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21.
22.
Rezler EM Khan DR Lauer-Fields J Cudic M Baronas-Lowell D Fields GB 《Journal of the American Chemical Society》2007,129(16):4961-4972
Nanotechnology-based drug delivery systems (nanoDDSs) have seen recent popularity due to their favorable physical, chemical, and biological properties, and great efforts have been made to target nanoDDSs to specific cellular receptors. CD44/chondroitin sulfate proteoglycan (CSPG) is among the receptors overexpressed in metastatic melanoma, and the sequence to which it binds within the type IV collagen triple-helix has been identified. A triple-helical "peptide-amphiphile" (alpha1(IV)1263-1277 PA), which binds CD44/CSPG, has been constructed and incorporated into liposomes of differing lipid compositions. Liposomes containing distearoyl phosphatidylcholine (DSPC) as the major bilayer component, in combination with distearoyl phosphatidylglycerol (DSPG) and cholesterol, were more stable than analogous liposomes containing dipalmitoyl phosphatidylcholine (DPPC) instead of DSPC. When dilauroyl phosphatidylcholine (DLPC):DSPG:cholesterol liposomes were prepared, monotectic behavior was observed. The presence of the alpha1(IV)1263-1277 PA conferred greater stability to the DPPC liposomal systems and did not affect the stability of the DSPC liposomes. A positive correlation was observed for cellular fluorophore delivery by the alpha1(IV)1263-1277 PA liposomes and CD44/CSPG receptor content in metastatic melanoma and fibroblast cell lines. Conversely, nontargeted liposomes delivered minimal fluorophore to these cells regardless of the CD44/CSPG receptor content. When metastatic melanoma cells and fibroblasts were treated with exogeneous alpha1(IV)1263-1277, prior to incubation with alpha1(IV)1263-1277 PA liposomes, to potentially disrupt receptor/liposome interactions, a dose-dependent decrease in the amount of fluorophore delivered was observed. Overall, our results suggest that PA-targeted liposomes can be constructed and rationally fine-tuned for drug delivery applications based on lipid composition. The selectivity of alpha1(IV)1263-1277 PA liposomes for CD44/CSPG-containing cells represents a targeted-nanoDDS with potential for further development and application. 相似文献
23.
The classical fatigue limit is often an important characteristic in fatigue design regarding metallic material. The limit is usually obtained from a staircase test in combination with some assumption about the statistical distribution of the limit. This distribution can be of a normal, log-normal or of extreme value type and no particular physical argument gives favor to any specific distribution. This leads to a certain ambiguity in the evaluation of test results which forces the designer to introduce large safety factors. In order to find a physically based statistical distribution for use in staircase tests to determine the fatigue limit we present here a random model for the fatigue limit based on the following assumptions; (i) The square root area model according to Murakami and co-workers is valid, (ii) the randomness in the fatigue limit is induced by the randomness of the maximum defect size, (iii) the random maximum defect size has an extreme value distribution of Gumbel type. This leads to the fatigue limit distribution based on Gumbel (FLG), which is recommended to replace the normal distribution in the evaluation of staircase fatigue tests in case of hard materials. It turns out that the skewness of the resulting distribution depends on the coefficient of variation; with a normal-like non-skewed distribution at the coefficient of variation of five percent. 相似文献
24.
An acrylate based pressure sensitive adhesive (PSA) was synthesized to design a drug‐in‐adhesive (DIA) type transdermal therapeutic system (TTS) for nitroglycerin used in the treatment of angina pectoris. 2‐Ethylhexyl acrylate (EHA), methyl methacrylate (MMA) and acrylic acid (AA) were used to synthesize the PSA by free radical solution polymerization. The effects of reaction time, reaction temperature, initiator concentration and solvent on polymerization were studied. The synthesized terpolymer was characterized by 1H‐NMR, FT‐IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and also evaluated for intrinsic viscosity, refractive index, peel strength, moisture uptake and skin irritation potential. The PSA was used to develop DIA type patches of nitroglycerin. The patches were cast using solvent evaporation technique and dried at controlled temperature. The patches were evaluated for thickness uniformity, weight variation, peel strength and moisture pick‐up. The percent drug content and in vitro drug release was determined by high pressure liquid chromatography (HPLC) method. On the basis of in vitro release profile, patches were selected for in vitro skin permeation studies. The developed formulation TP‐1 (K = 24.892 mcg/cm2/hr) followed zero‐order rate kinetics and showed better skin permeation rate in comparison to the marketed TTS (MTTS) (K = 17.413 mcg/cm2/hr). TP‐1 was subjected to stability testing for a period of 1 year according to ICH guidelines. The patches were found to be stable and an expiry date of 2 years was predicted with storage at 25 °C or below. Copyright © 2001 John Wiley & Sons, Ltd. 相似文献
25.
Mareš Kamil Vavřinec Šebesta Ferdinand John Jan 《Journal of Radioanalytical and Nuclear Chemistry》2019,322(2):377-387
Journal of Radioanalytical and Nuclear Chemistry - A novel metal sulfide: potassium niobium sulfide (KNbS) was prepared by hydrothermal method. The morphology and composition of KNbS were... 相似文献
26.
Summary This paper outlines an alternative exposition of the structure of quantum thermodynamics which is essentially based on Carnot's
theory where fluxes of caloric are identified with negative information fluxes. It is further assumed that the thermal energy
evolved by thermal processes is identical with the electromagnetic zero-point background energy evolved by the destruction
of information inscribed in a structural unit (qubit). Theoretical arguments on an elementary level are accompanied by illustrative
examples. 相似文献
27.
