157 research outputs found
The international community and post-war reconciliation in Africa: A case study of the Sierra Leone Truth and Reconciliation Commission
The decade-long armed conflict and political unrest in Sierra Leone deeply affected the civilian population. Since the end of the war in 2002, the government of Sierra Leone and the international community have been involved in peacebuilding activities, national reconciliation and reconstruction. The reconciliatory process necessitated the setting up of a Truth and Reconciliation Commission (TRC) which was also a product of the Lomé Peace Agreement between the Government of Sierra Leone and the now defunct Revolutionary United Front (RUF). The international community invested US$ 4,6 million in the Sierra Leone TRC mission. The TRC examined the causes of the war, human rights violations and the role played by foreign actors. This paper analyses the TRC as an internationally driven process to enhance reconciliation, peace, development and democracy in Sierra Leone. It also evaluates the impact of the implementation of the recommendations of the TRC. Beyond this, it makes some suggestions on how the international community can better promote transitional justice and the peacebuilding process by supporting local initiatives and promoting national ownership for sustainability
New, efficient, and accurate high order derivative and dissipation operators satisfying summation by parts, and applications in three-dimensional multi-block evolutions
We construct new, efficient, and accurate high-order finite differencing
operators which satisfy summation by parts. Since these operators are not
uniquely defined, we consider several optimization criteria: minimizing the
bandwidth, the truncation error on the boundary points, the spectral radius, or
a combination of these. We examine in detail a set of operators that are up to
tenth order accurate in the interior, and we surprisingly find that a
combination of these optimizations can improve the operators' spectral radius
and accuracy by orders of magnitude in certain cases. We also construct
high-order dissipation operators that are compatible with these new finite
difference operators and which are semi-definite with respect to the
appropriate summation by parts scalar product. We test the stability and
accuracy of these new difference and dissipation operators by evolving a
three-dimensional scalar wave equation on a spherical domain consisting of
seven blocks, each discretized with a structured grid, and connected through
penalty boundary conditions.Comment: 16 pages, 9 figures. The files with the coefficients for the
derivative and dissipation operators can be accessed by downloading the
source code for the document. The files are located in the "coeffs"
subdirector
A genomic survey of the fish parasite Spironucleus salmonicida indicates genomic plasticity among diplomonads and significant lateral gene transfer in eukaryote genome evolution
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
Transcriptome analyses of the Giardia lamblia life cycle
Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular and Biochemical Parasitology 174 (2010): 62-65, doi:10.1016/j.molbiopara.2010.05.010.We quantified mRNA abundance from 10 stages in the Giardia lamblia life cycle in vitro using
Serial Analysis of Gene Expression (SAGE). 163 abundant transcripts were expressed
constitutively. 71 transcripts were upregulated specifically during excystation and 42 during
encystation. Nonetheless, the transcriptomes of cysts and trophozoites showed major
differences. SAGE detected co-expressed clusters of 284 transcripts differentially expressed in
cysts and excyzoites and 287 transcripts in vegetative trophozoites and encysting cells. All
clusters included known genes and pathways as well as proteins unique to Giardia or
diplomonads. SAGE analysis of the Giardia life cycle identified a number of kinases,
phosphatases, and DNA replication proteins involved in excystation and encystation, which
could be important for examining the roles of cell signaling in giardial differentiation. Overall,
these data pave the way for directed gene discovery and a better understanding of the biology
of Giardia lamblia.BJD, DSR, and FDG were supported by NIH grants AI42488, GM61896, DK35108, and
AI051687. DP and SGS were supported by grants from the Swedish Natural Science Research
Council, the Swedish Medical Research Council, and the Karolinska Institutet. AGM, SRB,
SPP, and MJC were supported by NIH grant AI51089 and by the Marine Biological Laboratory’s
Program in Global Infectious Diseases, funded by the Ellison Medical Foundation
An Improved High Order Finite Difference Method for Non-conforming Grid Interfaces for the Wave Equation
