Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd. 相似文献
Crystallography Reports - Crystals that contain water molecules spaced by distances excluding their chemical interaction are model systems for studying the so-called “water... 相似文献
In the Friedmann cosmology, the deceleration of the expansion q plays a fundamental role. We derive the deceleration as a function of redshift q(z) in two scenarios: ΛCDM model and modified Chaplygin gas (MCG) model. The function for the MCG model is then fitted to the cosmological data in
order to obtain the cosmological parameters that minimize χ2. We use the Fisher matrix to construct the covariance matrix of our parameters and reconstruct the q(z) function. We use Supernovae Ia, WMAP5, and BAO measurements to obtain the observational constraints. We determined the present
acceleration as q0 = − 0.65 ±0.19 for the MCG model using the Union2 dataset of SNeIa, BAO, and CMB and q0 = − 0.67 ±0.17 for the Constitution dataset, BAO and CMB. The transition redshift from deceleration to acceleration was found
to be around 0.80 for both datasets. We have also determined the dark energy parameter for the MCG model: ΩX0 = 0.81 ±0.03 for the Union2 dataset and ΩX0 = 0.83 ±0.03 using the Constitution dataset. 相似文献
Using a novel differential magneto-optical imaging technique we investigate the phenomenon of vortex lattice melting in crystals
of Bi2Sr2CaCu2O8 (BSCCO). The images of melting reveal complex patterns in the formation and evolution of the vortex solid-liquid interface
with varying field (H)/temperature (T). We believe that the complex melting patterns are due to a random distribution of material disorder/inhomogeneities across
the sample, which create fluctuations in the local melting temperature or field value. To study the fluctuations in the local
melting temperature/field, we have constructed maps of the melting landscape Tm(H, r), viz., the melting temperature (Tm) at a given location (r) in the sample at a given field (H). A study of these melting landscapes reveals an unexpected feature: the melting landscape is not fixed, but changes rather
dramatically with varying field and temperature along the melting line. It is concluded that the changes in both the scale
and shape of the landscape result from the competing contributions of different types of quenched disorder which have opposite
effects on the local melting transition. 相似文献
This is a continuation of our earlier investigation (Gurtuet al 1974Phys. Lett.50 B 391) on multiparticle production in proton-nucleus collisions based on an exposure of emulsion stack to 200 GeV/c beam at the NAL. It is found that the ratioRem = 〈ns〉/〈nch〉, where 〈nch〉 is the charged particle multiplicity in pp-collisions, increases slowly from about 1 at 10 GeV/c to 1·6 at 68 GeV/c and attains a constant value of 1·71 ± 0·04 in the region 200 to 8000 GeV/c. Furthermore,Rem = 1·71 implies an effectiveA-dependence ofRA =A0.18,i.e., a very weak dependence. Predictions ofRem on various models are discussed and compared with the emulsion data. Data seem to favour models of hadron-nucleon collisions in which production of particles takes place through adouble step mechanism,e.g., diffractive excitation, hydrodynamical and energy flux cascade as opposed to models which envisage instantaneous production. 相似文献
Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior.
Results
We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle.
Conclusion
Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise. The data shown here provide a basic framework for the intraneural pharmacology of this tripartite complex. The pharmacologically efficacious drug delivery demonstrated here verify the fundamental feasibility of using axonal transport for targeted drug delivery. 相似文献
We have tested the conduction band electrons of lanthanum hexaboride that is among the most effective electron-beam sources with one of the highest brightness of thermionic emission. We performed infrared spectroscopic, DC (direct current) resistivity and Hall-effect studies of LaB6 single crystals with various 10B and 11B isotope contents. We find that only a small amount of conduction electrons behave as Drude-type charge carriers while about 70% of the electrons are involved in collective oscillations of electron density coupled to vibrations of both the Jahn-Teller unstable rigid boron cage and rattling modes of La-ions loosely bound to the lattice. We suggest that exactly these non-equilibrium conduction electrons determine the extraordinary low work function of thermoemission in LaB6.