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Showing papers by "Radboud University Nijmegen published in 2007"


Journal ArticleDOI
TL;DR: In this paper, it was shown that micrometre-size sensors made from graphene are capable of detecting individual events when a gas molecule attaches to or detaches from graphene's surface.
Abstract: The ultimate aim of any detection method is to achieve such a level of sensitivity that individual quanta of a measured entity can be resolved. In the case of chemical sensors, the quantum is one atom or molecule. Such resolution has so far been beyond the reach of any detection technique, including solid-state gas sensors hailed for their exceptional sensitivity1, 2, 3, 4. The fundamental reason limiting the resolution of such sensors is fluctuations due to thermal motion of charges and defects5, which lead to intrinsic noise exceeding the sought-after signal from individual molecules, usually by many orders of magnitude. Here, we show that micrometre-size sensors made from graphene are capable of detecting individual events when a gas molecule attaches to or detaches from graphene's surface. The adsorbed molecules change the local carrier concentration in graphene one by one electron, which leads to step-like changes in resistance. The achieved sensitivity is due to the fact that graphene is an exceptionally low-noise material electronically, which makes it a promising candidate not only for chemical detectors but also for other applications where local probes sensitive to external charge, magnetic field or mechanical strain are required.

7,318 citations


Journal ArticleDOI
TL;DR: This paper forms a null hypothesis and shows that the nonparametric test controls the false alarm rate under this null hypothesis, enabling neuroscientists to construct their own statistical test, maximizing the sensitivity to the expected effect.

6,502 citations


Journal ArticleDOI
01 Mar 2007-Nature
TL;DR: These studies by transmission electron microscopy reveal that individual graphene sheets freely suspended on a microfabricated scaffold in vacuum or air are not perfectly flat: they exhibit intrinsic microscopic roughening such that the surface normal varies by several degrees and out-of-plane deformations reach 1 nm.
Abstract: Graphene — a recently isolated one-atom-thick layered form of graphite — is a hot topic in the materials science and condensed matter physics communities, where it is proving to be a popular model system for investigation. An experiment involving individual graphene sheets suspended over a microscale scaffold has allowed structure determination using transmission electron microscopy and diffraction, perhaps paving the way towards an answer to the question of why graphene can exist at all. The 'two-dimensional' sheets, it seems, are not flat, but wavy. The undulations are less pronounced in a two-layer system, and disappear in multilayer samples. Learning more about this 'waviness' may reveal what makes these extremely thin carbon membranes so stable. Investigations of individual graphene sheets freely suspended on a microfabricated scaffold in vacuum or in air reveal that the membranes are not perfectly flat, but exhibit an intrinsic waviness, such that the surface normal varies by several degrees, and out-of-plane deformations reach 1 nm. The recent discovery of graphene has sparked much interest, thus far focused on the peculiar electronic structure of this material, in which charge carriers mimic massless relativistic particles1,2,3. However, the physical structure of graphene—a single layer of carbon atoms densely packed in a honeycomb crystal lattice—is also puzzling. On the one hand, graphene appears to be a strictly two-dimensional material, exhibiting such a high crystal quality that electrons can travel submicrometre distances without scattering. On the other hand, perfect two-dimensional crystals cannot exist in the free state, according to both theory and experiment4,5,6,7,8,9. This incompatibility can be avoided by arguing that all the graphene structures studied so far were an integral part of larger three-dimensional structures, either supported by a bulk substrate or embedded in a three-dimensional matrix1,2,3,9,10,11,12. Here we report on individual graphene sheets freely suspended on a microfabricated scaffold in vacuum or air. These membranes are only one atom thick, yet they still display long-range crystalline order. However, our studies by transmission electron microscopy also reveal that these suspended graphene sheets are not perfectly flat: they exhibit intrinsic microscopic roughening such that the surface normal varies by several degrees and out-of-plane deformations reach 1 nm. The atomically thin single-crystal membranes offer ample scope for fundamental research and new technologies, whereas the observed corrugations in the third dimension may provide subtle reasons for the stability of two-dimensional crystals13,14,15.

