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51.
Sun Q Tafesse L Islam K Zhou X Victory SF Zhang C Hachicha M Schmid LA Patel A Rotshteyn Y Valenzano KJ Kyle DJ 《Bioorganic & medicinal chemistry letters》2003,13(20):3611-3616
A series of 4-(2-pyridyl)piperazine-1-carboxamide analogues based on the lead compound 1 was synthesized and evaluated for VR1 antagonist activity in capsaicin-induced (CAP) and pH (5.5)-induced (pH) FLIPR assays in a rat VR1-expressing HEK293 cell line. Potent VR1 antagonists were identified through SAR studies. From these studies, 18 was found to be very potent in the in vitro assay [IC(50)=4.8 nM (pH) and 35 nM (CAP)] and orally available in rat (F%=15.1). 相似文献
52.
Nadia Aboulaich Lamiaa Achmakh Hassan Bouziane M. Mar Trigo Marta Recio Mohamed Kadiri Baltasar Cabezudo Hassane Riadi Mohamed Kazzaz 《International journal of biometeorology》2013,57(2):197-205
Poaceae pollen is one of the most prevalent aeroallergens causing allergenic reactions. The aim of this study was to characterise the grass pollen season in Tetouan during the years 2008–2010, to analyse the effect of some meteorological parameters on the incidence of the airborne Poaceae pollen, and to establish forecasting variables for daily pollen concentrations. Aerobiological sampling was undertaken over three seasons using the volumetric method. The pollen season started in April and showed the highest pollen index in May and June, when the maximum temperature ranged from 23 to 27 °C, respectively. The annual pollen score recorded varied from year to year between 2,588 and 5,404. The main pollen season lasted 114–173 days, with peak days occurring mainly in May; the highest concentration reached 308 pollen grains/m3. Air temperature was the most important meteorological parameter and correlated positively to daily pollen concentration increase. An increase in relative humidity and precipitation was usually related to a decrease in airborne pollen content. External validation of the models performed using data from 2011 showed that Poaceae pollen concentration can be highly predicted (64.2–78.6 %) from the maximum temperature, its mean concentration for the same day in other years, and its concentration recorded on the previous day. Sensitive patients suffering allergy to Poaceae pollen are at moderate to highest risk of manifesting allergic symptoms to grass pollen over 33–42 days. The results obtained provide new information on the quantitative contribution of the Poaceae pollen to the airborne pollen of Tetouan and on its temporal distribution. Airborne pollen can be surveyed and forecast in order to warn the atopic population. 相似文献
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An efficient method for the synthesis of 5'-O-monomethoxytrityl-2',3'-dideoxy-2'-fluoro-3'-thioarabinothymidine [(5'MMT)araF-T(3'SH), (5)] and its 3'-phosphoramidite derivative (6) suitable for automated incorporation into oligonucleotides, is demonstrated. A key step in the synthesis involves reaction of 5'-O-MMT-2,3'-O-anhydrothymidine (4) (Eleuteri, A.; Reese, C.B.; Song, Q. J. Chem. Soc. Perkin Trans. 1 1996, 2237 pp.) with sodium thioacetate to give (5'-MMT)araF-T(3'SAc) (5) (Elzagheid, M.I.; Mattila, K.; Oivanen, M.; Jones, B.C.N.M.; Cosstick, L?nnberg, H. Eur. J. Org. Chem. 2000, 1987-1991). This nucleoside was then converted to its corresponding phosphoramidite derivative, 6, as described previously ((a) Sun, S.; Yoshida, A.; Piccirilli, J.A. RNA, 1997, 3, 1352-1363; (b) Matulic-Adamic, J.; Beigelman, L. Helvetica Chemica Acta 1999, 82, 2141-2150: (c) Fettes, K.J.; O'Neil, I.; Roberts, S.M.; Cosstick, R. Nucleosides, Nucleotides and Nucl. Acids 2001, 20, 1351-1354). 相似文献
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Javelle A Lupo D Li XD Merrick M Chami M Ripoche P Winkler FK 《Journal of structural biology》2007,159(2):243-252
Amt/Rh proteins, which mediate movement of ammonium across cell membranes, are spread throughout the three kingdoms of life. Most functional studies on various members of the family have been performed using cellular assays in heterologous expression systems, which are, however, not very well suited for detailed mechanistic studies. Although now generally considered to be ammonia conducting channels, based on a number of experimental studies and structural insights, the possibility remains that some plant Amts facilitate net ammonium ion transport. The Escherichia coli channel AmtB has become the model system of choice for analysis of the mechanism of ammonia conductance, increasingly also through molecular dynamics simulations. Further progress in a more detailed mechanistic understanding of these proteins requires a reliable in vitro assay using purified protein, allowing quantitative kinetic measurements under a variety of experimental conditions for different Amt/Rh proteins, including mutants. Here, we critically review the existing functional data in the context of the most interesting and unresolved mechanistic questions and we present our results, obtained using an in vitro assay set up with the purified E. coli channel AmtB. 相似文献
56.
