Showing papers by "University of Marburg published in 2003"

An optimal and progressive algorithm for skyline queries

Abstract: The skyline of a set of d-dimensional points contains the points that are not dominated by any other point on all dimensions. Skyline computation has recently received considerable attention in the database community, especially for progressive (or online) algorithms that can quickly return the first skyline points without having to read the entire data file. Currently, the most efficient algorithm is NN (nearest neighbors), which applies the divide -and-conquer framework on datasets indexed by R-trees. Although NN has some desirable features (such as high speed for returning the initial skyline points, applicability to arbitrary data distributions and dimensions), it also presents several inherent disadvantages (need for duplicate elimination if d>2, multiple accesses of the same node, large space overhead). In this paper we develop BBS (branch-and-bound skyline), a progressive algorithm also based on nearest neighbor search, which is IO optimal, i.e., it performs a single access only to those R-tree nodes that may contain skyline points. Furthermore, it does not retrieve duplicates and its space overhead is significantly smaller than that of NN. Finally, BBS is simple to implement and can be efficiently applied to a variety of alternative skyline queries. An analytical and experimental comparison shows that BBS outperforms NN (usually by orders of magnitude) under all problem instances.

An angiogenic role for the human peptide antibiotic LL-37/hCAP-18

Abstract: Antimicrobial peptides are effector molecules of the innate immune system and contribute to host defense and regulation of inflammation. The human cathelicidin antimicrobial peptide LL-37/hCAP-18 is expressed in leukocytes and epithelial cells and secreted into wound and airway surface fluid. Here we show that LL-37 induces angiogenesis mediated by formyl peptide receptor-like 1 expressed on endothelial cells. Application of LL-37 resulted in neovascularization in the chorioallantoic membrane assay and in a rabbit model of hind-limb ischemia. The peptide directly activates endothelial cells, resulting in increased proliferation and formation of vessel-like structures in cultivated endothelial cells. Decreased vascularization during wound repair in mice deficient for CRAMP, the murine homologue of LL-37/hCAP-18, shows that cathelicidin-mediated angiogenesis is important for cutaneous wound neovascularization in vivo. Taken together, these findings demonstrate that LL-37/hCAP-18 is a multifunctional antimicrobial peptide with a central role in innate immunity by linking host defense and inflammation with angiogenesis and arteriogenesis.

Biosynthesis of nonribosomal peptides1.

Abstract: Bacteria and fungi use large multifunctional enzymes, the so-called nonribosomal peptide synthetases (NRPSs), to produce peptides of broad structural and biological activity. Biochemical studies have contributed substantially to the understanding of the key principles of these modular enzymes that can draw on a much larger number of catalytic tools for the incorporation of unusual features compared with the ribosomal system. Several crystal structures of NRPS-domains have yielded deep insight into the catalytic mechanisms involved and have led to a better prediction of the products assembled and to the construction of hybrid enzymes. In addition to the structure-function relationship of the core- and tailoring-domains of NRPSs, which is the main focus of this review, different biosynthetic strategies and essential enzymes for posttranslational modification and editing are discussed.

Toward a relational economic geography

Abstract: In this paper, we argue that a paradigmatic shift is occurring in economic geography toward a relational economic geography. This rests on three propositions. First, from a structural perspective economic actors are situated in contexts of social and institutional relations. Second, in dynamic perspective economic processes are path-dependent, constrained by history. Third, economic processes are contingent in that the agents’ strategies and actions are open-ended. Drawing on Storper’s holy trinity, we define four ions as the basis for analysis in economic geography: organization, evolution, innovation, and interaction. Therein, we employ a particular spatial perspective of economic processes using a geographical lens.

SARS — beginning to understand a new virus

Abstract: The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralysed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again.

The Ebola Virus VP35 Protein Inhibits Activation of Interferon Regulatory Factor 3

Abstract: The Ebola virus VP35 protein was previously found to act as an interferon (IFN) antagonist which could complement growth of influenza delNS1 virus, a mutant influenza virus lacking the influenza virus IFN antagonist protein, NS1. The Ebola virus VP35 could also prevent the virus- or double-stranded RNA-mediated transcriptional activation of both the beta IFN (IFN-β) promoter and the IFN-stimulated ISG54 promoter (C. Basler et al., Proc. Natl. Acad. Sci. USA 97:12289-12294, 2000). We now show that VP35 inhibits virus infection-induced transcriptional activation of IFN regulatory factor 3 (IRF-3)-responsive mammalian promoters and that VP35 does not block signaling from the IFN-α/β receptor. The ability of VP35 to inhibit this virus-induced transcription correlates with its ability to block activation of IRF-3, a cellular transcription factor of central importance in initiating the host cell IFN response. We demonstrate that VP35 blocks the Sendai virus-induced activation of two promoters which can be directly activated by IRF-3, namely, the ISG54 promoter and the ISG56 promoter. Further, expression of VP35 prevents the IRF-3-dependent activation of the IFN-α4 promoter in response to viral infection. The inhibition of IRF-3 appears to occur through an inhibition of IRF-3 phosphorylation. VP35 blocks virus-induced IRF-3 phosphorylation and subsequent IRF-3 dimerization and nuclear translocation. Consistent with these observations, Ebola virus infection of Vero cells activated neither transcription from the ISG54 promoter nor nuclear accumulation of IRF-3. These data suggest that in Ebola virus-infected cells, VP35 inhibits the induction of antiviral genes, including the IFN-β gene, by blocking IRF-3 activation.

