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Showing papers by "University of Udine published in 2007"


Journal ArticleDOI
TL;DR: This work proposes the first unified hierarchical classification system, designed on the basis of the transposition mechanism, sequence similarities and structural relationships, that can be easily applied by non-experts.
Abstract: Our knowledge of the structure and composition of genomes is rapidly progressing in pace with their sequencing. The emerging data show that a significant portion of eukaryotic genomes is composed of transposable elements (TEs). Given the abundance and diversity of TEs and the speed at which large quantities of sequence data are emerging, identification and annotation of TEs presents a significant challenge. Here we propose the first unified hierarchical classification system, designed on the basis of the transposition mechanism, sequence similarities and structural relationships, that can be easily applied by non-experts. The system and nomenclature is kept up to date at the WikiPoson web site.

2,425 citations


Journal ArticleDOI
Justin Albert1, E. Aliu2, H. Anderhub3, P. Antoranz4  +146 moreInstitutions (18)
TL;DR: The MAGIC telescope was used to observe the blazar Markarian 501 (Mrk 501) at energies above 100 GeV from May through July 2005 as mentioned in this paper, and the high sensitivity of the instrument enabled the determination of the flux and spectrum of the source on a night-by-night basis.
Abstract: The blazar Markarian 501 (Mrk 501) was observed at energies above 100 GeV with the MAGIC telescope from May through July 2005. The high sensitivity of the instrument enabled the determination of the flux and spectrum of the source on a night-by-night basis. Throughout our observational campaign, the flux from Mrk 501 was found to vary by an order of magnitude, and to be correlated with spectral changes. Intra-night flux variability with flux-doubling times down to 2 minutes was also observed. The strength of variability increased with the energy of the {gamma}-ray photons. The energy spectra were found to harden significantly with increasing flux, and a spectral peak clearly showed up during very active states. The position of the spectral peak seems to be correlated with the source luminosity.

606 citations


Journal ArticleDOI
11 Aug 2007-Planta
TL;DR: Results demonstrate that manipulation of abiotic stress through applied water deficits not only modulates compositional changes during berry ripening, but also alters the timing of particular aspects of the ripening process.
Abstract: Water deficits consistently promote higher concentrations of anthocyanins in red winegrapes and their wines. However, controversy remains as to whether there is any direct effect on berry metabolism other than inhibition of growth. Early (ED) and late (LD) season water deficits, applied before or after the onset of ripening (veraison), were imposed on field grown Vitis vinifera “Cabernet Sauvignon”, and the responses of gene expression in the flavonoid pathway and their corresponding metabolites were determined. ED accelerated sugar accumulation and the onset of anthocyanin synthesis. Both ED and LD increased anthocyanin accumulation after veraison. Expression profiling revealed that the increased anthocyanin accumulation resulted from earlier and greater expression of the genes controlling flux through the anthocyanin biosynthetic pathway, including F3H, DFR, UFGT and GST. Increases in total anthocyanins resulted predominantly from an increase of 3′4′5′-hydroxylated forms through the differential regulation of F3′H and F3′5′H. There were limited effects on proanthocyanidin, other flavonols, and on expression of genes committed to their synthesis. These results demonstrate that manipulation of abiotic stress through applied water deficits not only modulates compositional changes during berry ripening, but also alters the timing of particular aspects of the ripening process.

531 citations


Journal ArticleDOI
TL;DR: Among patients with newly diagnosed myeloma, survival in recipients of a hematopoietic stem- cell autograft followed by a stem-cell allograft from an HLA-identical sibling is superior to that in recipient of tandem stem- Cell autografteds.
Abstract: Background In this trial of the treatment of newly diagnosed multiple myeloma, we compared a protocol that entailed a hematopoietic stem-cell autograft followed by an allograft from an HLA-identical sibling with a protocol of tandem autografts. Methods We enrolled 162 consecutive patients with newly diagnosed myeloma who were 65 years of age or younger and who had at least one sibling. All patients were initially treated with vincristine, doxorubicin, and dexamethasone, followed by melphalan and autologous stem-cell rescue. Patients with an HLA-identical sibling then received nonmyeloablative total-body irradiation and stem cells from the sibling. Patients without an HLA-identical sibling received two consecutive myeloablative doses of melphalan, each of which was followed by autologous stem-cell rescue. The primary end points were overall survival and event-free survival. Results After a median follow-up of 45 months (range, 21 to 90), the median overall survival and event-free survival were longer in th...

497 citations


Journal ArticleDOI
TL;DR: The induction in WS plants of structural and regulatory genes of the flavonoid pathway and of genes that trigger brassinosteroid hormonal onset of maturation suggested that the interrelationships between developmental and environmental signalling pathways were magnified by water deficit which actively promoted fruit maturation and, in this context, anthocyanin biosynthesis.
Abstract: Anthocyanin biosynthesis is strongly up-regulated in ripening fruit of grapevines (Vitis vinifera L.) grown under drought conditions. We investigated the effects of long-term water deficit on the expression of genes coding for flavonoid and anthocyanin biosynthetic enzymes and related transcription factors, genes sensitive to endogenous [sugars, abscisic acid (ABA)] and environmental (light) stimuli connected to drought stress, and genes developmentally regulated in ripening berries. Total anthocyanin content has increased at harvest in water-stressed (WS) fruits by 37-57% in two consecutive years. At least 84% of the total variation in anthocyanin content was explained by the linear relationship between the integral of mRNA accumulation of the specific anthocyanin biosynthetic gene UDP-glucose : flavonoid 3-O-glucosyltransferase (UFGT) and metabolite content during time series from veraison through ripening. Chalcone synthase (CHS2, CHS3) and flavanone 3-hydroxylase (F3H) genes of the flavonoid pathway showed high correlation as well. Genes coding for flavonoid 3',5'-hydroxylase (F3'5'H) and O-methyltransferase (OMT) were also up-regulated in berries from dehydrated plants in which anthocyanin composition enriched in more hydroxylated and more methoxylated derivatives such as malvidin and peonidin, the grape anthocyanins to which human gastric bilitranslocase displays the highest affinity. The induction in WS plants of structural and regulatory genes of the flavonoid pathway and of genes that trigger brassinosteroid hormonal onset of maturation suggested that the interrelationships between developmental and environmental signalling pathways were magnified by water deficit which actively promoted fruit maturation and, in this context, anthocyanin biosynthesis.

