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Despite the beneficial actions of antibiotics against bacterial infections, the use of antibiotics is a crucial etiological factor influencing microbial dysbiosis-associated adverse outcomes in human health. Based on the assumption that gut microbial dysbiosis can provoke behavioral or psychological disorders, the present study evaluated anxiety-linked behavioral changes in a mouse model of streptomycin-induced dysbiosis. Measuring anxiety-like behavior using the light–dark box and elevated plus maze tests indicated that streptomycin treatment caused acute anxiety in mice. As an intervention for dysbiosis-associated distress, the probiotic strain Escherichia coli Nissle 1917 (EcN) was evaluated for its effects on streptomycin-induced behavioral changes in mice. EcN supplementation persistently ameliorated anxiety responses in mice with streptomycin-induced dysbiosis. As an outcome of anxiety, body weight changes were marginally affected by antibiotic treatment. However, mice supplemented with EcN displayed acute retardation of body weight gain, since EcN is known to reduce food intake and increase energy expenditure. Taken together, EcN treatment prominently counteracted streptomycin-induced anxiety in mice, with the metabolically beneficial retardation of body weight gain. The present model simulates psychological disorders in antibiotic users. As a promising intervention, EcN treatment can facilitate psychological relief under conditions of dysbiotic stress by blocking the pathologic gut–brain circuit.

Through Silicon Via (TSV) Package (PKG) technology that forms a 3D stack with chip to chip or wafer to wafer contact, uses a variety of wet chemicals unlike conventional package technology. Therefore, new kinds of defects related to the wet chemical occur. In this a new failure mode of disappeared Al pad will be presented, a problem came up to disappear Al pad, which served as the fiducial key during the metal residue removal process after forming the TSV PKG front bump, the mechanism of disappearance of Al pad was investigated. Through chemical analysis of process and equipment, we found that Cu etchant (including H3PO4) can damage for Al pad. The process simulation demonstrated that Al pad actually disappeared. Therefore, it confirmed that it needs to be removed through sufficient rinsing time after applying the wet chemical applied to the TSV PKG process. As a result we solved problem through modified equipment and increased rinsing time.

Sediment erosion is the wear phenomenon from the hard abrasive particle found in the rivers. Sediment erosion is an inevitable process in the hydropower. It deteriorates the turbine shape and structure and increasing the maintenance expenses. There are various methods to improve the runner to operate against the sediment erosion. Firstly, the turbine material can be modified to the harder material but it will be costly and difficult for the manufacturing. Secondly, regular maintenance of the turbine needs to be done but it is the tedious task and hinder the power generation from the hydropower. Thirdly, the critical area of the runner blade surface which is vulnerable to sediment erosion need to identify and modification of the turbine shape according to it by altering the design parameter of the blade. The modification such as a change in thickness, blade angle and coating is possible for minimizing the effect of sediment erosion. The determination of the vulnerable area in the runner for the sediment erosion is a difficult task considering the many parameters included in sediment erosion phenomenon. The parameter such as sediment size, sediment shape, sediment concentration, sediment velocity, sediment hardness, impact angle and operating condition of hydropower. The precise prediction of the sediment erosion in the turbine is the difficult task due to the synergetic effect of parameters. The accurate and precise indication of the sediment erosion required both experimental and computational analysis. After identification of the susceptible area of sediment erosion, modification and optimization will be performed to reduce the effect of the sediment erosion without falling in the performance of the turbine.

Through research and review of a blackout case, This study offers basis for choosing the time and range of Response about energy emergency. Focusing the blackout, this study is listed case that is overall of world black out, Total 18 cases. After that, it has stated that damage duration more than 1 hour is Long Term, damage duration less than 1 hour is Short Term thorough review of a blackout case. According to standard, this study analyzes main causes of blackout and damage by blackout.

