Asset pricing across asset classes: the impacts of fines and flows

This thesis consists of four empirical studies that examine two types of information, using a unique set of fines and fund flow data, on a multi–asset setting. The first study finds underperformance of between 29 and 57 basis points per month measured as Carhart model alphas on long-term stock returns of firms after announcements of monetary fines. Additionally, environmental fines are perceived by investors to be more of a concern while social, governance and also long-term aspects matter somewhat less. In the second study, I extend the research on fines by examining the inter-link between equities and bonds using short selling ratios and bond returns. Analysis using a fixed-income model shows that high short selling in the context of fines induces negative underperformances in bond returns. In addition, the underperformances are more profound for portfolios with longer remaining years to maturity and in crisis periods. The third study examines short-term reaction of Credit Default Swaps (CDS) spread changes and stock returns to fines. I find the CDS market is able to anticipate illegality news. Both markets react very differently to fines in different legal stages, industries and also by type of fine. Environmental issues are also a key concern in both CDS and stock markets and they also react more to higher fines per market cap. These empirical studies show that information about fines are valuable for investors as on average companies with illegalities underperform relevant benchmarks in the short and long-term. The fourth study involves fund flows on a global scale in Exchange Traded Funds (ETFs). I use panel data models and find that the explanatory power of ETF fund flows are similar to macro-economic variables in explaining indices returns. I also find investors could use ETF fund flows as information to understand market movements especially globally

Breast Cancer: From Transcriptional Control to Clinical Outcome

Breast cancer is the most common malignancy in women worldwide. The risk of breast cancer in women increases with age, and this is partly attributable to the accumulation of genetic lesions. Growing evidence demonstrates the role played by epigenetic modifiers and the tumor microenvironment in contributing to the increased risk of breast cancer. This chapter provides a comprehensive overview of the epigenetic regulatory signatures that impact the well-studied signaling pathways in breast tissues. Additionally, we will also delve into the therapeutic and diagnostic potential of noncoding RNAs in breast cancer

Lysine acetyltransferase Tip60 is required for hematopoietic stem cell maintenance.

Hematopoietic stem cells (HSCs) have the potential to replenish the blood system for the lifetime of the organism. Their 2 defining properties, self-renewal and differentiation, are tightly regulated by the epigenetic machineries. Using conditional gene-knockout models, we demonstrated a critical requirement of lysine acetyltransferase 5 (Kat5, also known as Tip60) for murine HSC maintenance in both the embryonic and adult stages, which depends on its acetyltransferase activity. Genome-wide chromatin and transcriptome profiling in murine hematopoietic stem and progenitor cells revealed that Tip60 colocalizes with c-Myc and that Tip60 deletion suppress the expression of Myc target genes, which are associated with critical biological processes for HSC maintenance, cell cycling, and DNA repair. Notably, acetylated H2A.Z (acH2A.Z) was enriched at the Tip60-bound active chromatin, and Tip60 deletion induced a robust reduction in the acH2A.Z/H2A.Z ratio. These results uncover a critical epigenetic regulatory layer for HSC maintenance, at least in part through Tip60-dependent H2A.Z acetylation to activate Myc target genes.Cancer Research UK, Wellcome Trust, National Institutes of Health, Singapore state fundin

Decreased Prevalence of Lymphatic Filariasis among Diabetic Subjects Associated with a Diminished Pro-Inflammatory Cytokine Response (CURES 83)

Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF) and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416) as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%]) compared to pre-diabetic subjects [9.1%] (p = 0.0095) and non-diabetic subjects [10.4%] (p = 0.0463). A significant decrease in filarial antigen load (p = 0.04) was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines—IL-6 and GM-CSF—were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines—IL-10, IL-13 and TGF-β—between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF

MECHANISTIC CHARACTERIZATION OF THE TUMOR SUPPRESSIVE ROLE OF TIP60 IN CANCER

Ph.DDOCTOR OF PHILOSOPHY (SOM

Exfoliated Graphite Nanofibers: Structure, Adsorption, and Electric Double-layer Capacitance

