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Showing papers by "University of Bonn published in 2009"


Journal ArticleDOI
Denise Harold1, Richard Abraham2, Paul Hollingworth2, Rebecca Sims2, Amy Gerrish2, Marian L. Hamshere3, Jaspreet Singh Pahwa2, Valentina Moskvina2, Kimberley Dowzell2, Amy L. Williams2, Nicola L. Jones2, Charlene Thomas2, Alexandra Stretton2, Angharad R. Morgan2, Simon Lovestone4, John Powell5, Petroula Proitsi5, Michelle K. Lupton5, Carol Brayne6, David C. Rubinsztein7, Michael Gill6, Brian A. Lawlor6, Aoibhinn Lynch6, Kevin Morgan8, Kristelle Brown8, Peter Passmore9, David Craig9, Bernadette McGuinness9, Stephen Todd9, Clive Holmes10, David M. A. Mann11, A. David Smith12, Seth Love3, Patrick G. Kehoe3, John Hardy, Simon Mead13, Nick C. Fox13, Martin N. Rossor13, John Collinge13, Wolfgang Maier14, Frank Jessen14, Britta Schürmann14, Hendrik van den Bussche15, Isabella Heuser16, Johannes Kornhuber17, Jens Wiltfang18, Martin Dichgans19, Lutz Frölich20, Harald Hampel19, Harald Hampel21, Michael Hüll22, Dan Rujescu19, Alison Goate23, John S. K. Kauwe24, Carlos Cruchaga23, Petra Nowotny23, John C. Morris23, Kevin Mayo23, Kristel Sleegers25, Karolien Bettens25, Sebastiaan Engelborghs25, Peter Paul De Deyn25, Christine Van Broeckhoven25, Gill Livingston26, Nicholas Bass26, Hugh Gurling26, Andrew McQuillin26, Rhian Gwilliam27, Panagiotis Deloukas27, Ammar Al-Chalabi28, Christopher Shaw28, Magda Tsolaki29, Andrew B. Singleton30, Rita Guerreiro30, Thomas W. Mühleisen14, Markus M. Nöthen14, Susanne Moebus18, Karl-Heinz Jöckel18, Norman Klopp, H-Erich Wichmann19, Minerva M. Carrasquillo31, V. Shane Pankratz31, Steven G. Younkin31, Peter Holmans2, Michael Conlon O'Donovan2, Michael John Owen2, Julie Williams2 
TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.
Abstract: We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 10-157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 10-9) and 5' to the PICALM gene (rs3851179, P = 1.9 10-8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 10-10, odds ratio = 0.86; rs3851179, P = 1.3 10-9, odds ratio = 0.86).

2,956 citations


Posted Content
TL;DR: This paper studied the behavior of money, credit, and macroeconomic indicators over the long run based on a newly constructed historical dataset for 12 developed countries over the years 1870-2008, utilizing the data to study rare events associated with financial crisis episodes.
Abstract: The crisis of 2008-09 has focused attention on money and credit fluctuations, financial crises, and policy responses. In this paper we study the behavior of money, credit, and macroeconomic indicators over the long run based on a newly constructed historical dataset for 12 developed countries over the years 1870-2008, utilizing the data to study rare events associated with financial crisis episodes. We present new evidence that leverage in the financial sector has increased strongly in the second half of the twentieth century as shown by a decoupling of money and credit aggregates, and we also find a decline in safe assets on banks' balance sheets. We also show for the first time how monetary policy responses to financial crises have been more aggressive post-1945, but how despite these policies the output costs of crises have remained large. Importantly, we can also show that credit growth is a powerful predictor of financial crises, suggesting that such crises are

2,021 citations


Journal ArticleDOI
TL;DR: The data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-α.
Abstract: Hepatitis C virus (HCV) infects 3% of the world's population. Treatment of chronic HCV consists of a combination of PEGylated interferon-alpha (PEG-IFN-alpha) and ribavirin (RBV). To identify genetic variants associated with HCV treatment response, we conducted a genome-wide association study of sustained virological response (SVR) to PEG-IFN-alpha/RBV combination therapy in 293 Australian individuals with genotype 1 chronic hepatitis C, with validation in an independent replication cohort consisting of 555 individuals. We report an association to SVR within the gene region encoding interleukin 28B (IL28B, also called IFNlambda3; rs8099917 combined P = 9.25 x 10(-9), OR = 1.98, 95% CI = 1.57-2.52). IL28B contributes to viral resistance and is known to be upregulated by interferons and by RNA virus infection. These data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-alpha.

