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Since the reactor pressure vessel (RPV) lower head failure determines the subsequent ex-vessel accident progression, it is a key issue to understanding the accident progression of the Fukushima Daiichi Nuclear Power Station (1F). The RPV failure is largely affected by thermal loads on the vessel wall, and thus, it is inevitable that the thermal behavior of the molten metallic pool with the co-existence of solid oxide fuel debris must be understood. In past decades, numerous experiments have been conducted to investigate homogeneous molten pool behavior. Few experiments, however, address the melting and heat transfer process of the debris bed consisting of materials with different melting temperatures. The LIVE-J2 experiment aims to provide experimental data on a solid-liquid mixture pool in a simulated RPV lower head under various conditions. The experiment was performed in the LIVE-3D facility at the Karlsruhe Institute of Technology. The LIVE-J2 experiment started from the end state of the previous LIVE-J1 experiment where a eutectic binary mixture of KNO3-NaNO3 (nitrate) was solidified and filled the gap of the ceramic beads inside the LIVE-vessel. The information obtained in the LIVE-J2 experiment includes transient and steady-state melting temperature and vessel wall temperature distributions. The extensive measurements of the melting temperature indicate the heat transfer regimes in a solid-liquid mixture pool. The test results showed that the conductive heat transfer is dominant during steady state along the vessel wall boundary and that convective heat transfer takes place inside the mixture pool. After the addition of liquid nitrate on top of the mixture pool, different behavior was observed in each layer. In the upper pure-liquid nitrate layer, convective heat transfer was well developed, resulting in a homogeneous temperature, while within the lower solid/liquid debris mixture zone a large temperature gradient was observed, suggesting that conductive heat transfer was dominant. Besides the experimental performance, the test case was numerically simulated using Ansys Fluent. The simulation results generally agree with the measured experimental data. The flow regime and transient melt evolution were able to be estimated by the calculated velocity field and the crust thickness, respectively. [ABSTRACT FROM AUTHOR]

We recently identified Eph receptor A10 (EphA10) as a novel breast cancer-specific protein. Moreover, we also showed that an in-house developed anti-EphA10 monoclonal antibody (mAb) significantly inhibited proliferation of breast cancer cells, suggesting EphA10 as a promising target for breast cancer therapy. However, the only other known report for EphA10 was its expression in the testis at the mRNA level. Therefore, the potency of EphA10 as a drug target against cancers other than the breast is not known. The expression of EphA10 in a wide variety of cancer cells was studied and the potential of EphA10 as a drug target was evaluated. Screening of EphA10 mRNA expression showed that EphA10 was overexpressed in breast cancer cell lines as well as in prostate and colon cancer cell lines. Thus, we focused on prostate cancers in which EphA10 expression was equivalent to that in breast cancers. As a result, EphA10 expression was clearly shown in clinical prostate tumor tissues as well as in cell lines at the mRNA and protein levels. In order to evaluate the potential of EphA10 as a drug target, we analyzed complement-dependent cytotoxicity effects of anti-EphA10 mAb and found that significant cytotoxicity was mediated by the expression of EphA10. Therefore, the idea was conceived that the overexpression of EphA10 in prostate cancers might have a potential as a target for prostate cancer therapy, and formed the basis for the studies reported here. [ABSTRACT FROM AUTHOR]

There is no established standard second-line chemotherapy after the failure of the first-line cisplatin-based chemotherapy for patients with advanced or metastatic urothelial carcinoma. With regards to second-line chemotherapy, methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) was used from July 2009 onwards, and paclitaxel and carboplatin (TC) was introduced in April 2014 at the National Kyushu Cancer Center. The present study aimed to assess the prognostic factors for overall survival (OS) in second-line treatment that included best supportive care (BSC), and the tolerability and efficacy of TC chemotherapy. In total, 52 patients who were confirmed to have disease progression with first-line gemcitabine and cisplatin (GC) between June 2009 and November 2016 were enrolled in the current study. In addition, 28 patients selected BSC as second-line treatment, while 24 patients received second-line chemotherapy (MVAC, n=8; TC, n=16). The median OS for BSC, MVAC and TC was 2.8, 5.4, and 12.7 months, respectively. The difference between BSC and MVAC was not statistically significant (P=0.596). However, the difference between BSC and TC was statistically significant after Bonferroni correction (P=0.002). Multivariate analyses revealed that anemia [hazard ratio (HR), 7.047; 95% confidence interval (CI), 1.553-35.636; P=0.011], the presence of visceral metastasis (HR, 4.174; 95% CI, 1.506-13.429; P=0.005) and second-line treatment (TC HR, 0.296; 95% CI, 0.124-0.636; P=0.003) were independent prognostic factors. TC achieved an 18.7% overall response rate and a 56.2% disease control rate. Myelosuppression was the most common grade ≥3 toxicity, but no treatment-associated mortalities occurred during the study period. TC was associated with favorable benefits and safety, and may be considered a preferred regimen after the failure of GC. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the association between clinical parameters and the overall survival (OS) of Japanese patients with metastatic renal cell carcinoma (mRCC). The medical records of 59 consecutive mRCC patients receiving molecular-targeted therapy were retrospectively assessed. Kaplan-Meier and log-rank analyses were used to evaluate the progression-free survival (PFS) and OS, and a multivariate Cox proportional hazard model was used to analyze the clinical parameters for their prognostic relevance. The median OS for all patients was 23.7 months [95% confidence interval (CI): 17.9-30 months], and the median OS stratified by the Memorial Sloan Kettering Cancer Center risk classification was 28.5, 20.9 and 8.1 months for the favorable-, intermediate- and poor-risk groups, respectively (P=0.137; degree of freedom: 2). Univariate analyses identified prior nephrectomy, number of metastatic sites, anemia, best response to first-line treatment and PFS with first-line treatment as prognostic variables. Multivariate analyses identified number of metastatic sites [2: hazard ratio (HR)=3.351, 95% CI: 1.460-8.201, P=0.004; ≥3: HR=6.397, 95% CI: 1.939-20.209, P=0.003], time from diagnosis to therapy (≥1 year: HR=0.334, 95% CI: 0.137-0.755, P=0.008), PFS with first-line treatment (≥5.1 months: HR=0.353, 95% CI: 0.156-0.766, P=0.008) and number of lines of molecular-targeted agents (≥3: HR=0.248, 95% CI: 0.091-0.664, P=0.006) as independent prognostic factors. The results indicated that the PFS of first-line treatment may be a meaningful intermediate endpoint for OS in patients with mRCC who received treatment with molecular-targeted therapy. [ABSTRACT FROM AUTHOR]

