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Showing papers by "Charles University in Prague published in 2007"


Proceedings ArticleDOI
25 Jun 2007
TL;DR: An open-source toolkit for statistical machine translation whose novel contributions are support for linguistically motivated factors, confusion network decoding, and efficient data formats for translation models and language models.
Abstract: We describe an open-source toolkit for statistical machine translation whose novel contributions are (a) support for linguistically motivated factors, (b) confusion network decoding, and (c) efficient data formats for translation models and language models. In addition to the SMT decoder, the toolkit also includes a wide variety of tools for training, tuning and applying the system to many translation tasks.

6,008 citations


Journal ArticleDOI
12 Apr 2007-Nature
TL;DR: Previous two-dimensional electronic spectroscopy investigations of the FMO bacteriochlorophyll complex are extended, and direct evidence is obtained for remarkably long-lived electronic quantum coherence playing an important part in energy transfer processes within this system is obtained.
Abstract: Photosynthesis provides the primary energy source for almost all life on Earth. One of its remarkable features is the efficiency with which energy is transferred within the light harvesting complexes comprising the photosynthetic apparatus. Suspicions that quantum trickery might be involved in the energy transfer processes at the core of photosynthesis are now confirmed by a new spectroscopic study. The study reveals electronic quantum beats characteristic of wavelike energy motion within the bacteriochlorophyll complex from the green sulphur bacterium Chlorobium tepidum. This wavelike characteristic of the energy transfer process can explain the extreme efficiency of photosynthesis, in that vast areas of phase space can be sampled effectively to find the most efficient path for energy transfer. A spectroscopic study has directly monitored the quantum beating arising from remarkably long-lived electronic quantum coherence in a bacteriochlorophyll complex. This wavelike characteristic of the energy transfer process can explain the extreme efficiency of photosynthesis, in that vast areas of phase space can be sampled effectively to find the most efficient path for energy transfer. Photosynthetic complexes are exquisitely tuned to capture solar light efficiently, and then transmit the excitation energy to reaction centres, where long term energy storage is initiated. The energy transfer mechanism is often described by semiclassical models that invoke ‘hopping’ of excited-state populations along discrete energy levels1,2. Two-dimensional Fourier transform electronic spectroscopy3,4,5 has mapped6 these energy levels and their coupling in the Fenna–Matthews–Olson (FMO) bacteriochlorophyll complex, which is found in green sulphur bacteria and acts as an energy ‘wire’ connecting a large peripheral light-harvesting antenna, the chlorosome, to the reaction centre7,8,9. The spectroscopic data clearly document the dependence of the dominant energy transport pathways on the spatial properties of the excited-state wavefunctions of the whole bacteriochlorophyll complex6,10. But the intricate dynamics of quantum coherence, which has no classical analogue, was largely neglected in the analyses—even though electronic energy transfer involving oscillatory populations of donors and acceptors was first discussed more than 70 years ago11, and electronic quantum beats arising from quantum coherence in photosynthetic complexes have been predicted12,13 and indirectly observed14. Here we extend previous two-dimensional electronic spectroscopy investigations of the FMO bacteriochlorophyll complex, and obtain direct evidence for remarkably long-lived electronic quantum coherence playing an important part in energy transfer processes within this system. The quantum coherence manifests itself in characteristic, directly observable quantum beating signals among the excitons within the Chlorobium tepidum FMO complex at 77 K. This wavelike characteristic of the energy transfer within the photosynthetic complex can explain its extreme efficiency, in that it allows the complexes to sample vast areas of phase space to find the most efficient path.