4,653 citations


Journal ArticleDOI
09 Mar 2007-Science
TL;DR: In this article, it was shown that in a single atomic layer of carbon, the quantum Hall effect can be measured reliably even at room temperature, which makes possible QHE resistance standards becoming available to a broader community, outside a few national institutions.
Abstract: The quantum Hall effect (QHE), one example of a quantum phenomenon that occurs on a truly macroscopic scale, has attracted intense interest since its discovery in 1980 and has helped elucidate many important aspects of quantum physics. It has also led to the establishment of a new metrological standard, the resistance quantum. Disappointingly, however, the QHE has been observed only at liquid-helium temperatures. We show that in graphene, in a single atomic layer of carbon, the QHE can be measured reliably even at room temperature, which makes possible QHE resistance standards becoming available to a broader community, outside a few national institutions.

2,492 citations


Journal ArticleDOI
TL;DR: Results show that promoter sequence and gene function are major predictors of promoter methylation states and that inactive unmethylated CpG island promoters show elevated levels of dimethylation of Lys4 of histone H3, suggesting that this chromatin mark may protect DNA from methylation.
Abstract: To gain insight into the function of DNA methylation at cis-regulatory regions and its impact on gene expression, we measured methylation, RNA polymerase occupancy and histone modifications at 16,000 promoters in primary human somatic and germline cells. We find CpG-poor promoters hypermethylated in somatic cells, which does not preclude their activity. This methylation is present in male gametes and results in evolutionary loss of CpG dinucleotides, as measured by divergence between humans and primates. In contrast, strong CpG island promoters are mostly unmethylated, even when inactive. Weak CpG island promoters are distinct, as they are preferential targets for de novo methylation in somatic cells. Notably, most germline-specific genes are methylated in somatic cells, suggesting additional functional selection. These results show that promoter sequence and gene function are major predictors of promoter methylation states. Moreover, we observe that inactive unmethylated CpG island promoters show elevated levels of dimethylation of Lys4 of histone H3, suggesting that this chromatin mark may protect DNA from methylation.

2,101 citations


Journal ArticleDOI
TL;DR: Induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck.
Abstract: BACKGROUND: Phase 2 studies suggest that the standard regimen of cisplatin and fluorouracil (PF) plus docetaxel (TPF) improves outcomes in squamous-cell carcinoma of the head and neck. We compared TPF with PF as induction chemotherapy in patients with locoregionally advanced, unresectable disease. METHODS: We randomly assigned eligible patients between the ages of 18 and 70 years who had stage III or stage IV disease and no distant metastases to receive either TPF (docetaxel and cisplatin, day 1; fluorouracil by continuous infusion, days 1 to 5) or PF every 3 weeks for four cycles. Patients without progression of disease received radiotherapy within 4 to 7 weeks after completing chemotherapy. The primary end point was progression-free survival. RESULTS: A total of 358 patients underwent randomization, with 177 assigned to the TPF group and 181 to the PF group. At a median follow-up of 32.5 months, the median progression-free survival was 11.0 months in the TPF group and 8.2 months in the PF group (hazard ratio for disease progression or death in the TPF group, 0.72; P=0.007). Treatment with TPF resulted in a reduction in the risk of death of 27% (P=0.02), with a median overall survival of 18.8 months, as compared with 14.5 months in the PF group. There were more grade 3 or 4 events of leukopenia and neutropenia in the TPF group and more grade 3 or 4 events of thrombocytopenia, nausea, vomiting, stomatitis, and hearing loss in the PF group. The rates of death from toxic effects were 2.3% in the TPF group and 5.5% in the PF group. CONCLUSIONS: As compared with the standard regimen of cisplatin and fluorouracil, induction chemotherapy with the addition of docetaxel significantly improved progression-free and overall survival in patients with unresectable squamous-cell carcinoma of the head and neck. (ClinicalTrials.gov number, NCT00003888 [ClinicalTrials.gov].).

1,468 citations


Journal ArticleDOI
TL;DR: In this article, the electronic structure of a graphene sheet on top of a hexagonal boron nitride (h-BN) substrate was determined using ab initio density functional calculations.
Abstract: We determine the electronic structure of a graphene sheet on top of a lattice-matched hexagonal boron nitride (h-BN) substrate using ab initio density functional calculations. The most stable configuration has one carbon atom on top of a boron atom, and the other centered above a BN ring. The resulting inequivalence of the two carbon sites leads to the opening of a gap of 53 meV at the Dirac points of graphene and to finite masses for the Dirac fermions. Alternative orientations of the graphene sheet on the BN substrate generate similar band gaps and masses. The band gap induced by the BN surface can greatly improve room temperature pinch-off characteristics of graphene-based field effect transistors.

