An improved method for the preparations of nanostructured lipid carriers containing heat-sensitive bioactives

Heat-sensitive bioactive compounds such as β-carotene and tocols, are widely used in the pharmaceutical and cosmetic fields. Their chemical stability in delivery systems is one of the major concerns in the production of nanostructured lipid carriers (NLCs). A previously established high-temperature high-pressure homogenisation technique involved in the preparation of NLCs can cause degradation of heat-sensitive compounds. Therefore, a novel preparation process needs to be developed to minimise the degradation of heat-sensitive active compounds during the preparation of NLCs. In this work, modified methods A and B were designed to minimise the degradation of β-carotene and tocols during the production of NLCs. These methods improved the chemical stability of heat-sensitive bioactive compounds (β-carotene and tocols) significantly compared to the previously established method. The physical stability of the formulation was maintained throughout study duration.     

以硅胶为载体通过γ-胺丙基三甲氧基硅烷偶联剂制备季铵盐类水不溶性杀菌剂的方法研究(II)

在利用硅胶表面上的羟基通过g -胺丙基硅烷把季铵盐固载到硅胶载体上制成水不溶性杀菌剂的基础上,考察了原料硅胶对制备产品杀菌性能的影响。在相同操作条件下,使用同一种原料硅胶,随着原料粒度的减小,所制备杀菌剂产品的杀菌率有所增加,但不明显;选用不同种原料硅胶合成的水不溶性季铵盐类杀菌剂的杀菌结果表明,原料比表面积越大,孔体积越小,合成产品的杀菌率越高。红外光谱证明了 -胺丙基三甲氧基硅烷已通过与硅胶表面羟基的反应键合到硅胶表面,叔胺化的硅胶中间体和产物上存在的很强的烷基峰也证明了硅胶上确实固载上了烷基官能团。交叉极化的硅核磁共振谱有效地表征了硅胶上表面羟基的反应情况,为-106处峰的基本消失证明了原料硅胶表面的硅羟基与胺丙基硅烷的键合反应比较完全。使用后的杀菌剂再生结果表明,其再生性能良好,具备重复使用的特点。     

Functional human 5-HT6 receptor assay for high throughput screening of chemical ligands and binding proteins

Continuous identification and validation of novel drug targets require the development of rapid, reliable, and sensitive cell-based high-throughput screening (HTS) methods for proposed targets. Recently, the 5-HT(6) receptor (5-HT(6)R), a member of the class of recently discovered 5-HT receptors, has received considerable attention for its possible implications in depression, cognition, and anxiety. However, the cellular signaling mechanisms of 5-HT(6)R are poorly understood due to the lack of selective 5-HT(6)R ligands. In the present study, we examined functional coupling of the human 5-HT(6)R, 5-HT(7A)R, or 5-HT(7B)R with various Galpha-proteins (Galpha(15), Galpha(qs5), or Galpha(qG66Ds5)) to develop a reliable cell-based HTS method for 5-HT receptors. Among variable couplings between 5-HT receptors and G-proteins, we found that functional coupling of human 5-HT(6)R with Galpha(qG66Ds5) produced the highest levels of Ca(2+) signaling in HEK293 cells as measured by the fluorescence-based HTS plate reader, FDSS6000. After validation of this new 5-HT(6)R HTS system (Z'-factor = 0.56) in 96-well plates and characterization of the pharmacological profile of the 5-HT(6)R, we screened approximately 500 synthetic chemical compounds including butanamide and benzenesulfonamide derivatives. Based on this preliminary screening, we found that the butanamide derivative LSG11104 produced an IC(50) value of 6.3 microM. This compound will serve as a lead structure for further chemical modification to develop novel 5-HT(6)R ligands. Furthermore, we demonstrated that this HTS method can be utilized to identify proteins that modulate 5-HT(6)R function and present Fyn tyrosine kinase as an example, which is already known as a 5-HT(6)R interacting protein. Taken together, these results suggest that the 5-HT(6)R/Galpha(qG66Ds5) FDSS6000 system can be utilized to screen for selective 5-HT(6)R ligands and to examine any functional relationships between 5-HT(6)R and its binding proteins.     

