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Showing papers by "University of Cologne published in 2009"


Journal ArticleDOI
30 Jul 2009-Blood
TL;DR: The classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.

4,274 citations


Journal ArticleDOI
13 Feb 2009-Science
TL;DR: This study experimentally establishes magnetic materials lacking inversion symmetry as an arena for new forms of crystalline order composed of topologically stable spin states in the chiral itinerant-electron magnet MnSi.
Abstract: Skyrmions represent topologically stable field configurations with particle-like properties. We used neutron scattering to observe the spontaneous formation of a two-dimensional lattice of skyrmion lines, a type of magnetic vortex, in the chiral itinerant-electron magnet MnSi. The skyrmion lattice stabilizes at the border between paramagnetism and long-range helimagnetic order perpendicular to a small applied magnetic field regardless of the direction of the magnetic field relative to the atomic lattice. Our study experimentally establishes magnetic materials lacking inversion symmetry as an arena for new forms of crystalline order composed of topologically stable spin states.

3,651 citations


Journal ArticleDOI
TL;DR: In this paper, a large-scale Monte-Carlo simulation was conducted to compare the performance of covariance-based and partial least squares (PLS) analysis with PLS and CBSEM.

1,864 citations


Journal ArticleDOI
TL;DR: In this article, a large-scale Monte-Carlo simulation was conducted to compare the performance of covariance-based and partial least squares (PLS) analysis with PLS.
Abstract: Variance-based SEM, also known under the term partial least squares (PLS) analysis, is an approach that has gained increasing interest among marketing researchers in recent years. During the last 25 years, more than 30 articles have been published in leading marketing journals that have applied this approach instead of the more traditional alternative of covariance-based SEM (CBSEM). However, although an analysis of these previous publications shows that there seems to be at least an implicit agreement about the factors that should drive the choice between PLS analysis and CBSEM, no research has until now empirically compared the performance of these approaches given a set of different conditions. Our study addresses this open question by conducting a large-scale Monte-Carlo simulation. We show that justifying the choice of PLS due to a lack of assumptions regarding indicator distribution and measurement scale is often inappropriate, as CBSEM proves extremely robust with respect to violations of its underlying distributional assumptions. Additionally, CBSEM clearly outperforms PLS in terms of parameter consistency and is preferable in terms of parameter accuracy as long as the sample size exceeds a certain threshold (250 observations). Nevertheless, PLS analysis should be preferred when the emphasis is on prediction and theory development, as the statistical power of PLS is always larger than or equal to that of CBSEM; already, 100 observations can be sufficient to achieve acceptable levels of statistical power given a certain quality of the measurement model.

1,378 citations


Journal ArticleDOI
TL;DR: This work reports a distinct additional contribution to the Hall effect in the temperature and magnetic field range of the proposed Skyrmion lattice, where such a contribution is neither seen nor expected for a normal helical state.
Abstract: Recent small angle neutron scattering suggests that the spin structure in the A phase of MnSi is a so-called triple-Q state, i.e., a superposition of three helices under 120 degrees. Model calculations indicate that this structure in fact is a lattice of so-called Skyrmions, i.e., a lattice of topologically stable knots in the spin structure. We report a distinct additional contribution to the Hall effect in the temperature and magnetic field range of the proposed Skyrmion lattice, where such a contribution is neither seen nor expected for a normal helical state. Our Hall effect measurements constitute a direct observation of a topologically quantized Berry phase that identifies the spin structure seen in neutron scattering as the proposed Skyrmion lattice.

1,255 citations


Journal ArticleDOI
16 Apr 2009-Nature
TL;DR: These experiments provide the first direct demonstration that Fto is functionally involved in energy homeostasis by the control of energy expenditure, and leads to postnatal growth retardation and a significant reduction in adipose tissue and lean body mass.
Abstract: Variations in the human FTO gene have been linked to obesity-related traits in several genome-wide association studies. A functional correlation is now reported between Fto, the equivalent gene in the mouse, and obesity. In Fto-deficient mice there is postnatal growth retardation and a lean phenotype with high energy expenditure and reduced fat accumulation. This suggests that Fto/FTO is involved in homeostasis via the control of energy expenditure. This study shows that mice lacking the Fto gene do not grow properly after birth, and have less adipose tissue and lean body mass. This is due to increased energy expenditure and systemic sympathetic activation, even though these mice move less and eat lots. Several independent, genome-wide association studies have identified a strong correlation between body mass index and polymorphisms in the human FTO gene1,2,3,4. Common variants in the first intron define a risk allele predisposing to obesity, with homozygotes for the risk allele weighing approximately 3 kilograms more than homozygotes for the low risk allele1. Nevertheless, the functional role of FTO in energy homeostasis remains elusive. Here we show that the loss of Fto in mice leads to postnatal growth retardation and a significant reduction in adipose tissue and lean body mass. The leanness of Fto-deficient mice develops as a consequence of increased energy expenditure and systemic sympathetic activation, despite decreased spontaneous locomotor activity and relative hyperphagia. Taken together, these experiments provide, to our knowledge, the first direct demonstration that Fto is functionally involved in energy homeostasis by the control of energy expenditure.

