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Showing papers by "University of Udine published in 2013"


Journal ArticleDOI
22 May 2013-Nature
TL;DR: The draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm, is presented, revealing numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs, which opens up new genomic avenues for conifer forestry and breeding.
Abstract: Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.

1,299 citations


Journal ArticleDOI
TL;DR: Comparisons showed that peach has not undergone recent whole-genome duplication, and even though the ancestral triplicated blocks in peach are fragmentary compared to those in grape, all seven paleosets of paralogs from the putative paleoancestor are detectable.
Abstract: Rosaceae is the most important fruit-producing clade, and its key commercially relevant genera (Fragaria, Rosa, Rubus and Prunus) show broadly diverse growth habits, fruit types and compact diploid genomes. Peach, a diploid Prunus species, is one of the best genetically characterized deciduous trees. Here we describe the high-quality genome sequence of peach obtained from a completely homozygous genotype. We obtained a complete chromosome-scale assembly using Sanger whole-genome shotgun methods. We predicted 27,852 protein-coding genes, as well as noncoding RNAs. We investigated the path of peach domestication through whole-genome resequencing of 14 Prunus accessions. The analyses suggest major genetic bottlenecks that have substantially shaped peach genome diversity. Furthermore, comparative analyses showed that peach has not undergone recent whole-genome duplication, and even though the ancestral triplicated blocks in peach are fragmentary compared to those in grape, all seven paleosets of paralogs from the putative paleoancestor are detectable.

935 citations


Journal ArticleDOI
TL;DR: It is shown that CyPD binds the oligomycin sensitivity-conferring protein subunit of the enzyme at the same site as the ATP synthase inhibitor benzodiazepine 423 (Bz-423), which sensitizes the PTP to Ca2+.
Abstract: Here we define the molecular nature of the mitochondrial permeability transition pore (PTP), a key effector of cell death. The PTP is regulated by matrix cyclophilin D (CyPD), which also binds the lateral stalk of the FOF1 ATP synthase. We show that CyPD binds the oligomycin sensitivity-conferring protein subunit of the enzyme at the same site as the ATP synthase inhibitor benzodiazepine 423 (Bz-423), that Bz-423 sensitizes the PTP to Ca2+ like CyPD itself, and that decreasing oligomycin sensitivity-conferring protein expression by RNAi increases the sensitivity of the PTP to Ca2+. Purified dimers of the ATP synthase, which did not contain voltage-dependent anion channel or adenine nucleotide translocator, were reconstituted into lipid bilayers. In the presence of Ca2+, addition of Bz-423 triggered opening of a channel with currents that were typical of the mitochondrial megachannel, which is the PTP electrophysiological equivalent. Channel openings were inhibited by the ATP synthase inhibitor AMP-PNP (γ-imino ATP, a nonhydrolyzable ATP analog) and Mg2+/ADP. These results indicate that the PTP forms from dimers of the ATP synthase.

835 citations


Journal ArticleDOI
B. S. Acharya1, Marcos Daniel Actis2, T. Aghajani3, G. Agnetta4  +979 moreInstitutions (122)
TL;DR: The Cherenkov Telescope Array (CTA) as discussed by the authors is a very high-energy (VHE) gamma ray observatory with an international collaboration with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America.

