scispace - formally typeset
Search or ask a question

Showing papers by "University of Turku published in 2011"


Journal ArticleDOI
15 Jul 2011-Science
TL;DR: This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles.
Abstract: Until recently, large apex consumers were ubiquitous across the globe and had been for millions of years. The loss of these animals may be humankind's most pervasive influence on nature. Although such losses are widely viewed as an ethical and aesthetic problem, recent research reveals extensive cascading effects of their disappearance in marine, terrestrial, and freshwater ecosystems worldwide. This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles. These findings emphasize the urgent need for interdisciplinary research to forecast the effects of trophic downgrading on process, function, and resilience in global ecosystems.

3,130 citations


Journal ArticleDOI
Georg Ehret1, Georg Ehret2, Georg Ehret3, Patricia B. Munroe4  +388 moreInstitutions (110)
06 Oct 2011-Nature
TL;DR: A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function, and these findings suggest potential novel therapeutic pathways for cardiovascular disease prevention.
Abstract: Blood pressure is a heritable trait(1) influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (>= 140 mm Hg systolic blood pressure or >= 90 mm Hg diastolic blood pressure)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.

1,829 citations


Journal ArticleDOI
Marcos Daniel Actis1, G. Agnetta2, Felix Aharonian3, A. G. Akhperjanian  +682 moreInstitutions (109)
TL;DR: The ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes as mentioned in this paper, which is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100GeV and above 100 TeV.
Abstract: Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA.

1,006 citations


Journal ArticleDOI
TL;DR: To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011.
Abstract: The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis.

929 citations


Journal ArticleDOI
TL;DR: The therapeutic potential of etch-and-rinse adhesives has yet to be fully exploited, and incorporation of protease inhibitors in etchants and/or cross-linking agents in primers may increase the durability of resin-dentin bonds.

807 citations


Journal ArticleDOI
TL;DR: Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable.
Abstract: Several studies have shown that gut bacteria have a role in diabetes in murine models. Specific bacteria have been correlated with the onset of diabetes in a rat model. However, it is unknown whether human intestinal microbes have a role in the development of autoimmunity that often leads to type 1 diabetes (T1D), an autoimmune disorder in which insulin-secreting pancreatic islet cells are destroyed. High-throughput, culture-independent approaches identified bacteria that correlate with the development of T1D-associated autoimmunity in young children who are at high genetic risk for this disorder. The level of bacterial diversity diminishes overtime in these autoimmune subjects relative to that of age-matched, genotype-matched, nonautoimmune individuals. A single species, Bacteroides ovatus, comprised nearly 24% of the total increase in the phylum Bacteroidetes in cases compared with controls. Conversely, another species in controls, represented by the human firmicute strain CO19, represented nearly 20% of the increase in Firmicutes compared with cases overtime. Three lines of evidence are presented that support the notion that, as healthy infants approach the toddler stage, their microbiomes become healthier and more stable, whereas, children who are destined for autoimmunity develop a microbiome that is less diverse and stable. Hence, the autoimmune microbiome for T1D may be distinctly different from that found in healthy children. These data also suggest bacterial markers for the early diagnosis of T1D. In addition, bacteria that negatively correlated with the autoimmune state may prove to be useful in the prevention of autoimmunity development in high-risk children.

719 citations


Journal ArticleDOI
TL;DR: BAT appears to be differently activated by insulin and cold; in response to insulin, BAT displays high glucose uptake without increased perfusion, but when activated by cold, it dissipates energy in a perfusion-dependent manner.