854 citations


Journal ArticleDOI
11 Dec 2009-Cell
TL;DR: The results show that maintenance of the ovarian phenotype is an active process throughout life and might have important medical implications for the understanding and treatment of some disorders of sexual development in children and premature menopause in women.

794 citations


Journal ArticleDOI
Daniel F. Gudbjartsson1, Unnur S. Bjornsdottir1, Unnur S. Bjornsdottir2, Eva Halapi1, Anna Helgadottir1, Patrick Sulem1, Gudrun M. Jonsdottir1, Gudmar Thorleifsson1, Hafdis T. Helgadottir1, Valgerdur Steinthorsdottir1, Hreinn Stefansson1, Carolyn Williams3, Jennie Hui3, John Beilby3, Nicole M. Warrington3, Alan L. James4, Alan L. James3, Lyle J. Palmer3, Gerard H. Koppelman5, Andrea Heinzmann6, Marcus Krueger6, H. Marike Boezen7, Amanda Wheatley8, Janine Altmüller9, Hyoung Doo Shin10, Soo-Taek Uh11, Hyun Sub Cheong11, Brynja Jonsdottir, David Gislason, Choon-Sik Park11, Linda M. Rasmussen12, Celeste Porsbjerg12, Jakob Werner Hansen12, Vibeke Backer12, Thomas Werge, Christer Janson13, Ulla-Britt Jönsson13, Maggie C.Y. Ng14, Juliana C.N. Chan14, Wing-Yee So14, Ronald C.W. Ma14, Svati H. Shah15, Christopher B. Granger15, Arshed A. Quyyumi16, Allan I. Levey16, Viola Vaccarino16, Muredach P. Reilly17, Daniel J. Rader17, Michael J.A. Williams18, Andre M. van Rij18, Gregory T. Jones18, Elisabetta Trabetti19, Giovanni Malerba19, Pier Franco Pignatti19, Attilio Boner19, Lydia Pescollderungg, Domenico Girelli19, Oliviero Olivieri19, Nicola Martinelli19, Bjorn R. Ludviksson2, Dora Ludviksdottir, Gudmundur I. Eyjolfsson, David O. Arnar2, Gudmundur Thorgeirsson2, Klaus A. Deichmann6, Philip J. Thompson3, Matthias Wjst, Ian P. Hall9, Dirkje S. Postma7, Thorarinn Gislason2, Jeffrey R. Gulcher1, Augustine Kong1, Ingileif Jonsdottir2, Ingileif Jonsdottir1, Unnur Thorsteinsdottir1, Unnur Thorsteinsdottir2, Kari Stefansson2, Kari Stefansson1 
TL;DR: A genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly with myocardial infarction in six different populations.
Abstract: Eosinophils are pleiotropic multifunctional leukocytes involved in initiation and propagation of inflammatory responses and thus have important roles in the pathogenesis of inflammatory diseases. Here we describe a genome-wide association scan for sequence variants affecting eosinophil counts in blood of 9,392 Icelanders. The most significant SNPs were studied further in 12,118 Europeans and 5,212 East Asians. SNPs at 2q12 (rs1420101), 2q13 (rs12619285), 3q21 (rs4857855), 5q31 (rs4143832) and 12q24 (rs3184504) reached genome-wide significance (P = 5.3 x 10(-14), 5.4 x 10(-10), 8.6 x 10(-17), 1.2 x 10(-10) and 6.5 x 10(-19), respectively). A SNP at IL1RL1 associated with asthma (P = 5.5 x 10(-12)) in a collection of ten different populations (7,996 cases and 44,890 controls). SNPs at WDR36, IL33 and MYB that showed suggestive association with eosinophil counts were also associated with atopic asthma (P = 4.2 x 10(-6), 2.2 x 10(-5) and 2.4 x 10(-4), respectively). We also found that a nonsynonymous SNP at 12q24, in SH2B3, associated significantly (P = 8.6 x 10(-8)) with myocardial infarction in six different populations (6,650 cases and 40,621 controls).

