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941.
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Molecular dynamics (MD) simulations of phosphatidylinositol (4,5)-bisphosphate (PIP2) and phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in 1-palmitoyl 2-oleoyl phosphatidylcholine (POPC) bilayers indicate that the inositol rings are tilted ∼40° with respect to the bilayer surface, as compared with 17° for the P-N vector of POPC. Multiple minima were obtained for the ring twist (analogous to roll for an airplane). The phosphates at position 1 of PIP2 and PIP3 are within an Ångström of the plane formed by the phosphates of POPC; lipids in the surrounding shell are depressed by 0.5-0.8 Å, but otherwise the phosphoinositides do not substantially perturb the bilayer. Finite size artifacts for ion distributions are apparent for systems of ∼26 waters/lipid, but, based on simulations with a fourfold increase of the aqueous phase, the phosphoinositide positions and orientations do not show significant size effects. Electrostatic potentials evaluated from Poisson-Boltzmann (PB) calculations show a strong dependence of potential height and ring orientation, with the maxima on the −25 mV surfaces (17.1 ± 0.1 Å for PIP2 and 19.4 ± 0.3 Å for PIP3) occurring near the most populated orientations from MD. These surfaces are well above the background height of 10 Å estimated for negatively charged cell membranes, as would be expected for lipids involved in cellular signaling. PB calculations on microscopically flat bilayers yield similar maxima as the MD-based (microscopically rough) systems, but show less fine structure and do not clearly indicate the most probable regions. Electrostatic free energies of interaction with pentalysine are also similar for the rough and flat systems. These results support the utility of a rigid/flat bilayer model for PB-based studies of PIP2 and PIP3 as long as the orientations are judiciously chosen. 相似文献
945.
Jürgen Sühnel 《Bulletin of mathematical biology》1998,60(2):197-213
A possible experimental design for combination experiments is to compare the doseresponse curve of a single agent with the
corresponding curve of the same agent using either a fixed amount of a second one or a fixed dose ratio. No interaction is
then often defined by a parallel shift of these curves. We have performed a systematic study for various types of doseresponse
relations both for the dose-additivity (Loewe additivity) and for the independence (Bliss independence) criteria for defining
zero interaction. Parallelism between doseresponse curves of a single agent and those of the same agent in the presence of
a fixed amount of another one is found for the Loewe-additivity criterion for linear doseresponse relations. For nonlinear
relations, one has to differentiate between effect parallelism (parallel shift on the effect scale) and dose parallelism (parallel
shift on the dose scale). In the case of Loewe additivity, zero-interaction dose parallelism is found for power, Weibull,
median-effect and logistic doseresponse relations, given that special parameter relationships are fulfilled. The mechanistic
model of competitive interaction exhibits dose parallelism but not effect parallelism for Loewe additivity. Bliss independence
and Loewe additivity lead to identical results for exponential doseresponse curves. This is the only case for which dose parallelism
was found for Bliss independence. Parallelism between single-agent doseresponse relations and Loewe additivity mixture relations
is found for examples with a fixed doseratio design. However, this is again not a general property of the design adopted but
holds only if special conditions are fulfilled. The comparison of combination doseresponse curves with single-agent relations
has to be performed taking into account both potency and shape parameters. The results of this analysis lead to the conclusion
that parallelism between zero interaction combination and single-agent doseresponse relations is found only for special cases
and cannot be used as a general criterion for defining zero-interaction in combined-action assessment even if the correct
potency shift is taken into account. 相似文献
946.
947.
V T Kondakov A B Okulov M A Filippkin R Z Tandilava I U Artamonov O A Voronenko A N Sazonov 《Vestnik rentgenologii i radiologii》1991,(4):31-35
The paper is concerned with analysis of the results of intraoperative phlebotesticulography, performed in 50 patients with varicocele of degree I-II during Ivanissevich's operation. The effect of surgical intervention was shown to depend upon the quality of ligation of the testicular vein, some parts of which are anastomosed between themselves. The localization of this anastomosis is revealed by means of intraoperative phlebotesticulography, which permits increasing the results of surgical treatment and predicting a course of a postoperative period. 相似文献
948.
The results of recent randomized trials to test the influence of antioxidants on coronary-event rates and prognosis in patients
with coronary-artery disease were disappointing. In none of these studies did the use of vitamin E improve prognosis. In contrast,
treatment of coronary-artery disease with angiotensin-converting-enzyme (ACE) inhibitors reduced coronary-event rates and
improved prognosis. ACE inhibition prevents the formation of angiotensin II, which has been shown to be a potent stimulus
of superoxide-producing enzymes in atherosclerosis. The findings suggest that inhibition of superoxide production at enzymatic
levels, rather than symptomatic superoxide scavenging, may be the better choice of treatment. 相似文献
949.
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