632 citations


Journal ArticleDOI
24 Mar 2011-Oncogene
TL;DR: It is shown that vimentin functionally contributes to EMT and is required for induction of Axl expression, and regulation of breast cancer cell migration in two- and three-dimensional matrices by vimentsin is Axl- dependent and that Axl functional contributes to lung extravasation of breast cancers cells in mice.
Abstract: Epithelial-to-mesenchymal transition (EMT) is a critical event in the progression toward cancer metastasis. The intermediate filament protein vimentin is an important marker of EMT and a requisite regulator of mesenchymal cell migration. However, it is not known how vimentin functionally contributes to cancer cell invasion. Here, we report that ectopic expression of oncogenic H-Ras-V12G and Slug induces vimentin expression and migration in pre-malignant breast epithelial cells. Conversely, vimentin expression is necessary for Slug- or H-Ras-V12G-induced EMT-associated migration. Furthermore, silencing of vimentin in breast epithelial cells results in specific changes in invasiveness-related gene expression including upregulation of RAB25 (small GTPase Rab25) and downregulation of AXL (receptor tyrosine kinase Axl), PLAU (plasminogen activator, urokinase) and ITGB4 (integrin β4-subunit). Importantly, gene expression profiling analyses reveal that vimentin expression correlates positively/negatively with these genes also in multiple breast cancer cell lines and breast cancer patient samples. Focusing on the tyrosine kinase Axl, we show that induction of vimentin by EMT is associated with upregulation of Axl expression and that Axl enhances the migratory activity of pre-malignant breast epithelial cells. Using null and knock-down cells and overexpression models, we also show that regulation of breast cancer cell migration in two- and three-dimensional matrices by vimentin is Axl- dependent and that Axl functionally contributes to lung extravasation of breast cancer cells in mice. In conclusion, our data show that vimentin functionally contributes to EMT and is required for induction of Axl expression. Moreover, these results provide a molecular explanation for vimentin-dependent cancer cell migration during EMT by identifying Axl as a key proximal component in this process.

603 citations


Journal ArticleDOI
TL;DR: The results indicate that the KiVa program is effective in reducing school bullying and victimization in Grades 4-6 and suggest that well-conceived school-based programs can reduce victimization.
Abstract: This study demonstrates the effectiveness of the KiVa antibullying program using a large sample of 8,237 youth from Grades 4-6 (10-12 years). Altogether, 78 schools were randomly assigned to intervention (39 schools, 4,207 students) and control conditions (39 schools, 4,030 students). Multilevel regression analyses revealed that after 9 months of implementation, the intervention had consistent beneficial effects on 7 of the 11 dependent variables, including self- and peer-reported victimization and self-reported bullying. The results indicate that the KiVa program is effective in reducing school bullying and victimization in Grades 4-6. Despite some evidence against school-based interventions, the results suggest that well-conceived school-based programs can reduce victimization.

587 citations


Book
06 Dec 2011
TL;DR: This chapter discusses automata in terms of Matrices, and discusses Commuting Variables: Decidability and Parikh's Theorem, as well as algebraic systems and Context-Free Languages.
Abstract: I. Linear Algebra.- 1. Semirings and Power Series.- 2. Convergence, Equations and Identities.- 3. Strong Convergence and Cycle-Free Power Series.- 4. Matrices, Linear Systems and Identities.- 5. Semirings with Particular Properties.- 6. Morphisms and Representations.- II. Automata.- 7. Automata in Terms of Matrices.- 8. Rational Power Series and Decidability.- 9. Rational Transductions.- 10. Pushdown Automata.- 11. Abstract Families of Power Series.- 12. Substitutions.- 13. Reset Pushdown Automata and Counter Automata.- III. Algebraic Systems.- 14. Algebraic Series and Context-Free Languages.- 15. The Super Normal Form.- 16. Commuting Variables: Decidability and Parikh's Theorem.- Historical and Bibliographical Remarks.- References.- Symbol Index.

550 citations


Journal ArticleDOI
TL;DR: In this paper, a meta-analysis integrates 296 effect sizes reported in eye-tracking research on expertise differences in the comprehension of visualizations, concluding that experts had shorter fixation durations, more fixations on task-relevant areas, and fewer fixations in task-redundant areas; experts also had longer saccades and shorter times to first fixate relevant information.
Abstract: This meta-analysis integrates 296 effect sizes reported in eye-tracking research on expertise differences in the comprehension of visualizations. Three theories were evaluated: Ericsson and Kintsch’s (Psychol Rev 102:211–245, 1995) theory of long-term working memory, Haider and Frensch’s (J Exp Psychol Learn Mem Cognit 25:172–190, 1999) information-reduction hypothesis, and the holistic model of image perception of Kundel et al. (Radiology 242:396–402, 2007). Eye movement and performance data were cumulated from 819 experts, 187 intermediates, and 893 novices. In support of the evaluated theories, experts, when compared with non-experts, had shorter fixation durations, more fixations on task-relevant areas, and fewer fixations on task-redundant areas; experts also had longer saccades and shorter times to first fixate relevant information, owing to superiority in parafoveal processing and selective attention allocation. Eye movements, reaction time, and performance accuracy were moderated by characteristics of visualization (dynamics, realism, dimensionality, modality, and text annotation), task (complexity, time-on-task, and task control), and domain (sports, medicine, transportation, other). These findings are discussed in terms of their implications for theories of visual expertise in professional domains and their significance for the design of learning environments.

