343 research outputs found

    Can Risk Models Extract Inflation Expectations from Financial Market Data? Evidence from the Inflation Protected Securities of Six Countries

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    We consider an arbitrage strategy which exactly replicates the cash of a sovereign inflation-indexed bond using inflation swaps and nominal sovereign bonds. The strategy reveals a violation of the law of one price in the G7 countries which is largest for the eurozone. Testing the strategy\u27s exposure to deflation, volatility, liquidity, economic and policy risks suggests that the observed pricing differential is an economic tail risk premium which is more pronounced in the eurozone. We conclude that inflation expectations implied by models that view this pricing differential as compensation for risk are likely to be accurate and useful for policy-making

    SISTEM PENILAIAN OTOMATIS JAWABAN ESSAY MENGGUNAKAN ONTOLOGI PADA MOODLE

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    This paper proposes a combination technique that called hybrid algorithm to be applied into automated scoring for essay e-learning system. This algorithm consists of two main processes: synonym comparison based on WordNet-based semantic similarity measurement and scoring process based on ontology structure. The process for searching a synonym will produce some outputs on different levels. This difference will stimulate a difference calculation of score due to every level reflects to a different similarity of degree. The matching process from input with key answer will generate an accurate matching process. In addition it also added with investigation of ontology class relationship. A different relationship will cause a different score. The last step is integrating this hybrid algorithm and ontology concept into Moodle e-learning system. The evaluation process will evaluate whether the hybrid algorithm can run very well inside ontology system that has been built. Besides that, it is expected that the integration process of hybrid algorithm into Moodle system can support the performance of Moodle e-learning system from essay auto grading perspective

    Fumarate respiration of Fasciola flukes as a potential drug target

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    Fascioliasis is a neglected tropical zoonotic disease caused by liver flukes belonging to the genus Fasciola. The emergence of resistance to triclabendazole, the only World Health Organization-recommended drug for this disease, highlights the need for the development of new drugs. Helminths possess an anaerobic mitochondrial respiratory chain (fumarate respiration) which is considered a potential drug target. This study aimed to evaluate the occurrence of fumarate respiration in Fasciola flukes. We analyzed the properties of the respiratory chain of Fasciola flukes in both adults and newly excysted juveniles (NEJs). Fasciola flukes travel and mature through the stomach, bowel, and abdominal cavity to the liver, where oxygen levels gradually decline. High fumarate reductase activity was observed in the mitochondrial fraction of adult Fasciola flukes. Furthermore, rhodoquinone-10 (RQ10 Em’= −63 mV), a low-potential electron mediator used in fumarate respiration was found to be predominant in adults. In contrast, the activity of oxygen respiration was low in adults. Rotenone, atpenin A5, and ascochlorin, typical inhibitors of mitochondrial enzymes in complexes I, II, and III, respectively, inhibit the activity of each enzyme in the adult mitochondrial fraction. These inhibitors were then used for in vitro viability tests of NEJs. Under aerobic conditions, NEJs were killed by rotenone or ascochlorin, which inhibit aerobic respiration (complex I–III), whereas atpenin A5, which inhibits complex II involved in fumarate respiration, did not affect NEJs. Moreover, ubiquinone-10 (UQ10 Em’= +110 mV), which is used in oxidative respiration, was detected in NEJs, in addition to RQ10. In contrast, under anaerobic conditions, rotenone and atpenin A5, which inhibit fumarate respiration (complex I–II), were crucial for NEJs. These findings demonstrate that NEJs have active hybrid respiration, in which they can properly use both oxygen and fumarate respiration, depending on oxygen availability. Thus, fumarate respiration is a promising drug target for Fasciola flukes, because it plays an essential role in both adults and NEJs

    Functional importance of Crenarchaea-specific extra-loop revealed by an X-ray structure of a heterotetrameric crenarchaeal splicing endonuclease