1,414 citations


Journal ArticleDOI
TL;DR: In this paper, the authors address the nature of these height fluctuations by means of straightforward atomistic Monte Carlo simulations based on a very accurate many-body interatomic potential for carbon and find that ripples spontaneously appear due to thermal fluctuations with a size distribution peaked around 70 \AA which is compatible with experimental findings (50-100 \AA) but not with the current understanding of flexible membranes.
Abstract: The stability of two-dimensional (2D) layers and membranes is subject of a long standing theoretical debate. According to the so called Mermin-Wagner theorem, long wavelength fluctuations destroy the long-range order for 2D crystals. Similarly, 2D membranes embedded in a 3D space have a tendency to be crumpled. These dangerous fluctuations can, however, be suppressed by anharmonic coupling between bending and stretching modes making that a two-dimensional membrane can exist but should present strong height fluctuations. The discovery of graphene, the first truly 2D crystal and the recent experimental observation of ripples in freely hanging graphene makes these issues especially important. Beside the academic interest, understanding the mechanisms of stability of graphene is crucial for understanding electronic transport in this material that is attracting so much interest for its unusual Dirac spectrum and electronic properties. Here we address the nature of these height fluctuations by means of straightforward atomistic Monte Carlo simulations based on a very accurate many-body interatomic potential for carbon. We find that ripples spontaneously appear due to thermal fluctuations with a size distribution peaked around 70 \AA which is compatible with experimental findings (50-100 \AA) but not with the current understanding of stability of flexible membranes. This unexpected result seems to be due to the multiplicity of chemical bonding in carbon.

1,367 citations


Journal ArticleDOI
TL;DR: In this article, the authors show how magnetism can be induced at the interface between the otherwise non-magnetic insulating perovskites SrTiO3 and LaAlO3.
Abstract: The electronic reconstruction at the interface between two insulating oxides can give rise to a highly conductive interface. Here we show how, in analogy to this remarkable interfaceinduced conductivity, magnetism can be induced at the interface between the otherwise non-magnetic insulating perovskites SrTiO3 and LaAlO3. A large negative magnetoresistance of the interface is found, together with a logarithmic temperature dependence of the sheet resistance.At lowtemperatures, the sheet resistance reveals magnetic hysteresis.Magnetic ordering is a key issue in solid-state science and its underlying mechanisms are still the subject of intense research. In particular, the interplay between localized magnetic moments and the spin of itinerant conduction electrons in a solid gives rise to intriguingmany-body effects such as Ruderman–Kittel–Kasuya–Yosida interactions3, the Kondo effect4 and carrier-induced ferromagnetism in diluted magnetic semiconductors5. The conducting oxide interface now provides a versatile system to induce and manipulate magnetic moments in otherwise non-magnetic materials.

1,355 citations


Journal ArticleDOI
15 Jun 2007-Science
TL;DR: It is proposed that the pattern of synchronization flexibly determines thepattern of neuronal interactions, and that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups.
Abstract: Brain processing depends on the interactions between neuronal groups. Those interactions are governed by the pattern of anatomical connections and by yet unknown mechanisms that modulate the effective strength of a given connection. We found that the mutual influence among neuronal groups depends on the phase relation between rhythmic activities within the groups. Phase relations supporting interactions between the groups preceded those interactions by a few milliseconds, consistent with a mechanistic role. These effects were specific in time, frequency, and space, and we therefore propose that the pattern of synchronization flexibly determines the pattern of neuronal interactions.

