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The turbulent patch arising from internal gravity wave breaking is investigated with direct numerical simulation of a stably stratified flow over a two-dimensional hill. The turbulent patch is distinguished from the non-turbulent wave region with potential vorticity. The turbulent patch is highly intermittent, and its location fluctuates with space and time. The buoyancy Reynolds number slowly decays with time in the turbulent patch and the mixing efficiency stays around 0.2. The turbulent patch is separated from the non-turbulent wave region by a turbulent/non-turbulent interfacial (TNTI) layer, whose thickness is about five times the Kolmogorov scale. The kinetic energy dissipation rate also sharply decreases from the turbulent to the wave region while the potential energy dissipation rate has a large peak within the TNTI layer. Both shear and stable stratification are strong in the upper area of the turbulent patch. On the other hand, the lower area has a small mean density gradient, i.e., weak stratification, which is related to the strong intermittency of the turbulent patch in the lower area. Furthermore, weak stratification in the lower area results in a low gradient Richardson number, which is below the critical value for the shear instability, and the roller vortex appears. The outer edge of the turbulent patch aligns with the perimeter of the roller vortex, and the vortex affects the spatial distribution of the turbulent patch. [ABSTRACT FROM AUTHOR]

Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant congenital disorder characterized by progressive heterotopic bone formation. Currently, no definitive treatment exists for FOP. The activin receptor type IA / activin-like kinase 2 (ACVR1/ALK2) gene has been identified as the responsible gene for FOP, and disease-associated ALK2 mutations have been found. Chemical inhibitors to the pathogenic ALK2 receptors are considered possible medical agents for FOP, but their adverse effects on normal ALK2 and other receptors cannot be excluded. Here we describe another treatment strategy for FOP using allele-specific RNA interference (ASP-RNAi), and show modified small interfering RNAs (siRNAs) conferring allele-specific silencing against disease-causing ALK2 mutants found in FOP, without affecting normal ALK2 allele. Thus, the siRNAs presented here may become novel therapeutic agents for FOP, and their induced ASP-RNAi may pave the way for the achievement of radical treatment of FOP and/or for the relief of its severe symptoms. [ABSTRACT FROM AUTHOR]

K. Ishiyama, T. Katagiri, K. Ohata, K. Hosokawa, Y. Kondo, H. Yamazaki, A. Takami, S. Nakao. Safety of pre-engraftment prophylactic foscarnet administration after allogeneic stem cell transplantation. Transpl Infect Dis 2011. All rights reserved Abstract: Human herpesvirus-6 (HHV-6) is a major cause of limbic encephalitis with a dismal prognosis after allogeneic hematopoietic stem cell transplantation (SCT). Because our previous trial of preemptive therapy with foscarnet sodium (phosphonoformic acid; PFA) failed to prevent HHV-6 encephalitis, we conducted a prospective study to examine the safety of prophylactic PFA administration and elucidate the changes in the plasma HHV-6 DNA levels in the early post-SCT period. Plasma HHV-6 DNA was measured thrice weekly from day 6. PFA, 90 mg/kg/day, was administered from days 7 to 21 after bone marrow or peripheral blood SCT and to day 25 after umbilical cord blood transplantation. Of the 10 patients enrolled, 2 dropped out of the study, 1 because of early death, and 1 with a low glomerular filtration rate. Grade 3 or greater adverse events occurred in 9 of the 10 prophylactic PFA patients and in 7 of the 10 control patients who had clinical backgrounds similar to the study subjects and underwent SCT during the same period. Neurological disorders developed in none of the study subjects but in 4 of the 10 control patients, including 2 with HHV-6 encephalitis. HHV-6 reactivation occurred in 3 of the 10 study subjects. The prophylactic PFA regimen was thus safe and it may reduce the risk of limbic encephalitis, but is not considered to be potent enough to prevent HHV-6 reactivation. [ABSTRACT FROM AUTHOR]

Human herpesvirus-6 (HHV-6) is a major cause of limbic encephalitis with a dismal prognosis after allogeneic hematopoietic SCT (HSCT). A prospective, multicenter study was conducted to assess the safety and efficacy of preemptive therapy with foscarnet sodium (PFA) for the prevention of HHV-6 encephalitis. Plasma HHV-6 DNA was measured thrice weekly from day 7 until day 36 after umbilical cord blood transplantation (UCBT) or HSCT from HLA-haploidentical relatives. PFA, 90 mg/kg/day, was started when HHV-6 DNA exceeded 5 × 102 copies/mL. Mild and transient adverse events were associated with PFA in 7 of 8 patients. Twelve of 15 UCBT recipients became positive for HHV-6 DNAemia, defined by greater than 1 × 102 copies/mL of HHV-6 DNA in plasma. The virus exceeded 5 × 102 copies/mL in seven patients, whereas none of the five HLA-haploidentical HSCT recipients became positive. One patient developed mild limbic encephalitis just after initial PFA administration. Preemptive PFA therapy is safe, but as HHV-6 DNAemia can abruptly develop before neutrophil engraftment in UCBT recipients, prophylactic PFA administration from day 7 or earlier after UCBT may be needed. [ABSTRACT FROM AUTHOR]

SMES of the 10 MVA for the power control in power system has been manufactured, and connected to a real power grid. In addition, innovative basic researches, for example, low cost converter, maintenance-free cryo-coolers, inter-locks system and so on, have also been developed. The SMES was installed in the metal rolling factory with hydro power plant. Field test has been carried out for load fluctuation compensation. SMES was able to compensate for the active power according to the fluctuating load, and confirm the situation with a smooth load change of 11 kV bus of hydro power stations. In this paper, field test results will be presented. [ABSTRACT FROM AUTHOR]

