Application of Double Piping Theory to Parallel-Arrayed Low-Pressure Membrane Module Header Pipe and Experimental Verification of Flow Distribution Evenness.

In this study, the improvement effect of flow distribution evenness is evaluated quantitatively by applying the double piping theory to a parallel-arrayed low-pressure membrane module header pipe structure, and its feasibility is discussed. Orifice inner pipes to be inserted into a full-scale membrane module header pipe are designed via the computational fluid dynamics (CFD) technique, and the flow rates into 10 membrane modules are measured in real time using a portable ultrasonic flowmeter during operation to verify the effect. Results of CFD simulation and actual measurements show that the outflow rate from the branch pipe located at the end of the existing header pipe is three times higher than the flow rate from the branch pipe near the inlet. By inserting two inner pipes (with an open end and a closed end into the existing header pipe) and applying the double pipe theory, the flow distribution evenness is improved. The CFD simulation and experimental results show that the flow uniformity can be improved by more than 70% and 50%, respectively.

A Study on the Evaluation of Flow Distribution Evenness in Parallel-Arrayed-Type Low-Pressure Membrane Module Piping.

The objectives of this study were to measure the flow rate distribution from a header pipe to each module installed in parallel for a water treatment membrane filtration process in operation and to investigate the reason for an uneven distribution of the flow rate via the CFD technique. In addition, this study attempted to propose the ratio of the branch pipe to the header pipe required to equalize the flow distribution for the same membrane filtration process. Finally, the relationship between the Reynolds number in the header pipe and the degree of the manifold flow distribution evenness was investigated. Mobile ultrasonic flow meter was used to measure the flow rate flowing from the membrane module pipe to each module, and the CFD technique was used to verify this. From the results of the actual measurement using ultrasonic flow meter and CFD simulation, it was confirmed that the outflow flow rate from the branch pipe located at the end of the header pipe was three times higher than that of the branch pipe near the inlet. The reason was that the differential pressure generated between each membrane module was higher toward the end of the header pipe. When the ratio of the sum of the cross-sectional area of the branch pipe and the cross-sectional area of the header pipe was reduced by about 30 times, it was confirmed that the flow rate flowing from each branch pipe to the membrane module was almost equal. Also, if the flow in the header pipe is transitional or laminar (Reynolds No. is approximately 4000 or less), the flow rate flowing from each branch pipe to the membrane module can be more even.

Anti-Inflammatory Effect of Mangostenone F in Lipopolysaccharide-Stimulated RAW264.7 Macrophages by Suppressing NF-κB and MAPK Activation.

Mangostenone F (MF) is a natural xanthone isolated from Garcinia mangostana. However, little is known about the biological activities of MF. This study was designed to investigate the anti-inflammatory effect and underlying molecular mechanisms of MF in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. MF dose-dependently inhibited the production of NO, iNOS, and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in LPS-stimulated RAW264.7 macrophages. Moreover, MF decreased the NF-κB luciferase activity and NF-κB DNA binding capacity in LPS-stimulated RAW264.7 macrophages. Furthermore, MF suppressed the NF-κB activation by inhibiting the degradation of IκBα and nuclear translocation of p65 subunit of NF-κB. In addition, MF attenuated the AP-1 luciferase activity and phosphorylation of ERK, JNK, and p38 MAP kinases. Taken together, these results suggest that the anti-inflammatory effect of MF is associated with the suppression of NO production and iNOS expression through the down-regulation of NF-κB activation and MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages.

Relaxin augments BMP-2-induced osteoblast differentiation and bone formation.