1,327 citations


Journal ArticleDOI
TL;DR: It is found that ripples spontaneously appear owing to thermal fluctuations with a size distribution peaked around 80 A which is compatible with experimental findings and might be due to the multiplicity of chemical bonding in carbon.
Abstract: The stability of two-dimensional (2D) layers and membranes is the subject of a long-standing theoretical debate. According to the so-called Mermin–Wagner theorem1, long-wavelength fluctuations destroy the long-range order of 2D crystals. Similarly, 2D membranes embedded in a 3D space have a tendency to be crumpled2. These fluctuations can, however, be suppressed by anharmonic coupling between bending and stretching modes meaning that a 2D membrane can exist but will exhibit strong height fluctuations2,3,4. The discovery of graphene, the first truly 2D crystal5,6, and the recent experimental observation of ripples in suspended graphene7 make these issues especially important. Besides the academic interest, understanding the mechanisms of the stability of graphene is crucial for understanding electronic transport in this material that is attracting so much interest owing to its unusual Dirac spectrum and electronic properties8,9,10,11. We address the nature of these height fluctuations by means of atomistic Monte Carlo simulations based on a very accurate many-body interatomic potential for carbon12. We find that ripples spontaneously appear owing to thermal fluctuations with a size distribution peaked around 80 A which is compatible with experimental findings7 (50–100 A). This unexpected result might be due to the multiplicity of chemical bonding in carbon.

Journal ArticleDOI
TL;DR: It is experimentally demonstrate that the magnetization can be reversed in a reproducible manner by a single 40 femtosecond circularly polarized laser pulse, without any applied magnetic field, revealing an ultrafast and efficient pathway for writing magnetic bits at record-breaking speeds.
Abstract: We experimentally demonstrate that the magnetization can be reversed in a reproducible manner by a single 40 femtosecond circularly polarized laser pulse, without any applied magnetic field. This optically induced ultrafast magnetization reversal previously believed impossible is the combined result of femtosecond laser heating of the magnetic system to just below the Curie point and circularly polarized light simultaneously acting as a magnetic field. The direction of this opto-magnetic switching is determined only by the helicity of light. This finding reveals an ultrafast and efficient pathway for writing magnetic bits at record-breaking speeds.

Journal ArticleDOI
Herman Jan Pel1, Johannes H. de Winde1, Johannes H. de Winde2, David B. Archer3, Paul S. Dyer3, Gerald Hofmann4, Peter J. Schaap5, Geoffrey Turner6, Ronald P. de Vries7, Richard Albang8, Kaj Albermann8, Mikael Rørdam Andersen4, Jannick Dyrløv Bendtsen9, Jacques A.E. Benen5, Marco A. van den Berg1, Stefaan Breestraat1, Mark X. Caddick10, Roland Contreras11, Michael Cornell12, Pedro M. Coutinho13, Etienne Danchin13, Alfons J. M. Debets5, Peter J. T. Dekker1, Piet W.M. van Dijck1, Alard Van Dijk1, Lubbert Dijkhuizen14, Arnold J. M. Driessen14, Christophe d'Enfert15, Steven Geysens11, Coenie Goosen14, Gert S.P. Groot1, Piet W. J. de Groot16, Thomas Guillemette17, Bernard Henrissat13, Marga Herweijer1, Johannes Petrus Theodorus Wilhelmus Van Den Hombergh1, Cees A. M. J. J. van den Hondel18, René T. J. M. van der Heijden19, Rachel M. van der Kaaij14, Frans M. Klis16, Harrie J. Kools5, Christian P. Kubicek, Patricia Ann van Kuyk18, Jürgen Lauber, Xin Lu, Marc J. E. C. van der Maarel, Rogier Meulenberg1, Hildegard Henna Menke1, Martin Mortimer10, Jens Nielsen4, Stephen G. Oliver12, Maurien M.A. Olsthoorn1, K. Pal5, K. Pal20, Noël Nicolaas Maria Elisabeth Van Peij1, Arthur F. J. Ram18, Ursula Rinas, Johannes Andries Roubos1, Cornelis Maria Jacobus Sagt1, Monika Schmoll, Jibin Sun, David W. Ussery4, János Varga20, Wouter Vervecken11, Peter J.J. Van De Vondervoort18, Holger Wedler, Han A. B. Wösten7, An-Ping Zeng, Albert J. J. van Ooyen1, Jaap Visser, Hein Stam1 
TL;DR: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid, and the sequenced genome revealed a large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors.
Abstract: The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.