754 citations


Journal ArticleDOI
12 Aug 2009-Nature
TL;DR: The biosynthetic pathways leading to both types of cofactor have common mechanistic aspects relating to scaffold formation, metal activation and cofactor insertion into apoenzymes, and have served as an evolutionary 'toolbox' to mediate additional cellular functions in eukaryotic metabolism.
Abstract: The trace element molybdenum is essential for nearly all organisms and forms the catalytic centre of a large variety of enzymes such as nitrogenase, nitrate reductases, sulphite oxidase and xanthine oxidoreductases. Nature has developed two scaffolds holding molybdenum in place, the iron-molybdenum cofactor and pterin-based molybdenum cofactors. Despite the different structures and functions of molybdenum-dependent enzymes, there are important similarities, which we highlight here. The biosynthetic pathways leading to both types of cofactor have common mechanistic aspects relating to scaffold formation, metal activation and cofactor insertion into apoenzymes, and have served as an evolutionary 'toolbox' to mediate additional cellular functions in eukaryotic metabolism.

669 citations


Journal ArticleDOI
A. Léger1, Daniel Rouan2, Jean Schneider3, Pierre Barge4  +159 moreInstitutions (17)
TL;DR: In this paper, the authors reported the discovery of very shallow (ΔF/F ≈ 3.4× 10 −4 ) periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which they interpret as caused by a transiting companion.
Abstract: Aims. We report the discovery of very shallow (ΔF/F ≈ 3.4× 10 −4 ), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as caused by a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We used CoRoT colours information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy, and preliminary results from radial velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star were derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. Results. We examined all conceivable cases of false positives carefully, and all the tests support the planetary hypothesis. Blends with separation >0.40 �� or triple systems are almost excluded with a 8 × 10 −4 risk left. We conclude that, inasmuch we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 ± 3 × 10 −5 day and a radius of Rp = 1.68 ± 0.09 REarth .A nalysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. Conclusions. CoRoT-7b is very likely the first Super-Earth with a measured radius. This object illustrates what will probably become a common situation with missions such as Kepler, namely the need to establish the planetary origin of transits in the absence of a firm radial velocity detection and mass measurement. The composition of CoRoT-7b remains loosely constrained without a precise mass. A very high surface temperature on its irradiated face, ≈1800–2600 K at the substellar point, and a very low one, ≈50 K, on its dark face assuming no atmosphere, have been derived.

665 citations


Journal ArticleDOI
TL;DR: It is reported that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses and represents a novel adaptive pro‐survival response against stress.
Abstract: Mitochondria are dynamic organelles, the morphology of which results from an equilibrium between two opposing processes, fusion and fission. Mitochondrial fusion relies on dynamin-related GTPases, the mitofusins (MFN1 and 2) in the outer mitochondrial membrane and OPA1 (optic atrophy 1) in the inner mitochondrial membrane. Apart from a role in the maintenance of mitochondrial DNA, little is known about the physiological role of mitochondrial fusion. Here we report that mitochondria hyperfuse and form a highly interconnected network in cells exposed to selective stresses. This process precedes mitochondrial fission when it is triggered by apoptotic stimuli such as UV irradiation or actinomycin D. Stress-induced mitochondrial hyperfusion (SIMH) is independent of MFN2, BAX/BAK, and prohibitins, but requires L-OPA1, MFN1, and the mitochondrial inner membrane protein SLP-2. In the absence of SLP-2, L-OPA1 is lost and SIMH is prevented. SIMH is accompanied by increased mitochondrial ATP production and represents a novel adaptive pro-survival response against stress.