Relaxin (Rln), a polypeptide hormone of the insulin superfamily, is an ovarian peptide hormone that is involved in a diverse range of physiological and pathological reactions. In this study, we investigated the effect of Rln on bone morphogenetic protein 2 (BMP-2)-induced osteoblast differentiation and bone formation. Expression of Rln receptors was examined in the primary mouse bone marrow stem cells (BMSCs) and mouse embryonic fibroblast cell line C3H/10T1/2 cells by RT-PCR and Western blot during BMP-2-induced osteoblast differentiation. The effect of Rln on osteoblast differentiation and mineralization was evaluated by measuring the alkaline phosphatase activity, osteocalcin production, and Alizarin red S staining. For the in vivo evaluation, BMP-2 and/or Rln were administered with type I collagen into the back of mice, and after 3 weeks, bone formation was analyzed by micro-computed tomography (µCT). Western blot was performed to determine the effect of Rln on osteoblast differentiation-related signaling pathway. Expression of Rxfp 1 in BMSCs and C3H/10T1/2 cells was significantly increased by BMP-2. In vitro, Rln augmented BMP-2-induced alkaline phosphatase expression, osteocalcin production, and matrix mineralization in BMSCs and C3H/10T1/2 cells. In addition, in vivo administration of Rln enhanced BMP-2-induced bone formation in a dose-dependent manner. Interestingly, Rln synergistically increased and sustained BMP-2-induced Smad, p38, and transforming growth factor-ß activated kinase (TAK) 1 phosphorylation. BMP-2-induced Runx 2 expression and activity were also significantly augmented by Rln. These results show that Rln enhanced synergistically BMP-2-induced osteoblast differentiation and bone formation through its receptor, Rxfp 1, by augmenting and sustaining BMP-2-induced Smad and p38 phosphorylation, which upregulate Runx 2 expression and activity. These results suggest that Rln might be useful for therapeutic application in destructive bone diseases.

Comparative proteomic analysis of advanced serous epithelial ovarian carcinoma: possible predictors of chemoresistant disease.

To identify specific proteins associated with chemotherapeutic responses, we analyzed protein expression patterns in stage IIIc primary serous epithelial ovarian cancer tissues displaying differential responses to first-line postoperative adjuvant chemotherapy. The expression profiles of five chemoresistant tissues [progression-free survival (PFS) ≤12 months] and five chemosensitive tissues (PFS ≥48 months) were analyzed with 2D electrophoresis, and the spot intensities of differentially expressed proteins were quantified. To validate these proteins as markers for chemoresistant disease, we analyzed tissues from an additional 17 patients. All the patients were allocated to the over- or underexpressing group according to protein spot intensity, and survival analysis was performed. In chemoresistant tissues, four proteins (thioredoxin domain containing four, similar to RIKEN cDNA 1700016G05, tubulin α 1A chain, and the pyruvate dehydrogenase E1-ß subunit precursor) were overexpressed, and seven proteins [keratin 1, vitamin D-binding protein, creatine kinase B, annexin V, SH3-containing guanine nucleotide exchange factor (SGEF), tryptophan-aspartate repeat protein-1 (WDR 1), and WDR 1 isoform 1] were underexpressed. The underexpression of keratin 1, creatine kinase B, annexin V, SGEF, WDR1, and WDR1 isoform 1 were significantly correlated with poor overall survival. A combination of keratin 1 and SGEF showed the highest sensitivity of 0.800, specificity of 0.917, PPV of 0.800, and NPV of 0.917 in predicting chemoresistant disease. These proteins may be useful as predictive markers of chemoresistant disease. However, further analyses in large-scale should be performed before they can be considered reliable predictive markers of chemoresistant disease.

Up-regulation of the BTG2 gene in TPA- or RA-treated HL-60 cell lines.

The key pathogenesis of leukemia is the defection of the differentiation processes of hematopoietic stem cells. There are five APRO (anti-proliferative) genes, BTG1, BTG2, BTG3, TOB and TOB2, and it was reported that certain APRO genes are associated with cell differentiation. However, it is still unknown whether APRO genes are related with the differentiation process of blood cells. In this study, we investigated the expression of APRO genes in 12-O-tetra-decanoylphorbol-13-acetate (TPA) or retinoic acid (RA)-treated HL-60 cell lines. Our data show that the expression of the BTG2 gene was increased in 32 nM TPA-treated and 1 microM RA-treated HL-60 cells, but the expression of the BTG1 and BTG3 genes was not increased. The expression of BTG2 in TPA- or RA-treated HL-60 cells was also increased even in the presence of cyclohexamide, which is an inhibitor of translation, implying that the increased expression of BTG2 mRNA did not require the new synthesis of another protein. Notably, the up-regulation of BTG2 in TPA- or RA-treated HL-60 cells was observed prior to the increased expression of p21. Our data show that PKC pathways are uninvolved with the up-regulation of BTG2 in TPA- or RA-treated HL-60 cells. Thus, the up-regulation of BTG2 genes may be involved in the differentiation process of HL-60 cells after TPA or RA treatment. Furthermore, this event occurred prior to p21 expression, implying that the BTG2 expression plays a role at a very early point during the differentiation processes of hematopoietic cells.

