ABSTRACT
We study the effects of the magnetic field on the dynamics of non-rotating stellar cores by performing 2D, magnetohydrodynamic (MHD) simulations. To this end, we have updated our ...neutrino-radiation-hydrodynamics supernova code to include MHD employing a divergence cleaning method with both careful treatments of finite volume and area reconstructions. By changing the initial strength of the magnetic field, the evolution of 15.0, 18.4, and $27.0\,\rm M_\odot$ pre-supernova progenitors is investigated. An intriguing finding in our study is that the neutrino-driven explosion occurs regardless of the strength of the initial magnetic field. For the 2D models presented in this work, the neutrino heating is the main driver for the explosion, whereas the magnetic field secondary contributes to the pre-explosion dynamics. Our results show that the strong magnetic field weakens the growth of the neutrino-driven turbulence in the small scale compared to the weak magnetic field. This results in the slower increase of the turbulent kinetic energy in the post-shock region, leading to the slightly delayed onset of the shock revival for models with the stronger initial magnetic field.
Male genital morphology of animals with internal fertilization and promiscuous mating systems have been one of the most diverse and rapidly evolving morphological traits. The male genital morphology ...in general is known to have low phenotypic and genetic variations, but the genetic basis of the male genital variation remains unclear. Drosophila melanogaster and its closely related species are morphologically very similar, but the shapes of the posterior lobe, a cuticular projection on the male genital arch are distinct from each other, representing a model system for studying the genetic basis of male genital morphology. In this study, we used highly inbred whole genome sequenced strains of D. melanogaster to perform genome wide association analysis on posterior lobe morphology. We quantified the outline shape of posterior lobes with Fourier coefficients obtained from elliptic Fourier analysis and performed principal component analysis, and posterior lobe size. The first and second principal components (PC1 and PC2) explained approximately 88% of the total variation of the posterior lobe shape. We then examined the association between the principal component scores and posterior lobe size and 1902142 single nucleotide polymorphisms (SNPs). As a result, we obtained 15, 14 and 15 SNPs for PC1, PC2 and posterior lobe size with P-values smaller than 10(-5). Based on the location of the SNPs, 13, 13 and six protein coding genes were identified as potential candidates for PC1, PC2 and posterior lobe size, respectively. In addition to the previous findings showing that the intraspecific posterior shape variation are regulated by multiple QTL with strong effects, the present study suggests that the intraspecific variation may be under polygenic regulation with a number of loci with small effects. Further studies are required for investigating whether these candidate genes are responsible for the intraspecific posterior lobe shape variation.
Background
The optimal surgical resection method in patients with HCC to minimize the risk of local recurrence has not yet been determined. The aim of this study was to compare the prognosis ...following anatomical versus non‐anatomical hepatic resection for hepatocellular carcinoma (HCC).
Methods
Consecutive patients with HCC without macroscopic vascular invasion, treated by curative resection between 1981 and 2012 at Osaka Medical Centre, were included in this retrospective study. The outcomes of patients selected by propensity score matching were compared.
Results
Some 1102 patients were included, 577 in the anatomical and 525 in the non‐anatomical resection group. By propensity score matching, 329 patients were selected into each group. Demographic, preoperative and tumour variables were similar between the propensity score‐matched groups, including tumour size, tumour multiplicity, α‐fetoprotein level and 15‐min indocyanine green retention rate at 15 min. The incidence of microvascular invasion was higher in the matched anatomical resection group (P = 0·048). Stratified analysis of recurrence‐free and overall survival rates revealed no statistically significant differences between the two propensity score‐matched groups (P = 0·704 and P = 0·381 respectively). There was also no significant difference in the early recurrence rate within 2 years after resection between these groups (P = 0·726). Subset analysis of the early recurrence‐free survival rate in patients with and without microvascular invasion revealed no significant differences between the groups (P = 0·312 and P = 0·479 respectively).
Conclusion
The resection method had no impact on the risk of HCC recurrence or survival.
