Showing papers by "University of Luxembourg published in 2004"

UCHL1 is a Parkinson's disease susceptibility gene

Abstract: The reported inverse association between the S18Y variant of the ubiquitin carboxy-terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility. If confirmed, genetic association of this variant with PD may support molecular targeting of the UCHL1 gene and its product as a therapeutic strategy for PD. In this light, we performed a collaborative pooled analysis of individual-level data from all 11 published studies of the UCHL1 S18Y gene variant and PD. There were 1,970 cases and 2,224 unrelated controls. We found a statistically significant inverse association of S18Y with PD. Carriers of the variant allele (Y/Y plus Y/S vs S/S) had an odds ratio (OR) of 0.84 (95% confidence interval [CI], 0.73-0.95) and homozygotes for the variant allele (Y/Y vs S/S plus Y/S) had an OR of 0.71 (95% CI, 0.57-0.88). There was a linear trend in the log OR consistent with a gene dose effect (p = 0.01). The inverse association was most apparent for young cases compared with young controls. There was no evidence for publication bias and the associations remained significant after excluding the first published, hypothesis-generating study. These findings confirm that UCHL1 is a susceptibility gene for PD and a potential target for disease-modifying therapies.

The Link between R&D Subsidies, R&D Spending and Technological Performance

Abstract: This paper analyzes the effects of public R&D funding on R&D expenditure and patenting behavior of German firms. The main focus is the direct impact of subsidies on R&D and the indirect effect on innovation output measured by patent applications. We distinguish the productivity of purely privately financed R&D and additional R&D induced by public incentive schemes. For this, a treatment effects analysis is conducted in a first step. The results are implemented into the estimation of a patent production function. It turns out that both purely privately financed R&D and publicly induced R&D show a positive productivity.

International entrepreneurship and the small business

Abstract: The topic of ‘international entrepreneurship’ is becoming increasingly popular with researchers concerned with examining how international and entrepreneurial activities intersect when people in organizations engage in pro-active brokering and risk-taking behaviour in cross-border contexts. Some caution is needed in over-generalizing the meaning and significance of international entrepreneurship – especially in relation to small businesses. Not all entrepreneurial risk-taking, brokering and opportunity-seeking activities lead to internationalization (as the statistics on small business international activities indicate). This might suggest then that the only truly internationally entrepreneurial firms are those that are ‘born global’. However, their entrepreneurial activities are more ‘spatial’, concerned with what can be constructed again in relation to global markets rather than in relation to the local/regional context in which the business is located. For small firms that internationalize a few years ...

Indicators and Targets for Social Inclusion in the European Union

Abstract: In December 2001, the Laeken European Council adopted a set of commonly agreed and defined indicators for social inclusion. These should play a central role in monitoring the performance of Member States in making progress towards the key EU objectives in this area set by the Nice European Council in 2000, and represent a major step forward in the development of EU social policy. This article reviews the scientific and political basis on which the indicators were selected, and the implications for the future development of policy-making in Europe. It describes the key features of the indicators and some of the ways in which they can be developed. Finally, it investigates some important issues that need to be addressed when setting quantitative targets in the context of the social inclusion process.

A Benchmark for Methods in Reverse Engineering and Model Discrimination: Problem Formulation and Solutions

Abstract: A benchmark problem is described for the reconstruction and analysis of biochemical networks given sampled experimental data. The growth of the organisms is described in a bioreactor in which one substrate is fed into the reactor with a given feed rate and feed concentration. Measurements for some intracellular components are provided representing a small biochemical network. Problems of reverse engineering, parameter estimation, and identifiability are addressed. The contribution mainly focuses on the problem of model discrimination. If two or more model variants describe the available experimental data, a new experiment must be designed to discriminate between the hypothetical models. For the problem presented, the feed rate and feed concentration of a bioreactor system are available as control inputs. To verify calculated input profiles an interactive Web site (http://www.sysbio.de/projects/benchmark/) is provided. Several solutions based on linear and nonlinear models are discussed.

Novel homozygous p.E64D mutation in DJ1 in early onset Parkinson disease (PARK7).

