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Ginsenosides have poor oral bioavailability and undergo rapid biological transformation in the complex gastrointestinal environment. Most studies on the metabolism of ginsenosides have focused on gut bacteria, yet gastric juice remains a nonnegligible factor. Metabolic profiles of ginsenoside monomers formed in artificial gastric juice were separately investigated and qualitatively identified using ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap MSn). A common pattern of their metabolic pathways was established, showing that ginsenosides were transformed via deglycosylation, hydration, and dehydration pathways. Two major structure types, 20(S), 20(R)-protopanaxatriols and 20(S), 20(R)-protopanaxadiols, basically shared similar transformation pathways and yielded deglycosylated, hydrated, and dehydrated products. Fragmentation patterns of major ginsenosides were also discussed. Consequently, gastric juice, as the primary link in ginsenoside metabolism and as important as the intestinal flora, produces considerable amounts of degraded ginsenosides, providing a partial explanation for the low bioavailabilities of primary ginsenosides.

The synthesis and characterization of the chiral bifunctional NHC ligands based on the imidazo[1,5-a]pyridine (ImPy) scaffold are described. These ligands possess a fluxional biaryl axis and a chiral center. The configurational stability of the biaryl axis in their gold(I) complexes is investigated. The application of these axially chiral ImPy-based AuCl complexes in a series of gold catalysis is explored, and varying degrees of asymmetric induction are observed. In most cases, the ligand (aS,R)-L8-H with its cyclohexyl group pointing to the reaction site and hence exerting asymmetric steric influence is more effective in asymmetric induction.

Using Fourier series representations of functions on axisymmetric domains, we find weighted Sobolev norms of the Fourier coefficients of a function that yield norms equivalent to the standard Sobolev norms of the function. This characterization is universal in the sense that the equivalence constants are independent of the domain. In particular it is uniform whether the domain contains a part of its axis of rotation or is disjoint from, but maybe arbitrarily close to, the axis. Our characterization using step-weighted norms involving the distance to the axis is different from the one obtained earlier in the book [Bernardi, Dauge, Maday "Spectral methods for axisymmetric domains", Gauthier-Villars, 1999], which involves trace conditions and is domain dependent. We also provide a complement for non cylindrical domains of the proof given in loc. cit. .

Guo-Tian Ruan1 ,* Yi-Zhen Gong1 ,* Li-Chen Zhu,2 Feng Gao,1 Xi-Wen Liao,3 Xiang-Kun Wang,3 Guang-Zhi Zhu,3 Cun Liao,1 Shuai Wang,1 Ling Yan,1 Hai-Lun Xie,1 Xin Zhou,3 Jun-Qi Liu,3 Meng-Nan Shao,4 Jia-Liang Gan1 1Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Immunology, School of Preclinical Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 4Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jia-Liang GanDepartment of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaEmail gjl5172@163.comBackground: This study was mainly to explore and study the potential application of lipoxygenases (ALOX) family genes in the diagnostic and prognostic values of colon adenocarcinoma (COAD).Methods: Data sets related to the ALOX genes of COAD were obtained from The Cancer Genome Atlas and the University of California, Santa Cruz Xena browser. Then, the relevant biological information was downloaded from the public data platform. Finally, the bioinformatics technologies and clinical verification were employed to comprehensively analyze the potential values of ALOX genes.Results: The Pearson correlation analysis indicated that there were correlations among ALOXE3, ALOX5, ALOX12, and ALOX12B. The diagnostic receiver operating characteristic (ROC) curves suggested that ALOXE3 and ALOX12 had significant diagnosis in COAD: ALOXE3; P&

International Computer Music Conference Proceedings: vol. 2014, (dlps) bbp2372.2014.092, http://hdl.handle.net/2027/spo.bbp2372.2014.092, This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. Please contact mpub-help@umich.edu to use this work in a way not covered by the license.

International Computer Music Conference Proceedings: vol. 2014, (dlps) bbp2372.2014.092, http://hdl.handle.net/2027/spo.bbp2372.2014.092, This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. Please contact mpub-help@umich.edu to use this work in a way not covered by the license.

