Demyelination in brain cell aggregate cultures, induced by a monoclonal antibody against the myelin/oligodendrocyte glycoprotein (MOG).

Previous work has shown that aggregate cultures prepared from fetal rat telencephalon and grown in a chemically defined medium offer a useful model to study developmental processes such as myelin synthesis. Since compact myelin is formed in these cultures, we investigated the possibility to use this culture system to study demyelinating mechanisms. In particular, we examined the effect of a monoclonal antibody (8-18C5) directed against the myelin/oligodendrocyte glycoprotein (MOG). We found that addition of anti-MOG antibodies and complement to aggregate cultures led to a highly significant decrease in myelin basic protein (MBP) content and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) specific activity. These results indicate that, in our culture system, anti-MOG antibodies have a strong demyelinating effect.

Technology shocks and aggregate fluctuations in an estimated hybrid RBC model

This paper contributes to the on-going empirical debate regarding the role of the RBC model and in particular of technology shocks in explaining aggregate fluctuations. To this end we estimate the model’s posterior density using Markov-Chain Monte-Carlo (MCMC) methods. Within this framework we extend Ireland’s (2001, 2004) hybrid estimation approach to allow for a vector autoregressive moving average (VARMA) process to describe the movements and co-movements of the model’s errors not explained by the basic RBC model. The results of marginal likelihood ratio tests reveal that the more general model of the errors significantly improves the model’s fit relative to the VAR and AR alternatives. Moreover, despite setting the RBC model a more difficult task under the VARMA specification, our analysis, based on forecast error and spectral decompositions, suggests that the RBC model is still capable of explaining a significant fraction of the observed variation in macroeconomic aggregates in the post-war U.S. economy.

International Evidence on the New Keynesian Phillips Curve Using Aggregate and Disaggregate Data

We present a unique empirical analysis of the properties of the New Keynesian Phillips Curve using an international dataset of aggregate and disaggregate sectoral in ation. Our results from panel time-series estimation clearly indicate that sectoral heterogeneity has important consequences for aggregate in ation behaviour. Heterogeneity helps to explain the overestimation of in ation persistence and underestimation of the role of marginal costs in empirical investigations of the NKPC that use aggregate data. We nd that combining disaggregate information with heterogeneous-consistent estimation techniques helps to reconcile, to a large extent, the NKPC with the data.

Minu, Startu and all that:- Pitfalls in estimating the sensitivity of a worker’s wage to aggregate unemployment

In this paper we show that the inclusion of unemployment-tenure interaction variates in Mincer wage equations is subject to serious pitfalls. These variates were designed to test whether or not the sensitivity to the business cycle of a worker’s wage varies according to her tenure. We show that three canonical variates used in the literature - the minimum unemployment rate during a worker’s time at the firm(min u), the unemployment rate at the start of her tenure(Su) and the current unemployment rate interacted with a new hire dummy(δu) - can all be significant and "correctly" signed even when each worker in the firm receives the same wage, regardless of tenure (equal treatment). In matched data the problem can be resolved by the inclusion in the panel of firm-year interaction dummies. In unmatched data where this is not possible, we propose a solution for min u and Su based on Solon, Barsky and Parker’s(1994) two step method. This method is sub-optimal because it ignores a large amount of cross tenure variation in average wages and is only valid when the scaled covariances of firm wages and firm employment are acyclical. Unfortunately δu cannot be identified in unmatched data because a differential wage response to unemployment of new hires and incumbents will appear under both equal treatment and unequal treatment.

Productivity shocks and aggregate fluctuations in an estimated endogenous growth model with human capital

Employing an endogenous growth model with human capital, this paper explores how productivity shocks in the goods and human capital producing sectors contribute to explaining aggregate fluctuations in output, consumption, investment and hours. Given the importance of accounting for both the dynamics and the trends in the data not captured by the theoretical growth model, we introduce a vector error correction model (VECM) of the measurement errors and estimate the model’s posterior density function using Bayesian methods. To contextualize our findings with those in the literature, we also assess whether the endogenous growth model or the standard real business cycle model better explains the observed variation in these aggregates. In addressing these issues we contribute to both the methods of analysis and the ongoing debate regarding the effects of innovations to productivity on macroeconomic activity.

