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排序方式: 共有218条查询结果,搜索用时 31 毫秒
1.
VB Lang P Langguth C Ottiger H Wunderli-Allenspach D Rognan B Rothen-Rutishauser JC Perriard S Lang J Biber HP Merkle 《Canadian Metallurgical Quarterly》1997,86(7):846-853
Due to the low effective permeabilities of peptides at many absorption sites, their structure-permeation relations are of high interest. In this work structure-permeation relations of Met-enkephalin analogues are presented using confluent Caco-2 cells as an in vitro permeation model. Four model peptides (Met-enkephalin, [D-Ala2]Met-enkephalin, [D-Ala2]Met-enkephalinamide, and metkephamid) were tested in terms of permeability, lipophilicity, charge, and molecular size. Permeability coefficients (P(eff)) across Caco-2 cells were low, 3.3 x 10(-8) to 9.5 x 10(-8) cm s-1, and were similar to typical paracellular markers. No correlation of permeability and the log(apparent octanol/buffer partition coefficient) was observed. A 40-fold increase of the permeability of metkephamid in the presence of 10 mM EDTA suggested a significant contribution of paracellular transport. Independent support for this conclusion was obtained by visualizing the pathway of the fluorescein isocyanate isomer I 1-metkephamid by confocal laser scanning microscopy (CLSM). The fluorophore-labeled peptide was observed in the intercallular space only. Metkephamid permeabilities were found to be direction-specific. Permeabilities from basolateral to apical (b-to-a) were significantly higher (ca. 4-fold) than in the opposite (a-to-b) direction. The addition of verapamil equalized the permeabilities in the a-to-b and b-to-a directions, suggesting the involvement of a P-glycoprotein-mediated secretion mechanism. Similar observations were obtained with [D-Ala2]Met-enkephalinamide, but not with Met-enkephalin and [D-Ala2]Met-enkephalin. In contrast to the other analogues, metkephamid and [D-Ala2]Met-enkephalinamide are positively charged at neutral pH, as demonstrated by their isoelectric points (pl = 8.6 for [D-Ala2]Met-enkephalinamide and metkephamid and 5.3 for [D-Ala2]Met-enkephalin and Met-enkephalin). The data is in agreement with the literature showing that most compounds secreted by the P-glycoprotein transporter carry a positive charge. 相似文献
2.
Fon-Chieh Chang R. R. Fessler B. D. Merkle J. M. Borton W. M. Goldberger 《Particulate Science and Technology》2004,22(1):35-50
Electroconsolidation® is a process for densifying complex-shaped parts by using electrically conductive particulate solids as a pressure-transmitting medium. The part is immersed in a bed of the particulate medium contained in a die chamber. Sintering temperature is achieved by resistive heating of the medium while applying compaction pressure. The process is capable of ultrahigh temperatures and short cycle times and offers the potential for low processing costs.
Control of the process and selection of process conditions require knowledge of the temperatures within the die. Temperature gradients exist because of the high heating rate and because of variations of density and electrical resistivity of the medium due to the presence of the part. Direct measurement of temperature with thermocouples or other conventional means is impractical because of the high temperatures, high currents, and high pressures that are involved. Therefore, a computer model was developed to predict temperature as a function of time and applied voltage for any location in the die. The computer model is composed of three parts: a geometrical model to approximate the density and resistivity variations in the medium, a finite-element model to calculate the rate of resistive heating within each element, and a finite-difference model to calculate the temperature distribution based on solution of the heat-transfer equations. Predicted temperatures have been shown to be in excellent agreement with measurements, and numerical simulation provided encouraging consistency and reasonably accurate predictions of temperature profiles within the die. The model demonstrated the feasibility of a new process to achieve simultaneous application of pressure and heat to powder densification in Electroconsolidation. 相似文献
Control of the process and selection of process conditions require knowledge of the temperatures within the die. Temperature gradients exist because of the high heating rate and because of variations of density and electrical resistivity of the medium due to the presence of the part. Direct measurement of temperature with thermocouples or other conventional means is impractical because of the high temperatures, high currents, and high pressures that are involved. Therefore, a computer model was developed to predict temperature as a function of time and applied voltage for any location in the die. The computer model is composed of three parts: a geometrical model to approximate the density and resistivity variations in the medium, a finite-element model to calculate the rate of resistive heating within each element, and a finite-difference model to calculate the temperature distribution based on solution of the heat-transfer equations. Predicted temperatures have been shown to be in excellent agreement with measurements, and numerical simulation provided encouraging consistency and reasonably accurate predictions of temperature profiles within the die. The model demonstrated the feasibility of a new process to achieve simultaneous application of pressure and heat to powder densification in Electroconsolidation. 相似文献
3.