496 citations


Journal ArticleDOI
TL;DR: Aspergillus species is the most frequently detected agent in patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers, and aspergillosis is characterized by a high mortality rate.
Abstract: Background. The purpose of our study was to evaluate the incidence and outcome of invasive fungal infection (IFI) among patients who underwent autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at 11 Italian transplantation centers. Methods. This cohort-retrospective study, conducted during 1999-2003, involved HSCT patients admitted to 11 tertiary care centers or university hospitals in Italy, who developed IFIs (proven or probable). Results. Among 3228 patients who underwent HSCT (1249 allogeneic HSCT recipients and 1979 autologous HSCT recipients), IFI occurred in 121 patients (overall incidence, 3.7%). Ninety-one episodes (2.8% of all patients) were due to molds, and 30 (0.9%) were due to yeasts. Ninety-eight episodes (7.8%) occurred among the 1249 allogeneic HSCT recipients, and 23 (1.2%) occurred among the 1979 autologous HSCT recipients. The most frequent etiological agents were Aspergillus species (86 episodes) and Candida species (30 episodes). The overall mortality rate was 5.7% among allogeneic HSCT recipients and 0.4% among autologous HSCT recipients, whereas the attributable mortality rate registered in our population was 65.3% (72.4% for allogeneic HSCT recipients and 34.7% for autologous HSCT recipients). Etiology influenced the patients' outcomes: the attributable mortality rate for aspergillosis was 72.1% (77.2% and 14.3% for allogeneic and autologous HSCT recipients, respectively), and the rate for Candida IFI was 50% (57.1% and 43.8% for allogeneic and autologous HSCT recipients, respectively). Conclusions. IFI represents a common complication for allogeneic HSCT recipients. Aspergillus species is the most frequently detected agent in these patients, and aspergillosis is characterized by a high mortality rate. Conversely, autologous HSCT recipients rarely develop aspergillosis, and the attributable mortality rate is markedly lower. Candidemia was observed less often than aspergillosis among both allogeneic and autologous HSCT recipients; furthermore, there was no difference in either the incidence of or the attributable mortality rate for candidemia among recipients of the 2 transplant types.

382 citations


Journal ArticleDOI
TL;DR: A new method for smooth trajectory planning of robot manipulators is described, which enables one to set kinematic constraints on the robot motion, expressed as upper bounds on the absolute values of velocity, acceleration and jerk.

373 citations


Journal ArticleDOI
01 Nov 2007-Blood
TL;DR: The findings demonstrate that an in vitro protocol to generate and expand cells from multiple organs that could be induced to acquire morphologic and functional features of mature cells even embryologically not related to the tissue of origin.

359 citations


Journal ArticleDOI
TL;DR: The educational use of virtual reality based on Web3D technologies is introduced, including the main positive and negative results obtained so far, and some of the current research directions are pointed out.
Abstract: Web3D open standards allow the delivery of interactive 3D virtual learning environments through the Internet, reaching potentially large numbers of learners worldwide, at any time. This paper introduces the educational use of virtual reality based on Web3D technologies. After briefly presenting the main Web3D technologies, we summarize the pedagogical basis that motivate their exploitation in the context of education and highlight their interesting features. We outline the main positive and negative results obtained so far, and point out some of the current research directions.

350 citations


Journal ArticleDOI
TL;DR: The ad hoc methodological concepts and procedures developed to improve the comparability of Nutrient databases (NDBs) across the 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) provide a useful tool for nutritional research as well as end-user recommendations to improve NDBs in the future.
Abstract: Objective: This paper describes the ad hoc methodological concepts and procedures developed to improve the comparability of Nutrient databases (NDBs) across the 10 European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). This was required because there is currently no European reference NDB available. Design: A large network involving national compilers, nutritionists and experts on food chemistry and computer science was set up for the 'EPIC Nutrient DataBase' (ENDB) project. A total of 550-1500 foods derived from about 37 000 standardized EPIC 24-h dietary recalls (24-HDRS) were matched as closely as possible to foods available in the 10 national NDBs. The resulting national data sets (NDS) were then successively documented, standardized and evaluated according to common guidelines and using a DataBase Management System specifically designed for this project. The nutrient values of foods unavailable or not readily available in NDSs were approximated by recipe calculation, weighted averaging or adjustment for weight changes and vitamin-mineral losses, using common algorithms. Results: The final ENDB contains about 550-1500 foods depending on the country and 26 common components. Each component value was documented and standardized for unit, mode of expression, definition and chemical method of analysis, as far as possible. Furthermore, the overall completeness of NDSs was improved (≥99%), particularly for β-carotene and vitamin E. Conclusion: The ENDB constitutes a first real attempt to improve the comparability of NDBs across European countries. This methodological work will provide a useful tool for nutritional research as well as end-user recommendations to improve NDBs in the future. Chemicals / CAS: alcohol, 64-17-5; alpha tocopherol, 1406-18-4, 1406-70-8, 52225-20-4, 58-95-7, 59-02-9; ascorbic acid, 134-03-2, 15421-15-5, 50-81-7; beta carotene, 7235-40-7; calcium, 7440-70-2; cholesterol, 57-88-5; cyanocobalamin, 53570-76-6, 68-19-9, 8064-09-3; iron, 14093-02-8, 53858-86-9, 7439-89-6; magnesium, 7439-95-4; phosphorus, 7723-14-0; potassium, 7440-09-7; protein, 67254-75-5; pyridoxine, 12001-77-3, 58-56-0, 65-23-6, 8059-24-3; retinol, 68-26-8, 82445-97-4; riboflavin, 83-88-5; starch, 9005-25-8, 9005-84-9; thiamine, 59-43-8, 67-03-8; water, 7732-18-5