Ethoxyquin (EQ) has been used as an antioxidant in livestock, aquaculture and pet foods. Animal food safety law has established the upper limit of EQ in animal feed at 150 mg kg−1. However, the risk of EQ at the approved level for aquaculture feed (150 mg kg−1) to fish health is unknown. Here, we examine the effect of EQ on the immunity of tilapia ( Oreochromis niloticus). EQ concentration in the blood reached 0.16 mg L−1 in fish fed EQ at the approved level. This level of EQ inhibited phagocytic activity of leucocytes in vitro and antibacterial activity of whole blood in vivo. Furthermore, pyknosis in the liver was observed throughout the duration of feeding. However, after 30 days of experimental challenge with feed containing 150 mg kg−1 of EQ, no significant difference was observed in mortality. Although EQ at the approved level in feed causes immunosuppression in fish, the severity of immunosuppression does not lead to a lowering of disease resistance for short feeding periods. [ABSTRACT FROM AUTHOR]

Abstract: The present study characterizes the clinical picture of viral encephalopathy and retinopathy associated with betanodavirus infection in hatchery-reared juvenile thread-sail filefish. Necrotic encephalomyelitis was clearly evident in the spinal cord, the medulla oblongata, and the cerebellum. Necrotic retinitis and gastroenteritis were also noted. Immunohistochemistry using an anti-betanodavirus rabbit serum revealed that the viral antigens were present in the gastrointestinal tract, the spinal cord, the brain and the retina correlating with the histopathological changes. Strong positive immunohistochemical reactions in the stomach and intestine suggest that the gastrointestinal tract was a possible portal of entry into fish. [Copyright &y& Elsevier]

We determined the alleles of five polymorphic molecules including HA-1 and four adhesion molecules for 106 patients transplanted with HLA-identical stem cell grafts and investigated the association of mismatches as correlates of relapse and graft-versus-host disease (GVHD). All 106 recipients underwent stem cell transplantation (SCT) after myeloablative conditioning between 1985 and 2002. Risk status of disease at SCT was standard (n=63) and high (n=42). After SCT, 36, 49 and 33 developed acute GVHD, chronic GVHD and relapsed, respectively. Our patients relapsed at rates of 16.7 and 38.6% with one or more and without incompatibilities (P=0.013). The relapse rates of patients with CD62L, CD31 codon 563, CD31 codon 125, HA-1 and CD49b incompatibilities were 5.9, 11.8, 15.4, 16.0 and 33.3%, respectively. The frequency of acute GVHD did not differ regardless of incompatibilities. In standard-risk group, the accumulated relapse rates of 19 and 44 patients with and without minor histocompatibility antigen incompatibility were 22% and unexpectedly 66%, respectively (P=0.02). The probability of 12-year survival was 88% in the former and 66% in the latter patients (P=0.03). Our data suggest that incompatibility of CD62L, CD31 codon 563 and CD31 codon 125 contributes to a graft-versus-leukemia effect rather than to GVHD, resulting in prolonged survival after HLA-identical SCT.Bone Marrow Transplantation (2006) 38, 681–686. doi:10.1038/sj.bmt.1705506; published online 18 September 2006 [ABSTRACT FROM AUTHOR]

Bacterial artificial chromosome (BAC) libraries are important tools for genomic research. We have constructed seven genomic BAC libraries from three fish species, rainbow trout (Oncorhynchus mykiss), carp (Cyprinus carpio) and tilapia (Oreochromis niloticus). The two rainbow trout BAC libraries have average insert sizes of 58 and 110 kb. The average size of inserts in the carp BAC library is 160 kb. The average insert sizes of the four tilapia BAC libraries are 65, 105, 145 and 194 kb, respectively. These libraries represent good coverage of each genome (2–64 × coverage). The libraries can be screened by conventional colony hybridization and provide a starting point for the construction of high-density filtres or polymerase chain reaction (PCR) screening approaches. These BAC libraries will facilitate the positional cloning of quantitative trait loci (QTLs) for a variety of economically important traits in these species. [ABSTRACT FROM AUTHOR]

Highlights: [•] Doping-dependence of uniaxial pressure effects in Ba(Fe1−xCo x )2As2 was investigated. [•] The single crystals of Ba(Fe1−xCo x )2As2 were grown by self-flux method. [•] Transport measurements under the c-axis pressure were performed. [•] Not only the SC state but also the normal state under pressure were examined. [•] Superconductivity and the competing SDW order were sensitive to the c-axis pressure. [ABSTRACT FROM AUTHOR]

Abstract: We have succeeded in growing single crystals of the Sr2VFeAsO3 superconductor, which are large enough to experimentally elucidate the anisotropic physical properties in this system. Using the obtained single crystals, superconducting properties under magnetic fields parallel to the c-axis (H//c) and ab-plane (H//ab) have been evaluated. It is found that the irreversibility field/temperature, below which the superconducting critical current density (J c) becomes finite, is highly anisotropic in Sr2VFeAsO3: the irreversible region is reduced by approximately half for the case of H//c as compared with H//ab. The suppression of the irreversibility temperature by H//c is found to be the largest among the Fe-based superconductors and comparable to the highly anisotropic Bi–Cu-based high-T c superconductors. The rapid decrease of J c with increasing H//c and T in the irreversible region is also observed. Therefore, there are pronounced fluctuations in the mixed state of Sr2VFeAsO3, suggesting that the vortices are in the pancake state as discussed in the Bi–Cu-based high-T c superconductors. [Copyright &y& Elsevier]

A broadband terahertz time-domain spectroscopy (TDS) system for frequencies of up to 15 THz, including the phonon resonance frequency range, has been developed using a transferred thin-film photoconductive switch (PCS) detector. The thin-film PCSs, based on low-temperature-grown GaAs, were fabricated using epitaxial layer transfer onto high-resistivity Si substrates. We observed a reduction of phonon resonant absorption, including between 7 and 10 THz, in a forward radiation configuration. Numerically calculated absorption spectra show good agreement with our experimental results. This technique will provide compact, broadband TDS systems. [ABSTRACT FROM AUTHOR]