Comparison of detrended fluctuation analysis and spectral analysis for heart rate variability in sleep and sleep apnea

Abstract: Sleep has been regarded as a testing situation for the autonomic nervous system, because its activity is modulated by sleep stages. Sleep-related breathing disorders also influence the autonomic nervous system and can cause heart rate changes known as cyclical variation. We investigated the effect of sleep stages and sleep apnea on autonomic activity by analyzing heart rate variability (HRV). Since spectral analysis is suited for the identification of cyclical variations and detrended fluctuation analysis can analyze the scaling behavior and detect long-range correlations, we compared the results of both complementary techniques in 14 healthy subjects, 33 patients with moderate, and 31 patients with severe sleep apnea. The spectral parameters VLF, LF, HF, and LF/HF confirmed increasing parasympathetic activity from wakefulness and REM over light sleep to deep sleep, which is reduced in patients with sleep apnea. Discriminance analysis was used on a person and sleep stage basis to determine the best method for the separation of sleep stages and sleep apnea severity. Using spectral parameters 69.7% of the apnea severity assignments and 54.6% of the sleep stage assignments were correct, while using scaling analysis these numbers increased to 74.4% and 85.0%, respectively. We conclude that changes in HRV are better quantified by scaling analysis than by spectral analysis.

Traveling waves in pipe flow

Abstract: A family of three-dimensional traveling waves for flow through a pipe of circular cross section is identified. The traveling waves are dominated by pairs of downstream vortices and streaks. They originate in saddle-node bifurcations at Reynolds numbers as low as 1250. All states are immediately unstable. Their dynamical significance is that they provide a skeleton for the formation of a chaotic saddle that can explain the intermittent transition to turbulence and the sensitive dependence on initial conditions in this shear flow.

Cathelicidins--a family of multifunctional antimicrobial peptides.

Abstract: One component of host defence at mucosal surfaces are epithelial-derived antimicrobial peptides. Cathelicidins are one family of antimicrobial peptides characterized by conserved pro-peptide sequences that have been identified in several mammalian species. LL-37/hCAP-18 is the only cathelicidin found in humans and is expressed in inflammatory and epithelial cells. Besides their direct antimicrobial function, cathelicidins have multiple roles as mediators of inflammation influencing diverse processes such as cell proliferation and migration, immune modulation, wound healing, angiogenesis and the release of cytokines and histamine. Finally, cathelicidin antimicrobial peptides qualify as prototypes of innovative drugs that may be used to treat infection and/or modulate the immune response. This review provides an overview of antimicrobial peptides of the cathelicidin family, the structures of their genes and peptides and their biological functions.

Myotonic dystrophy type 2 Molecular, diagnostic and clinical spectrum

Abstract: Background: Myotonic dystrophy types 1 (DM1) and 2 (DM2/proximal myotonic myopathy PROMM) are dominantly inherited disorders with unusual multisystemic clinical features. The authors have characterized the clinical and molecular features of DM2/PROMM, which is caused by a CCTG repeat expansion in intron 1 of the zinc finger protein 9 (ZNF9) gene. Methods: Three-hundred and seventy-nine individuals from 133 DM2/PROMM families were evaluated genetically, and in 234 individuals clinical and molecular features were compared. Results: Among affected individuals 90% had electrical myotonia, 82% weakness, 61% cataracts, 23% diabetes, and 19% cardiac involvement. Because of the repeat tract’s unprecedented size (mean ∼5,000 CCTGs) and somatic instability, expansions were detectable by Southern analysis in only 80% of known carriers. The authors developed a repeat assay that increased the molecular detection rate to 99%. Only 30% of the positive samples had single sizeable expansions by Southern analysis, and 70% showed multiple bands or smears. Among the 101 individuals with single expansions, repeat size did not correlate with age at disease onset. Affected offspring had markedly shorter expansions than their affected parents, with a mean size difference of −17 kb (−4,250 CCTGs). Conclusions: DM2 is present in a large number of families of northern European ancestry. Clinically, DM2 resembles adult-onset DM1, with myotonia, muscular dystrophy, cataracts, diabetes, testicular failure, hypogammaglobulinemia, and cardiac conduction defects. An important distinction is the lack of a congenital form of DM2. The clinical and molecular parallels between DM1 and DM2 indicate that the multisystemic features common to both diseases are caused by CUG or CCUG expansions expressed at the RNA level.