2,981 citations


Journal ArticleDOI
Sabeeha S. Merchant1, Simon E. Prochnik2, Olivier Vallon3, Elizabeth H. Harris4, Steven J. Karpowicz1, George B. Witman5, Astrid Terry2, Asaf Salamov2, Lillian K. Fritz-Laylin6, Laurence Maréchal-Drouard7, Wallace F. Marshall8, Liang-Hu Qu9, David R. Nelson10, Anton A. Sanderfoot11, Martin H. Spalding12, Vladimir V. Kapitonov13, Qinghu Ren, Patrick J. Ferris14, Erika Lindquist2, Harris Shapiro2, Susan Lucas2, Jane Grimwood15, Jeremy Schmutz15, Pierre Cardol3, Pierre Cardol16, Heriberto Cerutti17, Guillaume Chanfreau1, Chun-Long Chen9, Valérie Cognat7, Martin T. Croft18, Rachel M. Dent6, Susan K. Dutcher19, Emilio Fernández20, Hideya Fukuzawa21, David González-Ballester22, Diego González-Halphen23, Armin Hallmann, Marc Hanikenne16, Michael Hippler24, William Inwood6, Kamel Jabbari25, Ming Kalanon26, Richard Kuras3, Paul A. Lefebvre11, Stéphane D. Lemaire27, Alexey V. Lobanov17, Martin Lohr28, Andrea L Manuell29, Iris Meier30, Laurens Mets31, Maria Mittag32, Telsa M. Mittelmeier33, James V. Moroney34, Jeffrey L. Moseley22, Carolyn A. Napoli33, Aurora M. Nedelcu35, Krishna K. Niyogi6, Sergey V. Novoselov17, Ian T. Paulsen, Greg Pazour5, Saul Purton36, Jean-Philippe Ral7, Diego Mauricio Riaño-Pachón37, Wayne R. Riekhof, Linda A. Rymarquis38, Michael Schroda, David B. Stern39, James G. Umen14, Robert D. Willows40, Nedra F. Wilson41, Sara L. Zimmer39, Jens Allmer42, Janneke Balk18, Katerina Bisova43, Chong-Jian Chen9, Marek Eliáš44, Karla C Gendler33, Charles R. Hauser45, Mary Rose Lamb46, Heidi K. Ledford6, Joanne C. Long1, Jun Minagawa47, M. Dudley Page1, Junmin Pan48, Wirulda Pootakham22, Sanja Roje49, Annkatrin Rose50, Eric Stahlberg30, Aimee M. Terauchi1, Pinfen Yang51, Steven G. Ball7, Chris Bowler25, Carol L. Dieckmann33, Vadim N. Gladyshev17, Pamela J. Green38, Richard A. Jorgensen33, Stephen P. Mayfield29, Bernd Mueller-Roeber37, Sathish Rajamani30, Richard T. Sayre30, Peter Brokstein2, Inna Dubchak2, David Goodstein2, Leila Hornick2, Y. Wayne Huang2, Jinal Jhaveri2, Yigong Luo2, Diego Martinez2, Wing Chi Abby Ngau2, Bobby Otillar2, Alexander Poliakov2, Aaron Porter2, Lukasz Szajkowski2, Gregory Werner2, Kemin Zhou2, Igor V. Grigoriev2, Daniel S. Rokhsar6, Daniel S. Rokhsar2, Arthur R. Grossman22 
University of California, Los Angeles1, United States Department of Energy2, University of Paris3, Duke University4, University of Massachusetts Medical School5, University of California, Berkeley6, Centre national de la recherche scientifique7, University of California, San Francisco8, Sun Yat-sen University9, University of Tennessee Health Science Center10, University of Minnesota11, Iowa State University12, Genetic Information Research Institute13, Salk Institute for Biological Studies14, Stanford University15, University of Liège16, University of Nebraska–Lincoln17, University of Cambridge18, Washington University in St. Louis19, University of Córdoba (Spain)20, Kyoto University21, Carnegie Institution for Science22, National Autonomous University of Mexico23, University of Münster24, École Normale Supérieure25, University of Melbourne26, University of Paris-Sud27, University of Mainz28, Scripps Research Institute29, Ohio State University30, University of Chicago31, University of Jena32, University of Arizona33, Louisiana State University34, University of New Brunswick35, University College London36, University of Potsdam37, Delaware Biotechnology Institute38, Boyce Thompson Institute for Plant Research39, Macquarie University40, Oklahoma State University Center for Health Sciences41, İzmir University of Economics42, Academy of Sciences of the Czech Republic43, Charles University in Prague44, St. Edward's University45, University of Puget Sound46, Hokkaido University47, Tsinghua University48, Washington State University49, Appalachian State University50, Marquette University51
12 Oct 2007-Science
TL;DR: Analyses of the Chlamydomonas genome advance the understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.
Abstract: Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the approximately 120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella.

2,554 citations


Journal ArticleDOI
TL;DR: In this article, the authors investigated the combination treatment of the humanised anti-VEGF monoclonal antibody bevacizumab with interferon alfa, and reported a significant improvement in progression-free survival.

2,167 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: Rosuvastatin did not reduce the primary outcome or the number of deaths from any cause in older patients with systolic heart failure, although the drug did reduce the numberOf cardiovascular hospitalizations and the drugdid not cause safety problems.
Abstract: As compared with the placebo group, patients in the rosuvastatin group had de- creased levels of low-density lipoprotein cholesterol (difference between groups, 45.0%; P<0.001) and of high-sensitivity C-reactive protein (difference between groups, 37.1%; P<0.001). During a median follow-up of 32.8 months, the primary outcome occurred in 692 patients in the rosuvastatin group and 732 in the placebo group (hazard ratio, 0.92; 95% confidence interval (CI), 0.83 to 1.02; P = 0.12), and 728 patients and 759 patients, respectively, died (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P = 0.31). There were no significant differences between the two groups in the coronary outcome or death from cardiovascular causes. In a prespecified secondary analysis, there were fewer hospitalizations for cardiovascular causes in the rosuvastatin group (2193) than in the placebo group (2564) (P<0.001). No excessive episodes of muscle-related or other adverse events occurred in the rosuvastatin group. Conclusions Rosuvastatin did not reduce the primary outcome or the number of deaths from any cause in older patients with systolic heart failure, although the drug did reduce the number of cardiovascular hospitalizations. The drug did not cause safety problems. (ClinicalTrials.gov number, NCT00206310.)

1,355 citations


Journal ArticleDOI
TL;DR: Four protocols for sample preparation (suspensions of intact cell nuclei) and the analysis of nuclear DNA amounts using FCM are presented and the most frequent problems encountered with plant material such as the interference of secondary metabolites are described.
Abstract: Flow cytometry (FCM) using DNA-selective fluorochromes is now the prevailing method for the measurement of nuclear DNA content in plants. Ease of sample preparation and high sample throughput make it generally better suited than other methods such as Feulgen densitometry to estimate genome size, level of generative polyploidy, nuclear replication state and endopolyploidy (polysomaty). Here we present four protocols for sample preparation (suspensions of intact cell nuclei) and describe the analysis of nuclear DNA amounts using FCM. We consider the chemicals and equipment necessary, the measurement process, data analysis, and describe the most frequent problems encountered with plant material such as the interference of secondary metabolites. The purpose and requirement of internal and external standardization are discussed. The importance of using a correct terminology for DNA amounts and genome size is underlined, and its basic principles are explained.

