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Showing papers by "University of Cologne published in 2005"


Journal ArticleDOI
TL;DR: The new HITRAN is greatly extended in terms of accuracy, spectral coverage, additional absorption phenomena, added line-shape formalisms, and validity, and molecules, isotopologues, and perturbing gases have been added that address the issues of atmospheres beyond the Earth.
Abstract: This paper describes the contents of the 2016 edition of the HITRAN molecular spectroscopic compilation. The new edition replaces the previous HITRAN edition of 2012 and its updates during the intervening years. The HITRAN molecular absorption compilation is composed of five major components: the traditional line-by-line spectroscopic parameters required for high-resolution radiative-transfer codes, infrared absorption cross-sections for molecules not yet amenable to representation in a line-by-line form, collision-induced absorption data, aerosol indices of refraction, and general tables such as partition sums that apply globally to the data. The new HITRAN is greatly extended in terms of accuracy, spectral coverage, additional absorption phenomena, added line-shape formalisms, and validity. Moreover, molecules, isotopologues, and perturbing gases have been added that address the issues of atmospheres beyond the Earth. Of considerable note, experimental IR cross-sections for almost 300 additional molecules important in different areas of atmospheric science have been added to the database. The compilation can be accessed through www.hitran.org. Most of the HITRAN data have now been cast into an underlying relational database structure that offers many advantages over the long-standing sequential text-based structure. The new structure empowers the user in many ways. It enables the incorporation of an extended set of fundamental parameters per transition, sophisticated line-shape formalisms, easy user-defined output formats, and very convenient searching, filtering, and plotting of data. A powerful application programming interface making use of structured query language (SQL) features for higher-level applications of HITRAN is also provided.

7,638 citations


Journal ArticleDOI
TL;DR: Overall safety and tolerability was good with no change in the safety profile of pioglitazone identified; mortality rates from heart failure did not differ between groups.

3,899 citations


Journal ArticleDOI
TL;DR: The Cologne Database for Molecular Spectroscopy (CDMS) as discussed by the authors contains a catalog of transition frequencies from the radio-frequency to the far-infrared region covering atomic and molecular species that (may) occur in the interstellar or circumstellar medium or in planetary atmospheres.

1,842 citations


Journal ArticleDOI
Ludwig Eichinger1, Justin A. Pachebat1, Justin A. Pachebat2, Gernot Glöckner, Marie-Adèle Rajandream3, Richard Sucgang4, Matthew Berriman3, J. Song4, Rolf Olsen5, Karol Szafranski, Qikai Xu4, Budi Tunggal1, Sarah K. Kummerfeld2, Martin Madera2, Bernard Anri Konfortov2, Francisco Rivero1, Alan T. Bankier2, Rüdiger Lehmann, N. Hamlin3, Robert L. Davies3, Pascale Gaudet6, Petra Fey6, Karen E Pilcher6, Guokai Chen4, David L. Saunders3, Erica Sodergren4, P. Davis3, Arnaud Kerhornou3, X. Nie4, Neil Hall3, Christophe Anjard5, Lisa Hemphill4, Nathalie Bason3, Patrick Farbrother1, Brian A. Desany4, Eric M. Just6, Takahiro Morio7, René Rost8, Carol Churcher3, J. Cooper3, Stephen F. Haydock9, N. van Driessche4, Ann Cronin3, Ian Goodhead3, Donna M. Muzny4, T. Mourier3, Arnab Pain3, Mingyang Lu4, D. Harper3, R. Lindsay4, Heidi Hauser3, Kylie R. James3, M. Quiles4, M. Madan Babu2, Tsuneyuki Saito10, Carmen Buchrieser11, A. Wardroper2, A. Wardroper12, Marius Felder, M. Thangavelu, D. Johnson3, Andrew J Knights3, H. Loulseged4, Karen Mungall3, Karen Oliver3, Claire Price3, Michael A. Quail3, Hideko Urushihara7, Judith Hernandez4, Ester Rabbinowitsch3, David Steffen4, Mandy Sanders3, Jun Ma4, Yuji Kohara13, Sarah Sharp3, Mark Simmonds3, S. Spiegler3, Adrian Tivey3, Sumio Sugano14, Brian White3, Danielle Walker3, John Woodward3, Thomas Winckler, Yoshiaki Tanaka7, Gad Shaulsky4, Michael Schleicher8, George M. Weinstock4, André Rosenthal, Edward C. Cox15, Rex L. Chisholm6, Richard A. Gibbs4, William F. Loomis5, Matthias Platzer, Robert R. Kay2, Jeffrey G. Williams16, Paul H. Dear2, Angelika A. Noegel1, Bart Barrell3, Adam Kuspa4 
05 May 2005-Nature
TL;DR: A proteome-based phylogeny shows that the amoebozoa diverged from the animal–fungal lineage after the plant–animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.
Abstract: The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

