267 research outputs found

    Analysing the use of compellence during peace operations

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    Compellence is a strategy that employs pressure to induce others to take specific actions. Contemporary international peace operations are expected to use force, if necessary, to protect civilians and/or maintain and restore order in the very volatile environment of post-civil war states. This challenging task requires peacekeepers to proactively change the status quo through compelling local warring factions to stop violence, disarm, and join peace processes. This thesis adopts a comparative case study approach, systematically analyses peace operations in East Timor, Sierra Leone, and Somalia, and identifies conditions under which compellence is likely to succeed in peace operations. The overall finding of the thesis is that there are five conditions which favour the success of compellence in peace operations: the use of the gradual-turning-of-the-screw strategy; the actual use of force as the source of credibility; the achievement of counter-coercion negation as a form of denial; the achievement of stronghold neutralisation, which is another form of denial; and the absence of third-party support on the target side. Thus, a clearly one-sided situation in favour of compellers is necessary because target armed groups are evasive, and they have higher interests and stronger motivation than compellers in what is in dispute. This thesis provides the first systematic attempt to specifically analyse conditions for the success of compellence in international peace operations. This study contributes to the literature of compellence by identifying conditions for its success, focusing on the understudied context of compellence against non-state actors. The study also contributes to the field of peace operations by demonstrating how compellence can be a causal mechanism for achieving their objectives and when it is likely to work. The findings have practical implications as well. The conditions indicate what practitioners should achieve to successfully employ the strategy in peace operations

    Glycerol as a chemical chaperone enhances radiation-induced apoptosis in anaplastic thyroid carcinoma cells

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    INTRODUCTION: Anaplastic thyroid carcinoma, which is one of the most aggressive, malignant tumors in humans, results in an extremely poor prognosis despite chemotherapy and radiotherapy. The present study was designed to evaluate therapeutic effects of radiation by glycerol on p53-mutant anaplastic thyroid carcinoma cells (8305c cells). To examine the effectiveness of glycerol in radiation induced lethality for anaplastic thyroid carcinoma 8305c cells, we performed colony formation assay and apoptosis analysis. RESULTS: Apoptosis was analyzed with Hoechst 33342 staining and DNA ladder formation assay. 8305c cells became radiosensitive when glycerol was added to culture medium before X-ray irradiation. Apoptosis was induced by X-rays in the presence of glycerol. However, there was little apoptosis induced by X-ray irradiation or glycerol alone. The binding activity of whole cell extracts to bax promoter region was induced by X-rays in the presence of glycerol but not by X-rays alone. CONCLUSION: These findings suggest that glycerol is effective against radiotherapy of p53-mutant thyroid carcinomas

    Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma

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    <p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined.</p> <p>Methods</p> <p>Cells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins.</p> <p>Results</p> <p>When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.</p> <p>Conclusion</p> <p>These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.</p

    Post-Hartree-Fock method in Quantum Chemistry for Quantum Computer

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    Quantum computational chemistry is a potential application of quantum computers that is expected to effectively solve several quantum-chemistry problems, particularly the electronic structure problem. Quantum computational chemistry can be compared to the conventional computational devices. This review comprehensively investigates the applications and overview of quantum computational chemistry, including a review of the Hartree-Fock method for quantum information scientists. Quantum algorithms, quantum phase estimation, and variational quantum eigensolver, have been applied to the post-Hartree-Fock method.Comment: 31 pages, 6 figure

    The hemolytic and cytolytic activities of Serratia marcescens phospholipase A (PhlA) depend on lysophospholipid production by PhlA

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    <p>Abstract</p> <p>Background</p> <p><it>Serratia marcescens </it>is a gram-negative bacterium and often causes nosocomial infections. There have been few studies of the virulence factors of this bacterium. The only <it>S. marcescens </it>hemolytic and cytotoxic factor reported, thus far, is the hemolysin ShlA.</p> <p>Results</p> <p>An <it>S. marcescens shl</it>AB deletion mutant was constructed and shown to have no contact hemolytic activity. However, the deletion mutant retained hemolytic activity on human blood agar plates, indicating the presence of another <it>S. marcescens </it>hemolytic factor. Functional cloning of <it>S. marcescens </it>identified a phospholipase A (PhlA) with hemolytic activity on human blood agar plates. A <it>phl</it>AB deletion mutant lost hemolytic activity on human blood agar plates. Purified recombinant PhlA hydrolyzed several types of phospholipids and exhibited phospholipase A1 (PLA1), but not phospholipase A2 (PLA2), activity. The cytotoxic and hemolytic activities of PhlA both required phospholipids as substrates.</p> <p>Conclusion</p> <p>We have shown that the <it>S. marcescens phlA </it>gene produces hemolysis on human blood agar plates. PhlA induces destabilization of target cell membranes in the presence of phospholipids. Our results indicated that the lysophospholipids produced by PhlA affected cell membranes resulting in hemolysis and cell death.</p

    Royal Jelly Prevents Osteoporosis in Rats: Beneficial Effects in Ovariectomy Model and in Bone Tissue Culture Model

