Investigating emerging market economies Reverse REIT-Bond Yield Gap anomalies: a case for tactical asset allocation under the multivariate Markov regime switching model

Submitted in partial fulfilment of the requirements for the degree of Masters of Management in Finance and Investments In the Faculty of Commerce, Law and Management University of the Witwatersrand, Wits Business School, 2016This paper presents a first time application of a variant of the concepts underpinning the Fed Model, amalgamated with the Bond-Stock Earnings Yield Differential, by applying it to the dividend yields of REIT indices. This modification is termed the yield gap, quantitatively constructed and adapted in this paper as the Reverse REIT-Bond Yield Gap. This metric is then used as the variable of interest in a multivariate Markov regime switching model framework, along with a set of three regressors. The REIT indices trailing dividend yield and associated metrics are the FTSE/EPRA NAREIT series. All data are from Bloomberg Terminals. This paper examines 11 markets, of which the EMEs are classified as Brazil, Mexico, Turkey and South Africa, whereas the advanced market counterparts are Australia, France, Japan, the Netherlands, Singapore, the United Kingdom, and the United States. The time-frame spans the period June 2013 until November 2015 for the EMEs, whilst their advanced market counterparts time-span covers the period November 2009 until November 2015. This paper encompasses a tri-fold research objective, and aims to accomplish them in a scientifically-based, objective and coherent fashion. Specifically, the purpose is in an attempt to gauge the reasons underlying EMEs observed anomalies entailing reverse REIT-Bond yield gaps, whereby their tenyear nominal government bonds out-yield their trailing dividend yields on their associated REIT indices; what drives fluctuations in this metric; and whether or not profitable tactical asset allocation strategies can be formulated to exploit any arbitrage mispricing opportunities. The Markov models were unable to generate clear-cut, definitive reasons regarding why EMEs experience this anomaly. Objectives two and three were achieved, except for France and Mexico. The third objective was also met. The REIT-Bond Yield Gaps static conditions have high probabilities of continuing in the same direction and magnitude into the future. In retrospection, the results suggest that by positioning an investment strategy, taking cognisance of the chain of economic events that are likely to occur following static REIT-Bond Yield Gaps, then investors, portfolio rebalancing and risk management techniques, hedging, targeted, tactical and strategic asset allocation strategies could be formulated to exploit any potential arbitrage profits. The REIT-Bond Yield Gaps are considered highly contentious, yet encompasses the potential for significant reward. The Fed Model insinuates that EME REIT markets are overvalued relative to their respective government bonds, whereas their advanced market counterparts exhibit the opposite phenomenon.XL201

Gene Therapy Combined with IPC Cell Induction to Treat Huntington’s Disease

Huntington’s disease (HD) results from expansion of CAG repeats in the huntingtin gene in chromosome 4, resulting in misfolded and aggregated huntingtin protein inside medium spiny neurons. In HD, these neurons ultimately die, resulting in the classical symptoms of the disease. Current treatments for HD are ineffective, as none attempt to treat the source of the disease. A new method that attempts to correct the expanded huntingtin gene is needed for effective, long term treatment of the disease. Recent advances in the field of induced pluripotent stem cells and gene therapy have shown that induction of pluripotency combined with homologous recombination can correct genetic disease in mice. We propose the hypothesis that fibroblasts from HD model mice and human HD patients can be transformed into IPS cells. After IPS cell formation, the huntingtin gene will be repaired using homologous recombination, and the cells will be directly differentiated into medium spiny neurons. Transplantation of the neurons into HD mice models representing healthy, mild, and severe forms of the disease will follow, and improvements in HD related symptoms will be evaluated. Perfection of our methods is vital to future use of IPS cells and gene therapy to treat disease