701 citations


Journal ArticleDOI
Keith Bradnam1, Joseph Fass1, Anton Alexandrov, Paul Baranay2, Michael Bechner, Inanc Birol, Sébastien Boisvert3, Jarrod Chapman4, Guillaume Chapuis5, Guillaume Chapuis6, Rayan Chikhi6, Rayan Chikhi5, Hamidreza Chitsaz7, Wen-Chi Chou8, Jacques Corbeil3, Cristian Del Fabbro9, T. Roderick Docking, Richard Durbin10, Dent Earl11, Scott J. Emrich12, Pavel Fedotov, Nuno A. Fonseca13, Ganeshkumar Ganapathy14, Richard A. Gibbs15, Sante Gnerre16, Elenie Godzaridis3, Steve Goldstein, Matthias Haimel13, Giles Hall16, David Haussler11, Joseph B. Hiatt17, Isaac Ho4, Jason T. Howard14, Martin Hunt10, Shaun D. Jackman, David B. Jaffe16, Erich D. Jarvis14, Huaiyang Jiang15, Sergey Kazakov, Paul J. Kersey13, Jacob O. Kitzman17, James R. Knight, Sergey Koren18, Tak-Wah Lam, Dominique Lavenier5, Dominique Lavenier6, François Laviolette3, Yingrui Li, Zhenyu Li, Binghang Liu, Yue Liu15, Ruibang Luo, Iain MacCallum16, Matthew D. MacManes19, Nicolas Maillet5, Sergey Melnikov, Bruno Vieira20, Delphine Naquin5, Zemin Ning10, Thomas D. Otto10, Benedict Paten11, Octávio S. Paulo20, Adam M. Phillippy18, Francisco Pina-Martins20, Michael Place, Dariusz Przybylski16, Xiang Qin15, Carson Qu15, Filipe J. Ribeiro16, Stephen Richards15, Daniel S. Rokhsar19, Daniel S. Rokhsar4, J. Graham Ruby21, J. Graham Ruby22, Simone Scalabrin9, Michael C. Schatz23, David C. Schwartz, Alexey Sergushichev, Ted Sharpe16, Timothy I. Shaw8, Jay Shendure17, Yujian Shi, Jared T. Simpson10, Henry Song15, Fedor Tsarev, Francesco Vezzi24, Riccardo Vicedomini9, Jun Wang, Kim C. Worley15, Shuangye Yin16, Siu-Ming Yiu, Jianying Yuan, Guojie Zhang, Hao Zhang, Shiguo Zhou, Ian F Korf1 
TL;DR: The Assemblathon 2 as mentioned in this paper presented a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and a snake) from 21 participating teams.
Abstract: Background - The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results - In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. Conclusions - Many current genome assemblers produced useful assemblies, containing a significant representation of their genes, regulatory sequences, and overall genome structure. However, the high degree of variability between the entries suggests that there is still much room for improvement in the field of genome assembly and that approaches which work well in assembling the genome of one species may not necessarily work well for another.

690 citations


Journal ArticleDOI
S. Schael1, R. Barate2, R. Brunelière2, D. Buskulic2  +1672 moreInstitutions (143)
TL;DR: In this paper, the results of the four LEP experiments were combined to determine fundamental properties of the W boson and the electroweak theory, including the branching fraction of W and the trilinear gauge-boson self-couplings.

684 citations


Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah  +2942 moreInstitutions (201)
TL;DR: In this paper, the spin and parity quantum numbers of the Higgs boson were studied based on the collision data collected by the ATLAS experiment at the LHC, and the results showed that the standard model spin-parity J(...