1,289 citations


Journal ArticleDOI
TL;DR: The Gastrointestinal Quality of Life Index (GIQLI) is ready to be used in clinical practice and research and validated against other generic measures of quality of life.
Abstract: At present, an instrument for measuring the quality of life, specifically for patients with gastrointestinal disease, is not available. A new instrument for gastrointestinal disorders that is system-specific has been developed in three phases. In the first phase, questions were collated and then tested on 70 patients with gastrointestinal diseases and those that worked well were retained. In the second phase, the questions were modified and tested on 204 patients and the results verified by international experts. The instrument was also validated against other generic measures of quality of life. During the third phase, the instrument was validated with 168 normal individuals. Reproducibility was tested on 25 patients with stable gastrointestinal disease and responsiveness was tested on 194 patients undergoing laparoscopic cholecystectomy. The result is a bilingual (German and English) questionnaire containing 36 questions each with five response categories. The responses to questions are summed to give a numerical score. It is concluded that the Gastrointestinal Quality of Life Index (GIQLI) is ready to be used in clinical practice and research.

1,141 citations


Journal ArticleDOI
Müller Jm1, H. Erasmi1, M Stelzner1, Zieren U1, H. Pichlmaier1 
TL;DR: Although it may be possible to further reduce postoperative complications and mortality, the chances of improving the long‐term prognosis of patients with oesophageal carcinoma seem small.
Abstract: During the past 10 years, postoperative mortality associated with surgical treatment of oesophageal carcinoma has been reduced by one-half. However, it appears that all efforts to improve long-term survival with extensive excisional procedures and adjuvant chemotherapy and radiotherapy have failed. Fifty-six of 100 patients presenting to the surgeon with an oesophageal carcinoma have resectable disease. Recent studies suggest that seven of them will die from postoperative complications and 49 patients will be discharged from the hospital after an average of 3 weeks. Of these patients, 27 will survive the first, 12 the second, and ten the fifth year. Although it may be possible to further reduce postoperative complications and mortality, the chances of improving the long-term prognosis of patients with oesophageal carcinoma seem small.

839 citations


Journal ArticleDOI
TL;DR: A new identification system for a trimer using three Arabic numerals, based on the alpha, beta and gamma chain numbers is introduced, which is introduced for laminin trimers.

836 citations


Journal ArticleDOI
25 Apr 2005
TL;DR: In this article, two-component relativistic pseudopotentials (i.e., scalar-relativistic and spin-orbit (SO) potentials) of the energy-consistent variety have been adjusted for the group 11 and 12 atoms Cu, Zn, Ag, Cd, Au, Hg, replacing the 1s−2p, 1s-3d, 1 s−3d and 1s −4f cores, respectively.
Abstract: Two-component relativistic pseudopotentials (i.e., scalar-relativistic and spin–orbit (SO) potentials) of the energy-consistent variety have been adjusted for the group 11 and 12 atoms Cu, Zn; Ag, Cd; Au, Hg, replacing the 1s–2p; 1s–3d; and 1s–4f cores, respectively. The adjustment has been done for the valence-energy spectrum of (near-)neutral atoms, to reference data from numerical all-electron four-component multi-configuration Dirac–Hartree–Fock (MCDHF) calculations, including the two-electron Breit interaction. For use in molecular calculations, the potentials have been supplemented by energy-optimized (12s12p9d3f2g)/[6s6p4d3f2g] valence basis sets. First benchmark applications of the potentials and basis sets are presented for atomic excitation energies and SO splittings at a correlated level, and for ground and excited state spectroscopic properties of group 11 monohalides and group 12 dimers.