1,143 citations


Journal ArticleDOI
01 Sep 2007-Gut
TL;DR: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn’s disease naive to anti-TNF treatment in a follow-on randomised controlled trial.
Abstract: Background: Adalimumab induced clinical remission after four weeks in patients with active Crohn’s disease in the CLASSIC I trial. Objective: To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn’s disease in a follow-on randomised controlled trial (CLASSIC II). Methods: In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re-randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week. With non-response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI Results: Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p Conclusions: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn’s disease naive to anti-TNF treatment.

926 citations


Journal ArticleDOI
David P. Schmitt1, Jüri Allik2, Robert R. McCrae3, Verónica Benet-Martínez4, Lidia Alcalay5, Lara Ault6, Ivars Austers7, Kevin Bennett8, Gabriel Bianchi9, Fredric Boholst10, Mary Ann Borg Cunen11, Johan Braeckman12, Edwin G. Brainerd13, Leo Gerard A. Caral10, Gabrielle Caron14, María Martina Casullo15, Michael Cunningham6, Ikuo Daibo16, Charlotte J. S. De Backer12, Eros De Souza17, Rolando Díaz-Loving18, Glaucia Ribeiro Starling Diniz19, Kevin Durkin20, Marcela Echegaray21, Ekin Eremsoy22, Harald A. Euler23, Ruth Falzon11, Maryanne L. Fisher24, Dolores Foley25, Douglas P. Fry26, Sirspa Fry26, M. Arif Ghayur27, Debra L. Golden28, Karl Grammer, Liria Grimaldi29, Jamin Halberstadt30, Shamsul Haque31, Dora Herrera21, Janine Hertel32, Heather Hoffmann33, Danica Hooper25, Zuzana Hradilekova34, Jasna Hudek-Kene-Evi35, Jas Laile Suzana Binti Jaafar36, Margarita Jankauskaite37, Heidi Kabangu-Stahel, Igor Kardum35, Brigitte Khoury38, Hayrran Kwon39, Kaia Laidra5, Anton Laireiter40, Dustin Lakerveld41, Ada Lampert, Mary Anne Lauri11, Marguerite Lavallée14, Suk Jae Lee42, Luk Chung Leung43, Kenneth D. Locke44, Vance Locke20, Ivan Lukšík9, Ishmael Magaisa45, Dalia Marcinkeviciene37, André Mata46, Rui Mata46, Barry Mccarthy47, Michael E. Mills48, Nhlanhla Mkhize49, João Manuel Moreira46, Sérgio Moreira46, Miguel Moya50, M. Munyae51, Patricia Noller25, Adrian Opre52, Alexia Panayiotou53, Nebojša Petrović54, Karolien Poels12, Miroslav Popper9, Maria Poulimenou55, Volodymyr P'yatokh, Michel Raymond56, Ulf-Dietrich Reips57, Susan E. Reneau58, Sofía Rivera-Aragón18, Wade C. Rowatt59, Willibald Ruch60, Velko S. Rus61, Marilyn P. Safir62, Sonia Salas63, Fabio Sambataro29, Kenneth Sandnabba26, Marion K. Schulmeyer, Astrid Schütz32, Tullio Scrimali29, Todd K. Shackelford64, Phillip R. Shaver65, Francis J Sichona66, Franco Simonetti2, Tilahun Sineshaw67, Tom Speelman12, Spyros Spyrou68, H. Canan Sümer69, Nebi Sümer69, Marianna Supekova9, Tomasz Szlendak70, Robin Taylor71, Bert Timmermans72, William Tooke73, Ioannis Tsaousis74, F. S.K. Tungaraza66, Griet Vandermassen12, Tim Vanhoomissen72, Frank Van Overwalle72, Ine Vanwesenbeeck, Paul L. Vasey75, João Veríssimo46, Martin Voracek76, Wendy W.N. Wan77, Ta Wei Wang78, Peter Weiss79, Andik Wijaya, Liesbeth Woertman41, Gahyun Youn80, Agata Zupanèiè61, Mithila B. Sharan81 
Bradley University1, University of Tartu2, National Institutes of Health3, University of California4, Pontifical Catholic University of Chile5, University of Louisville6, University of Latvia7, Pennsylvania State University8, Slovak Academy of Sciences9, University of San Carlos10, University of Malta11, Ghent University12, Clemson University13, Laval University14, University of Buenos Aires15, Osaka University16, Illinois State University17, National Autonomous University of Mexico18, University of Brasília19, University of Western Australia20, University of Lima21, Boğaziçi University22, University of Kassel23, York University24, University of Queensland25, Åbo Akademi University26, Al Akhawayn University27, University of Hawaii at Manoa28, University of Catania29, University of Otago30, University of Dhaka31, Chemnitz University of Technology32, Knox College33, Comenius University in Bratislava34, University of Rijeka35, University of Malaya36, Vilnius University37, American University of Beirut38, Kwangju Health College39, University of Salzburg40, Utrecht University41, National Computerization Agency42, City University of Hong Kong43, University of Idaho44, University of Zimbabwe45, University of Lisbon46, University of Central Lancashire47, Loyola Marymount University48, University of KwaZulu-Natal49, University of Granada50, University of Botswana51, Babeș-Bolyai University52, University of Cyprus53, University of Belgrade54, KPMG55, University of Montpellier56, University of Zurich57, University of Alabama58, Baylor University59, Queen's University Belfast60, University of Ljubljana61, University of Haifa62, University of La Serena63, Florida Atlantic University64, University of California, Davis65, University of Dar es Salaam66, Ramapo College67, Cyprus College68, Middle East Technical University69, Nicolaus Copernicus University in Toruń70, University of the South Pacific71, Vrije Universiteit Brussel72, University at Albany, SUNY73, University of the Aegean74, University of Lethbridge75, University of Vienna76, University of Hong Kong77, Yuan Ze University78, Charles University in Prague79, Chonnam National University80, Indian Institutes of Technology81
TL;DR: The Big Five Inventory (BFI) is a self-report measure designed to assess the high-order personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness as discussed by the authors.
Abstract: The Big Five Inventory (BFI) is a self-report measure designed to assess the high-order personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness. As part of the International Sexuality Description Project, the BFI was translated from English into 28 languages and administered to 17,837 individuals from 56 nations. The resulting cross-cultural data set was used to address three main questions: Does the factor structure of the English BFI fully replicate across cultures? How valid are the BFI trait profiles of individual nations? And how are personality traits distributed throughout the world? The five-dimensional structure was robust across major regions of the world. Trait levels were related in predictable ways to self-esteem, sociosexuality, and national personality profiles. People from the geographic regions of South America and East Asia were significantly different in openness from those inhabiting other world regions. The discussion focuses on limitations of t...