Abstract: Mutations in the parkin gene have been identified as a common cause of autosomal recessive inherited Parkinson disease (PD) associated with early disease manifestation. However, based on linkage data, mutations in other genes contribute to the genetic heterogeneity of early-onset PD (EOPD). Recently, two mutations in the DJ1 gene were described as a second cause of autosomal recessive EOPD (PARK7). Analyzing the PARK7/DJ1 gene in 104 EOPD patients, we identified a third mutation, c.192G>C (p.E64D), associated with EOPD in a patient of Turkish ancestry and characterized the functional significance of this amino acid substitution. In the patient, a substantial reduction of dopamine uptake transporter (DAT) binding was found in the striatum using [18F]FP-CIT and PET, indicating a serious loss of presynaptic dopaminergic afferents. His sister, homozygous for E64D, was clinically unaffected but showed reduced dopamine uptake when compared with a clinically unaffected brother, who is heterozygous for E64D. We demonstrate by crystallography that the E64D mutation does not alter the structure of the DJ1 protein, however we observe a tendency towards decreased levels of the mutant protein when overexpressed in HEK293 or COS7 cells. Using immunocytochemistry in contrast to the homogenous nuclear and cytoplasmic staining in HEK293 cells overexpressing wild-type DJ1, about 5% of the cells expressing E64D and up to 80% of the cells expressing the recently described L166P mutation displayed a predominant nuclear localization of the mutant DJ1 protein. Hum Mutat 24:321–329, 2004. © 2004 Wiley-Liss, Inc.

Rhombic embeddings of planar quad-graphs

Abstract: Given a finite or infinite planar graph all of whose faces have degree 4, we study embeddings in the plane in which all edges have length 1, that is, in which every face is a rhombus. We give a necessary and sucient condition for the existence of such an embedding, as well as a description of the set of all such embeddings. R´´ Etant donne un graphe planaire, fini ou infini, dont toutes les faces sont de degre 4, onetudie ses plongements dans le plan dont toutes les aretes sont de longueur 1, c'estdire dont toutes les faces sont des losanges. On donne une condition necessaire et susante pour l'existence d'un tel plongement, et on decrit l'ensemble de ces plongements.

What Lies Behind Income Mobility? Reranking and Distributional Change in Belgium, Western Germany and the USA

Abstract: The paper presents a decomposition of income mobility indices into two basic sources: mobility induced by a change of the income distribution shape, and mobility induced by a reordering of individuals in the income pecking order The decomposition procedure, based on counterfactual distributions, results in a decomposition that is applicable to a broad class of mobility measures Application to income 'movement' indices with data for Belgium, Western Germany and the USA indicates that reranking has been the major force behind income mobility

Life satisfaction of older people in six European countries: Findings from the European Study on adult well-being

Abstract: The European Study on Adult Well-being (ESAW), funded by the European Union, was conducted during 2002 and 2003 in Austria, Italy, Luxembourg, The Netherlands, United Kingdom and Sweden. The aim of the interdisciplinary study was the conceptual clarification and the identification of factors contributing to life satisfaction for older people. Five key components were included in the study: (1) physical health and functional status; (2) self-resources; (3) material security; (4) social support resources; and (5) life activity. A representative population of adults aged 50–90 years living independently (not institutionalised) was selected in each participating country, and the actual sample size came very close to the target of 2,000, ranging from 1,854 to 2,417. The total European sample comprised 12,478 respondents. In this paper, mean differences in general and domain-specific life satisfaction between the six countries including age groups and gender are reported and discussed with respect to contextual national characteristics. In general the findings showed a high level in all chosen indicators of life satisfaction across the six countries. National differences depended on the domain under consideration, but the results showed in general that The Netherlands, United Kingdom, Luxembourg and Austria had higher values of life satisfaction compared to Sweden and Italy.

Visualization of individual DNA loops and a map of loop domains in the human dystrophin gene.

Abstract: The organization of the human dystrophin gene into loop domains has been studied using two different experimental approaches: excision of DNA loops mediated by nuclear matrix-bound topoisomerase II and in situ hybridization of different probes with histone-depleted nuclei (nuclear halos). Our objective was to examine if the DNA loops mapped by this biochemical approach coincide with loops visualized by microscopy. The results obtained using both approaches were in good agreement. Eight loops separated by attachment regions of different length were mapped in the upstream part (up to exon 54) of the gene by topoisomerase II-mediated excision. One of these loops was then directly visualized by in situ hybridization of the corresponding bacmid clone with nuclear halos. This is the first direct demonstration that a DNA domain mapped as a loop using a biochemical approach corresponds to a loop visible on cytological preparations. The validity of this result and of the whole map of loop domains was confirmed by in situ hybridization using probes derived from other attachment regions or loops mapped by topoisomerase II-mediated cleavage; these probes hybridized on the core or halo region, respectively, of nuclear halos. Our results demonstrate that a single transcription unit may be organized into several loops and that DNA loop attachment regions may be fairly long. Three out of four replication origins mapped in this gene co-localize with loop attachment regions, and the major deletion hot spot is harbored in an attachment region. These results strongly suggest that partitioning of genomic DNA into specific loops attached to a skeletal structure is a characteristic feature of eukaryotic chromosome organization in interphase.

Deterministic Polynomial Time Equivalence of Computing the RSA Secret Key and Factoring.