1,858 citations


Journal ArticleDOI
TL;DR: In this article, the chain-of-spheres exchange (COSX) algorithm was proposed to speed up Hartree-Fock and hybrid density functional calculations by forming the Coulomb and exchange parts of the Fock matrix by different approximations.

1,813 citations


Journal ArticleDOI
TL;DR: It is demonstrated that an unequivocal role for common genetic variants in the etiology of typical PD and population-specific genetic heterogeneity in this disease is suggested, and supporting evidence that common variation around LRRK2 modulates risk for PD is provided.
Abstract: We performed a genome-wide association study (GWAS) in 1,713 individuals of European ancestry with Parkinson's disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, we observed two strong association signals, one in the gene encoding a-synuclein (SNCA; rs2736990, OR = 1.23, P = 2.24 x 10(-16)) and another at the MAPT locus (rs393152, OR = 0.77, P = 1.95 x 10(-16)). We exchanged data with colleagues performing a GWAS in Japanese PD cases. Association to PD at SNCA was replicated in the Japanese GWAS1, confirming this as a major risk locus across populations. We replicated the effect of a new locus detected in the Japanese cohort (PARK16, rs823128, OR = 0.66, P = 7.29 x 10(-8)) and provide supporting evidence that common variation around LRRK2 modulates risk for PD (rs1491923, OR = 1.14, P = 1.55 x 10(-5)). These data demonstrate an unequivocal role for common genetic variants in the etiology of typical PD and suggest population-specific genetic heterogeneity in this disease.

1,793 citations


Journal ArticleDOI
TL;DR: In this article, the authors combined information drawn from studies of individual clouds into a combined and updated statistical analysis of star-formation rates and efficiencies, numbers and lifetimes for spectral energy distribution (SED) classes, and clustering properties.
Abstract: The c2d Spitzer Legacy project obtained images and photometry with both IRAC and MIPS instruments for five large, nearby molecular clouds. Three of the clouds were also mapped in dust continuum emission at 1.1 mm, and optical spectroscopy has been obtained for some clouds. This paper combines information drawn from studies of individual clouds into a combined and updated statistical analysis of star-formation rates and efficiencies, numbers and lifetimes for spectral energy distribution (SED) classes, and clustering properties. Current star-formation efficiencies range from 3% to 6%; if star formation continues at current rates for 10 Myr, efficiencies could reach 15-30%. Star-formation rates and rates per unit area vary from cloud to cloud; taken together, the five clouds are producing about 260 M ☉ of stars per Myr. The star-formation surface density is more than an order of magnitude larger than would be predicted from the Kennicutt relation used in extragalactic studies, reflecting the fact that those relations apply to larger scales, where more diffuse matter is included in the gas surface density. Measured against the dense gas probed by the maps of dust continuum emission, the efficiencies are much higher, with stellar masses similar to masses of dense gas, and the current stock of dense cores would be exhausted in 1.8 Myr on average. Nonetheless, star formation is still slow compared to that expected in a free-fall time, even in the dense cores. The derived lifetime for the Class I phase is 0.54 Myr, considerably longer than some estimates. Similarly, the lifetime for the Class 0 SED class, 0.16 Myr, with the notable exception of the Ophiuchus cloud, is longer than early estimates. If photometry is corrected for estimated extinction before calculating class indicators, the lifetimes drop to 0.44 Myr for Class I and to 0.10 for Class 0. These lifetimes assume a continuous flow through the Class II phase and should be considered median lifetimes or half-lives. Star formation is highly concentrated to regions of high extinction, and the youngest objects are very strongly associated with dense cores. The great majority (90%) of young stars lie within loose clusters with at least 35 members and a stellar density of 1 M ☉ pc–3. Accretion at the sound speed from an isothermal sphere over the lifetime derived for the Class I phase could build a star of about 0.25 M ☉, given an efficiency of 0.3. Building larger mass stars by using higher mass accretion rates could be problematic, as our data confirm and aggravate the "luminosity problem" for protostars. At a given T bol, the values for L bol are mostly less than predicted by standard infall models and scatter over several orders of magnitude. These results strongly suggest that accretion is time variable, with prolonged periods of very low accretion. Based on a very simple model and this sample of sources, half the mass of a star would be accreted during only 7% of the Class I lifetime, as represented by the eight most luminous objects.

