| 1. |
- Haas, Brian J., et al.
(författare)
-
Genome sequence and analysis of the Irish potato famine pathogen Phytophthora infestans
- 2009
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 461:7262, s. 393-398
-
Tidskriftsartikel (refereegranskat)abstract
- Phytophthora infestans is the most destructive pathogen of potato and a model organism for the oomycetes, a distinct lineage of fungus-like eukaryotes that are related to organisms such as brown algae and diatoms. As the agent of the Irish potato famine in the mid-nineteenth century, P. infestans has had a tremendous effect on human history, resulting in famine and population displacement(1). To this day, it affects world agriculture by causing the most destructive disease of potato, the fourth largest food crop and a critical alternative to the major cereal crops for feeding the world's population(1). Current annual worldwide potato crop losses due to late blight are conservatively estimated at $6.7 billion(2). Management of this devastating pathogen is challenged by its remarkable speed of adaptation to control strategies such as genetically resistant cultivars(3,4). Here we report the sequence of the P. infestans genome, which at similar to 240 megabases (Mb) is by far the largest and most complex genome sequenced so far in the chromalveolates. Its expansion results from a proliferation of repetitive DNA accounting for similar to 74% of the genome. Comparison with two other Phytophthora genomes showed rapid turnover and extensive expansion of specific families of secreted disease effector proteins, including many genes that are induced during infection or are predicted to have activities that alter host physiology. These fast-evolving effector genes are localized to highly dynamic and expanded regions of the P. infestans genome. This probably plays a crucial part in the rapid adaptability of the pathogen to host plants and underpins its evolutionary potential.
|
|
| 2. |
- Aamodt, K., et al.
(författare)
-
The ALICE experiment at the CERN LHC
- 2008
-
Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08002
-
Forskningsöversikt (refereegranskat)abstract
- ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
|
|
| 3. |
- Polshin, Victor, et al.
(författare)
-
Attaining control by design over the hydrolytic stability of Fe-TAML oxidation catalysts
- 2008
-
Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 130:13, s. 4497-4506
-
Tidskriftsartikel (refereegranskat)abstract
- The iron(III) complexes of tetra amidato macrocyclic ligands (TAMLs) ([Fe{1-X-1-2-X2C6H2-4,5-(NCOCMe2NCO)(2)CR2}(OH2)](-), 1: X-1 = X-2 = H, R-2 = Me-2 (a), R-2 = (CH2)(2) (b); X-1 = X-2 = Cl, R-2 = F-2, (c), etc.), which the proton is known to demetalate at pH < 3, are also subject to catalyzed demetalation by Bronsted acid buffer components at pH 4-9 such as H2PO4-, HSO3-, and CH3- CO2H, HO2CCH2CO2-. Buffers based on pyridine (py) and tris(hydroxymethyl)aminomethane (TRIS) are catalytically inactive. Where reactions proceed, the products are demetalated TAMLs and iron species of variable composition. Pseudo-first-order rate constants for the demetalation (k(obs)) are linear functions of the acid concentrations, and the effective second-order rate constants k(1),(eff) have a hyperbolic dependence on [H+] (k(1),eff = a(1)[H+]/(b(1)+[H+]). The rate of demetalation of 1a in H2PO4-/HPO42- buffer is appreciable, but the k(obs) values for 1b and 1c are immeasurably low, showing that the rates are strongly affected by the CR2 or "tail" fragments, which are known to potently affect the TAML basicity. The reactivities of 1 depend insignificantly on the aromatic ring or "head" group of 1. The proposed mechanism involves precoordination of the acidic buffer species followed by hydrolysis. The demetalating abilities of buffer species depend on their structures and acidities. Thus, although pyridine-2-carboxylic (picolinic) acid catalyzes the demetalation, its 3- and 4-isomers (nicotinic and isonicotininc acids) are inactive. The difference is rationalized to result from the ability that only coordinated picolinic acid has to deliver a proton to an amidato nitrogen in an intramolecular manner. The reaction order in picolinic acid equals one for la and two for 1a. For 1b, "inactive" pyridine and nicotinic acid speed up the demetalation in the presence of picolinic acid, suggesting that the second order arises from the axial binding of two pyridine molecules, one of which must be picolinic acid. The binding of pyridine- and imidazole-type ligands was confirmed by UV/vis equilibrium measurements and X-ray crystallography. The implications of these mechanistic findings for designing superior Fe-TAML oxidation catalysts and catalyst formulations are discussed using the results of DFT calculations.
|
|
| 4. |
- Andersson, Jan O., et al.