Abstract: We address one of the most fundamental problems concerning the RSA cryptosystem: does the knowledge of the RSA public and secret key-pair (e, d) yield the factorization of N = pq in polynomial time? It is well-known that there is a probabilistic polynomial time algorithm that on input (N, e, d) outputs the factors p and q. We present the first deterministic polynomial time algorithm that factors N provided that e, d < φ(N). Our approach is an application of Coppersmith’s technique for finding small roots of univariate modular polynomials.

Accounting for Income Distribution Trends: A Density FunctionDecomposition Approach

Abstract: This paper develops methods for decomposing changes in the income distribution using subgroup decompositions of the income density function. Overall changes are related to changes in subgroup shares and changes in subgroup densities, where the latter are broken down further using elementary transformations of individual incomes. These density decompositions are analogous to the widely-used decompositions of inequality indices by population subgroup, except that they summarize multiple features of the income distribution (using graphs), rather than focusing on a specific feature such as dispersion, and are not dependent on the choice of a specific summary index. Nonetheless, since inequality and poverty indices can be expressed as PDF functionals, our density-based methods can also be used to provide numerical decompositions of these. An application of the methods reveals the multi-faceted nature of UK income distribution trends during the 1980s.

Extended mutation analysis and association studies of Nurr1 (NR4A2) in Parkinson disease

Abstract: Mutations in four genes (α -synuclein, UCH-L1, parkin , and DJ-1 ) have been identified in familial Parkinson disease (PD). Recently, two mutations in the 5′-region of the orphan nuclear receptor Nurr1 ( NR4A2 ) gene have been found in 10% of familial PD cases, of which one-third were of German ancestry.1 Furthermore, a polymorphism in intron 6 of the Nurr1 gene was associated with PD in two independent studies.2,3⇓ The transcription factor Nurr1 is highly expressed in dopaminergic cells of the substantia nigra. Deficiency of Nurr1 in mice leads to a lack of dopaminergic neurons.4 Based on these data, we explored the 7048G7049 polymorphism in intron 6 as well as two novel sequence variations, −291Tdel and −245T→G, in exon 1 of Nurr1 in a large cohort of PD patients. For analysis of the 7048G7049 polymorphism, 424 PD patients were investigated (mean age at disease onset 55.4 ± 12.1 years; 54.6% male, 45.4% female; with 55 patients [13.0%] having a positive family history). For analysis of the two novel sequence variations, −291Tdel and −245T→G, …

The dynamics of Agglomeration: Evidence from Ireland and Portugal

Abstract: This paper analyses and compares the dynamics of agglomeration in Portuguese and Irish manufacturing industries between 1985 and 1998 implementing Dumais, Ellison and Glaeser (2002) methodology. Using comparable and exhaustive micro-level data sets, we find that s industries tend to be subject to strong geographical mobility despite little net aggregate changes in agglomeration in both countries. When the aggregate concentration changes are decomposed into portions attributable to the different stages of the plant life cycle, we discover that births consistently play a deagglomerating role, which continues at least into the early stages of the life cycle, whereas deaths have acted to reinforce agglomeration in both countries. Nevertheless, there are some differences across countries and industries.

Self-controlled learning of a complex motor skill: Effects of the learner's preferences on performance and self-efficacy.

Abstract: SUMMARY The present study exammes whether self-controlled practice enhances motor learning and self-efficacy beliefs more when it refers to an aspect of the learning situation which is preferred by the learner, rather than to an aspect which is not. Participants (N=52) practiced the forehand top spin stroke in table tennis and were randomly assigned to one of four groups. Two groups of learners (self-control) were given the option to control either a preferred practice condition (eg. schedule of video instruction) or a non-preferred practice condition (eg. variability of practice), whereas another two groups (yoked) had no influence on these practice schedules. While no group differences were found during the practice phase, both self-control groups showed learning benefits regarding the movement form on a delayed retention test. Moreover, self-control participants reported significantly higher self-efficacy beliefs than yoked participants. The results suggest that the effectiveness of self-controlled practice is independent of the learner's preferences regarding the practice situation. Future research should include cognitive and motivational variables in order to explain the learning advantages of self-controlled practice schedules.

Conformational subspace in simulation of early-stage protein folding.

Abstract: A probability calculus was used to simulate the early stages of protein folding in ab initio structure prediction The probabilities of particular phi and psi angles for each of 20 amino acids as they occur in crystal forms of proteins were used to calculate the amount of information necessary for the occurrence of given phi and psi angles to be predicted It was found that the amount of information needed to predict phi and psi angles with 5 degrees precision is much higher than the amount of information actually carried by individual amino acids in the polypeptide chain To handle this problem, a limited conformational space for the preliminary search for optimal polypeptide structure is proposed based on a simplified geometrical model of the polypeptide chain and on the probability calculus These two models, geometric and probabilistic, based on different sources, yield a common conclusion concerning how a limited conformational space can represent an early stage of polypeptide chain-folding simulation The ribonuclease molecule was used to test the limited conformational space as a tool for modeling early-stage folding

The Spatial Solow Model

Abstract: In this paper, we solve a Solow model in continuous time and space. We prove the existence of a solution to the problem and its convergence to a stationary solution. The simulation of various scenarios in the last section of the paper illustrates the convergence issue.

