Three-dimensional flow phenomena in a wire-wrapped 37-pin fuel bundle for SFR

AbstractThree-dimensional flow phenomena in a wire-wrapped 37-pin fuel assembly mock-up of a Japanese loop-type sodium-cooled fast reactor, Monju, were investigated with a numerical analysis using a general-purpose commercial computational fluid dynamics code, CFX. Complicated and vortical flow phenomena in the wire-wrapped 37-pin fuel assembly were captured by a Reynolds-averaged Navier–Stokes flow simulation using a shear stress transport turbulence model. The main purpose of the current study is to understand the three-dimensional complex flow phenomena in a wire-wrapped fuel assembly to support the license issue for the core design. Computational fluid dynamics results show good agreement with friction factor correlation models. The secondary flow in the corner and edge subchannels is much stronger than that in an interior subchannel. The axial velocity averaged in the corner and edge subchannels is higher than that averaged in the interior subchannels. Three-dimensional multiscale vortex structures start to be formed by an interaction between secondary flows around each wire-wrapped pin. Behavior of the large-scale vortex structures in the corner and edge subchannels is closely related to the relative position between the hexagonal duct wall and the helically wrapped wire spacer. The small-scale vortex is axially developed in the interior subchannels. Furthermore, a driving force on each wire spacer surface is closely related to the relative position between the hexagonal duct wall and the wire spacer

Selenoprotein W enhances skeletal muscle differentiation by inhibiting TAZ binding to 14-3-3 protein

AbstractSelenoprotein W (SelW) is expressed in various tissues, particularly in skeletal muscle. We have previously reported that SelW is up-regulated during C2C12 skeletal muscle differentiation and inhibits binding of 14-3-3 to its target proteins. 14-3-3 reduces myogenic differentiation by inhibiting nuclear translocation of transcriptional co-activator with PDZ-binding motif (TAZ). Phosphorylation of TAZ at Ser89 is required for binding to 14-3-3, leading to cytoplasmic retention of TAZ and a delay in myogenic differentiation. Here, we show that myogenic differentiation was delayed in SelW-knockdown C2C12 cells. Down-regulation of SelW also increased TAZ binding to 14-3-3, which eventually resulted in decreasing translocation of TAZ to the nucleus. However, phosphorylation of TAZ at Ser89 was not affected. Although phosphorylation of TAZ at Ser89 was sustained by the phosphatase inhibitor okadaic acid, nuclear translocation of TAZ was increased by ectopic expression of SelW. This result was due to decreased binding of TAZ to 14-3-3. We also found that the interaction between TAZ and MyoD was increased by ectopic expression of SelW. Taken together, these findings strongly demonstrate that SelW enhances C2C12 cell differentiation by inhibiting TAZ binding to 14-3-3

The orphan nuclear receptor SHP is a positive regulator of osteoblastic bone formation

The orphan nuclear receptor small heterodimer partner (SHP; NR0B2) interacts with a diverse array of transcription factors and regulates a variety of cellular events such as cell proliferation, differentiation, and metabolism. However, the role of SHP in bone formation has not yet been elucidated. SHP expression is significantly increased during osteoblast differentiation, and its expression is partially regulated by bone morphogenetic protein 2 (BMP-2), which plays an important role in bone formation. In our study, inhibition of SHP expression significantly repressed BMP-2-induced osteoblast differentiation and ectopic bone formation. In accordance with these in vitro and in vivo results, osteoblast differentiation in SHP −/− mice primary osteoblasts was significantly repressed, and the mice showed decreased bone mass resulting from decreased numbers of osteoblasts. Finally, SHP physically interacts and forms a complex with runt-related transcription factor 2 (Runx2) on the osteocalcin gene promoter, and overexpression of SHP increased Runx2 transactivity via competition with histone deacetylase 4 (HDAC4), an enzyme that inhibits DNA binding of Runx2 to its target genes. Taken together, these results indicate that SHP acts as a novel positive regulator of bone formation by augmenting osteoblast differentiation through regulation of the transcriptional activity of Runx2. © 2010 American Society for Bone and Mineral ResearchPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65055/1/90718_ftp.pd

C1-Ten is a PTPase of nephrin, regulating podocyte hypertrophy through mTORC1 activation

Hypertrophy is a prominent feature of damaged podocytes in diabetic kidney disease (DKD). mTORC1 hyperactivation leads to podocyte hypertrophy, but the detailed mechanism of how mTORC1 activation occurs under pathological conditions is not completely known. Moreover, reduced nephrin tyrosine phosphorylation has been observed in podocytes under pathological conditions, but the molecular mechanism linking nephrin phosphorylation and pathology is unclear so far. In this study, we observed a significant increase in C1-Ten level in diabetic kidney and in high glucose-induced damaged podocytes. C1-Ten acts as a protein tyrosine phosphatase (PTPase) at the nephrin-PI3K binding site and renders PI3K for IRS-1, thereby activating mTORC1. Furthermore, C1-Ten causes podocyte hypertrophy and proteinuria by increasing mTORC1 activity in vitro and in vivo. These findings demonstrate the relationship between nephrin dephosphorylation and the mTORC1 pathway, mediated by C1-Ten PTPase activity. We suggest that C1-Ten contributes to the pathogenesis of DKD by inducing podocyte hypertrophy under high glucose conditions.111Ysciescopu