Makes no difference
Recent studies revealed that Amblyomma or Ixodes tick bites may cause red meat allergy, in which galactose‐α‐1,3‐galactose (α‐Gal) is a major IgE‐binding epitope. The incidence of red meat allergy is ...high in Shimane Prefecture, as is tick‐transmitted Japanese spotted fever. Therefore, we speculated that tick bites may cause these meat allergies. The carbohydrate α‐Gal was detected in the salivary gland protein of Haemaphysalis longicornis (H. longicornis), the vector for Japanese spotted fever, by immunoblotting using anti‐α‐Gal antibody. H. longicornis salivary gland protein‐specific IgE was detected in the sera of 24 of 30 patients with red meat allergies. Sensitization to tick salivary gland protein containing α‐Gal is possibly a major etiology of red meat allergy; the carbohydrate plays a crucial role in its allergenicity. These results further indicate that the α‐Gal epitope is present not only in Amblyomma or Ixodes, but also in Haemaphysalis.
Tumor-associated B7-H1 molecules inhibit antitumor immunity in some malignancies. We found that B7-H1 expression on patient myeloma cells and human myeloma cell lines (HMCLs) was upregulated by ...cultivating the cells with autologous stromal cells and the human stromal cell line HS-5. Among major cytokines produced by HS-5 cells, interleukin (IL)-6-induced B7-H1 expression on HMCLs. Moreover, HS-5 cell-mediated B7-H1 expression was downregulated by inhibiting IL-6. B7-H1(+) HMCLs were more proliferative and less susceptible to antimyeloma chemotherapy compared with B7-H1(-) HMCLs. Moreover, the former cells showed higher levels of Bcl-2 and FasL expression than the latter. Finally, B7-H1 molecules on HMCLs induced T-cell apoptosis and anergy of tumor-specific T cells. Consistent with these in vitro observations, patients whose myeloma cells expressed high levels of B7-H1 had higher myeloma cell percentages in the bone marrow (BM) and higher serum lactate dehydrogenase levels compared with other myeloma patients. In addition, B7-H1 expression levels were often upregulated after myeloma patients relapsed or became refractory to therapy. Our data indicate that the BM microenvironment upregulates B7-H1 expression on myeloma cells, which links to the two biological actions of inducing T-cell downregulation and enhancing aggressive myeloma-cell characteristics. Modulating the B7-H1 pathway may be worthwhile in myeloma.
Although Drosophila suzukii Matsumura (Diptera: Drosophilidae) infests fresh and ripening fruits, it is attracted to fermented fruits as well. Because fermented fruits attract other flies too, if D. ...suzukii utilizes fermented fruits as oviposition substrates, competition can be more intense on them. To avoid such competition, D. suzukii may change oviposition preference when particular species of competitor flies are present, but the effect of odor cues associated with competitors on the oviposition preference of D. suzukii is still unknown. To examine such an effect, we investigated the oviposition preference of D. suzukii in the presence of four competitor fly species – Drosophila melanogaster Meigen, Drosophila lutescens Malloch, Drosophila rufa Kikkawa & Peng, and Drosophila auraria Peng – and D. suzukii itself. We prepared artificial substrates with yeast treatment (Y+: yeast supplementation, Y−: control) and competitor fly treatment (F+: pre‐inoculated with competitor fly odor, F−: control), and performed two‐choice experiments using the substrates with various Y and F treatments. Our results showed that D. suzukii oviposited more eggs on Y+ substrates than on Y− substrates when no competitor flies were present and the presence of competitor flies influenced D. suzukii’s oviposition preference for yeast‐supplemented substrates and its effect changed depending on the competitor fly species. If the presence of competitors around fallen fruits on the ground suppresses D. suzukii’s oviposition on the fallen fruits and facilitates the oviposition on non‐fermenting substrates in nature, it may drive D. suzukii to use ripening fruits on the tree. Such selective pressure may facilitate the evolution of morphological traits such as a serrated ovipositor in D. suzukii.
To avoid intra‐ and interspecific competition, Drosophila suzukii (Diptera: Drosophilidae) may change oviposition preference when competitor flies are present, but the effect of odor cues associated with competitors on the oviposition preference of D. suzukii was unknown. The current study demonstrated that chemical cues associated with the presence of competitors could influence D. suzukii’s oviposition preference for the yeast‐supplemented substrates for the first time.
There is no standard first-line chemotherapy for recurrent/metastatic (RM) or unresectable locally advanced (LA) salivary gland carcinoma (SGC).
We conducted a single institution, open-label, single ...arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75mg every 4weeks. Bicalutamide was administered orally at a daily dose of 80mg. Patients were treated until progressive disease or unacceptable toxicities.