1,752 citations


Journal ArticleDOI
Hreinn Stefansson1, Hreinn Stefansson2, Roel A. Ophoff3, Roel A. Ophoff4, Roel A. Ophoff1, Stacy Steinberg1, Stacy Steinberg2, Ole A. Andreassen5, Sven Cichon6, Dan Rujescu7, Thomas Werge8, Olli Pietilainen9, Ole Mors10, Preben Bo Mortensen11, Engilbert Sigurdsson12, Omar Gustafsson2, Mette Nyegaard11, Annamari Tuulio-Henriksson13, Andres Ingason2, Thomas Hansen8, Jaana Suvisaari13, Jouko Lönnqvist13, Tiina Paunio, Anders D. Børglum11, Anders D. Børglum10, Annette M. Hartmann7, Anders Fink-Jensen8, Merete Nordentoft14, David M. Hougaard, Bent Nørgaard-Pedersen, Yvonne Böttcher2, Jes Olesen15, René Breuer16, Hans-Jürgen Möller7, Ina Giegling7, Henrik B. Rasmussen8, Sally Timm8, Manuel Mattheisen6, István Bitter17, János Réthelyi17, Brynja B. Magnusdottir12, Thordur Sigmundsson12, Pall I. Olason2, Gisli Masson2, Jeffrey R. Gulcher2, Magnús Haraldsson12, Ragnheidur Fossdal2, Thorgeir E. Thorgeirsson2, Unnur Thorsteinsdottir12, Unnur Thorsteinsdottir2, Mirella Ruggeri18, Sarah Tosato18, Barbara Franke19, Eric Strengman4, Lambertus A. Kiemeney19, Ingrid Melle5, Srdjan Djurovic5, Lilia I. Abramova20, Kaleda Vg20, Julio Sanjuán21, Rosa de Frutos21, Elvira Bramon22, Evangelos Vassos22, Gillian Fraser23, Ulrich Ettinger22, Marco Picchioni22, Nicholas Walker, T. Toulopoulou22, Anna C. Need24, Dongliang Ge24, Joeng Lim Yoon3, Kevin V. Shianna24, Nelson B. Freimer3, Rita M. Cantor3, Robin M. Murray22, Augustine Kong2, Vera Golimbet20, Angel Carracedo25, Celso Arango26, Javier Costas, Erik G. Jönsson27, Lars Terenius27, Ingrid Agartz27, Hannes Petursson12, Markus M. Nöthen6, Marcella Rietschel16, Paul M. Matthews28, Pierandrea Muglia29, Leena Peltonen9, David St Clair23, David Goldstein24, Kari Stefansson12, Kari Stefansson2, David A. Collier30, David A. Collier22 
06 Aug 2009-Nature
TL;DR: Findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.
Abstract: Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the 'genomic disorders', have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition.