329 citations


Journal ArticleDOI
TL;DR: In the long-term, both adrenalectomy and spironolactone are effective in reducing left ventricular mass in patients with primary aldosteronism, with effects that are partially independent of blood pressure changes.
Abstract: Exposure to excess aldosterone results in cardiac damage in hypertensive states. We evaluated the long-term cardiac structural and functional evolution in patients with primary aldosteronism after surgical or medical treatment. Fifty-four patients with primary aldosteronism were enrolled in a prospective study and were followed for a mean of 6.4 years after treatment with adrenalectomy (n=24) or spironolactone (n=30). At baseline, echocardiographic measurements of patients with primary aldosteronism were compared with those of 274 patients with essential hypertension. Patients with primary aldosteronism had greater left ventricular mass, more prevalent left ventricular hypertrophy, lower early:late-wave diastolic filling velocities ratio, and longer deceleration time than patients with essential hypertension but no differences in relative wall thickness and systolic function. During follow-up, average blood pressure was 135/82 and 137/82 mm Hg in patients treated with adrenalectomy and spironolactone, respectively. In the initial 1-year period, left ventricular mass decreased significantly only in adrenalectomized patients. Subsequent changes in left ventricular mass were greater in patients treated with spironolactone, with an overall change from baseline to the end of follow-up that was comparable in the 2 groups. Prevalence of hypertrophy decreased in both treatment groups, whereas diastolic parameters had only mild and nonsignificant improvement. Changes in blood pressure and pretreatment plasma aldosterone were independent predictors of left ventricular mass decrease in both treatment groups. Thus, in the long-term, both adrenalectomy and spironolactone are effective in reducing left ventricular mass in patients with primary aldosteronism, with effects that are partially independent of blood pressure changes.

Journal ArticleDOI
TL;DR: MRI of the spine and pelvis still remains the gold standard imaging technique for the detection of bone marrow involvement in MM but 18F-FDG PET-CT provides additional and valuable information for the assessment of myeloma bone disease in areas not covered by MRI.
Abstract: Background and Objectives Bone lesions in multiple myeloma (MM) have been traditionally detected by whole body X-ray (WBXR) survey although magnetic resonance imaging (MRI) has become the gold standard for detecting MM involvement of the spine and pelvis. The aim of this study was to compare a new technique, positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) integrated with computed tomography (18F-FDG PET-CT), with MRI and WBXR for baseline assessment of bone disease in MM. Design and Methods We prospectively compared 18F-FDG PET-CT, MRI of the spine-pelvis and WBXR for baseline assessment of bone disease in a series of 46 patients with newly diagnosed MM. In 23 patients who received up front autologous transplantation, we also compared post-treatment PET-CT scans with MR images of the spine and pelvis. Results Overall, PET-CT was superior to planar radiographs in 46% of patients, including 19% with negative WBXR. In 30% of patients, PET-CT scans of the spine and pelvis failed to show abnormal findings in areas in which MRI revealed an abnormal pattern of bone marrow involvement, more frequently of diffuse type. In contrast, in 35% of patients PET-CT enabled the detection of myelomatous lesions in areas which were out of the field of view of MRI. By combining MRI of the spine-pelvis and 18F-FDG PET-CT, the ability to detect sites of active MM, both medullary and extramedullary, was as high as 92%. Following transplantation, 15 patients had negative PET-CT scans (including 13 with a very good partial response or at least near complete response), but only 8 had normal MRI. Interpretation and Conclusions MRI of the spine and pelvis still remains the gold standard imaging technique for the detection of bone marrow involvement in MM. 18F-FDG PET-CT provides additional and valuable information for the assessment of myeloma bone disease in areas not covered by MRI.

Journal ArticleDOI
TL;DR: In this paper, it was shown that the observed transparency is naturally produced by an oscillation mechanism, which can occur inside intergalactic magnetic fields, where a photon can become a new spin-zero boson with mass m<<10{sup -10} eV.
Abstract: Recent findings by imaging atmospheric Cherenkov telescopes indicate a large transparency of the Universe to gamma rays, which can be hardly explained within the current models of extragalactic background light. We show that the observed transparency is naturally produced by an oscillation mechanism--which can occur inside intergalactic magnetic fields--whereby a photon can become a new spin-zero boson with mass m<<10{sup -10} eV. Because the latter particle travels unimpeded throughout the Universe, photons can reach the observer even if the distance from the source considerably exceeds their mean free path. We compute the expected flux of gamma rays from blazar 3C279 at different energies. Our predictions can be tested in the near future by the gamma-ray telescopes H.E.S.S., MAGIC, CANGAROO, and VERITAS. Moreover, our result provides an important observational test for models of dark energy wherein quintessence is coupled to the photon through an effective dimension-five operator.


Journal ArticleDOI
TL;DR: Fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression find abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.
Abstract: Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects' identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey-Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.

Journal ArticleDOI
TL;DR: These brain maps are consistent with previous voxel-based morphometry reports of greater GMD in portions of the anterior limbic network in bipolar patients and suggest neurotrophic effects of lithium as a possible etiology of these neuroanatomic differences.

