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  • American Institute of Physics (AIP)  (3)
  • The American Association of Immunologists (AAI)  (3)
  • The American Society for Pharmacology and Experimental Therapeutics (ASPET)  (3)
  • 1
    Electronic Resource
    Electronic Resource
    Charge and spin transfer and optical properties in conducting porphyrin compounds (1991)
    College Park, Md. : American Institute of Physics (AIP)
    The Journal of Chemical Physics 95 (1991), S. 403-417 
    Details
    ISSN: 1089-7690
    Source: AIP Digital Archive
    Topics: Physics , Chemistry and Pharmacology
    Notes: Anisotropic materials made from stacked macrocycles have potential applications as organic conductors and nonlinear optical materials. Using self-consistent-field local density theory, we have been exploring the ground and excited state electronic structures of metal substituted tetraazaporphyrins, phthalocyanines, and tetrabenzoporphyrins. The calculated and measured polarized optical absorption peaks are in satisfactory agreement. The theoretical dipole oscillator strengths provide absolute intensities for verification of transition assignments, which are helpful for identifying low-lying states and excitation mechanisms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.461442
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Magnetic entropy change in La0.54Ca0.32MnO3−δ (2001)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 90 (2001), S. 524-526 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: A La-deficient manganite perovskite sample La0.54Ca0.32MnO3−δ was prepared by conventional solid-state reaction method. The Curie temperature TC is 272 K, about 10 K higher than that of La1−xCaxMnO3. A large magnetic entropy change has been observed and the maximum −ΔSM(approximate)2.9 J/kg K appears at its Curie temperature upon a 0.9 T magnetic field change. The easy fabrication and higher chemical stability make La0.54Ca0.32MnO3−δ a suitable candidate as a working substance in magnetic refrigeration technology. © 2001 American Institute of Physics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.1379047
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  • 3
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    T Cell Antigen Discovery Using Soluble Vaccinia Proteome Reveals Recognition of Antigens with Both Virion and Nonvirion Association [IMMUNOTHERAPY AND VACCINES] (2014)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2014-08-02
    Description: Vaccinia virus (VACV) is a useful model system for understanding the immune response to a complex pathogen. Proteome-wide Ab profiling studies reveal the humoral response to be strongly biased toward virion-associated Ags, and several membrane proteins induce Ab-mediated protection against VACV challenge in mice. Some studies have indicated that the CD4 response is also skewed toward proteins with virion association, whereas the CD8 response is more biased toward proteins with early expression. In this study, we have leveraged a VACV strain Western Reserve (VACV-WR) plasmid expression library, produced previously for proteome microarrays for Ab profiling, to make a solubilized full VACV-WR proteome for T cell Ag profiling. Splenocytes from VACV-WR–infected mice were assayed without prior expansion against the soluble proteome in assays for Th1 and Th2 signature cytokines. The response to infection was polarized toward a Th1 response, with the distribution of reactive T cell Ags comprising both early and late VACV proteins. Interestingly, the proportions of different functional subsets were similar to that present in the whole proteome. In contrast, the targets of Abs from the same mice were enriched for membrane and other virion components, as described previously. We conclude that a "nonbiasing" approach to T cell Ag discovery reveals a T cell Ag profile in VACV that is broader and less skewed to virion association than the Ab profile. The T cell Ag mapping method developed in the present study should be applicable to other organisms where expressible "ORFeome" libraries are also available, and it is readily scalable for larger pathogens.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
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  • 4
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    Multiple Tumor-Associated MicroRNAs Modulate the Survival and Longevity of Dendritic Cells by Targeting YWHAZ and Bcl2 Signaling Pathways [TUMOR IMMUNOLOGY] (2013)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2013-02-16
