Scalar BEKK and indirect DCC

The paper derives the scalar special case of the well‐known BEKK multivariate GARCH model using a multivariate extension of the random coefficient autoregressive (RCA) model. This representation establishes the relevant structural and asymptotic properties of the scalar BEKK model using the theoretical results available in the literature for general multivariate GARCH. Sufficient conditions for the (direct) DCC model to be consistent with a scalar BEKK representation are established. Moreover, an indirect DCC model that is consistent with the scalar BEKK representation is obtained, and is compared with the direct DCC model using an empirical example. The paper shows, within an asset allocation and risk measurement framework, that the two models are similar in terms of providing parameter estimates and forecasting value‐at‐risk thresholds for equally weighted and minimum variance portfolios. Copyright © 2008 John Wiley & Sons, Ltd.     

Forecasting euro area variables with German pre‐EMU data

It is investigated whether euro area variables can be forecast better based on synthetic time series for the pre‐euro period or by using just data from Germany for the pre‐euro period. Our forecast comparison is based on quarterly data for the period 1970Q1–2003Q4 for 10 macroeconomic variables. The years 2000–2003 are used as forecasting period. A range of different univariate forecasting methods is applied. Some of them are based on linear autoregressive models and we also use some nonlinear or time‐varying coefficient models. It turns out that most variables which have a similar level for Germany and the euro area such as prices can be better predicted based on German data, while aggregated European data are preferable for forecasting variables which need considerable adjustments in their levels when joining German and European Monetary Union (EMU) data. These results suggest that for variables which have a similar level for Germany and the euro area it may be reasonable to consider the German pre‐EMU data for studying economic problems in the euro area. Copyright © 2008 John Wiley & Sons, Ltd.     

Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function

Left ventricular mass (LVM) is a highly heritable trait and an independent risk factor for all-cause mortality. So far, genome-wide association studies have not identified the genetic factors that underlie LVM variation, and the regulatory mechanisms for blood-pressure-independent cardiac hypertrophy remain poorly understood. Unbiased systems genetics approaches in the rat now provide a powerful complementary tool to genome-wide association studies, and we applied integrative genomics to dissect a highly replicated, blood-pressure-independent LVM locus on rat chromosome 3p. Here we identified endonuclease G (Endog), which previously was implicated in apoptosis but not hypertrophy, as the gene at the locus, and we found a loss-of-function mutation in Endog that is associated with increased LVM and impaired cardiac function. Inhibition of Endog in cultured cardiomyocytes resulted in an increase in cell size and hypertrophic biomarkers in the absence of pro-hypertrophic stimulation. Genome-wide network analysis unexpectedly implicated ENDOG in fundamental mitochondrial processes that are unrelated to apoptosis. We showed direct regulation of ENDOG by ERR-α and PGC1α (which are master regulators of mitochondrial and cardiac function), interaction of ENDOG with the mitochondrial genome and ENDOG-mediated regulation of mitochondrial mass. At baseline, the Endog-deleted mouse heart had depleted mitochondria, mitochondrial dysfunction and elevated levels of reactive oxygen species, which were associated with enlarged and steatotic cardiomyocytes. Our study has further established the link between mitochondrial dysfunction, reactive oxygen species and heart disease and has uncovered a role for Endog in maladaptive cardiac hypertrophy.     

Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells

Transformed, oncogenic precursors, possessing both defining neural-stem-cell properties and the ability to initiate intracerebral tumours, have been identified in human brain cancers. Here we report that bone morphogenetic proteins (BMPs), amongst which BMP4 elicits the strongest effect, trigger a significant reduction in the stem-like, tumour-initiating precursors of human glioblastomas (GBMs). Transient in vitro exposure to BMP4 abolishes the capacity of transplanted GBM cells to establish intracerebral GBMs. Most importantly, in vivo delivery of BMP4 effectively blocks the tumour growth and associated mortality that occur in 100% of mice after intracerebral grafting of human GBM cells. We demonstrate that BMPs activate their cognate receptors (BMPRs) and trigger the Smad signalling cascade in cells isolated from human glioblastomas (GBMs). This is followed by a reduction in proliferation, and increased expression of markers of neural differentiation, with no effect on cell viability. The concomitant reduction in clonogenic ability, in the size of the CD133+ population and in the growth kinetics of GBM cells indicates that BMP4 reduces the tumour-initiating cell pool of GBMs. These findings show that the BMP-BMPR signalling system--which controls the activity of normal brain stem cells--may also act as a key inhibitory regulator of tumour-initiating, stem-like cells from GBMs and the results also identify BMP4 as a novel, non-cytotoxic therapeutic effector, which may be used to prevent growth and recurrence of GBMs in humans.     

Ex post and ex ante analysis of provisional data

In this paper we suggest a framework to assess the degree of reliability of provisional estimates as forecasts of final data, and we re‐examine the question of the most appropriate way in which available data should be used for ex ante forecasting in the presence of a data‐revision process. Various desirable properties for provisional data are suggested, as well as procedures for testing them, taking into account the possible non‐stationarity of economic variables. For illustration, the methodology is applied to assess the quality of the US M1 data production process and to derive a conditional model whose performance in forecasting is then tested against other alternatives based on simple transformations of provisional data or of past final data. Copyright © 1999 John Wiley & Sons, Ltd.     

Neurotrophin-conjugated nanoparticles prevent retina damage induced by oxidative stress

Glaucoma and other optic neuropathies are characterized by a loss of retinal ganglion cells (RGCs), a cell layer located in the posterior eye segment. Several preclinical studies demonstrate that neurotrophins (NTs) prevent RGC loss. However, NTs are rarely investigated in the clinic due to various issues, such as difficulties in reaching the retina, the very short half-life of NTs, and the need for multiple injections. We demonstrate that NTs can be conjugated to magnetic nanoparticles (MNPs), which act as smart drug carriers. This combines the advantages of the self-localization of the drug in the retina and drug protection from fast degradation. We tested the nerve growth factor and brain-derived neurotrophic factor by comparing the neuroprotection of free versus conjugated proteins in a model of RGC loss induced by oxidative stress. Histological data demonstrated that the conjugated proteins totally prevented RGC loss, in sharp contrast to the equivalent dose of free proteins, which had no effect. The overall data suggest that the nanoscale MNP-protein hybrid is an excellent tool in implementing ocular drug delivery strategies for neuroprotection and therapy.