As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including 'epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication., National Institute of General Medical Sciences (U.S.) (Ruth L. Kirschstein Postdoctoral Fellowship ), United States. Defense Advanced Research Projects Agency, National Institutes of Health (U.S.) (R24 Grant), Wyss Institute for Biologically Inspired Engineering, Howard Hughes Medical Institute

Autoantibody production is a hallmark of autoimmune diseases, such as lupus and rheumatoid arthritis. Accumulating evidence suggests a role of invariant NKT (iNKT) cells in their pathogenesis. Mechanisms underlying the role of iNKT cells in these diseases, however, remain unclear. In this study, we show that iNKT cells suppress IgG anti-DNA Ab and rheumatoid factor production and reduce IL-10-secreting B cells in a contact-dependent manner, but increase total IgG production and enhance activation markers on B cells via soluble factors. In vivo reconstitution with iNKT cells also reduces autoantibody production in iNKT-deficient mice and in SCID mice implanted with B cells. Using an anti-DNA transgenic model, we found that autoreactive B cells spontaneously produce IL-10 and are activated in vivo. In the presence of activated iNKT cells, these autoreactive B cells are selectively reduced, whereas nonautoreactive B cells are markedly activated. Because iNKTs recognize CD1d, we reasoned that CD1d might play a role in the differential regulation of autoreactive versus nonautoreactive B cells by iNKT cells. Indeed, autoreactive B cells express more CD1d than nonautoreactive B cells, and CD1d deficiency in lupus mice exacerbates autoantibody production and enhances Ab response to a self-peptide but not to a foreign peptide. Importantly, iNKT cells fail to inhibit autoantibody production by CD1d-deficient B cells. Thus, iNKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner but activate nonautoreactive B cells via cytokines. Such ability of iNKTs to suppress autoantibody production, without causing global suppression of B cells, has important implications for the development of iNKT-based therapy for autoimmune diseases.

Autoantibody production is a hallmark of autoimmune diseases, such as lupus and rheumatoid arthritis. Accumulating evidence suggests a role of invariant NKT (iNKT) cells in their pathogenesis. Mechanisms underlying the role of iNKT cells in these diseases, however, remain unclear. In this study, we show that iNKT cells suppress IgG anti-DNA Ab and rheumatoid factor production and reduce IL-10-secreting B cells in a contact-dependent manner, but increase total IgG production and enhance activation markers on B cells via soluble factors. In vivo reconstitution with iNKT cells also reduces autoantibody production in iNKT-deficient mice and in SCID mice implanted with B cells. Using an anti-DNA transgenic model, we found that autoreactive B cells spontaneously produce IL-10 and are activated in vivo. In the presence of activated iNKT cells, these autoreactive B cells are selectively reduced, whereas nonautoreactive B cells are markedly activated. Because iNKTs recognize CD1d, we reasoned that CD1d might play a role in the differential regulation of autoreactive versus nonautoreactive B cells by iNKT cells. Indeed, autoreactive B cells express more CD1d than nonautoreactive B cells, and CD1d deficiency in lupus mice exacerbates autoantibody production and enhances Ab response to a self-peptide but not to a foreign peptide. Importantly, iNKT cells fail to inhibit autoantibody production by CD1d-deficient B cells. Thus, iNKT cells inhibit autoreactive B cells in a contact- and CD1d-dependent manner but activate nonautoreactive B cells via cytokines. Such ability of iNKTs to suppress autoantibody production, without causing global suppression of B cells, has important implications for the development of iNKT-based therapy for autoimmune diseases.

In this paper, we study how to construct f(R) gravity models. Cosmological observations and local gravity tests imply that a viable f(R) model should be very close to the LCDM model. We create procedures to construct viable LCDM-like f(R) models, and present multiple models of three types. The connections between some of these models are discussed. We also study the cosmological evolution of the LCDM-like f(R) gravity. Exact numerical integration can generate accurate cosmological evolution, but the numerical simulation in the early-universe stage is slow due to the oscillations of the field phi(= f') near the minimum of the effective potential. To avoid this problem, we take the minimum of the effective potential as an approximate solution for phi, and obtain the cosmological evolution. This approximate method describes the cosmological evolution well except in the late universe. Therefore, we use the approximate method in the early-universe evolution, and use the exact method in the late-universe one., Comment: 11 pages, 17 figures

In this paper, we revisit the solar system tests of f(R) gravity. When the Sun sits in a vacuum, the field f' is light, which leads to a metric different from the observations. We reobtain this result in a simpler way by directly focusing on the equations of motion for f(R) gravity in the Jordan frame. The discrepancy between the metric in the f(R) gravity and the observations can be alleviated by the chameleon mechanism. The implications from the chameleon mechanism on the functional form f(R) are discussed. Considering the analogy of the solar system tests to the false vacuum decay problem, the effective potentials in different cases are also explored. The combination of analytic and numerical approaches enables us to ascertain whether an f(R) model can pass the solar system tests or not., Comment: 12 pages, 6 figures. minor change