(författare)
-
A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plasticity among diplomonads and significant lateral gene transfer in eukaryote genome evolution
- 2007
-
Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 8, s. 51-
-
Forskningsöversikt (refereegranskat)abstract
- Background: Comparative genomic studies of the mitochondrion-lacking protist group Diplomonadida (diplomonads) has been lacking, although Giardia lamblia has been intensively studied. We have performed a sequence survey project resulting in 2341 expressed sequence tags (EST) corresponding to 853 unique clones, 5275 genome survey sequences (GSS), and eleven finished contigs from the diplomonad fish parasite Spironucleus salmonicida (previously described as S. barkhanus). Results: The analyses revealed a compact genome with few, if any, introns and very short 3′ untranslated regions. Strikingly different patterns of codon usage were observed in genes corresponding to frequently sampled ESTs versus genes poorly sampled, indicating that translational selection is influencing the codon usage of highly expressed genes. Rigorous phylogenomic analyses identified 84 genes - mostly encoding metabolic proteins - that have been acquired by diplomonads or their relatively close ancestors via lateral gene transfer (LGT). Although most acquisitions were from prokaryotes, more than a dozen represent likely transfers of genes between eukaryotic lineages. Many genes that provide novel insights into the genetic basis of the biology and pathogenicity of this parasitic protist were identified including 149 that putatively encode variant-surface cysteine-rich proteins which are candidate virulence factors. A number of genomic properties that distinguish S. salmonicida from its human parasitic relative G. lamblia were identified such as nineteen putative lineage-specific gene acquisitions, distinct mutational biases and codon usage and distinct polyadenylation signals. Conclusion: Our results highlight the power of comparative genomic studies to yield insights into the biology of parasitic protists and the evolution of their genomes, and suggest that genetic exchange between distantly-related protist lineages may be occurring at an appreciable rate in eukaryote genome evolution.
|
|
| 5. |
- Lindh, Christina, et al.
(författare)
-
Combination of radiographic measurement of cortical width and clinical risk index for diagnosis of osteoporosis : the OSTEDENT study
- 2006
-
Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by an Active Shape Model (ASM) method in combination with a clinical risk index, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry (DXA) of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. A questionnaire was completed for each subject to identify factors related to osteoporosis risk and calculate a clinical risk index (OSIRIS). A manually initialised ASM method was used to derive cortical width measurements from each radiograph. ROC analysis was used to identify the most effective clinical index. Logistic regression analysis was used to build a model, with the presence or absence of osteoporosis as the dichotomous dependent variable and OSIRIS and the radiographic data as independent variables. Results: ROC analysis gave an Az value for OSIRIS of 0.841 (95% CI: 0.811 to 0.868). The sensitivity and specificity of the combined radiographic-clinical risk assessment were 38.6% and 97.9% respectively. Conclusions: Combining the cortical width measurement and the clinical risk index provided a high specificity method for detection of subjects with osteoporosis, although sensitivity was modest. This model would be most suitable for use in the context of restricted availability of DXA. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
|
|
| 6. |
- Lindh, Christina, et al.
(författare)
-
Mandibular cortical index for osteoporosis diagnosis : the OSTEODENT project
- 2006
-
Konferensbidrag (refereegranskat)abstract
- Objectives: to determine the diagnostic validity of the mandibular cortical index (MCI) for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made an assessment of porosity of the cortex of the lower border of the mandible using MCI. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. MCI data for each observer were dichotomosed so that MCI grade 3 indicated a positive test result and grades 1 and 2 a negative test result. The sensitivities and specificties of MCI for osteoporosis diagnosis were determined: Osteoporosis at any site Osteoporosis at femoral neck Observer Sensitivity (%) Specificity (%) Sensitivity (%) Specificity (%) 1 24.8 93.3 27.3 91.3 2 23.4 93.2 24.2 91.3 3 23.4 91.5 24.2 89.8 4 20.6 99.8 22.7 91.8 5 19.1 91.1 22.7 90.3 Interobserver repeatability (using weighted Kappa) showed a range of 0.183 to 0.780, with a median value of 0.467. This median indicated moderate agreement. Conclusions: MCI had low sensitivity but high specificity for diagnosis of osteoporosis. This high specificity might prove to be more appropriate for use in primary dental care than using a different diagnostic threshold. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
|
|
| 7. |
- Lindh, Christina, et al.