Components involved in assembly and dislocation of iron-sulfur clusters on the scaffold protein Isu1p.

Abstract: The mitochondrial proteins Isu1p and Isu2p play an essential role in the maturation of cellular iron–sulfur (Fe/S) proteins in eukaryotes. By radiolabelling of yeast cells with 55Fe we demonstrate that Isu1p binds an oxygen-resistant non-chelatable Fe/S cluster providing in vivo evidence for a scaffolding function of Isu1p during Fe/S cluster assembly. Depletion of the cysteine desulfurase Nfs1p, the ferredoxin Yah1p or the yeast frataxin homologue Yfh1p by regulated gene expression causes a strong decrease in the de novo synthesis of Fe/S clusters on Isu1p. In contrast, depletion of the Hsp70 chaperone Ssq1p, its co-chaperone Jac1p or the glutaredoxin Grx5p markedly increased the amount of Fe/S clusters bound to Isu1p, even though these mitochondrial proteins are crucial for maturation of Fe/S proteins. Hence Ssq1p/Jac1p and Grx5p are required in a step after Fe/S cluster synthesis on Isu1p, for instance in dissociation of preassembled Fe/S clusters from Isu1p and/or their insertion into apoproteins. We propose a model that dissects Fe/S cluster biogenesis into two major steps and assigns its central components to one of these two steps.

An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1.

Abstract: Depletion of the mitochondrial matrix protein frataxin is the molecular cause of the neurodegenerative disease Friedreich ataxia. The function of frataxin is unclear, although recent studies have suggested a function of frataxin (yeast Yfh1) in iron/sulphur (Fe/S) protein biogenesis. Here, we show that Yfh1 specifically binds to the central Fe/S-cluster (ISC)-assembly complex, which is composed of the scaffold protein Isu1 and the cysteine desulphurase Nfs1. Association between Yfh1 and Isu1/Nfs1 was markedly increased by ferrous iron, but did not depend on ISCs on Isu1. Functional analyses in vivo showed an involvement of Yfh1 in de novo ISC synthesis on Isu1. Our data demonstrate a crucial function of Yfh1 in Fe/S protein biogenesis by defining its function in an early step of this essential process. The iron-dependent binding of Yfh1 to Isu1/Nfs1 suggests a role of frataxin/Yfh1 in iron loading of the Isu scaffold proteins.

Electrospun nanofibers: Internal structure and intrinsic orientation

Abstract: Electrospinning gives rise to polymer nanofibers. The spinning process is characterized by strong deformations of the polymer material taking place during the spinning process and a very rapid structure formation process happening within milliseconds. We were interested in the influence of the peculiar spinning process on the structures of nanofibers. For this purpose, we analyzed the internal structures of nanofibers spun from polyamide-6 and polylactide with an average diameter of about 50 nm. The fibers were partially crystalline, with degrees of crystallinity not significantly smaller than those found for less rapidly quenched and much thicker melt-extruded fibers. The annealing of polyamide fibers at elevated temperatures resulted in a transformation from the disordered γ modification to the more highly ordered α modification, and this again was in close agreement with the response of melt-extruded fibers. The orientation of the crystals along the fiber axis was strongly inhomogeneous: it was, on average, very weak, yet it could be quite pronounced locally. Small elongations of approximately 10% resulted in well-developed homogeneous crystal orientations. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 545–553, 2003

Chronic systemic complex I inhibition induces a hypokinetic multisystem degeneration in rats.

Abstract: In Parkinson's disease, nigral dopaminergic neurones degenerate, whereas post-synaptic striatal target neurones are spared. In some atypical parkinsonian syndromes, both nigral and striatal neurones degenerate. Reduced activity of complex I of the mitochondrial respiratory chain has been implicated in both conditions, but it remains unclear if this affects the whole organism or only the degenerating brain structures. We therefore investigated the differential vulnerability of various brain structures to generalized complex I inhibition. Male Lewis rats infused with rotenone, a lipophilic complex I inhibitor [2.5 mg/kg/day intraveneously (i.v.) for 28 days], were compared with vehicle-infused controls. They showed reduced locomotor activity and loss of striatal dopaminergic fibres (54%), nigral dopaminergic neurones (28.5%), striatal serotoninergic fibres (34%), striatal DARPP-32-positive projection neurones (26.5%), striatal cholinergic interneurones (22.1%), cholinergic neurones in the pedunculopontine tegmental nucleus (23.7%) and noradrenergic neurones in the locus ceruleus (26.4%). Silver impregnation revealed pronounced degeneration in basal ganglia and brain stem nuclei, whereas the hippocampus, cerebellum and cerebral cortex were less affected. These data suggest that a generalized mitochondrial failure may be implicated in atypical parkinsonian syndromes but do not support the hypothesis that a generalized complex I inhibition results in the rather selective nigral lesion observed in Parkinson's disease.