Role of the programmed death-1 pathway in regulation of alloimmune responses in vivo 总被引:7,自引:0,他引:7
Sandner SE Clarkson MR Salama AD Sanchez-Fueyo A Domenig C Habicht A Najafian N Yagita H Azuma M Turka LA Sayegh MH 《Journal of immunology (Baltimore, Md. : 1950)》2005,174(6):3408-3415
Programmed death-1 (PD-1), an inhibitory receptor up-regulated on activated T cells, has been shown to play a critical immunoregulatory role in peripheral tolerance, but its role in alloimmune responses is poorly understood. Using a novel alloreactive TCR-transgenic model system, we examined the functions of this pathway in the regulation of alloreactive CD4+ T cell responses in vivo. PD-L1, but not PD-1 or PD-L2, blockade accelerated MHC class II-mismatched skin graft (bm12 (I-Abm12) into B6 (I-Ab)) rejection in a similar manner to CTLA-4 blockade. In an adoptive transfer model system using the recently described anti-bm12 (ABM) TCR-transgenic mice directly reactive to I-Abm12, PD-1 and PD-L1 blockade enhanced T cell proliferation early in the immune response. In contrast, at a later time point preceding accelerated allograft rejection, only PD-L1 blockade enhanced T cell proliferation. In addition, PD-L1 blockade enhanced alloreactive Th1 cell differentiation. Apoptosis of alloantigen-specific T cells was inhibited significantly by PD-L1 but not PD-1 blockade, indicating that PD-1 may not be the receptor for the apoptotic effect of the PD-L1-signaling pathway. Interestingly, the effect of PD-L1 blockade was dependent on the presence of CD4+ CD25+ regulatory T cells in vivo. These data demonstrate a critical role for the PD-1 pathway, particularly PD-1/PD-L1 interactions, in the regulation of alloimmune responses in vivo. 相似文献
57.
Mohamed E El-Khouly 《Photochemical & photobiological sciences》2007,6(5):539-544
Photoinduced bimolecular electron transfer processes of fullerenes (C60/C70) with fluorene derivatives, namely 9,9-bis(4-amino-3-methylphenyl)fluorene (BAMF), 9,9-bis(4-amino-3-fluorophenyl)fluorene (BAFF) and 9,9-bis(3-amino-4-hydroxyphenyl)fluorene (BAHF) have been comparatively studied in benzonitrile by nanosecond laser photolysis technique in the visible/near-IR regions. By the selective excitation of C60/C70 using 532 nm laser light, it has been proved that electron transfer takes place from the ground state fluorenes to the triplet excited state of C60/C70. The observed rates and efficiencies of the electron transfer processes are found to be significantly associated with the substitution patterns on the 9,9-bisphenylfluorenes, and to be correlative with the free energy changes on the basis of the Rehm-Weller relation. 相似文献
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Purkis Sam J. Gleason Arthur C. R. Purkis Charlotte R. Dempsey Alexandra C. Renaud Philip G. Faisal Mohamed Saul Steven Kerr Jeremy M. 《Coral reefs (Online)》2019,38(3):467-488
Coral Reefs - With compelling evidence that half the world’s coral reefs have been lost over the last four decades, there is urgent motivation to understand where reefs are located and their... 相似文献