(författare)
-
Quantitative analysis of the tradigraphic trabecular pattern as a predictor for BMD-values : the OSTEODENT study
- 2006
-
Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of computer aided analysis of the radiographic trabecular pattern as a predictor of BMD-values of peri- and post-menopausal women to support the diagnosis of osteoporosis. Methods: Panoramic and intra-oral radiographs were obtained from volunteer female subjects in the 45 to 70 year age band, recruited from four European centres. These volunteers also underwent dual x-ray energy absorptiometry (DXA) of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis. A computer aided analysis of the radiographic trabecular pattern was performed on the radiographs in relevant regions of interest, and used to predict the BMD values of hip and spine by multiple regression techniques. Results: Data of 525 subjects (mean age 54.6 y; sd = 6.0 y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. The most suitable ROIs for the panoramic images were in the mandibular premolar region and in the ramus. For the intra-oral radiographs (upper- and lower jaw) an area in between the first and second premolar was chosen. Including age as a parameter improved the results. Az values are given below: ROI BMD-hip BMD-spine panoramic radiograph 0.65 0.71 panoramic radiograph + age 0.77 0.79 intra-oral radiograph 0.71 0.73 intra-oral radiograph + age 0.79 0.82 panoramic + intraoral radiographs 0.72 0.75 panoramic + intraoral radiographs + age 0.80 0.84 Conclusions: Quantitative analysis of the radiographic trabecular pattern together with the age of the patient is a promising parameter for the prediction of BMD values as an indicator of osteoporosis. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
|
|
| 8. |
- Lindh, Christina, et al.
(författare)
-
ROC analysis of automatically measured mandibular cortical width from panoramic radiographs for diagnosis of osteoporosis : the OSTEDENT study
- 2006
-
Konferensbidrag (refereegranskat)abstract
- 1School of Dentistry and 2Imaging Science and Biomedical Engineering, The University of Manchester, United Kingdom 3School of Dentistry, Oral Pathology and Maxillofacial Surgery, Oral Imaging Centre, Katholieke Universiteit Leuven, Belgium 4Oral Diagnosis and Radiology, The National and Kapodistrian University of Athens, Greece 5Oral Radiology, Malmö University, Sweden 6Oral Radiology, ACTA, Amsterdam, The Netherlands Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured by Active Shape Model (ASM) methods, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Two ASM methods, one entirely automatic and one manually initialised, were used to derive measurements of mandibular cortical width. ROC analysis was used to determine the diagnostic ability of manual and ASM methods. Results: 652 subjects were examined (mean age 54.9y; sd=6.10), with 140 (21.5%) being classified as having osteoporosis. Using the manually initialized ASM method, Az values for the diagnosis of osteoporosis at any site and at femoral neck alone were 0.816 (95% CI: 0.784 to 0.845) and 0.835, (95% CI: 0.805-0.863), respectively. Using the automatically initialized ASM method, the Az values for the diagnosis of osteoporosis at any site and at the femoral neck alone were 0.759 (95% CI: 0.724-0.791) and 0.805 (95% CI: 0.773 -0.835), respectively. The difference in Az of the two methods for the diagnosis of osteoporosis at either the hip or spine was significant (p<0.001), but not significant at the femoral neck alone. Conclusions: ASM-based methods ofmandibular cortical width measurement were effective in the diagnosis of osteoporosis. The manually initialized method, involving a small amount of user interaction, performed best. Further analysis is necessary to establish the appropriate diagnostic threshold for clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
|
|
| 9. |
- Lindh, Christina, et al.