Biological significance of cancer antigen 125

Morphological changes including fibrosis, vascular degeneration and loss of mesothelium occur to the peritoneal membrane during peritoneal dialysis. The loss of mesothelium is thought to effect peritoneal homeostasis and host defence, as these cells play a pivotal role in these organs response to inflammation. Cancer antigen 125 (CA125), a mucilaginous high molecular weight glycoprotein, has been used as a marker of peritoneal mesothelial cells mass/turnover and membrane functional integrity in peritoneal dialysis patients. The use of new more biocompatible dialysis solutions is associated with an increase in CA125 effluent concentration, however it's precise molecular nature, function and regulation is poorly defined. This study investigates the transcriptional mechanisms regulating CA125 expression in human peritoneal mesothelial cells as well as CA125's regulation in response to inflammation. Additionally, CA125's function in the process of mesothelial cell repair is examined using a novel mesothelial wound healing system. These investigations have: Successfully reconstructed the genomic structure of CA125 and characterised its proximal promoter region. Demonstrated regulation of CA125 cell surface expression and shedding in response to IL-1 p and IL-6 trans-signalling. Shown the retardation of human peritoneal mesothelial cell CA125 shedding in response to high levels of glucose degradation products present within peritoneal dialysis fluids. Shown the improved wound healing of mesothelial cells in response to elevated CA125 levels. These investigations have clarified existing discrepancies regarding CA125 regulation during inflammation by demonstrating its altered expression at the cell surface, in response to inflammatory mediators. Additionally, this work has linked clinical Observations regarding CA125 effluent levels during peritoneal dialysis to a potential role of CA125 in wound healing of the mesothelium.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Biological significance of cancer antigen 125.

Morphological changes including fibrosis, vascular degeneration and loss of mesothelium occur to the peritoneal membrane during peritoneal dialysis. The loss of mesothelium is thought to effect peritoneal homeostasis and host defence, as these cells play a pivotal role in these organs response to inflammation. Cancer antigen 125 (CA125), a mucilaginous high molecular weight glycoprotein, has been used as a marker of peritoneal mesothelial cells mass/turnover and membrane functional integrity in peritoneal dialysis patients. The use of new more biocompatible dialysis solutions is associated with an increase in CA125 effluent concentration, however it's precise molecular nature, function and regulation is poorly defined. This study investigates the transcriptional mechanisms regulating CA125 expression in human peritoneal mesothelial cells as well as CA125's regulation in response to inflammation. Additionally, CA125's function in the process of mesothelial cell repair is examined using a novel mesothelial wound healing system. These investigations have: Successfully reconstructed the genomic structure of CA125 and characterised its proximal promoter region; Demonstrated regulation of CA125 cell surface expression and shedding in response to IL-1 p and IL-6 trans-signalling; Shown the retardation of human peritoneal mesothelial cell CA125 shedding in response to high levels of glucose degradation products present within peritoneal dialysis fluids; Shown the improved wound healing of mesothelial cells in response to elevated CA125 levels. These investigations have clarified existing discrepancies regarding CA125 regulation during inflammation by demonstrating its altered expression at the cell surface, in response to inflammatory mediators. Additionally, this work has linked clinical observations regarding CA125 effluent levels during peritoneal dialysis to a potential role of CA125 in wound healing of the mesothelium

Active immunisation of mice with GnRH lipopeptide vaccine candidates: importance of T helper or multi-dimer GnRH epitope

Active immunisation against gonadotropin releasing hormone (GnRH) is a potential alternative to surgical castration. This study focused on the development of a GnRH subunit lipopeptide vaccine. A library of vaccine candidates that contained one or more (up to eight) copies of monomeric or dimeric GnRH peptide antigen, an adjuvanting lipidic moiety based on lipoamino acids, and an additional T helper epitope, was synthesised by solid phase peptide synthesis. The candidates were evaluated in vivo in order to determine the minimal components of this vaccine necessary to induce a systemic immune response. BALB/c mice were immunised with GnRH lipopeptide conjugates, co-administered with or without Complete Freund's Adjuvant, followed by two additional immunisations. Significant GnRH-specific IgG titres were detected in sera obtained from mice immunised with four of the seven lipopeptides tested, with an increase in titres observed after successive immunisations. This study highlights the importance of for epitope optimisation and delivery system design when producing anti-hapten antibodies in vivo. The results of this study also contribute to the development of future clinical and veterinary immunocontraceptives

A unique combination of nutritionally active ingredients can prevent several key processes associated with atherosclerosis in vitro

Atherosclerosis is the underlying cause of cardiovascular disease that leads to more global mortalities each year than any other ailment. Consumption of active food ingredients such as phytosterols, omega-3 polyunsaturated fatty acids and flavanols are known to impart beneficial effects on cardiovascular disease although the combined actions of such agents in atherosclerosis is poorly understood. The aim of this study was to screen a nutritional supplement containing each of these active components for its anti-atherosclerotic effect on macrophages in vitro.The supplement attenuated the expression of intercellular adhesion molecule-1 and macrophage chemoattractant protein-1 in human and murine macrophages at physiologically relevant doses. The migratory capacity of human monocytes was also hindered, possibly mediated by eicosapentaenoic acid and catechin, while the ability of foam cells to efflux cholesterol was improved. The polarisation of murine macrophages towards a pro-inflammatory phenotype was also attenuated by the supplement.The formulation was able to hinder multiple key steps of atherosclerosis development in vitro by inhibiting monocyte recruitment, foam cell formation and macrophage polarisation towards an inflammatory phenotype. This is the first time a combination these ingredients has been shown to elicit such effects and supports its further study in preclinical in vivo models