608 citations


Journal ArticleDOI
Keith Bradnam, Joseph Fass, Anton Alexandrov, Paul Baranay1, Michael Bechner, Inanc Birol2, Sébastien Boisvert3, Jarrod Chapman4, Guillaume Chapuis5, Guillaume Chapuis6, Rayan Chikhi6, Rayan Chikhi5, Hamidreza Chitsaz7, Wen-Chi Chou8, Jacques Corbeil3, Cristian Del Fabbro, Roderick R. Docking2, Richard Durbin9, Dent Earl10, Scott J. Emrich11, Pavel Fedotov, Nuno A. Fonseca12, Ganeshkumar Ganapathy13, Richard A. Gibbs14, Sante Gnerre15, Elenie Godzaridis3, Steve Goldstein, Matthias Haimel12, Giles Hall15, David Haussler10, Joseph B. Hiatt16, Isaac Ho4, Jason T. Howard13, Martin Hunt9, Shaun D. Jackman2, David B. Jaffe15, Erich D. Jarvis13, Huaiyang Jiang14, Sergey Kazakov, Paul J. Kersey12, Jacob O. Kitzman16, James R. Knight, Sergey Koren17, Tak-Wah Lam18, Dominique Lavenier19, Dominique Lavenier5, Dominique Lavenier6, François Laviolette3, Yingrui Li18, Zhenyu Li, Binghang Liu, Yue Liu14, Ruibang Luo18, Iain MacCallum15, Matthew D. MacManes20, Nicolas Maillet19, Nicolas Maillet5, Sergey Melnikov, Delphine Naquin19, Delphine Naquin5, Zemin Ning9, Thomas D. Otto9, Benedict Paten10, Octávio S. Paulo21, Adam M. Phillippy17, Francisco Pina-Martins21, Michael Place, Dariusz Przybylski15, Xiang Qin14, Carson Qu14, Filipe J. Ribeiro, Stephen Richards14, Daniel S. Rokhsar22, Daniel S. Rokhsar4, J. Graham Ruby23, J. Graham Ruby24, Simone Scalabrin, Michael C. Schatz25, David C. Schwartz, Alexey Sergushichev, Ted Sharpe15, Timothy I. Shaw8, Jay Shendure16, Yujian Shi, Jared T. Simpson9, Henry Song14, Fedor Tsarev, Francesco Vezzi26, Riccardo Vicedomini27, Bruno Vieira21, Jun Wang, Kim C. Worley14, Shuangye Yin15, Siu-Ming Yiu18, Jianying Yuan, Guojie Zhang, Hao Zhang, Shiguo Zhou, Ian F Korf 
TL;DR: The Assemblathon 2 as discussed by the authors presented a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and a snake) from 21 participating teams.
Abstract: Background: The process of generating raw genome sequence data continues to become cheaper, faster, and more accurate. However, assembly of such data into high-quality, finished genome sequences remains challenging. Many genome assembly tools are available, but they differ greatly in terms of their performance (speed, scalability, hardware requirements, acceptance of newer read technologies) and in their final output (composition of assembled sequence). More importantly, it remains largely unclear how to best assess the quality of assembled genome sequences. The Assemblathon competitions are intended to assess current state-of-the-art methods in genome assembly. Results: In Assemblathon 2, we provided a variety of sequence data to be assembled for three vertebrate species (a bird, a fish, and snake). This resulted in a total of 43 submitted assemblies from 21 participating teams. We evaluated these assemblies using a combination of optical map data, Fosmid sequences, and several statistical methods. From over 100 different metrics, we chose ten key measures by which to assess the overall quality of the assemblies. (Continued on next page)

602 citations


Journal ArticleDOI
TL;DR: The molecular mechanism through which clothianidin adversely affects the insect immune response and promotes replication of a viral pathogen in honey bees bearing covert infections is described and shed light on a further level of regulation of the immune response in insects and has implications for bee conservation.
Abstract: Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture.

558 citations


Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2942 moreInstitutions (200)
TL;DR: In this article, the production properties and couplings of the recently discovered Higgs boson using the decays into boson pairs were measured using the complete pp collision data sample recorded by the ATLAS experiment at the CERN Large Hadron Collider at centre-of-mass energies of 7 TeV and 8 TeV, corresponding to an integrated luminosity of about 25/fb.

513 citations


Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, J. Abdallah4  +2897 moreInstitutions (184)
TL;DR: In this article, the luminosity calibration for the ATLAS detector at the LHC during pp collisions at root s = 7 TeV in 2010 and 2011 is presented, and a luminosity uncertainty of delta L/L = +/- 3.5 % is obtained.
Abstract: The luminosity calibration for the ATLAS detector at the LHC during pp collisions at root s = 7 TeV in 2010 and 2011 is presented. Evaluation of the luminosity scale is performed using several luminosity-sensitive detectors, and comparisons are made of the long-term stability and accuracy of this calibration applied to the pp collisions at root s = 7 TeV. A luminosity uncertainty of delta L/L = +/- 3.5 % is obtained for the 47 pb(-1) of data delivered to ATLAS in 2010, and an uncertainty of delta L/L = +/- 1.8 % is obtained for the 5.5 fb(-1) delivered in 2011.

