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991.
Propyl-4-yn-valproic acid (2-propyl-4-pentynoic acid), an analogue of valproic acid with a triple bond in one alkyl side chain, potently induces exencephaly in mice. Given that propyl-4-yn-valproic acid is a branched chain carboxylic acid, we synthesized a series of analogues with n-alkyl side chains of increasing length and correlated their potential to induce neural tube defects and to inhibit proliferation and induce differentiation in cells of neural origin, the latter being crucial to the orderly structuring of the embryo. All analogues significantly increased the incidence of neural tube defects in the embryos of dams exposed to a single dose of 1.25 mmol/kg on day 8 of gestation. This effect occurred in a dose-dependent manner and the rate of exencephaly increased with the progressive increase in n-alkyl side chain length. Moreover, increasing chain length resulted in a dose-dependent inhibition of C6 glioma proliferation rate over a concentration range of 0-3 mM and this was independent of the cell type employed and mode of estimating proliferative rate. The antiproliferative action of these analogues was associated with profound shape change in neuro-2A neuroblastoma involving extensive neuritogenesis and an associated increase in neural cell adhesion molecule (NCAM) prevalence at points of cell-cell contact, the latter exhibiting a dose-dependent increase when the n-alkyl chain was extended to five carbon units. These results suggest an interaction with a specific site in which the n-alkyl side is proposed to serve as an 'anchor' within a hydrophobic pocket to facilitate the ionic and/or H-bonding of the carboxylic acid and high electron density of the carbon-carbon triple bond. 相似文献
992.
PJ Dekker MT Ryan J Brix H Müller A H?nlinger N Pfanner 《Canadian Metallurgical Quarterly》1998,18(11):6515-6524
The preprotein translocase of the outer mitochondrial membrane (Tom) is a multisubunit machinery containing receptors and a general import pore (GIP). We have analyzed the molecular architecture of the Tom machinery. The receptor Tom22 stably associates with Tom40, the main component of the GIP, in a complex with a molecular weight of approximately 400,000 ( approximately 400K), while the other receptors, Tom20 and Tom70, are more loosely associated with this GIP complex and can be found in distinct subcomplexes. A yeast mutant lacking both Tom20 and Tom70 can still form the GIP complex when sufficient amounts of Tom22 are synthesized. Besides the essential proteins Tom22 and Tom40, the GIP complex contains three small subunits, Tom5, Tom6, and Tom7. In mutant mitochondria lacking Tom6, the interaction between Tom22 and Tom40 is destabilized, leading to the dissociation of Tom22 and the generation of a subcomplex of approximately 100K containing Tom40, Tom7, and Tom5. Tom6 is required to promote but not to maintain a stable association between Tom22 and Tom40. The following conclusions are suggested. (i) The GIP complex, containing Tom40, Tom22, and three small Tom proteins, forms the central unit of the outer membrane import machinery. (ii) Tom20 and Tom70 are not essential for the generation of the GIP complex. (iii) Tom6 functions as an assembly factor for Tom22, promoting its stable association with Tom40. 相似文献
993.
994.
Apoptosis in the male gonad 总被引:1,自引:0,他引:1
D Royère F Guerif MT Rochereau de Reviers S Panthier J Lansac 《Canadian Metallurgical Quarterly》1998,26(7-8):517-521
1. Previous work has shown that enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), potentiated the actions of alpha 1-adrenoceptor antagonists; it was hypothesized that angiotensin II (AngII) modulated the activity of alpha 1-adrenoceptors. This hypothesis was tested in Sprague-Dawley rat isolated perfused tail arteries using the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD123319. 2. Losartan had no alpha 1-adrenoceptor antagonist effects at concentrations below 1 mumol/L. Similarly, losartan (0.1 mumol/L) had no effect on the alpha 1-adrenoceptor antagonist action of doxazosin (1, 10 nmol/L) nor on the potentiation of doxazosin by enalaprilat (1 mumol/L). 3. PD123319 (0.1 mumol/L) had no alpha 1-adrenoceptor antagonist effect but altered the mode of action of the alpha 1-adrenoceptor antagonist doxazosin: PD123319 changed doxazosin from a competitive to a non-competitive antagonist, as evidenced by the reduced slope of the dose-response curve for the alpha 1-adrenoceptor agonist phenylephrine. 4. These results suggest that AngII can modulate alpha 1-adrenoceptor function in rat tail arteries via an indirect action at AT2 receptors. However, the present results do not rule out the involvement of bradykinin, endothelin or prostaglandin in the modulation of alpha 1-adrenoceptor function by angiotensin II. 相似文献
995.