876 citations


Journal ArticleDOI
TL;DR: In this article, the authors examine the biogeography and the determinants of composition and structure of riparian vegetation in temperate and subtropical regions and conceptualize the components of resilience in these systems.
Abstract: Rivers are conduits for materials and energy; this, the frequent and intense disturbances that these systems experience, and their narrow, linear nature, create problems for conservation of biodiversity and ecosystem functioning in the face of increasing human influence. In most parts of the world, riparian zones are highly modified. Changes caused by alien plants — or environmental changes that facilitate shifts in dominance creating novel ecosystems — are often important agents of perturbation in these systems. Many restoration projects are underway. Objective frameworks based on an understanding of biogeographical processes at different spatial scales (reach, segment, catchment), the specific relationships between invasive plants and resilience and ecosystem functioning, and realistic endpoints are needed to guide sustainable restoration initiatives. This paper examines the biogeography and the determinants of composition and structure of riparian vegetation in temperate and subtropical regions and conceptualizes the components of resilience in these systems. We consider changes to structure and functioning caused by, or associated with, alien plant invasions, in particular those that lead to breached abiotic- or biotic thresholds. These pose challenges when formulating restoration programmes. Pervasive and escalating human-mediated changes to multiple factors and at a range of scales in riparian environments demand innovative and pragmatic approaches to restoration. The application of a new framework accommodating such complexity is demonstrated with reference to a hypothetical riparian ecosystem under three scenarios: (1) system unaffected by invasive plants; (2) system initially uninvaded, but with flood-generated incursion of alien plants and escalating invasion-driven alteration; and (3) system affected by both invasions and engineering interventions. The scheme has been used to derive a decision-making framework for restoring riparian zones in South Africa and could guide similar initiatives in other parts of the world.

849 citations


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
Felix Aharonian1, A. G. Akhperjanian1, A. R. Bazer-Bachi, M. Beilicke1, Wystan Benbow1, David Berge1, Konrad Bernlöhr1, Catherine Boisson, O. Bolz1, V. Borrel2, Ilana M. Braun1, E. Brion, A. M. Brown3, Rolf Bühler1, I. Büsching4, Timothé Boutelier5, Svenja Carrigan1, P. M. Chadwick3, L.-M. Chounet, G. Coignet, R. Cornils1, Luigi Costamante1, B. Degrange, Hugh Dickinson3, A. Djannati-Ataï, L. O'Connor-Drury6, Guillaume Dubus, Kathrin Egberts1, Dimitrios Emmanoulopoulos7, P. Espigat, C. Farnier, F. Feinstein, E. Ferrero1, A. Fiasson, G. Fontaine, Seb. Funk1, M. Fuling1, Y. A. Gallant, B. Giebels, J.F. Glicenstein, B. Glück8, P. Goret, C. Hadjichristidis3, D. Hauser1, M. Hauser7, G. Heinzelmann9, Gilles Henri5, German Hermann1, Jim Hinton1, A. Hoffmann10, Werner Hofmann1, M. Holleran4, S. Hoppe1, Dieter Horns1, A. Jacholkowska, O. C. de Jager4, Eckhard Kendziorra10, M. Kerschhaggl11, B. Khélifi, Nu. Komin, K. Kosack1, G. Lamanna, I. J. Latham3, R. Le Gallou3, Anne Lemiere, M. Lemoine-Goumard, Thomas Lohse11, Jean Michel Martin, Olivier Martineau-Huynh, A. Marcowith, Conor Masterson1, Gilles Maurin, T. J. L. McComb3, Emmanuel Moulin, M. de Naurois1, D. Nedbal1, S. J. Nolan3, A. Noutsos12, J.-P. Olive, K. J. Orford1, J. L. Osborne1, M. Panter1, Guy Pelletier5, P.-O. Petrucci, S. Pita, G. Pühlhofer1, Michael Punch, S. Ranchon, B. C. Raubenheimer4, M. Raue1, S. M. Rayner3, A. Reimer5, Olaf Reimer5, J. Ripken9, L. Rob13, L. Rolland, S. Rosier-Lees, Gavin Rowell1, V. Sahakian14, Andrea Santangelo1, L. Saugé5, S. Schlenker11, Reinhard Schlickeiser15, R. Schröder15, U. Schwanke11, S. Schwarzburg10, S. Schwemmer7, A. Shalchi15, Helene Sol, D. Spangler3, Felix Spanier5, R. Steenkamp16, C. Stegmann8, G. Superina, P. H. Tam7, J. P. Tavernet, Regis Terrier, M. Tluczykont, C. van Eldik1, G. Vasileiadis, Christo Venter4, J. P. Vialle, P. Vincent, Heinrich J. Völk1, Stefan Wagner7, Martin Ward3 
TL;DR: In this paper, the average flux observed during an extreme gamma-ray outburst is I(>200 GeV) = (1.72$\pm$$0.05_{\rm stat}
Abstract: The high-frequency peaked BL Lac PKS 2155-304 at redshift z=0.116 is a well-known VHE (>100 GeV) gamma-ray emitter. Since 2002 its VHE flux has been monitored using the H.E.S.S. stereoscopic array of imaging atmospheric-Cherenkov telescopes in Namibia. During the July 2006 dark period, the average VHE flux was measured to be more than ten times typical values observed from the object. This article focuses solely on an extreme gamma-ray outburst detected in the early hours of July 28, 2006 (MJD 53944). The average flux observed during this outburst is I(>200 GeV) = (1.72$\pm$$0.05_{\rm stat}$$\pm$$0.34_{\rm syst}$) $\times$ 10$^{-9}$ cm$^{-2}$ s$^{-1}$, corresponding to ~7 times the flux, I(>200 GeV), observed from the Crab Nebula. Peak fluxes are measured with one-minute time scale resolution at more than twice this average value. Variability is seen up to ~600 s in the Fourier power spectrum, and well-resolved bursts varying on time scales of ~200 seconds are observed. There are no strong indications for spectral variability within the data. Assuming the emission region has a size comparable to the Schwarzschild radius of a ~10$^9 M_\odot$ black hole, Doppler factors greater than 100 are required to accommodate the observed variability time scales.