In this paper, we study the cosmological viability conditions, the phase-space dynamics, and the cosmological evolution of f(R) gravity. In contrast to most previous works in the literature, which analyzed the background dynamics of f(R) gravity by means of a dynamical system, we proceed by focusing on the equivalent scalar field description of the theory, which we believe is a more intuitive way of treating the problem. In order to study how the physical solutions evolve in f(R) cosmology, we explore the cosmological dynamics of a range of f(R) models, including models that yield a large hierarchy of scales and are singularity free. We present generic features of the phase-space dynamics in f(R) cosmology. We study the global structure of the phase space in f(R) gravity by compactifying the infinite phase space into a finite space via the Poincare transformation. On the expansion branch of the phase space, the constraint surface has a repeller and a de Sitter attractor; while on the contraction branch, the constraint surface has an attractor and a de Sitter repeller. Generally, the phase currents originate from the repeller and terminate at the corresponding attractor in each space. The trajectories between the repeller and the attractor in the presence of matter density are different from those in the vacuum case. The phase analysis techniques developed in this paper are very general, and can be applied to other similar dynamical systems., Comment: 17 pages, 8 figures. minor change

In this paper, we study how to construct f(R) gravity models. Cosmological observations and local gravity tests imply that a viable f(R) model should be very close to the LCDM model. We create procedures to construct viable LCDM-like f(R) models, and present multiple models of three types. The connections between some of these models are discussed. We also study the cosmological evolution of the LCDM-like f(R) gravity. Exact numerical integration can generate accurate cosmological evolution, but the numerical simulation in the early-universe stage is slow due to the oscillations of the field phi(= f') near the minimum of the effective potential. To avoid this problem, we take the minimum of the effective potential as an approximate solution for phi, and obtain the cosmological evolution. This approximate method describes the cosmological evolution well except in the late universe. Therefore, we use the approximate method in the early-universe evolution, and use the exact method in the late-universe one., Comment: 11 pages, 17 figures

In this paper, we study the cosmological viability conditions, the phase-space dynamics, and the cosmological evolution of f(R) gravity. In contrast to most previous works in the literature, which analyzed the background dynamics of f(R) gravity by means of a dynamical system, we proceed by focusing on the equivalent scalar field description of the theory, which we believe is a more intuitive way of treating the problem. In order to study how the physical solutions evolve in f(R) cosmology, we explore the cosmological dynamics of a range of f(R) models, including models that yield a large hierarchy of scales and are singularity free. We present generic features of the phase-space dynamics in f(R) cosmology. We study the global structure of the phase space in f(R) gravity by compactifying the infinite phase space into a finite space via the Poincare transformation. On the expansion branch of the phase space, the constraint surface has a repeller and a de Sitter attractor; while on the contraction branch, the constraint surface has an attractor and a de Sitter repeller. Generally, the phase currents originate from the repeller and terminate at the corresponding attractor in each space. The trajectories between the repeller and the attractor in the presence of matter density are different from those in the vacuum case. The phase analysis techniques developed in this paper are very general, and can be applied to other similar dynamical systems., Comment: 17 pages, 8 figures. minor change

In this paper, we revisit the solar system tests of f(R) gravity. When the Sun sits in a vacuum, the field f' is light, which leads to a metric different from the observations. We reobtain this result in a simpler way by directly focusing on the equations of motion for f(R) gravity in the Jordan frame. The discrepancy between the metric in the f(R) gravity and the observations can be alleviated by the chameleon mechanism. The implications from the chameleon mechanism on the functional form f(R) are discussed. Considering the analogy of the solar system tests to the false vacuum decay problem, the effective potentials in different cases are also explored. The combination of analytic and numerical approaches enables us to ascertain whether an f(R) model can pass the solar system tests or not., Comment: 12 pages, 6 figures. minor change