Abstract: We study the dynamic properties of the vortex-solid driven by a radial current I in the Corbino-disk (CD) of a thick amorphous a-Mo x Si1−x film with moderately strong pinning and a thick a-Mo x Ge1−x film with weaker pinning. In CD, vortices rotate around the center of the sample by feeling a Lorentz force f L inversely proportional to the radius r of rotation. We measure the voltages, V(r 12) and V(r 23), induced at the two voltage probes placed radially (r 12 < r 23), as a function of f L (or I). For both films the initial dynamic state of driven solid is the plastic flow, indicating significant pinning effects. For the a-Mo x Si1−x film the large difference between V(r 12) and V(r 23) is observed at lowest I, which is attributed to the stronger pinning effects in the a-Mo x Si1−x film. [Copyright &y& Elsevier]

Abstract We found a glutamine/arginine polymorphism at codon 349 of the hBUBR1 gene, encoding a protein kinase required for spindle assembly checkpoint function. The observed heterozygosity was estimated to be 45% in the Japanese population. This polymorphism may be helpful for genetic studies of many cancer types in which chromosomal instability is observed. [ABSTRACT FROM AUTHOR]

To investigate the real-world data on overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT) with or without consolidation durvalumab, and to perform an exploratory analysis on effective radiation dose to the immune cells (EDIC). In our multi-institutional retrospective study, patients who received CCRT between July 2018 and July 2019 for stage III NSCLC in Japan were investigated. EDIC was estimated using mean lung dose, mean heart dose, body volume, body mean dose, and body weight, as reported in the secondary analysis of RTOG 0617. The cut-off value of EDIC was calculated using the maximally selected log-rank statistics. One hundred and seventy-eight patients were eligible for the analysis (136 patients, CCRT with consolidation durvalumab [CCRT+D] cohort; 42 patients, CCRT cohort). The median follow-up period was 42.5 months. Three-year OS rates were 59.8% in the overall cohort: 60.5% in the CCRT+D cohort, and 58.0% in the CCRT cohort with no significant difference (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.45–1.27; P = 0.29). Univariate analysis showed that ECOG-PS, smoking history, histology, EGFR mutational status, gross tumor volume and EDIC were significantly associated with OS. Multivariate analysis showed that ECOG-PS 2, gross tumor volume ≥ 57 cm3 and EDIC ≥ 4.4 Gy were associated with poor OS. Among 21 EGFR-mutated patients, 3 year-OS rates were 64.7% in the CCRT+D cohort and 100% in the CCRT cohort, while 3 year-OS rates were 68.8% and 58.7% among 90 EGFR wild-type patients. Three-year OS rates were 64.6% and 47.6% for EDIC < 4.4 Gy and EDIC ≥ 4.4 Gy in the overall cohort (HR, 1.82; 95% CI, 1.14–2.90; P = 0.015). In the subgroup analysis, 66.3% vs. 44.4% in the CCRT+D cohort (HR, 2.01; 95% CI, 1.17–3.47; P = 0.016), and 59.0% vs. 56.1% in the CCRT cohort (HR, 1.20; 95% CI, 0.48–3.01; P = 0.70), respectively. Our real-world data in Japan showed that there was no significant difference in OS between the CCRT+D cohort and the CCRT cohort. High EDIC could be a risk for poor OS in patients treated with CCRT and consolidation durvalumab compared with those treated with CCRT. [ABSTRACT FROM AUTHOR]

We have isolated a novel human gene that is expressed specifically in primary spermatocytes in the testis. The cDNA contains an open reading frame of 1356 bp, encoding a 452-amino-acid protein that includes a basic Helix-Loop-Helix (bHLH) motif. The gene, which was mapped to chromosome region 20q13.3→qter by fluorescence in situ hybridization, consists of six exons and spans approximately 24 kb of genomic DNA. Immunohistochemical staining located the gene product exclusively in cell nuclei of primary spermatocytes at the pachytene stage, but not in those at the leptonema stage. We named this gene TCFL5 (transcription factor-like 5, basic helix-loop-helix). The cell-type and stage-specific expression of TCFL5 indicates that this protein may function in a crucial role in spermatogenesis as a transcription factor by regulating cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules. [ABSTRACT FROM AUTHOR]

Geranylgeraniol, a polyprenylalcohol composing the side chain of vitamin K2 (VK2), was previously reported to be a potent inducer of apoptosis in tumor cell lines (Ohzumi H et al, J Biochem 1995; 117: 11-13). We examined the apoptosis-inducing ability of VK2 (menaquinone 3 (MK3), MK4 and MK5) and its derivatives such as phytonadione (VK1), as well as polyprenylalcohols with side chains of various lengths including farnesol (C15-OH; FO), geranylgeraniol (C20-OH; GGO), and geranylfarnesol (C25-OH; GFO) toward leukemia cells in vitro. MK3, MK4, MK5 and GFO (at 10 microM) showed a potent apoptosis-inducing activity for all freshly isolated leukemia cells tested and for leukemia cell lines such as NB4, an acute promyelocytic leukemia (APL)-derived cell line and MDS92, a cell line derived from a patient with myelodysplastic syndrome, although there were some differences depending on the cells tested. In contrast, VK1 showed no effect on any of the leukemia cells. The combination of MK5 plus all-trans retinoic acid (ATRA) resulted in enhanced induction of apoptosis in both freshly isolated APL cells and NB4 cells as compared to each reagent alone. These data suggest the possibility of using VK2 and its derivatives for the treatment of myelogenous leukemias, including APL. [ABSTRACT FROM AUTHOR]

