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101.
102.
M F Boehm P Fitzgerald A Zou M G Elgort E D Bischoff L Mere D E Mais R P Bissonnette R A Heyman A M Nadzan M Reichman E A Allegretto 《Chemistry & biology》1999,6(5):265-275
BACKGROUND: The secosteroid 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) acts through the vitamin D receptor (VDR) to elicit many activities that make it a promising drug candidate for the treatment of a number of diseases, including cancer and psoriasis. Clinical use of 1,25(OH)2D3 has been limited by hypercalcemia elicited by pharmacologically effective doses. We hypothesized that structurally distinct, nonsecosteroidal mimics of 1,25(OH)2D3 might have different activity profiles from vitamin D analogs, and set out to discover such compounds by screening small-molecule libraries. RESULTS: A bis-phenyl derivative was found to activate VDR in a transactivation screening assay. Additional related compounds were synthesized that mimicked various activities of 1,25(OH)2D3, including growth inhibition of cancer cells and keratinocytes, as well as induction of leukemic cell differentiation. In contrast to 1, 25(OH)2D3, these synthetic compounds did not demonstrate appreciable binding to serum vitamin D binding protein, a property that is correlated with fewer calcium effects in vivo. Two mimics tested in mice showed greater induction of a VDR target gene with less elevation of serum calcium than 1,25(OH)2D3. CONCLUSIONS: These novel VDR modulators may have potential as therapeutics for cancer, leukemia and psoriasis with less calcium mobilization side effects than are associated with secosteroidal 1,25(OH)2D3 analogs. 相似文献
103.
Arnon Avron 《Journal of Geometry》1990,38(1-2):12-15
We show that every point in the plane which can be constructed by a compass and a ruler, given a setS of points, can be constructed using a compass alone so that the following restriction is met. LetO andK be two arbitrarily chosen distinct points ofS. Then every point is obtained as a proper intersection of two circles that are either completely symmetrical with respect to the lineOK or have both their centers on this line. 相似文献
104.
105.
Fast gradient echo sequences, such as echo planer imaging (EPI) and spiral imaging, are vulnerable to artifacts resulting from B(0) inhomogeneities. A major contribution to these artifacts is the susceptibility variation across the head, which is most severe in regions adjacent to air-tissue interfaces, such as the mouth, nasal sinuses, ears and the cortex. Susceptibility artifacts can cause geometrical distortions in the image as well as loss of signal due to T(2)* dephasing. The extent of these artifacts increases with the main field, thus compromising the signal-to-noise ratio (SNR) benefit gained in higher fields. In the current work, inhomogeneity caused by susceptibility variations at the external boundary of the human body has been corrected by surrounding the organs with a liquid without hydrogen atoms and whose susceptibility is similar to that of the imaged organ. EPI experiments were conducted on head-sized phantom, human brain, hand and legs. This method causes minimal patient inconvenience and no interference with any function of the scanner, thus yielding a simple and efficient solution for the correction of B(0) variation. 相似文献
106.
D. P. Heyman 《Annals of Operations Research》1987,8(1):57-73
Network models in which each node is a loss system frequently arise in telephony. Models with several hundred nodes are common. Suppose a customer requires a server from each of several nodes. It would be convenient if the probability that the required servers are all free were approximately a product, where each term is the probability a required node has a free server. We present some theorems to support this approximation. Most of the theorems are restricted to nodes with one server. Some of the difficulties in analyzing nodes with multiple servers are described. 相似文献
107.
Asymmetric synthesis of (-)-[9]helicene, as well as preparation of its lower homologues, completes the series of carbon-sulfur [5]-, [7]-, [9]-, and [11]helicenes. Spectroscopic and electrochemical studies of this series provide an absorption onset-based band gap, E(g) = 3.40 eV, for a cross-conjugated (C(2)S)(n) helix; this value may be compared to E(g) = 3.59 eV obtained from TD-DFT computed excitation energies for a series of dimethyl-substituted [n]helicenes (n ≤ 31). 相似文献