A multivariate generalized ARCH approach to modeling risk premia in forward foreign exchange rate markets

Assuming that daily spot exchange rates follow a martingale process, we derive the implied time series process for the vector of 30-day forward rate forecast errors from using weekly data. The conditional second moment matrix of this vector is modelled as a multivariate generalized ARCH process. The estimated model is used to test the hypothesis that the risk premium is a linear function of the conditional variances and covariances as suggested by the standard asset pricing theory literature. Little supportt is found for this theory; instead lagged changes in the forward rate appear to be correlated with the 'risk premium.'. © 1990.

beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi.

Phosphorylation of the beta(2) adrenoreceptor (beta(2)AR) by cAMP-activated protein kinase A (PKA) switches its predominant coupling from stimulatory guanine nucleotide regulatory protein (G(s)) to inhibitory guanine nucleotide regulatory protein (G(i)). beta-Arrestins recruit the cAMP-degrading PDE4 phosphodiesterases to the beta(2)AR, thus controlling PKA activity at the membrane. Here we investigate a role for PDE4 recruitment in regulating G protein switching by the beta(2)AR. In human embryonic kidney 293 cells overexpressing a recombinant beta(2)AR, stimulation with isoprenaline recruits beta-arrestins 1 and 2 as well as both PDE4D3 and PDE4D5 to the receptor and stimulates receptor phosphorylation by PKA. The PKA phosphorylation status of the beta(2)AR is enhanced markedly when cells are treated with the selective PDE4-inhibitor rolipram or when they are transfected with a catalytically inactive PDE4D mutant (PDE4D5-D556A) that competitively inhibits isoprenaline-stimulated recruitment of native PDE4 to the beta(2)AR. Rolipram and PDE4D5-D556A also enhance beta(2)AR-mediated activation of extracellular signal-regulated kinases ERK12. This is consistent with a switch in coupling of the receptor from G(s) to G(i), because the ERK12 activation is sensitive to both inhibitors of PKA (H89) and G(i) (pertussis toxin). In cardiac myocytes, the beta(2)AR also switches from G(s) to G(i) coupling. Treating primary cardiac myocytes with isoprenaline induces recruitment of PDE4D3 and PDE4D5 to membranes and activates ERK12. Rolipram robustly enhances this activation in a manner sensitive to both pertussis toxin and H89. Adenovirus-mediated expression of PDE4D5-D556A also potentiates ERK12 activation. Thus, receptor-stimulated beta-arrestin-mediated recruitment of PDE4 plays a central role in the regulation of G protein switching by the beta(2)AR in a physiological system, the cardiac myocyte.

Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study.

Duchenne muscular dystrophy is caused by dystrophin deficiency and muscle deterioration and preferentially affects boys. Antisense-oligonucleotide-induced exon skipping allows synthesis of partially functional dystrophin. We investigated the efficacy and safety of drisapersen, a 2'-O-methyl-phosphorothioate antisense oligonucleotide, given for 48 weeks.

Postcolonial futures: postcolonial literature and the Obama moment

In an analysis of President Obama's Acceptance Speech, this article argues that postcolonial theory is now being re-formulated for a global, transnational sensibility.

Postcolonial futures: postcolonial literature and the Obama moment

Since the late 1970s the western academy has encouraged the development of postcolonial literary theory and the formulation of a postcolonial literary canon existing outside the prescriptive narratives of the ‘mother’ country and empire. Having lost faith in the binary oppositions underpinning such narratives, we turned to alternative fictions that contested the construction of the ‘other’, the world divided between the ‘West and the Rest’. The publication of Edward Said’s Orientalism in 1978 marked the beginning of the discipline now known as postcolonial studies with its new ways of understanding ‘the west’s’ relationship with ‘the east’ and, by extension, all the former colonies of empire. Despite these radical origins, however, postcolonialism’s more recent emphasis on the psychological and its affirmation of the hybrid text and self has, for many, served to obscure real economic social realities that have very little to do with the magical or wondrous textual expression of a postcolonial identity. This paper considers problems associated with defining the postcolonial and proposes that, in a literary context, we broaden its meaning to include texts traditionally outside the category of postcolonial literature. To extend the meaning of postcolonial is timely as we are now witnessing its relocation from ‘margin’ to ‘centre’ with the election of Barack Obama. This moment may be seen as a disruption of conventional understandings of what constitutes postcolonial literature, essentially as oppositional discourse that could only define itself as peripheral to, or ‘post’, metropolitan and economic concerns. [From the Author]

p53 Regulates the Formation of Lamellipodia and Circular Dorsal Ruffles Through Caldesmon and PTEN