Journal ArticleDOI
TL;DR: The synthesis of flavonoids, their import and export in plant cell compartments, as well as their involvement in the response to stress, with particular reference to grapevine are analyzed.
Abstract: This paper aims at analysing the synthesis of flavonoids, their import and export in plant cell compartments, as well as their involvement in the response to stress, with particular reference to grapevine (Vitis vinifera L.). A multidrug and toxic compound extrusion (MATE) as well as ABC transporters have been demonstrated in the tonoplast of grape berry, where they perform a flavonoid transport. The involvement of a glutathione S-transferase (GST) gene has also been inferred. Recently, a putative flavonoid carrier, similar to mammalian bilitranslocase (BTL), has been identified in both grape berry skin and pulp. In skin the pattern of BTL expression increases from veraison to harvest, while in the pulp its expression reaches the maximum at the early ripening stage. Moreover, the presence of BTL in vascular bundles suggests its participation in long distance transport of flavonoids. In addition, the presence of a vesicular trafficking in plants responsible for flavonoid transport is discussed. Finally, the involvement of flavonoids in the response to stress is described.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, J. Abdallah4  +2912 moreInstitutions (183)
TL;DR: Two-particle correlations in relative azimuthal angle and pseudorapidity are measured using the ATLAS detector at the LHC and the resultant Δø correlation is approximately symmetric about π/2, and is consistent with a dominant cos2Δø modulation for all ΣE(T)(Pb) ranges and particle p(T).
Abstract: Two-particle correlations in relative azimuthal angle (Delta phi) and pseudorapidity (Delta eta) are measured in root S-NN = 5.02 TeV p + Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1 mu b(-1) of data as a function of transverse momentum (p(T)) and the transverse energy (Sigma E-T(Pb)) summed over 3.1 < eta < 4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2 < vertical bar Delta eta vertical bar < 5) "near-side" (Delta phi similar to 0) correlation that grows rapidly with increasing Sigma E-T(Pb). A long-range "away-side" (Delta phi similar to pi) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small Sigma E-T(Pb), is found to match the near-side correlation in magnitude, shape (in Delta eta and Delta phi) and Sigma E-T(Pb) dependence. The resultant Delta phi correlation is approximately symmetric about pi/2, and is consistent with a dominant cos2 Delta phi modulation for all Sigma E-T(Pb) ranges and particle p(T).

Journal ArticleDOI
TL;DR: This paper provides easy to use protocols for the collection, identification, diagnosis, rearing, breeding, marking and measurement of infestation rates and fertility of V. destructor and describes pros and cons for all methods for the user to know which method to use under which circumstances.
Abstract: SummaryVery rapidly after Varroa destructor invaded apiaries of Apis mellifera, the devastating effect of this mite prompted an active research effort to understand and control this parasite. Over a few decades, varroa has spread to most countries exploiting A. mellifera. As a consequence, a large number of teams have worked with this organism, developing a diversity of research methods. Often different approaches have been followed to achieve the same goal. The diversity of methods made the results difficult to compare, thus hindering our understanding of this parasite. In this paper, we provide easy to use protocols for the collection, identification, diagnosis, rearing, breeding, marking and measurement of infestation rates and fertility of V. destructor. We also describe experimental protocols to study orientation and feeding of the mite, to infest colonies or cells and measure the mite's susceptibility to acaricides. Where relevant, we describe which mite should be used for bioassays since their beha...

Journal ArticleDOI
TL;DR: Grape seed extracts obtained from seeds defatted by ultrasound (US) and then extracted by maceration resulted the highest in polyphenol concentration (105.20mg GAE/ g flour) and antioxidant activity (109 Eq αToc/g flour).

Journal ArticleDOI
TL;DR: This work conclusively demonstrate the piezoresistive effect in graphene in a nanoelectromechanical membrane configuration that provides direct electrical readout of pressure to strain transduction and acts as a strain gauge independent of crystallographic orientation.
Abstract: Monolayer graphene exhibits exceptional electronic and mechanical properties, making it a very promising material for nanoelectromechanical devices. Here, we conclusively demonstrate the piezoresistive effect in graphene in a nanoelectromechanical membrane configuration that provides direct electrical readout of pressure to strain transduction. This makes it highly relevant for an important class of nanoelectromechanical system (NEMS) transducers. This demonstration is consistent with our simulations and previously reported gauge factors and simulation values. The membrane in our experiment acts as a strain gauge independent of crystallographic orientation and allows for aggressive size scalability. When compared with conventional pressure sensors, the sensors have orders of magnitude higher sensitivity per unit area.

