| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
-
Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 3. |
- Beecham, Ashley H, et al.
(author)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
-
Journal article (peer-reviewed)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 4. |
- Chigrinova, Ekaterina, et al.
(author)
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Two main genetic pathways lead to the transformation of chronic lymphocytic leukemia to Richter syndrome
- 2013
-
In: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 122:15, s. 2673-2682
-
Journal article (peer-reviewed)abstract
- Richter syndrome (RS) occurs in up to 15% of patients with chronic lymphocytic leukemia (CLL). Although RS, usually represented by the histologic transformation to a diffuse large B-cell lymphoma (DLBCL), is associated with a very poor outcome, especially when clonally related to the preexisting CLL, the mechanisms leading to RS have not been clarified. To better understand the pathogenesis of RS, we analyzed a series of cases including 59 RS, 28 CLL phase of RS, 315 CLL, and 127 de novo DLBCL. RS demonstrated a genomic complexity intermediate between CLL and DLBCL. Cell-cycle deregulation via inactivation of TP53 and of CDKN2A was a main mechanism in the histologic transformation from CLL phase, being present in approximately one half of the cases, and affected the outcome of the RS patients. A second major subgroup was characterized by the presence of trisomy 12 and comprised one third of the cases. Although RS shared some of the lesions seen in de novo DLBCL, its genomic profile was clearly separate. The CLL phase preceding RS had not a generalized increase in genomic complexity compared with untransformed CLL, but it presented clear differences in the frequency of specific genetic lesions.
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| 5. |
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| 6. |
- Mattsson, Niklas, 1979, et al.
(author)
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The Alzheimer's Association external quality control program for cerebrospinal fluid biomarkers.
- 2011
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In: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 7:4
-
Journal article (peer-reviewed)abstract
- The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ)-42, total-tau (T-tau), and phosphorylated-tau (P-tau) demonstrate good diagnostic accuracy for Alzheimer's disease (AD). However, there are large variations in biomarker measurements between studies, and between and within laboratories. The Alzheimer's Association has initiated a global quality control program to estimate and monitor variability of measurements, quantify batch-to-batch assay variations, and identify sources of variability. In this article, we present the results from the first two rounds of the program.
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| 7. |
- Pignata, Giuliano, et al.
(author)
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SN 2009bb : A PECULIAR BROAD-LINED TYPE Ic SUPERNOVA
- 2011
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 728:1, s. 14-
-
Journal article (peer-reviewed)abstract
- Ultraviolet, optical, and near-infrared photometry and optical spectroscopy of the broad-lined Type Ic supernova (SN) 2009bb are presented, following the flux evolution from -10 to +285 days past B-band maximum. Thanks to the very early discovery, it is possible to place tight constraints on the SN explosion epoch. The expansion velocities measured from near maximum spectra are found to be only slightly smaller than those measured from spectra of the prototype broad-lined SN 1998bw associated with GRB 980425. Fitting an analytical model to the pseudobolometric light curve of SN 2009bb suggests that 4.1 +/- 1.9M(circle dot) of material was ejected with 0.22 +/- 0.06 M(circle dot) of it being (56)Ni. The resulting kinetic energy is 1.8 +/- 0.7 x 10(52) erg. This, together with an absolute peak magnitude of M(B) = -18.36 +/- 0.44, places SN 2009bb on the energetic and luminous end of the broad-lined Type Ic (SN Ic) sequence. Detection of helium in the early time optical spectra accompanied with strong radio emission and high metallicity of its environment makes SN 2009bb a peculiar object. Similar to the case for gamma-ray bursts (GRBs), we find that the bulk explosion parameters of SN 2009bb cannot account for the copious energy coupled to relativistic ejecta, and conclude that another energy reservoir (a central engine) is required to power the radio emission. Nevertheless, the analysis of the SN 2009bb nebular spectrum suggests that the failed GRB detection is not imputable to a large angle between the line-of-sight and the GRB beamed radiation. Therefore, if a GRB was produced during the SN 2009bb explosion, it was below the threshold of the current generation of gamma-ray instruments.