Herringbone graphite nanofibers (GNF) provide an interesting candidate for carbon exfoliation, with their slit-pore geometry, nano-scale dimensions, high aspect ratio, and graphitic layers that terminate along the fiber axis. Well-established graphite exfoliation techniques of acid intercalation followed by thermal treatment were applied to herringbone GNF, and the resulting fibers were characterized by HRTEM, XRD, EELS, EDS, TPO, gas adsorption, and cyclic voltammetry. Variations in thermal treatment led to drastic variations in the resulting fiber structure: A mild thermal treatment led to dislocations within the graphitic lattice and a 5% lattice expansion, whereas an extended thermal treatment led to an estimated 20-fold expansion and a ten-fold increase in surface area. The latter fiber had a unique structure with repeating interior amorphous carbon mesopores sandwiched between graphitic regions from the original herringbone morphology. The increased surface area of the exfoliated GNF correlated with increased low temperature hydrogen physisorption, whereas the observed dislocations in the graphitic structure correlated with ambient temperature hydrogen adsorption. Mild oxidation of the exfoliated GNF allowed access to the interior mesopores and led to an increased electrical double layer capacitance. These results suggest that selective exfoliation of a nanocarbon is a means to induce interior mesorpores with a controlled pore size distribution which in turn will control the relative adsorption binding energy and the accessibility of mesopores for electrical double layer capacitors. Work to control the interior pore size to provide optimal lattice spacing for a given application will be discussed

The oncogenic E3 ligase TRIP12 suppresses epithelial-mesenchymal transition (EMT) and mesenchymal traits through ZEB1/2

10.1038/s41420-021-00479-zCELL DEATH DISCOVERY7

The large protein ``L' of Peste-des-petits-ruminants virus exhibits RNA triphosphatase activity, the first enzyme in mRNA capping pathway

Peste-des-petits-ruminants is a highly contagious and fatal disease of goats and sheep caused by non-segmented, negative strand RNA virus belonging to the Morbillivirus genusPeste-des-petits-ruminants virus (PPRV) which is evolutionarily closely related to Rinderpest virus (RPV). The large protein L' of the members of this genus is a multifunctional catalytic protein, which transcribes and replicates the viral genomic RNA as well as possesses mRNA capping, methylation and polyadenylation activities; however, the detailed mechanism of mRNA capping by PPRV L protein has not been studied. We have found earlier that the L protein of RPV has RNA triphosphatase (RTPase), guanylyltransferase (GTase) and methyltransferase activities, and unlike vesicular stomatitis virus (VSV), follows the conventional pathway of mRNA capping. In the present work, using a 5-end labelled viral RNA as substrate, we demonstrate that PPRV L protein has RTPase activity when present in the ribonucleoprotein complex of purified virus as well as recombinant L-P complex expressed in insect cells. Further, a minimal domain in the C-terminal region (aa1640-1840) of the L protein has been expressed in E. coli and shown to exhibit RTPase activity. The RTPase activity of PPRV L protein is metal-dependent and functions with a divalent cation, either magnesium or manganese. In addition, RTPase associated nucleotide triphosphatase activity (NTPase) of PPRV L protein is also demonstrated. This work provides the first detailed study of RTPase activity and identifies the RTPase domain of PPRV L protein

Decreased prevalence of lymphatic filariasis among diabetic subjects associated with a diminished pro-inflammatory cytokine response (CURES 83). PLoS Negl Trop Dis 4: e707. doi: 10.1371/journal.pntd.0000707

Abstract Epidemiological studies have shown an inverse correlation between the incidence of lymphatic filariasis (LF) and the incidence of allergies and autoimmunity. However, the interrelationship between LF and type-2 diabetes is not known and hence, a cross sectional study to assess the baseline prevalence and the correlates of sero-positivity of LF among diabetic subjects was carried out (n = 1416) as part of the CURES study. There was a significant decrease in the prevalence of LF among diabetic subjects (both newly diagnosed [5.7%] and those under treatment [4.3%]) compared to pre-diabetic subjects [9.1%] (p = 0.0095) and non-diabetic subjects [10.4%] (p = 0.0463). A significant decrease in filarial antigen load (p = 0.04) was also seen among diabetic subjects. Serum cytokine levels of the pro-inflammatory cytokines-IL-6 and GM-CSF-were significantly lower in diabetic subjects who were LF positive, compared to those who were LF negative. There were, however, no significant differences in the levels of anti-inflammatory cytokines-IL-10, IL-13 and TGF-b-between the two groups. Although a direct causal link has yet to be shown, there appears to be a striking inverse relationship between the prevalence of LF and diabetes, which is reflected by a diminished pro-inflammatory cytokine response in Asian Indians with diabetes and concomitant LF