This paper presents an extension of a recently developed high order finite difference method for the wave equation on a grid with non-conforming interfaces. The stability proof of the existing methods relies on the interpolation operators being norm-contracting, which is satisfied by the second and fourth order operators, but not by the sixth order operator. We construct new penalty terms to impose interface conditions such that the stability proof does not require the norm-contracting condition. As a consequence, the sixth order accurate scheme is also provably stable. Numerical experiments demonstrate the improved stability and accuracy property
Circulating secretory IgA antibodies against cyclic citrullinated peptides in early rheumatoid arthritis associate with inflammatory activity and smoking
Outcome and reproducibility of data concerning the Oxford unicompartmental knee arthroplasty: A structured literature review including arthroplasty registry data
Protein phosphatase 2A plays a crucial role in Giardia lamblia differentiation
Author Posting. © The Authors, 2006. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Molecular and Biochemical Parasitology 152 (2007): 80-89, doi:10.1016/j.molbiopara.2006.12.001.The ability of Giardia lamblia to undergo two distinct differentiations in
response to physiologic stimuli is central to its pathogenesis. The giardial
cytoskeleton changes drastically during encystation and excystation. However, the
signal transduction pathways mediating these transformations are poorly
understood. We tested the hypothesis that PP2A, a highly conserved
serine/threonine protein phosphatase, might be important in giardial differentiation.
We found that in vegetatively growing trophozoites, gPP2A-C protein localizes to
basal bodies/centrosomes, and to cytoskeletal structures unique to Giardia: the
ventral disk, and the dense rods of the anterior, posterior-lateral, and caudal
flagella. During encystation, gPP2A-C protein disappears from only the anterior
flagellar dense rods. During excystation, gPP2A-C localizes to the cyst wall in
excysting cysts but is not found in the wall of cysts with emerging excyzoites.
Transcriptome and immunoblot analyses indicated that gPP2A-C mRNA and
protein are upregulated in mature cysts and during the early stage of excystation
that models passage through the host stomach. Stable expression of gPP2A-C
antisense RNA did not affect vegetative growth, but strongly inhibited the
formation of encystation secretory vesicles (ESV) and water-resistant cysts.
Moreover, the few cysts that formed were highly defective in excystation.
Thus, gPP2A-C localizes to universal cytoskeletal structures and to
structures unique to Giardia. It is also important for encystation and excystation,
crucial giardial transformations that entail entry into and exit from dormancy.This work was funded
by NIH grants GM61896, AI51687, AI42488, and DK35108. Dr. A.G. McArthur was
supported by NIH grant AI51089 and the Marine Biological Laboratory’s Program
in Global Infectious Diseases, funded by the Ellison Medical Foundation
The Crystal Structure of the Human Co-Chaperone P58IPK
P58IPK is one of the endoplasmic reticulum- (ER-) localised DnaJ (ERdj) proteins which interact with the chaperone BiP, the mammalian ER ortholog of Hsp70, and are thought to contribute to the specificity and regulation of its diverse functions. P58IPK, expression of which is upregulated in response to ER stress, has been suggested to act as a co-chaperone, binding un- or misfolded proteins and delivering them to BiP. In order to give further insights into the functions of P58IPK, and the regulation of BiP by ERdj proteins, we have determined the crystal structure of human P58IPK to 3.0 Ã… resolution using a combination of molecular replacement and single wavelength anomalous diffraction. The structure shows the human P58IPK monomer to have a very elongated overall shape. In addition to the conserved J domain, P58IPK contains nine N-terminal tetratricopeptide repeat motifs, divided into three subdomains of three motifs each. The J domain is attached to the C-terminal end via a flexible linker, and the structure shows the conserved Hsp70-binding histidine-proline-aspartate (HPD) motif to be situated on the very edge of the elongated protein, 100 Ã… from the putative binding site for unfolded protein substrates. The residues that comprise the surface surrounding the HPD motif are highly conserved in P58IPK from other organisms but more varied between the human ERdj proteins, supporting the view that their regulation of different BiP functions is facilitated by differences in BiP-binding
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