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| 8. |
- Soffitta, Paolo, et al.
(author)
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XIPE : the X-ray imaging polarimetry explorer
- 2013
-
In: Experimental astronomy. - : Springer Science and Business Media LLC. - 0922-6435 .- 1572-9508. ; 36:3, s. 523-567
-
Journal article (peer-reviewed)abstract
- X-ray polarimetry, sometimes alone, and sometimes coupled to spectral and temporal variability measurements and to imaging, allows a wealth of physical phenomena in astrophysics to be studied. X-ray polarimetry investigates the acceleration process, for example, including those typical of magnetic reconnection in solar flares, but also emission in the strong magnetic fields of neutron stars and white dwarfs. It detects scattering in asymmetric structures such as accretion disks and columns, and in the so-called molecular torus and ionization cones. In addition, it allows fundamental physics in regimes of gravity and of magnetic field intensity not accessible to experiments on the Earth to be probed. Finally, models that describe fundamental interactions (e.g. quantum gravity and the extension of the Standard Model) can be tested. We describe in this paper the X-ray Imaging Polarimetry Explorer (XIPE), proposed in June 2012 to the first ESA call for a small mission with a launch in 2017. The proposal was, unfortunately, not selected. To be compliant with this schedule, we designed the payload mostly with existing items. The XIPE proposal takes advantage of the completed phase A of POLARIX for an ASI small mission program that was cancelled, but is different in many aspects: the detectors, the presence of a solar flare polarimeter and photometer and the use of a light platform derived by a mass production for a cluster of satellites. XIPE is composed of two out of the three existing JET-X telescopes with two Gas Pixel Detectors (GPD) filled with a He-DME mixture at their focus. Two additional GPDs filled with a 3-bar Ar-DME mixture always face the Sun to detect polarization from solar flares. The Minimum Detectable Polarization of a 1 mCrab source reaches 14 % in the 2-10 keV band in 10(5) s for pointed observations, and 0.6 % for an X10 class solar flare in the 15-35 keV energy band. The imaging capability is 24 arcsec Half Energy Width (HEW) in a Field of View of 14.7 arcmin x 14.7 arcmin. The spectral resolution is 20 % at 6 keV and the time resolution is 8 mu s. The imaging capabilities of the JET-X optics and of the GPD have been demonstrated by a recent calibration campaign at PANTER X-ray test facility of the Max-Planck-Institut fur extraterrestrische Physik (MPE, Germany). XIPE takes advantage of a low-earth equatorial orbit with Malindi as down-link station and of a Mission Operation Center (MOC) at INPE (Brazil). The data policy is organized with a Core Program that comprises three months of Science Verification Phase and 25 % of net observing time in the following 2 years. A competitive Guest Observer program covers the remaining 75 % of the net observing time.
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| 9. |
- Aerts, Joel, et al.
(author)
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Guidance on current good radiopharmacy practice for the small-scale preparation of radiopharmaceuticals using automated modules : a European perspective
- 2014
-
In: Journal of labelled compounds & radiopharmaceuticals. - : Wiley-Blackwell. - 0362-4803 .- 1099-1344. ; 57:10, s. 615-620
-
Journal article (peer-reviewed)abstract
- This document is meant to complement Part B of the EANM Guidelines on current good radiopharmacy practice (cGRPP) in the preparation of radiopharmaceuticals issued by the Radiopharmacy Committee of the European Association of Nuclear Medicine, covering small-scale in-house preparation of radiopharmaceuticals with automated modules. The aim is to provide more detailed and practice-oriented guidance to those who are involved in the small-scale preparation of radiopharmaceuticals, which are not intended for commercial purposes or distribution.
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| 10. |
- Brizuela, Fernando, et al.