1,625 citations


Journal ArticleDOI
TL;DR: In this article, the nuclear forces can be derived using effective chiral Lagrangians consistent with the symmetries of QCD, and the status of the calculations for two and three nucleon forces and their applications in few-nucleon systems are reviewed.
Abstract: Nuclear forces can be systematically derived using effective chiral Lagrangians consistent with the symmetries of QCD. I review the status of the calculations for two- and three-nucleon forces and their applications in few-nucleon systems. I also address issues like the quark mass dependence of the nuclear forces and resonance saturation for four-nucleon operators.

1,455 citations


Journal ArticleDOI
26 Feb 2009-Nature
TL;DR: The ability of stimulated emission depletion (STED) far-field fluorescence nanoscopy to detect single diffusing (lipid) molecules in nanosized areas in the plasma membrane of living cells is demonstrated.
Abstract: Cholesterol-mediated lipid interactions are thought to have a functional role in many membrane-associated processes such as signalling events. Although several experiments indicate their existence, lipid nanodomains ('rafts') remain controversial owing to the lack of suitable detection techniques in living cells. The controversy is reflected in their putative size of 5-200 nm, spanning the range between the extent of a protein complex and the resolution limit of optical microscopy. Here we demonstrate the ability of stimulated emission depletion (STED) far-field fluorescence nanoscopy to detect single diffusing (lipid) molecules in nanosized areas in the plasma membrane of living cells. Tuning of the probed area to spot sizes approximately 70-fold below the diffraction barrier reveals that unlike phosphoglycerolipids, sphingolipids and glycosylphosphatidylinositol-anchored proteins are transiently ( approximately 10-20 ms) trapped in cholesterol-mediated molecular complexes dwelling within <20-nm diameter areas. The non-invasive optical recording of molecular time traces and fluctuation data in tunable nanoscale domains is a powerful new approach to study the dynamics of biomolecules in living cells.

1,434 citations


Journal ArticleDOI
TL;DR: This review describes many examples of how modern molecular-biological methods can enable us to understand the various synergistic mechanisms underlying these effects of herbal drug combinations.

1,004 citations


Journal ArticleDOI
TL;DR: An overview of the properties that can be calculated with DFT, such as geometries, energies, reaction mechanisms, and spectroscopic properties, is provided.
Abstract: Density functional theory (DFT) finds increasing use in applications related to biological systems. Advancements in methodology and implementations have reached a point where predicted properties of reasonable to high quality can be obtained. Thus, DFT studies can complement experimental investigations, or even venture with some confidence into experimentally unexplored territory. In the present contribution, we provide an overview of the properties that can be calculated with DFT, such as geometries, energies, reaction mechanisms, and spectroscopic properties. A wide range of spectroscopic parameters is nowadays accessible with DFT, including quantities related to infrared and optical spectra, X-ray absorption and Mossbauer, as well as all of the magnetic properties connected with electron paramagnetic resonance spectroscopy except relaxation times. We highlight each of these fields of application with selected examples from the recent literature and comment on the capabilities and limitations of current methods.

Book ChapterDOI
01 Jan 2009
TL;DR: In this paper, the magnetic properties of magnetic nanoparticles have been investigated and a number of methods for nanoparticle synthesis including the preparation of metallic magnetic particles have been described in the literature, including the control of particle size, shape, and monodispersity as well as their stability towards oxidation.
Abstract: As compared to bulk materials, magnetic nanoparticles possess distinct magnetic properties and attempts have been made to exploit their beneficial properties for technical and biomedical applications, e.g. for magnetic fluids, high-density magnetic recording, or biomedical diagnosis and therapy. Early magnetic fluids (MFs) were produced by grinding magnetite with heptane or long chain hydrocarbon and a grinding agent, e.g. oleic acid [152]. Later procedures for MFs precipitated Fe 3+/Fe 2+ of an aqueous solution with a base, coated the particles by oleic acid, and dispersed them in carrier liquid [161]. However, besides the elemental composition and crystal structure of the applied magnetic particles, particle size and particle size distribution determine the properties of the resulting MF. Many methods for nanoparticle synthesis including the preparation of metallic magnetic particles have been described in the literature. However, there still remain important questions, e.g. concerning control of particle size, shape, and monodispersity as well as their stability towards oxidation. Moreover, peptization by suitable surfactants or polymers into stable MFs is an important issue since each application in engineering or biomedicine needs special MFs with properties adjusted to the requirements of the system.