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    Royal jelly (RJ) has been used worldwide for many years as medical products, health foods and cosmetics. Since RJ contains testosterone and has steroid hormone-type activities, we hypothesized that it may have beneficial effects on osteoporosis. We used both an ovariectomized rat model and a tissue culture model. Rats were divided into eight groups as follows: sham-operated (Sham), ovariectomized (OVX), OVX given 0.5% (w/w) raw RJ, OVX given 2.0% (w/w) RJ, OVX given 0.5% (w/w) protease-treated RJ (pRJ), OVX given 2.0% (w/w) pRJ, OVX given 17β-estradiol and OVX given its vehicle, respectively. The Ovariectomy decreased tibial bone mineral density (BMD) by 24%. Administration of 17β-estradiol to OVX rats recovered the tibial BMD decrease by 100%. Administration of 2.0% (w/w) RJ and 0.5–2.0% (w/w) pRJ to OVX rats recovered it by 85% or more. These results indicate that both RJ and pRJ are almost as effective as 17β-estradiol in preventing the development of bone loss induced by ovariectomy in rats. In tissue culture models, both RJ and pRJ increased calcium contents in femoral-diaphyseal and femoral-metaphyseal tissue cultures obtained from normal male rats. However, in a mouse marrow culture model, they neither inhibited the parathyroid hormone (PTH)-induced calcium loss nor affected the formation of osteoclast-like cells induced by PTH in mouse marrow culture system. Therefore, our results suggest that both RJ and pRJ may prevent osteoporosis by enhancing intestinal calcium absorption, but not by directly antagonizing the action of PTH

    Genomic surveillance of Neisseria gonorrhoeae to investigate the distribution and evolution of antimicrobial-resistance determinants and lineages

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    The first extensively drug resistant (XDR) Neisseria gonorrhoeae strain with high resistance to the extended-spectrum cephalosporin ceftriaxone was identified in 2009 in Japan, but no other strain with this antimicrobial-resistance profile has been reported since. However, surveillance to date has been based on phenotypic methods and sequence typing, not genome sequencing. Therefore, little is known about the local population structure at the genomic level, and how resistance determinants and lineages are distributed and evolve. We analysed the whole-genome sequence data and the antimicrobial-susceptibility testing results of 204 strains sampled in a region where the first XDR ceftriaxone-resistant N. gonorrhoeae was isolated, complemented with 67 additional genomes from other time frames and locations within Japan. Strains resistant to ceftriaxone were not found, but we discovered a sequence type (ST)7363 sub-lineage susceptible to ceftriaxone and cefixime in which the mosaic penA allele responsible for reduced susceptibility had reverted to a susceptible allele by recombination. Approximately 85 % of isolates showed resistance to fluoroquinolones (ciprofloxacin) explained by linked amino acid substitutions at positions 91 and 95 of GyrA with 99 % sensitivity and 100 % specificity. Approximately 10 % showed resistance to macrolides (azithromycin), for which genetic determinants are less clear. Furthermore, we revealed different evolutionary paths of the two major lineages: single acquisition of penA X in the ST7363-associated lineage, followed by multiple independent acquisitions of the penA X and XXXIV in the ST1901-associated lineage. Our study provides a detailed picture of the distribution of resistance determinants and disentangles the evolution of the two major lineages spreading worldwide

    Immunohistochemical analyses of parathyroid hormone-dependent downregulation of renal type II Na-Pi cotransporters by cryobiopsy

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    The “in vivo cryotechnique” (IVCT) is a new method of morphological analysis which has the advantage of freezing tissues in living animals without stopping their blood circulation. The purpose of this study was to investigate the effect of parathyroid hormone (PTH) on renal type II Na-Pi transporters (NaPi-IIa and NaPi-IIc) and ”cryobiopsy” (CB) using special cryoforceps as a simple method of the IVCT. The kidney tissues were biopsied at various time points after PTH administration by CB using liquid nitrogen as the cryogen. By hematoxylin-eosin (HE) staining the kidney tissues, well-frozen areas without visible ice crystals were obtained in the tissue surface areas, and the brush border membrane (BBM) of proximal tubules was well preserved at a light microscopic level. Immunohistochemical evaluation showed that PTH downregulated NaPi-IIa and NaPi-IIc at the BBM, being controlled by a different mechanism. In this method, the PTHinduced internalization of NaPi-IIc from microvilli to subapical compartments was not observed in the tissue preparations. NaPi-IIc protein appears to be degraded in microvilli of the proximal tubular cells after the injection of PTH. We suggest that CB using liquid nitrogen is useful to investigate renal type II Na-Pi transporters at the light microscopic level

    Control of phosphate appetite in young rats

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    In the present study, we investigated whether a diet deficient in inorganic phosphate (Pi) stimulates an ingestive behavior to seek sources of Pi. Male Wistar rats were placed in individual cages with unrestricted access to tap water and a low (LPD, 0.02% Pi) or normal (NPD, 0.6% Pi) Pi diet for 6 days. On day 7, LDP rats were given unlimited access to a solution of 25 mM potassium phosphate water (Pi-water) for 9 additional days. Rats fed LPD consumed 70-100% more Pi-water then those fed NPD. The increase in Pi-water intake resulted in a marked rise in the growth rate of rats fed LPD during day 9. A similar intake of Pi was induced after only 2 days of LPD and was associated with significant reductions in both plasma and cerebrospinal fluid (CSF) levels of Pi ; these levels remained low throughout Pi restriction, despite a significant intake of Pi-water. Replenishment with a high-Pi diet rapidly quenched the appetite for Pi-water and was associated with restoration of both plasma and CSF Pi levels. These findings suggest that an appetite for Pi can be induced in rats, perhaps through lowered plasma and CSF Pi levels
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