Journal ArticleDOI
TL;DR: The results based on observational data support safety concerns surrounding the mitogenic properties of glargine in diabetic patients, and considering the overall relationship between insulin dose and cancer, the cancer incidence with glargin was higher than expected compared with human insulin.
Abstract: Aims/hypothesis The aim of this cohort study was to investigate the risk of malignant neoplasms and mortality in patients with diabetes treated either with human insulin or with one of three insulin analogues. Methods Data were provided by the largest German statutory health insurance fund (time-frame: January 1998 to June 2005 inclusive), on patients without known malignant disease who had received first-time therapy for diabetes mellitus exclusively with human insulin, aspart, lispro or glargine. The primary outcome was the diagnosis of a malignant neoplasm. Data were analysed by multiple Cox regression models adjusting for potential confounders. Results A total of 127,031 patients were included, with a mean follow-up time of 1.63 (median 1.41, maximum 4.41) years. A positive association between cancer incidence and insulin dose was found for all insulin types. Because patients receiving combined therapy with insulin analogues and human insulin were excluded, the mean daily dose was much lower for glargine than for human insulin, and a slightly lower cancer incidence in the glargine group was found. After adjusting for dose, a dose-dependent increase in cancer risk was found for treatment with glargine compared with human insulin (p<0.0001): the adjusted HR was 1.09 (95% CI 1.00 to 1.19) for a daily dose of 10 IU, 1.19 (95% CI 1.10 to 1.30) for a daily dose of 30 IU, and 1.31 (95% CI 1.20 to 1.42) for a daily dose of 50 IU. No increased risk was found for aspart (p=0.30) or lispro (p=0.96) compared with human insulin. Conclusions/interpretation Considering the overall relationship between insulin dose and cancer, and the lower dose with glargine, the cancer incidence with glargine was higher than expected compared with human insulin. Our results based on observational data support safety concerns surrounding the mitogenic properties of glargine in diabetic patients. Prospective long-term studies are needed to further evaluate the safety of insulin analogues, especially glargine.

Journal ArticleDOI
TL;DR: Nitrogen stress-induced LB production in C. reinhardtii has the hallmarks of a discrete pathway that should be amenable to additional genetic and culture condition manipulation.
Abstract: When the unicellular green soil alga Chlamydomonas reinhardtii is deprived of nitrogen after entering stationary phase in liquid culture, the cells produce abundant cytoplasmic lipid bodies (LBs), as well as abundant starch, via a pathway that accompanies a regulated autophagy program After 48 h of N starvation in the presence of acetate, the wild-type LB content has increased 15-fold When starch biosynthesis is blocked in the sta6 mutant, the LB content increases 30-fold, demonstrating that genetic manipulation can enhance LB production The use of cell wall-less strains permitted development of a rapid “popped-cell” microscopic assay to quantitate the LB content per cell and permitted gentle cell breakage and LB isolation The highly purified LBs contain 90% triacylglycerol (TAG) and 10% free fatty acids (FFA) The fatty acids associated with the TAGs are ∼50% saturated (C16 and C18) fatty acids and ∼50% unsaturated fatty acids, half of which are in the form of oleic acid (C18:1) The FFA are ∼50% C16 and ∼50% C18 The LB-derived TAG yield from a liter of sta6 cells at 107 cells/ml after starvation for 48 h is calculated to approach 400 mg The LB fraction also contains low levels of charged glycerolipids, with the same profile as whole-cell charged glycerolipids, that presumably form LB membranes; chloroplast-specific neutral glycerolipids (galactolipids) are absent Very low levels of protein are also present, but all matrix-assisted laser desorption ionization-identified species are apparent contaminants Nitrogen stress-induced LB production in C reinhardtii has the hallmarks of a discrete pathway that should be amenable to additional genetic and culture condition manipulation

Journal ArticleDOI
TL;DR: In this paper, the authors used the Hf-W systematics of meteoritic and planetary samples to provide firm constraints on the chronology of the accretion and earliest evolution of asteroids and terrestrial planets and lead to the following succession and duration of events in the earliest solar system.

Journal ArticleDOI
TL;DR: The results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.
Abstract: We identified 15q13.3 microdeletions encompassing the CHRNA7 gene in 12 of 1,223 individuals with idiopathic generalized epilepsy (IGE), which were not detected in 3,699 controls (joint P = 5.32 x 10(-8)). Most deletion carriers showed common IGE syndromes without other features previously associated with 15q13.3 microdeletions, such as intellectual disability, autism or schizophrenia. Our results indicate that 15q13.3 microdeletions constitute the most prevalent risk factor for common epilepsies identified to date.