820 citations


Journal ArticleDOI
TL;DR: In this paper, the critical blow-up exponent for a Keller-Segel-type chemotaxis model was determined, where the chemotactic sensitivity equals some nonlinear function of the particle density.

801 citations


Journal ArticleDOI
TL;DR: It is shown that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT, and the use of iDTR mice is validated as a tool for cell ablation in vivo.
Abstract: A new system for lineage ablation is based on transgenic expression of a diphtheria toxin receptor (DTR) in mouse cells and application of diphtheria toxin (DT). To streamline this approach, we generated Cre-inducible DTR transgenic mice (iDTR) in which Cre-mediated excision of a STOP cassette renders cells sensitive to DT. We tested the iDTR strain by crossing to the T cell- and B cell-specific CD4-Cre and CD19-Cre strains, respectively, and observed efficient ablation of T and B cells after exposure to DT. In MOGi-Cre/iDTR double transgenic mice expressing Cre recombinase in oligodendrocytes, we observed myelin loss after intraperitoneal DT injections. Thus, DT crosses the blood-brain barrier and promotes cell ablation in the central nervous system. Notably, we show that the developing DT-specific antibody response is weak and not neutralizing, and thus does not impede the efficacy of DT. Our results validate the use of iDTR mice as a tool for cell ablation in vivo.

740 citations


Journal ArticleDOI
TL;DR: The results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo and conclude that microglia paralysis inhibits the development and maintenance of inflammatory CNS lesions.
Abstract: Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo.

Journal ArticleDOI
TL;DR: It is demonstrated that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.
Abstract: Multiple hormones controlling energy homeostasis regulate the expression of neuropeptide Y (NPY) and agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus. Nevertheless, inactivation of the genes encoding NPY and/or AgRP has no impact on food intake in mice. Here we demonstrate that induced selective ablation of AgRP-expressing neurons in adult mice results in acute reduction of feeding, demonstrating direct evidence for a critical role of these neurons in the regulation of energy homeostasis.

Journal ArticleDOI
TL;DR: A panel of experienced European pathologists and a foreign expert evaluated a large number of representative slides of trephine biopsies from patients with myelofibrosis in an attempt to reach a consensus on how to grade cellularity and fibrosis to allow for precise grading during the disease process and after therapy.
Abstract: Quantification of characteristic bone marrow biopsy features includes basic parameters such as cellularity and fiber content. These are important to assess the dynamics of disease processes with a significant impact on risk stratification, survival patterns and, especially, therapy-related changes. A panel of experienced European pathologists and a foreign expert evaluated, at a multi-headed microscope, a large number of representative slides of trephine biopsies from patients with myelofibrosis in an attempt to reach a consensus on how to grade cellularity and fibrosis. This included a critical evaluation of previously described scoring systems. During the microscopic analysis and subsequent discussion and voting, the importance of age-dependent decrease in cellularity was recognized. Grading of myelofibrosis was simplified by using four easily reproducible categories including differentiation between reticulin and collagen. A consensus was reached that the density of fibers must be assessed in relation to the hematopoietic tissue. This feature is especially important in order to avoid a false impression of a reduced fiber content in fatty and/or edematous bone marrow samples after treatment. The consensus for measuring myelofibrosis by clear and reproducible guidelines achieved by our group should allow for precise grading during the disease process and after therapy.

Journal ArticleDOI
08 Dec 2005-Nature
TL;DR: The temperature and density profiles, as determined by the Huygens Atmospheric Structure Instrument (HASI), from an altitude of 1,400 km down to the surface were higher than expected and the extent of atmospheric electricity was also hitherto unknown.
Abstract: On the basis of previous ground-based and fly-by information, we knew that Titan's atmosphere was mainly nitrogen, with some methane, but its temperature and pressure profiles were poorly constrained because of uncertainties in the detailed composition. The extent of atmospheric electricity (‘lightning’) was also hitherto unknown. Here we report the temperature and density profiles, as determined by the Huygens Atmospheric Structure Instrument (HASI), from an altitude of 1,400 km down to the surface. In the upper part of the atmosphere, the temperature and density were both higher than expected. There is a lower ionospheric layer between 140 km and 40 km, with electrical conductivity peaking near 60 km. We may also have seen the signature of lightning. At the surface, the temperature was 93.65 ± 0.25 K, and the pressure was 1,467 ± 1 hPa.