Journal ArticleDOI
12 Jan 2007-Science
TL;DR: The genome sequence of the protist Trichomonas vaginalis predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
Abstract: We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the similar to 160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.

Journal ArticleDOI
01 Apr 2007-Leukemia
TL;DR: The European Study Group on MRD detection in ALL (ESG-MRD-ALL), consisting of 30 MRD-PCR laboratories worldwide, has developed guidelines for the interpretation of real-time quantitative PCR-based MRD data.
Abstract: Most modern treatment protocols for acute lymphoblastic leukaemia (ALL) include the analysis of minimal residual disease (MRD). To ensure comparable MRD results between different MRD-polymerase chain reaction (PCR) laboratories, standardization and quality control are essential. The European Study Group on MRD detection in ALL (ESG-MRD-ALL), consisting of 30 MRD-PCR laboratories worldwide, has developed guidelines for the interpretation of real-time quantitative PCR-based MRD data. The application of these guidelines ensures identical interpretation of MRD data between different laboratories of the same MRD-based clinical protocol. Furthermore, the ESG-MRD-ALL guidelines will facilitate the comparison of MRD data obtained in different treatment protocols, including those with new drugs.

Journal ArticleDOI
05 Dec 2007-Allergy
TL;DR: This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education that are recommended for clinical practice in Europe as well as in North America.
Abstract: Asthma is the leading chronic disease among children in most industrialized countries. However, the evidence base on specific aspects of pediatric asthma, including therapeutic strategies, is limited and no recent international guidelines have focused exclusively on pediatric asthma. As a result, the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma and Immunology nominated expert teams to find a consensus to serve as a guideline for clinical practice in Europe as well as in North America. This consensus report recommends strategies that include pharmacological treatment, allergen and trigger avoidance and asthma education. The report is part of the PRACTALL initiative, which is endorsed by both academies.


Journal ArticleDOI
TL;DR: In this article, a double-blind, placebo-controlled trial was conducted to see whether agalsidase beta delayed the onset of a composite clinical outcome of renal, cardiovascular, and cerebrovascular events and death in patients with advanced Fabry disease.
Abstract: Background Fabry disease (alpha-galactosidase A deficiency) is a rare, X-linked lysosomal storage disorder that can cause early death from renal, cardiac, and cerebrovascular involvement. Objective To see whether agalsidase beta delays the onset of a composite clinical outcome of renal, cardiovascular, and cerebrovascular events and death in patients with advanced Fabry disease. Design Randomized (2:1 treatment-to-placebo randomization), double-blind, placebo-controlled trial. Setting 41 referral centers in 9 countries. Patients 82 adults with mild to moderate kidney disease; 74 of whom were protocol-adherent. Intervention Intravenous infusion of agalsidase beta (1 mg per kg of body weight) or placebo every 2 weeks for up to 35 months (median, 18.5 months). Measurements The primary end point was the time to first clinical event (renal, cardiac, or cerebrovascular event or death). Six patients withdrew before reaching an end point: 3 to receive commercial therapy and 3 due to positive or inconclusive serum IgE or skin test results. Three patients assigned to agalsidase beta elected to transition to open-label treatment before reaching an end point. Results Thirteen (42%) of the 31 patients in the placebo group and 14 (27%) of the 51 patients in the agalsidase-beta group experienced clinical events. Primary intention-to-treat analysis that adjusted for an imbalance in baseline proteinuria showed that, compared with placebo, agalsidase beta delayed the time to first clinical event (hazard ratio, 0.47 [95% CI, 0.21 to 1.03]; P = 0.06). Secondary analyses of protocol-adherent patients showed similar results (hazard ratio, 0.39 [CI, 0.16 to 0.93]; P = 0.034). Ancillary subgroup analyses found larger treatment effects in patients with baseline estimated glomerular filtration rates greater than 55 mL/min per 1.73 m2 (hazard ratio, 0.19 [CI, 0.05 to 0.82]; P = 0.025) compared with 55 mL/min per 1.73 m2 or less (hazard ratio, 0.85 [CI, 0.32 to 2.3]; P = 0.75) (formal test for interaction, P = 0.09). Most treatment-related adverse events were mild or moderate infusion-associated reactions, reported by 55% of patients in the agalsidase-beta group and 23% of patients in the placebo group. Limitations The study sample was small. Only one third of the patients experienced clinical events, and some patients withdrew before experiencing any event. Conclusions Agalsidase-beta therapy slowed progression to the composite clinical outcome of renal, cardiac, and cerebrovascular complications and death compared with placebo in patients with advanced Fabry disease. Therapeutic intervention before irreversible organ damage may provide greater clinical benefit.