Journal ArticleDOI
TL;DR: Findings indicate that NF-κB signalling acts in non-immune cells to control the maintenance of tissue immune homeostasis and prevents the pathogenesis of inflammatory diseases.
Abstract: The nuclear factor-kappaB (NF-kappaB) signalling pathway regulates immune responses and is implicated in the pathogenesis of many inflammatory diseases. Given the well established pro-inflammatory functions of NF-kappaB, inhibition of this pathway would be expected to have anti-inflammatory effects. However, recent studies in mouse models have led to surprising and provocative results, as NF-kappaB inhibition in epithelial cells resulted in the spontaneous development of severe chronic inflammatory conditions. These findings indicate that NF-kappaB signalling acts in non-immune cells to control the maintenance of tissue immune homeostasis. This Review discusses the mechanisms by which NF-kappaB activity in non-immune cells regulates tissue immune homeostasis and prevents the pathogenesis of inflammatory diseases.

Journal ArticleDOI
TL;DR: Epitaxial graphene on Ir(111) prepared in excellent structural quality is investigated by angle-resolved photoelectron spectroscopy and clearly displays a Dirac cone with the Dirac point shifted only slightly above the Fermi level.
Abstract: Epitaxial graphene on Ir(111) prepared in excellent structural quality is investigated by angle-resolved photoelectron spectroscopy. It clearly displays a Dirac cone with the Dirac point shifted only slightly above the Fermi level. The moire resulting from the overlaid graphene and Ir(111) surface lattices imposes a superperiodic potential giving rise to Dirac cone replicas and the opening of minigaps in the band structure.

Journal ArticleDOI
TL;DR: The cleavage by OMA1 causes an accumulation of the short OPA1 variants, and the role ofm-AAA proteases in ensuring a balance of long and short Opa1 isoforms is investigated.
Abstract: Mitochondrial fusion depends on the dynamin-like guanosine triphosphatase OPA1, whose activity is controlled by proteolytic cleavage. Dysfunction of mitochondria induces OPA1 processing and results in mitochondrial fragmentation, allowing the selective removal of damaged mitochondria. In this study, we demonstrate that two classes of metallopeptidases regulate OPA1 cleavage in the mitochondrial inner membrane: isoenzymes of the adenosine triphosphate (ATP)-dependent matrix AAA (ATPase associated with diverse cellular activities [m-AAA]) protease, variable assemblies of the conserved subunits paraplegin, AFG3L1 and -2, and the ATP-independent peptidase OMA1. Functionally redundant isoenzymes of the m-AAA protease ensure the balanced accumulation of long and short isoforms of OPA1 required for mitochondrial fusion. The loss of AFG3L2 in mouse tissues, down-regulation of AFG3L1 and -2 in mouse embryonic fibroblasts, or the expression of a dominant-negative AFG3L2 variant in human cells decreases the stability of long OPA1 isoforms and induces OPA1 processing by OMA1. Moreover, cleavage by OMA1 causes the accumulation of short OPA1 variants if mitochondrial DNA is depleted or mitochondrial activities are impaired. Our findings link distinct peptidases to constitutive and induced OPA1 processing and shed new light on the pathogenesis of neurodegenerative disorders associated with mutations in m-AAA protease subunits.

Journal ArticleDOI
TL;DR: This Review intends to shed light onto the versatility that iron-catalyzed cross-coupling reactions offer, summarize major achievements, and clear the way for further use of such superior methodologies in the synthesis of fine chemicals, bioactive molecules, and materials.
Abstract: Iron-catalyzed cross-coupling reactions have, over the past years, developed to maturity and today are an integral part of the organic chemist's toolkit. They benefit from low costs, operational simplicity, and high reactivity and thus constitute the "green" sister of the palladium and nickel establishment. This timely Review traces back major achievements, discusses their mechanistic background, and highlights numerous applications to molecular synthesis.Iron-catalyzed carbon-carbon bond-forming reactions have matured to an indispensable class of reactions in organic synthesis. The advent of economically and ecologically attractive iron catalysts in the past years has stepped up the competition with the established palladium and nickel catalyst systems that have dominated the field for more than 30 years, but suffer from high costs, toxicity, and sometimes low reactivity. Iron-catalyzed protocols do not merely benefit from economic advantages but entertain a rich manifold of reactivity patterns and tolerate various functional groups. The past years have witnessed a rapid development with ever-more-efficient protocols for the cross-coupling between alkyl, alkenyl, alkynyl, aryl, and acyl moieties becoming available to organic chemists. This Review intends to shed light onto the versatility that iron-catalyzed cross-coupling reactions offer, summarize major achievements, and clear the way for further use of such superior methodologies in the synthesis of fine chemicals, bioactive molecules, and materials.