Journal ArticleDOI
TL;DR: Fundamental issues relating to the basic definition of margin adequacy, uniform reporting standards for margins, optimal method of specimen dissection, and the role of intraoperative frozen section evaluation, require further clarification and standardization.
Abstract: Adequate resection margins are critical to the treatment decisions and prognosis of patients with head and neck squamous cell carcinoma (HNSCC). However, there are numerous controversies regarding reporting and interpretation of the status of resection margins. Fundamental issues relating to the basic definition of margin adequacy, uniform reporting standards for margins, optimal method of specimen dissection, and the role of intraoperative frozen section evaluation, all require further clarification and standardization. Future horizons for margin surveillance offer the possible use of novel methods such as "molecular margins" and contact microscopic endoscopy, However, the limitations of these approaches need to be understood. The goal of this review was to evaluate these issues to define a more rational, standardized approach for achieving resection margin adequacy for patients with HNSCC undergoing curative resection.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2954 moreInstitutions (201)
TL;DR: In this paper, the results of a search for pair production of supersymmetric partners of the Standard Model third-generation quarks are reported using 20.1 fb-1 of pp collisions collected by the ATLAS experiment at the Large Hadron Collider.
Abstract: The results of a search for pair production of supersymmetric partners of the Standard Model third-generation quarks are reported. This search uses 20.1 fb-1 of pp collisions at sqrt{s}=8 TeV collected by the ATLAS experiment at the Large Hadron Collider. The lightest bottom and top squarks (b1 and t1 respectively) are searched for in a final state with large missing transverse momentum and two jets identified as originating from b-quarks. No excess of events above the expected level of Standard Model background is found. The results are used to set upper limits on the visible cross section for processes beyond the Standard Model. Exclusion limits at the 95% confidence level on the masses of the third-generation squarks are derived in phenomenological supersymmetric R-parity-conserving models in which either the bottom or the top squark is the lightest squark. The b1 is assumed to decay via b1->b chi0 and the t via t1->b chipm, with undetectable products of the subsequent decay of the chipm due to the small mass splitting between the chipm and the chi0.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, Jalal Abdallah4  +2931 moreInstitutions (200)
TL;DR: In this paper, a search for new phenomena in events with a high-energy jet and large missing transverse momentum is performed using data from proton-proton collisions at root s = 7 TeV with the ATLAS experiment at the Large flatiron Collider.
Abstract: A search for new phenomena in events with a high-energy jet and large missing transverse momentum is performed using data from proton-proton collisions at root s = 7 TeV with the ATLAS experiment at the Large flatiron Collider. Four kinematic regions are explored using a dataset corresponding to an integrated luminosity of 4.7 fb(-1). No excess of events beyond expectations from Standard Model processes is observed, and limits are set on large extra dimensions and the pair production of dark matter particles.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, J. Abdallah3, S. Abdel Khalek4  +2849 moreInstitutions (179)
TL;DR: In this paper, the authors measured the effect of jet suppression in heavy ion collisions at the LHC and provided a direct sensitivity to the physics of jet quenching, using a sample of lead-lead collisions at root S-NN = 2.76 TeV.

Journal ArticleDOI
TL;DR: The potential predictive value of plasma VEGF-A is consistent with findings in HER2-negative LR/MBC, warranting prospective evaluation.
Abstract: Purpose The AVEREL trial [A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab)/Docetaxel in Patients With HER2-Positive Metastatic Breast Cancer] evaluated first-line bevacizumab-containing therapy for human epidermal growth factor receptor 2 (HER2) –positive locally recurrent/metastatic breast cancer (LR/MBC). Patients and Methods Patients with measurable/evaluable HER2-positive LR/MBC who had not received trastuzumab or chemotherapy for LR/MBC were stratified by prior adjuvant trastuzumab, prior (neo)adjuvant taxane, hormone receptor status, and measurable disease and were randomly assigned to receive docetaxel 100 mg/m2 plus trastuzumab 8 mg/kg loading dose followed by 6 mg/kg either with bevacizumab 15 mg/kg or without bevacizumab, all administered every 3 weeks. The primary end point was progression-free survival (PFS). Additional end points included overall survival, response rate (RR), safety, quality of life, and translational research. Results Baseline characteristics of t...