Journal ArticleDOI
TL;DR: In this paper, the decoherence in a single photon is controlled by rotating an optical filter, which can be used to tune the information flow between the photon and its environment.
Abstract: An open quantum system loses its ‘quantumness’ when information about the state leaks into its surroundings. Researchers now control this so-called decoherence in a single photon. By rotating an optical filter, the information flow between the photon and its environment can be tuned. This concept could be harnessed for future quantum technologies.

Journal ArticleDOI
TL;DR: It is suggested that bystander responses influence the frequency of bullying, which makes them suitable targets for antibullying interventions.
Abstract: This study investigated whether the bystanders’ behaviors (reinforcing the bully vs. defending the victim) in bullying situations are related to the frequency of bullying in a classroom. The sample consisted of 6,764 primary school children from Grades 3 to 5 (9–11 years of age), who were nested within 385 classrooms in 77 schools. The students filled out Internet-based questionnaires in their schools’ computer labs. The results from multilevel models showed that defending the victim was negatively associated with the frequency of bullying in a classroom, whereas the effect of reinforcing the bully was positive and strong. The results suggest that bystander responses influence the frequency of bullying, which makes them suitable targets for antibullying interventions.

Journal ArticleDOI
23 Dec 2011-Zootaxa
TL;DR: This dissertation aims to provide a history of web exceptionalism from 1989 to 2002, a period chosen in order to explore its roots as well as specific cases up to and including the year in which descriptions of “Web 2.0” began to circulate.
Abstract: van Nieukerken, Erik J.; Kaila, Lauri; Kitching, Ian J.; Kristensen, Niels Peder; Lees, David C.; Minet, Joël; Mitter, Charles; Mutanen, Marko; Regier, Jerome C.; Simonsen, Thomas J.; Wahlberg, Niklas; Yen, Shen-Horn; Zahiri, Reza; Adamski, David; Baixeras, Joaquin; Bartsch, Daniel; Bengtsson, Bengt Å.; Brown, John W.; Bucheli, Sibyl Rae; Davis, Donald R.; de Prins, Jurate; de Prins, Willy; Epstein, Marc E.; Gentili-Poole, Patricia; Gielis, Caes; Hättenschwiler, Peter; Hausmann, Axel; Holloway, Jeremy D.; Kallies, Axel; Karsholt, Ole; Kawahara, Akito Y.; Koster, Sjaak; Kozlov, Mikhail; Lafontaine, J. Donald; Lamas, Gerardo; Landry, JeanFrançois; Lee, Sangmi; Nuss, Matthias; Park, Kyu-Tek; Penz, Carla; Rota, Jadranka; Schintlmeister, Alexander; Schmidt, B. Christian; Sohn, Jae-Cheon; Solis, M. Alma; Tarmann, Gerhard M.; Warren, Andrew D.; Weller, Susan; Yakovlev, Roman V.; Zolotuhin, Vadim V.; Zwick, Andreas