Vascular smooth muscle cell migration is a significant contributor to many aspects of heart disease, and specifically atherosclerosis. Tissue damage in the arteries can result in the formation of a fatty streak. Smooth muscle cells (SMC) can then migrate to this site to form a fibrous cap, stabilizing the fatty plaque. Since cardiovascular disease is the leading cause of death in developed countries, this function of SMC is an essential area of study. The formation of lamellipodia and circular dorsal ruffles were studied in this project as indicators that cell migration is occurring. The roles of the proteins p53, Rac, caldesmon and PTEN were investigated with regards to these actin-based structures. The tumour suppressor p53 is often reported to cause apoptosis, senescence or cell cycle arrest when stress is placed on a cell, but has recently been shown to regulate cell migration as well. It was determined in this project that p53 could inhibit the formation of both lamellipodia and circular dorsal ruffles. It was also shown that this could occur directly through an inhibition of the GTPase Rac. Previous studies have shown that p53 can upregulate caldesmon, a protein which is known to bind to and stabilize actin filaments while inhibiting Arp2/3-mediated branching. It was confirmed that p53 could upregulate caldesmon, and that caldesmon could inhibit the formation of lamellipodia and circular dorsal ruffles. The phosphorylation of caldesmon by p21-associated kinase (PAK) or extracellular signal-related kinase (Erk) was shown to effectively reverse the ability of caldesmon to inhibit these structures. The role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) was also studied with regards to this signalling pathway. PTEN was shown to inhibit lamellipodia and circular dorsal ruffles through its lipid phosphatase activity. It was concluded that p53 can inhibit the formation of lamellipodia and circular dorsal ruffles in vascular SMC, and that this occurs through Rac, caldesmon and PTEN.

Breaking New Ground: The First Generation of Women to Work as Professional Authors in English Canada (1880-1920)

In the later decades of the nineteenth century and the early decades of the twentieth, large numbers of Canadian women were stepping out of the shadows of private life and into the public world of work and political action. Among them, both a cause and an effect of these sweeping social changes, was the first generation of Canadian women to work as professional authors. Although these women were not unified by ideology, genre, or date of birth, they are studied here as a generation defined by their time and place in history, by their material circumstances, and by their collective accomplishment. Chapters which focus on E. Pauline Johnson (Tekahionwake), the Eaton sisters (Sui Sin Far and Onoto Watanna), Joanna E. Wood, and Sara Jeannette Duncan explore some of the many commonalities and interrelationships among the members of this generation as a whole. This project combines archival research with analytical bibliography in order to clarify and extend our knowledge of Johnson’s and Duncan’s professional lives and publishing histories, and to recover some of Wood’s “lost” stories. This research offers a preliminary sketch of the long tradition of the platform performance (both Native and non-Native) with which Johnson and others engaged. It explores the uniquely innovative ethnographic writings of Johnson, Duncan, and the Eaton sisters, among others, and it explores thematic concerns which relate directly to the experiences of working women. Whether or not I convince other scholars to treat these authors as a generation, with more in common than has previously been supposed, the strong parallels revealed in these pages will help to clarify and contextualize some of their most interesting work.

A precisely-dated lake-level rise marked by diatomite formation in northeastern Ireland

The intercorrelation of palaeoclimate events from various studies is often hindered by a lack of precise chronological control. Tephra isochrons can overcome this problem by providing direct site linkages. This paper outlines a study of Holocene peat and diatomite deposits that accumulated within the floodplain of Lough Neagh, Northern Ireland. The Icelandic Hekla 4 tephra has been identified at the base of diatomite deposits at a number of sites and provides firm dating evidence for a widespread flooding event in the area at ca. 2300 BC. The evidence is consistent with other studies in Ireland and elsewhere for increased wetness at this time. The results demonstrate that the terrestrial deposits around Lough Neagh contain an important record of Holocene lake-level change. Dendrochronological evidence from the Lough Neagh area provides additional information about lake-level fluctuations over the past two millennia.

Testing solar forcing of pervasive Holocene climate cycles

The temporal and spatial extent of Holocene climate change is an area of considerable uncertainty, with solar forcing recently proposed to be the origin of cycles identified in the North Atlantic region. To address these issues we have developed an annually resolved record of changes in Irish bog tree populations over the last 7468 years which, together with radiocarbon-dated bog and lake-edge populations, extend the dataset back to 9000 yr ago. The Irish trees underpin the internationally accepted radiocarbon calibration curve, used to derive a proxy of solar activity, and allow us to test solar forcing of Holocene climate change. Tree populations and age structures provide unambiguous evidence of major shifts in Holocene surface moisture, with a dominant cyclicity of 800 yr, similar to marine cycles in the North Atlantic, indicating significant changes in the latitude and intensity of zonal atmospheric circulation across the region. The cycles, however, are not coherent with changes in solar activity (both being on the same absolute timescale), indicating that Holocene North Atlantic climate variability at the millennial and centennial scale is not driven by a linear response to changes in solar activity.

Holocene climate change and past Irish societal response

The extent to which North Atlantic Holocene climatic perturbations influenced past human societies is an area of considerable uncertainty and fierce debate. Ireland is ideally placed to help resolve this issue, being occupied for over 9000 yr and located on the eastern Atlantic seaboard, a region dominated by westerly airflow. Irish bog and lake tree populations provide unambiguous evidence of major shifts in surface moisture through the Holocene similar to cycles recorded in the marine realm of the North Atlantic, indicating significant changes in the latitude and intensity of zonal atmospheric circulation across the region. To test for human response to these cycles we summed the probabilities of 465 radiocarbon ages obtained from Irish archaeological contexts and observe enhanced archaeological visibility during periods of sustained wet conditions. These results suggest either increasing density of human populations in key, often defensive locations, and/or the development of subsistence strategies to overcome changing conditions, the latter recently proposed as a significant factor in avoiding societal collapse. Regardless, we demonstrate environmental change is a significantly more important factor in influencing human activity in the landscape than has hitherto been acknowledged.