Journal ArticleDOI
17 Oct 2007-PLOS ONE
TL;DR: This study presents an approach to the identification and classification of putative hub regions in brain networks on the basis of multiple network attributes and charts potential links between the structural embedding of such regions and their functional roles.
Abstract: Brain regions in the mammalian cerebral cortex are linked by a complex network of fiber bundles. These inter-regional networks have previously been analyzed in terms of their node degree, structural motif, path length and clustering coefficient distributions. In this paper we focus on the identification and classification of hub regions, which are thought to play pivotal roles in the coordination of information flow. We identify hubs and characterize their network contributions by examining motif fingerprints and centrality indices for all regions within the cerebral cortices of both the cat and the macaque. Motif fingerprints capture the statistics of local connection patterns, while measures of centrality identify regions that lie on many of the shortest paths between parts of the network. Within both cat and macaque networks, we find that a combination of degree, motif participation, betweenness centrality and closeness centrality allows for reliable identification of hub regions, many of which have previously been functionally classified as polysensory or multimodal. We then classify hubs as either provincial (intra-cluster) hubs or connector (inter-cluster) hubs, and proceed to show that lesioning hubs of each type from the network produces opposite effects on the small-world index. Our study presents an approach to the identification and classification of putative hub regions in brain networks on the basis of multiple network attributes and charts potential links between the structural embedding of such regions and their functional roles.

Journal ArticleDOI
TL;DR: A consistent and descriptive nomenclature is suggested for reactors in which the anammox process is employed, and Reactors with a high specific surface area like the granular sludge reactor employed in Rotterdam provide the highest volumetric loading rates.

Journal ArticleDOI
TL;DR: A second genetic variant in the 8q24 region that, in conjunction with another variant recently discovered, accounts for about 11%–13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans is reported.
Abstract: Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.

Journal ArticleDOI
TL;DR: It is demonstrated how different theories can be used to generate testable hypotheses regarding factors that influence the implementation of change, and it shows how different theoretical assumptions lead to different quality-improvement strategies.
Abstract: A consistent finding in articles on quality improvement in health care is that change is difficult to achieve. According to the research literature, the majority of interventions are targeted at health care professionals. But success in achieving change may be influenced by factors other than those relating to individual professionals, and theories may help explain whether change is possible. This article argues for a more systematic use of theories in planning and evaluating quality-improvement interventions in clinical practice. It demonstrates how different theories can be used to generate testable hypotheses regarding factors that influence the implementation of change, and it shows how different theoretical assumptions lead to different quality-improvement strategies.

Journal ArticleDOI
05 Oct 2007-Cell
TL;DR: Experiments reveal crosstalk between histone modifications and the transcription factor TFIID, which has important implications for regulation of RNA polymerase II-mediated transcription in higher eukaryotes.

Journal ArticleDOI
J. Abraham1, P. Abreu2, Marco Aglietta3, C. Aguirre  +449 moreInstitutions (69)
09 Nov 2007-Science
TL;DR: In this article, the authors demonstrate that there is a correlation between the arrival directions of cosmic rays with energy above 6 x 10{sup 19} eV and the positions of active galactic nuclei lying within 75 Mpc.
Abstract: Using data collected at the Pierre Auger Observatory during the past 3.7 years, we demonstrate that there is a correlation between the arrival directions of cosmic rays with energy above {approx} 6 x 10{sup 19} eV and the positions of active galactic nuclei (AGN) lying within {approx} 75 Mpc. We reject the hypothesis of an isotropic distribution of these cosmic rays at over 99% confidence level from a prescribed a priori test. The correlation we observe is compatible with the hypothesis that the highest energy particles originate from nearby extragalactic sources whose flux has not been significantly reduced by interaction with the cosmic background radiation. AGN or objects having a similar spatial distribution are possible sources.

Journal ArticleDOI
TL;DR: Two SNPs consistently associated with breast cancer are identified: rs3803662 is near the 5′ end of TNRC9 , a high mobility group chromatin–associated protein whose expression is implicated in breast cancer metastasis to bone.
Abstract: Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.