Journal ArticleDOI
Tuomas O. Kilpeläinen1, Lu Qi2, Soren Brage1, Stephen J. Sharp1, Emily Sonestedt3, Ellen W. Demerath4, Tariq Ahmad5, Samia Mora2, Marika Kaakinen6, Camilla H. Sandholt7, Christina Holzapfel8, Christine S. Autenrieth, Elina Hyppönen9, Stéphane Cauchi, Meian He2, Zoltán Kutalik10, Meena Kumari9, Alena Stančáková11, Karina Meidtner, Beverley Balkau, Jonathan T. Tan12, Massimo Mangino13, Nicholas J. Timpson14, Yiqing Song2, M. Carola Zillikens, Kathleen A. Jablonski15, Melissa E. Garcia16, Stefan Johansson17, Jennifer L. Bragg-Gresham18, Ying Wu19, Jana V. van Vliet-Ostaptchouk20, N. Charlotte Onland-Moret21, Esther Zimmermann22, Natalia V. Rivera23, Toshiko Tanaka16, Heather M. Stringham18, Günther Silbernagel24, Stavroula Kanoni25, Mary F. Feitosa26, Soren Snitker27, Jonatan R. Ruiz28, Jeffery Metter16, María Teresa Martínez Larrad29, Mustafa Atalay11, Maarit Hakanen30, Najaf Amin23, Christine Cavalcanti-Proença, Anders Grøntved31, Göran Hallmans32, John-Olov Jansson33, Johanna Kuusisto11, Mika Kähönen, Pamela L. Lutsey4, John J. Nolan22, Luigi Palla1, Oluf Pedersen22, Louis Pérusse34, Frida Renström32, Robert A. Scott1, Dmitry Shungin32, Ulla Sovio35, Tuija Tammelin, Tapani Rönnemaa30, Timo A. Lakka11, Matti Uusitupa11, Manuel Serrano Ríos29, Luigi Ferrucci16, Claude Bouchard36, Aline Meirhaeghe37, Mao Fu27, Mark Walker38, Ingrid B. Borecki26, George Dedoussis25, Andreas Fritsche24, Claes Ohlsson33, Michael Boehnke18, Stefania Bandinelli, Cornelia M. van Duijn, Shah Ebrahim35, Debbie A Lawlor14, Vilmundur Gudnason39, Tamara B. Harris16, Thorkild I. A. Sørensen22, Karen L. Mohlke19, Albert Hofman23, André G. Uitterlinden23, Jaakko Tuomilehto40, Terho Lehtimäki, Olli T. Raitakari30, Bo Isomaa, Pål R. Njølstad17, Jose C. Florez41, Simin Liu42, Andy R Ness14, Tim D. Spector13, E. Shyong Tai12, Philippe Froguel43, Heiner Boeing, Markku Laakso11, Michael Marmot9, Sven Bergmann10, Chris Power9, Kay-Tee Khaw44, Daniel I. Chasman2, Paul M. Ridker2, Torben Hansen31, Keri L. Monda19, Thomas Illig, Marjo-Riitta Järvelin45, Nicholas J. Wareham1, Frank B. Hu2, Leif Groop3, Marju Orho-Melander3, Ulf Ekelund1, Paul W. Franks32, Ruth J. F. Loos1 
TL;DR: In this paper, a meta-analysis of data from 45 studies of adults and nine studies of children and adolescents was conducted to confirm or refute unambiguously whether physical activity attenuates the association of FTO with obesity risk.
Abstract: Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTOxPA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

Journal ArticleDOI
Peter A. R. Ade1, Nabila Aghanim2, Monique Arnaud3, M. Ashdown4  +284 moreInstitutions (66)
TL;DR: The first all-sky sample of galaxy clusters detected blindly by the Planck satellite through the Sunyaev-Zeldovich (SZ) effect from its six highest frequencies was presented in this paper.
Abstract: We present the first all-sky sample of galaxy clusters detected blindly by the Planck satellite through the Sunyaev-Zeldovich (SZ) effect from its six highest frequencies. This early SZ (ESZ) sample is comprised of 189 candidates, which have a high signal-to-noise ratio ranging from 6 to 29. Its high reliability (purity above 95%) is further ensured by an extensive validation process based on Planck internal quality assessments and by external cross-identification and follow-up observations. Planck provides the first measured SZ signal for about 80% of the 169 previouslyknown ESZ clusters. Planck furthermore releases 30 new cluster candidates, amongst which 20 meet the ESZ signal-to-noise selection criterion. At the submission date, twelve of the 20 ESZ candidates were confirmed as new clusters, with eleven confirmed using XMM-Newton snapshot observations, most of them with disturbed morphologies and low luminosities. The ESZ clusters are mostly at moderate redshifts (86% with z below 0.3) and span more than a decade in mass, up to the rarest and most massive clusters with masses above 1 × 10 15 M� .

