Breakdown parameter for kinetic modeling of multiscale gas flows.

Multiscale methods built purely on the kinetic theory of gases provide information about the molecular velocity distribution function. It is therefore both important and feasible to establish new breakdown parameters for assessing the appropriateness of a fluid description at the continuum level by utilizing kinetic information rather than macroscopic flow quantities alone. We propose a new kinetic criterion to indirectly assess the errors introduced by a continuum-level description of the gas flow. The analysis, which includes numerical demonstrations, focuses on the validity of the Navier-Stokes-Fourier equations and corresponding kinetic models and reveals that the new criterion can consistently indicate the validity of continuum-level modeling in both low-speed and high-speed flows at different Knudsen numbers.

Multiscale lattice Boltzmann approach to modeling gas flows.

For multiscale gas flows, the kinetic-continuum hybrid method is usually used to balance the computational accuracy and efficiency. However, the kinetic-continuum coupling is not straightforward since the coupled methods are based on different theoretical frameworks. In particular, it is not easy to recover the nonequilibrium information required by the kinetic method, which is lost by the continuum model at the coupling interface. Therefore, we present a multiscale lattice Boltzmann (LB) method that deploys high-order LB models in highly rarefied flow regions and low-order ones in less rarefied regions. Since this multiscale approach is based on the same theoretical framework, the coupling precess becomes simple. The nonequilibrium information will not be lost at the interface as low-order LB models can also retain this information. The simulation results confirm that the present method can achieve modeling accuracy with reduced computational cost.

Gauss-Hermite quadratures and accuracy of lattice Boltzmann models for nonequilibrium gas flows.

Recently, kinetic theory-based lattice Boltzmann (LB) models have been developed to model nonequilibrium gas flows. Depending on the order of quadratures, a hierarchy of LB models can be constructed which we have previously shown to capture rarefaction effects in the standing-shear wave problems. Here, we further examine the capability of high-order LB models in modeling nonequilibrium flows considering gas and surface interactions and their effect on the bulk flow. The Maxwellian gas and surface interaction model, which has been commonly used in other kinetic methods including the direct simulation Monte Carlo method, is used in the LB simulations. In general, the LB models with high-order Gauss-Hermite quadratures can capture flow characteristics in the Knudsen layer and higher order quadratures give more accurate prediction. However, for the Gauss-Hermite quadratures, the present simulation results show that the LB models with the quadratures obtained from the even-order Hermite polynomials perform significantly better than those from the odd-order polynomials. This may be attributed to the zero-velocity component in the odd-order discrete set, which does not participate in wall and gas collisions, and thus underestimates the wall effect.

Decreased glucagon responsiveness by bile acids: a role for protein kinase Calpha and glucagon receptor phosphorylation.

Dihydroxy bile acids like chenodeoxycholic acid (CDCA) induce heterologous glucagon receptor desensitization. We previously demonstrated that protein kinase C (PKC) was activated by certain bile acids and mediated the CDCA-induced decrease in glucagon responsiveness. The aim of the present study was to explore the role of PKC in the phosphorylation and desensitization of the glucagon receptor by CDCA. Desensitization was evaluated by measuring adenylyl cyclase activity. Receptor phosphorylation was assayed by metabolic labeling with [gamma-(32)P] ATP. Protein kinase C (PKC) translocation and activation was visualized by fluorescence microscopy. CDCA decreased cAMP production induced by glucagon in a dose-dependent manner without affecting cAMP synthesis through stimulation of either stimulatory GTP-binding protein (Gs) by NaF or adenylyl cyclase by forskolin. The CDCA-induced inhibition of adenylyl cyclase activity was potentiated by the phosphatase inhibitor, okadaic acid. The desensitizing effect of CDCA was bile acid-specific and was significantly reduced in the presence of PKC inhibitors and after PKC down-regulation by phorbol 12-myristate 13-acetate. CDCA increased glucagon receptor phosphorylation more than 3-fold at concentrations as low as 25 mum. Furthermore, CDCA significantly stimulated human recombinant PKCalpha autophosphorylation in vitro, as well as PKCalpha translocation to the plasma membrane and phosphorylation in vivo at concentrations as low as 25 mum. CDCA also stimulated PKCdelta translocation to the perinuclear region. Activated PKCalpha, PKCzeta, and to a lesser extent, PKCdelta, phosphorylated the glucagon receptor in vitro. This study demonstrates that certain bile acids, such as CDCA, stimulate phosphorylation and heterologous desensitization of the glucagon receptor, involving at least PKCalpha activation.

Bile acids stimulate PKCalpha autophosphorylation and activation: role in the attenuation of prostaglandin E1-induced cAMP production in human dermal fibroblasts.