Journal ArticleDOI
TL;DR: It is proposed that further pharmacokinetic modelling-based research is required to enable the design of robust dosing regimens for drugs affected by altered protein binding and the clinical consequences that these may have on therapy, using examples from the critical care area.
Abstract: Controversy reigns as to how protein binding changes alter the time course of unbound drug concentrations in patients. Given that the unbound concentration is responsible for drug efficacy and potential drug toxicity, this area is of significant interest to clinicians and academics worldwide. The present uncertainty means that many questions relating to this area exist, including “How important is protein binding?”, “Is protein binding always constant?”, “Do pH and temperature changes alter binding?” and “How do protein binding changes affect dosing requirements?”. In this paper, we seek to address these questions and consider the data associated with altered pharmacokinetics in the presence of changes in protein binding and the clinical consequences that these may have on therapy, using examples from the critical care area. The published literature consistently indicates that a change in the protein binding and unbound concentrations of some drugs are common in certain specific patient groups such as the critically ill. Changes in pharmacokinetic parameters, including clearance and apparent volume of distribution (Vd), may be dramatic. Drugs with high protein binding, high intrinsic clearance (e.g. clearance by glomerular filtration) and where dosing is not titrated to effect are most likely to be affected in a clinical context. Drugs such as highly protein bound antibacterials with multiple half-lives within a dosing interval and that have some level of renal clearance, such as ertapenem, teicoplanin, ceftriaxone and flucloxacillin, are commonly affected. In response to these challenges, clinicians need to adapt dosing regimens rationally based on the pharmacokinetic/pharmacodynamic characteristics of the drug. We propose that further pharmacokinetic modelling-based research is required to enable the design of robust dosing regimens for drugs affected by altered protein binding.

Journal ArticleDOI
TL;DR: Performing ab initio DFT+U molecular dynamics calculations of cluster models in explicit water solution, insight is provided into the pathways for oxygen evolution of a cobalt-based catalyst (CoCat) and suggests interesting similarities between the CoCat and the Mn4Ca-oxo oxygen evolving complex of photosystem II.
Abstract: The in-depth understanding of the molecular mechanisms regulating the water oxidation catalysis is of key relevance for the rationalization and the design of efficient oxygen evolution catalysts based on earth-abundant transition metals. Performing ab initio DFT+U molecular dynamics calculations of cluster models in explicit water solution, we provide insight into the pathways for oxygen evolution of a cobalt-based catalyst (CoCat). The fast motion of protons at the CoCat/water interface and the occurrence of cubane-like Co-oxo units at the catalyst boundaries are the keys to unlock the fast formation of O–O bonds. Along the resulting pathways, we identified the formation of Co(IV)-oxyl species as the driving ingredient for the activation of the catalytic mechanism, followed by their geminal coupling with O atoms coordinated by the same Co. Concurrent nucleophilic attack of water molecules coming directly from the water solution is discouraged by high activation barriers. The achieved results suggest also...

Journal ArticleDOI
TL;DR: The focus of this review paper is on the influence of DFs (inulin, fructo-oligofructose, β-glucans, arabinoxylans and resistant starch) supplementation on the quality and nutritional aspects of common foods containing cereals- pasta, bread, muffins/cakes and extruded snacks.

Journal ArticleDOI
TL;DR: Solubility and mobility of As were increased by biochar addition to this soil, but uptake to plant was reduced, and toxicity-transfer risk was negligible, therefore leaching rather than food chain transfer appears the most probable immediate consequence of biochar added to As contaminated soils.

Journal ArticleDOI
Georges Aad, T. Abajyan1, Brad Abbott2, J. Abdallah3  +2863 moreInstitutions (179)
TL;DR: In this article, the authors measured the jet energy resolution using data recorded with the ATLAS detector in proton-proton collisions at root s = 7 TeV, which corresponds to an integrated luminosity of 35 pb(-1).
Abstract: The measurement of the jet energy resolution is presented using data recorded with the ATLAS detector in proton-proton collisions at root s = 7 TeV. The sample corresponds to an integrated luminosity of 35 pb(-1). Jets are reconstructed from energy deposits measured by the calorimeters and calibrated using different jet calibration schemes. The jet energy resolution is measured with two different in situ methods which are found to be in agreement within uncertainties. The total uncertainties on these measurements range from 20 % to 10 % for jets within vertical bar y vertical bar < 2.8 and with transverse momenta increasing from 30 GeV to 500 GeV. Overall, the Monte Carlo simulation of the jet energy resolution agrees with the data within 10 %.

Journal ArticleDOI
15 Feb 2013-Talanta
TL;DR: The aim of the present review is to give an overview of the most recent sample preparation and analytical approaches (such as pressurized liquid extraction, solid-phase microextraction, supercritical fluid extraction, etc.), to introduce such a topic to researchers who want to approach it for the first time.

