5-氟-4-脱氧-β-L-尿苷的合成

L-核苷是天然核苷的对映异构体，虽然早在20世纪60年代就有人报道L-核苷的合成，但直到最近人们对它才开始重视．生物活性研究发现，在合成核苷和DNA的酶中，细胞脱氧胞苷激酶(deK)缺乏立体专一性，它可对一些核苷类如3TC，FTC和ddC的2个对映体同时磷酸化，细胞脱氧胞苷激酶不仅可活化胞嘧啶衍生物，而且可活化腺嘌呤类的2个对映体(如D-，L-ddA；D-，L-d4A)．     

A Precise Chemical Strategy To Alter the Receptor Specificity of the Adeno‐Associated Virus

The ability to target the adeno‐associated virus (AAV) to specific types of cells, by altering the cell‐surface receptor it binds, is desirable to generate safe and efficient therapeutic vectors. Chemical attachment of receptor‐targeting agents onto the AAV capsid holds potential to alter its tropism, but is limited by the lack of site specificity of available conjugation strategies. The development of an AAV production platform is reported that enables incorporation of unnatural amino acids (UAAs) into specific sites on the virus capsid. Incorporation of an azido‐UAA enabled site‐specific attachment of a cyclic‐RGD peptide onto the capsid, retargeting the virus to the α_vβ₃ integrin receptors, which are overexpressed in tumor vasculature. Retargeting ability was site‐dependent, underscoring the importance of achieving site‐selective capsid modification. This work provides a general chemical approach to introduce various receptor binding agents onto the AAV capsid with site selectivity to generate optimized vectors with engineered infectivity.     

Hedging entry and exit decisions: optimizing location under exchange rate uncertainty

^** Email: alexru00{at}ms41.hinet.net^*** Email: ctlin{at}mail.yust.edu.tw The Cobb–Douglas production function with Abel's (1983,Am. Econ. Rev., 173, 228–233) model is extended herein,and real options analysis (ROA) for entry–exit decision-makingestablished utilizing Dixit's (1989b) decision model under exchangerate uncertainty. This work considers the effects of real exchangerates on strategies that determine the locations of productionby firms that are entering markets in two countries. The ROAis also adopted to evaluate the switching location between twocountries. A continuous-time model optimization problem is solvedin closed-form. This provides a useful beginning to an importantanalysis of the effects on industry of exchange rate fluctuationswhen the optimal entry (exit) trigger for transferring locationsis important for a basic global logistics model. Furthermore,a myopic solution of the optimal entry (exit) trigger, sensitivityanalysis and some characteristics of the optimal productionstrategy are sought. This paper contributes to the problem ofchoice of foreign production strategy.     

Study of intact virus‐like particles of human papillomavirus by capillary electrophoresis

Virus‐like particles of human papillomavirus (HPV‐VLP), resulting from the self‐assembly of the capsid proteins (L1 or L1 and L2), have been widely used to study HPV as they are similar to the native virion. Moreover, two prophylactic vaccines, Gardasil^® and Cervarix^®, are based on HPV‐VLP L1. Analytical techniques currently used to characterize HPV‐VLP, such as SDS‐PAGE, Western blot, ELISA, are time‐consuming and semiquantitative. In this study, CE was evaluated for the analysis of intact HPV16‐VLP. The usefulness of capillary inner wall coating as well as various BGEs, pH, and detergent additives were investigated. Reproducible HPV‐VLP analysis in CE was achieved using poly(ethylene oxide)‐coated capillary and a BGE containing high salt concentration and low SDS concentration. The developed method enables HPV‐VLP detection in less than 10 min (migration times RSD: 1.6%). The identity of HPV‐VLP peak was confirmed by comparison with a sample obtained from a wild‐type baculovirus and with VLP‐based vaccine, Gardasil^®, after adjuvant dissolution. Finally, we applied the developed methodology to VLP‐based vaccines, demonstrating that CE could be successfully used for vaccine quality control.     

Synthesis and biological evaluation of echinocystic acid derivatives as HCV entry inhibitors

A series of echinocystic acid (EA) 28-COOH derivatives was synthesized, and their anti-HCV entry activity was evaluated by HCVpp and VSVpp entry assay. It was found that some of them showed moderate anti-HCV entry activity, especially compound 12, and these modifications also removed the undesired hemolytic effect.     

Efficiency of MS2 phage and Qβ phage removal by membrane filtration in water treatment: Applicability of real-time RT-PCR method

MS2 phage is currently used as a surrogate to evaluate pathogenic virus removal efficiency by filtration membrane during water treatment. Phage removal is commonly defined upon comparing number of infectious units in permeate with that in feed solution by PFU method. This method may lead to overestimation of the virus removal because of possible occurrence of viruses aggregation.     

Synthesis of benzocycloheptene derivatives as CCR5 antagonists with potent anti-HIV activity

A series of novel benzocycloheptene derivatives have been synthesized.Their structures were confirmed by MS and ^1H-NMR. These compounds exhibited potent anti-HIV-1 activities.     

Effect of bioparticle size on dispersion and retention in monolithic and perfusive beds

Single-component pulse response studies were used to compare the retention and transport behavior of small molecules, proteins, and a virus on commercially available monolithic and perfusive ion-exchangers. Temporal distortion and extra-column effects were corrected for using a simple algorithm based on the method of moments. It was found that temporal distortion is inversely related to the number of theoretical plates. With increasing bioparticle size, retention increased and the transition from a non-eluting to a non-adsorbing state with increasing ionic strength became more abrupt. Both of these observations are qualitatively explained by calculations of particle-surface electrostatic attractive energy. Calculations also suggest that, for sufficiently large bioparticles, such as viruses or cells, hydrodynamic drag can promote elution. Under non-adsorbing conditions, plate height increased only weakly with flow rate and the skew remained unchanged. With increasing retention, plate height increased dramatically for proteins. Plate height was scaled by permeability rather than bead diameter to enable comparison among different stationary phases.     

Review: Carbon nanotube based electrochemical sensors for biomolecules

Carbon nanotubes (CNTs) have been incorporated in electrochemical sensors to decrease overpotential and improve sensitivity. In this review, we focus on recent literature that describes how CNT-based electrochemical sensors are being developed to detect neurotransmitters, proteins, small molecules such as glucose, and DNA. Different types of electrochemical methods are used in these sensors including direct electrochemical detection with amperometry or voltammetry, indirect detection of an oxidation product using enzyme sensors, and detection of conductivity changes using CNT-field effect transistors (FETs). Future challenges for the field include miniaturizing sensors, developing methods to use only a specific nanotube allotrope, and simplifying manufacturing.