M Terpstra WB High Y Luo RA de Graaf H Merkle M Garwood 《Canadian Metallurgical Quarterly》1996,9(5):185-194
Increased capacity for glycolytic metabolism is a well-known characteristic of neoplastic cells. Because lactic acid is the end product of glycolysis, in vivo MRS measurements of tumor lactate concentration ([lac]t) may provide valuable information about tumor metabolism, which will aid the development of therapies and the clinical diagnosis and treatment of tumors. In the present study, several hemodynamic and histologic parameters were evaluated with respect to their influence on [lac]t. Pronounced differences in [lac]t in two distinct populations of tumors suggested a putative perfusion threshold. Above this threshold, [lac]t was independent of hemodynamic and histologic factors including tumor blood flow (measured using MRS and the method of D2O washout), extent of necrosis and inflammatory cell infiltrate. Thus, for most tumors, [lac]t was not determined by any one single factor such as hypoxia, venous clearance, glucose supply, extent of necrosis or degree of inflammatory cell infiltrate. Rather, [lac]t may be equilibrated, at least in part, by an interplay of forces involving hemodynamics and substrate supply. In general, the data are consistent with the hypothesis that elevated lactate in most tumors is related to the high glycolytic activity of adequately perfused, viable neoplastic cells. 相似文献
4.
Three examples are revisited in which the reaction rate could be reliably correlated with point defect chemistry highlighting
the role of point defects as acid–base active centers. In the case of dehydrohalogenation of tertiary butyl chloride, AgCl
becomes increasingly active as heterogeneous catalyst, if AgCl is homogeneously or heterogeneously doped. By such a procedure
the silver vacancy concentration is adequately increased. The oxygen incorporation into SrTiO3 offers an example in which the surface mechanism in terms of adsorbed species, oxygen vacancies and electronic centers has
been elucidated. Appropriate surface coatings give rise to significant catalytic effects. Increasing iron (acceptor) doping
not only changes the point defect chemistry but also the nature of the rate determining step. Lastly, the electrocatalytic
function of Sr-doped LaMnO3 is considered as regards oxygen reduction reaction and O2− incorporation into Y-doped ZrO2 in the context of solid oxide fuel cells. Again the defect chemistry is of prime importance for the reaction rate. 相似文献
5.
Avishek Sarbajna Andres Georg Rösch Leonard Franke Uli Lemmer Md Mofasser Mallick 《Advanced Engineering Materials》2023,25(2):2200980
One of the simplest ways to generate electric power from waste heat is thermoelectric (TE) energy conversion. So far, most of the research on thermoelectrics has focused on inorganic bulk TE materials and their device applications. However, high production costs per power output and limited shape conformity hinder applications of state-of-the-art thermoelectric devices (TEDs). In recent years, printed thermoelectrics has emerged as an exciting pathway for their potential in the production of low-cost shape-conformable TEDs. Although several inorganic bulk TE materials with high performance are successfully developed, achieving high performance in inorganic-based printed TE materials is still a challenge. Nevertheless, significant progress has been made in printed thermoelectrics in recent years. In this review article, it is started with an introduction signifying the importance of printed thermoelectrics followed by a discussion of theoretical concepts of thermoelectricity, from fundamental transport phenomena to device efficiency. Afterward, the general process of inorganic TE ink formulation is summarized, and the current development of the inorganic and hybrid inks with the mention of their TE properties and their influencing factors is elaborated. In the end, TEDs with different architecture and geometries are highlighted by documenting their performance and fabrication techniques. 相似文献
6.
7.
Brandon M. Turner Mark Steyvers Edgar C. Merkle David V. Budescu Thomas S. Wallsten 《Machine Learning》2014,95(3):261-289
It is known that the average of many forecasts about a future event tends to outperform the individual assessments. With the goal of further improving forecast performance, this paper develops and compares a number of models for calibrating and aggregating forecasts that exploit the well-known fact that individuals exhibit systematic biases during judgment and elicitation. All of the models recalibrate judgments or mean judgments via a two-parameter calibration function, and differ in terms of whether (1) the calibration function is applied before or after the averaging, (2) averaging is done in probability or log-odds space, and (3) individual differences are captured via hierarchical modeling. Of the non-hierarchical models, the one that first recalibrates the individual judgments and then averages them in log-odds is the best relative to simple averaging, with 26.7 % improvement in Brier score and better performance on 86 % of the individual problems. The hierarchical version of this model does slightly better in terms of mean Brier score (28.2 %) and slightly worse in terms of individual problems (85 %). 相似文献
8.