Overexpression of the α-2,6-Sialyltransferase in MDCK Cells Increases Influenza Virus Sensitivity to Neuraminidase Inhibitors

Abstract: No reliable cell culture assay is currently available for monitoring human influenza virus sensitivity to neuraminidase inhibitors (NAI). This can be explained by the observation that because of a low concentration of sialyl-alpha2,6-galactose (Sia[alpha2,6]Gal)-containing virus receptors in conventional cell lines, replication of human virus isolates shows little dependency on viral neuraminidase. To test whether overexpression of Sia(alpha2,6)Gal moieties in cultured cells could make them suitable for testing human influenza virus sensitivity to NAI, we stably transfected MDCK cells with cDNA of human 2,6-sialyltransferase (SIAT1). Transfected cells expressed twofold-higher amounts of 6-linked sialic acids and twofold-lower amounts of 3-linked sialic acids than parent MDCK cells as judged by staining with Sambucus nigra agglutinin and Maackia amurensis agglutinin, respectively. After transfection, binding of a clinical human influenza virus isolate was increased, whereas binding of its egg-adapted variant which preferentially bound 3-linked receptors was decreased. The sensitivity of human influenza A and B viruses to the neuraminidase inhibitor oseltamivir carboxylate was substantially improved in the SIAT1-transfected cell line and was consistent with their sensitivity in neuraminidase enzyme assay and with the hemagglutinin (HA) receptor-binding phenotype. MDCK cells stably transfected with SIAT1 may therefore be a suitable system for testing influenza virus sensitivity to NAI.

Noninvasive arrhythmia risk stratification in idiopathic dilated cardiomyopathy: results of the Marburg Cardiomyopathy Study.

Abstract: Background— Arrhythmia risk stratification with regard to prophylactic implantable cardioverter-defibrillator therapy is a completely unsolved issue in idiopathic dilated cardiomyopathy (IDC). Methods and Results— Arrhythmia risk stratification was performed prospectively in 343 patients with IDC, including analysis of left ventricular (LV) ejection fraction and size by echocardiography, signal-averaged ECG, arrhythmias on Holter ECG, QTc dispersion, heart rate variability, baroreflex sensitivity, and microvolt T-wave alternans. During 52±21 months of follow-up, major arrhythmic events, defined as sustained ventricular tachycardia, ventricular fibrillation, or sudden death, occurred in 46 patients (13%). On multivariate analysis, LV ejection fraction was the only significant arrhythmia risk predictor in patients with sinus rhythm, with a relative risk of 2.3 per 10% decrease of ejection fraction (95% CI, 1.5 to 3.3; P=0.0001). Nonsustained ventricular tachycardia on Holter was associated with a trend towa...

Does obesity surgery improve psychosocial functioning? A systematic review

Abstract: OBJECTIVE: The objective of this study is to present a review of the psychosocial outcome of bariatric surgery with special consideration of psychiatric comorbidity, psychopathology, psychosocial functioning, econometric data, and general quality of life (QoL). PURPOSE: A review of all (non-) controlled trials of the last two decades both with a retrospective and prospective design and a follow-up period of at least 1 y. RESEARCH METHODS AND PROCEDURES: The relevant literature was identified by a search of computerized databases. All articles published in English and German since 1980 were reviewed. Based on the requirements of the evidenced-based guidelines of the Agency for Health Care Policy and Research and the Scottish Intercollegiate Guidelines Network, each study was rated by a level of evidence. RESULTS: In all, 171 publications were reviewed. Using the above inclusion/exclusion criteria, 63 articles including two systematic reviews were identified. A total of 40 studies focused on psychosocial outcome after obesity surgery. CONCLUSION: Mental health and psychosocial status including social relations and employment opportunities improve for the majority of people after bariatric surgery thus leading to an improved QoL. Psychiatric comorbidity, predominantly affective disorders, and psychopathologic symptoms decrease postsurgically. A substantial percentage of bariatric surgery patients suffer from binge eating disorder or binge eating symptoms. The effect of bariatric surgery on the outcome of binge eating symptoms largely depends on the type of operation. With the exception of patients with a severe psychiatric comorbidity, the concern that obesity surgery will reinforce psychic symptoms and lead to a reduction in the QoL seems to be unfounded.