Background aims. Haplo-identical hematopoietic stem cell transplantation (HSCT) with add-back of donor lymphocytes expressing die herpes simplex virus diymidine kinase suicide gene (TK cells) is one of the most widely applied promising new gene therapy approaches. However, the immunological status of added-back TK cells after HSCT has yet to be well characterized. Methods. We investigated TK cells through the use of flow cytometry, T-cell receptor (TCR) V/β repertoire spectratyping and linear amplification-mediated polymerase chain reaction followed by insertion site analysis in a patient enrolled in our clinical trial. Results. A comparison of onset with remission of acute graft-versus-host disease confirmed that TK cells were predominantly eliminated and that prolifera tive CD8H non-TK cells were also depleted in response to ganciclovir administration. The TCR V/3-chain repertoire of both TK cells and non-TK cells markedly changed after administration of ganciclovir, and, whereas the TCR repertoire of non-TK cells returned to a normal spectratype long after transplantation, that of TK cells remained skewed. With the long-term prophylactic administration of acyclovir, TK cells oligoclonally expanded and the frequency of spliced variants of TK cells increased. Known cancer-associated genes were not evident near die oligoclonally expanded herpes simplex virus (HSV)-TK insertion sites. Conclusions. We demonstrate obvious differences in immunological status between TK cells and non-TK cells. In addition, we speculate that long-term prophylactic administration of acyclovir increases the risk of oligoclonal expansion of spliced forms of TK cells. [ABSTRACT FROM AUTHOR]

Fermi systems in the cross-over regime between weakly coupled Bardeen-Cooper-Schrieffer (BCS) and strongly coupled Bose-Ein-stein-condensate (BEC) limits are among the most fascinating objects to study the behavior of an assembly of strongly interact ing particles. The physics of this cross-over has been of consider able interest both in the fields of condensed matter and ultracold atoms. One of the most challenging issues in this regime is the effect of large spin imbalance on a Fermi system under magnetic fields. Although several exotic physical properties have been predicted theoretically, the experimental realization of such an un usual superconducting state has not been achieved so far. Here we show that pure single crystals of superconducting FeSe offer the possibility to enter the previously unexplored realm where the three energies, Fermi energy εF, superconducting gap Δ, and Zee-man energy, become comparable. Through the superfluid response, transport, thermoelectric response, and spectroscopic-imaging scan ning tunneling microscopy, we demonstrate that εF of FeSe is extremely small, with the ratio Δ/εF ∼ 1(∼0.3) in the electron (hole) band. Moreover, thermal-conductivity measurements give evidence of a distinct phase line below the upper critical field, where the Zeeman energy becomes comparable to εF and Δ. The observation of this field-induced phase provides insights into previously poorly understood aspects of the highly spin-polarized Fermi liquid in the BCS-BEC cross-over regime. [ABSTRACT FROM AUTHOR]

Ephrin receptor A10 (EphA10) is a relatively uncharacterized protein which is expressed in many breast cancers but not expressed in normal breast tissues. Here, we examined the potential of EphA10 as a drug target in breast cancer. Immunohistochemical staining of clinical tissue sections revealed that EphA10 was expressed in various breast cancer subtypes, including triple negative breast cancers (TNBCs), with no expression observed in normal tissues apart from testis. Ligand-dependent proliferation was observed in EphA10-transfected MDA-MB-435 cells (MDA-MB-435EphA10) and native TNBC cells (MDA-MB-436). However, this phenomenon was not observed in parental MDA-MB-435 cells which express a low level of EphA10. Finally, tumor growth was significantly suppressed by administration of an anti-EphA10 monoclonal antibody in a xenograft mouse model. These results suggest that inhibition of EphA10 signaling may be a novel therapeutic option for management of breast cancer, including TNBCs which are currently not treated with molecularly targeted agents. [ABSTRACT FROM AUTHOR]