by TETA treatment, which normalized SOD1 activity with consequent bolstering of anti-oxidant defenses. Furthermore, diabetes depressed levels of additional intracellular copper-transporting proteins, including antioxidant-protein-1 (ATOX1) and copper-transporting-ATPase-2 (ATP7B), whereas TETA elevated copper-transporting-ATPase-1 (ATP7A). CONCLUSIONS: Myocardial copper deficiency and defective cellular copper transport/trafficking are revealed as key molecular defects underlying LV impairment in diabetes, and TETA-mediated restoration of copper regulation provides a potential new class of therapeutic molecules for DCM

Comprehensive Analysis of the Relationship Between RAS and RAF Mutations and MSI Status of Colorectal Cancer in Northeastern China

Background/Aims: Colorectal cancer (CRC) is mainly caused by chromosomal instability (CIN) and microsatellite instability (MSI). The RAS and RAF genes are essential components of the CIN pathway, and several studies have found that RAS and RAF mutations are associated with MSI status in CRC. Here, we examined these three factors in CRC in Northeast China and aimed to reveal new details of the relationship between these mutations and MSI status. Methods: This study involved 290 patients with CRC who had RAS or RAF gene mutation detected using fluorescence-based allele-specific polymerase chain reaction or Sanger sequencing. The majority of the identified patients were found to harbor MSI (MSI status). Accurate molecular detection was carried out using formalin-fixed paraffin-embedded tissue or blood samples. Results: The rates of RAS and RAF mutations were 58.5% and 4.1%, respectively. The prevalence of RAS mutation in CRC was clearly higher and that of RAF mutation was lower in Northeast China compared with previously reported cohorts in other locations. High MSI level (MSI-H status) was more complex, at around 10%. This was consistent with previous data from China. However, compared with data reported from other continents, MSI-H was higher than that of Japan or South Korea in Asia, and lower than that of Europe or the United States. Conclusion: RAS/RAF mutations and MSI status in CRC are closely associated with tumor location and ethnicity. Further studies investigating the relationship between these three factors can help in the development of treatment strategies for patients with CRC