Rosemary ( Rosmarinus officinalis ) is a new therapeutic agent against streptococcosis and monogenean infections in fish. However, the toxicity of rosemary and the kinetics of one of its major component (1,8-Cineole) are unclear. In the present study, liver, kidney and intestine histopathology, plasma chemistry, kinetics of 1,8-Cineole in blood and mucus were examined in common carp fed a diet containing rosemary extract. Feeding the fish ≥20 ml aqueous extract/100 g feed caused nuclear pyknosis and cell atrophy in the liver. Fish fed ≥40 ml aqueous extract/100 g developed pyknotic cells with cytoplasmic vacuoles in the kidney, leading to tubular necrosis. Feeding the fish the rosemary diet for 10 and 20 days increased plasma aspartate aminotransferase levels, a sign of liver damage. Following oral administration of 80 ml aqueous extract/100 g feed, the 1,8-Cineole blood level peaked at 60 min at 117.9 ± 3.5 ng/ml. The elimination half-life (T 1/2 ) of 1,8-Cineole in the blood was 248 min. In mucus, the levels of 1,8-Cineole at the end of 5, 10 and 20 days were 1.5 ± 0.8 ng, 5 ± 4.1 ng and 6.1 ± 3.8 ng per mg crude dried mucus, respectively. These results suggest that at high doses, rosemary aqueous extract diets can cause liver and kidney damage in common carp. Further studies are needed to establish a suitable dosage for oral treatment of parasitic diseases. [ABSTRACT FROM AUTHOR]

Monogenean parasites are important ectoparasites of fish, and are responsible for severe economic impacts in the aquaculture industry. They are usually treated with chemicals, but the chemicals can have harmful side effects in the fish and may pose threats to human health. Rosemary ( Rosmarinus officinalis ) is a common medicinal herb, with antimicrobial and antitumor properties. Here, we examined the anthelmintic activity of rosemary extract against the monogenean ( Dactylogyrus minutus ) in vitro and in vivo using bath treatment and oral administration. The in vitro experiments showed that parasite survival was affected by both rosemary extract concentration and the solvent (water and ethanol). Parasites were dead at 61.8 ± 5.6 and 7.8 ± 1.4 min when exposed to 100 and 200 g aqueous rosemary extract solution/L of water respectively. It took 166.7 ± 48.2 and 5.4 ± 1.01 min to kill the parasites when exposed to 1 and 32 g ethanol rosemary extract solution/L of water respectively. Moreover, pure component of rosemary extract obtained commercially used in in vitro experiments showed that 1,8-Cineole was the most toxic component of the main components tested. Parasite intensity and prevalence in fish exposed to 50 and 100 g aqueous rosemary solution/L water for 30 min were significantly lower than they were in controls ( p < 0.05). In oral treatment experiments, diets of Cyprinus carpio were supplemented with eight different concentrations of aqueous rosemary extract. The intensity of parasites was significantly less in fish fed for 30 days with feed containing 60, 80 and 100 ml aqueous extract/100 g feed than in control ( p < 0.05). Together these results indicate that rosemary is a promising candidate for prevention and control of monogenean infection. [ABSTRACT FROM AUTHOR]

In 2013, an outbreak of ulcerative disease associated with ranavirus infection occurred in barcoo grunter, Scortum barcoo (McCulloch & Waite), farms in Thailand. Affected fish exhibited extensive haemorrhage and ulceration on skin and muscle. Microscopically, the widespread haemorrhagic ulceration and necrosis were noted in gill, spleen and kidney with the presence of intracytoplasmic eosinophilic inclusion bodies. When healthy barcoo grunter were experimentally challenged via intraperitoneal and oral modes with homogenized tissue of naturally infected fish, gross and microscopic lesions occurred with a cumulative mortality of 70-90%. Both naturally and experimentally infected fish yielded positive results to the ranavirus-specific PCR. The full-length nucleotide sequences of major capsid protein gene of ranaviral isolates were similar to largemouth bass virus ( LMBV) and identical to largemouth bass ulcerative syndrome virus ( LBUSV), previously reported in farmed largemouth bass ( Micropterus salmoides L.), which also produced lethal ulcerative skin lesions. To the best of our knowledge, this is the first report of a LMBV-like infection associated with skin lesions in barcoo grunter, adding to the known examples of ranavirus infection associated with skin ulceration in fish. [ABSTRACT FROM AUTHOR]

The article offers information on the recording of new regional and national bryophyte species, and mentions the distribution of species in various countries. Topics discussed include Brotherella harveyana of the Sematophyllaceae family found in India; the moss species Bryum pseudotriquetrum found in Antartica; Bryum tenuisetum found in Hungary; and Frullania subarctica found in Japan.

The article discusses a study that focuses on somatic mutations and clonal hematopoiesis in patients with acquired aplastic anemia. Study highlights include the use of next-generation sequencing and array-based karyotyping for the study, the pattern of somatic clones in individual patients, and chronology of clonal architecture in aplastic anemia.