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A. Adare1, S. Afanasiev2, Christine Angela Aidala3, N. N. Ajitanand4  +442 moreInstitutions (48)
TL;DR: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured electrons with 0.3 < p(T) < 9 GeV/c at midrapidity (y < 0.35) from heavy-flavor (charm and bottom) decays in Au + Au collisions at root s(NN) = 200 GeV as mentioned in this paper.
Abstract: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured electrons with 0.3 < p(T) < 9 GeV/c at midrapidity (y < 0.35) from heavy-flavor (charm and bottom) decays in Au + Au collisions at root s(NN) = 200 GeV. The nuclear modification factor R-AA relative to p + p collisions shows a strong suppression in central Au + Au collisions, indicating substantial energy loss of heavy quarks in the medium produced at RHIC energies. A large azimuthal anisotropy v(2) with respect to the reaction plane is observed for 0.5 < p(T) < 5 GeV/c indicating substantial heavy-flavor elliptic flow. Both R-AA and v(2) show a p(T) dependence different from those of neutral pions. A comparison to transport models which simultaneously describe R-AA(p(T)) and v(2)(p(T)) suggests that the viscosity to entropy density ratio is close to the conjectured quantum lower bound, i.e., near a perfect fluid.

Journal ArticleDOI
A. Adare1, S. Afanasiev2, Christine Angela Aidala3, N. N. Ajitanand4  +438 moreInstitutions (46)
TL;DR: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured J/psi production for rapidities -2.2 < y < 2.2 in Au+Au collisions at root s(NN)=200 GeV as mentioned in this paper.
Abstract: The PHENIX experiment at the BNL Relativistic Heavy Ion Collider (RHIC) has measured J/psi production for rapidities -2.2 < y < 2.2 in Au+Au collisions at root s(NN)=200 GeV. The J/psi invariant yield and nuclear modification factor R-AA as a function of centrality, transverse momentum, and rapidity are reported. A suppression of J/psi relative to binary collision scaling of proton-proton reaction yields is observed. Models which describe the lower energy J/psi data at the CERN Super Proton Synchrotron invoking only J/psi destruction based on the local medium density predict a significantly larger suppression at RHIC and more suppression at midrapidity than at forward rapidity. Both trends are contradicted by our data.

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TL;DR: This Review revisits and update previous recommendations on natalizumab for treatment of patients with RRMS, based on additional long-term follow-up of clinical studies and post-marketing observations, including appropriate patient selection and management recommendations.
Abstract: Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very active disease. The expected benefits of natalizumab treatment have to be weighed against risks, especially the rare but serious adverse event of progressive multifocal leukoencephalopathy. In this Review, we revisit and update previous recommendations on natalizumab for treatment of patients with RRMS, based on additional long-term follow-up of clinical studies and post-marketing observations, including appropriate patient selection and management recommendations.

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TL;DR: The results show that tip-localized ROS produced by a NOX enzyme is needed to sustain the normal rate of pollen tube growth and that this is likely to be a general mechanism in the control of tip growth of polarized plant cells.
Abstract: Tip-localized reactive oxygen species (ROS) were detected in growing pollen tubes by chloromethyl dichlorodihydrofluorescein diacetate oxidation, while tip-localized extracellular superoxide production was detected by nitroblue tetrazolium (NBT) reduction. To investigate the origin of the ROS we cloned a fragment of pollen specific tobacco NADPH oxidase (NOX) closely related to a pollen specific NOX from Arabidopsis. Transfection of tobacco pollen tubes with NOX-specific antisense oligodeoxynucleotides (ODNs) resulted in decreased amount of NtNOX mRNA, lower NOX activity and pollen tube growth inhibition. The ROS scavengers and the NOX inhibitor diphenylene iodonium chloride (DPI) inhibited growth and ROS formation in tobacco pollen tube cultures. Exogenous hydrogen peroxide (H2O2) rescued the growth inhibition caused by NOX antisense ODNs. Exogenous CaCl2 increased NBT reduction at the pollen tube tip, suggesting that Ca2+ increases the activity of pollen NOX in vivo. The results show that tip-localized ROS produced by a NOX enzyme is needed to sustain the normal rate of pollen tube growth and that this is likely to be a general mechanism in the control of tip growth of polarized plant cells.

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TL;DR: In this paper, aniline and pyrrole have been oxidized with ammonium peroxydisulfate in aqueous solutions, in the presence of equimolar quantities of hydrochloric acid.

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TL;DR: The time elapsed between injury and operation should be minimised for patients in need of urgent surgical bleeding control, and patients presenting with haemorrhagic shock and an identified source of bleeding should undergo immediate surgical bleed control unless initial resuscitation measures are successful.
Abstract: Introduction Evidence-based recommendations can be made with respect to many aspects of the acute management of the bleeding trauma patient, which when implemented may lead to improved patient outcomes.