Journal ArticleDOI
TL;DR: Electron microscopy and biochemical and molecular analyses showed that primary cultures derived from tumors bearing disruptive mutations failed to maintain the mutations and the oncocytic phenotype, and it is concluded that disruptive mutations in complex I subunits are markers of thyroid onccytic tumors.
Abstract: Oncocytic tumors are a distinctive class of proliferative lesions composed of cells with a striking degree of mitochondrial hyperplasia that are particularly frequent in the thyroid gland. To understand whether specific mitochondrial DNA (mtDNA) mutations are associated with the accumulation of mitochondria, we sequenced the entire mtDNA in 50 oncocytic lesions (45 thyroid tumors of epithelial cell derivation and 5 mitochondrion-rich breast tumors) and 52 control cases (21 nononcocytic thyroid tumors, 15 breast carcinomas, and 16 gliomas) by using recently developed technology that allows specific and reliable amplification of the whole mtDNA with quick mutation scanning. Thirteen oncocytic lesions (26%) presented disruptive mutations (nonsense or frameshift), whereas only two samples (3.8%) presented such mutations in the nononcocytic control group. In one case with multiple thyroid nodules analyzed separately, a disruptive mutation was found in the only nodule with oncocytic features. In one of the five mitochondrion-rich breast tumors, a disruptive mutation was identified. All disruptive mutations were found in complex I subunit genes, and the association between these mutations and the oncocytic phenotype was statistically significant (P = 0.001). To study the pathogenicity of these mitochondrial mutations, primary cultures from oncocytic tumors and corresponding normal tissues were established. Electron microscopy and biochemical and molecular analyses showed that primary cultures derived from tumors bearing disruptive mutations failed to maintain the mutations and the oncocytic phenotype. We conclude that disruptive mutations in complex I subunits are markers of thyroid oncocytic tumors.

Journal ArticleDOI
Justin Albert1, E. Aliu2, H. Anderhub3, P. Antoranz4, A. Armada2, C. Baixeras5, Juan Abel Barrio4, H. Bartko6, Denis Bastieri7, Julia Becker8, W. Bednarek, K. Berger1, Ciro Bigongiari7, Adrian Biland3, R. K. Bock6, R. K. Bock7, Pol Bordas9, Valentí Bosch-Ramon9, Thomas Bretz1, I. Britvitch3, M. Camara4, E. Carmona6, Ashot Chilingarian10, J. A. Coarasa6, S. Commichau3, Jose Luis Contreras4, Juan Cortina2, M. T. Costado11, M. T. Costado12, V. Curtef8, V. Danielyan10, Francesco Dazzi7, A. De Angelis13, C. Delgado12, R. de los Reyes4, B. De Lotto13, E. Domingo-Santamaría2, Daniela Dorner1, Michele Doro7, Manel Errando2, Michela Fagiolini14, Daniel Ferenc15, Enrique Fernández2, R. Firpo2, Jose Flix2, M. V. Fonseca4, Ll. Font5, M. Fuchs6, Nicola Galante6, R. J. García-López11, R. J. García-López12, M. Garczarczyk6, Markus Gaug12, Maria Giller, Florian Goebel6, D. Hakobyan10, Masaaki Hayashida6, T. Hengstebeck16, Artemio Herrero11, Artemio Herrero12, D. Höhne1, J. Hose6, C. C. Hsu6, P. Jacon, T. Jogler6, R. Kosyra6, D. Kranich3, R. Kritzer1, A. Laille15, Elina Lindfors, Saverio Lombardi7, Francesco Longo13, J. López2, M. López4, E. Lorenz3, E. Lorenz6, P. Majumdar6, G. Maneva, K. Mannheim1, Oriana Mansutti13, Mosè Mariotti7, M. I. Martínez2, Daniel Mazin2, C. Merck6, Mario Meucci14, M. Meyer1, Jose Miguel Miranda4, R. Mirzoyan6, S. Mizobuchi6, Abelardo Moralejo2, Daniel Nieto4, K. Nilsson, Jelena Ninkovic6, E. Oña-Wilhelmi2, N. Otte16, N. Otte6, I. Oya4, M. Panniello12, Riccardo Paoletti14, J. M. Paredes9, M. Pasanen, D. Pascoli7, F. Pauss3, R. Pegna14, Massimo Persic17, Massimo Persic13, L. Peruzzo7, A. Piccioli14, Elisa Prandini7, N. Puchades2, A. Raymers10, Wolfgang Rhode8, Marc Ribó9, J. Rico2, M. Rissi3, A. Robert5, S. Rügamer1, A. Saggion7, Takashi Saito6, Alvaro Sanchez5, P. Sartori7, V. Scalzotto7, V. Scapin13, R. Schmitt1, T. Schweizer6, M. Shayduk6, M. Shayduk16, K. Shinozaki6, Steven N. Shore18, N. Sidro2, A. Sillanpää, Dorota Sobczyńska, Antonio Stamerra14, L. S. Stark3, L. O. Takalo, Petar Temnikov, D. Tescaro2, Masahiro Teshima6, Diego F. Torres19, Nicola Turini14, H. Vankov, V. Vitale13, Robert Wagner6, Tadeusz Wibig, W. Wittek6, F. Zandanel7, Roberta Zanin2, J. Zapatero5 
TL;DR: The MAGIC observations were performed for a total of 40 hours during 26 nights, spanning the period between 2006 June and November, and the results from the observations in the very high energy band (VHE; GeV) of the black E = 100 g hole X-ray binary (BHXB) Cygnus X-1 were reported in this article.
Abstract: We report on the results from the observations in the very high energy band ( VHE; GeV) of the black E = 100 g hole X- ray binary ( BHXB) Cygnus X- 1. The observations were performed with the MAGIC telescope, for a total of 40 hr during 26 nights, spanning the period between 2006 June and November. Searches for steady gamma - ray signals yielded no positive result, and upper limits to the integral flux ranging between 1% and 2% of the Crab Nebula flux, depending on the energy, have been established. We also analyzed each observation night independently, obtaining evidence of gamma- ray signals at the 4.0 j significance level ( 3.2 j after trial correction) for 154 minutes of effective on- time ( EOT) on September 24 between 20: 58 and 23: 41 UTC, coinciding with an X- ray flare seen by RXTE, Swift, and INTEGRAL. A search for faster- varying signals within a night resulted in an excess with a significance of 4.9 j ( 4.1 j after trial correction) for 79 minutes EOT between 22: 17 and 23: 41 UTC. The measured excess is compatible with a pointlike source at the position of Cygnus X- 1 and excludes the nearby radio nebula powered by its relativistic jet. The differential energy spectrum is well fitted by an unbroken power law described as dN/(dA dt dE) = ( 2.3 +/- 0.6)* 10 ( E/1TeV). This is the first experimental evidence of VHE emission from a stellar mass black hole and therefore from a confirmed accreting X- ray binary.