Journal ArticleDOI
TL;DR: In this article, the effects of fluoxetine in comparison with other antidepressive agents for depression compared with tricyclics (TCAs), SSRIs, serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and newer agents, and other conventional and unconventional agents were evaluated.
Abstract: Background Depression is common in primary care and is associated with marked personal, social and economic morbidity, thus creating significant demands on service providers. The antidepressant fluoxetine has been studied in many randomised controlled trials (RCTs) in comparison with other conventional and unconventional antidepressants. However, these studies have produced conflicting findings. Other systematic reviews have considered selective serotonin reuptake inhibitor (SSRIs) as a group which limits the applicability of the findings for fluoxetine alone. Therefore, this review intends to provide specific and clinically useful information regarding the effects of fluoxetine for depression compared with tricyclics (TCAs), SSRIs, serotonin-noradrenaline reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs) and newer agents, and other conventional and unconventional agents. Objectives To assess the effects of fluoxetine in comparison with all other antidepressive agents for depression in adult individuals with unipolar major depressive disorder. Search methods We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Review Group Controlled Trials Register (CCDANCTR) to 11 May 2012. This register includes relevant RCTs from the Cochrane Central Register of Controlled Trials (CENTRAL) (all years), MEDLINE (1950 to date), EMBASE (1974 to date) and PsycINFO (1967 to date). No language restriction was applied. Reference lists of relevant papers and previous systematic reviews were handsearched. The pharmaceutical company marketing fluoxetine and experts in this field were contacted for supplemental data. Selection criteria All RCTs comparing fluoxetine with any other AD (including non-conventional agents such as hypericum) for patients with unipolar major depressive disorder (regardless of the diagnostic criteria used) were included. For trials that had a cross-over design only results from the first randomisation period were considered. Data collection and analysis Data were independently extracted by two review authors using a standard form. Responders to treatment were calculated on an intention-to-treat basis: dropouts were always included in this analysis. When data on dropouts were carried forward and included in the efficacy evaluation, they were analysed according to the primary studies; when dropouts were excluded from any assessment in the primary studies, they were considered as treatment failures. Scores from continuous outcomes were analysed by including patients with a final assessment or with the last observation carried forward. Tolerability data were analysed by calculating the proportion of patients who failed to complete the study due to any causes and due to side effects or inefficacy. For dichotomous data, odds ratios (ORs) were calculated with 95% confidence intervals (CI) using the random-effects model. Continuous data were analysed using standardised mean differences (SMD) with 95% CI. Main results A total of 171 studies were included in the analysis (24,868 participants). The included studies were undertaken between 1984 and 2012. Studies had homogenous characteristics in terms of design, intervention and outcome measures. The assessment of quality with the risk of bias tool revealed that the great majority of them failed to report methodological details, like the method of random sequence generation, the allocation concealment and blinding. Moreover, most of the included studies were sponsored by drug companies, so the potential for overestimation of treatment effect due to sponsorship bias should be considered in interpreting the results. Fluoxetine was as effective as the TCAs when considered as a group both on a dichotomous outcome (reduction of at least 50% on the Hamilton Depression Scale) (OR 0.97, 95% CI 0.77 to 1.22, 24 RCTs, 2124 participants) and a continuous outcome (mean scores at the end of the trial or change score on depression measures) (SMD 0.03, 95% CI -0.07 to 0.14, 50 RCTs, 3393 participants). On a dichotomous outcome, fluoxetine was less effective than dothiepin or dosulepin (OR 2.13, 95% CI 1.08 to 4.20; number needed to treat (NNT) = 6, 95% CI 3 to 50, 2 RCTs, 144 participants), sertraline (OR 1.37, 95% CI 1.08 to 1.74; NNT = 13, 95% CI 7 to 58, 6 RCTs, 1188 participants), mirtazapine (OR 1.46, 95% CI 1.04 to 2.04; NNT = 12, 95% CI 6 to 134, 4 RCTs, 600 participants) and venlafaxine (OR 1.29, 95% CI 1.10 to 1.51; NNT = 11, 95% CI 8 to 16, 12 RCTs, 3387 participants). On a continuous outcome, fluoxetine was more effective than ABT-200 (SMD -1.85, 95% CI -2.25 to -1.45, 1 RCT, 141 participants) and milnacipran (SMD -0.36, 95% CI -0.63 to -0.08, 2 RCTs, 213 participants); conversely, it was less effective than venlafaxine (SMD 0.10, 95% CI 0 to 0.19, 13 RCTs, 3097 participants). Fluoxetine was better tolerated than TCAs considered as a group (total dropout OR 0.79, 95% CI 0.65 to 0.96; NNT = 20, 95% CI 13 to 48, 49 RCTs, 4194 participants) and was better tolerated in comparison with individual ADs, in particular amitriptyline (total dropout OR 0.62, 95% CI 0.46 to 0.85; NNT = 13, 95% CI 8 to 39, 18 RCTs, 1089 participants), and among the newer ADs ABT-200 (total dropout OR 0.18, 95% CI 0.08 to 0.39; NNT = 3, 95% CI 2 to 5, 1 RCT, 144 participants), pramipexole (total dropout OR 0.12, 95% CI 0.03 to 0.42, NNT = 3, 95% CI 2 to 5, 1 RCT, 105 participants), and reboxetine (total dropout OR 0.60, 95% CI 0.44 to 0.82, NNT = 9, 95% CI 6 to 24, 4 RCTs, 764 participants). Authors' conclusions The present study detected differences in terms of efficacy and tolerability between fluoxetine and certain ADs, but the clinical meaning of these differences is uncertain. Moreover, the assessment of quality with the risk of bias tool showed that the great majority of included studies failed to report details on methodological procedures. Of consequence, no definitive implications can be drawn from the studies' results. The better efficacy profile of sertraline and venlafaxine (and possibly other ADs) over fluoxetine may be clinically meaningful, as already suggested by other systematic reviews. In addition to efficacy data, treatment decisions should also be based on considerations of drug toxicity, patient acceptability and cost.