Background Oral lichen planus (OLP) is a chronic inflammatory disease characterized by cell-mediated immune responses, but the exact cause is unknown. Sulfasalazine has shown efficacy in the treatment of cutaneous lichen planus. Objective Our purpose was to assess the usefulness of sulfasalazine in treatment of OLP resistant to corticosteroid therapy. This study provides a new option for controlling OLP symptoms. Methods Two patients with the symptomatic reticular form of OLP were treated with 30 mg/5 ml of topical sulfasalazine for 8 to 15 weeks and were evaluated for symptom severity using a numerical analog scale during each week of treatment. The lesion size was measured using a 2 mm² grid. Results After 2 weeks of application, both patients reported improvements in their symptoms and lesions. Most of the lesions disappeared after 8 weeks of treatment without any side effects. Conclusion Topical sulfasalazine can be a successful treatment option for patients with oral lichen planus resistant to steroid therapy.

The purpose of this study was to evaluate the usefulness of topical sulfasalazine in the treatment of oral lichen planus (OLP) resistant to corticosteroid therapy.Twenty-one unresponsive OLP patients were treated with topical sulfasalazine 3 times a day for 4 weeks. Each patient's symptoms and lesion size were evaluated at the beginning of therapy, and then after 4 weeks to determine the efficacy of topical sulfasalazine. Inflammatory cytokines levels in saliva were measured by ELISA.Seventeen patients (81%) reported improvement of discomfort and 12 patients (57%) had lesions decrease in size over 50%. Patients who had higher levels of IL-1β and IL-8 were more responsive to topical sulfasalazine therapy.Topical sulfasalazine should be considered when OLP does not respond to corticosteroid therapy. Furthermore, high concentrations of IL-1β and IL-8 in the saliva are useful indicators for the application of topical sulfasalazine in OLP patients refractory to steroid treatment.

Context: The oncogenic RET/PTC tyrosine kinase causes papillary thyroid cancer (PTC). The use of inhibitors specific for RET/PTC may be useful for targeted therapy of PTC. Objective: The objective of the study was to evaluate the efficacies of the recently developed kinase inhibitors SU11248, SU5416, and SU6668 in inhibition of RET/PTC. Design: SU11248, SU5416, and SU6668 were synthesized, and their inhibitory potencies were evaluated using an in vitro RET/PTC kinase assay. The inhibitory effects of the compounds on RET/PTC were evaluated by quantifying the autophosphorylation of RET/PTC, signal transducer and activator of transcription (STAT)-3 activation, and the morphological reversal of RET/PTC-transformed cells. Results: An in vitro kinase assay revealed that SU5416, SU6668, and SU11248 inhibited phosphorylation of the synthetic tyrosine kinase substrate peptide E4Y by RET/PTC3 in a dose-dependent manner with IC50 of approximately 944 nm for SU5416, 562 nm for SU6668, and 224 nm for SU11248. Thus, SU11248 effectively inhibits the kinase activity of RET/PTC3. RET/PTC-mediated Y705 phosphorylation of STAT3 was inhibited by addition of SU11248, and the inhibitory effects of SU11248 on the tyrosine phosphorylation and transcriptional activation of STAT3 were very closely correlated with decreased autophosphorylation of RET/PTC. SU11248 caused a complete morphological reversion of transformed NIH-RET/PTC3 cells and inhibited the growth of TPC-1 cells that have an endogenous RET/PTC1. Conclusion: SU11248 is a highly effective tyrosine kinase inhibitor of the RET/PTC oncogenic kinase.

