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  • 1
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    Equations of state in the Fe–FeSi system at high pressures and temperatures (2014)
    Wiley-Blackwell
    Details
    Publication Date: 2014-03-16
    Description: Earth's core is an iron-rich alloy containing several weight percent of light element(s), possibly including silicon. Therefore the high pressure-temperature equations of state of iron–silicon alloys can provide understanding of the properties of Earth's core. We performed X-ray diffraction experiments using laser-heated diamond anvil cells to achieve simultaneous high pressures and temperatures, up to ~200 GPa for Fe–9wt%Si alloy and ~145 GPa for stoichiometric FeSi. We determined equations of state of the D0 3 , hcp + B2, and hcp phases of Fe–9Si, and the B20 and B2 phases of FeSi. We also calculated equations of state of Fe, Fe 11 Si, Fe 5 Si, Fe 3 Si, and FeSi using ab initio methods, finding that iron and silicon atoms have similar volumes at high pressures. By comparing our experimentally-determined equations of state to the observed core density deficit, we find that the maximum amount of silicon in the outer core is ~11 wt%, while the maximum amount in the inner core is 6–8 wt%, for a purely Fe–Si–Ni core. Bulk sound speeds predicted from our equations of state also match those of the inner and outer core for similar ranges of compositions. We find a compositional contrast between the inner and outer core of 3.5–5.6 wt% silicon, depending on the seismological model used. Theoretical and experimental equations of state agree at high pressures. We find a good match to the observed density, density profile, and sound speed of the Earth's core, suggesting that silicon is a viable candidate for the dominant light element.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley-Blackwell on behalf of American Geophysical Union (AGU).
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  • 2
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    Metaphosphate Stabilization in the Myosin ATPase [Enzymology] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-12-07
    Description: It has been proposed recently that ATP hydrolysis in ATPase enzymes proceeds via an initial intermediate in which the dissociated γ-phosphate of ATP is bound in the protein as a metaphosphate (PγO3−). A combined quantum/classical analysis of this dissociated nucleotide state inside myosin provides a quantitative understanding of how the enzyme stabilizes this unusual metaphosphate. Indeed, in vacuum, the energy of the ADP3−·PγO3−·Mg2+ complex is much higher than that of the undissociated ATP4−. The protein brings it to a surprisingly low value. Energy decomposition reveals how much each interaction in the protein stabilizes the metaphosphate state; backbone peptides of the P-loop contribute 50% of the stabilization energy, and the side chain of Lys-185+ contributes 25%. This can be explained by the fact that these groups make strong favorable interactions with the α- and β-phosphates, thus favoring the charge distribution of the metaphosphate state over that of the ATP state. Further stabilization (16%) is achieved by a hydrogen bond between the backbone C=O of Ser-237 (on loop Switch-1) and a water molecule perfectly positioned to attack the PγO3− in the subsequent hydrolysis step. The planar and singly negative PγO3− is a much better target for the subsequent nucleophilic attack by a negatively charged OH− than the tetrahedral and doubly negative PγO42− group of ATP. Therefore, we argue that the present mechanism of metaphosphate stabilization is common to the large family of nucleotide-hydrolyzing enzymes. Methodologically, this work presents a computational approach that allows us to obtain a truly quantitative conception of enzymatic strategy.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 3
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    The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy (2013)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2013-06-21
    Description: Severe congenital neutropenia as well as primary myelofibrosis are rare in infancy. Elucidation of the underlying mechanism is important because it extends our understanding of the more common adult forms of these disorders. Using homozygosity mapping followed by exome sequencing, we identified a Thr224Asn mutation in the VPS45 gene in infants from consanguineous families who suffered from life-threatening neutropenia, which was refractory to granulocyte CSF, from defective platelet aggregation and myelofibrosis. The mutation segregated in the families, was not present in controls, affected a highly conserved codon, and apparently destabilized the Vps45 protein, which was reduced in the patients’ leukocytes. Introduction of the corresponding mutation into yeast resulted in reduced cellular levels of Vps45 and also of the cognate syntaxin Tlg2, which is required for membrane traffic through the endosomal system. A defect in the endosomal-lysosomal pathway, the homologous system in humans, was suggested by the absence of lysosomes in the patients’ fibroblasts and by the depletion of α granules in their platelets. Importantly, accelerated apoptosis was observed in the patients’ neutrophils and bone marrow. This is the first report of a Vps45-related disease in humans, manifesting by neutropenia, thrombasthenia, myelofibrosis, and progressive bone marrow failure.