Journal ArticleDOI
Eugene R. Schiff1, Cjing Lung Lai2, Stephanos J. Hadziyannis, Peter Nuehaus3, Norah A. Terrault4, Massimo Colombo5, Hans L. Tillmann6, Didler Samuel, Stefan Zuezem7, Jean Pierre Villenueve8, Sarah Arteburn, Katyna Borroto-Esoda, Carol L. Brosgart, Steven Chuck, Ahmad Obaid Shakil9, Jhon Fung9, Alfredo Alberti10, Anna Lok11, Antonio Picciotto12, Francesco Torre12, Caroline A. Riely13, Christian Trepo, Thierry Bizollon, Danielle Bottaa-Fridlund, Rene Gerolami, David D. Douglas14, Dinesh Ranjan15, D Faust7, Joerg Trojan7, Edward Gane16, Erica Villa17, Modentina Boarino17, Etienne Sokal18, Peter Stärkel18, Ferruccio Bonino19, Brunetto Maurizio19, Fred Gordon20, Jo Anne Pratt20, Frieder Berr21, Ingolf Schiefke21, Geoff McCaughan22, Simone I. Strasser22, Geoffrey Dusheiko23, G.-P. Pageaux, Dominique Larrey, Giuseppe Pastore, Teresa Santantonio, Graeme J.M. Alexander24, Tracy Woodall24, Han Van Vlierberghe25, Isabelle Colle25, Hugh Harley26, Jean Guggenheim, Aline Myx-Staccini, Jean Michel Metreau, Philippe Mavier, John M. Vierling27, Tram Tran27, Nigel Girgrah28, Lisa M. Nyberg29, Man-Fung Yuen2, Mang Ma30, Manuel Delgado Balnco31, Manuela Merli32, Paola Tanzilli32, Mario Angelico, Daniele Di Paolo, Mario Rizzetto, Alfredo Marzano, Pietro Lampertico5, Martín Prieto, Marina Berenguer, Martina Felder, Martina Sterneck33, Marc Willems33, Michael Charlton14, Timothy J. Gunneson14, Michael Ritter, Michael Voight34, Judy Swift34, Mitchell L. Shiffman35, Nicholas Tassopoulos, Isidoros Klissas, Nikolai Naourmov23, Patrick Chamouard, Patrick Marcellin, François Durand, Peter W Angus36, Connelly Nathan36, Pierluigi Toniutto37, Elisabetta Fumo37, Pietro Andreone38, Carmela Cursaro38, Rafael Bárcena, Fernando Garcia Hoz, Reinhard Zachoval39, Maria Christina39, Robert A. de Man40, Herold J. Metselaar40 
TL;DR: Adefovir dipivoxil is effective and safe in wait‐listed or post–liver transplantation chronic hepatitis B patients with lamivudine‐resistant HBV and prevents graft reinfection with or without HBIg.

Journal ArticleDOI
TL;DR: The phylogenetic relationships among phy toplasmas were generally in agreement with those obtained on the basis of the 16S rRNA gene in the present and previous works, however, the rp gene-based phylogeny allowed for finer resolution of distinct lineages within the phytoplasma 16Sr groups.
Abstract: Extensive phylogenetic analyses were performed based on sequences of the 16S rRNA gene and two ribosomal protein (rp) genes, rplV (rpl22) and rpsC (rps3), from 46 phytoplasma strains representing 12 phytoplasma 16Sr groups, 16 other mollicutes and 28 Gram-positive walled bacteria. The phylogenetic tree inferred from rp genes had a similar overall topology to that inferred from the 16S rRNA gene. However, the rp gene-based tree gave a more defined phylogenetic interrelationship among mollicutes and Gram-positive walled bacteria. Both phylogenies indicated that mollicutes formed a monophyletic group. Phytoplasmas clustered with Acholeplasma species and formed one clade paraphyletic with a clade consisting of the remaining mollicutes. The closest relatives of mollicutes were low-G+C-content Gram-positive bacteria. Comparative phylogenetic analyses using the 16S rRNA gene and rp genes were performed to evaluate their efficacy in resolving distinct phytoplasma strains. A phylogenetic tree was constructed based on analysis of rp gene sequences from 87 phytoplasma strains belonging to 12 16Sr phytoplasma groups. The phylogenetic relationships among phytoplasmas were generally in agreement with those obtained on the basis of the 16S rRNA gene in the present and previous works. However, the rp gene-based phylogeny allowed for finer resolution of distinct lineages within the phytoplasma 16Sr groups. RFLP analysis of rp gene sequences permitted finer differentiation of phytoplasma strains in a given 16Sr group. In this study, we also designed several semi-universal and 16Sr group-specific rp gene-based primers that allow for the amplification of 11 16Sr group phytoplasmas.

Journal ArticleDOI
TL;DR: The developing view of transcriptional regulation as a complex and modular system, in which long-range interactions and the involvement of transposable elements are frequently observed, lends support to the possibility of an important functional role for the dispensable genome and could make it less dispensable than previously thought.