Thirty-six eligible patients were enrolled. Thirty-three patients had RM disease and three patients had LA disease. The pathological diagnoses were salivary duct carcinoma (34 patients, 94%) and adenocarcinoma, NOS (two patients, 6%). The best overall response rate was 41.7% n=15, 95% confidence interval (CI), 25.5%–59.2%, the clinical benefit rate was 75.0% (n=27, 95% CI, 57.8%–87.9%). The median progression-free survival was 8.8months (95% CI, 6.3–12.3months) and the median overall survival was 30.5months (95% CI, 16.8months to not reached). Additional analyses between treatment outcomes and clinicopathological factors or biomarkers including AR positivity, human epidermal growth factor receptor 2 status, and its complex downstream signaling pathway gene mutations showed no statistically significant differences. Elevated grade 3 liver transaminases and increased serum creatinine were reported in two patients, respectively. Discontinuation of leuprorelin acetate or bicalutamide due to adverse event occurred in one patient.
This study suggests that CAB has equivalent efficacy and less toxicity for patients with AR-positive RM or unresectable LA SGC compared with conventional chemotherapy, which warrants further study.
UMIN-CTR (http://www.umin.ac.jp/ctr/index-j.htm), identification number: UMIN000005703
Acoustic Radiation Force Impulse (ARFI) imaging is a novel ultrasound‐based elastography method that is integrated in a conventional ultrasound machine enabling the exact localization of ...measurement site. It might present an alternative method to transient elastography for the noninvasive assessment of liver fibrosis. At present, studies with small patient population have shown promising results. A systematic review and meta‐analysis of pooled patient data were performed to evaluate the overall performance of ARFI for the staging of liver fibrosis. Literature databases were searched up to 10/2010. The authors of the original publication were contacted, and the original patient data were requested. A meta‐analysis was performed using a random effect meta‐analytic method for diagnostic tests. In addition, available data comparing ARFI with FibroScan with the DeLong test were evaluated. Literature search yielded nine full‐paper publications evaluating ARFI while using liver biopsy as reference method. Original patient data were available from eight studies including 518 patients. The mean diagnostic accuracy of ARFI expressed as areas under ROC curves (AUROC) was 0.87 for the diagnosis of significant fibrosis (F ≥ 2), 0.91 for the diagnosis of severe fibrosis (F ≥ 3), and 0.93 for the diagnosis of cirrhosis. ARFI can be performed with good diagnostic accuracy for the noninvasive staging of liver fibrosis.
Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ...ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. We herein demonstrate that SFTPD downregulates ligand-independent signaling in cells harboring EGFR mutations such as TKI-sensitive exon 19 deletion (Ex19del) and L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing cellular growth and motility. Lectin blotting and ligand blotting in lung cancer cell lines suggested that EGFR mutants express oligomannose-type N-glycans and interact with SFTPD directly. Cross-linking assay indicated that SFTPD inhibits ligand-independent dimerization of EGFR mutants. We also demonstrated that SFTPD reduced dimerization-independent phosphorylation of Ex19del and T790M EGFR mutants using point mutations that disrupted the asymmetric dimer interface. It was confirmed that SFTPD augmented the viability-suppressing effects of EGFR-TKIs. Furthermore, retrospective analysis of 121 patients with lung adenocarcinoma to examine associations between serum SFTPD levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, including Ex19del or L858R, high serum SFTPD levels correlated with a lower number of distant metastases and prolonged overall survival and progression-free survival. These findings suggest that SFTPD downregulates both TKI-sensitive and -resistant EGFR mutant signaling, and SFTPD level is correlated with clinical outcome. These findings illustrate the use of serum SFTPD level as a potential marker to estimate the efficacy of EGFR-TKIs.
Topologically nontrivial materials host protected edge states associated with the bulk band inversion through the bulk-edge correspondence. Manipulating such edge states is highly desired for ...developing new functions and devices practically using their dissipation-less nature and spin-momentum locking. Here we introduce a transition-metal dichalcogenide VTe
, that hosts a charge density wave (CDW) coupled with the band inversion involving V3d and Te5p orbitals. Spin- and angle-resolved photoemission spectroscopy with first-principles calculations reveal the huge anisotropic modification of the bulk electronic structure by the CDW formation, accompanying the selective disappearance of Dirac-type spin-polarized topological surface states that exist in the normal state. Thorough three dimensional investigation of bulk states indicates that the corresponding band inversion at the Brillouin zone boundary dissolves upon the CDW formation, by transforming into anomalous flat bands. Our finding provides a new insight to the topological manipulation of matters by utilizing CDWs' flexible characters to external stimuli.
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