    Keywords: Pediatric Hematology, Phagocytes, Granulocytes, and Myelopoiesis
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
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  • 4
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    The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS (2014)
    Nature Publishing Group (NPG)
    In: Leukemia
    Details
    Publication Date: 2014-01-09
    Description: The clinical relevance of minor paroxysmal nocturnal hemoglobinuria clones in refractory cytopenia of childhood: a prospective study by EWOG-MDS Leukemia 28, 189 (January 2014). doi:10.1038/leu.2013.195 Authors: A M Aalbers, V H J van der Velden, A Yoshimi, A Fischer, P Noellke, C M Zwaan, I Baumann, H B Beverloo, M Dworzak, H Hasle, F Locatelli, B De Moerloose, G Göhring, M Schmugge, J Stary, M Zecca, A W Langerak, J J M van Dongen, R Pieters, C M Niemeyer & M M van den Heuvel-Eibrink
    Print ISSN: 0887-6924
    Electronic ISSN: 1476-5551
    Topics: Medicine
    Published by Nature Publishing Group (NPG)
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  • 5
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    A survey of tools for variant analysis of next-generation genome sequencing data (2014)
    Oxford University Press
    Details
    Publication Date: 2014-03-18
    Description: Recent advances in genome sequencing technologies provide unprecedented opportunities to characterize individual genomic landscapes and identify mutations relevant for diagnosis and therapy. Specifically, whole-exome sequencing using next-generation sequencing (NGS) technologies is gaining popularity in the human genetics community due to the moderate costs, manageable data amounts and straightforward interpretation of analysis results. While whole-exome and, in the near future, whole-genome sequencing are becoming commodities, data analysis still poses significant challenges and led to the development of a plethora of tools supporting specific parts of the analysis workflow or providing a complete solution. Here, we surveyed 205 tools for whole-genome/whole-exome sequencing data analysis supporting five distinct analytical steps: quality assessment, alignment, variant identification, variant annotation and visualization. We report an overview of the functionality, features and specific requirements of the individual tools. We then selected 32 programs for variant identification, variant annotation and visualization, which were subjected to hands-on evaluation using four data sets: one set of exome data from two patients with a rare disease for testing identification of germline mutations, two cancer data sets for testing variant callers for somatic mutations, copy number variations and structural variations, and one semi-synthetic data set for testing identification of copy number variations. Our comprehensive survey and evaluation of NGS tools provides a valuable guideline for human geneticists working on Mendelian disorders, complex diseases and cancers.
    Print ISSN: 1467-5463
    Electronic ISSN: 1477-4054
    Topics: Biology , Computer Science
    Published by Oxford University Press
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  • 6
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    Localized shear in the deep lithosphere beneath the San Andreas fault system (2014)
    Geological Society of America (GSA)
    In: Geology
    Details
    Publication Date: 2014-03-15
    Description: Seismic images of the base of the lithosphere across the San Andreas fault system (California, USA) yield new constraints on the distribution of deformation in the deep lithosphere beneath this strike-slip plate boundary. We show that conversions of shear to compressional waves (Sp) across the base of the lithosphere are systematically weaker on the western side of the plate boundary, indicating that the drop in seismic shear-wave velocity from lithosphere to asthenosphere is either smaller or occurs over a larger depth range. In central and northern California, the lithosphere-asthenosphere boundary changes character across a distance of 〈50 km, and does so directly beneath the San Andreas fault along its simple central segment, and beneath the Calaveras–Green Valley–Bartlett Springs faults to the north. Given the absolute velocities of the North America and Pacific plates, and low viscosities inferred for the asthenosphere, these results indicate the juxtaposition of mantle lithospheres with different properties across these faults. The spatial correlation between the central San Andreas fault and the laterally abrupt change in the velocity structure of the deepest mantle lithosphere points to the accommodation of relative plate motion on a narrow shear zone (〈50 km in width), and a rheology that enables strain localization throughout the thickness of the lithosphere.
    Print ISSN: 0091-7613
    Electronic ISSN: 1943-2682
    Topics: Geosciences
    Published by Geological Society of America (GSA)
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  • 7
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    Feasibility of semiquantitative liver perfusion assessment by ferucarbotran bolus injection in double-contrast hepatic MRI (2012)
    Wiley-Blackwell
    Details
    Publication Date: 2012-04-16
    Description: Purpose: To evaluate the feasibility of semiquantitative measurement of liver perfusion from analysis of ferucarbotran induced signal-dynamics in double-contrast liver MR-imaging (DC-MRI). Materials and Methods: In total 31 patients (21 men; 58 ± 10 years) including 18 patients with biopsy proven liver cirrhosis prospectively underwent clinically indicated DC-MRI at 1.5 Tesla (T) with dynamic T2*-weighted gradient-echo imaging after ferucarbotran bolus injection. Breathing artefacts in tissue and input time curves were reduced by Savitzky-Golay-filtering and semiquantitative perfusion maps were calculated using a model free approach. Hepatic blood flow index (HBFI) and splenic blood flow index (SBFI) were determined by normalization of arbitrary perfusion values to the perfusion of the erector spinae muscle resulting in a semiquantitative perfusion measure. Results: In 30 of 31 patients the evaluated protocol could successfully be applied. Mean HBF was 7.7 ± 2.46 (range, 4.6–12.8) and mean SBF was 13.20 ± 2.57 (range, 8.5–17.8). A significantly lower total HBF was seen in patients with cirrhotic livers as compared to patients with noncirrhotic livers ( P 〈 0.05). In contrast, similar SBF was observed in cirrhotic and noncirrhotic patients ( P = 0.11). Conclusion: Capturing the signal dynamics during bolus injection of ferucarbotran in DC-MRI of the liver allows for semiquantitative assessment of hepatic perfusion that may be helpful for a more precise characterisation of liver cirrhosis and focal liver lesions. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.