The role of mitogen-activated protein kinases and sterol receptor coactivator-1 in TGF-β-regulated expression of genes implicated in macrophage cholesterol uptake

The anti-atherogenic cytokine TGF-β inhibits macrophage foam cell formation by suppressing the expression of key genes implicated in the uptake of modified lipoproteins. We have previously shown a critical role for p38 MAPK and JNK in the TGF-β-mediated regulation of apolipoprotein E expression in human monocytes. However, the roles of these two MAPK pathways in the control of expression of key genes involved in the uptake of modified lipoproteins in human macrophages is poorly understood and formed the focus of this study. TGF-β activated both p38 MAPK and JNK, and knockdown of p38 MAPK or c-Jun, a key downstream target of JNK action, demonstrated their requirement in the TGF-β-inhibited expression of several key genes implicated in macrophage lipoprotein uptake. The potential role of c-Jun and specific co-activators in the action of TGF-β was investigated further by studies on the lipoprotein lipase gene. c-Jun did not directly interact with the minimal promoter region containing the TGF-β response elements and a combination of transient transfection and knock down assays revealed an important role for SRC-1. These studies provide novel insights into the mechanisms underlying the TGF-β-mediated inhibition of macrophage gene expression associated with the control of cholesterol homeostasis

The phosphoinositide 3-kinase signaling pathway is involved in the control of modified low-density lipoprotein uptake by human macrophages

The transformation of macrophages into lipid-loaded foam cells is a critical early event in the pathogenesis of atherosclerosis. Both receptor-mediated uptake of modified LDL, mediated primarily by scavenger receptors-A (SR-A) and CD36 along with other proteins such as lipoprotein lipase (LPL), and macropinocytosis contribute to macrophage foam cell formation. The signaling pathways that are involved in the control of foam cell formation are not fully understood. In this study, we have investigated the role of phosphoinositide 3-kinase (PI3K) in relation to foam cell formation in human macrophages. The pan PI3K inhibitor LY294002 attenuated the uptake of modified LDL and macropinocytosis, as measured by Lucifer Yellow uptake, by human macrophages. In addition, the expression of SR-A, CD36 and LPL was attenuated by LY294002. The use of isoform-selective PI3K inhibitors showed that PI3K-β, -γ and -δ were all required for the expression of SR-A and CD36 whereas only PI3K-γ was necessary in the case of LPL. These studies reveal a pivotal role of PI3K in the control of macrophage foam cell formation and provide further evidence for their potential as therapeutic target against atherosclerosis

Phase II Study of Celecoxib and Docetaxel in Non-small Cell Lung Cancer (NSCLC) Patients with Progression after Platinum-Based Therapy

IntroductionTo evaluate the efficacy and toxicity of the combination of celecoxib and docetaxel in patients with advanced non-small cell lung cancer after failure of platinum-based therapy.MethodsPatients with relapsed non-small cell lung cancer received celecoxib 400 mg orally twice daily beginning 7 days before the first cycle of docetaxel and the celecoxib was continued with no interruption. Docetaxel 75 mg/m2 was administered intravenously on a 21-day cycle. The primary end point of the study was the 6-month survival rate.ResultsTwenty-four patients were enrolled and twenty patients were treated (median age 60, M:F 16:8). Most patients had a baseline performance status of 1. The objective response rate was 10% (95% confidence interval [CI], 0–25%) and the 6-month survival rate was 59% (95% CI 37–80%). Median survival time was 6.9 months (95% CI, 2.8–15.2 months) and the 1- and 2-year survival rates were 36% (95% CI, 15–57%) and 1% (95% CI, 0–10%), respectively. The most frequent grade ≥3 adverse events were neutropenia (58%) and neutropenic fever (21%) which resulted in early closure of the trial.ConclusionsThe addition of celecoxib to docetaxel did not seem to improve the response rate and survival compared with docetaxel alone. The combination demonstrated considerable neutropenia and complications from febrile neutropenia that suggests celecoxib may enhance the marrow toxicity of docetaxel