Papillary thyroid carcinoma (PTC) is a heterogenous disorder characterized by unique gene rearrangements and gene mutations that activate signaling pathways responsible for cellular transformation, survival, and antiapoptosis. Activation of protein kinase B (PKB) and its downstream signaling pathways appears to be an important event in thyroid tumorigenesis. In this study, we found that the thyroid-specific oncogenic RET/PTC tyrosine kinase is able to phosphorylate PKB in vitro and in vivo. RET/PTC-transfected cells showed tyrosine phosphorylation of endogenous and exogenous PKB, which was independent of phosphorylation of T308 and S473 regulated by the upstream kinases phosphoinositide-dependent kinase-1 and -2, respectively. The PKB Y315 residue, which is known to be phosphorylated by Src tyrosine kinase, was also a major site of phosphorylation by RET/PTC. RET/PTC-mediated tyrosine phosphorylation results in the activation of PKB kinase activity. The activation of PKB by RET/PTC blocked the activity of the forkhead transcription factor, FKHRL1, but a Y315F mutant of PKB failed to inhibit FKHRL1 activity. In summary, these observations suggest that RET/PTC is able to phosphorylate the Y315 residue of PKB, an event that results in maximal activation of PKB for RET/PTC-induced thyroid tumorigenesis.

We have isolated a basic helix-loop-helix (bHLH) gene homologous to the Drosophila proneural gene atonal, termed zath3, from zebrafish. zath3 is expressed in neurons of the central nervous system and in subsets of cranial ganglia. Zebrafish mindbomb (mib) mutants have a higher density of zath3 expressing cells and narrowminded (nrd) mutants lack zath3 expression in a domain corresponding to primary sensory neurons showing that the expression of zath3 is regulated by both mib and nrd. Injection of synthetic zath3 RNA into zebrafish embryos expands the neural plate size, promotes ectopic expression of neuronal markers, and partially rescues the deficit of sensory neurons seen in nrd mutants. Interfering with zath3 function using antisense morpholino oligonucleotides (MO) has no significant effect on early neurogenesis. However, a double knock down of zath3 and neurogenin1 (ngn1), another atonal homologue, with morpholinos (MOs) leads to more severe defects in neurogenesis than are seen with ngn1 MO alone: a subtle reduction of motor and inter-neurons, and an almost complete loss all cranial ganglia. This study suggests that zath3 and ngn1 have partially overlapping roles in early neurogenesis.

The pump sump, which connects forebay and intake of pump station, supplies good flow condition for the intake of the pump. If suction sumps are improperly shaped or sized, air entraining vortices or submerged vortices may develop. This may greatly affect pump operation if vortices grow to an appreciable extent. Moreover, the noise and vibration of the pump can be increased by the remaining of vortices in the pump flow passage. Therefore, the vortices in the pump flow passage have to be reduced for a good performance of pump sump station. In this study, the effect of suction pipe leaning angle on the pump sump internal flow with different water level has been investigated by CFD analysis. Moreover, an elbow type pipe was also investigated. There are 3 leaning angles with 0°, 45° and 90° for the suction pipe. The suction pipe inlet centre is kept same for all the cases. In addition, the three different water levels of H/D=1.85, 1.54, and 1.31, is applied to different suction pipe types. The result shows that the amount of air sucked into the suction pipe increases with increasing the suction pipe leaning angle. Especially for the horizontal suction pipe, there is maximum air sucked into the suction pipe. However, there is certain effect of the elbow type bell mouth installation in the horizontal suction pipe on suppressing the amount of air sucked into the pipe. Moreover, vertical suction pipe plays an effective role on reducing the free surface vortex intake area.

CR6-interacting factor 1 (CRIF1) was recently identified as a nuclear protein that interacts with the Gadd45 (growth arrest and DNA damage inducible 45) family of proteins and participates in the regulation of the G1/S phase of the cell cycle. However, the nuclear action of CRIF1 is largely unknown. In this study, we demonstrate that CRIF1 acts as a novel coregulator of transactivation of the orphan nuclear receptor Nur77. Both in vitro and in vivo studies show that CRIF1 interacts with Nur77 via the Nur77 AB domain and that it dramatically inhibits the AB domain-mediated transactivation of Nur77. Transient transfection assays demonstrate that CRIF1 inhibits steroid receptor coactivator-2-mediated Nur77 transactivation, and silencing of endogenous CRIF1 by small interfering RNA relieves this repression. CRIF1 possesses intrinsic repressor activities that are not affected by the histone deacetylase inhibitor Trichostatin A. In addition, overexpression of CRIF1 inhibits TSH/protein kinase A-induced Nur-responsive element promoter activity. CRIF1 inhibited Nur77-dependent induction of E2F1 promoter activity, mRNA expression, and Nur77-mediated G1/S progression in cell cycle. These results suggest that CRIF1 acts as a repressor of the orphan nuclear receptor Nur77 by inhibiting AB domain-mediated transcriptional activity.