    Description: Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways. Specifically, miR-22 targeted YWHAZ to interrupt the PI3K/Akt and MAPK signaling pathways, and miR-503 downregulated Bcl2 expression. The result of the increased expression of miR-22 and miR-503 in the tumor-associated DCs was their reduced survival and longevity. Thus, tumor-associated miRNAs can target multiple intracellular signaling molecules to cause the apoptosis of DCs in the tumor environment. Use of miR-22 and miR-503 as inhibitors may therefore represent a new strategy to improve DC-based immunotherapies against tumors.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
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  • 5
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    Interaction of 2,4-Diaminopyrimidine-Containing Drugs Including Fedratinib and Trimethoprim with Thiamine Transporters [Articles] (2016)
    The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Details
    Publication Date: 2016-12-18
    Description: Inhibition of thiamine transporters has been proposed as a putative mechanism for the observation of Wernicke’s encephalopathy and subsequent termination of clinical development of fedratinib, a Janus kinase inhibitor (JAKi). This study aimed to determine the potential for other JAKi to inhibit thiamine transport using human epithelial colorectal adenocarcinoma (Caco-2) and thiamine transporter (THTR) overexpressing cells and to better elucidate the structural basis for interacting with THTR. Only JAKi containing a 2,4-diaminopyrimidine were observed to inhibit thiamine transporters. Fedratinib inhibited thiamine uptake into Caco-2 cells (IC 50 = 0.940 µ M) and THTR-2 (IC 50 = 1.36 µ M) and, to a lesser extent, THTR-1 (IC 50 = 7.10 µ M) overexpressing cells. Two other JAKi containing this moiety, AZD1480 and cerdulatinib, were weaker inhibitors of the thiamine transporters. Other JAKi—including monoaminopyrimidines, such as momelotinib, and nonaminopyrimidines, such as filgotinib—did not have any inhibitory effects on thiamine transport. A pharmacophore model derived from the minimized structure of thiamine suggests that 2,4-diaminopyrimidine–containing compounds can adopt a conformation matching several key features of thiamine. Further studies with drugs containing a 2,4-diaminopyrimidine resulted in the discovery that the antibiotic trimethoprim also potently inhibits thiamine uptake mediated by THTR-1 (IC 50 = 6.84 µ M) and THTR-2 (IC 50 = 5.56 µ M). Fedratinib and trimethoprim were also found to be substrates for THTR, a finding with important implications for their disposition in the body. In summary, our results show that not all JAKi have the potential to inhibit thiamine transport and further establish the interaction of these transporters with xenobiotics.
    Print ISSN: 0090-9556
    Electronic ISSN: 1521-009X
    Topics: Chemistry and Pharmacology , Medicine
    Published by The American Society for Pharmacology and Experimental Therapeutics (ASPET)
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  • 6
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    In Vivo Hepatic Enhancer Elements in the Human ABCG2 Locus [Articles] (2017)
    The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Details
    Publication Date: 2017-01-14
    Description: ABCG2 encodes the mitoxantrone resistance protein (MXR; breast cancer resistance protein), an ATP-binding cassette (ABC) efflux membrane transporter. Computational analysis of the ~300 kb region of DNA surrounding ABCG2 (chr4:88911376-89220011, hg19) identified 30 regions with potential cis-regulatory capabilities. These putative regulatory regions were tested for their enhancer and suppressor activity in a human liver cell line using luciferase reporter assays. The in vitro enhancer and suppressor assays identified four regions that decreased gene expression and five regions that increased expression 〉1.6-fold. Four of five human hepatic in vitro enhancers were confirmed as in vivo liver enhancers using the mouse hydrodynamic tail vein injection assay. Two of the in vivo liver enhancers (ABCG2RE1 and ABCG2RE9) responded to 17β-estradiol or rifampin in human cell lines, and ABCG2RE9 had ChIP-seq evidence to support the binding of several transcription factors and the transcriptional coactivator p300 in human hepatocytes. This study identified genomic regions surrounding human ABCG2 that can function as regulatory elements, some with the capacity to alter gene expression upon environmental stimulus. The results from this research will drive future investigations of interindividual variation in ABCG2 expression and function that contribute to differences in drug response.
