In Vitro Chemosensitivity Using the Histoculture Drug Response Assay in Human Epithelial Ovarian Cancer

The choice of chemotherapeutic drugs to treat patients with epithelial ovarian cancer has not depended on individual patient characteristics. We have investigated the correlation between in vitro chemosensitivity, as determined by the histoculture drug response assay (HDRA), and clinical responses in epithelial ovarian cancer. Fresh tissue samples were obtained from 79 patients with epithelial ovarian cancer. The sensitivity of these samples to 11 chemotherapeutic agents was tested using the HDRA method according to established methods, and we analyzed the results retrospectively. HDRA showed that they were more chemosensitive to carboplatin, topotecan and belotecan, with inhibition rates of 49.2%, 44.7%, and 39.7%, respectively, than to cisplatin, the traditional drug of choice in epithelial ovarian cancer. Among the 37 patients with FIGO stage Ⅲ/Ⅳ serous adenocarcinoma who were receiving carboplatin combined with paclitaxel, those with carboplatin-sensitive samples on HDRA had a significantly longer median disease-free interval than patients with carboplatin- resistant samples (23.2 vs. 13.8 months, p＜0.05), but median overall survival did not differ significantly (60.4 vs. 37.3 months, p＝0.621). In conclusion, this study indicates that HDRA could provide useful information for designing individual treatment strategies in patients with epithelial ovarian cancer

Theory of correlated insulating behaviour and spin-triplet superconductivity in twisted double bilayer graphene

Two monolayers of graphene twisted by a small `magic' angle exhibit nearly flat bands leading to correlated electronic states and superconductivity, whose precise nature including possible broken symmetries, remain under debate. Here we theoretically study a related but different system with reduced symmetry - twisted {\em double} bilayer graphene (TDBLG), consisting of {\em two} Bernal stacked bilayer graphene sheets, twisted with respect to one another. Unlike the monolayer case, we show that isolated flat bands only appear on application of a vertical displacement field $D$. We construct a phase diagram as a function of twist angle and $D$, incorporating interactions via a Hartree-Fock approximation. At half filling, ferromagnetic insulators are stabilized, typically with valley Chern number $C_v=2$. Ferromagnetic fluctuations in the metallic state are argued to lead to spin triplet superconductivity from pairing between electrons in opposite valleys. Response of these states to a magnetic field applied either perpendicular or parallel to the graphene sheets is obtained, and found to compare favorably with a recent experiment. We highlight a novel orbital effect arising from in-plane fields that can exceed the Zeeman effect and plays an important role in interpreting experiments.Comment: main 15 pages, appendix 11 page

Evaluation of Creep-fatigue Damage for Heat Exchangers in the Stella Sodium Test Loop

AbstractCreep-fatigue damage evaluation of DHX (Decay Heat Exchanger) and AHX(Air Heat Exchanger) in the sodium test facility has been performed. The sodium test loop of the STELLA-1 is for component performance tests of the main components, heat exchangers and mechanical pumps which are to be installed in an integral sodium test loop (STELLA-2) for simulating thermal hydraulic decay heat removal behaviour of the Korean demonstration Sodium-cooled Fast Reactor. High temperature design and fabrication of the DHX and AHX have been conducted and the components were installed at KAERI site. Evaluation of creep-fatigue damage at critical locations of the two heat exchangers were conducted according to the elevated temperature design codes of the ASME-NH and RCC-MR and the evaluation results were compared

Biochemical characterization of a recombinant Japanese encephalitis virus RNA-dependent RNA polymerase

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis virus (JEV) NS5 is a viral nonstructural protein that carries both methyltransferase and RNA-dependent RNA polymerase (RdRp) domains. It is a key component of the viral RNA replicase complex that presumably includes other viral nonstructural and cellular proteins. The biochemical properties of JEV NS5 have not been characterized due to the lack of a robust <it>in vitro </it>RdRp assay system, and the molecular mechanisms for the initiation of RNA synthesis by JEV NS5 remain to be elucidated.</p> <p>Results</p> <p>To characterize the biochemical properties of JEV RdRp, we expressed in <it>Escherichia coli </it>and purified an enzymatically active full-length recombinant JEV NS5 protein with a hexahistidine tag at the N-terminus. The purified NS5 protein, but not the mutant NS5 protein with an Ala substitution at the first Asp of the RdRp-conserved GDD motif, exhibited template- and primer-dependent RNA synthesis activity using a poly(A) RNA template. The NS5 protein was able to use both plus- and minus-strand 3'-untranslated regions of the JEV genome as templates in the absence of a primer, with the latter RNA being a better template. Analysis of the RNA synthesis initiation site using the 3'-end 83 nucleotides of the JEV genome as a minimal RNA template revealed that the NS5 protein specifically initiates RNA synthesis from an internal site, U₈₁, at the two nucleotides upstream of the 3'-end of the template.</p> <p>Conclusion</p> <p>As a first step toward the understanding of the molecular mechanisms for JEV RNA replication and ultimately for the <it>in vitro </it>reconstitution of viral RNA replicase complex, we for the first time established an <it>in vitro </it>JEV RdRp assay system with a functional full-length recombinant JEV NS5 protein and characterized the mechanisms of RNA synthesis from nonviral and viral RNA templates. The full-length recombinant JEV NS5 will be useful for the elucidation of the structure-function relationship of this enzyme and for the development of anti-JEV agents.</p

Audit market concentration and audit fees: an international investigation

Several large auditor consolidations in the late 1980s-early 1990s, along with Arthur Andersen’s collapse in 2001, facilitated global audit market concentration. Subsequently, regulators have expressed serious concern over the potential detrimental effects of this concentration, including cartel pricing. This study investigates the association between audit market concentration and audit fees. Using a large sample from 17 countries, our study yields three principal findings. First, consistent with regulators’ concern, a significantly positive association exists between market concentration and fees. Second, the country-level legal regime changes this association dramatically: while significant and positive in countries with a weak legal regime, the association weakens and eventually becomes negative as the legal regime strengthens. Third, these associations are more pronounced among clients of non-Big 4 auditors than those of Big 4 auditors. These findings provide regulators and other stakeholders with important insights into the effects of audit market structure on audit pricing

Immunization decision-making in the Republic of Korea: The structure and functioning of the Korea Advisory Committee on Immunization Practices

AbstractThe Korea Advisory Committee on Immunization Practices (KACIP), established by law in the early 1990s, makes recommendations on a range of issues related to the National Immunization Program. The Committee consists of 15 members and always includes the two government officials who belong to the Korea Centers for Disease Control and Prevention and the Korea Food and Drug Administration. Other members usually come from affiliated organizations and serve for 2-year terms. The KACIP depends on special-topics sub-committees or temporary advisory committees to gather and analyze data and to make recommendations which are normally reached by consensus and implemented by public sector health providers and private providers