Abstract: Fibrodysplasia ossificans progressiva (FOP) is an autosomal dominant congenital disorder characterized by postnatal progressive heterotopic ossification in soft tissues, especially skeletal muscle. In FOP, acute heterotopic ossification is induced by muscle injury, such as accidental trauma or surgical operations. Currently, no definitive treatment exists for FOP. The activin receptor type IA/ activin-like kinase 2 (ACVR1/ALK2) gene has been identified as the responsible gene for both familial and sporadic cases of FOP, and disease-associated ALK2 mutations have been found. ALK2 protein, which is one of the signaling receptors for bone morphogenetic proteins (BMPs) and which induce heterotopic bone formation in skeletal muscle in vivo and initiate the differentiation pathway through which myoblasts convert to osteoblastic cells in vitro. Chemical inhibitors such as dorsomorphin to the pathogenic ALK2 receptors are considered possible medical agents for FOP, but their adverse effects on normal ALK2 and other receptors cannot be excluded. Here we describe another treatment strategy for FOP using allele-specific RNA interference (ASP-RNAi), and show modified small interfering RNAs (siRNAs) conferring allele-specific silencing against disease-causing ALK2 mutants (R206H and G356D) found in FOP, without affecting normal ALK2 allele. Thus, the siRNAs presented here may become novel therapeutic agents for FOP, and their induced ASP-RNAi may pave the way for the achievement of radical treatment of FOP and/or for the relief of its severe symptoms. Takahashi M et al. PNAS 2010;107(50):21731–6; Takahashi M et al. Gene Therapy 2011, in press. [Copyright &y& Elsevier]

Spindle cell sarcomas consist of tumors with different biological features, of which distant metastasis is the most ominous sign for a poor prognosis. However, metastasis is difficult to predict on the basis of current histopathological analyses. We have identified actin filament-associated protein 1-like 1 (AFAP1L1) as a candidate for a metastasis-predicting marker from the gene expression profiles of 65 spindle cell sarcomas. A multivariate analysis determined that AFAP1L1 was an independent factor for predicting the occurrence of distant metastasis (P=0.0001), which was further confirmed in another set of 41 tumors by a quantitative mRNA expression analysis. Immunohistochemical staining using paraffin-embedded tumor tissues revealed that the metastasis-free rate was significantly better in tumors negative for AFAP1L1 (P=0.0093 by log-rank test). Knocking down the AFAP1L1 gene in sarcoma cells resulted in inhibition of the cell invasion, and forced expression of AFAP1L1 in immortalized human mesenchymal stem cells induced anchorage-independent growth and increased cell invasiveness with high activity levels of matrix metallopeptidase. Furthermore, tumor growth in vivo was accelerated in AFAP1L1-transduced sarcoma cell lines. These results suggest that AFAP1L1 has a role in the progression of spindle cell sarcomas and is a prognostic biomarker. [ABSTRACT FROM AUTHOR]

Differential magneto-optics are used to study the effect of a dc in-plane magnetic field on hysteretic behavior due to geometrical barriers in Bi2Sr2CaCu2O8+δ crystals. In the absence of an in-plane field a vortex dome is visualized in the sample center surrounded by barrier-dominated flux-free regions. With an in-plane field, stacks of Josephson vortices form vortex chains, which are surprisingly found to protrude out of the dome and into the vortex-free regions. The chains are imaged to extend up to the sample edges, thus providing easy channels for vortex entry and for drain of the dome through geometrical barrier, suppressing the magnetic hysteresis. Reduction of the vortex energy due to crossing with Josephson vortices is evaluated to be about two orders of magnitude too small to account for the formation of the protruding chains. We present a model and numerical calculations that qualitatively describe the observed phenomena by taking into account the demagnetization effects in which flux expulsion from the pristine regions results in vortex focusing and in the chain protrusion. Comparative measurements on a sample with narrow etched grooves provide further support to the proposed model. [ABSTRACT FROM AUTHOR]

Satellite cells are the resident stem cells of adult skeletal muscle, supplying myonuclei for homoeostasis, hypertrophy and repair. In this study, we have examined the role of bone morphogenetic protein (BMP) signalling in regulating satellite cell function. Activated satellite cells expressed BMP receptor type 1A (BMPR-1A/Alk-3) and contained phosphorylated Smad proteins, indicating that BMP signalling is operating during proliferation. Indeed, exogenous BMP4 stimulated satellite cell division and inhibited myogenic differentiation. Conversely, interfering with the interactions between BMPs and their receptors by the addition of either the BMP antagonist Noggin or soluble BMPR-1A fragments, induced precocious differentiation. Similarly, blockade of BMP signalling by siRNA-mediated knockdown of BMPR-1A, disruption of the intracellular pathway by either Smad5 or Smad4 knockdown or inhibition of Smad1/5/8 phosphorylation with Dorsomorphin, also caused premature myogenic differentiation. BMP signalling acted to inhibit the upregulation of genes associated with differentiation, in part, through regulating Id1. As satellite cells differentiated, Noggin levels increased to antagonise BMP signalling, since Noggin knockdown enhanced proliferation and impeded myoblast fusion into large multinucleated myotubes. Finally, interference of normal BMP signalling after muscle damage in vivo perturbed the regenerative process, and resulted in smaller regenerated myofibres. In conclusion, BMP signalling operates during routine satellite cell function to help coordinate the balance between proliferation and differentiation, before Noggin is activated to antagonise BMPs and facilitate terminal differentiation. [ABSTRACT FROM AUTHOR]

Mass mortality of cultured yellowtail, Seriola quinqueradiata, has recently been reported from fish farms in western Japan. Previous studies revealed that diseased fish were characterized by encephalomyelitis and presporogonic stages of a myxosporean-like parasite in the spinal cord. However, the parasite has remained unidentified because of the lack of mature stages being present. Thus, in the present study, analysis of the small subunit ribosomal DNA (18S rDNA) of the parasite as well as in situ hybridization (ISH) studies using histological sections of the infected tissue was conducted. The 18S rDNA of the myxosporean had higher sequence similarities with those of bile-duct-infecting myxosporeans rather than those infecting nervous tissues and was identified as Myxobolus spirosulcatus. The ISH using specific probes demonstrated that the DNA amplified was derived from the multinuclear organisms found in histological sections. A highly sensitive and specific PCR-based assay for M. spirosulcatus was developed, which revealed a high prevalence of infection in cultured yellowtail that exhibited the clinical signs of encephalomyelitis. [ABSTRACT FROM AUTHOR]