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TL;DR: In this article, fast magnetosonic waves, detected by Cluster 3, can accelerate electrons between ∼10 keV and a few MeV inside the outer radiation belt, which is required to explain electron flux increases in the outer Van Allen radiation belt during magnetic storms.
Abstract: [1] Local acceleration is required to explain electron flux increases in the outer Van Allen radiation belt during magnetic storms. Here we show that fast magnetosonic waves, detected by Cluster 3, can accelerate electrons between ∼10 keV and a few MeV inside the outer radiation belt. Acceleration occurs via electron Landau resonance, and not Doppler shifted cyclotron resonance, due to wave propagation almost perpendicular to the ambient magnetic field. Using quasi-linear theory, pitch angle and energy diffusion rates are comparable to those for whistler mode chorus, suggesting that these waves are very important for local electron acceleration. Since pitch angle diffusion does not extend into the loss cone, these waves, on their own, are not important for loss to the atmosphere. We suggest that magnetosonic waves, which are generated by unstable proton ring distributions, are an important energy transfer process from the ring current to the Van Allen radiation belts.

Journal ArticleDOI
A. Adare1, S. Afanasiev2, Christine Angela Aidala3, N. N. Ajitanand4  +459 moreInstitutions (49)
TL;DR: In this paper, the scaling of elliptic flow (v(2) with eccentricity, system size, and transverse kinetic energy (KET) was shown to be compatible with hydrodynamic expansion of thermalized fluid.
Abstract: Differential measurements of elliptic flow (v(2)) for Au+Au and Cu+Cu collisions at root s(NN)=200 GeV are used to test and validate predictions from perfect fluid hydrodynamics for scaling of v(2) with eccentricity, system size, and transverse kinetic energy (KET). For KET equivalent to m(T)-m up to similar to 1 GeV the scaling is compatible with hydrodynamic expansion of a thermalized fluid. For large values of KET mesons and baryons scale separately. Quark number scaling reveals a universal scaling of v(2) for both mesons and baryons over the full KET range for Au+Au. For Au+Au and Cu+Cu the scaling is more pronounced in terms of KET, rather than transverse momentum.

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Felix Aharonian1, A. G. Akhperjanian1, A. R. Bazer-Bachi, M. Beilicke1, Wystan Benbow1, David Berge1, Konrad Bernlöhr1, Catherine Boisson, O. Bolz1, V. Borrel, Ilana M. Braun1, E. Brion, A. M. Brown2, Rolf Bühler1, I. Büsching3, Svenja Carrigan1, P. M. Chadwick2, L.-M. Chounet, G. Coignet, R. Cornils1, Luigi Costamante1, B. Degrange, Hugh Dickinson2, A. Djannati-Ataï, L. O'c. Drury4, Guillaume Dubus, Kathrin Egberts1, Dimitrios Emmanoulopoulos5, P. Espigat, F. Feinstein, E. Ferrero5, A. Fiasson, G. Fontaine, Seb. Funk6, Stefan Funk1, M. F¨ußling1, Y. A. Gallant, B. Giebels, J.F. Glicenstein, B. Glück7, P. Goret, C. Hadjichristidis2, D. Hauser1, M. Hauser5, G. Heinzelmann8, Gilles Henri, German Hermann1, Jim Hinton1, A. Hoffmann9, Werner Hofmann1, M. Holleran3, S. Hoppe1, Dieter Horns1, A. Jacholkowska, O. C. de Jager3, Eckhard Kendziorra9, M. Kerschhaggl6, B. Khélifi, Nu. Komin, A. Konopelko1, K. Kosack1, G. Lamanna, I. J. Latham2, R. Le Gallou2, Anne Lemiere, M. Lemoine-Goumard, Thomas Lohse6, Jean Michel Martin, Olivier Martineau-Huynh, A. Marcowith, Conor Masterson1, Gilles Maurin, T. J. L. McComb2, Emmanuel Moulin, M. de Naurois, D. Nedbal1, S. J. Nolan2, A. Noutsos2, J.-P. Olive, K. J. Orford1, J. L. Osborne1, M. Panter1, G. Pelletier, S. Pita, G. Pühlhofer1, Michael Punch, S. Ranchon, B. C. Raubenheimer3, M. Raue1, S. M. Rayner2, A. Reimer10, Olaf Reimer10, J. Ripken8, L. Rob11, L. Rolland, S. Rosier-Lees, Gavin Rowell1, V. Sahakian12, Andrea Santangelo1, L. Saugé, S. Schlenker6, Reinhard Schlickeiser10, R. Schröder10, U. Schwanke6, S. Schwarzburg9, S. Schwemmer5, A. Shalchi10, Helene Sol, D. Spangler2, Felix Spanier10, R. Steenkamp13, C. Stegmann7, G. Superina, P. H. Tam5, J. P. Tavernet, Regis Terrier, M. Tluczykont, C. van Eldik1, G. Vasileiadis, Christo Venter3, J. P. Vialle, P. Vincent, Heinrich J. Völk1, Stefan Wagner5, Martin Ward2 
TL;DR: The combined gamma-ray image of the 2004 and 2005 data reveals the morphology of RX J1713.7-3946 with unprecedented precision, as well as significantly increased statistics and energy coverage as compared to earlier 2003 & 2004 results.
Abstract: We present deep H.E.S.S. observations of the supernova remnant (SNR) RX J1713.7-3946. Combining data of three years - from 2003 to 2005 - we obtain significantly increased statistics and energy coverage as compared to earlier 2003 & 2004 results. The data are analysed separately for the different years. Very good agreement of the gamma-ray morphology and the differential spectra is found when comparing the three years. The combined gamma-ray image of the 2004 and 2005 data reveals the morphology of RX J1713.7-3946 with unprecedented precision. An angular resolution of 0.06 deg is achieved, revealing the detailed structure of the remnant. The combined spectrum of all three years extends over three orders of magnitude, with significant gamma-ray emission approaching 100 TeV. The cumulative significance above 30 TeV is 4.8 sigma, while for energies between 113 and 294 TeV an upper limit on the gamma-ray flux of 1.6 x 10^-16 cm^-2 s^-1 is obtained. The energy coverage of the H.E.S.S. data is presumably at the limit of present generation Cherenkov telescopes. The measurement of significant gamma-ray emission beyond 30 TeV formally implies the existence of primary particles of at least that energy. However, for realistic scenarios of very-high-energy gamma-ray production, the Inverse Compton scattering of very-high-energy electrons and pi^0 decay following inelastic proton-proton interactions, the measured gamma-ray energies imply that efficient acceleration of primary particles to energies exceeding 100 TeV is taking place in the shell of the SNR RX J1713.7-3946.