    Print ISSN: 0090-9556
    Electronic ISSN: 1521-009X
    Topics: Chemistry and Pharmacology , Medicine
    Published by The American Society for Pharmacology and Experimental Therapeutics (ASPET)
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  • 7
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    Targeted Disruption of Organic Cation Transporter 3 Attenuates the Pharmacologic Response to Metformin [Articles] (2015)
    The American Society for Pharmacology and Experimental Therapeutics (ASPET)
    Details
    Publication Date: 2015-05-24
    Description: Metformin, the most widely prescribed antidiabetic drug, requires transporters to enter tissues involved in its pharmacologic action, including liver, kidney, and peripheral tissues. Organic cation transporter 3 (OCT3, SLC22A3 ), expressed ubiquitously, transports metformin, but its in vivo role in metformin response is not known. Using Oct3 knockout mice, the role of the transporter in metformin pharmacokinetics and pharmacodynamics was determined. After an intravenous dose of metformin, a 2-fold decrease in the apparent volume of distribution and clearance was observed in knockout compared with wild-type mice ( P 〈 0.001), indicating an important role of OCT3 in tissue distribution and elimination of the drug. After oral doses, a significantly lower bioavailability was observed in knockout compared with wild-type mice (0.27 versus 0.58, P 〈 0.001). Importantly, metformin’s effect on the plasma glucose concentration-time curve was reduced in knockout compared with wild-type mice (12 versus 30% reduction, respectively, P 〈 0.05) along with its accumulation in skeletal muscle and adipose tissue ( P 〈 0.05). Furthermore, the effect of metformin on phosphorylation of AMP activated protein kinase, and expression of glucose transporter type 4 was absent in the adipose tissue of Oct3 –/– mice. Additional analysis revealed that an OCT3 3' untranslated region variant was associated with reduced activity in luciferase assays and reduced response to metformin in 57 healthy volunteers. These findings suggest that OCT3 plays an important role in the absorption and elimination of metformin and that the transporter is a critical determinant of metformin bioavailability, clearance, and pharmacologic action.
    Print ISSN: 0026-895X
    Electronic ISSN: 1521-0111
    Topics: Chemistry and Pharmacology , Medicine
    Published by The American Society for Pharmacology and Experimental Therapeutics (ASPET)
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  • 8
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    Study of periodic surface profile on improving the window capacity at single and repetitive pulses (2015)
    American Institute of Physics (AIP)
    Details
    Publication Date: 2015-09-11
    Description: The surface breakdown of dielectric windows seriously limits the transmission of high power microwaves (HPM), and has blocked the development of microwave technology in recent decades. In this paper, X-band HPM experiments of window breakdown at the vacuum/dielectric interface and the atmosphere/dielectric interface at single and repetitive pulses were conducted. The cross-linked polystyrene (CLPS) dielectric window with a periodic surface profile can significantly improve the breakdown threshold at single and repetitive pulses. Furthermore, the flat surface layer of CLPS was discovered to be carbonized to a depth of several millimeters and filled with electrical trees at repetitive pulses. Theoretical models were built to understand the underlying physics behind the phenomena in experiments. With the analysis of the electron resonance process breaking the molecular bond and the temperature rise caused by the traversing current in the dielectric material, a microscopic explanation for the carbonization of the dielectric window was introduced.
    Print ISSN: 1070-664X
    Electronic ISSN: 1089-7674
    Topics: Physics
    Published by American Institute of Physics (AIP)
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  • 9
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    Crucial Roles of TNFAIP8 Protein in Regulating Apoptosis and Listeria Infection [CLINICAL AND HUMAN IMMUNOLOGY] (2015)
    The American Association of Immunologists (AAI)
    Details
    Publication Date: 2015-06-06
    Description: TNF-α–induced protein 8 (TNFAIP8 or TIPE) is a newly described regulator of cancer and infection. However, its precise roles and mechanisms of actions are not well understood. We report in this article that TNFAIP8 regulates Listeria monocytogenes infection by controlling pathogen invasion and host cell apoptosis in a RAC1 GTPase-dependent manner. TNFAIP8-knockout mice were resistant to lethal L. monocytogenes infection and had reduced bacterial load in the liver and spleen. TNFAIP8 knockdown in murine liver HEPA1-6 cells increased apoptosis, reduced bacterial invasion into cells, and resulted in dysregulated RAC1 activation. TNFAIP8 could translocate to plasma membrane and preferentially associate with activated RAC1-GTP. The combined effect of reduced bacterial invasion and increased sensitivity to TNF-α–induced clearance likely protected the TNFAIP8-knockout mice from lethal listeriosis. Thus, by controlling bacterial invasion and the death of infected cells through RAC1, TNFAIP8 regulates the pathogenesis of L. monocytogenes infection.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
    Published by The American Association of Immunologists (AAI)
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