Modulation of mast-cell activation may provide novel ways to control allergic diseases. Here, we show that protein tyrosine phosphatase ε (PTPε; Ptpre) plays key regulatory roles during mast-cell activation mediated by the high-affinity IgE receptor (FcεRI). Bone marrow-derived mast cells (BMMC) from Ptpre−/− mice exhibited enhanced FcεRI-induced Ca2+ mobilization and mitogen-activated protein kinase (MAPK) (JNK and p38) activation, and showed corresponding enhancement of evoked degranulation and cytokine production, but not leukotriene production. Examination of proteins linking tyrosine kinase activation and Ca2+ mobilization revealed that the absence of PTPε leads to increased phosphorylation of the linker for activation of T cells and SH2 domain-containing leucocyte phosphoproteins of 76 kDa, but not Grb2-associated binder-2 (Gab2). Because Gab2 is considered to be situated downstream of Fyn kinase, we reasoned that Fyn may not be a target of PTPε. In the event, Syk but not Lyn was hyperphosphorylated in PTPε-deficient BMMC. Thus, PTPε most likely exerts its effects at the level of Syk, inhibiting downstream events including phosphorylation of SLP-76 and linker of activated T cells and mobilization of Ca2+. Consistent with the in vitro data, antigen- and IgE-mediated passive systemic anaphylactic reactions were augmented in Ptpre−/− mice. Given that the number of mast cells is unchanged in these mice, this observation most likely reflects alterations of mast cell-autonomous signalling events. These data suggest that PTPε negatively regulates FcεRI-mediated signalling pathways and thus constitutes a novel target for ameliorating allergic conditions. [ABSTRACT FROM AUTHOR]

We previously reported that Frizzled homologue 10 (FZD10), a member of the Wnt signal receptor family, was highly and specifically upregulated in synovial sarcoma and played critical roles in its cell survival and growth. We here report a possible molecular mechanism of the FZD10 signaling in synovial sarcoma cells. We found a significant enhancement of phosphorylation of the Dishevelled (Dvl)2/Dvl3 complex as well as activation of the Rac1–JNK cascade in synovial sarcoma cells in which FZD10 was overexpressed. Activation of the FZD10–Dvls–Rac1 pathway induced lamellipodia formation and enhanced anchorage-independent cell growth cells. FZD10 overexpression also caused the destruction of the actin cytoskeleton structure, probably through the downregulation of the RhoA activity. Our results have strongly implied that FZD10 transactivation causes the activation of the non-canonical Dvl–Rac1–JNK pathway and plays critical roles in the development/progression of synovial sarcomas.Oncogene (2009) 28, 1110–1120; doi:10.1038/onc.2008.467; published online 12 January 2009 [ABSTRACT FROM AUTHOR]

The continuing evolution of a variety of laparoscopic instrument and device has been gradually applied to the laparoscopic hepatectomy in many countries. Recent experience has persuaded us that there are great potential benefits derived from laparoscopic hepatectomy and much has been learned about patient selection, the grade of surgical difficulty with respect to tumor location, and the required instrumentation. Among these efforts, various ways of hepatic parenchymal transection with mechanical devices have been attempted and continuing to innovate to perform safe laparoscopic hepatectomy Important technologic developments and improved endoscopic procedures are being established equipment modifications. For safe laparoscopic hepatectomy, it is important to have all necessary equipment. The intraoperative laparoscopic ultrasonography, microwave coagulators, ultrasonic dissection, argon beam coagulators, laparoscopic coagulation shears, endolinear staplers and TissueLink monopolar sealer are essential. This procedure is in need that well experienced endoscopic surgeon and well-experienced liver surgeon should be collaborated in laparoscopic hepatectomy and the indications are strictly followed based upon the location and size of tumors. Finally critical determinant for success and safe laparoscopic hepatectomy is through familiarity with the relevant laparoscopic instruments and equipments. Laparoscopic hepatectomy is expected to develop further in the future as a new surgical instrument, equipment and method, which improves patients' quality of life. [ABSTRACT FROM AUTHOR]

To investigate the detailed molecular mechanism of mammary carcinogenesis and discover novel therapeutic targets, we previously analysed gene expression profiles of breast cancers. We here report characterization of a significant role of DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein) in mammary carcinogenesis. Semiquantitative RT–PCR and northern blot analyses confirmed upregulation of DTL/RAMP in the majority of breast cancer cases and all of breast cancer cell lines examined. Immunocytochemical and western blot analyses using anti-DTL/RAMP polyclonal antibody revealed cell-cycle-dependent localization of endogenous DTL/RAMP protein in breast cancer cells; nuclear localization was observed in cells at interphase and the protein was concentrated at the contractile ring in cytokinesis process. The expression level of DTL/RAMP protein became highest at G1/S phases, whereas its phosphorylation level was enhanced during mitotic phase. Treatment of breast cancer cells, T47D and HBC4, with small-interfering RNAs against DTL/RAMP effectively suppressed its expression and caused accumulation of G2/M cells, resulting in growth inhibition of cancer cells. We further demonstrate the in vitro phosphorylation of DTL/RAMP through an interaction with the mitotic kinase, Aurora kinase-B (AURKB). Interestingly, depletion of AURKB expression with siRNA in breast cancer cells reduced the phosphorylation of DTL/RAMP and decreased the stability of DTL/RAMP protein. These findings imply important roles of DTL/RAMP in growth of breast cancer cells and suggest that DTL/RAMP might be a promising molecular target for treatment of breast cancer.Oncogene (2008) 27, 5672–5683; doi:10.1038/onc.2008.186; published online 9 June 2008 [ABSTRACT FROM AUTHOR]