Journal ArticleDOI
06 Feb 2009-Cell
TL;DR: It is reported that exogenous expression of the germline-specific transcription factor Oct4 is sufficient to generate pluripotent stem cells from adult mouse NSCs and is demonstrated to be similar to embryonic stem cells in vitro and in vivo.

Journal ArticleDOI
TL;DR: This work quantifies geographic patterns of endemism-scaled richness (“endemism richness”) of vascular plants across 90 terrestrial biogeographic regions, including islands, worldwide and evaluates their congruence with terrestrial vertebrates.
Abstract: Endemism and species richness are highly relevant to the global prioritization of conservation efforts in which oceanic islands have remained relatively neglected. When compared to mainland areas, oceanic islands in general are known for their high percentage of endemic species but only moderate levels of species richness, prompting the question of their relative conservation value. Here we quantify geographic patterns of endemism-scaled richness (“endemism richness”) of vascular plants across 90 terrestrial biogeographic regions, including islands, worldwide and evaluate their congruence with terrestrial vertebrates. Endemism richness of plants and vertebrates is strongly related, and values on islands exceed those of mainland regions by a factor of 9.5 and 8.1 for plants and vertebrates, respectively. Comparisons of different measures of past and future human impact and land cover change further reveal marked differences between mainland and island regions. While island and mainland regions suffered equally from past habitat loss, we find the human impact index, a measure of current threat, to be significantly higher on islands. Projected land-cover changes for the year 2100 indicate that land-use-driven changes on islands might strongly increase in the future. Given their conservation risks, smaller land areas, and high levels of endemism richness, islands may offer particularly high returns for species conservation efforts and therefore warrant a high priority in global biodiversity conservation in this century.

Posted Content
TL;DR: It is argued that many recent objections against lab experiments are misguided and that even more lab experiments should be conducted, by comparing them to research based on nonexperimental data and to field experiments.
Abstract: Laboratory experiments are a widely used methodology for advancing causal knowledge in the physical and life sciences. With the exception of psychology, the adoption of laboratory experiments has been much slower in the social sciences, although during the last two decades, the use of lab experiments has accelerated. Nonetheless, there remains considerable resistance among social scientists who argue that lab experiments lack "realism" and "generalizability". In this article we discuss the advantages and limitations of laboratory social science experiments by comparing them to research based on nonexperimental data and to field experiments. We argue that many recent objections against lab experiments are misguided and that even more lab experiments should be conducted.

Journal ArticleDOI
Frank Neese1
TL;DR: In this paper, a detailed account of density functional theory and its application to the calculation of molecular properties of inorganic compounds is provided, including geometric, electric, magnetic and time-dependent perturbations.

Journal ArticleDOI
TL;DR: A novel DNA-sensing pathway involving RNA polymerase III and RIG-I is identified, which was important in the sensing of Epstein-Barr virus–encoded small RNAs, which were transcribed by RNA polymer enzyme III and then triggered Rig-I activation.
Abstract: After binding double-stranded RNA, RIG-I induces production of type 1 interferon. Hornung and colleagues find that RIG-I detects viral DNA via double-stranded RNA intermediates generated by RNA polymerase III.

Journal ArticleDOI
TL;DR: Meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs shows that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.
Abstract: To identify risk variants for glioma, we conducted a meta-analysis of two genome-wide association studies by genotyping 550K tagging SNPs in a total of 1,878 cases and 3,670 controls, with validation in three additional independent series totaling 2,545 cases and 2,953 controls. We identified five risk loci for glioma at 5p15.33 (rs2736100, TERT; P = 1.50 x 10(-17)), 8q24.21 (rs4295627, CCDC26; P = 2.34 x 10(-18)), 9p21.3 (rs4977756, CDKN2A-CDKN2B; P = 7.24 x 10(-15)), 20q13.33 (rs6010620, RTEL1; P = 2.52 x 10(-12)) and 11q23.3 (rs498872, PHLDB1; P = 1.07 x 10(-8)). These data show that common low-penetrance susceptibility alleles contribute to the risk of developing glioma and provide insight into disease causation of this primary brain tumor.