(author)
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Imaging at the Nanoscale With Practical Table-Top EUV Laser-Based Full-Field Microscopes
- 2012
-
In: IEEE Journal of Selected Topics in Quantum Electronics. - 1077-260X. ; 18:1, s. 434-442
-
Journal article (peer-reviewed)abstract
- The demonstration of table-top high average power extreme-ultraviolet (EUV) lasers combined with the engineering of specialized optics has enabled the demonstration of full-field microscopes that have achieved tens of nanometer spatial resolution. This paper describes the geometry of the EUV microscopes tailored to specific imaging applications. The microscope illumination characteristics are assessed and an analysis on the microscope's spatial resolution is presented. Examples of the capabilities of these table-top EUV aerial microscopes for imaging nanostructures and surfaces are presented.
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| 11. |
- Bufano, Filomena, et al.
(author)
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THE HIGHLY ENERGETIC EXPANSION OF SN 2010bh ASSOCIATED WITH GRB 100316D
- 2012
-
In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 753:1, s. 67-
-
Journal article (peer-reviewed)abstract
- We present the spectroscopic and photometric evolution of the nearby (z = 0.059) spectroscopically confirmed Type Ic supernova, SN 2010bh, associated with the soft, long-duration gamma-ray burst (X-ray flash) GRB 100316D. Intensive follow-up observations of SN 2010bh were performed at the ESO Very Large Telescope (VLT) using the X-shooter and FORS2 instruments. Thanks to the detailed temporal coverage and the extended wavelength range (3000-24800 angstrom), we obtained an unprecedentedly rich spectral sequence among the hypernovae, making SN 2010bh one of the best studied representatives of this SN class. We find that SN 2010bh has a more rapid rise to maximum brightness (8.0 +/- 1.0 rest-frame days) and a fainter absolute peak luminosity (L-bol approximate to 3 x 10(42) erg s(-1)) than previously observed SN events associated with GRBs. Our estimate of the ejected Ni-56 mass is 0.12 +/- 0.02 M-circle dot. From the broad spectral features, we measure expansion velocities up to 47,000 km s(-1), higher than those of SNe 1998bw (GRB 980425) and 2006aj (GRB 060218). Helium absorption lines He I lambda 5876 and He I 1.083 mu m, blueshifted by similar to 20,000-30,000 km s(-1) and similar to 28,000-38,000 km s(-1), respectively, may be present in the optical spectra. However, the lack of coverage of the He I 2.058 mu m line prevents us from confirming such identifications. The nebular spectrum, taken at similar to 186 days after the explosion, shows a broad but faint [O I] emission at 6340 angstrom. The light curve shape and photospheric expansion velocities of SN 2010bh suggest that we witnessed a highly energetic explosion with a small ejected mass (E-k approximate to 10(52) erg and M-ej approximate to 3 M-circle dot). The observed properties of SN 2010bh further extend the heterogeneity of the class of GRB SNe.
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| 12. |
- Deng, Hexiang, et al.
(author)
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Large pore apertures in a series of metal organic frameworks
- 2012
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 336:6084, s. 1018-1023
-
Journal article (peer-reviewed)abstract
- We report a strategy to expand the pore aperture of metal-organic frameworks (MOFs) into a previously unattained size regime (>32 angstroms). Specifically, the systematic expansion of a well-known MOF structure, MOF-74, from its original link of one phenylene ring (I) to two, three, four, five, six, seven, nine, and eleven (II to XI, respectively), afforded an isoreticular series of MOF-74 structures (termed IRMOF-74-I to XI) with pore apertures ranging from 14 to 98 angstroms. All members of this series have non-interpenetrating structures and exhibit robust architectures, as evidenced by their permanent porosity and high thermal stability (up to 300 degrees C). The pore apertures of an oligoethylene glycol-functionalized IRMOF-74-VII and IRMOF-74-IX are large enough for natural proteins to enter the pores.
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| 13. |
- dos Reis, Fabio Bueno, Jr., et al.