Journal ArticleDOI
01 Jan 2007-Leukemia
TL;DR: This review describes the history of the angiogenic switch illustrated in the literature and with particular reference to the three transgenic mouse models, namely RIP1-TAG2, keratin-14 (K14) (human papilloma virus) HPV16 and papillomas virus, used for stage-specific assessment of the effects of antiangiogenic and antitumorigenic agents.
Abstract: Spontaneously arising tumor cells are not usually angiogenic at first. The phenotypic switch to angiogenesis is usually accomplished by a substet that induces new capillaries that then converge toward the tumor. The switch clearly involves more than simple upregulation of angiogenic activity and is thought to be the result of a net balance of positive and negative regulators. Tumor growth is although to require disruption of this balance and hence this switch must turned on for cancer progression. Progenitor endothelial cells, the crosstalk between angiogenic factors and their receptors and the interaction between vasculogenesis and lymphangiogenesis are all factors that may contribute to the switch. Its promotion is also the outcome of genetic instability resulting in the emergence of tumor cell lines. This review describes the history of the angiogenic switch illustrated in the literature and with particular reference to the three transgenic mouse models, namely RIP1-TAG2, keratin-14 (K14) (human papilloma virus) HPV16 and papilloma virus, used for stage-specific assessment of the effects of antiangiogenic and antitumorigenic agents.

Journal ArticleDOI
Justin Albert1, E. Aliu2, H. Anderhub3, P. Antoranz4, A. Armada2, C. Baixeras5, Juan Abel Barrio4, H. Bartko6, Denis Bastieri7, Julia Becker8, W. Bednarek, K. Berger1, Ciro Bigongiari7, Adrian Biland3, R. K. Bock7, R. K. Bock6, Pol Bordas9, Valentí Bosch-Ramon9, Thomas Bretz1, I. Britvitch3, M. Camara4, E. Carmona6, Ashot Chilingarian10, J. A. Coarasa6, S. Commichau3, Jose Luis Contreras4, Juan Cortina2, M. T. Costado11, M. T. Costado12, V. Curtef8, V. Danielyan10, Francesco Dazzi7, A. De Angelis13, C. Delgado11, R. de los Reyes4, B. De Lotto13, E. Domingo-Santamaría2, Daniela Dorner1, Michele Doro7, Manel Errando2, Michela Fagiolini14, Daniel Ferenc15, Enrique Fernández2, R. Firpo2, Jose Flix2, M. V. Fonseca4, Ll. Font5, M. Fuchs6, Nicola Galante6, R. J. García-López12, R. J. García-López11, M. Garczarczyk6, Markus Gaug11, Maria Giller, Florian Goebel6, D. Hakobyan10, Masaaki Hayashida6, T. Hengstebeck16, Artemio Herrero12, Artemio Herrero11, D. Höhne1, J. Hose6, C. C. Hsu6, P. Jacon, T. Jogler6, R. Kosyra6, D. Kranich3, R. Kritzer1, A. Laille15, Elina Lindfors, Saverio Lombardi7, Francesco Longo13, J. López2, M. López4, E. Lorenz6, E. Lorenz3, P. Majumdar6, G. Maneva, K. Mannheim1, Oriana Mansutti13, Mosè Mariotti7, M. I. Martínez2, Daniel Mazin2, C. Merck6, Mario Meucci14, M. Meyer1, Jose Miguel Miranda4, R. Mirzoyan6, S. Mizobuchi6, Abelardo Moralejo2, Daniel Nieto4, K. Nilsson, Jelena Ninkovic6, E. Oña-Wilhelmi2, N. Otte16, N. Otte6, I. Oya4, David Paneque6, M. Panniello11, Riccardo Paoletti14, J. M. Paredes9, M. Pasanen, D. Pascoli7, F. Pauss3, R. Pegna14, Massimo Persic13, Massimo Persic17, L. Peruzzo7, A. Piccioli14, Elisa Prandini7, N. Puchades2, A. Raymers10, Wolfgang Rhode8, Marc Ribó9, J. Rico2, M. Rissi3, A. Robert5, S. Rügamer1, A. Saggion7, Takashi Saito6, Alvaro Sanchez5, P. Sartori7, V. Scalzotto7, V. Scapin13, R. Schmitt1, T. Schweizer6, M. Shayduk6, M. Shayduk16, K. Shinozaki6, S. N. Shore18, N. Sidro2, A. Sillanpää, Dorota Sobczyńska, Antonio Stamerra14, L. S. Stark3, L. O. Takalo, Petar Temnikov, D. Tescaro2, Masahiro Teshima6, Diego F. Torres19, Nicola Turini14, H. Vankov, V. Vitale13, Robert Wagner6, Tadeusz Wibig, W. Wittek6, F. Zandanel7, Roberta Zanin2, J. Zapatero5 
TL;DR: In this article, the MAGIC J0616 + 225 was used to detect a very high energy (VHE; E-gamma >= 100 GeV) gamma-ray emission located close to the Galactic plane, which is spatially coincident with supernova remnant IC 443.
Abstract: We report the detection of a new source of very high energy (VHE; E-gamma >= 100 GeV) gamma- ray emission located close to the Galactic plane, MAGIC J0616 + 225, which is spatially coincident with supernova remnant IC 443. The observations were carried out with the MAGIC telescope in the periods 2005 December-2006 January and 2006 December-2007 January. Here we present results from this source, leading to a VHE gamma-ray signal with a statistical significance of 5.7 sigma in the 2006/2007 data and a measured differential gamma-ray flux consistent with a power law, described as dN(gamma)/(dA dt dE) = (1.0 +/- 0.2) x 10(-11) (E/0.4 TeV)(-3.1 +/- 0.3) cm(-2) s(-1) TeV-1. We briefly discuss the observational technique used and the procedure implemented for the data analysis. The results are placed in the context of the multiwavelength emission and the molecular environment found in the region of IC 443.

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TL;DR: Colour variation of the grape berry conforms to a peculiar pattern of genotype-specific expression of the whole set of anthocyanin genes in a direct transcript-metabolite-phenotype relationship.
Abstract: Background Fruit coloration of red-skinned grapevines is mainly due to anthocyanin pigments. We analysed a panel of nine cultivars that included extreme phenotypes for berry colour, ranging from green (absence of anthocyanins) to red, purple, violet and blue. Expression of six genes of the anthocyanin pathway coding for flavanone-hydroxylase (F3H), flavonoid 3'-hydroxylase (F3'H), flavonoid 3',5'-hydroxylase (F3'5'H), UDP-glucose:flavonoid-3-O-glucosyltransferase (UFGT), glutathione-S-transferase (GST), O-methyltransferase (OMT) and four transcription factors (MybA, MybB, MybC, MybD) was analysed by quantitative RT-PCR at four developmental stages from before the onset of ripening until full maturity and compared to anthocyanin metabolites.