Journal ArticleDOI
Julius Gudmundsson1, Patrick Sulem1, Valgerdur Steinthorsdottir1, Jon Thor Bergthorsson1, Gudmar Thorleifsson1, Andrei Manolescu1, Thorunn Rafnar1, Daniel F. Gudbjartsson1, Bjarni A. Agnarsson, Adam Baker1, Asgeir Sigurdsson1, Kristrun R. Benediktsdottir, Margret Jakobsdottir1, Thorarinn Blondal1, Simon N. Stacey1, Agnar Helgason1, Steinunn Gunnarsdottir1, Adalheidur Olafsdottir1, Kari T. Kristinsson1, Birgitta Birgisdottir1, Shyamali Ghosh1, Steinunn Thorlacius1, Dana Magnusdottir1, Gerdur Stefansdottir1, Kristleifur Kristjansson1, Yu Z. Bagger, Robert L. Wilensky2, Muredach P. Reilly2, Andrew D. Morris3, Charlotte H. Kimber3, Adebowale Adeyemo4, Yuanxiu Chen4, Jie Zhou4, Wing-Yee So5, Peter C.Y. Tong5, Maggie C.Y. Ng5, Torben Hansen6, Gitte Andersen6, Knut Borch-Johnsen7, Knut Borch-Johnsen6, Knut Borch-Johnsen8, Torben Jørgensen9, Alejandro Tres10, Fernando Fuertes10, M. Ruiz-Echarri10, Laura Asín, Berta Saez, Erica Van Boven, Siem M. Klaver11, Dorine W. Swinkels11, Katja K.H. Aben11, Theresa Graif12, John Cashy12, Brian K. Suarez13, Onco Van Vierssen Trip, Michael L. Frigge1, Carole Ober14, Marten H. Hofker15, Marten H. Hofker16, Cisca Wijmenga17, Cisca Wijmenga16, Claus Christiansen, Daniel J. Rader2, Colin N. A. Palmer3, Charles N. Rotimi4, Juliana C.N. Chan5, Oluf Pedersen7, Oluf Pedersen6, Gunnar Sigurdsson, Rafn Benediktsson, Eirikur Jonsson, Gudmundur V. Einarsson, Jose I. Mayordomo10, William J. Catalona12, Lambertus A. Kiemeney11, Rosa B. Barkardottir, Jeffrey R. Gulcher1, Unnur Thorsteinsdottir1, Augustine Kong1, Kari Stefansson1 
TL;DR: Results from eight case-control groups demonstrate that this variant in TCF2 (HNF1β), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5, confers protection against type 2 diabetes.
Abstract: We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

Journal ArticleDOI
TL;DR: In this paper, an elaborated framing model is presented, and subsequently the constructionist approach is compared with priming and agenda setting, in order to develop a strategy to reconstruct frame packages.
Abstract: This article aims, within the constructionist paradigm, at integrating culture into the framing process. Four characteristics are important for this approach: the distinction between the event, the media content, and the frame; the explicit attention to the reconstruction of frame packages; the relationship between frame packages and cultural phenomena; and the interaction between frame sponsors, key events, media content, schemata, and the stock of frames. An elaborated framing model is presented, and, subsequently, the constructionist approach is compared with priming and agenda setting. Finally, the methodological implications are discussed, in order to develop a strategy to reconstruct frame packages.

Journal ArticleDOI
TL;DR: The most closely associated SNPs from six regions—four not previously implicated in the normal variation of human pigmentation—were tested and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch, and all met the criteria for genome-wide significance.
Abstract: Hair, skin and eye colors are highly heritable and visible traits in humans. We carried out a genome-wide association scan for variants associated with hair and eye pigmentation, skin sensitivity to sun and freckling among 2,986 Icelanders. We then tested the most closely associated SNPs from six regions--four not previously implicated in the normal variation of human pigmentation--and replicated their association in a second sample of 2,718 Icelanders and a sample of 1,214 Dutch. The SNPs from all six regions met the criteria for genome-wide significance. A variant in SLC24A4 is associated with eye and hair color, a variant near KITLG is associated with hair color, two coding variants in TYR are associated with eye color and freckles, and a variant on 6p25.3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R.