Single crystals of LuAG doped with Pr3+ ions (0.2 mol%) are grown by the micro-pulling-down (μ-PD) method with an RF heating system. The as-grown crystals are confirmed to be of garnet-type structure with the space group of Ia3d (230). The emission-excitation spectra and luminescence decay kinetics are measured in the temperature range of 5-310 K by using synchrotron radiation as an exciting light source. The intrinsic luminescence is observed at 250 nm at low temperatures. Four emission bands at 308, 325, 360, and 380 nm are ascribed to the 5d- > 4f transitions of Pr 3+ ions. From the decay kinetics measurements, it is pointed out that there exist two kinds of energy transfer mechanisms from the host LuAG lattice to the Pr 3+ ions. The mechanisms of energy transfer are discussed in connection with the formation of substitution-type defects. [ABSTRACT FROM AUTHOR]

CeF3 single crystals heavily doped with Sr2+ ions are grown by the micro-pulling-down (μ-PD) method. The deviation of the composition in as-grown crystals is found to be entirely negligible. Three dimensional emission-excitation spectra are measured in a wide temperature range of 5-300 K by using synchrotron radiation as an exciting light source. Two intense emission bands are observed at around 320 and 400 nm. The origin of these bands is discussed on the basis of the perturbation effects introduced by Sr doping. It is pointed out that the energy transfer takes place from Ce3+ sites to defect sites when the crystal is warmed from 5 to 300 K. [ABSTRACT FROM AUTHOR]

The p53 protein inhibits malignant transformation through direct and indirect regulation of transcription of many genes related to cell cycle, apoptosis and cellular senescence. A number of genes induced by p53 have been well characterized, but biological significance of genes whose expression was suppressed by p53 is still largely undisclosed. To clarify the roles of p53-suppressive genes in carcinogenesis, we analysed two data sets of whole-genome expression profiles, one for cells in which wild-type p53 was exogenously introduced and the other for a large number of clinical cancer tissues. Here, we identified CDC20 that was frequently upregulated in many types of malignancies and remarkably suppressed by ectopic introduction of p53. CDC20 expression was suppressed by genotoxic stresses in p53- and p21-dependent manners through CDE-CHR elements in the CDC20 promoter. Furthermore, small interference RNA (siRNA)-mediated silencing of p53 induced CDC20 expression in normal human dermal fibroblast cells. As we expected, treatment of cancer cells with siRNA against CDC20 induced G2/M arrest and suppressed cell growth. Our results indicate that p53 inhibits tumor cell growth through the indirect regulation of CDC20 and that CDC20 might be a good potential therapeutic target for a broad spectrum of human cancer.Oncogene (2008) 27, 1562–1571; doi:10.1038/sj.onc.1210799; published online 17 September 2007 [ABSTRACT FROM AUTHOR]

Background Interleukin-6 (IL-6) and metalloproteinases (MMPs) are involved in the instability of vulnerable plaque associated with the induction of acute myocardial infarction (AMI). We examined the regional changes of cytokines, MMPs and adhesion molecules in patients with AMI to elucidate how these factors are involved in the onset of AMI. Materials and methods One hundred and twenty-two patients with AMI were included. Blood was aspirated from the culprit coronary artery with a thrombectomy catheter, and was also sampled from peripheral veins during the coronary intervention. Control samples were obtained from the peripheral blood of age-matched patients. Results The serum levels of IL-6 ( P < 0·05), tumour necrosis factor-α ( P < 0·005), MMP-1 ( P < 0·001), MMP-13 ( P < 0·001), soluble intercellular adhesion molecule-1 ( P < 0·005), and soluble vascular cellular adhesion molecule-1 ( P < 0·05) in peripheral blood were significantly higher in the AMI group than in the controls. Aspirated serum contained significantly higher levels of IL-6 ( P < 0·001), MMP-1 ( P < 0·001), and MMP-13 ( P < 0·05) compared to the peripheral blood of AMI. Serum IL-6 levels were significantly higher in the aspirated than in the peripheral blood in the patients hospitalized within 6 h and 6–12 h, but were similar in the aspirated and peripheral blood of the patients hospitalized 12–24 h after the onset of AMI. There were no differences between the aspirated serum and peripheral blood in the levels of interleukin-1β and MMP-2. Conclusions The levels of MMP-1, MMP-13 and IL-6 were higher in the culprit coronary artery than in the peripheral blood. These factors appear to be involved in the early stage of AMI. [ABSTRACT FROM AUTHOR]

In the present work, the regenerative thermal oxidiser (RTO) with preheating and baking system was applied to treating volatile organic compounds (VOCs) discharged from the shell mould casting. As a result, it was found that the tar characterised by more than 523 K of high boiling point was formed by the shell mould casting. The Fourier transform infrared spectrometry analysis showed that the tar was composed of paraffin, zinc stearate and quartz. A part of the tar was deposited on the ceramic honeycombs in the heat exchanger. However, the tar can be almost completely removed by means of baking treatment at 623 K in the RTO. Regarding the decomposition of VOCs, it was found that the concentrations of all VOCs were reduced to less than 1 ppm. Further, 98% of offensive odour was removed by the treatment. Thus, it can be concluded that the RTO is suitable for decreasing VOCs from the shell mould casting in the foundry. [ABSTRACT FROM AUTHOR]

In an attempt to disclose mechanisms of bladder carcinogenesis and discover novel target molecules for development of treatment, we applied a cDNA microarray to screen genes that were significantly transactivated in bladder cancer cells. Among the upregulated genes, we here focused on a novel gene, (DEPDC1) DEP domain containing 1, whose overexpression was confirmed by northern blot and immunohistochemical analyses. Immunocytochemical staining analysis detected strong staining of endogenous DEPDC1 protein in the nucleus of bladder cancer cells. Since DEPDC1 expression was hardly detectable in any of 24 normal human tissues we examined except the testis, we considered this gene-product to be a novel cancer/testis antigen. Suppression of DEPDC1 expression with small-interfering RNA significantly inhibited growth of bladder cancer cells. Taken together, these findings suggest that DEPDC1 might play an essential role in the growth of bladder cancer cells, and would be a promising molecular-target for novel therapeutic drugs or cancer peptide-vaccine to bladder cancers.Oncogene (2007) 26, 6448–6455; doi:10.1038/sj.onc.1210466; published online 23 April 2007 [ABSTRACT FROM AUTHOR]