Journal ArticleDOI
01 May 2007-Genetics
TL;DR: The importance of dominance effects was confirmed by highly significant correlations between heterozygosity level and phenotypic performance, especially for GY, suggesting pleiotropic effects on overall plant vigor.
Abstract: The exploitation of heterosis is one of the most outstanding advancements in plant breeding, although its genetic basis is not well understood yet. This research was conducted on the materials arising from the maize single cross B73 × H99 to study heterosis by procedures of classical genetic and quantitative trait loci (QTL) analyses. Materials were the basic generations, the derived 142 recombinant inbred lines (RILs), and the three testcross populations obtained by crossing the 142 RILs to each parent and their F1. For seedling weight (SW), number of kernels per plant (NK), and grain yield (GY), heterosis was >100% and the average degree of dominance was >1. Epistasis was significant for SW and NK but not for GY. Several QTL were identified and in most cases they were in the additive–dominance range for traits with low heterosis and mostly in the dominance–overdominance range for plant height (PH), SW, NK, and GY. Only a few QTL with digenic epistasis were identified. The importance of dominance effects was confirmed by highly significant correlations between heterozygosity level and phenotypic performance, especially for GY. Some chromosome regions presented overlaps of overdominant QTL for SW, PH, NK, and GY, suggesting pleiotropic effects on overall plant vigor.

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TL;DR: The SSDDI is an adequate instrument to objectively measure damage in patients with SS, and that the SSDAI is a valid tool to measure disease activity when used either as a single-state index or as a transition index.
Abstract: Objective To develop valid instruments for the assessment of disease-related damage and disease activity in Sjogren's syndrome (SS). Methods Data on 206 patients with primary SS were collected in 12 Italian centers. Each patient was scored by 1 investigator, on the basis of a global assessment of the degree of disease damage and disease activity. Patients judged to have active disease at the time of enrollment underwent a second evaluation after 3 months. Univariate and multivariate analyses were performed to select the clinical and serologic variables that were the best predictors of damage and of disease activity, and these variables were used to construct the Sjogren's Syndrome Disease Damage Index (SSDDI) and the Sjogren's Syndrome Disease Activity Index (SSDAI). The weight of each variable in the index was determined by the β coefficients in multivariate regression models. Scores obtained using the SSDDI and the SSDAI were compared with scores initially given by the investigators. Finally, a receiver operating characteristic (ROC) curve was used to determine the cutoff value in the SSDAI with the highest level of accuracy in identifying patients with a significant level of disease activity. Results A multivariate model with 9 variables was the best predictor of investigator scores of damage. The scores obtained using the SSDDI were closely correlated with investigator ratings (R = 0.760, P < 0.0001). A model composed of 11 variables was the best predictor of investigator scores of disease activity. The scores obtained using the SSDAI were strongly correlated with the investigator ratings both at the time of enrollment and 3 months after enrollment (R = 0.872, P < 0.0001, and R = 0.817, P < 0.0001, respectively). The differences between scores given by investigators at study enrollment and after 3 months, a measure of variation of disease activity over time, were also closely correlated with the differences calculated using the SSDAI (R = 0.683, P < 0.0001). The ROC curve analysis showed that patients with the highest level of disease activity could be identified on the basis of an SSDAI score of ≥5. Conclusion Our findings indicate that the SSDDI is an adequate instrument to objectively measure damage in patients with SS, and that the SSDAI is a valid tool to measure disease activity when used either as a single-state index or as a transition index.

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TL;DR: The pharmacokinetic principles of CLCRRT of antimicrobial agents during the application of CVVH andCVVHDF are discussed and the most recent findings on this topic are summarised in order to understand the basis for optimal dosage adjustments of different antimacterial agents.
Abstract: Continuous renal replacement therapy (CRRT), particularly continuous venovenous haemofiltration (CVVH) and continuous venovenous haemodiafiltration (CVVHDF), are gaining increasing relevance in routine clinical management of intensive care unit patients. The application of CRRT, by leading to extracorporeal clearance (CLCRRT), may significantly alter the pharmacokinetic behaviour of some drugs. This may be of particular interest in critically ill patients presenting with life-threatening infections, since the risk of underdosing with antimicrobial agents during this procedure may lead to both therapeutic failure and the spread of breakthrough resistance. The intent of this review is to discuss the pharmacokinetic principles of CLCRRT of antimicrobial agents during the application of CVVH and CVVHDF and to summarise the most recent findings on this topic (from 1996 to December 2006) in order to understand the basis for optimal dosage adjustments of different antimicrobial agents. Removal of solutes from the blood through semi-permeable membranes during RRT may occur by means of two different physicochemical processes, namely, diffusion or convection. Whereas intermittent haemodialysis (IHD) is essentially a diffusive technique and CVVH is a convective technique, CVVHDF is a combination of both. As a general rule, the efficiency of drug removal by the different techniques is expected to be CVVHDF > CVVH > IHD, but indeed CLCRRT may vary greatly depending mainly on the peculiar physicochemical properties of each single compound and the CRRT device’s characteristics and operating conditions. Considering that RRT substitutes for renal function in clearing plasma, CLCRRT is expected to be clinically relevant for drugs with dominant renal clearance, especially when presenting a limited volume of distribution and poor plasma protein binding. Consistently, CLCRRT should be clinically relevant particularly for most hydrophilic antimicrobial agents (e.g. β-lactams, aminoglycosides, glycopeptides), whereas it should assume much lower relevance for lipophilic compounds (e.g. fluoroquinolones, oxazolidinones), which generally are nonrenally cleared. However, there are some notable exceptions: ceftriax-one and oxacillin, although hydrophilics, are characterised by primary biliary elimination; levofloxacin and ciprofloxacin, although lipophilics, are renally cleared. As far as CRRT characteristics are concerned, the extent of drug removal is expected to be directly proportional to the device’s surface area and to be dependent on the mode of replacement fluid administration (predilution or postdilution) and on the ultrafiltration and/or dialysate flow rates applied. Conversely, drug removal by means of CVVH or CVVHDF is unaffected by the drug size, considering that almost all antimicrobial agents have molecular weights significantly lower (<2000Da) than the haemofilter cut-off (30 000–50 000Da). Drugs that normally have high renal clearance and that exhibit high CLCRRT during CVVH or CVVHDF may need a significant dosage increase in comparison with renal failure or even IHD. Conversely, drugs that are normally nonrenally cleared and that exhibit very low CLCRRT during CVVH or CVVHDF may need no dosage modification in comparison with normal renal function. Bearing these principles in mind will almost certainly aid the management of antimicrobial therapy in critically ill patients undergoing CRRT, thus containing the risk of inappropriate exposure. However, some peculiar pathophys-iological conditions occurring in critical illness may significantly contribute to further alteration of the pharmacokinetics of antimicrobial agents during CRRT (i.e. hypoalbuminaemia, expansion of extracellular fluids or presence of residual renal function). Accordingly, therapeutic drug monitoring should be considered a very helpful tool for optimising drug exposure during CRRT.