Aggregate and welfare effects of long run inflation risk under inflation and price-level targeting

This paper presents a DSGE model in which long run inflation risk matters for social welfare. Aggregate and welfare effects of long run inflation risk are assessed under two monetary regimes: inflation targeting (IT) and price-level targeting (PT). These effects differ because IT implies base-level drift in the price level, while PT makes the price level stationary around a target price path. Under IT, the welfare cost of long run inflation risk is equal to 0.35 percent of aggregate consumption. Under PT, where long run inflation risk is largely eliminated, it is lowered to only 0.01 per cent. There are welfare gains from PT because it raises average consumption for the young and lowers consumption risk substantially for the old. These results are strongly robust to changes in the PT target horizon and fairly robust to imperfect credibility, fiscal policy, and model calibration. While the distributional effects of an unexpected transition to PT are sizeable, they are short-lived and not welfare-reducing.

Continuity of set-valued maps revisited in the light of tame geometry

Continuity of set-valued maps is hereby revisited: after recalling some basic concepts of variational analysis and a short description of the State-of-the-Art, we obtain as by-product two Sard type results concerning local minima of scalar and vector valued functions. Our main result though, is inscribed in the framework of tame geometry, stating that a closed-valued semialgebraic set-valued map is almost everywhere continuous (in both topological and measure-theoretic sense). The result –depending on stratification techniques– holds true in a more general setting of o-minimal (or tame) set-valued maps. Some applications are briefly discussed at the end.

The Causal effect of education on aggregate income

Empirical studies assume that the macro Mincer return on schooling is con- stant across countries. Using a large sample of countries this paper shows that countries with a better quality of education have on average relatively higher macro Mincer coeficients. As rich countries have on average better educational quality, differences in human capital between countries are larger than has been typically assumed in the development accounting literature. Consequently, factor accumulation explains a considerably larger share of income differences across countries than what is usually found.

Analyzing aggregate real exchange rate persistence through the lens of sectoral data

In this paper we analyze the persistence of aggregate real exchange rates (RERs) for a group of EU-15 countries by using sectoral data. The tight relation between aggregate and sectoral persistence recently investigated by Mayoral (2008) allows us to decompose aggregate RER persistence into the persistence of its different subcomponents. We show that the distribution of sectoral persistence is highly heterogeneous and very skewed to the right, and that a limited number of sectors are responsible for the high levels of persistence observed at the aggregate level. We use quantile regression to investigate whether the traditional theories proposed to account for the slow reversion to parity (lack of arbitrage due to nontradibilities or imperfect competition and price stickiness) are able to explain the behavior of the upper quantiles of sectoral persistence. We conclude that pricing to market in the intermediate goods sector together with price stickiness have more explanatory power than variables related to the tradability of the goods or their inputs.

Geometry and physics of knots

KNOTS are usually categorized in terms of topological properties that are invariant under changes in a knot's spatial configuration(1-4). Here we approach knot identification from a different angle, by considering the properties of particular geometrical forms which we define as 'ideal'. For a knot with a given topology and assembled from a tube of uniform diameter, the ideal form is the geometrical configuration having the highest ratio of volume to surface area. Practically, this is equivalent to determining the shortest piece of tube that can be closed to form the knot. Because the notion of an ideal form is independent of absolute spatial scale, the length-to-diameter ratio of a tube providing an ideal representation is constant, irrespective of the tube's actual dimensions. We report the results of computer simulations which show that these ideal representations of knots have surprisingly simple geometrical properties. In particular, there is a simple linear relationship between the length-to-diameter ratio and the crossing number-the number of intersections in a two-dimensional projection of the knot averaged over all directions. We have also found that the average shape of knotted polymeric chains in thermal equilibrium is closely related to the ideal representation of the corresponding knot type. Our observations provide a link between ideal geometrical objects and the behaviour of seemingly disordered systems, and allow the prediction of properties of knotted polymers such as their electrophoretic mobility(5).

Aggregate cultures of foetal rat liver cells: development and maintenance of liver gene expression.

Rotation-mediated aggregate cultures of foetal rat liver cells were prepared and grown in a chemically defined medium. Their capacity for cellular organisation and maturation was studied over a culture period of 3 wk by using both morphologic and biochemical criteria. It was found that within each aggregate, distinct liver cell types were present and attained their normal, differentiated phenotype. Parenchymal cells formed small acini with a central lumen. Within the first 2 wk in culture, albumin and ferritin mRNA levels were maintained, while the alpha-fetoprotein mRNA levels decreased, and tyrosine aminotransferase (TAT) gene expression increased. No significant response to glucocorticoids was observed in early cultures, whereas after 3 wk a marked increase in TAT mRNA levels was elicited by dexamethasone and glucagon (additive stimulatory effects). The results show that foetal rat liver cells cultured in a chemically defined medium are able to rearrange themselves into histotypic structures, and display a developmental pattern of gene expression comparable to that of perinatal rat liver in vivo. This culture system offers therefore a useful model to study the development and function of liver cells.