C Junquera C Martínez-Ciriano J Blasco J Aisa MT Peg MJ Azanza 《Canadian Metallurgical Quarterly》1998,23(10):1233-1240
Although insulin has been shown to raise plasma concentrations of endothelin (ET) and up regulate vascular smooth muscle ETA receptor expression, the interaction of vanadate, an insulinomimetic agent, with the vascular ET system has not been investigated. We compared the effects of oral vanadate treatment (0.5 mg/ml; p.o.) and insulin infusion (12 mU.kg-1.min-1 s.c.) for two weeks on plasma ET concentrations and vascular responses to endothelin-1 (ET-1) and the alpha-1 adrenoceptor agonist, methoxamine, in aortic ring preparations from streptozotocin (STZ) diabetic and non-diabetic adult male Sprague-Dawley rats. Plasma ET concentrations were lower (p < 0.01) in STZ diabetic rats compared with normal control rats. Insulin and vanadate treatment restored plasma ET to normal (p < 0.01) in STZ rats and increased ET concentrations in the control (p < 0.05) group. Higher maximal tension responses to both ET-1 (p < 0.01) and methoxamine (p < 0.05) were present in STZ rats in both endothelium intact and denuded aortic preparations compared with the control group. Both insulin and vanadate treatment returned these responses to normal. It is concluded that low plasma concentrations of insulin and high plasma glucose in STZ diabetic rats are accompanied by lower concentrations of plasma ET. Insulin and vanadate treatment restores diminished plasma ET to control concentrations and attenuates exaggerated agonist(s)-evoked vascular smooth muscle responses in STZ-induced diabetic rats. In addition to well known beneficial metabolic effects, insulin and vanadate may beneficially affect cardiovascular regulation in the STZ diabetic rat by correcting abnormal ET activity. 相似文献
996.
Reducing the power envelope fluctuation of OFDM systems using side information supported amplitude clipping approach
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Montadar Abas Taher JS Mandeep Mahamod Ismail Salina Abdul Samad MT Islam 《International Journal of Circuit Theory and Applications》2014,42(4):425-435
OFDM is an important modulation technique currently in development in the field of communications systems. OFDM signals can combat multipath propagation and fading channels and can support large data rates. However, OFDM systems are multicarrier systems and experience problems due to the required summation of sinusoids when the in‐phase subcarriers are combined, which produces high power peaks. The large power envelope fluctuations that occur at the output cause in‐band and out‐of‐band distortions that result in degraded BER performance. The literature contains many qualified approaches to resolving the peak‐to‐average power ratio problem, including selected mapping, partial transmit sequence, and amplitude clipping techniques. The simplest technique is the amplitude clipping technique, and the selected mapping and partial transmit sequence techniques are excessively complicated for real‐time implementation. In this paper, we suggest a modification to the amplitude clipping method to produce a novel clipping technique called the side information supported amplitude clipping (SI‐SAC) method. The SI‐SAC technique involves sending certain bits of extra information so that the receiver can recover all of the clipped data. The SI‐SAC technique does not add computational complexity to the system, and simulation results show that the proposed method is superior to the conventional method. The peak‐to‐average power ratio was reduced by ≈2.5 dB, and the magnitude of the mean squared error vector is the same as that of the original signal that is not clipped. In contrast, the conventional amplitude clipping method produces a mean squared error vector with a large magnitude. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
997.