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TL;DR: All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFRα rearrangement, and chronic imatinib treatment at doses as low as 100 mg daily ensures complete and durable responses.
Abstract: Background and Objectives The hypereosinophilic syndrome (HES) may be associated with the fusion of the platelet derived growth factor receptor α ( PDGFR α) gene with the FIP1L1 gene in chromosome 4 coding for a constitutively activated PDGFRα tyrosine kinase. These cases with FIP1L1-PDGFR α rearrangement have been reported to be very sensitive to the tyrosine kinase inhibitor imatinib mesylate. Design and Methods A prospective multicenter study of idiopathic or primary HES was established in 2001 (Study Protocol Registration no. NCT 0027 6929). One hundred and ninety-six patients were screened, of whom 72 where identified as having idiopathic or primary HES and 63 were treated with imatinib 100 to 400 mg daily. Results Twenty-seven male patients carried the FIP1L1-PDGFR α rearrangement. All 27 achieved a complete hematologic remission (CHR) and became negative for the fusion transcripts according to reverse transcriptase polymerase chain reaction (RT-PCR) analysis. With a median follow-up of 25 months (15–60 months) all 27 patients remain in CHR and RT-PCR negative, and continue treatment at a dose of 100 to 400 mg daily. In three patients imatinib treatment was discontinued for few months, the fusion transcript became rapidly detectable, and then again undetectable upon treatment reassumption. Thirty-six patients did not carry the rearrangement; of these, five (14%) achieved a CHR, which was lost in all cases after 1 to 15 months. Interpretation and Conclusions All patients meeting the criteria for idiopathic or primary HES should be screened for the FIP1L1-PDGFR α rearrangement. For all patients with this rearrangement, chronic imatinib treatment at doses as low as 100 mg daily ensures complete and durable responses.

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TL;DR: Transcripts of many NBS-LRR-encoding and related genes were defined, most were present at low levels and exhibited tissue-specific expression patterns, and no obvious correlation between expression pattern, phylogenetic relationship or genomic location was studied.
Abstract: Nucleotide binding site-leucine rich repeat (NBS-LRR)-encoding genes comprise the largest class of plant disease resistance genes. The 149 NBS-LRR-encoding genes and the 58 related genes that do not encode LRRs represent approximately 0.8% of all ORFs so far annotated in Arabidopsis ecotype Col-0. Despite their prevalence in the genome and functional importance, there was little information regarding expression of these genes. We analyzed the expression patterns of ~170 NBS-LRR-encoding and related genes in Arabidopsis Col-0 using multiple analytical approaches: expressed sequenced tag (EST) representation, massively parallel signature sequencing (MPSS), microarray analysis, rapid amplification of cDNA ends (RACE) PCR, and gene trap lines. Most of these genes were expressed at low levels with a variety of tissue specificities. Expression was detected by at least one approach for all but 10 of these genes. The expression of some but not the majority of NBS-LRR-encoding and related genes was affected by salicylic acid (SA) treatment; the response to SA varied among different accessions. An analysis of previously published microarray data indicated that ten NBS-LRR-encoding and related genes exhibited increased expression in wild-type Landsberg erecta (Ler) after flagellin treatment. Several of these ten genes also showed altered expression after SA treatment, consistent with the regulation of R gene expression during defense responses and overlap between the basal defense response and salicylic acid signaling pathways. Enhancer trap analysis indicated that neither jasmonic acid nor benzothiadiazole (BTH), a salicylic acid analog, induced detectable expression of the five NBS-LRR-encoding genes and one TIR-NBS-encoding gene tested; however, BTH did induce detectable expression of the other TIR-NBS-encoding gene analyzed. Evidence for alternative mRNA polyadenylation sites was observed for many of the tested genes. Evidence for alternative splicing was found for at least 12 genes, 11 of which encode TIR-NBS-LRR proteins. There was no obvious correlation between expression pattern, phylogenetic relationship or genomic location of the NBS-LRR-encoding and related genes studied. Transcripts of many NBS-LRR-encoding and related genes were defined. Most were present at low levels and exhibited tissue-specific expression patterns. Expression data are consistent with most Arabidopsis NBS-LRR-encoding and related genes functioning in plant defense responses but do not preclude other biological roles.

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TL;DR: In this paper, the antioxidant capacity of the main phenolic compounds present in wood smoke and smoke flavourings used in the food industry was investigated by three methods, based on a kinetic and thermodynamic approach: the bleaching of the carotenoid crocin, the scavenging of the DPPH radical, and the determination of the oxidation potential.