Sixty-four isolates of Flavobacterium psychrophilum from ayu, Plecoglossus altivelis altivelis (Temminck & Schlegel), and other fish ( n = 16) in Japan and the type strain (NCIMB 1947T) were typed using pulsed-field gel electrophoresis (PFGE) with endonuclease BlnI and XhoI. These isolates were classified into 20 clusters and 42 genotypes by PFGE analysis. The most predominant cluster of isolates from ayu was cluster XII ( n = 20), followed by clusters XVII, XVI, XX, XI, IX, X, XIII and XV; the remaining 17 isolates from other fish were divided into clusters I, II, III, IV, V, VI, VII, VIII, XIV, XVIII and XIX. The PFGE genotype of isolates from ayu clearly differed from those of other fish. The isolates from ayu in Gunma Prefecture belonged to clusters XII, XVI, XVII and XX, and the strains of three of these clusters (XII, XVII and XX) were isolated from ayu in 15 of 19 prefectures. PFGE typing enabled more accurate classification of isolates into clusters than previously achieved by analysing the restriction fragment length polymorphism of PCR products. These results suggest that F. psychrophilum isolated from ayu and other fish are genetically different and strains with several PFGE types have spread within Japan. [ABSTRACT FROM AUTHOR]

The involvement of bacterial translocation in small intestinal ischemia-reperfusion injuries and the efficacy of using anti-CINC antibodies for treatment were investigated. A model for ischemia-reperfusion injury of the small intestine was constructed by clamping the supramesenteric artery (for 90 min) in rats. Anti-CINC antibodies and saline were given just before the induction of ischemia in the treatment group and the control group, respectively. Six hours after reperfusion, bacteria were detected in the mesenteric lymph nodes, but the ‘bacteria-positive’ rate was significantly lower in the treatment group than in the control group. Bacterial cultures and endotoxins in the blood were negative in both groups up to 24 h later. The plasma cytokine levels showed similar variations, although the increases were significantly lower after reperfusion in the treatment group. In addition, the degrees of neutrophil infiltration and mucosal injury were attenuated in the small intestine, and the structure of the liver was maintained. Furthermore, the 1-week survival was improved. These results suggest that bacterial translocation occurred predominantly via the lymphatic system and that anti-CINC antibody treatment exerted a protective effect against small intestinal ischemia-reperfusion injury. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: The ligament of Marshall (LOM) or the oblique vein of Marshall (VOM) in the left atrium (LA) is one of the origins of nonpulmonary vein ectopies causing atrial fibrillation. The distributions of myocardial bundles (Marshall bundles; MBs) and autonomic nerves adjacent to the LOM have not been completely elucidated. Methods and Results: Twenty-eight human hearts were examined postmortem. The inferolateral LA myocardium was dissected en block and cut perpendicularly to the atrioventricular ring. The specimens were sectioned at 1-mm intervals and stained with hematoxylin and eosin, and Azan-Mallory. In addition, S-100 and tyrosine hydroxylase (TH) were employed for the immunohistochemical analysis of the sympathetic and parasympathetic fibers. In 25 cases, MBs were observed. Although the MBs surrounded the VOM at the coronary sinus (CS) juncture, they gradually diminished in density toward the distal venous branch. The connections of the MBs and LA myocardium were frequently observed in the CS juncture and anterior wall of the left pulmonary vein (PV)-LA junctions. TH-stained sympathetic nerve fibers were densely distributed around the PV-LA junctions. On the other hand, non-TH-stained parasympathetic ganglions were mainly observed at the CS juncture. Conclusions: MB-LA connections were mainly observed at the CS juncture and PV-LA junctions. The association between sympathetic nerve fibers and MBs was distinct at the PV-LA junctions. At the CS juncture, the regression of the sympathetic nerve fibers and the increase of parasympathetic ganglions were observed. The diverse arrangement and autonomic innervation of MBs seem to characterize the LOM region in humans. [ABSTRACT FROM AUTHOR]

We used three types of AMN to investigate the expression profiles of melanogenesis-related genes [tyrosinase, tyrosinase-related protein-1 (TRP1), dopachrome tautomerase (TRP2), Pmel-17/gp100, P-protein, and microphthalmia-associated transcription factor (MITF)], as well as tyrosinase, TRP1, Pmel-17/gp100, and MITF proteins. Results: All melanogenesis-related genes examined in the junctional type were expressed in the basal epidermal layer. In the compound and intradermal types, mRNA for tyrosinase, TRP2, and MITF was expressed in all of the AMN cells. However, the expression of TRP1, P-protein, and Pmel-17/gp100 in the compound type and TRP1 in the intradermal type became weaker in accordance with the depth of the dermis layer, as compared to those levels in the basal to upper dermis layer. Although tyrosinase and Pmel-17/gp100 mRNA in the compound and intradermal types was expressed in the intraepidermal and dermal components, immunohistochemical staining showed that tyrosinase proteins were not detected in the lower dermis layer and Pmel-17/gp100 proteins were not detected in the dermis. Conclusions: Our results suggest that all nevus cells that constitute AMN tissue originate from melanocytes. Further, there may be differences in the transcription levels of melanogenesis-related genes as well as in their post-transcriptional regulation between nevus cells located in the basal epidermal to upper dermis layer and those in the lower dermis layer. [ABSTRACT FROM AUTHOR]