(author)
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Nodulation and nitrogen fixation by Mimosa spp. in the Cerrado and Caatinga biomes of Brazil
- 2010
-
In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 186:4, s. 934-946
-
Journal article (peer-reviewed)abstract
- P>An extensive survey of nodulation in the legume genus Mimosa was undertaken in two major biomes in Brazil, the Cerrado and the Caatinga, in both of which there are high degrees of endemicity of the genus. Nodules were collected from 67 of the 70 Mimosa spp. found. Thirteen of the species were newly reported as nodulating. Nodules were examined by light and electron microscopy, and all except for M. gatesiae had a structure typical of effective Mimosa nodules. The endosymbiotic bacteria in nodules from all of the Mimosa spp. were identified as Burkholderia via immunolabelling with an antibody against Burkholderia phymatum STM815. Twenty of the 23 Mimosa nodules tested were shown to contain nitrogenase by immunolabelling with an antibody to the nitrogenase Fe- (nifH) protein, and using the delta 15N (15N natural abundance) technique, contributions by biological N-2 fixation of up to 60% of total plant N were calculated for Caatinga Mimosa spp. It is concluded that nodulation in Mimosa is a generic character, and that the preferred symbionts of Brazilian species are Burkholderia. This is the first study to demonstrate N-2 fixation by beta-rhizobial symbioses in the field.
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| 14. |
- Gustafsson, Mika, et al.
(author)
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Modules, networks and systems medicine for understanding disease and aiding diagnosis
- 2014
-
In: Genome Medicine. - : BioMed Central. - 1756-994X. ; 6:82
-
Research review (peer-reviewed)abstract
- Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.
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| 15. |
- Hecker, Yanina P., et al.
(author)
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A Neospora caninum vaccine using recombinant proteins fails to prevent foetal infection in pregnant cattle after experimental intravenous challenge
- 2014
-
In: Veterinary Immunology and Immunopathology. - : Elsevier BV. - 0165-2427 .- 1873-2534. ; 162:3-4, s. 142-153
-
Journal article (peer-reviewed)abstract
- The aim of the present study was to evaluate the immunogenicity and protective efficacy of rNcSAG1, rNcHSP20 and rNcGRA7 recombinant proteins formulated with immune stimulating complexes (ISCOMs) in pregnant heifers against vertical transmission of Neospora caninum. Twelve pregnant heifers were divided into 3 groups of 4 heifers each, receiving different formulations before mating. Immunogens were administered twice subcutaneously: group A animals were inoculated with three recombinant proteins (rNcSAG1, rNcHSP20, rNcGRA7) formulated with ISCOMs; group B animals received ISCOM-MATRIX (without antigen) and group C received sterile phosphate-buffered saline (PBS) only. The recombinant proteins were expressed in Escherichia coil and purified nickel resin. All groups were intravenously challenged with the NC-1 strain of N. caninum at Day 70 of gestation and dams slaughtered at week 17 of the experiment. Heifers from group A developed specific antibodies against rNcSAG1, rNcHSP20 and rNcGRA7 prior to the challenge. Following immunization, an statistically significant increase of antibodies against rNcSAG1 and rNcHSP20 in all animals of group A was detected compared to animals in groups B and C at weeks 5, 13 and 16 (P< 0.001). Levels of antibodies against rNcGRA7 were statistical higher in group A animals when compared with groups B and Cat weeks 5 and 16 (P> 0.001). There were no differences in IFN-gamma production among the experimental groups at any time point (P> 0.05). Transplacental transmission was determined in all foetuses of groups A, B and C by Western blot, immunohistochemistry and nested PCR. This work showed that rNcSAG1, rNcHSP20 and rNcGRA7 proteins while immunogenic in cattle failed to prevent the foetal infection in pregnant cattle challenged at Day 70 of gestation.
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| 16. |
- Kirchhof, Paulus, et al.