Journal ArticleDOI
Georges Aad1, T. Abajyan2, Brad Abbott3, J. Abdallah4  +2937 moreInstitutions (202)
TL;DR: In this article, a search for new particles decaying to large numbers (7 or more) of jets, with missing transverse momentum and no isolated electrons or muons, was presented for supersymmetry-inspired models where gluinos are pair produced.
Abstract: A search is presented for new particles decaying to large numbers (7 or more) of jets, with missing transverse momentum and no isolated electrons or muons. This analysis uses 20.3 fb−1 of pp collision data at s√=8 TeV collected by the ATLAS experiment at the Large Hadron Collider. The sensitivity of the search is enhanced by considering the number of b-tagged jets and the scalar sum of masses of large-radius jets in an event. No evidence is found for physics beyond the Standard Model. The results are interpreted in the context of various simplified supersymmetry-inspired models where gluinos are pair produced, as well as an mSUGRA/CMSSM model.

Journal ArticleDOI
T. Aaltonen1, S. Amerio, D. Amidei2, A. Anastassov3  +411 moreInstitutions (56)
TL;DR: In this article, the authors present new measurements of the inclusive forward-backward ttbar production asymmetry, AFB, and its dependence on several properties of the tt bar system.
Abstract: We present new measurements of the inclusive forward-backward ttbar production asymmetry, AFB, and its dependence on several properties of the ttbar system. The measurements are performed with the full Tevatron data set recorded with the CDF II detector during ppbar collisions at sqrt(s) = 1.96 TeV, corresponding to an integrated luminosity of 9.4 fb^(-1). We measure the asymmetry using the rapidity difference Delta-y=y_(t)-y_(tbar). Parton-level results are derived, yielding an inclusive asymmetry of 0.164+/-0.047 (stat + syst). We observe a linear dependence of AFB on the top-quark pair mass M(ttbar) and the rapidity difference |Delta-y| at detector and parton levels. Assuming the standard model, the probabilities to observe the measured values or larger for the detector-level dependencies are 7.4*10^(-3) and 2.2*10^(-3) for M(ttbar) and |Delta-y| respectively. Lastly, we study the dependence of the asymmetry on the transverse momentum of the ttbar system at the detector level. These results are consistent with previous lower-precision measurements and provide additional quantification of the functional dependencies of the asymmetry.