610 research outputs found

    Growth rate regulation of lac operon expression in Escherichia coli is cyclic AMP dependent

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    AbstractIn contrast to the ribosomal RNA gene expression increasing with growth rate, transcription of the lac operon is downregulated by cell growth rate. In continuous culture, growth rate regulation of lac promoter was independent of carbon substrate used and its location on the chromosome. Since the lac operon is activated by cyclic adenosine monophosphate (cAMP), which decreases with increasing cell growth rate, expression of plac-lacZ reporter fusion was analyzed in cya mutant under various growth conditions. The results demonstrated that expression of plac-lacZ in cya mutant was both lower and growth rate independent. In addition, ppGpp (guanosine tetraphosphate) was not involved in the mechanism of growth rate regulation of the lac promoter. Thus, the results of this study indicate that cAMP mediates the growth rate-dependent regulation of lac operon expression in Escherichia coli

    Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by insulin.

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    Angiopoietin-like 4 (Angptl4) is a glucocorticoid receptor (GR) primary target gene in hepatocytes and adipocytes. It encodes a secreted protein that inhibits extracellular LPL and promotes adipocyte lipolysis. In Angptl4 null mice, glucocorticoid-induced adipocyte lipolysis and hepatic steatosis are compromised. Markedly, insulin suppressed glucocorticoid-induced Angptl4 transcription. To unravel the mechanism, we utilized small molecules to inhibit insulin signaling components and found that phosphatidylinositol 3-kinase and Akt were vital for the suppression in H4IIE cells. A forkhead box transcription factor response element (FRE) was found near the 15 bp Angptl4 glucocorticoid response element (GRE). Mutating the Angptl4 FRE significantly reduced glucocorticoid-induced reporter gene expression in cells. Moreover, chromatin immunoprecipitation revealed that GR and FoxO1 were recruited to Angptl4 GRE and FRE in a glucocorticoid-dependent manner, and cotreatment with insulin abolished both recruitments. Furthermore, in 24 h fasted mice, significant occupancy of GR and FoxO1 at the Angptl4 GRE and FRE was found in the liver. In contrast, both occupancies were diminished after 24 h refeeding. Finally, overexpression of dominant negative FoxO1 mutant abolished glucocorticoid-induced Angptl4 expression, mimicking the insulin suppression. Overall, we demonstrate that both GR and FoxO1 are required for Angptl4 transcription activation, and that FoxO1 negatively mediates the suppressive effect of insulin

    Design of Dual-Band Microstrip Rat Race Coupler with Circuit Miniaturization

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    Abstract- Rat race ring coupler with stepped-impedance sections is designed to have a dual-band characteristic. This is realized by attaching open stubs to both ends of each stepped-impedance section to create a phase of 900 at two designated frequencies. Transcendental equations are derived for solving impedance ratio R and lengths of the stepped-impedance sections. Circuit with miniaturized area can be obtained ifR> 1 is chosen. Such microstrip ring hybrids operating at 2.45/5.2 GHz with R = 1 and R = 4 are designed and fabricated. Experiments are performed to confirm the theory

    Phase-controlled vibrational laser percussion drilling

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    In this study, a phase-controlled vibration was applied to a laser percussion drilling process to improve the depth of penetration. To investigate the effects of phase-controlled vibration on the depth of penetration, a novel method that controls the phase offset between the accelerating motion and the emission of the laser beam was developed. The method is based on coaxial sensing of the working surface using a photodiode, coupled with microcontroller control of the drilling laser operation. Through real-time optical signal acquisition and analysis of laser machining processes, correlations between the accelerating motion and the emission of the laser beam were simultaneously obtained. All of the processing work was performed in air at standard atmospheric conditions, and gas assist was not used. This study showed that the application of phase-controlled vibration improved the depth of penetration in laser percussion machining and can contribute to the development of precision drilling in the industry

    Propyl Gallate Exerts an Antimigration Effect on Temozolomide-Treated Malignant Glioma Cells through Inhibition of ROS and the NF- κ

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    In this study, we demonstrated that temozolomide (TMZ) and propyl gallate (PG) combination enhanced the inhibition of migration in human U87MG glioma cells. PG inhibited the TMZ-induced reactive oxygen species (ROS) generation. The mitochondrial complex III and NADPH oxidase are two critical sites that can be considered to regulate antimigration in TMZ-treated U87MG cells. PG can enhance the antimigration effect of TMZ through suppression of metalloproteinase-2 and metalloproteinase-9 activities, ROS generation, and the NF-κB pathway and possibly provide a novel prospective strategy for treating malignant glioma