Marginal zone B cells (MZB) mount a rapid antibody response, potently activate naïve T cells, and are enriched in autoreactive B cells. MZBs express high levels of CD1d, the restriction element for invariant natural killer T cells (iNKT). Here, we examined the effect of iNKT cells on MZB cell activation and numbers in vitro and in vivo in normal and autoimmune mice. Results show that iNKT cells activate MZBs, but restrict their numbers in vitro and in vivo in normal BALB/c and C57/BL6 mice. iNKT cells do so by increasing the activation-induced cell death and curtailing proliferation of MZB cells, whereas they promote the proliferation of follicular B cells. Sorted iNKT cells can directly execute this function, without help from other immune cells. Such MZB regulation by iNKTs is mediated, at least in part, via CD1d on B cells in a contact-dependent manner, whereas iNKT-induced proliferation of follicular B cells occurs in a contact- and CD1d-independent manner. Finally, we show that iNKT cells reduce 'autoreactive' MZB cells in an anti-DNA transgenic model, and limit MZB cell numbers in autoimmune-prone (NZB×NZW)F1 and non-obese diabetic mice, suggesting a potentially new mechanism whereby iNKT cells might regulate pathologic autoimmunity. Differential regulation of follicular B cells versus potentially autoreactive MZBs by iNKT cells has important implications for autoimmune diseases as well as for conditions that require a rapid innate B cell response.

In this paper, we explore an idea of having Newton's constant change its value depending on the curvature scale involved. Such modification leads to a particular scalar-tensor gravity theory, with the Lagrangian derived from renormalization group (RG) flow arguments. Several of the well-known f(R) modified gravity models have remarkably simple description in terms of the infrared renormalization group, but not the "designer" types in general. We find that de Sitter-like accelerated expansion can be generated even in the absence of cosmological constant term, entirely due to running of the Newton's constant. In hopes of tackling the problem of cosmological constant's smallness, we explore the flows which are capable of generating exponential hierarchy between infrared and ultraviolet scales, and investigate cosmological evolution in the models thus derived., Comment: 8 pages, 6 figures; version 2 is substantially expanded

Marginal zone B cells (MZB) mount a rapid antibody response, potently activate naïve T cells, and are enriched in autoreactive B cells. MZBs express high levels of CD1d, the restriction element for invariant natural killer T cells (iNKT). Here, we examined the effect of iNKT cells on MZB cell activation and numbers in vitro and in vivo in normal and autoimmune mice. Results show that iNKT cells activate MZBs, but restrict their numbers in vitro and in vivo in normal BALB/c and C57/BL6 mice. iNKT cells do so by increasing the activation-induced cell death and curtailing proliferation of MZB cells, whereas they promote the proliferation of follicular B cells. Sorted iNKT cells can directly execute this function, without help from other immune cells. Such MZB regulation by iNKTs is mediated, at least in part, via CD1d on B cells in a contact-dependent manner, whereas iNKT-induced proliferation of follicular B cells occurs in a contact- and CD1d-independent manner. Finally, we show that iNKT cells reduce 'autoreactive' MZB cells in an anti-DNA transgenic model, and limit MZB cell numbers in autoimmune-prone (NZB×NZW)F1 and non-obese diabetic mice, suggesting a potentially new mechanism whereby iNKT cells might regulate pathologic autoimmunity. Differential regulation of follicular B cells versus potentially autoreactive MZBs by iNKT cells has important implications for autoimmune diseases as well as for conditions that require a rapid innate B cell response.

In this paper, we explore an idea of having Newton's constant change its value depending on the curvature scale involved. Such modification leads to a particular scalar-tensor gravity theory, with the Lagrangian derived from renormalization group (RG) flow arguments. Several of the well-known f(R) modified gravity models have remarkably simple description in terms of the infrared renormalization group, but not the "designer" types in general. We find that de Sitter-like accelerated expansion can be generated even in the absence of cosmological constant term, entirely due to running of the Newton's constant. In hopes of tackling the problem of cosmological constant's smallness, we explore the flows which are capable of generating exponential hierarchy between infrared and ultraviolet scales, and investigate cosmological evolution in the models thus derived., Comment: 8 pages, 6 figures; version 2 is substantially expanded

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) beta. RELM-beta is essential for normal spontaneous expulsion and IL-4-induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-beta is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-beta-driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.