Aberrant p16INK4A RNA transcripts expressed in hepatocellular carcinoma cell lines regulate pRb phosphorylation by binding with CDK4, resulting in delayed cell cycle progression.

The inactivation of the p16INK4A (p16) gene by promoter hypermethylation has been reported in many human cancers. We previously reported that aberrant p16 RNA transcripts are expressed in hepatocellular carcinoma (HCC) cell lines having hypermethylated p16 promoters. In this study, we investigated the functional roles of aberrant p16 RNA transcripts in HCC cells to elucidate molecular events underlying hepatocarcinogenesis. The aberrant p16 RNA transcripts encoded key peptides (amino acids 84-103) involved in binding with cyclin-dependent kinase (CDK) 4. GST-aberrant p16 fusion proteins were found to interact with endogenous CDK4 in vitro. Furthermore, overexpression of these aberrant p16 RNA transcripts resulted in decreased cell proliferation rate, enlargement of cell shape and reduced level of hyperphosphorylated forms of pRb. Overall, our results suggest that the aberrant p16 RNA transcripts have functions similar to those of wild type p16 in controlling cell cycle.

Exogenous wild-type p16INK4A gene induces delayed cell proliferation and promotes chemosensitivity through decreased pRB and increased E2F-1 expressions.

Human gastric cancer SNU 484 cells express mutant p16, which migrates slower than the wild-type p16. We constructed an expression vector containing human p16 cDNA to evaluate the cytotoxic effects of exogenous p16 expression on SNU 484 cell proliferation and to explore the potential use of p16 in cancer gene therapy. The stable transfectant expressing wild-type p16, showed a 2-fold slower growth rate than mock and non-infected cells through down-regulation of CDK4-dependent kinase activity. When cells were transiently transfected with mock or p16 encoded vector, the mock cells showed larger survival colonies than those of wild-type p16. Furthermore, p16-expressing stable transfectant was readily progressed into cell death by combination with treatment of chemotherapeutic drug in a dose-dependent manner. According to western blot analysis, both decreased expression of pRB and increased expression of E2F-1 may contribute to the susceptibility of cell death. Our data indicate that exogenous wild-type p16 induces delayed cell proliferation and promotes chemo-sensitivity in the gastric cancer cell line, implying the promise of p16 in cancer gene therapy.

Epidemiological typing and prevalence of integrons in multiresistant Acinetobacter strains.

Seventy-seven Acinetobacter isolates were recovered from patients in a Korean hospital during the period from November to December 1998. The isolates were genotyped using randomly amplified polymorphic DNA (RAPD) analysis for epidemiological relationship, and investigated for antibiotic susceptibility and presence of integrons. Sixty-nine Acinetobacter baumannii isolates were distributed into five groups by RAPD profiles, with 5, 1, 60, 2 and 1 in each group. The major RAPD group of 60 isolates was further divided into six subgroups by antibiograms. Eight isolates belonging to Acinetobacter DNA group 13TU were distributed among six RAPD groups. Seventy-three of the Acinetobacter isolates were resistant to eight or more of the antibiotics tested. Integrase genes were detected in 66 of the 69 A. baumannii (96%) and in 5 of the 8 Acinetobacter DNA group 13TU isolates (63%). The intI1 and intI2 genes were found in 63 and 8 isolates, respectively. The intI3 gene was not detected. All integron-carrying isolates were resistant to multiple antibiotics. All strains isolated from more than one patient carried integrons. According to the results, the presence of integrons was significantly (p<0.01) associated with multiple antibiotic resistance and nosocomial spread in Acinetobacter strains.