Journal ArticleDOI
TL;DR: Men were more likely than women to die from respiratory disease, malignant neoplasm, and circulatory disease after hip fracture, while the most common causes of death were circulatory diseases, followed by dementia and Alzheimer's disease.
Abstract: The high mortality of hip fracture patients is well documented, but sex- and cause-specific mortality after hip fracture has not been extensively studied. The purpose of the present study was to evaluate mortality and cause of death in patients after hip fracture surgery and to compare their mortality and cause of death to those in the general population. Records of 428 consecutive hip fracture patients were collected on a population-basis and data on the general population comprising all Finns 65 years of age or older were collected on a cohort-basis. Cause of death was classified as follows: malignant neoplasms, dementia, circulatory disease, respiratory disease, digestive system disease, and other. Mean follow-up was 3.7 years (range 0-9 years). Overall 1-year postoperative mortality was 27.3% and mortality after hip fracture at the end of the follow-up was 79.0%. During the follow-up, age-adjusted mortality after hip fracture surgery was higher in men than in women with hazard ratio (HR) 1.55 and 95% confidence interval (95% CI) 1.21-2.00. Among hip surgery patients, the most common causes of death were circulatory diseases, followed by dementia and Alzheimer's disease. After hip fracture, men were more likely than women to die from respiratory disease, malignant neoplasm, and circulatory disease. During the follow-up, all-cause age- and sex-standardized mortality after hip fracture was 3-fold higher than that of the general population and included every cause-of-death category. During the study period, the risk of mortality in hip fracture patients was 3-fold higher than that in the general population and included every major cause of death.

Journal ArticleDOI
TL;DR: In this article, the authors examined tracking and predictiveness of childhood lipid levels, blood pressure, and body mass index for risk profile in adulthood and the best age to measure the childhood risk factor levels.

Journal ArticleDOI
TL;DR: A clear but detailed view of the chemical ecology of tannins and the methodology used to study them is given, and a new method to estimate the oxidative activity of all types of tANNins and other phenolics that might cause oxidative stress to herbivores is introduced.
Abstract: Summary 1. Tannins are one of the most studied groups of plant secondary metabolites in research related to chemical ecology. They are traditionally thought to form an important factor of plant defence against herbivorous insects. 2. For a long time, tannins’ anti-herbivore activity was thought to derive from their protein precipitation capacity that rendered plant tissues non-nutritious and unpalatable for herbivores. Recent evidence suggests that tannin activity cannot be explained quite this simply, as tannin oxidation should also be taken into account as a defence mechanism for plants. 3. Tannins show very high variability in their structures with several hundred unique molecules detected in plants. These molecules are unevenly distributed in the plant kingdom and only very seldom—if ever—do two plant species share the same tannin pool. In many cases tannin composition varies even within organs of the same plant species and individual. Still, the overall tannin composition of many plant species is as of yet unknown. 4. Chemical ecology of tannins is challenging due to its multi-disciplinary nature. To facilitate research on tannins, we must provide ecologists and chemists with methodological and collaborative alternatives that enable the true and holistic investigation of all important questions that may arise from the field. So far this has not been possible with the tannin oxidation hypothesis, since simple and widely usable methods have not been available. 5. The aim of this review is to give a clear but detailed view of the chemical ecology of tannins and the methodology used to study them. In addition, we introduce a new method to estimate the oxidative activity of all types of tannins and other phenolics that might cause oxidative stress to herbivores. Hopefully our arguments and method will lead to clear changes in the approaches we take to tannins and their exciting biological activities, and we will witness a new era of flourishing and productive research in the chemical ecology of tannins.

Journal ArticleDOI
Jelena Aleksić1, L. A. Antonelli2, P. Antoranz3, Michael Backes4  +156 moreInstitutions (22)
TL;DR: Very high energy (VHE) gamma-ray emission from the flat spectrum radio quasar (FSRQ) PKS 1222+21 (4C 21.432) was detected with the MAGIC Cherenkov telescopes during a short observation (similar to 0.5 hr) performed on 2010 June 17 as mentioned in this paper.
Abstract: Very high energy (VHE) gamma-ray emission from the flat spectrum radio quasar (FSRQ) PKS 1222+ 21 (4C 21.35, z = 0.432) was detected with the MAGIC Cherenkov telescopes during a short observation (similar to 0.5 hr) performed on 2010 June 17. The MAGIC detection coincides with high-energy MeV/ GeV gamma-ray activity measured by the Large Area Telescope (LAT) on board the Fermi satellite. The VHE spectrum measured by MAGIC extends from about 70 GeV up to at least 400 GeV and can be well described by a power-law dN/dE proportional to E-Gamma with a photon index Gamma = 3.75 +/- 0.27(stat) +/- 0.2(syst). The averaged integral flux above 100 GeV is (4.6 +/- 0.5) x 10(-10) cm(-2) s(-1) (similar to 1 Crab Nebula flux). The VHE flux measured by MAGIC varies significantly within the 30 minute exposure implying a flux doubling time of about 10 minutes. The VHE and MeV/GeV spectra, corrected for the absorption by the extragalactic background light (EBL), can be described by a single power law with photon index 2.72 +/- 0.34 between 3 GeV and 400 GeV, and is consistent with emission belonging to a single component in the jet. The absence of a spectral cutoff constrains the gamma-ray emission region to lie outside the broad-line region, which would otherwise absorb the VHE gamma-rays. Together with the detected fast variability, this challenges present emission models from jets in FSRQs. Moreover, the combined Fermi/LAT and MAGIC spectral data yield constraints on the density of the EBL in the UV-optical to near-infrared range that are compatible with recent models.