Prions are a novel class of infectious pathogens that cause a group of fatal prion diseases in which the benign cellular form of the prion protein (PrP(C)) is transformed into the disease-related scrapie variant (PrP(SC)). The two PrP isoforms differ in their structure and resistance to degradation. The molecular mechanism by which the PrP(SC) is formed and causes infectivity or neurodegeneration is not known. In a compelling and emerging view, post-translational modifications (or the lack thereof) play roles in the transformation of PrP(C) to PrP(SC). Human PrP contains two consensus sites for N-linked glycosylation, at Asn181 and Asn197. From the functional standpoint, glycosylation can modify either the conformation of PrP(C), or the stability of PrP(SC) and, hence, the rate of PrP(SC) clearance. So far the NMR structures of only recombinant, non-glycosylated prions are known, while the structure of the glycosylated form is estimated by molecular modeling. A number of native amino acid mutations in PrP can be mapped near the glycosylation sites. Normal prion protein has been demonstrated to be a copper binding protein, and increasing evidence has shown correlation between the level of PrP expression and tolerance to oxidative stress. Moreover, histochemistry for nitrotyrosine is used for detection of neuronal labeling, a sign of a peroxynitrite-mediated neuronal degradation and a marker for nitrative stress in scrapie-infected mouse brains. It is an intriguing proposition that the post-translational modifications alone, or in combination with amino acid changes, play dominant roles in the pathogenic transformation of PrP(C) to PrP(SC). 相似文献
28.
J. Mareš 《Czechoslovak Journal of Physics》1985,35(8):883-891
Laser excited luminescence has been used to study an energy transfer between Ce3+ and Nd3+ ions in YAlG:Nd,Ce laser crystal with varying small Ce concentrations. Radiative Ce3+Nd3+ energy transfer dominates in the studied single crystal samples but this process can also be accompanied by multistep transfer mechanisms (for example by (Ce3+Ce3+)n Nd3+ transfer mechanism). The Ce3+Nd3+ radiative energy transfer improves pumping of green and yellow excitation lines in YAlG:Nd,Ce laser rods because the contribution of the additional transfer pumping of Nd3+ ions from Ce3+ ions is more than three times greater than should be expected from concentration differences between Nd and Ce. This favourable behaviour is explained from high quantum efficiency of Ce3+ emission and higher Ce3+ absorption cross sections in comparison with the Nd3+ ones (more than one order of magnitude difference).This work was done in cooperation with Monokrystaly Turnov, Research Institute for Single Crystals. The author is grateful to Jos. Kvapil and J. Kubelka for supplying him with samples used in this work. He would like to acknowledge many fruitful discussions with J. Kvapil and K. Blaek of Monokrystaly Turnov. 相似文献
29.
Carina Lemke Dr. Adéla Jílková Dominic Ferber Dr. Annett Braune Anja On Dr. Patrick Johe Dr. Alena Zíková Prof. Dr. Tanja Schirmeister Dr. Michael Mareš Dr. Martin Horn Prof. Dr. Michael Gütschow 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(62):e202201636
Rhodesain is the major cysteine protease of the protozoan parasite Trypanosoma brucei and a therapeutic target for sleeping sickness, a fatal neglected tropical disease. We designed, synthesized and characterized a bimodal activity-based probe that binds to and inactivates rhodesain. This probe exhibited an irreversible mode of action and extraordinary potency for the target protease with a kinac/Ki value of 37,000 M−1s−1. Two reporter tags, a fluorescent coumarin moiety and a biotin affinity label, were incorporated into the probe and enabled highly sensitive detection of rhodesain in a complex proteome by in-gel fluorescence and on-blot chemiluminescence. Furthermore, the probe was employed for microseparation and quantification of rhodesain and for inhibitor screening using a competition assay. The developed bimodal rhodesain probe represents a new proteomic tool for studying Trypanosoma pathobiochemistry and antitrypanosomal drug discovery. 相似文献
30.
Lukáš Chytil Josef Cvačka Věra Marešová Branislav Štrauch Jiří Widimský Jr Martin Štícha Ondřej Slanař 《Journal of mass spectrometry : JMS》2010,45(10):1179-1185
Rilmenidine is an alpha 2 adrenoreceptor agonist used in the treatment of mild and moderate hypertension. In this study, a fast and accurate liquid chromatographic method with tandem mass spectrometric detection has been validated in order to assure quantification of rilmenidine in human serum. The fragmentation pathway of protonated rilmenidine was studied using high‐resolution mass spectrometry (HRMS). This study compared selectivity, linearity, accuracy, precision, extraction efficiency, matrix effect and sensitivity using common liquid–liquid extraction (LLE) and solid‐phase extraction (SPE) procedures. The limit of quantitation for both extraction techniques was 0.1 ng/ml. Several differences between the LLE and SPE have been observed in terms of linearity, accuracy, precision and matrix effect. Additionally, the advantages of SPE included less manual work load and increased recovery of rilmenidine in human serum to approximately 80% (LLE, 57%). The developed method involving SPE was found to be accurate (relative error (RE) < 5%), reproducible (relative standard deviation, RSD < 7%), robust and suitable for quantitative analysis of rilmenidine in serum samples obtained from patients under antihypertensive treatment. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献