Journal ArticleDOI
TL;DR: In this paper, it was shown that any interaction of pressureless dark matter with holographic dark energy, whose infrared cutoff is set by the Hubble scale, implies a constant ratio of the energy densities of both components thus solving the coincidence problem.

Journal ArticleDOI
TL;DR: A platform for mass spectral and retention time index libraries that will enable metabolite profiling and should ameliorate many of the problems that each laboratory will face both for the initial establishment of metabolome analysis and for its maintenance at a constant sample throughput.

Journal ArticleDOI
11 Oct 2005-Blood
TL;DR: First-line treatment with FC increases the response rates and the treatment-free interval in younger patients with advanced CLL and no difference in median overall survival has been observed.

Journal ArticleDOI
TL;DR: Insulin regulates phosphorylation of tau, metabolism of the amyloid precursor protein and clearance of beta-amyloid from the brain in vivo and indicates that neuronal IR signaling has a direct role in the link between energy homeostasis, reproduction and the development of neurodegenerative diseases.
Abstract: The insulin receptor (IR) is expressed in various regions of the developing and adult brain, and its functions have become the focus of recent research. Insulin enters the central nervous system (CNS) through the blood–brain barrier by receptor-mediated transport to regulate food intake, sympathetic activity and peripheral insulin action through the inhibition of hepatic gluconeogenesis and reproductive endocrinology. On a molecular level, some of the effects of insulin converge with those of the leptin signaling machinery at the point of activation of phosphatidylinositol 3-kinase (PI3K), resulting in the regulation of ATP-dependent potassium channels. Furthermore, insulin inhibits neuronal apoptosis via activation of protein kinase B in vitro , and it regulates phosphorylation of tau, metabolism of the amyloid precursor protein and clearance of β-amyloid from the brain in vivo . These findings indicate that neuronal IR signaling has a direct role in the link between energy homeostasis, reproduction and the development of neurodegenerative diseases.

Journal ArticleDOI
TL;DR: In this paper, the authors focus on the Karoo basins sensu stricto of south-central Africa, synthesizing their sedimentological and stratigraphic features in relation to the tectonic and climatic controls on accommodation and sedimentation.

Journal ArticleDOI
TL;DR: The MLST scheme provides a high level of resolution and an excellent tool for studying the population structure and long-term epidemiology of A. baumannii.
Abstract: In this study a multilocus sequence typing (MLST) scheme for Acinetobacter baumannii was developed and evaluated by using 40 clinical A. baumannii isolates recovered from outbreaks in Spanish and German hospitals during the years 1990 to 2001, as well as isolates from other European hospitals and two DSMZ reference strains of A. baumannii. For comparison, two isolates of Acinetobacter species 13 (sensu Tjernberg and Ursing), two clinical isolates, and three DSMZ strains of A. calcoaceticus (both belonging to the A. calcoaceticus-A. baumannii complex) were also investigated. Primers were designed for conserved regions of housekeeping genes, and 305- to 513-bp internal fragments of seven such genes—gltA, gyrB, gdhB, recA, cpn60, gpi, and rpoD—were sequenced for all strains. The number of alleles at individual loci ranged from 6 to 12, and a total of 20 allelic profiles or sequence types were distinguished among the investigated A. baumannii strains. The MLST data were in high concordance with the epidemiologic typing results generated by pulsed-field gel electrophoresis and amplified fragment length polymorphism fingerprinting. The MLST scheme provides a high level of resolution and an excellent tool for studying the population structure and long-term epidemiology of A. baumannii.

Book
01 Jan 2005
TL;DR: The framework for replicating use patterns and limits of replication are presented, and a meta-language model is proposed to describe the role of language in the development of language-based knowledge.
Abstract: The phenomenon of language contact, and how it affects the structure of languages, has been of great interest to linguists. This study looks at how grammatical forms and structures evolve when speakers of two languages come into contact, and offers an interesting insight into the mechanism that induces people to transfer grammatical structures from one language to another. Drawing on findings from languages all over the world, Language Contact and Grammatical Change shows that the transfer of linguistic material across languages is quite regular and follows universal patterns of grammaticalization - contrary to previous claims that it is a fairly irregular process - and argues that internal and external explanations of language structure and change are in no way mutually exclusive. Engaging and informative, this book will be of great interest to sociolinguists, linguistic anthropologists, and all those working on grammaticalization, language contact, and language change.