Establishment of an experimental model of ovalbumin-induced atopic dermatitis in canines

IntroductionA reliable standard model is required to evaluate the efficacy of new drugs for companion animals, especially dogs. Canine atopic dermatitis (cAD), also known as allergic inflammatory skin disease, is a common condition. Currently, the house dust mite animal model is used in the research of cAD; however, this model exhibits significant individual variation and is difficult to standardize. In this study, we used ovalbumin as an antigen to sensitize and stimulate dogs, thereby establishing a stable model mimicking the T-helper 2 (Th2) response seen in cAD. Our objective was to create a cAD model that could be employed to evaluate the efficacy of novel drugs and mimic the Th2 dominant allergic response observed in the pathogenesis of atopic dermatitis of dogs.MethodsIn this study, six beagles were used. Normal saline was applied to two animals, and ovalbumin to four, on their dorsal skin.ResultsThe ovalbumin-treated groups exhibited clinical cAD symptoms, such as pruritus and erythema. Moreover, plasma levels of the cAD markers immunoglobulin E and CCL17 chemokine were higher in the ovalbumin-treated group than in the vehicle control group. The skin thickness of the epidermis was significantly increased in the ovalbumin-treated group, with infiltration of inflammatory cells observed in the thickened dermis region. In conclusion, treatment of canine skin with an optimal concentration of ovalbumin induced typical cAD-like symptoms, and histological and molecular analyses confirmed an enhanced Th2-related immune response.ConclusionTherefore, we successfully established a suitable Th2-dominant response mimicking cAD, which will facilitate targeted research of atopic dermatitis in dogs

Effects of Berberine and Hwangryunhaedok-Tang on Oral Bioavailability and Pharmacokinetics of Ciprofloxacin in Rats

Hwangryunhaedok-Tang (HR) and berberine-containing single herbs are used to treat bacterial infection and inflammatory diseases in eastern Asia. The combination of berberine-containing herbal medicines and ciprofloxacin can be an excellent antibacterial chemotherapy against multidrug resistance bacteria. To evaluate the pretreatment effect of berberine and HR, vehicle, berberine (25 and 50 mg/kg/day), and HR (1.4 g/kg/day) were daily administered to rats for five consecutive days. On day 6, ciprofloxacin was administered (10 mg/kg, i.v. and 20 mg/kg, p.o.) to rats. To assess cotreatment effect of berberine and ciprofloxacin, berberine (50 mg/kg) and ciprofloxacin (20 mg/kg) were coadministered by single oral gavage. Pharmacokinetic data were estimated by noncompartmental model. Compared with ciprofloxacin alone (control group), coadministration of berberine (50 mg/kg) and ciprofloxacin significantly decreased Cmax of ciprofloxacin (P<0.05). In addition, the pretreatment of berberine (50 mg/kg/day) and HR (1.4 g/kg/day) significantly decreased Cmax and AUC0→∞, compared with control group (P<0.05). The oral bioavailability of ciprofloxacin was reduced by cotreatment of berberine and pretreatment of berberine and HR. Our results suggest that the expression of P-glycoprotein and organic anion and/or organic cation transporters (OAT/OCT) could take a role in reduced oral bioavailability of ciprofloxacin by berberine and HR

Evaluation of a Sodium–Water Reaction Event Caused by Steam Generator Tubes Break in the Prototype Generation IV Sodium-cooled Fast Reactor

AbstractThe prototype generation IV sodium-cooled fast reactor (PGSFR) has been developed by the Korea Atomic Energy Research Institute. This reactor uses sodium as a reactor coolant to transfer the core heat energy to the turbine. Sodium has chemical characteristics that allow it to violently react with materials such as a water or steam. When a sodium–water reaction (SWR) occurs due to leakage or breakage of steam generator tubes, high-pressure waves and corrosive reaction products are produced, which threaten the structural integrity of the components of the intermediate heat-transfer system (IHTS) and the safety of the primary heat-transfer system (PHTS). In the PGSFR, SWR events are included in the design-basis event. This event should be analyzed from the viewpoint of the integrities of the IHTS and fuel rods. To evaluate the integrity of the IHTS based on the consequences of the SWR, the behaviors of the generated high-pressure waves are analyzed at the major positions of a failed IHTS loop using a sodium–water advanced analysis method-II code. The integrity of the fuel rods must be consistently maintained below the safety acceptance criteria to avoid the consequences of the SWR. The integrity of the PHTS is evaluated using the multidimensional analysis of reactor safety-liquid metal reactor code to model the whole plant

Sequences of the Cytochrome C Oxidase Subunit I (COI) Gene are Suitable for Species Identification of Korean Calliphorinae Flies of Forensic Importance (Diptera: Calliphoridae)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75068/1/j.1556-4029.2009.01126.x.pd