Construction of receptors with binding sites of specific size, shape, and functional groups is important to both chemistry and biology. Covalent imprinting of a photocleavable template within surface–core doubly cross‐linked micelles yielded carboxylic acid‐containing hydrophobic pockets within the water‐soluble molecularly imprinted nanoparticles. The functionalized binding pockets were characterized by their binding of amine‐ and acid‐functionalized guests under different pH values. The nanoparticles, on average, contained one binding site per particle and displayed highly selective binding among structural analogues. The binding sites could be modified further by covalent chemistry to modulate their binding properties. 相似文献
Here we demonstrate that neat reactions of amphoteric azoles with more basic azoles give a family of finely tunable, nonstoichiometric liquids which are useful for N‐donor coordination chemistry. Reacting 4,5‐dicyanoimidazole (4,5‐DCNIm) with 1‐methylimidazole (1‐mim) gives new compounds with composition‐dependent speciation. Two crystalline compounds, a 1:1 protic salt, [H(1‐mim)][4,5‐DCNIm], and a 1:2 salt co‐crystal, [H(1‐mim)][4,5‐DCNIm]?4,5‐DCNIm, were isolated and structurally characterized, while differential scanning calorimetry revealed both suppression of crystallization and the presence of neutral and anionic species in the melt. Reactions of Cu(NO3)2?2.5 H2O, CuO, and ZnO with the neat 2:1 1‐mim/4,5‐DCNIm melt resulted in the isolation of entirely N‐donor ligated complexes of the formula M(4,5‐DCNIm)2(1‐mim)4 (M=Cu, Zn). 相似文献
Native mass spectrometry (MS) with electrospray ionization (ESI) has evolved as an invaluable tool for the characterization of intact native proteins and non-covalently bound protein complexes. Here we report the structural characterization by high resolution native top-down MS of human thrombin and its complex with the Bock thrombin binding aptamer (TBA), a 15-nucleotide DNA with high specificity and affinity for thrombin. Accurate mass measurements revealed that the predominant form of native human α-thrombin contains a glycosylation mass of 2205 Da, corresponding to a sialylated symmetric biantennary oligosaccharide structure without fucosylation. Native MS showed that thrombin and TBA predominantly form a 1:1 complex under near physiological conditions (pH 6.8, 200 mM NH4OAc), but the binding stoichiometry is influenced by the solution ionic strength. In 20 mM ammonium acetate solution, up to two TBAs were bound to thrombin, whereas increasing the solution ionic strength destabilized the thrombin–TBA complex and 1 M NH4OAc nearly completely dissociated the complex. This observation is consistent with the mediation of thrombin-aptamer binding through electrostatic interactions and it is further consistent with the human thrombin structure that contains two anion binding sites on the surface. Electron capture dissociation (ECD) top-down MS of the thrombin–TBA complex performed with a high resolution 15 Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer showed the primary binding site to be at exosite I located near the N-terminal sequence of the heavy chain, consistent with crystallographic data. High resolution native top-down MS is complementary to traditional structural biology methods for structurally characterizing native proteins and protein–DNA complexes.
Polycaprolactone (PCL) is widely used in biomedical applications as electrospun fibers or porous foams. As PCL is synthetic polymer, many researchers have explored blends of PCL–gelatin to combine mechanical and bioactive properties of individual components. High pressure carbon dioxide (CO2) has been studied to foam and impregnate many biocompatible polymers. In case of PCL–gelatin blends, certain compositions can be swelled reversibly under high pressure CO2 without permanent deformation. This allows successful impregnation of PCL–gelatin blends under CO2. This study summarizes effect of different treatments adopted during impregnation process including high pressure CO2 on several blend compositions of PCL–gelatin blends. Stress relaxation, polymer melting and dissolution were observed during several treatments which affects porosity and scaffold structure significantly. Results summarized in this study will aid in optimum selection of PCL–gelatin blend composition for biomedical applications. Furthermore, CO2 solubility in polymers is restricted due to thermodynamic limitations but can be altered in the presence of a co-solvent to produce better foams. PCL can be foamed using supercritical CO2. However, CO2 foaming of PCL–gelatin blend becomes challenging to simultaneous swelling of PCL and compression of gelatin providing blend structural stability. This study has demonstrated ability of supercritical CO2 to foam PCL–gelatin blends in presence of water to create porous structure. These foams were subjected post-fabrication crosslinking and supercritical CO2 without losing porosity of foams. Thus, creating a strategy to use environmentally benign processes to fabricate, crosslink and impregnate porous scaffolds for biomedical applications. 相似文献
Joint models for longitudinal and survival data are routinely used in clinical trials or other studies to assess a treatment effect while accounting for longitudinal measures such as patient-reported outcomes. In the Bayesian framework, the deviance information criterion (DIC) and the logarithm of the pseudo-marginal likelihood (LPML) are two well-known Bayesian criteria for comparing joint models. However, these criteria do not provide separate assessments of each component of the joint model. In this article, we develop a novel decomposition of DIC and LPML to assess the fit of the longitudinal and survival components of the joint model, separately. Based on this decomposition, we then propose new Bayesian model assessment criteria, namely, ΔDIC and ΔLPML, to determine the importance and contribution of the longitudinal (survival) data to the model fit of the survival (longitudinal) data. Moreover, we develop an efficient Monte Carlo method for computing the conditional predictive ordinate statistics in the joint modeling setting. A simulation study is conducted to examine the empirical performance of the proposed criteria and the proposed methodology is further applied to a case study in mesothelioma. Supplementary materials for this article are available online. 相似文献
Boolean functions play an important role in many symmetric cryptosystems and are crucial for their security. It is important to design boolean functions with reliable cryptographic properties such as balancedness and nonlinearity. Most of these properties are based on specific structures such as Möbius transform and Algebraic Normal Form. In this paper, we introduce the notion of Dirichlet product and use it to study the arithmetical properties of boolean functions. We show that, with the Dirichlet product, the set of boolean functions is an Abelian monoid with interesting algebraic structure. In addition, we apply the Dirichlet product to the sub-family of coincident functions and exhibit many properties satisfied by such functions. 相似文献