The aim was to identify the specific PKC isoform(s) and their mechanism of activation responsible for the modulation of cAMP production by bile acids in human dermal fibroblasts. Stimulation of fibroblasts with 25-100 microM of chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) led to YFP-PKCalpha and YFP-PKCdelta translocation in 30-60 min followed by a transient 24- to 48-h downregulation of the total PKCalpha, PKCdelta, and PKCepsilon protein expression by 30-50%, without affecting that of PKCzeta. Increased plasma membrane translocation of PKCalpha was associated with an increased PKCalpha phosphorylation, whereas increased PKCdelta translocation to the perinuclear domain was associated with an increased accumulation of phospho-PKCdelta Thr505 and Tyr311 in the nucleus. The PKCalpha specificity on the attenuation of cAMP production by CDCA was demonstrated with PKC downregulation or inhibition, as well as PKC isoform dominant-negative mutants. Under these same conditions, neither phosphatidylinositol 3-kinase, p38 MAP kinase, p42/44 MAP kinase, nor PKA inhibitors had any significant effect on the CDCA-induced cAMP production attenuation. CDCA concentrations as low as 10 microM stimulated PKCalpha autophosphorylation in vitro. This bile acid effect required phosphatidylserine and was completely abolished by the presence of Gö6976. CDCA at concentrations less than 50 microM enhanced the PKCalpha activation induced by PMA, whereas greater CDCA concentrations reduced the PMA-induced PKCalpha activation. CDCA alone did not affect PKCalpha activity in vitro. In conclusion, although CDCA and UDCA activate different PKC isoforms, PKCalpha plays a major role in the bile acid-induced inhibition of cAMP synthesis in fibroblasts. This study emphasizes potential consequences of increased systemic bile acid concentrations and cellular bile acid accumulation in extrahepatic tissues during cholestatic liver diseases.

Human prolactin receptor variants in breast cancer: low ratio of short forms to the long-form human prolactin receptor associated with mammary carcinoma.

Prolactin plays an essential role in the development of rodent mammary tumors and is a potent mitogen in human normal and cancerous breast tissues/cells. In this study, we have analyzed the expression of prolactin receptors, including the long receptor form (LF; stimulatory) and two novel short forms (SFs; S1a and S1b) derived from alternative splicing that are inhibitory of the activation induced by prolactin through the LF. Southern analysis of breast cancer profiling arrays revealed that 29 patients (group I) expressed an elevated LF, 10 patients (group II) showed decreased LF, and 8 patients (group III) had no change relative to the adjacent normal tissue. Their respective SF expression was increased in 21 patients of group I and generally decreased in groups II and III. However, the ratio of SF to LF was significantly decreased in 76% of the breast tumors and distributed evenly among the groups. Quantification of differential expression of prolactin receptor variants by real-time PCR in 15 pairs of human normal and tumor breast-matched tissues revealed a similar significant decrease in the ratio of SF to LF in the tumor tissue. Consistent lower ratio of SFs to LFs was confirmed in 8 of ten different breast cancer cell lines compared with normal mammary Hs578Bst and MCF10A cells. Because SFs act as dominant negative regulators of the stimulatory actions of the LF in vitro, their relatively reduced expression in cancer could cause gradations of unopposed prolactin-mediated LF stimulatory function and contribute to breast tumor development/progression.

Complex 5' genomic structure of the human prolactin receptor: multiple alternative exons 1 and promoter utilization.

Transcription of the prolactin receptor (PRLR) is under the control of multiple promoters. Following the recent demonstration of the human non-coding exon 1, hE1(N) (hE1(N1)) and the generic exon 1 hE1(3), we have identified their promoters and characterized four other novel human exons 1 (hE1(N2-5)) that are alternatively spliced to a common non-coding exon 2 in human tissues and breast cancer cells. Genomic regions containing these exons, and 5'-flanking and intronic sequences, were determined and their order was established in chromosome 5p14-13. Promoters utilized in the transcription of previously characterized PRLR exons 1 species hE1(3) (hPII) and hE1(N1) (hP(N1)) were found to employ distinct mechanisms for controlling hPRLR transcription. hPIII requires C/EBP beta and Sp1/Sp3 for basal transcriptional activity, while hP(N1) activity is conferred by domains containing an Ets element and an NR half-site. The complex promoter control system that governs transcription of the hPRLR in multiple tissues is of relevance for studies on the regulation of PRLR expression in physiological and pathological states.

[Investigation of multi-channel collecting and temperature calculating by using minimum error principle for thermal radiation spectra].

A new kind of method of multi-channel acquisition of thermal radiation spectra and temperature calculating was reported in this paper. Employing a tungsten lamp as thermal source, using an optical multi-channel analyzer(OMA) to collect the radiation spectra, the measured temperatures were calculated by using optimum simulation between the measured spectra and Planck black body radiation curves at the determine temperatures according to the minimum errors principle. The results are agreement with standard values, and the errors are near 1%. The advancing of the method is discussed.