Integrin receptor specificity for human red cell ICAM‐4 ligand

Abstract: The red cell intercellular adhesion molecule-4 (ICAM-4) binds to different members of the integrin receptor families. To better define the ICAM-4 integrin receptor specificity, cell transfectants individually expressing various integrins were used to demonstrate that {alpha}L{beta}2, {alpha}M{beta}2, and {alpha}IIb{beta}3 (activated) bind specifically and dose dependently to the recombinant ICAM-4-Fc protein. We also show that cell surface ICAM-4 interacts with the cell surface {alpha}V{beta}3 integrin. In addition, using a {alpha}4{beta}1 cell transfectant and {beta}2 integrin-deficient LAD cells, we show here that ICAM-4 failed to interact with {alpha}4{beta}1 even after {alpha}4{beta}1 activation by phorbol ester or with the monoclonal antibody TS2/16 (+ Mn2+). ICAM-4 amino acids that are critical for {alpha}IIb{beta}3 and {alpha}V{beta}3 interaction were identified by domain deletion analysis, site-directed mutagenesis and synthetic peptide inhibition. Our results provide evidence that the {beta}3 integrin binding sites encompass the first and second Ig-like domains of ICAM-4. However, while the {alpha}IIb{beta}3 contact site comprises the ABED face of domain D1 with an extension in the C'-E loop of domain D2, the {alpha}V{beta}3 contact site comprises residues on both faces of D1 and in the C'-E loop of D2. These data, together with our previous results, demonstrate that different integrins bind to different but partly overlapping sites on ICAM-4, and that ICAM-4 may accommodate multiple integrin receptors present on leukocytes, platelets and endothelial cells.

Automorphisms of quantum and classical Poisson algebras

Abstract: We prove Pursell-Shanks type results for the Lie algebra D(M ) of all linear differential operators of a smooth manifold M , for its Lie subalgebra D 1 (M ) of all linear first-order differential operators of M and for the Poisson algebra S(M )=P ol(T ∗ M ) of all poly- nomial functions on T ∗ M, the symbols of the operators in D(M ). Chiefly, however, we provide explicit formulas completely describing the automorphisms of the Lie algebras D 1 (M ) ,S (M )a ndD(M ). The initial objective of the present paper was to prove that the Lie algebra D(M ) of all linear differential operators D : C ∞ (M ) → C ∞ (M )o f as mooth manifoldM , determines the smooth structure of M. Beyond this conclusion, we present a description of all automorphisms of the Lie algebra D(M ) and even of the Lie subalgebra D 1 (M ) of all linear first-order differential operators of M and of the Poisson algebra S(M )=P ol(T ∗ M ) of polynomial functions on the cotangent bundle T ∗ M (the symbols of the operators in D(M )), the automorphisms of the two last algebras of course being canonically related with those of D(M ). In each situation we obtain an explicit formula, for instance - in the case of D(M ) - in terms of the automorphism of D(M ) implemented by a diffeomorphism of M , the conjugation-automorphism of D(M ) and the automorphism of D(M ) generated by the derivation of D(M ) associated to a closed 1-form of M. In the first part of our work, the approach is purely algebraic. In § 2 ,w e heaveD(M )a nd S(M ) on a general algebraic level and define the notions 'quantum Poisson algebra' D and 'classical Poisson algebra' S, the classical limit of D.I n§ 3 we show that if two (quantum or classical) Poisson algebras are isomorphic as Lie algebras, their 'basic algebras of functions' are isomorphic as associative algebras - an algebraic Shanks-Pursell type result, which naturally implies our previously described initial goal. The leading idea of the proof is the algebraic characterization, under a minimal

Indication of the uplift of the Ardenne in long‐term gravity variations in Membach (Belgium)

Abstract: SUMMARY We report on the results of 7 yr of collocated gravity observations made with an FG5 absolute (AG) gravimeter and a GWR C-Series superconducting gravimeter (SG) located at the Membach Geophysical Station in eastern Belgium. The SG gravity residuals track changes in gravity periodically observed by the AG, at the microgal level. Further, in the SG residual signal we distinguish a quasi-seasonal term that can be mostly explained by variations in local water storage effects. In the AG time-series we observe a small trend in the gravity of −0.6 ± 0.1 µGal yr −1 perhaps indicating that the Membach Station is being displaced upwards by about 3.0 mm yr −1 . An uplift of the region is confirmed by Global Positioning System (GPS) measurements performed 3 km away. We are able to explain the features in the gravity time-series in terms of water storage variability, post-glacial rebound and tectonic activity.