(author)
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Comprehensive risk reduction in patients with atrial fibrillation : emerging diagnostic and therapeutic options - a report from the 3rd Atrial Fibrillation Competence NETwork/European Heart Rhythm Association consensus conference
- 2012
-
In: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 14:1, s. 8-27
-
Research review (peer-reviewed)abstract
- While management of atrial fibrillation (AF) patients is improved by guideline-conform application of anticoagulant therapy, rate control, rhythm control, and therapy of accompanying heart disease, the morbidity and mortality associated with AF remain unacceptably high. This paper describes the proceedings of the 3rd Atrial Fibrillation NETwork (AFNET)/European Heart Rhythm Association (EHRA) consensus conference that convened over 60 scientists and representatives from industry to jointly discuss emerging therapeutic and diagnostic improvements to achieve better management of AF patients. The paper covers four chapters: (i) risk factors and risk markers for AF; (ii) pathophysiological classification of AF; (iii) relevance of monitored AF duration for AF-related outcomes; and (iv) perspectives and needs for implementing better antithrombotic therapy. Relevant published literature for each section is covered, and suggestions for the improvement of management in each area are put forward. Combined, the propositions formulate a perspective to implement comprehensive management in AF.
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| 17. |
- Krisciunas, Kevin, et al.
(author)
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THE MOST SLOWLY DECLINING TYPE Ia SUPERNOVA 2001ay
- 2011
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In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 142:3, s. 74-
-
Journal article (peer-reviewed)abstract
- We present optical and near-infrared photometry, as well as ground-based optical spectra and Hubble Space Telescope ultraviolet spectra, of the Type Ia supernova (SN) 2001ay. At maximum light the Si II and Mg II lines indicated expansion velocities of 14,000 km s-(1), while Si III and S II showed velocities of 9000 km s(-1). There is also evidence for some unburned carbon at 12,000 km s(-1). SN 2001ay exhibited a decline-rate parameter of Delta m(15)(B) = 0.68 +/- 0.05 mag; this and the B-band photometry at t greater than or similar to + 25 day past maximum make it the most slowly declining Type Ia SN yet discovered. Three of the four super-Chandrasekhar-mass candidates have decline rates almost as slow as this. After correction for Galactic and host-galaxy extinction, SN 2001ay had M(B) = -19.19 and M(V) = -19.17 mag at maximum light; thus, it was not overluminous in optical bands. In near-infrared bands it was overluminous only at the 2 sigma level at most. For a rise time of 18 days (explosion to bolometric maximum) the implied (56)Ni yield was (0.58 +/- 0.15)/alpha M(circle dot), with alpha = L(max)/E(Ni) probably in the range 1.0-1.2. The (56)Ni yield is comparable to that of many Type Ia SNe. The normal (56)Ni yield and the typical peak optical brightness suggest that the very broad optical light curve is explained by the trapping of gamma rays in the inner regions.
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| 18. |
- Loyola, C., et al.
(author)
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Onset of failure in argon by the effect of a shockwave : A molecular dynamics study
- 2010
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In: Computational materials science. - : Elsevier BV. - 0927-0256 .- 1879-0801. ; 49:3, s. 582-587
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Journal article (peer-reviewed)abstract
- Molecular dynamic simulations of shockwaves in solid argon were performed. The simulation cell contains 51,840 atoms at 5 K interacting by means of a pairwise potential. The shockwave itself was introduced explicitly in the simulation by a piston hitting the sample from one side of the simulation box, at speeds ranging from 1.2 to 1.3 times the speed of sound in solid argon at the chosen density. In order to characterize the sample in terms of both structural and dynamic properties, we determine the density and temperature profiles according the advance of the shockwave, evaluating, for different slabs, the pair-distribution function, coordination number as well as performing a common neighbor analysis for the atoms. Our simulations reproduce the experimental Hugoniot curve and show how the material is break due to rarefaction waves. The picture that emerges is that when the shockwave starts, a local melting is produced in a region of the sample. Then, as the shockwave travels through the sample, a high density disordered phase is identified. When the piston stops, a rarefaction wave develops, producing a large tensile stress, which finally causes the failure of the sample.
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| 19. |
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| 20. |
- McKay, James D., et al.
