4,986 research outputs found
The program FANS-3D (finite analytic numerical simulation 3-dimensional) and its applications
In this study, the program named FANS-3D (Finite Analytic Numerical Simulation-3 Dimensional) is presented. FANS-3D was designed to solve problems of incompressible fluid flow and combined modes of heat transfer. It solves problems with conduction and convection modes of heat transfer in laminar flow, with provisions for radiation and turbulent flows. It can solve singular or conjugate modes of heat transfer. It also solves problems in natural convection, using the Boussinesq approximation. FANS-3D was designed to solve heat transfer problems inside one, two and three dimensional geometries that can be represented by orthogonal planes in a Cartesian coordinate system. It can solve internal and external flows using appropriate boundary conditions such as symmetric, periodic and user specified
Interest Rate Rules, Target Policies, and Endogenous Economic Growth in an Open Economy
This paper sets up an endogenous growth model of an open economy in which the monetary authority implements a gradualist interest-rate rule with targets for inflation and economic growth. We show that, under a passive rule, a monetary equilibrium exists and is unique; moreover, the equilibrium is locally determinate. Under an active rule, the open economy either generates multiple equilibria or does not have any equilibrium. If equilibria exist, the high-growth equilibrium is locally determinate while the low-growth equilibrium is a source. Besides these, the stabilization and growth effects of alternative target policies are also explored in this study.Nominal interest rate rules, gradualism, endogenous economic growth
Repression of glucocorticoid-stimulated angiopoietin-like 4 gene transcription by insulin.
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
Fucosyltransferase 1 and 2 play pivotal roles in breast cancer cells.
FUT1 and FUT2 encode alpha 1, 2-fucosyltransferases which catalyze the addition of alpha 1, 2-linked fucose to glycans. Glycan products of FUT1 and FUT2, such as Globo H and Lewis Y, are highly expressed on malignant tissues, including breast cancer. Herein, we investigated the roles of FUT1 and FUT2 in breast cancer. Silencing of FUT1 or FUT2 by shRNAs inhibited cell proliferation in vitro and tumorigenicity in mice. This was associated with diminished properties of cancer stem cell (CSC), including mammosphere formation and CSC marker both in vitro and in xenografts. Silencing of FUT2, but not FUT1, significantly changed the cuboidal morphology to dense clusters of small and round cells with reduced adhesion to polystyrene and extracellular matrix, including laminin, fibronectin and collagen. Silencing of FUT1 or FUT2 suppressed cell migration in wound healing assay, whereas FUT1 and FUT2 overexpression increased cell migration and invasion in vitro and metastasis of breast cancer in vivo. A decrease in mesenchymal like markers such as fibronectin, vimentin, and twist, along with increased epithelial like marker, E-cadherin, was observed upon FUT1/2 knockdown, while the opposite was noted by overexpression of FUT1 or FUT2. As expected, FUT1 or FUT2 knockdown reduced Globo H, whereas FUT1 or FUT2 overexpression showed contrary effects. Exogenous addition of Globo H-ceramide reversed the suppression of cell migration by FUT1 knockdown but not the inhibition of cell adhesion by FUT2 silencing, suggesting that at least part of the effects of FUT1/2 knockdown were mediated by Globo H. Our results imply that FUT1 and FUT2 play important roles in regulating growth, adhesion, migration and CSC properties of breast cancer, and may serve as therapeutic targets for breast cancer
Maintaining the structural integrity of thebamboo mosaic virus 3′ untranslated region isnecessary for retaining the catalytic constant forminus-strand RNA synthesis