Journal ArticleDOI
TL;DR: Experimental evidence is presented that the mitochondrial 16S rRNA gene fulfills the requirements for a universal DNA barcoding marker in amphibians and in terms of universality of priming sites and identification of major vertebrate clades the studied 16S fragment is superior to COI.
Abstract: Background Identifying species of organisms by short sequences of DNA has been in the center of ongoing discussions under the terms DNA barcoding or DNA taxonomy. A C-terminal fragment of the mitochondrial gene for cytochrome oxidase subunit I (COI) has been proposed as universal marker for this purpose among animals.

Journal ArticleDOI
TL;DR: Results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach for HIV-1-positive individuals prescreened for the absence of CXCR4-using virus.
Abstract: We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=16 log(10) copies/ml at all twice daily doses >or=100 mg These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach


Journal ArticleDOI
TL;DR: In this article, the authors analyzed intraand interspecific patterns of mitochondrial variation in two distantly related groups of amphibians, mantellid frogs and salamanders, to determine the promise of DNA barcoding with cytochrome oxidase subunit I (cox1) sequences in this taxon.
Abstract: Amphibians globally are in decline, yet there is still a tremendous amount of unrecognized diversity, calling for an acceleration of taxonomic exploration. This process will be greatly facilitated by a DNA barcoding system; however, the mitochondrial population structure of many amphibian species presents numerous challenges to such a standardized, single locus, approach. Here we analyse intraand interspecific patterns of mitochondrial variation in two distantly related groups of amphibians, mantellid frogs and salamanders, to determine the promise of DNA barcoding with cytochrome oxidase subunit I (cox1) sequences in this taxon. High intraspecific cox1 divergences of 7‐14% were observed (18% in one case) within the whole set of amphibian sequences analysed. These high values are not caused by particularly high substitution rates of this gene but by generally deep mitochondrial divergences within and among amphibian species. Despite these high divergences, cox1 sequences were able to correctly identify species including disparate geographic variants. The main problems with cox1 barcoding of amphibians are (i) the high variability of priming sites that hinder the application of universal primers to all species and (ii) the observed distinct overlap of intraspecific and interspecific divergence values, which implies difficulties in the definition of threshold values to identify candidate species. Common discordances between geographical signatures of mitochondrial and nuclear markers in amphibians indicate that a single-locus approach can be problematic when high accuracy of DNA barcoding is required. We suggest that a number of mitochondrial and nuclear genes may be used as DNA barcoding markers to complement cox1.

Journal ArticleDOI
TL;DR: The real-time PCR expression profile of human ETT, with strong expression in CD71+ cells, is consistent with a pivotal function ofET in erythrocytes, and prominent expression of ETT in monocytes and SLC22A4 polymorphism associations suggest a protective role of ET in chronic inflammatory disorders.
Abstract: Variants of the SLC22A4 gene are associated with susceptibility to rheumatoid arthritis and Crohn's disease. SLC22A4 codes for an integral membrane protein, OCTN1, that has been presumed to carry organic cations like tetraethylammonium across the plasma membrane. Here, we show that the key substrate of this transporter is in fact ergothioneine (ET). Human OCTN1 was expressed in 293 cells. A substrate lead, stachydrine (alias proline betaine), was identified by liquid chromatography MS difference shading, a new substrate search strategy. Analysis of transport efficiency of stachydrine-related solutes, affinity, and Na+ dependence indicates that the physiological substrate is ET. Efficiency of transport of ET was as high as 195 μl per min per mg of protein. By contrast, the carnitine transporter OCTN2 from rat did not transport ET at all. Because ET is transported >100 times more efficiently than tetraethylammonium and carnitine, we propose the functional name ETT (ET transporter) instead of OCTN1. ET, all of which is absorbed from food, is an intracellular antioxidant with metal ion affinity. Its particular purpose is unresolved. Cells with expression of ETT accumulate ET to high levels and avidly retain it. By contrast, cells lacking ETT do not accumulate ET, because their plasma membrane is virtually impermeable for this compound. The real-time PCR expression profile of human ETT, with strong expression in CD71+ cells, is consistent with a pivotal function of ET in erythrocytes. Moreover, prominent expression of ETT in monocytes and SLC22A4 polymorphism associations suggest a protective role of ET in chronic inflammatory disorders. erythrocyte inflammation