    A Postverification Method for Solving Forced Duffing Oscillator Problems without Prescribed Periods

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    This paper proposes a postverification method (PVM) for solving forced Duffing oscillator problems without prescribed periods. Comprising a postverification procedure and small random perturbation, the proposed PVM improves the sensitivity of the convergence of Newton’s iteration. Numerical simulations revealed that the PVM is more accurate and robust than Kubíček’s approach. We applied the PVM to previous research on bifurcation problems

    Introduction of a strong temperature-sensitive phenotype into enterovirus 71 by altering an amino acid of virus 3D polymerase

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    AbstractIn 1998, an enterovirus 71 (EV71) epidemic in Taiwan resulted in 78 deaths; however, the molecular basis of EV71 pathogenicity remains poorly understood. Comparison of the deduced amino acid sequences in 3D polymerases of EV71clinical isolates showed the T251V or T251I substitution from 1986 and 1998 outbreaks. An EV71 replicon system showed that introducing an I251T mutation did not affect luciferase activities at 35 °C when compared with wild type; however, lower luciferase activities were observed when they were incubated at 39.5 °C. In addition, the I251T mutation in the EV71 infectious clone not only reduced viral replication at 39.5 °C in vitro but also decreased the virulence of the mouse adaptive strain MP4 in neonatal mice in an i.p. infection model. Therefore, these results suggested that the threonine at position 251 results in a temperature sensitivity phenotype of EV71 which may contribute to the attenuation of circulating strains

    Genome-Wide Gene-Environment Interaction Analysis Using Set-Based Association Tests

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    The identification of gene-environment interactions (G × E) may eventually guide health-related choices and medical interventions for complex diseases. More powerful methods must be developed to identify G × E. The “adaptive combination of Bayes factors method” (ADABF) has been proposed as a powerful genome-wide polygenic approach to detect G × E. In this work, we evaluate its performance when serving as a gene-based G × E test. We compare ADABF with six tests including the “Set-Based gene-EnviRonment InterAction test” (SBERIA), “gene-environment set association test” (GESAT), etc. With extensive simulations, SBERIA and ADABF are found to be more powerful than other G × E tests. However, SBERIA suffers from a power loss when 50% SNP main effects are in the same direction with the SNP × E interaction effects while 50% are in the opposite direction. We further applied these seven G × E methods to the Taiwan Biobank data to explore gene× alcohol interactions on blood pressure levels. The ADAMTS7P1 gene at chromosome 15q25.2 was detected to interact with alcohol consumption on diastolic blood pressure (p = 9.5 × 10−7, according to the GESAT test). At this gene, the P-values provided by other six tests all reached the suggestive significance level (p < 5 × 10−5). Regarding the computation time required for a genome-wide G × E analysis, SBERIA is the fastest method, followed by ADABF. Considering the validity, power performance, robustness, and computation time, ADABF is recommended for genome-wide G × E analyses

    Long-term follow-up of patients with surgical intractable acromegaly after linear accelerator radiosurgery

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    Background/PurposeRadiotherapy is a crucial treatment for acromegalic patients with growth hormone (GH)-secreting pituitary tumors. However, its effect takes time. We retrospectively reviewed the long-term outcome of linear accelerator stereotactic radiosurgery (LINAC SRS) for patients with acromegaly from the perspective of biochemical remission and associated factors.MethodsTwenty-two patients presenting with residual or recurrent (GH)-secreting functional pituitary tumor between 1994 and 2004 who received LINAC SRS were enrolled and followed up for at least 3 years. Residual or recurrent tumor was defined as persistent elevated GH or insulin-like growth factor-1 (IGF-1) level and image-confirmed tumor after previous surgical treatment. Biochemical remission was defined as fasting GH less than 2.5 ng/mL with normal sex-and-age adjusted IGF-1.ResultsThe mean follow-up period was 94.7 months (range 36–161 months). Overall mean biochemical remission time was 53 months (median 30 months). Biochemical control was achieved in 15 patients (68.2%) over the follow up period. One patient experienced recurrence after SRS and underwent another operation. Initial GH at diagnosis and pre-SRS GH correlated with biochemical control (p = 0.005 and p < 0.0001, respectively). Further evaluation demonstrated that biochemical control stabilized after 7.5 years. Overall post-SRS hormone deficit persisted in five patients (22.7%).ConclusionIn comparison to other radiosurgery modalities, LINAC radiosurgery also provides a satisfactory outcome. SRS has maximum effect over the first 2 years and stabilizes after 7.5 years. Moreover, SRS elicits long-term biochemical effects and requires longer follow-up for better biochemical remission
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