Journal ArticleDOI
Shahana Ahmed1, Gilles Thomas2, Maya Ghoussaini1, Catherine S. Healey1, Manjeet K. Humphreys1, Radka Platte1, Jonathan J. Morrison1, Melanie Maranian1, Karen A. Pooley1, Robert Luben1, Diana Eccles3, D. Gareth Evans4, Olivia Fletcher, Nichola Johnson, Isabel dos Santos Silva, Julian Peto, Michael R. Stratton5, Nazneen Rahman, Kevin B. Jacobs2, Kevin B. Jacobs6, Ross L. Prentice7, Garnet L. Anderson7, Aleksandar Rajkovic8, J. David Curb9, Regina G. Ziegler2, Christine D. Berg2, Saundra S. Buys10, Catherine A. McCarty11, Heather Spencer Feigelson12, Eugenia E. Calle12, Michael J. Thun12, W. Ryan Diver12, Stig E. Bojesen13, Børge G. Nordestgaard13, Henrik Flyger13, Thilo Dörk14, Peter Schürmann14, Peter Hillemanns14, Johann H. Karstens14, Natalia Bogdanova14, Natalia Antonenkova, Iosif V. Zalutsky, Marina Bermisheva14, S. A. Fedorova15, Elza Khusnutdinova, Daehee Kang16, Keun-Young Yoo16, Dong Young Noh16, Sei Hyun Ahn16, Peter Devilee17, Christi J. van Asperen17, R.A.E.M. Tollenaar17, Caroline Seynaeve18, Montserrat Garcia-Closas2, Jolanta Lissowska19, Louise A. Brinton2, Beata Peplonska20, Heli Nevanlinna21, Tuomas Heikkinen21, Kristiina Aittomäki21, Carl Blomqvist21, John L. Hopper22, Melissa C. Southey22, Letitia D. Smith23, Amanda B. Spurdle23, Marjanka K. Schmidt24, Annegien Broeks24, Richard van Hien24, Sten Cornelissen24, Roger L. Milne25, Gloria Ribas25, Anna González-Neira25, Javier Benitez25, Rita K. Schmutzler26, Barbara Burwinkel27, Barbara Burwinkel28, Claus R. Bartram27, Alfons Meindl29, Hiltrud Brauch30, Hiltrud Brauch31, Christina Justenhoven30, Christina Justenhoven31, Ute Hamann28, Jenny Chang-Claude28, Rebecca Hein28, Shan Wang-Gohrke32, Annika Lindblom33, Sara Margolin33, Arto Mannermaa34, Veli-Matti Kosma34, Vesa Kataja34, Janet E. Olson35, Xianshu Wang35, Zachary S. Fredericksen35, Graham G. Giles36, Graham G. Giles22, Gianluca Severi36, Gianluca Severi22, Laura Baglietto36, Laura Baglietto22, Dallas R. English22, Dallas R. English25, Susan E. Hankinson37, David G. Cox37, Peter Kraft37, Lars J. Vatten38, Kristian Hveem38, Merethe Kumle, Alice J. Sigurdson2, Michele M. Doody2, Parveen Bhatti2, Bruce H. Alexander39, Maartje J. Hooning18, Ans M.W. van den Ouweland18, Rogier A. Oldenburg18, Mieke Schutte18, Per Hall33, Kamila Czene33, Jianjun Liu40, Yuqing Li40, Angela Cox41, Graeme Elliott41, Ian W. Brock41, Malcolm W.R. Reed41, Chen-Yang Shen42, Chen-Yang Shen43, Jyh Cherng Yu44, Giu Cheng Hsu44, Shou Tung Chen, Hoda Anton-Culver45, Argyrios Ziogas45, Irene L. Andrulis46, Julia A. Knight46, Jonathan Beesley23, Ellen L. Goode35, Fergus J. Couch35, Georgia Chenevix-Trench23, Robert N. Hoover2, Bruce A.J. Ponder47, Bruce A.J. Ponder1, David J. Hunter37, Paul D.P. Pharoah1, Alison M. Dunning1, Stephen J. Chanock2, Douglas F. Easton1 
TL;DR: Strong evidence is found for additional susceptibility loci on 3p and 17q and potential causative genes include SLC4A7 and NEK10 on3p and COX11 on 17q.
Abstract: Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.