Journal ArticleDOI
TL;DR: Present knowledge about the pharmacokinetics, drug responses, and outcomes of clinical studies in individuals with different CYP2C9 genotypes is summarized.
Abstract: The gene coding for the cytochrome P450 (CYP) enzyme 2C9 (CYP2C9) carries numerous inherited polymorphisms. Those coding for R144C (*2) and I359L (*3) amino acid substitutions have both significant functional effects and appreciable high population frequencies, and their in vivo consequences have been studied in humans with regard to drug metabolism. This review summarizes present knowledge about the pharmacokinetics, drug responses, and outcomes of clinical studies in individuals with different CYP2C9 genotypes. Tentative estimates of how CYP2C9 genotyping might be applied to dose adjustments in clinical therapy were based on dose-related pharmacokinetic parameters such as clearance or trough drug concentrations. Mean clearances in homozygous carriers of the *3 allele were below 25% of that of the wild type for S -warfarin, tolbutamide, glipizide, celecoxib, and fluvastatin. In the more frequent heterozygous carriers (genotype *1/*3), the clearances were between 40% and 75%. In these cases in which individual dosages are derived from clinical drug effects, such as for the oral anticoagulants, the pharmacogenetics-based dose adjustments showed a good correlation with the genotype-specific empirically derived doses. In addition to its role in pharmacokinetics, CYP2C9 contributes to the metabolism of fatty acids, prostanoids, and steroid hormones, and it may catalyze potentially toxic bioactivation reactions. However, our current understanding of the role of CYP2C9 in biotransformation of endogenous signaling molecules and in drug toxicity is relatively meager.

Journal ArticleDOI
TL;DR: Cardiac resynchronization therapy appears to offer benefit in pediatric and CHD patients who differ substantially from the adult populations in whom this therapy has been most thoroughly evaluated to date.

Journal ArticleDOI
TL;DR: In the first Global Entrepreneurship Monitor (GEM) special issue as discussed by the authors, the authors considered new venture creation as the hallmark of entrepreneurship and found a positive effect of entrepreneurial activity on economic growth in highly developed countries but a negative effect for developing nations.
Abstract: This paper is an introduction to the present special issue dedicated to scientific research using data collected as part of the Global Entrepreneurship Monitor (GEM) and considering new venture creation as the hallmark of entrepreneurship. After a short description of GEM’s theoretical and methodological background, this introduction highlights the main results of seven papers which were presented at the First GEM Research Conference in Berlin from 1 to 3 April 2004. First, there is empirical evidence that the role of entrepreneurial activity differs across the stages of economic development, in that there appears to be a U-shaped relationship between the level of development and the rate of entrepreneurship. Consequently, a positive effect of entrepreneurial activity on economic growth is found for highly developed countries but a negative effect for developing nations. Second, it is shown that different types of entrepreneurship may have a different impact on a nation’s innovativeness and economic growth rate. In particular, potentially high-growth business start-ups and so-called opportunity entrepreneurship enhance knowledge spillovers and economic growth. Third, entrepreneurship is again shown to be a regional event that can only be understood if regional framework conditions, including networks and regional policies, are taken into consideration.

Posted Content
TL;DR: In this paper, the authors compare trading in a market with online feedback (as implemented by many Internet markets) to a market without feedback, as well as a market in which the same people interact with one another repeatedly (partners market).
Abstract: Electronic reputation or feedback mechanisms aim to mitigate the moral hazard problems associated with exchange among strangers by providing the type of information available in more traditional close-knit groups, where members are frequently involved in one another's dealings. In this paper, we compare trading in a market with online feedback (as implemented by many Internet markets) to a market without feedback, as well as to a market in which the same people interact with one another repeatedly (partners market). We find that while the feedback mechanism induces quite a substantial improvement in transaction efficiency, it also exhibits a kind of public goods problem in that, unlike in the partners market, the benefits of trust and trustworthy behavior go to the whole community and are not completely internalized. We discuss the implications of this perspective for improving feedback systems.