(author)
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A Genome-Wide Association Study of Upper Aerodigestive Tract Cancers Conducted within the INHANCE Consortium
- 2011
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In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 7:3
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have been successful in identifying common genetic variation involved in susceptibility to etiologically complex disease. We conducted a GWAS to identify common genetic variation involved in susceptibility to upper aero-digestive tract (UADT) cancers. Genome-wide genotyping was carried out using the Illumina HumanHap300 beadchips in 2,091 UADT cancer cases and 3,513 controls from two large European multi-centre UADT cancer studies, as well as 4,821 generic controls. The 19 top-ranked variants were investigated further in an additional 6,514 UADT cancer cases and 7,892 controls of European descent from an additional 13 UADT cancer studies participating in the INHANCE consortium. Five common variants presented evidence for significant association in the combined analysis (p <= 5 x 10(-7)). Two novel variants were identified, a 4q21 variant (rs1494961, p = 1 x 10(-8)) located near DNA repair related genes HEL308 and FAM175A (or Abraxas) and a 12q24 variant (rs4767364, p = 2 x 10(-8)) located in an extended linkage disequilibrium region that contains multiple genes including the aldehyde dehydrogenase 2 (ALDH2) gene. Three remaining variants are located in the ADH gene cluster and were identified previously in a candidate gene study involving some of these samples. The association between these three variants and UADT cancers was independently replicated in 5,092 UADT cancer cases and 6,794 controls non-overlapping samples presented here (rs1573496-ADH7, p = 5 x 10(-8); rs1229984-ADH1B, p = 7 x 10(-9); and rs698-ADH1C, p = 0.02). These results implicate two variants at 4q21 and 12q24 and further highlight three ADH variants in UADT cancer susceptibility.
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| 21. |
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| 22. |
- Penacho, Nuno, et al.
(author)
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Physicochemical properties of transferrin-associated lipopolyplexes and their role in biological activity
- 2010
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In: Colloids and Surfaces B: Biointerfaces. - : Elsevier BV. - 1873-4367 .- 0927-7765. ; 76:1, s. 207-214
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Journal article (peer-reviewed)abstract
- The combination of polyethylenimine (PEI), as a plasmid DNA pre-condensing agent, and cationic lipids has been reported to result in a synergistic effect on transfection. Recently, we have explored this effect by associating low-molecular weight PEIs with transferrin-associated lipoplexes using different cationic liposome formulations. The resulting lipopolyplexes that have shown to be the most efficient in mediating transfection were those prepared from cationic liposomes composed of DOTAP:Chol (associated or not with transferrin) and from a pH-sensitive liposome formulation (DOTAP:Chol: DOPE:CHEMS). In the present work, the physicochemical properties of these lipopolyplexes were studied aiming at establishing a correlation with their transfection efficiency. For this purpose, the lipopolyplexes were characterized in terms of their morphology by performing ultrastructural Studies using cryo-TEM microscopy, investigating inner DNA Structure using circular dichroism and characterizing particle size by photon correlation spectroscopy. A correlation between efficiency of transfection and more compact inner DNA structure and smaller particle sizes (around 250 nm) was found. In addition, the visualization of liposomes and lipopolyplexes at the ultrastructural level revealed that the particles presenting enhanced transfection efficiencies are associated with higher electron density. Recently, PEI-based lipopolyplexes were reported to gain entry into the cell through the caveolae-mediated pathway. Based on the present finding that DOTAP:Chol liposomes exhibit the ability to form hexagonal structures when prepared at high concentrations, we propose that the lipopolyplexes containing DOTAP:Chol take advantage of such capacity to escape from the endocytotic vesicles, which will contribute to the observed high transfection efficiencies. (C) 2009 Elsevier B.V. All rights reserved.
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| 23. |
- Sokka, Tuulikki, et al.
(author)
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Work disability remains a major problem in rheumatoid arthritis in the 2000s : data from 32 countries in the QUEST-RA Study
- 2010
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In: Arthritis Research & Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 12:2, s. R42-
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Journal article (peer-reviewed)abstract
- INTRODUCTION:Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries.METHODS:The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses.RESULTS:At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant identifier of work disability in all subgroups was Health Assessment Questionnaire (HAQ) functional disability score.CONCLUSIONS:Work disability rates remain high among people with RA during this millennium. In low-GDP countries, people remain working with high levels of disability and disease activity. Cultural and economic differences between societies affect work disability as an outcome measure for RA.