Journal ArticleDOI
TL;DR: In patients with AML who are older than 60 years of age, escalation of the dose of daunorubicin to twice the conventional dose, with the entire dose administered in the first induction cycle, effects a more rapid response and a higher response rate than does the conventional doses, without additional toxic effects.
Abstract: BACKGROUND: A complete remission is essential for prolonging survival in patients with acute myeloid leukemia (AML). Daunorubicin is a cornerstone of the induction regimen, but the optimal dose is unknown. In older patients, it is usual to give daunorubicin at a dose of 45 to 50 mg per square meter of body-surface area. METHODS: Patients in whom AML or high-risk refractory anemia had been newly diagnosed and who were 60 to 83 years of age (median, 67) were randomly assigned to receive cytarabine, at a dose of 200 mg per square meter by continuous infusion for 7 days, plus daunorubicin for 3 days, either at the conventional dose of 45 mg per square meter (411 patients) or at an escalated dose of 90 mg per square meter (402 patients); this treatment was followed by a second cycle of cytarabine at a dose of 1000 mg per square meter for 6 days. The primary end point was event-free survival. RESULTS: The complete remission rates were 64% in the group that received the escalated dose of daunorubicin and 54% in the group that received the conventional dose (P=0.002); the rates of remission after the first cycle of induction treatment were 52% and 35%, respectively (P<0.001). There was no significant difference between the two groups in the incidence of hematologic toxic effects, 30-day mortality (11% and 12% in the two groups, respectively), or the incidence of moderate, severe, or life-threatening adverse events (P=0.08). Survival end points in the two groups did not differ significantly overall, but patients in the escalated-treatment group who were 60 to 65 years of age, as compared with the patients in the same age group who received the conventional dose, had higher rates of complete remission (73% vs. 51%), event-free survival (29% vs. 14%), and overall survival (38% vs. 23%). CONCLUSIONS: In patients with AML who are older than 60 years of age, escalation of the dose of daunorubicin to twice the conventional dose, with the entire dose administered in the first induction cycle, effects a more rapid response and a higher response rate than does the conventional dose, without additional toxic effects. (Current Controlled Trials number, ISRCTN77039377; and Netherlands National Trial Register number, NTR212.)

Journal ArticleDOI
TL;DR: In this article, the authors provide an overview of the most frequently functional surface structures of plants and their potential for technical use, leading to biomimetic inspired smart surfaces, which can be transferred into technical "biomimetic" materials.

Journal ArticleDOI
17 Jul 2009-Immunity
TL;DR: A chemical approach for 5' triphosphate oligoribonucleotide synthesis is established and it is found that synthetic single-stranded 5'Triphosphates were unable to bind and activate RIG-I, and the addition of the synthetic complementary strand resulted in optimal binding and activation of Rig-I.

Journal ArticleDOI
TL;DR: In this paper, Silicon surfaces patterned with pillars and deposited with a hydrophobic coating were studied to demonstrate how the effects of pitch value, droplet size and impact velocity influence the transition from a composite state to a wetted state.
Abstract: Superhydrophobic surfaces exhibit extreme water-repellent properties. These surfaces with high contact angle and low contact angle hysteresis also exhibit a self-cleaning effect and low drag for fluid flow. Certain plant leaves, such as lotus leaves, are known to be superhydrophobic and self-cleaning due to the hierarchical roughness of their leaf surfaces. The self-cleaning phenomenon is widely known as the ‘lotus effect’. Superhydrophobic and self-cleaning surfaces can be produced by using roughness combined with hydrophobic coatings. In this paper, the effect of micro- and nanopatterned polymers on hydrophobicity is reviewed. Silicon surfaces patterned with pillars and deposited with a hydrophobic coating were studied to demonstrate how the effects of pitch value, droplet size and impact velocity influence the transition from a composite state to a wetted state. In order to fabricate hierarchical structures, a low-cost and flexible technique that involves replication of microstructures and self-assembly of hydrophobic waxes is described. The influence of micro-, nano- and hierarchical structures on superhydrophobicity is discussed by the investigation of static contact angle, contact angle hysteresis, droplet evaporation and propensity for air pocket formation. In addition, their influence on adhesive force as well as efficiency of selfcleaning is discussed.

