We report direct evidence for the control of the oscillator strength of the exciton state in a single quantum dot by the application of a vertical electric field. This is achieved through the study of the radiative lifetime of a single InGaN-GaN quantum dot in a p-i-n diode structure. Our results are in good quantitative agreement with theoretical predictions from an atomistic tight-binding model. Furthermore, the increase of the overlap between the electron and hole wave functions due to the applied field is shown experimentally to increase the attractive Coulomb interaction leading to a change in the sign of the biexcitonic binding energy. 相似文献
Large strain fixed-end torsion of circular solid rubber bars is studied semi-analytically. The analyses are based on various
non-Gaussian network models for rubber elasticity, some of which were proposed very recently. Results are presented in terms
of predicted torque vs. twist curves and axial force vs. twist curves. In some cases, the predicted stress distributions are
also given. The sensitivity of the second-order axial force to the employed models is considered. The predicted results are
compared with experimental results found in the literature. 相似文献
Serum proteins represent an important class of drug and imaging agent delivery vectors. In this minireview, key advantages of using serum proteins are discussed, followed by the particular advantages and challenges associated with employing soluble folate binding protein. In particular, approaches employing drugs that target folate metabolism are reviewed. Additionally, the slow-onset, tightbinding interaction of folate with folate binding protein and the relationship to a natural oligomerization mechanism is discussed. These unique aspects of folate binding protein suggest interesting applications for the protein as a vector for further drug and imaging agent development. 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.
Protein tyrosine phosphatases (PTPs) like dual specificity phosphatase 5 (DUSP5) and protein tyrosine phosphatase 1B (PTP1B) are drug targets for diseases that include cancer, diabetes, and vascular disorders such as hemangiomas. The PTPs are also known to be notoriously difficult targets for designing inihibitors that become viable drug leads. Therefore, the pipeline for approved drugs in this class is minimal. Furthermore, drug screening for targets like PTPs often produce false positive and false negative results.
Results
Studies presented herein provide important insights into: (a) how to detect such artifacts, (b) the importance of compound re-synthesis and verification, and (c) how in situ chemical reactivity of compounds, when diagnosed and characterized, can actually lead to serendipitous discovery of valuable new lead molecules. Initial docking of compounds from the National Cancer Institute (NCI), followed by experimental testing in enzyme inhibition assays, identified an inhibitor of DUSP5. Subsequent control experiments revealed that this compound demonstrated time-dependent inhibition, and also a time-dependent change in color of the inhibitor that correlated with potency of inhibition. In addition, the compound activity varied depending on vendor source. We hypothesized, and then confirmed by synthesis of the compound, that the actual inhibitor of DUSP5 was a dimeric form of the original inhibitor compound, formed upon exposure to light and oxygen. This compound has an IC50 of 36 μM for DUSP5, and is a competitive inhibitor. Testing against PTP1B, for selectivity, demonstrated the dimeric compound was actually a more potent inhibitor of PTP1B, with an IC50 of 2.1 μM. The compound, an azo-bridged dimer of sulfonated naphthol rings, resembles previously reported PTP inhibitors, but with 18-fold selectivity for PTP1B versus DUSP5.
Conclusion
We report the identification of a potent PTP1B inhibitor that was initially identified in a screen for DUSP5, implying common mechanism of inhibitory action for these scaffolds.
To acquire fertilization competence, spermatozoa must undergo several biochemical and motility changes in the female reproductive tract, collectively called capacitation. Actin polymerization and the development of hyperactivated motility (HAM) are part of the capacitation process. In a recent study, we showed that irradiation of human sperm with visible light stimulates HAM through a mechanism involving reactive‐oxygen‐species (ROS), Ca2+ influx, protein kinases A (PKA), and sarcoma protein kinase (Src). Here, we showed that this effect of light on HAM is mediated by ROS‐dependent activation of the epidermal growth factor receptor (EGFR). Interestingly, ROS‐mediated HAM even when the EGFR was activated by EGF, the physiological ligand of EGFR. Light irradiation stimulated ROS‐dependent actin polymerization, and this effect was abrogated by PBP10, a peptide which activates the actin‐severing protein, gelsolin, and causes actin‐depolymerization in human sperm. Light‐stimulated tyrosine phosphorylation of Src‐dependent gelsolin, resulting in enhanced HAM. Thus, light irradiation stimulates HAM through a mechanism involving Src‐mediated actin polymerization. Light‐stimulated HAM and in vitro‐fertilization (IVF) rate in mouse sperm, and these effects were mediated by ROS and EGFR. In conclusion, we show here that irradiation of sperm with visible light, enhances their fertilization capacity via a mechanism requiring ROS, EGFR and HAM. 相似文献
Coating hydrogel films or microspheres by an adsorbed colloidal shell is one synthesis method for forming colloidosomes. The colloidal shell allows control of the release rate of encapsulated materials, as well as selective transport. Previous studies found that the packing density of self-assembled, adsorbed colloidal monolayers is independent of the colloidal particle size. In this paper we develop an equilibrium model that correlates the packing density of charged colloidal particles in an adsorbed shell to the particle dimensions in monodisperse and bidisperse systems. In systems where the molar concentration in solution is fixed, the increase in adsorption energy with increasing particle size leads to a monotonic increase in the monolayer packing density with particle radius. However, in systems where the mass fraction of the particles in the adsorbing solutions is fixed, increasing particle size also reduces the molar concentration of particles in solution, thereby reducing the probability of adsorption. The result is a nonmonotonic dependence of the packing density in the adsorbed layer on the particle radius. In bidisperse monolayers composed of two particle sizes, the packing density in the layer increases significantly with size asymmetry. These results may be utilized to design the properties of colloidal shells and coatings to achieve specific properties such as transport rate and selectivity. 相似文献
We have prepared a range of well-defined copolymers of styrene and L-proline functionalized styrene (5-11 kDa) using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques and explored their use in supported catalysis. Upon deprotection of the L-proline functionalities, the solution self-assembly of these copolymers was investigated in mixed solvent systems. The resulting assemblies were characterized by dynamic light scattering, transmission electron microscopy (on graphene oxide substrates, along with cryo-TEM and tomography), and scanning electron microscopy. The application of these functional assemblies as supported catalysts for the aldol condensation reaction was explored using cyclohexanone and 4-nitrobenzaldehyde. The rate and selectivity of solution catalysis in our self-assembled system were comparable to those of L-proline, and a significant advantage of our system was that the polymer support could be utilized at lower catalyst loadings with comparable activity and also could be recycled a number of times while maintaining activity and selectivity. 相似文献