Journal ArticleDOI
TL;DR: In this paper, two growth methods for graphene on Ir(111), namely temperature programmed growth (TPG) and direct exposure of the hot substrate at 870-1320 K (CVD), are investigated in detail by scanning tunneling microscopy.
Abstract: Catalytic decomposition of hydrocarbons on transition metals attracts a renewed interest as a route toward high-quality graphene prepared in a reproducible manner. Here we employ two growth methods for graphene on Ir(111), namely room temperature adsorption and thermal decomposition at 870–1470 K (temperature programmed growth (TPG)) as well as direct exposure of the hot substrate at 870–1320 K (chemical vapor deposition (CVD)). The temperature- and exposure-dependent growth of graphene is investigated in detail by scanning tunneling microscopy. TPG is found to yield compact graphene islands bounded by C zigzag edges. The island size may be tuned from a few to a couple of tens of nanometers through Smoluchowski ripening. In the CVD growth, the carbon in ethene molecules arriving on the Ir surface is found to convert with probability near unity to graphene. The temperature-dependent nucleation, interaction with steps and coalescence of graphene islands are analyzed and a consistent model for CVD growth is developed.

Journal ArticleDOI
TL;DR: In this paper, a comprehensive review of the actual knowledge on climatologies of mid-latitude cyclones for the Northern and Southern Hemisphere for the present climate and for its possible changes under anthropogenic climate conditions is presented.
Abstract: Based on the availability of hemispheric gridded data sets from observations, analysis and global climate models, objective cyclone identification methods were developed and applied to these data sets. Due to the large amount of investigation methods combined with the variety of different datasets, a multitude of results exist, not only for the recent climate period but also for the next century, assuming anthropogenic changed conditions. Different thresholds, different physical quantities, and considerations of different atmospheric vertical levels add to a picture that is difficult to combine into a common view of cyclones, their variability and trends, in the real world and in GCM studies. Thus, this paper will give a comprehensive review of the actual knowledge on climatologies of mid-latitude cyclones for the Northern and Southern Hemisphere for the present climate and for its possible changes under anthropogenic climate conditions.

Journal ArticleDOI
TL;DR: The authors used a simple, three-item test for cognitive abilities to investigate whether established behavioral biases that play a prominent role in behavioral economics and finance are related to cognitive abilities and found that higher test scores on the cognitive reflection test of Frederick [Frederick, S., 2005] indeed are correlated with lower incidences of the conjunction fallacy and conservatism in updating probabilities.
Abstract: We use a simple, three-item test for cognitive abilities to investigate whether established behavioral biases that play a prominent role in behavioral economics and finance are related to cognitive abilities. We find that higher test scores on the cognitive reflection test of Frederick [Frederick, S., 2005. Cognitive reflection and decision-making. Journal of Economic Perspectives 19, 25–42] indeed are correlated with lower incidences of the conjunction fallacy and conservatism in updating probabilities. Test scores are also significantly related to subjects’ time and risk preferences. Test scores have no influence on the amount of anchoring, although there is evidence of anchoring among all subjects. Even if incidences of most biases are lower for people with higher cognitive abilities, they still remain substantial.

Journal ArticleDOI
TL;DR: It is demonstrated that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat3 activation and defines neuronal MyD88-dependent signaling as a key regulator of diet-induced leptin and insulin resistance in vivo.

Journal ArticleDOI
TL;DR: In this article, an intensive observational campaign carried out with HARPS at the 3.6 m telescope at La Silla on the star CoRoT-7 was reported, where several approaches were used to extract the radial velocity signal of the planet(s) from the stellar activity signal.
Abstract: We report on an intensive observational campaign carried out with HARPS at the 3.6 m telescope at La Silla on the star CoRoT-7. Additional simultaneous photometric measurements carried out with the Euler Swiss telescope have demonstrated that the observed radial velocity variations are dominated by rotational modulation from cool spots on the stellar surface. Several approaches were used to extract the radial velocity signal of the planet(s) from the stellar activity signal. First, a simple pre-whitening procedure was employed to find and subsequently remove periodic signals from the complex frequency structure of the radial velocity data. The dominant frequency in the power spectrum was found at 23 days, which corresponds to the rotation period of CoRoT-7. The 0.8535 day period of CoRoT-7b planetary candidate was detected with an amplitude of 3.3 m s −1 . Most other frequencies, some with amplitudes larger than the CoRoT-7b signal, are most likely associated with activity. A second approach used harmonic decomposition of the rotational period and up to the first three harmonics to filter out the activity signal from radial velocity variations caused by orbiting planets. After correcting the radial velocity data for activity, two periodic signals are detected: the CoRoT-7b transit period and a second one with a period of 3.69 days and an amplitude of 4 m s −1 . This second signal was also found in the pre-whitening analysis. We attribute the second signal to a second, more remote planet CoRoT-7c . The orbital solution of both planets is compatible with circular orbits. The mass of CoRoT-7b is 4.8 ± 0. 8( M⊕) and that of CoRoT-7c is 8.4 ± 0. 9( M⊕), assuming both planets are on coplanar orbits. We also investigated the false positive scenario of a blend by a faint stellar binary, and this may be rejected by the stability of the bisector on a nightly scale. According to their masses both planets belong to the super-Earth planet category. The average density of CoRoT-7b is ρ = 5.6 ± 1. 3gc m −3 , similar to the Earth. The CoRoT-7 planetary system provides us with the first insight into the physical nature of short period super-Earth planets recently detected by radial velocity surveys. These planets may be denser than Neptune and therefore likely made of rocks like the Earth, or a mix of water ice and rocks.