Journal ArticleDOI
TL;DR: A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia, bipolar disorder, and autism, while the reciprocal microdeletion was associated only with autism and developmental disorders.
Abstract: Recurrent microdeletions and microduplications of a 600-kb genomic region of chromosome 16p11.2 have been implicated in childhood-onset developmental disorders1, 2, 3. We report the association of 16p11.2 microduplications with schizophrenia in two large cohorts. The microduplication was detected in 12/1,906 (0.63%) cases and 1/3,971 (0.03%) controls (P = 1.2 10-5, OR = 25.8) from the initial cohort, and in 9/2,645 (0.34%) cases and 1/2,420 (0.04%) controls (P = 0.022, OR = 8.3) of the replication cohort. The 16p11.2 microduplication was associated with a 14.5-fold increased risk of schizophrenia (95% CI (3.3, 62)) in the combined sample. A meta-analysis of datasets for multiple psychiatric disorders showed a significant association of the microduplication with schizophrenia (P = 4.8 10-7), bipolar disorder (P = 0.017) and autism (P = 1.9 10-7). In contrast, the reciprocal microdeletion was associated only with autism and developmental disorders (P = 2.3 10-13). Head circumference was larger in patients with the microdeletion than in patients with the microduplication (P = 0.0007).

Journal ArticleDOI
TL;DR: The use of chitosan in antimicrobial systems should be based on sufficient knowledge of the complex mechanisms of its antimicrobial mode of action, which in turn would help to arrive at an appreciation of its entire antimicrobial potential.
Abstract: Chitosan, an aminopolysaccharide biopolymer, has a unique chemical structure as a linear polycation with a high charge density, reactive hydroxyl and amino groups as well as extensive hydrogen bonding. It displays excellent biocompatibility, physical stability and processability. The term 'chitosan' describes a heterogeneous group of polymers combining a group of physicochemical and biological characteristics, which allow for a wide scope of applications that are both fascinating and as yet uncharted. The increased awareness of the potentials and industrial value of this biopolymer lead to its utilization in many applications of technical interest, and increasingly in the biomedical arena. Although not primarily used as an antimicrobial agent, its utility as an ingredient in both food and pharmaceutical formulations lately gained more interest, when a scientific understanding of at least some of the pharmacological activities of this versatile carbohydrate began to evolve. However, understanding the various factors that affect its antimicrobial activity has become a key issue for a better usage and a more efficient optimization of chitosan formulations. Moreover, the use of chitosan in antimicrobial systems should be based on sufficient knowledge of the complex mechanisms of its antimicrobial mode of action, which in turn would help to arrive at an appreciation of its entire antimicrobial potential.

Journal ArticleDOI
TL;DR: The structural basics of superhydrophobic andsuperhydrophilic plant surfaces and their biological functions are introduced and further types of plant surface structuring leading to superHydrophobicity and Superhydrophilicity are presented.
Abstract: The diversity of plant surface structures, evolved over 460 million years, has led to a large variety of highly adapted functional structures. The plant cuticle provides structural and chemical modifications for surface wetting, ranging from superhydrophilic to superhydrophobic. In this paper, the structural basics of superhydrophobic and superhydrophilic plant surfaces and their biological functions are introduced. Wetting in plants is influenced by the sculptures of the cells and by the fine structure of the surfaces, such as folding of the cuticle, or by epicuticular waxes. Hierarchical structures in plant surfaces are shown and further types of plant surface structuring leading to superhydrophobicity and superhydrophilicity are presented. The existing and potential uses of superhydrophobic and superhydrophilic surfaces for self-cleaning, drag reduction during moving in water, capillary liquid transport and other biomimetic materials are shown.