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| 26. |
- Stuart-Smith, Rick D., et al.
(author)
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Integrating abundance and functional traits reveals new global hotspots of fish diversity
- 2013
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 501:7468, s. 539-
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Journal article (peer-reviewed)abstract
- Species richness has dominated our view of global biodiversity patterns for centuries(1,2). The dominance of this paradigm is reflected in the focus by ecologists and conservation managers on richness and associated occurrence-based measures for understanding drivers of broad-scale diversity patterns and as a biological basis for management(3,4). However, this is changing rapidly, as it is now recognized that not only the number of species but the species present, their phenotypes and the number of individuals of each species are critical in determining the nature and strength of the relationships between species diversity and a range of ecological functions (such as biomass production and nutrient cycling)(5). Integrating these measures should provide a more relevant representation of global biodiversity patterns in terms of ecological functions than that provided by simple species counts. Here we provide comparisons of a traditional global biodiversity distribution measure based on richness with metrics that incorporate species abundances and functional traits. We use data from standardized quantitative surveys of 2,473 marine reef fish species at 1,844 sites, spanning 133 degrees of latitude from all ocean basins, to identify new diversity hotspots in some temperate regions and the tropical eastern Pacific Ocean. These relate to high diversity of functional traits amongst individuals in the community (calculated using Rao's Q(6)), and differ from previously reported patterns in functional diversity and richness for terrestrial animals, which emphasize species-rich tropical regions only(7,8). There is a global trend for greater evenness in the number of individuals of each species, across the reef fish species observed at sites ('community evenness'), at higher latitudes. This contributes to the distribution of functional diversity hotspots and contrasts with well-known latitudinal gradients in richness(2,4). Our findings suggest that the contribution of species diversity to a range of ecosystem functions varies over large scales, and imply that in tropical regions, which have higher numbers of species, each species contributes proportionally less to community-level ecological processes on average than species in temperate regions. Metrics of ecological function usefully complement metrics of species diversity in conservation management, including when identifying planning priorities and when tracking changes to biodiversity values.
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| 27. |
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| 28. |
- Thiele, I., et al.
(author)
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A community-driven global reconstruction of human metabolism
- 2013
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In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 31:5, s. 419-
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Journal article (peer-reviewed)abstract
- Multiple models of human metabolism have been reconstructed, but each represents only a subset of our knowledge. Here we describe Recon 2, a community-driven, consensus 'metabolic reconstruction', which is the most comprehensive representation of human metabolism that is applicable to computational modeling. Compared with its predecessors, the reconstruction has improved topological and functional features, including similar to 2x more reactions and similar to 1.7x more unique metabolites. Using Recon 2 we predicted changes in metabolite biomarkers for 49 inborn errors of metabolism with 77% accuracy when compared to experimental data. Mapping metabolomic data and drug information onto Recon 2 demonstrates its potential for integrating and analyzing diverse data types. Using protein expression data, we automatically generated a compendium of 65 cell type-specific models, providing a basis for manual curation or investigation of cell-specific metabolic properties. Recon 2 will facilitate many future biomedical studies and is freely available at http://humanmetabolism.org/.
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| 29. |
- Tovar, Eduardo, et al.
(author)
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Networked Embedded Systems for Active Flow Control in Aircraft
- 2012
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Reports (peer-reviewed)abstract
- Abstract— Aerodynamic drag is known to be one of the factorscontributing more to increased aircraft fuelconsumption. Theprimary source of skin friction drag during flight is theboundary layer separation. This is the layer ofair movingsmoothly in the immediate vicinity of the aircraft. In this paperwe discuss a cyber-physical system approachable ofperforming an efficient suppression of the turbulent flow byusing a dense sensing deployment to detect the lowpressureregion and a similarly dense deployment of actuators tomanage the turbulent flow. With this concept, onlytheactuators in the vicinity of a separation layer are activated,minimizing power consumption and also the induced drag.
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