Oscillation and decay of particle current due to a quench and dephasing in an interacting fermionic system

We study the response of a particle current to dissipative dephasing in an interacting, few body fermionic lattice system. The particles are prepared in the many-body interacting ground state in presence of an artificial magnetic gauge field, which is subsequently quenched to zero. The initial current decays non-trivially in the dissipative environment and we explore the emerging dynamics, time scales and their dependence on the various system parameters.     

Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism

DnaK is a molecular chaperone responsible for multiple aspects of bacterial proteostasis. The intrinsically slow ATPase activity of DnaK is stimulated by its co-chaperone, DnaJ, and these proteins often work in concert. To identify inhibitors we screened plant-derived extracts against a reconstituted mixture of DnaK and DnaJ. This approach resulted in the identification of flavonoids, including myricetin, which inhibited activity by up to 75%. Interestingly, myricetin prevented DnaJ-mediated stimulation of ATPase activity, with minimal impact on either DnaK's intrinsic turnover rate or its stimulation by another co-chaperone, GrpE. Using NMR, we found that myricetin binds DnaK at an unanticipated site between the IB and IIB subdomains and that it allosterically blocked binding of DnaK to DnaJ. Together, these results highlight a "gray box" screening approach, which might facilitate the identification of inhibitors of other protein-protein interactions.     

A note on functions whose local minima are global

In this note, a simple proof of a theorem concerning functions whose local minima are global is presented and some closedness properties of this class of functions are discussed.The authors would like to thank Dr. Tatsuro Ichiishi of CORE for outlining the new proof of Theorem 2.1.This research was done while the author was a research fellow at the Center for Operations Research and Econometrics, University of Louvain, Heverlee, Belgium.     

Finite element scheme for the viscous Cahn-Hilliard equation with a nonconstant gradient energy coefficient

A finite element scheme is considered for the viscous Cahn-Hilliard equation with the nonconstant gradient energy coefficient. The scheme inherits energy decay property and mass conservation as for the classical solution. We obtain the corresponding error estimate using the extended Lax-Richtmyer equivalence theorem.     

Optimal Criterion Weights in Repetitive Multicriteria Decision-Making

In repetitive judgmental discrete decision-making with multiple criteria, the decision maker usually behaves as if there is a set of appropriate criterion weights such that the decisions chosen are based on the weighted sum of all the criteria. Many different procedures for estimating these implied criterion weights have been proposed. Most of these procedures emphasize the preference trade-off among the multiple criteria of the decision maker, and thus the criterion weights obtained are not directly related to the hit ratio of matching decisions. Based on past data, statistical discriminant analysis can be used to determine the implied criterion weights that would reflect the past decisions. The most interesting performance measure is the hit ratio. In this work, we use the integer linear goal-programming technique to determine optimal criterion weights which minimize the number of misclassification of decisions. The linear goal-programming formulation has m constraints and m + k + 1 variables, where m is the number of cases and k is the number of criteria. Empirical study is done by using two different procedures on the actual past admission data of an M.B.A. programme. The hit ratios of the different procedures are compared.     

A conservative nonlinear difference scheme for the viscous Cahn-Hilliard equation

Numerical solutions for the viscous Cahn-Hilliard equation are considered using the crank-Nicolson type finite difference method which conserves the mass. The corresponding stability and error analysis of the scheme are shown. The decay speeds of the solution inH ¹-norm are shown. We also compare the evolution of the viscous Cahn-Hilliard equation with that of the Cahn-Hilliard equation numerically and computationally, which has been given as an open question in Novick-Cohen[13].     

On an optimal control problem involving first order hyperbolic systems with boundary controls

In this paper, we consider an optimal control problem involving a class of first order hyperbolic systems with boundary controls. A computational algorithm which generates minimizing sequences of controls is devised and the convergence properties of the algorithm are investigated. Moreover, a necessary and sufficient condition for optimality is derived and a result on the existence of optimal controls is obtained.