Th2 cells drive protective immunity against most parasitic helminths, but few mechanisms have been demonstrated that facilitate pathogen clearance. We show that IL-4 and IL-13 protect against intestinal lumen-dwelling worms primarily by inducing intestinal epithelial cells (IECs) to differentiate into goblet cells that secrete resistin-like molecule (RELM) beta. RELM-beta is essential for normal spontaneous expulsion and IL-4-induced expulsion of Nippostrongylus brasiliensis and Heligmosomoides polygyrus, which both live in the intestinal lumen, but it does not contribute to immunity against Trichinella spiralis, which lives within IEC. RELM-beta is nontoxic for H. polygyrus in vitro but directly inhibits the ability of worms to feed on host tissues during infection. This decreases H. polygyrus adenosine triphosphate content and fecundity. Importantly, RELM-beta-driven immunity does not require T or B cells, alternative macrophage activation, or increased gut permeability. Thus, we demonstrate a novel mechanism for host protection at the mucosal interface that explains how stimulation of epithelial cells by IL-4 and IL-13 contributes to protection against parasitic helminthes that dwell in the intestinal lumen.

The Larmor formula for scalar and gravitational radiation from a pointlike particle is derived in any even higher-dimensional flat spacetime. General expressions for the field in the wave zone and the energy flux are obtained in closed form. The explicit results in four and six dimensions are used to illustrate the effect of extra dimensions on linear and uniform circular motion. Prospects for detection of bulk gravitational radiation are briefly discussed., Comment: 5 pages, no figures

This paper described the theoretical basis of extreme value orientation in detail, which is used to examine the dimension of hole and axle with double point one coordinate measure instrument, and it's quality and feature and calculation method of survey error on dimension, which is caused by turn back point error, The paper also provides a practical chart, which is used to revise at the same time also introduced the study method which is designed by the author., Presented at Display Technologies III, International Optoelectronics Symposium, Taipei, Taiwan, 26-27 Jul 2000. Pub. in Proceedings of SPIE, v4079 p247-250, 2000. ISSN 0277-786X. This article is from ADA398270 Display Technologies III Held in Taipei, Taiwan on 26-27 July 2000

At present, the way to test plane level of terrace are all indirect survey methods at first, author choose some survey sections and get dates from these sections according to stipulation with survey method and then proceeding the dates, through which can strive the plane level error. The plane level dates calculated with these dates can't make an overall plane level assessment to the terrace, especially to the partial position so, it can't be describe in detail on all terrace because of not been survived usually. Author all the error and plane level in the partial range the partial plane level, its assessment is very important to control the microcosmic quality. The paper also discuss the theory issue on speckle method and plane fluctuate capacity method with exist for a long term., Presented at Display Technologies III, International Optoelectronics Symposium, Taipei, Taiwan, 26-27 Jul 2000. Pub. in Proceedings of SPIE, v4079 p251-254, 2000. ISSN 0277-786X. This article is from ADA398270 Display Technologies III Held in Taipei, Taiwan on 26-27 July 2000

The Li+ extraction properties of a lithium ionic sieve, spinel LiMn2O4, using hydrochloric acid, ammonium persulphate or sodium persulphate as eluants and the Li+ adsorption performance of the Li+ extracted samples immersed in Li+ containing aqueous solutions were studied using chemical analysis (atomic absorption spectroscopy), X-ray powder diffraction, Fourier-transform infrared spectroscopy and thermogravimetry/differential thermal analysis. The results indicated that, when hydrochloric acid was used as the eluant, the lithium could not be completely extracted and the manganese dissolved loss reached 12.94%, whereas the use of the persulphates as eluants gave a high extraction of lithium with little manganese loss (0.01%). Two different mechanisms for the Li+ extraction process - manganese loss or without manganese loss - are proposed and these showed that Li+ elution from the ionic-sieve precursor was incomplete., The Li+ extraction properties of a lithium ionic sieve, spinel LiMn2O4, using hydrochloric acid, ammonium persulphate or sodium persulphate as eluants and the Li+ adsorption performance of the Li+ extracted samples immersed in Li+ containing aqueous solutions were studied using chemical analysis (atomic absorption spectroscopy), X-ray powder diffraction, Fourier-transform infrared spectroscopy and thermogravimetry/differential thermal analysis. The results indicated that, when hydrochloric acid was used as the eluant, the lithium could not be completely extracted and the manganese dissolved loss reached 12.94%, whereas the use of the persulphates as eluants gave a high extraction of lithium with little manganese loss (0.01%). Two different mechanisms for the Li+ extraction process - manganese loss or without manganese loss - are proposed and these showed that Li+ elution from the ionic-sieve precursor was incomplete.