DETERMINATION OF CELL-SPECIFIC NEUROTOXICITY OF MALONATE, METHYLMALONATE AND PROPIONATE IN A 3D RAT BRAIN CELL AGGREGATE SYSTEM

Malonate, methylmalonate and propionate are potentially neurotoxic metabolites in branched-chain organic acidurias. Their effects were tested on cultured 3D rat brain cell aggregates, using dosages of 0.1, 1.0 and 10.0 mM with a short but intense (twice a day over 3 days) and a longer but less intense treatment (every 3 rdday over 9 days). CNS cell-specific immunohistochemical stainings allowed the follow-up of neurons (axons, phosphorylated medium-weight neurofilament), astrocytes (glial fibrillary acidic protein) and oligodendrocytes (myelin basic protein). Methylmalonate and malonate were quantified by tandem mass spectrometry. Tandem mass spectrometry analysis of harvested brain cell aggregates revealed clear intracellular accumulation of methylmalonate and malonate. In immunohistochemical stainings oligodendrocytes appeared the most affected brain cells. The MBP signal disappeared already at 0.1 mM treatment with each metabolite. Mature astrocytes were not affected by propionate, while immature astrocytes on intense treatment with propionate developed cell swelling. 1 mM methylmalonate induced cell swelling of both immature and mature astrocytes , while 1 mM malonate only affected mature astrocytes. Neurons were not affected by methylmalonate, but 10.0 mM malonate on less intense treatment and 0.1, 1.0 and 10.0 mM propionate on intense treatment affected axonal growth. Our study shows significant uptake and deleterious effects of these metabolites on brain cells, principally on astrocytes and oligodendrocytes. This may be explained by the absence of the pathway in glial cells, which thus are not able to degrade these metabolites. Further studies are ongoing to elucidate the underlying mechanisms of the observed neurotoxic effects.

A simple model of aggregate pension expenditure

This paper develops a simple model that can be used to analyze the long-term sustainability of the contributive pension system and the steady-state response of pension expenditure to changes in some key demographic and economic variables, in the characteristics of the average pensioner and in the parameters that describe how pensions are calculated in Spain as a function of workers' Social Security contribution histories.

Wing geometry as a tool for studying the Lutzomyia longipalpis (Diptera: Psychodidae) complex

Toro Toro (T) and Yungas (Y) have been described as genetically well differentiated populations of the Lutzomyia longipalpis (Lutz & Neiva, 1912) complex in Bolivia. Here we use geometric morphometrics to compare samples from these populations and new populations (Bolivia and Nicaragua), representing distant geographical origins, qualitative morphological variation ("one-spot" or "two-spots" phenotypes), ecologically distinct traits (peridomestic and silvatic populations), and possibly different epidemiological roles (transmitting or nor transmitting Leishmania chagasi). The Nicaragua (N) (Somotillo) sample was "one-spot" phenotype and a possible peridomestic vector. The Bolivian sample of the Y was also "one-spot" phenotype and a demonstrated peridomestic vector of visceral leishmaniasis (VL). The three remaining samples were silvatic, "two-spots" phenotypes. Two of them (Uyuni and T) were collected in the highlands of Bolivian where VL never has been reported. The last one (Robore, R) came from the lowlands of Bolivia, where human cases of VL are sporadically reported. The decomposition of metric variation into size and shape by geometric morphometric techniques suggests the existence of two groups (N/Y/R, and U/T). Several arguments indicate that such subdivision of Lu. longipalpis could correspond to different evolutionary units.

Geometry and physics of catenanes applied to the study of DNA replication.

The concept of ideal geometric configurations was recently applied to the classification and characterization of various knots. Different knots in their ideal form (i.e., the one requiring the shortest length of a constant-diameter tube to form a given knot) were shown to have an overall compactness proportional to the time-averaged compactness of thermally agitated knotted polymers forming corresponding knots. This was useful for predicting the relative speed of electrophoretic migration of different DNA knots. Here we characterize the ideal geometric configurations of catenanes (called links by mathematicians), i.e., closed curves in space that are topologically linked to each other. We demonstrate that the ideal configurations of different catenanes show interrelations very similar to those observed in the ideal configurations of knots. By analyzing literature data on electrophoretic separations of the torus-type of DNA catenanes with increasing complexity, we observed that their electrophoretic migration is roughly proportional to the overall compactness of ideal representations of the corresponding catenanes. This correlation does not apply, however, to electrophoretic migration of certain replication intermediates, believed up to now to represent the simplest torus-type catenanes. We propose, therefore, that freshly replicated circular DNA molecules, in addition to forming regular catenanes, may also form hemicatenanes.