Journal ArticleDOI
Louise V. Wain1, Germaine C. Verwoert2, Paul F. O'Reilly3, Gang Shi4  +226 moreInstitutions (70)
TL;DR: Findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP, as well as two new MAP loci associated with both of these traits.
Abstract: Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans(1-3). We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 x 10(-8) to P = 2.3 x 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

Journal ArticleDOI
TL;DR: Findings provide general support to the largely untested hypotheses that migratory birds are becoming ecologically mismatched and that failure to respond to climate change can have severe negative impacts on their populations.
Abstract: Climate is changing at a fast pace, causing widespread, profound consequences for living organisms. Failure to adjust the timing of life-cycle events to climate may jeopardize populations by causing ecological mismatches to the life cycle of other species and abiotic factors. Population declines of some migratory birds breeding in Europe have been suggested to depend on their inability to adjust migration phenology so as to keep track of advancement of spring events at their breeding grounds. In fact, several migrants have advanced their spring arrival date, but whether such advancement has been sufficient to compensate for temporal shift in spring phenophases or, conversely, birds have become ecologically mismatched, is still an unanswered question, with very few exceptions. We used a novel approach based on accumulated winter and spring temperatures (degree-days) as a proxy for timing of spring biological events to test if the progress of spring at arrival to the breeding areas by 117 European migratory bird species has changed over the past five decades. Migrants, and particularly those wintering in sub-Saharan Africa, now arrive at higher degree-days and may have therefore accumulated a ‘thermal delay’, thus possibly becoming increasingly mismatched to spring phenology. Species with greater ‘thermal delay’ have shown larger population decline, and this evidence was not confounded by concomitant ecological factors or by phylogenetic effects. These findings provide general support to the largely untested hypotheses that migratory birds are becoming ecologically mismatched and that failure to respond to climate change can have severe negative impacts on their populations. The novel approach we adopted can be extended to the analysis of ecological consequences of phenological response to climate change by other taxa.

Journal ArticleDOI
A. A. Abdo1, A. A. Abdo2, Markus Ackermann3, Marco Ajello3  +418 moreInstitutions (73)
TL;DR: In this paper, the gamma-ray activity of the high-synchrotron-peaked BL Lacertae object Markarian 421 (Mrk 421) during the first 1.5 years of Fermi operation was reported.
Abstract: We report on the gamma-ray activity of the high-synchrotron-peaked BL Lacertae object Markarian 421 (Mrk 421) during the first 1.5 years of Fermi operation, from 2008 August 5 to 2010 March 12. We find that the Large Area Telescope (LAT) gamma-ray spectrum above 0.3 GeV can be well described by a power-law function with photon index Gamma = 1.78 +/- 0.02 and average photon flux F(>0.3 GeV) = (7.23 +/- 0.16) x 10(-8) ph cm(-2) s(-1). Over this time period, the Fermi-LAT spectrum above 0.3 GeV was evaluated on seven-day-long time intervals, showing significant variations in the photon flux (up to a factor similar to 3 from the minimum to the maximum flux) but mild spectral variations. The variability amplitude at X-ray frequencies measured by RXTE/ASM and Swift/BAT is substantially larger than that in gamma-rays measured by Fermi-LAT, and these two energy ranges are not significantly correlated. We also present the first results from the 4.5 month long multifrequency campaign on Mrk 421, which included the VLBA, Swift, RXTE, MAGIC, the F-GAMMA, GASP-WEBT, and other collaborations and instruments that provided excellent temporal and energy coverage of the source throughout the entire campaign (2009 January 19 to 2009 June 1). During this campaign, Mrk 421 showed a low activity at all wavebands. The extensive multi-instrument (radio to TeV) data set provides an unprecedented, complete look at the quiescent spectral energy distribution (SED) for this source. The broadband SED was reproduced with a leptonic (one-zone synchrotron self-Compton) and a hadronic model (synchrotron proton blazar). Both frameworks are able to describe the average SED reasonably well, implying comparable jet powers but very different characteristics for the blazar emission site.