Journal ArticleDOI
10 Jul 2009-Science
TL;DR: In this experiment, a quantum walk on the line with single neutral atoms is implemented by deterministically delocalizing them over the sites of a one-dimensional spin-dependent optical lattice and its spatial coherence is demonstrated.
Abstract: The quantum walk is the quantum analog of the well-known random walk, which forms the basis for models and applications in many realms of science. Its properties are markedly different from the classical counterpart and might lead to extensive applications in quantum information science. In our experiment, we implemented a quantum walk on the line with single neutral atoms by deterministically delocalizing them over the sites of a one-dimensional spin-dependent optical lattice. With the use of site-resolved fluorescence imaging, the final wave function is characterized by local quantum state tomography, and its spatial coherence is demonstrated. Our system allows the observation of the quantum-to-classical transition and paves the way for applications, such as quantum cellular automata.

Journal ArticleDOI
TL;DR: A review of the state of the art in understanding the processes involved in the exchange of trace gases and aerosols between the earth's surface and the atmosphere can be found in this article.

Journal ArticleDOI
TL;DR: In this paper, the hierarchical structure of the Lotus leaf has been recreated to characterize the influence of hierarchical roughness on superhydrophobicity and adhesion, and a flat surface, microstructured Lotus leaf replica and a micropatterned Si replica were fabricated.
Abstract: The superhydrophobic and self-cleaning leaves of Lotus (Nelumbo nucifera, Gaertn.) have been used as a model for the development of artificial biomimetic surfaces. The hierarchical structure of the Lotus leaf has been recreated to characterize the influence of hierarchical roughness on superhydrophobicity and adhesion. Hierarchical structures were fabricated by a fast and precise molding of the Lotus leaf microstructure, and self-assembly of the natural Lotus wax deposited by thermal evaporation to create the wax tubules nanostructures. Tubule formation was initiated by exposure of the specimens to a solvent vapor phase at a selected temperature. In order to study the influence of structures at different scale sizes on superhydrophobicity, a flat surface, microstructured Lotus leaf replica and a micropatterned Si replica, and a nanostructure were fabricated. Static contact angle, contact angle hysteresis, tilt angle and adhesive forces were measured. The data show that microstructures and nanostructures lead to superhydrophobicity, whereas hierarchical structures further improve this property and show low contact angle hysteresis, superior to that of the natural Lotus leaves.

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Jörn Piel1
TL;DR: This review describes secondary metabolites that have been shown to be synthesized by symbiotic bacteria, or for which this possibility has been discussed, and includes 365 references.

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TL;DR: The Greenland ice core from NorthGRIP (NGRIP) contains a proxy climate record across the Pleistocene-Holocene boundary of unprecedented clarity and resolution, which enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision as discussed by the authors.
Abstract: The Greenland ice core from NorthGRIP (NGRIP) contains a proxy climate record across the Pleistocene-Holocene boundary of unprecedented clarity and resolution. Analysis of an array of physical and chemical parameters within the ice enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision. This climatic event is most clearly reflected in an abrupt shift in deuterium excess values, accompanied by more gradual changes in d 18 O, dust concentration, a range of chemical species, and annual layer thickness. A timescale based on multi-parameter annual layer counting provides an age of 11 700 calendar yr b2 k (before AD 2000) for the base of the Holocene, with a maximum counting error of 99 yr. A proposal that an archived core from this unique sequence should constitute the Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period) has been ratified by the International Union of Geological Sciences. Five auxiliary stratotypes for the Pleistocene-Holocene boundary have also been recognised. Copyright # 2008 John Wiley & Sons, Ltd.