(författare)
-
ROC analysis of densitometric measurements on intraoral radiographs for detection of osteoporosis as part of the OSTEDENT study
- 2006
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: To determine the diagnostic validity of mandibular and maxillary bone density, measured between the premolars (mm Aleq) in detecting osteoporosis at the hip or lumbar spine. Methods: Female subjects between 45 and 70 years of age, were recruited from 4 European centres. They underwent dual x-ray energy absorptiometry of the hip and lumber spine, to provide a gold standard diagnosis of osteoporosis. In addition, intra-oral radiography of upper and lower right premolar region was performed, using an aluminum wedge as a densitometric reference. Jaw bone density in 4 selected regions of interest (ROI) was determined using dedicated software Osteop (Nackaerts et al 2005**). Two ROIs were determined between the upper premolar teeth and another 2 between the lower premolars. 5 observers performed the analysis. Intra- and inter-observer differences and ROC curves were analyzed. Results: Results from 660 subjects (mean age 54.8y; sd 6.19) were suitable for analysis. 136 of these subjects were classified as having osteoporosis. For ROC analysis, measurement data from all observers were averaged, since there was no significant inter-observer difference. Az values as well as 95% confidence intervals are shown in the table: Detecting osteoporosis at any site (spine, hip, femoral neck): ROI1 upper jaw Az 0.691 (0.653 to 0.726) ROI2 upper jaw Az 0.708 (0.671 to 0.743) ROI1 lower jaw Az 0.709 (0.672 o 0.745) ROI2 lower jaw Az 0.702 (0.655 to 0.738) None of the differences in Az between sites was statistically significant (p always > >0.05). Conclusions: Density of the premolar region expressed in mm Aleq is a fair indication for the presence of osteoporosis. More extensive analysis of the OSTEODENT results might reveal an even better predictive tool for osteoporosis screening. **Nackaerts O, Jacobs R, Pillen M, Engelen L, Gijbels F, Devlin H, Lindh C, Nicopolou-Karayianni K, van der Stelt P, Horner K. Accuracy and precision of a densitometric tool for jaw bone. DentoMaxilloFacial Radiology. In press This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
|
|
| 10. |
- Lindh, Christina, et al.
(författare)
-
ROC analysis of directly measured mandibular cortical width from panoramic radiogarphs for diagnosis of osteoporosis : the OSTEODENT study
- 2006
-
Konferensbidrag (refereegranskat)abstract
- Objectives: To determine the diagnostic validity of the width of the inferior mandibular cortex on dental panoramic radiographs (DPRs), as measured directly by observers, for the diagnosis of osteoporosis in peri- and post-menopausal women. Methods: Volunteer female subjects in the 45 to 70 year age band, recruited from four European centres, underwent dual x-ray energy absorptiometry of the hip and lumbar spine, to provide a gold standard diagnosis of osteoporosis, and a DPR examination. Five observers, all oral radiologists but of different experience, made manual measurements of width of the mandibular lower border cortex below the mental foramina bilaterally. Results: Data of 661 subjects (mean age 54.8y; sd = 6.19y) were available for analysis, with 140 (21.2%) being classified as having osteoporosis. Az values are given below: Osteoporosis at any site Osteoporosis at femoral neck Observer Az (se) 95% CI Az (se) 95% CI 1 0.782 0.748-0.813 0.804 0.771-0.833 2 0.766 0.731-0.799 0.757 0.722-0.791 3 0.756 0.721-0.788 0.790 0.757-0.821 4 0.746 0.711-0.779 0.762 0.727-0.794 5 0.710 0.673-0.744 0.752 0.718-0.785 A diagnostic threshold of 3mm resulted in a sensitivity of 50.7% and a specificity of 80.4% (data for median observer, 2). Mean within-subject variance for the five observers was 0.126mm (sd = 0.355mm). Repeatability is the difference between two measurements made by any pair of observers for the same subject and was expected to be less than 0.983 mm for 95% of pairs of observations. Conclusions: Direct measurement of mandibular cortical width was diagnostically effective in diagnosis of osteoporosis. However, repeatability may be a problem in clinical use. This work was supported by a research and technological development project grant from the European Commission FP5 'Quality of Life and Management of Living Resources' (QLK6-2002-02243).
|
|