Journal ArticleDOI
TL;DR: In this article, a systematic review was performed using PubMed and EMBASE to calculate pooled risk estimates for the association of human papillomavirus (HPV) with oral carcinoma (OSCC) and potentially malignant disorders (OPMD).
Abstract: Oral Diseases (2011) 17 (Suppl. 1), 58–72 Objectives: Human papillomavirus (HPV) in oral carcinoma (OSCC) and potentially malignant disorders (OPMD) is controversial. The primary aim was to calculate pooled risk estimates for the association of HPV with OSCC and OPMD when compared with healthy oral mucosa as controls. We also examined the effects of sampling techniques on HPV detection rates. Methods: Systematic review was performed using PubMed (January 1966–September 2010) and EMBASE (January 1990–September 2010). Eligible studies included randomized controlled, cohort and cross-sectional studies. Pooled data were analysed by calculating odds ratios, using a random effects model. Risk of bias was based on characteristics of study group, appropriateness of the control group and prospective design. Results: Of the 1121 publications identified, 39 cross-sectional studies met the inclusion criteria. Collectively, 1885 cases and 2248 controls of OSCC and 956 cases and 675 controls of OPMD were available for analysis. Significant association was found between pooled HPV-DNA detection and OSCC (OR = 3.98; 95% CI: 2.62–6.02) and even for HPV16 only (OR = 3.86; 95% CI: 2.16–6.86). HPV was also associated with OPMD (OR = 3.87; 95% CI: 2.87–5.21). In a subgroup analysis of OPMD, HPV was also associated with oral leukoplakia (OR = 4.03; 95% CI: 2.34–6.92), oral lichen planus (OR = 5.12; 95% CI: 2.40–10.93), and epithelial dysplasia (OR = 5.10; 95% CI: 2.03–12.80). Conclusions: The results suggest a potentially important causal association between HPV and OSCC and OPMD.

Journal ArticleDOI
TL;DR: A proper integration across biological disciplines seems essential for the field's transition from affirming patterns to understanding mechanisms and making robust predictions regarding future consequences of shifting phenologies.
Abstract: Recent shifts in phenology in response to climate change are well established but often poorly understood. Many animals integrate climate change across a spatially and temporally dispersed annual life cycle, and effects are modulated by ecological interactions, evolutionary change and endogenous control mechanisms. Here we assess and discuss key statements emerging from the rapidly developing study of changing spring phenology in migratory birds. These well-studied organisms have been instrumental for understanding climate-change effects, but research is developing rapidly and there is a need to attack the big issues rather than risking affirmative science. Although we agree poorly on the support for most claims, agreement regarding the knowledge basis enables consensus regarding broad patterns and likely causes. Empirical data needed for disentangling mechanisms are still scarce, and consequences at a population level and on community composition remain unclear. With increasing knowledge, the overall support ('consensus view') for a claim increased and between-researcher variability in support ('expert opinions') decreased, indicating the importance of assessing and communicating the knowledge basis. A proper integration across biological disciplines seems essential for the field's transition from affirming patterns to understanding mechanisms and making robust predictions regarding future consequences of shifting phenologies.