    Print ISSN: 1053-1807
    Electronic ISSN: 1522-2586
    Topics: Medicine
    Published by Wiley-Blackwell
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  • 8
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    MOF thin films: existing and future applications (2011)
    Royal Society of Chemistry (RSC)
    Details
    Publication Date: 2011-01-12
    Description: O. Shekhah, J. Liu, R. A. Fischer, Ch. Woll (Critical Review from Chem. Soc. Rev.) O. Shekhah, Chem. Soc. Rev., 2011, DOI: 10.1039/c0cs00147c To cite this article before page numbers are assigned, use the DOI form of citation above. The content of this RSS Feed (c) The Royal Society of Chemistry
    Print ISSN: 0306-0012
    Electronic ISSN: 1460-4744
    Topics: Chemistry and Pharmacology
    Published by Royal Society of Chemistry (RSC)
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  • 9
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    The cumulative effect of assisted reproduction procedures on placental development and epigenetic perturbations in a mouse model (2015)
    Oxford University Press
    Details
    Publication Date: 2015-11-21
    Description: Assisted reproductive technologies (ART) are associated with several complications including low birth weight, abnormal placentation and increased risk for rare imprinting disorders. Indeed, experimental studies demonstrate ART procedures independent of existing infertility induce epigenetic perturbations in the embryo and extraembryonic tissues. To test the hypothesis that these epigenetic perturbations persist and result in adverse outcomes at term, we assessed placental morphology and methylation profiles in E18.5 mouse concepti generated by in vitro fertilization (IVF) in two different genetic backgrounds. We also examined embryo transfer (ET) and superovulation procedures to ascertain if they contribute to developmental and epigenetic effects. Increased placental weight and reduced fetal-to-placental weight ratio were observed in all ART groups when compared with naturally conceived controls, demonstrating that non-surgical embryo transfer alone can impact placental development. Furthermore, superovulation further induced overgrowth of the placental junctional zone. Embryo transfer and superovulation defects were limited to these morphological changes, as we did not observe any differences in epigenetic profiles. IVF placentae, however, displayed hypomethylation of imprinting control regions of select imprinted genes and a global reduction in DNA methylation levels. Although we did not detect significant differences in DNA methylation in fetal brain or liver samples, rare IVF concepti displayed very low methylation and abnormal gene expression from the normally repressed allele. Our findings suggest that individual ART procedures cumulatively increase placental morphological abnormalities and epigenetic perturbations, potentially causing adverse neonatal and long-term health outcomes in offspring.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation (2015)
    American Society of Hematology (ASH)
    In: Blood
    Details
    Publication Date: 2015-10-16
    Description: Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of severe congenital neutropenia (SCN), but data on outcome are scarce. We report on the outcome of 136 SCN patients who underwent HSCT between 1990 and 2012 in European and Middle East centers. The 3-year overall survival (OS) was 82%, and transplant-related mortality (TRM) was 17%. In multivariate analysis, transplants performed under the age of 10 years, in recent years, and from HLA-matched related or unrelated donors were associated with a significantly better OS. Frequency of graft failure was 10%. Cumulative incidence (day +90) of acute graft-versus-host disease (GVHD) grade 2-4 was 21%. In multivariate analysis, HLA-matched related donor and prophylaxis with cyclosporine A and methotrexate were associated with lower occurrence of acute GVHD. Cumulative incidence (1 year) of chronic GVHD was 20%. No secondary malignancies occurred after a median follow-up of 4.6 years. These data show that the outcome of HSCT for SCN from HLA-matched donors, performed in recent years, in patients younger than 10 years is acceptable. Nevertheless, given the TRM, a careful selection of HSCT candidates should be undertaken.
    Keywords: Hematopoiesis and Stem Cells, Pediatric Hematology, Transplantation, Free Research Articles, Phagocytes, Granulocytes, and Myelopoiesis, CME article, Clinical Trials and Observations
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
    Published by American Society of Hematology (ASH)
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