Journal ArticleDOI
TL;DR: It is emphasized that adolescent alcohol use primarily takes place in a social context, and that therefore studies should not solely focus on intra-individual factors predicting substance use and misuse but also on interpersonal social factors.
Abstract: This paper presents a review and a model of the development of addictive behaviors in (human) adolescents, with a focus on alcohol. The model proposes that addictive behaviors develop as the result of an imbalance between two systems: an appetitive, approach-oriented system that becomes sensitized with repeated alcohol use and a regulatory executive system that is not fully developed and that is compromised by exposure to alcohol. Self-regulation critically depends on two factors: ability and motivation to regulate the appetitive response tendency. The motivational aspect is often still weak in heavy drinking adolescents, who typically do not recognize their drinking as problematic. Motivation to regulate use often develops only years later, after the individual has encountered serious alcohol-related problems. Unfortunately, at that point behavioral change becomes harder due to several neurocognitive adaptations that result from heavy drinking. As we document, there is preliminary support for the central elements of the model (appetitive motivation vs. self-regulation), but there is a paucity of research directly addressing these mechanisms in human adolescents. Further, we emphasize that adolescent alcohol use primarily takes place in a social context, and that therefore studies should not solely focus on intra-individual factors predicting substance use and misuse but also on interpersonal social factors. Finally, we discuss implications of the model for interventions.

Journal ArticleDOI
TL;DR: The European Guidelines for Quality Assurance in Breast Cancer Screening and Diagnosis (EQAQD) as mentioned in this paper have been developed as a global standard for quality assurance in breast cancer screening and diagnosis.

Journal ArticleDOI
TL;DR: Investigations assessing the impact of anti-TNF agents on intermediary metabolism suggest that TNF-alpha blockade may improve insulin resistance and lipid profiles in patients with chronic inflammatory diseases.

Book Chapter
01 Jan 2007
TL;DR: In this article, an elaborated framing model is presented, and subsequently the constructionist approach is compared with priming and agenda setting, in order to develop a strategy to reconstruct frame packages.
Abstract: This article aims, within the constructionist paradigm, at integrating culture into the framing process. Four characteristics are important for this approach: the distinction between the event, the media content, and the frame; the explicit attention to the reconstruction of frame packages; the relationship between frame packages and cultural phenomena; and the interaction between frame sponsors, key events, media content, schemata, and the stock of frames. An elaborated framing model is presented, and, subsequently, the constructionist approach is compared with priming and agenda setting. Finally, the methodological implications are discussed, in order to develop a strategy to reconstruct frame packages.

Journal ArticleDOI
TL;DR: In this paper, a detailed transmission electron microscopy and electron diffraction study of the thinnest possible membrane, a single layer of carbon atoms suspended in vacuum and attached only at its edges, is presented.

Journal ArticleDOI
TL;DR: Graphene is the first example of truly two-dimensional crystals as mentioned in this paper, and it is a gapless semiconductor with unique electronic properties resulting from the fact that charge carriers in graphene demonstrate charge-conjugation symmetry between electrons and holes and possess an internal degree of freedom similar to "chirality" for ultrarelativistic elementary particles.

Journal ArticleDOI
TL;DR: Four groups of drugs account for more than 50% of the drug groups associated with preventable drug-related hospital admissions, and concentrating interventions on these drug groups could reduce appreciably the number of preventable drugs-related admissions to hospital from primary care.
Abstract: Aim: Previous systematic reviews have found that drug-related morbidity accounts for 4.3% of preventable hospital admissions. None, however, has identified the drugs most commonly responsible for preventable hospital admissions. The aims of this study were to estimate the percentage of preventable drug-related hospital admissions, the most common drug causes of preventable hospital admissions and the most common underlying causes of preventable drug-related admissions. Methods: Bibliographic databases and reference lists from eligible articles and study authors were the sources for data. Seventeen prospective observational studies reporting the proportion of preventable drug-related hospital admissions, causative drugs and/or the underlying causes of hospital admissions were selected. Included studies used multiple reviewers and/or explicit criteria to assess causality and preventability of hospital admissions. Two investigators abstracted data from all included studies using a purpose-made data extraction form. Results: From 13 papers the median percentage of preventable drug-related admissions to hospital was 3.7% (range 1.4-15.4). From nine papers the majority (51%) of preventable drug-related admissions involved either antiplatelets (16%), diuretics (16%), nonsteroidal anti-inflammatory drugs (11%) or anticoagulants (8%). From five studies the median proportion of preventable drug-related admissions associated with prescribing problems was 30.6% (range 11.1-41.8), with adherence problems 33.3% (range 20.9-41.7) and with monitoring problems 22.2% (range 0-31.3). Conclusions: Four groups of drugs account for more than 50% of the drug groups associated with preventable drug-related hospital admissions. Concentrating interventions on these drug groups could reduce appreciably the number of preventable drug-related admissions to hospital from primary care.