Journal ArticleDOI
TL;DR: In this paper, the authors report the effects of KiVa on nine different forms of being bullied in a sample of 5,651 fourth to sixth graders from 78 schools (39 intervention, 39 control).
Abstract: In 2006, the Finnish Ministry of Education mandated our research group to develop an antibullying program for comprehensive schools. The new program, KiVa, includes both universal and indicated actions to reduce bullying. The present study reports the effects of KiVa on nine different forms of being bullied in a sample of 5,651 fourth to sixth graders from 78 schools (39 intervention, 39 control). The findings showed positive effects on each form of being bullied assessed. After 9 months of intervention, control school students were 1.32-- 1.94 times as likely to be bullied as students in intervention schools. A well-designed, research-based program can thus reduce multiple forms of being bullied, and there might be no need to develop specific programs for different forms of bullying.

Journal ArticleDOI
TL;DR: In this article, the authors analyzed the validity of the value added intellectual coefficient (VAIC) method as an indicator of intellectual capital and tested the hypothesis according to which VAIC correlates with a company's stock market value.
Abstract: Purpose – The purpose of this study is to analyse the validity of the value added intellectual coefficient (VAIC) method as an indicator of intellectual capital.Design/methodology/approach – The paper describes VAIC through its calculation formulae and aims to establish what exactly it is that the method measures. It also looks in detail at how intellectual capital is understood in the method, and discusses its conceptual confusions. Furthermore, the paper tests the hypothesis according to which VAIC correlates with a company's stock market value, and reflects the contradictory results of earlier studies.Findings – The analyses show, first, that VAIC indicates the efficiency of the company's labour and capital investments, and has nothing to do with intellectual capital. Furthermore, the calculation method uses overlapping variables and has other serious validity problems. Second, the results do not lend support to the hypothesis that VAIC correlates with a company's stock market value. The main reasons b...

Journal ArticleDOI
TL;DR: Optimized methods for separation of higher plant thylakoid membrane protein complexes by native-PAGE addressing particularly the use of detergent, use of solubilization buffer, and the gel electrophoresis method are described.
Abstract: Gel-based analysis of thylakoid membrane protein complexes represents a valuable tool to monitor the dynamics of the photosynthetic machinery Native-PAGE preserves the components and often also the conformation of the protein complexes, thus enabling the analysis of their subunit composition Nevertheless, the literature and practical experimentation in the field sometimes raise confusion owing to a great variety of native-PAGE and thylakoid-solubilization systems In the present paper, we describe optimized methods for separation of higher plant thylakoid membrane protein complexes by native-PAGE addressing particularly: (i) the use of detergent; (ii) the use of solubilization buffer; and (iii) the gel electrophoresis method Special attention is paid to separation of high-molecular-mass thylakoid membrane super- and mega-complexes from Arabidopsis thaliana leaves Several novel super- and mega-complexes including PS (photosystem) I, PSII and LHCs (light-harvesting complexes) in various combinations are reported

Journal ArticleDOI
TL;DR: It is established that miRNAs interacting with the long 3'UTR of the AR gene are important regulators of AR protein levels, with implications for developing new therapeutic strategies to inhibit AR function and androgen-dependent cell growth.
Abstract: Androgen receptor (AR) is expressed in all stages of prostate cancer progression, including in castration-resistant tumors. Eliminating AR function continues to represent a focus of therapeutic investigation, but AR regulatory mechanisms remain poorly understood. To systematically characterize mechanisms involving microRNAs (miRNAs), we conducted a gain-of function screen of 1129 miRNA molecules in a panel of human prostate cancer cell lines and quantified changes in AR protein content using protein lysate microarrays. In this way, we defined 71 unique miRNAs that influenced the level of AR in human prostate cancer cells. RNA sequencing data revealed that the 3'UTR of AR (and other genes) is much longer than currently used in miRNA target prediction programs. Our own analyses predicted that most of the miRNA regulation of AR would target an extended 6 kb 3'UTR. 3'UTR-binding assays validated 13 miRNAs that are able to regulate this long AR 3'UTR (miR-135b, miR-185, miR-297, miR-299-3p, miR-34a, miR-34c, miR-371-3p, miR-421, miR-449a, miR-449b, miR-634, miR-654-5p, and miR-9). Fifteen AR downregulating miRNAs decreased androgen-induced proliferation of prostate cancer cells. In particular, analysis of clinical prostate cancers confirmed a negative correlation of miR-34a and miR-34c expression with AR levels. Our findings establish that miRNAs interacting with the long 3'UTR of the AR gene are important regulators of AR protein levels, with implications for developing new therapeutic strategies to inhibit AR function and androgen-dependent cell growth.