Chimeric RET/PTC (rearranged in transformation/papillary thyroid carcinoma) oncoproteins are constitutively active tyrosine kinases found in thyroid papillary carcinoma and nonneoplastic Hashimoto’s thyroiditis. Although several proteins have been identified to be substrates of RET/PTC kinases, the pathogenic roles played by RET/PTC in malignant and benign thyroid diseases and the molecular mechanisms that are involved are not fully understood. We found that RET/PTC expression phosphorylates the Y701 residue of STAT1, a type II interferon (IFN)-responsive protein. RET/PTC-mediated signal transducer and activator of transcription 1 (STAT1) phosphorylation requires RET/PTC kinase activity to be intact but other tyrosine kinases, such as Janus kinases or c-Src, are not involved. RET/PTC-induced STAT1 transcriptional activation was not inhibited by suppressor of cytokine signaling-1 or -3, or protein inhibitors of activated STAT3 [(protein inhibitor of activated STAT (PIAS3)], but PIAS1 strongly repressed the RET/PTC-induced transcriptional activity of STAT1. RET/PTC-induced STAT1 activation caused IFN regulatory factor-1 expression. We found that STAT1 and IFN regulatory factor-1 cooperated to significantly increase transcription from type IV IFN-γresponsive promoters of class II transactivator genes. Significantly, cells stably expressing RET/PTC expressed class II transactivator and showed enhanced de novo membrane expression of major histocompatibility complex (MHC) class II proteins. Furthermore, RET/PTC1-bearing papillary thyroid carcinoma cells strongly expressed MHC class II (human leukocyte-associated antigen-DRα) genes, whereas the surrounding normal tissues did not. Thus, RET/PTC is able to phosphorylate and activate STAT1. This may lead to enhanced MHC class II expression, which may explain why the tissues surrounding RET/PTC-positive cancers are infiltrated with lymphocytes. Such immune response-promoting activity of RET/PTC may also relate to the development of Hashimoto’s thyroiditis.

Background: This study examined the cardiovascular responses to double-lumen endobronchial intubation during rapid sequence induction of anesthesia, and compared the effect of remifentanil and alfentanil in a randomized, double-blind, placebo-controlled study in three groups of 20 elderly patients each. Methods: Anesthesia was induced with intravenous thiopental (4－6 mg/kg) immediately followed by either remifentanil 2 μg/kg, alfentanil 30μg/kg, or saline (placebo) given over 30 sec. Succinylcholine 1 .5 mg/kg was given for neuromuscular block. The laryngoscopy and intubation were performed 60 sec later. Results: The intubation significantly increased systolic arterial pressure (SAP) and heart rate (HR) in all groups. The maximum pressure changes in the remifentanil and alfentanil groups (36 ± 26 and 33 ± 30 mmHg, respectively) were significantly lower than the 83 ± 35 mmHg in the control group. The maximum HR in the remifentanil (77 ± 13 bpm) and alfentanil (80 ± 13 bpm) groups was lower when compared to controls (93 ± 11 bpm). The norepinephrine and epinephrine concentrations increased after intubation in the control group but remained unaltered in both the alfentanil and remifentanil groups. There were no significant differences between the remifentanil and alfentanil groups in HR, SAP or catecholamines at any time. Five patients in the remifentanil group and three in the alfentanil group received ephedrine for hypotension. Conclusions: Endobronchial intubation elicited a significant pressor response, and that both remifentanil and alfentanil similarly attenuated the pressor response. However, the incidence of hypotension confirms that both drugs should be used with caution in elderly patients. (Korean J Anesthesiol 2007; 52: S 14～20)