Journal ArticleDOI
TL;DR: Natalizumab has a sustained effect in preventing the formation of new lesions in patients with relapsing multiple sclerosis.
Abstract: Background: In a 2-year, placebo-controlled trial (the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis [AFFIRM] study), involving 942 patients with relapsing multiple sclerosis (MS), natalizumab significantly reduced the relapse rate by 68% and progression of sustained disability by 42% vs placebo. We report the effect of natalizumab on MRI measures from the AFFIRM study. Methods: The number and volume of gadolinium (Gd)-enhancing, new or enlarging T2-hyperintense, and new T1-hypointense lesions and brain parenchymal fraction were measured from annual scans obtained at baseline, 1 year, and 2 years. Results: Compared with placebo, natalizumab produced a 92% decrease in Gd-enhancing lesions (means 2.4 vs 0.2; p p p p p Conclusion: Natalizumab has a sustained effect in preventing the formation of new lesions in patients with relapsing multiple sclerosis.

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A. Aktas, Calin Alexa, V. P. Andreev, T. Anthonis1  +283 moreInstitutions (35)
TL;DR: In this article, a new set of diffractive parton distribution functions is obtained through a simultaneous fit to the diffractive inclusive and dijet cross sections, which allows for a precise determination of both diffractive quark and gluon distributions in the range 0.05 < zIP < 0.9.
Abstract: Differential dijet cross sections in diffractive deep-inelastic scattering are measured with the H1 detector at HERA using an integrated luminosity of 51.5 pb−1. The selected events are of the type ep → eXY , where the system X contains at least two jets and is well separated in rapidity from the low mass proton dissociation system Y . The dijet data are compared with QCD predictions at next-to-leading order based on diffractive parton distribution functions previously extracted from measurements of inclusive diffractive deepinelastic scattering. The prediction describes the dijet data well at low and intermediate zIP (the fraction of the momentum of the diffractive exchange carried by the parton entering the hard interaction) where the gluon density is well determined from the inclusive diffractive data, supporting QCD factorisation. A new set of diffractive parton distribution functions is obtained through a simultaneous fit to the diffractive inclusive and dijet cross sections. This allows for a precise determination of both the diffractive quark and gluon distributions in the range 0.05 < zIP < 0.9. In particular, the precision on the gluon density at high momentum fractions is improved compared to previous extractions.

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TL;DR: The incidence of persistent antibody positivity associated with natalizumab is 6%.
Abstract: Objective: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. Methods: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon β-1a [INFβ1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as “transiently positive” if they had detectable antibodies (≥0.5 μg/mL) at a single time point or “persistently positive” if they had antibodies at two or more time points ≥6 weeks apart. Results: In the AFFIRM study, antibodies were detected in 57 of 625 (9%) of natalizumab-treated patients: Twenty (3%) were transiently positive and 37 (6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression ( p ≤ 0.05), relapse rate ( p = 0.009), and MRI ( p ≤ 0.05) compared with antibody-negative patients. In transiently positive patients, full efficacy was achieved after approximately 6 months of treatment, the time when patients were becoming antibody negative. The incidence of infusion-related adverse events was significantly higher in persistently positive patients. Results of SENTINEL were similar to AFFIRM, except with regard to sustained disability progression; differences between persistently positive and antibody-negative patients were not statistically significant. Conclusions: The incidence of persistent antibody positivity associated with natalizumab is 6%. Reduced clinical efficacy is apparent in persistently positive patients. Patients with a suboptimal clinical response or persistent infusion-related adverse events should be considered for antibody testing. GLOSSARY: BLQ = below the limit of quantification; EDSS = Expanded Disability Status Scale; Gd+ = gadolinium enhancing; IFNβ1a = interferon β-1a; MS = multiple sclerosis; MSFC = multiple sclerosis functional composite; OD = optical density.

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TL;DR: It is hypothesized that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR), and the absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR Syndrome.
Abstract: Thrombocytopenia-absent radius (TAR) syndrome is characterized by hypomegakaryocytic thrombocytopenia and bilateral radial aplasia in the presence of both thumbs. Other frequent associations are congenital heart disease and a high incidence of cow's milk intolerance. Evidence for autosomal recessive inheritance comes from families with several affected individuals born to unaffected parents, but several other observations argue for a more complex pattern of inheritance. In this study, we describe a common interstitial microdeletion of 200 kb on chromosome 1q21.1 in all 30 investigated patients with TAR syndrome, detected by microarray-based comparative genomic hybridization. Analysis of the parents revealed that this deletion occurred de novo in 25% of affected individuals. Intriguingly, inheritance of the deletion along the maternal line as well as the paternal line was observed. The absence of this deletion in a cohort of control individuals argues for a specific role played by the microdeletion in the pathogenesis of TAR syndrome. We hypothesize that TAR syndrome is associated with a deletion on chromosome 1q21.1 but that the phenotype develops only in the presence of an additional as-yet-unknown modifier (mTAR).