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    Archaeal splicing endonucleases (EndAs) are currently classified into three groups. Two groups require a single subunit protein to form a homodimer or homotetramer. The third group requires two nonidentical protein components for the activity. To elucidate the molecular architecture of the two-subunit EndA system, we studied a crenarchaeal splicing endonuclease from Pyrobaculum aerophilum. In the present study, we solved a crystal structure of the enzyme at 1.7-Å resolution. The enzyme adopts a heterotetrameric form composed of two catalytic and two structural subunits. By connecting the structural and the catalytic subunits of the heterotetrameric EndA, we could convert the enzyme to a homodimer that maintains the broad substrate specificity that is one of the characteristics of heterotetrameric EndA. Meanwhile, a deletion of six amino acids in a Crenarchaea-specific loop abolished the endonuclease activity even on a substrate with canonical BHB motif. These results indicate that the subunit architecture is not a major factor responsible for the difference of substrate specificity between single- and two-subunit EndA systems. Rather, the structural basis for the broad substrate specificity is built into the crenarchaeal splicing endonuclease itself

    Revealing the Deposition Mechanism of the Powder Aerosol Deposition Method Using Ceramic Oxide Core–Shell Particles

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    The powder aerosol deposition (PAD) method is a process to manufacture ceramic films completely at room temperature. Since the first reports by Akedo in the late 1990s, much research has been conducted to reveal the exact mechanism of the deposition process. However, it is still not fully understood. This work tackles this challenge using core–shell particles. Two coated oxides, Al2O3 core with a SiO2 shell and LiNi0.6Mn0.2Co0.2O2 core with a LiNbO3 shell, are investigated. Initially, the element ratios Al:Si and Ni:Nb of the powder are determined by energy-dispersive X-ray spectroscopy (EDX). In a second step, the change in the element ratios of Al:Si and Ni:Nb after deposition is investigated. The element ratios from powder to film strongly shift toward the shell elements, indicating that the particles fracture and only the outer parts of the particles are deposited. In the last step, this work investigates cross-sections of the deposited films with scanning transmission electron microscopy (STEM combined with EDX and an energy-selective back-scattered electron (EsB) detector to unveil the element distribution within the film itself. Therefore, the following overall picture emerges: particles impact on the substrate or on previously deposited particle, fracture, and only a small part of the impacting particles that originate from the outer part of the impacting particle gets deposited

    Microenvironmental Geometry Guides Platelet Adhesion and Spreading: A Quantitative Analysis at the Single Cell Level

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    To activate clot formation and maintain hemostasis, platelets adhere and spread onto sites of vascular injury. Although this process is well-characterized biochemically, how the physical and spatial cues in the microenvironment affect platelet adhesion and spreading remain unclear. In this study, we applied deep UV photolithography and protein micro/nanostamping to quantitatively investigate and characterize the spatial guidance of platelet spreading at the single cell level and with nanoscale resolution. Platelets adhered to and spread only onto micropatterned collagen or fibrinogen surfaces and followed the microenvironmental geometry with high fidelity and with single micron precision. Using micropatterned lines of different widths, we determined that platelets are able to conform to micropatterned stripes as thin as 0.6 µm and adopt a maximum aspect ratio of 19 on those protein patterns. Interestingly, platelets were also able to span and spread over non-patterned regions of up to 5 µm, a length consistent with that of maximally extended filopodia. This process appears to be mediated by platelet filopodia that are sensitive to spatial cues. Finally, we observed that microenvironmental geometry directly affects platelet biology, such as the spatial organization and distribution of the platelet actin cytoskeleton. Our data demonstrate that platelet spreading is a finely-tuned and spatially-guided process in which spatial cues directly influence the biological aspects of how clot formation is regulated

    Serological Survey of \u3ci\u3eLeptospira\u3c/i\u3e Infection in Arabian Horses in Poland

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    Leptospirosis is one of the most common zoonotic infections worldwide, including in most livestock, some companion animals, horses, wildlife, and humans. Epidemiological estimation of its prevalence in all species is difficult due to the variety of clinical presentations and challenges regarding laboratory diagnosis. The purpose of this study was to measure the seroprevalence of leptospiral infection in Arabian horses kept in the largest breeding farms in Poland, representing over 15% of the Polish Arabian horse population. Leptospira antibodies were detected by MAT (cut-off 1:100) in 33.2% of serum samples (204 of 615 animals) (CI 95%: 29.6–37.0%), most frequently reacting with the serovar Grippotyphosa, similar to previous reports in populations of randomly selected horses. These results indicated high Leptospira seropositivity, thus, although any form of clinical leptospirosis is rare, it may be postulated that the leptospiral exposure is widespread

    Selective cytotoxicity of dihydroorotate dehydrogenase inhibitors to human cancer cells under hypoxia and nutrient-deprived conditions