Background: Bamboo mosaic virus (BaMV) and the Potato virus X (PVX) are members of the genus Potexvirus andhave a single-stranded positive-sense RNA genome. The 3′-untranslated region (UTR) of the BaMV RNA genomewas mapped structurally into ABC (a cloverleaf-like), D (a stem-loop), and E (pseudoknot) domains. The BaMVreplicase complex that was isolated from the infected plants was able to recognize the 3′ UTR of PVX RNA toinitiate minus-strand RNA synthesis in vitro.Results: To investigate whether the 3′ UTR of PVX RNA is also compatible with BaMV replicase in vivo, weconstructed chimera mutants using a BaMV backbone containing the PVX 3′ UTR, which was inserted in or used toreplace the various domains in the 3′ UTR of BaMV. None of the mutants, except for the mutant with the PVX3′ UTR inserted upstream of the BaMV 3′ UTR, exhibited a detectable accumulation of viral RNA in Nicotianabenthamiana plants. The in vitro BaMV RdRp replication assay demonstrated that the RNA products were generatedby the short RNA transcripts, which were derived from the chimera mutants to various extents. Furthermore, theVmax/KM of the BaMV 3′ UTR (rABCDE) was approximately three fold higher than rABCP, rP, and rDE in minus-strandRNA synthesis. These mutants failed to accumulate viral products in protoplasts and plants, but were adequatelyreplicated in vitro.Conclusions: Among the various studied BaMV/PVX chimera mutants, the BaMV-S/PABCDE that containednon-interrupted BaMV 3′ UTR was the only mutant that exhibited a wild-type level of viral product accumulation inprotoplasts and plants. These results indicate that the continuity of the domains in the 3′ UTR of BaMV RNA wasnot interrupted and the domains were not replaced with the 3′ UTR of PVX RNA in vivo
Angelica Sinensis promotes myotube hypertrophy through the PI3K/Akt/mTOR pathway
BACKGROUND: Angelica Sinensis (AS), a folk medicine, has long been used in ergogenic aids for athletes, but there is little scientific evidence supporting its effects. We investigated whether AS induces hypertrophy in myotubes through the phosphatidylinositol 3-kinase (PI3K)/Akt (also termed PKB)/mammalian target of the rapamycin (mTOR) pathway. METHODS: An in vitro experiment investigating the induction of hypertrophy in myotubes was conducted. To investigate whether AS promoted the hypertrophy of myotubes, an established in vitro model of myotube hypertrophy with and without AS was used and examined using microscopic images. The role of the PI3K/Akt/mTOR signaling pathway in AS-induced myotube hypertrophy was evaluated. Two inhibitors, wortmannin (an inhibitor of PI3K) and rapamycin (an inhibitor of mTOR), were used. RESULT: The results revealed that the myotube diameters in the AS-treated group were significantly larger than those in the untreated control group (P < 0.05). Wortmannin and rapamycin inhibited AS-induced hypertrophy. Furthermore, AS increased Akt and mTOR phosphorylation through the PI3K pathway and induced myotube hypertrophy. CONCLUSION: The results confirmed that AS induces hypertrophy in myotubes through the PI3K/Akt/mTOR pathway
Presentation and Outcomes After Medical and Surgical Treatment Versus Medical Treatment Alone of Spontaneous Infectious Spondylodiscitis: A Systematic Literature Review and Meta-Analysis.
Study Design: Systematic literature review.
Objectives: The aims of this study were to (1) describe the clinical features, disabilities, and incidence of neurologic deficits of pyogenic spondylodiscitis prior to treatment and (2) compare the functional outcomes between patients who underwent medical treatment alone or in combination with surgery for pyogenic spondylodiscitis.
Methods: A systematic literature review was performed using PubMed according to PRISMA guidelines. No year restriction was put in place. Statistical analysis of pooled data, when documented in the original report (ie, number of patients with desired variable and number of patients evaluated), was conducted to determine the most common presenting symptoms, incidence of pre- and postoperative neurologic deficits, associated comorbidities, infectious pathogens, approach for surgery when performed, and duration of hospitalization. Outcomes data, including return to work status, resolution of back pain, and functional recovery were also pooled among all studies and surgery-specific studies alone. Meta-analysis of studies with subgroup analysis of pain-free outcome in surgical and medical patients was performed.
Results: Fifty of 1286 studies were included, comprising 4173 patients undergoing either medical treatment alone or in combination with surgery. Back pain was the most common presenting symptom, reported in 91% of patients. Neurologic deficit was noted in 31% of patients.
Conclusion: Medical management remains first-line treatment of infectious pyogenic spondylodiscitis. Surgery may be indicated for progressive pain, persistent infection on imaging, deformity or neurologic deficits. If surgery is required, reported literature shows potential for significant pain reduction, improved neurologic function and a high number of patients returning to a normal functional/work status
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