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TL;DR: It is shown that the electron Larmor radius plays the role of a dissipation scale in space plasma turbulence and the spectra form a quasiuniversal spectrum following the Kolmogorov's law at MHD scales.
Abstract: To investigate the universality of magnetic turbulence in space plasmas, we analyze seven time periods in the free solar wind under different plasma conditions. Three instruments on Cluster spacecraft operating in different frequency ranges give us the possibility to resolve spectra up to 300 Hz. We show that the spectra form a quasiuniversal spectrum following the Kolmogorov's law $\ensuremath{\sim}{k}^{\ensuremath{-}5/3}$ at MHD scales, a $\ensuremath{\sim}{k}^{\ensuremath{-}2.8}$ power law at ion scales, and an exponential $\ensuremath{\sim}\mathrm{exp} [\ensuremath{-}\sqrt{k{\ensuremath{\rho}}_{e}}]$ at scales $k{\ensuremath{\rho}}_{e}\ensuremath{\sim}[0.1,1]$, where ${\ensuremath{\rho}}_{e}$ is the electron gyroradius. This is the first observation of an exponential magnetic spectrum in space plasmas that may indicate the onset of dissipation. We distinguish for the first time between the role of different spatial kinetic plasma scales and show that the electron Larmor radius plays the role of a dissipation scale in space plasma turbulence.

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TL;DR: A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance.
Abstract: We conducted a genome-wide association study involving 224 cases and 383 controls of Central European origin to identify susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL/P). A 640-kb region at chromosome 8q24.21 was found to contain multiple markers with highly significant evidence for association with the cleft phenotype, including three markers that reached genome-wide significance. The 640-kb cleft-associated region was saturated with 146 SNP markers and then analyzed in our entire NSCL/P sample of 462 unrelated cases and 954 controls. In the entire sample, the most significant SNP (rs987525) had a P value of 3.34 x 10(-24). The odds ratio was 2.57 (95% CI = 2.02-3.26) for the heterozygous genotype and 6.05 (95% CI = 3.88-9.43) for the homozygous genotype. The calculated population attributable risk for this marker is 0.41, suggesting that this study has identified a major susceptibility locus for NSCL/P.

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TL;DR: Data from the first three rounds of the European Social Survey is used to study the trend of anti-immigration attitudes between 2002 and 2007 in 17 European countries to offer an explanation for the observed trends using a dynamic version of group conflict theory.

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TL;DR: For media production and media consumption, the establishment of a central media content archive is recommended and the development of a unified content analytical system and the promotion of cross-national comparisons are recommended.
Abstract: Mass media are defind as media which have their proper program and constitute their own audience. Mass media research, accordingly, deals with the production of programs and the consumption of the audience. For both perspectives, research topics are justified, data sources are introduced, and recommendation for the research infrastructure are given. As for media production, the establishment of a central media content archive is recommended where content analytic time series of public agencies as well as of individual researchers are collected. Furthermore, the development of a unified content analytical system and the promotion of cross-national comparisons are recommended. As for media consumption, the provision of privately funded data for the scientific community, the promotion of cross-national comparisons and the linkage of programs and audience data are recommended.

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TL;DR: The ring-like assembly of prohibitins and their sequence similarity with lipid raft-associated SPFH-family members suggests a scaffolding function of prohibitin, which may lead to functional compartmentalization in the inner membrane of mitochondria.