Mined pyrite and chalcopyrite as catalysts for spontaneous acidic pH adjustment in Fenton and LED photo‐Fenton‐like processes
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998.
A De Ascentiis R Bettini G Caponetti PL Catellani MT Peracchia P Santi P Colombo 《Canadian Metallurgical Quarterly》1996,13(5):734-738
PURPOSE: Delivery of nasal powders of granulated beta-cyclodextrin by insufflation was studied in order to find the relationship between powder properties and delivery behavior. METHODS: Three nasal powder formulations, prepared by granulating beta-cyclodextrin with different binders, were delivered from a powder insufflation device, in which the dose to be emitted was loaded in a gelatin capsule. The delivery sequence of powder was recorded and characterized using an image analysis program. RESULTS: Particle size was the main parameter affecting nasal powder delivery, both as to the amount of dose sprayed and the aspect of cloud produced. Between 50-150 mu m of particle size a substantial change in delivery behavior of powders was observed. Powder of around 100 mu m in size showed useful insufflation characteristics for nasal delivery. Bioavailability of nasal formulations of progesterone/beta-cyclodextrin powders was discussed in term of delivery behavior. CONCLUSIONS: The formulation approaches for improving nasal delivery of powders require the use of size optimized carriers. Insufflation of powders over 50 mu m can favour the particle deposition by impaction, whereas for powders below 50 mu m, deposition by sedimentation is moved. beta-cyclodextrin is a suitable carrier for achieving high systemic availability following nasal administration of powder formulations. 相似文献
999.
The gene parC encodes the A subunit of topoisomerase IV of Escherichia coli. Mutations in the parC region analogous to those in the quinolone resistance-determining region of gyrA were investigated in 27 clinical isolates of E. coli for which ciprofloxacin MICs were 0.0007 to 128 micrograms/ml. Of 15 isolates for which ciprofloxacin MICs were > or = 1 microgram/ml, 8 showed a change in the serine residue at position 80 (Ser-80), 4 showed a change in Glu-84, and 3 showed changes in both amino acids. No mutations were detected in 12 clinical isolates for which ciprofloxacin MICs were < or = 0.25 micrograms/ml. These findings suggest that ParC from E. coli may be another target for quinolones and that mutations at residues Ser-80 and Glu-84 may contribute to decreased fluoroquinolone susceptibility. 相似文献
1000.
The relative contributions of T-lymphocyte subsets to host defense in cattle infected with Mycobacterium avium subsp. paratuberculosis is reported. The subsets were purified with appropriate monoclonal antibodies and a magnetic bead column separation system, and their purity was verified by flow cytometry. Biological activity of each subset, expressed as lymphoproliferation and gamma interferon (IFN-gamma) production, was measured in response to phytohemagglutinin (PHA) and an M. avium antigen preparation (A-PPD). IFN-gamma was measured by antibody capture enzyme-linked immunosorbent assay. The results showed a correlation between proliferation and IFN-gamma production in response to A-PPD but not to PHA. In response to PHA, CD4+ lymphocytes were the most prolific producers of IFN-gamma. CD8+ lymphocytes produced IFN-gamma to a lesser extent, whereas gammadelta+ T lymphocytes produced little or no IFN-gamma. Differences observed between the amount of IFN-gamma produced by CD4+ versus CD8+ cells and CD4+ versus gammadelta+ cells were significant (P < 0.01), but those between peripheral blood mononuclear cells (PBMC) and CD4+ T cells were not. Similar responses to A-PPD were observed except that PBMC produced higher levels of IFN-gamma than did CD4+ T cells. These data for cattle are similar to observations made for other animal species, where CD4+ cells are the major type of T lymphocytes producing IFN-gamma. They further suggest that whatever the role gammadelta+ T cells may play in paratuberculosis, it is not likely to be mediated by IFN-gamma production. 相似文献