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    Human dihydroorotate dehydrogenase (HsDHODH) is a key enzyme of pyrimidine de novo biosynthesis pathway. It is located on the mitochondrial inner membrane and contributes to the respiratory chain by shuttling electrons to the ubiquinone pool. We have discovered ascofuranone (1), a natural compound produced by Acremonium sclerotigenum, and its derivatives are a potent class of HsDHODH inhibitors. We conducted a structure–activity relationship study and have identified functional groups of 1 that are essential for the inhibition of HsDHODH enzymatic activity. Furthermore, the binding mode of 1 and its derivatives to HsDHODH was demonstrated by co-crystallographic analysis and we show that these inhibitors bind at the ubiquinone binding site. In addition, the cytotoxicities of 1 and its potent derivatives 7, 8, and 9were studied using human cultured cancer cells. Interestingly, they showed selective and strong cytotoxicity to cancer cells cultured under microenvironment (hypoxia and nutrient-deprived) conditions. The selectivity ratio of 8 under this microenvironment show the most potent inhibition which was over 1000-fold higher compared to that under normal culture condition. Our studies suggest that under microenvironment conditions, cancer cells heavily depend on the pyrimidine de novo biosynthesis pathway. We also provide the first evidence that 1 and its derivatives are potential lead candidates for drug development which target the HsDHODH of cancer cells living under a tumor microenvironment

    Effect of the anti-parasitic compounds pyrvinium pamoate and artemisinin in enzymatic and culture assays: Data on the search for new anti-echinococcal drugs

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    The dataset presented herein is related to a previous research article titled “Mitochondrial Complex III in Larval Stage of Echinococcus multilocularis as a Potential Chemotherapeutic Target and in vivo Efficacy of Atovaquone Against Primary Hydatid Cysts” [1]. In this report, data were collected by screening drugs for echinococcosis. We investigated the inhibitory activities of artemisinin and pyrvinium pamoate against the mitochondrial respiratory enzymes in E. multilocularis protoscoleces. Artemisinin did not inhibit mitochondrial complexes I, II, and III. However, pyrvinium pamoate inhibited complex I at 11 μM,although complexes II and III were not inhibited. In the culture assay, E. multilocularis protoscoleces were treated with atovaquone (ATV), rotenone, praziquantel, artemisinin, and pyrvinium pamoate at a final concentration of 50 µM in different culture media. The viability of protoscoleces was compared under aerobic and anaerobic conditions via culture experiments. The survival days of E. multilocularis protoscoleces were evaluated in the drug-treated group compared with those in the non-treated group. The results of these culture assays revealed that praziquantel and artemisinin did not eliminate the protoscoleces under both aerobic and anaerobic conditions. However, a stronger elimination ability was observed with the co-administration of praziquantel or artemisinin with ATV than with ATV alone under aerobic conditions. Pyrvinium pamoate completely killed protoscoleces at 5 and 7 days under aerobic and anaerobic conditions, respectively. Pyrvinium pamoate behaved identically to rotenone, the complex I inhibitor, in the culture treatment assay.The data serve as a reference for the development of novel anti-echinococcal drugs

    Effect of dimethyl fumarate on lymphocyte subsets in patients with relapsing multiple sclerosis.

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    Background: In patients treated with dimethyl fumarate, absolute lymphocyte count decline typically occurs during the first year and then plateaus; early drops have been associated with the development of severe prolonged lymphopenia. Objective: We investigated the effect of dimethyl fumarate on absolute lymphocyte counts and CD4+/CD8+ T cells in patients with relapsing-remitting multiple sclerosis treated with dimethyl fumarate in routine practice. Methods: Lymphocyte data were collected via medical chart abstraction. Primary endpoint: change from baseline in absolute lymphocyte count and CD4+/CD8+ counts at 6-month intervals following dimethyl fumarate initiation. Results: Charts of 483 patients were abstracted and 476 patients included in the analysis. Mean baseline absolute lymphocyte count (2.23 × 10 Conclusion: Dimethyl fumarate-associated decline in absolute lymphocyte count in the first 12 months correlated with decline in CD4+ and CD8+ T cells and was independent of prior natalizumab. Absolute lymphocyte count monitoring continues to be an effective strategy to identify patients at risk of prolonged lymphopenia
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