Effect of several additives and their admixtures on the physico-chemical properties of a calcium phosphate cement 总被引:2,自引:0,他引:2
Bohner M Merkle HP Landuyt PV Trophardy G Lemaitre J 《Journal of materials science. Materials in medicine》2000,11(2):111-116
Combinations of citrate (C6H5O
7
3-–
), pyrophosphate (P2O
7
4–
) and sulfate (SO
4
2–
) ions were used to modify the physico-chemical properties of a calcium phosphate cement (CPC) composed of -tricalcium phosphate (-TCP) and phosphoric acid (PA) solution. The results obtained with only one additive at a time are similar to those previously published. New facts are: the positive effect of C6H5O
7
3–
ions on cement failure strain and their negative effect on cement pH. The position of the setting time maximum measured at an SO
4
2–
concentration of 0.09 M was not displaced by the addition of C6H5O
7
3–
and P2O
7
4–
ions. However, the effect of SO
4
2–
ions on the setting time was depressed by C6H5O
7
3–
ions. Moreover, no increase in tensile strength was observed when increasing amounts of SO
4
2–
were added into a C6H5O
7
3–
-containing cement. The latter results suggest a competitive effect of C6H5O
7
3–
and SO
4
2–
on setting time and tensile strength. Anhydrous dicalcium phosphate (DCP; CaHPO4) appeared in cement samples dried just after setting, but not in cement samples incubated for 24 h in deionized water before the drying step. It is believed that the setting reaction is stopped by the drying step, leaving a low internal pH in the sample, hence providing favorable conditions for the transformation of dicalcium phosphate dihydrate (DCPD) into DCP. Interestingly, even though C6H5O
7
3–
ions dramatically lowered the equilibrium pH of the cement with 5 ml of deionized water, they still prevented the occurrence of the transformation of DCPD into DCP. 相似文献
9.
M Terpstra R Gruetter WB High M Mescher L DelaBarre H Merkle M Garwood 《Canadian Metallurgical Quarterly》1998,58(22):5083-5088
Elevated tissue lactate concentrations typically found in tumors can be measured by in vivo nuclear magnetic resonance (NMR) spectroscopy. In this study, lactate turnover in rat C6 glioma was determined from in vivo 1H NMR measurements of [3-13C]lactate buildup during steady-state hyperglycemia with [1-13C]glucose. With this tumor model, a narrow range of values was observed for the first-order rate constant that describes lactate efflux, k2 = 0.043 +/- 0.007 (n = 12) SD min-1. For individual animals, the standard error in k2 was small (< 18%), which indicated that the NMR data fit the kinetic model well. Lactate measurements before and after infusing [1-13C]glucose showed that the majority of the tumor lactate pool was metabolically active. Signals from 13C-labeled glutamate in tumors were at least 10-fold smaller than the [3-13C]lactate signal, whereas spectra of the contralateral hemispheres revealed the expected labeling of [4-13C]glutamate, as well as [2-13C] and [3-13C]glutamate, which indicates that label cycled through the tricarboxylic acid cycle in the brain tissue. Lack of significant 13C labeling of glutamate was consistent with low respiratory metabolism in this glioma. It is concluded that lactate in rat C6 glioma is actively turning over and that the kinetics of lactate efflux can be quantified noninvasively by 1H NMR detection of 13C label. This noninvasive NMR approach may offer a valuable tool to help evaluate tumor growth and metabolic responsiveness to therapies. 相似文献
10.
W. I. Higuchi Norman F. H. Ho Hans P. Merkle 《Drug development and industrial pharmacy》1983,9(7):1227-1239
This paper reviews the past and the present thinking about peroral delivery research and development and how future approaches may be significantly different, both qualitatively and quantitatively. The future should involve the use of comprehensive models capable of incorporating physico-chemical data and biological information such as gastrointestinal flow, how and where drug absorption occurs, and whether and where metabolism of the drug occurs during gastrointestinal transit. Special challenges would involve the use of such models in research protocols in the optimization of drug delivery systems. 相似文献