Novel functional hyperbranched polyether polyols as prospective drug delivery systems

Multifunctional hyperbranched polyether polyols bearing protective poly(ethylene glycol) (PEG) chains with or without the folate targeting ligand at their end have been prepared. Solubilization in these polymers of a fluorescent probe, pyrene, and an anticancer drug, tamoxifen, was physicochemically investigated. It was found that PEG chains attached at the surface of these hyperbranched polymers, in addition to their well-established protective role, enhance the encapsulation efficiency of the polymers. The release of pyrene and tamoxifen observed upon addition of sodium chloride is, in most of the cases, significant only at concentrations exceeding the physiological extracellular concentration. Thus, a significant amount of the probe or drug remains solubilized inside the carriers, which is an encouraging result if the polymers are to be used for drug delivery.     

Antioxidant Effects of Anthocyanin-Rich Riceberry™ Rice Flour Prepared Using Dielectric Barrier Discharge Plasma Technology on Iron-Induced Oxidative Stress in Mice

Redox-active iron generates reactive oxygen species that can cause oxidative organ dysfunction. Thus, the anti-oxidative systems in the body and certain dietary antioxidants, such as anthocyanins, are needed to control oxidative stress. We aimed to investigate the effects of dielectric barrier discharge (DBD) plasma technology in the preparation of Riceberry™ rice flour (PRBF) on iron-induced oxidative stress in mice. PRBF using plasma technology was rich in anthocyanins, mainly cyanidine-3-glucoside and peonidine-3-glucoside. PRBF (5 mg AE/mg) lowered WBC numbers in iron dextran (FeDex)-loaded mice and served as evidence of the reversal of erythrocyte superoxide dismutase activity, plasma total antioxidant capacity, and plasma and liver thiobarbituric acid-reactive substances in the loading mice. Consequently, the PRBF treatment was observed to be more effective than NAC treatment. PRBF would be a powerful supplementary and therapeutic antioxidant product that is understood to be more potent than NAC in ameliorating the effects of iron-induced oxidative stress.     

Preparation and Evaluation of Novel Folate Isonitrile 99mTc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [^99mTc]Tc-CN5FA and [^99mTc]Tc-CNPFA had specific tumor uptake. Compared with [^99mTc]Tc-CN5FA, the tumor/muscle ratios of [^99mTc]Tc-CNPFA were higher, resulting in a better SPECT/CT imaging background. According to the results, the two ^99mTc complexes have potential as tumor imaging agents to target folate receptors.     

Combined muta- and semisynthesis: a powerful synthetic hybrid approach to access target specific antitumor agents based on ansamitocin P3

Access of four new tumor specific folic acid/ansamitocin conjugates is reported that relies on a synthetic strategy based on the combination of mutasynthesis and semisynthesis. Two bromo‐ansamitocin derivatives were prepared by mutasynthesis or by a modified fermentation protocol, respectively, that served as starting point for the semisynthetic introduction of an allyl amine linker under Stille conditions. A sequence of standard coupling steps introduced the pteroic acid/glutamic acid/cysteine unit to the modified ansamitocins. All new derivatives, including those that are expected to be generated after internalization of the folic acid/ansamitocin conjugates into the cancer cell and reductive cleavage of the disulfide linkage showed good to strong antiproliferative activity (IC₅₀ <10 nM ) for different cancer cell lines. Finally, the four conjugates were exposed to two cancer cell lines [cervix carcinoma, KB‐3‐1 (FR+) and lung carcinoma, A‐459 (FR?)], the latter devoid of the membrane‐bound folic acid receptor (FR?). All four conjugates showed strong antiproliferative activity for the FR+ cancer cell line but were inactive against the FR? cell line. The synthetic strategy pursued is based on the combination of mutasynthesis and semisynthesis and proved to be powerful for accessing new ansamitocin derivatives that are difficult to prepare by total synthesis.     

Synthesis of Folate Conjugated Fluorescent Nanoparticle Probe and Its Application in Cervical Cancer Cell Imaging

Abstract

Cervical cancer is the second most common cancer in women worldwide with 80% of cases arising in the developing world, following cancer of the breast. The mortality associated with cervical cancer can be reduced if this disease is detected in a timely fashion. In this study, a folate conjugated fluorescent nanoparticle (FCFN) probe was used to detect cervical cancer cells. Fluorescent nanoparticles (FNs), with excellent characteristics such as nontoxicity and photostability, were first synthesized with a simple, cost-effective, and environmentally friendly modified St?ber synthesis method and then successfully modified with folate. This kind of fluorescence probe based on FCFNs has been used to detect cervical cancer cells with fluorescence microscopy imaging technology. The experimental results demonstrate that the FCFNs can effectively recognize cervical cancer cells and exhibit good sensitivity and exceptional photostability; they would provide a novel way for the diagnosis and curative effect observation of cervical cancer cells and offer a new method in detecting folate receptors (FR).     

侵彻过载测试信号的数据处理方法

研究了实测侵彻过载数据分析处理方法,提出了对试验弹及测试装置进行模态分析和实测数据频谱分析相结合的方法,选择低通滤波截止频率对测试数据进行滤波,获得相应的刚体过载。用该方法对实测数据进行分析处理得到的刚体过载与柱形空腔膨胀理论（CCET）计算结果吻合较好;对滤波后的刚体过载进行积分得到的弹体侵彻速度和位移与实测结果吻合较好。     

A model for predicting the retardation effect following a single overload

Many engineering components are subjected to variable amplitude loading history. It is well known that retardation in fatigue crack growth occurs due to application of single overloads in a constant amplitude loading block. Many models have been proposed to capture this counter intuitive phenomenon which has resulted in improved understanding of retardation effect following tensile overloads and consequently resulting in better life prediction models. The proposed study is focused on to evaluation of retardation in fatigue life due to application of a single overload. A model for prediction of crack growth and crack growth rate following single overloads is presented. Several modifications to Wheeler’s growth idea are proposed, which incorporate a consideration for effective stress intensity factor, based on Elber’s concept of crack closure, relationship between overload ratio and the Wheeler’s exponent, and fatigue growth rate calculations. The results presented here show that plastic zone interaction following overload and the consideration of crack closure explain retardation effect following a single overload. Correlation between analysis and experimental data obtained from several sources in literature show that the scheme, is robust and provides an insight into the nonlinear aspect of crack growth results. The model has been tested for 2024-T3 aluminum alloy and 6061-T6 aluminum alloy and thorough calibrations performed, established the fidelity of the program.     

Performance of Organizational Design Models and Their Impact on Organization Learning

The performance of various organizational structures is an essential parameter in the reengineering of organizations, particularly in the current rapidly changing, competitive and information technology-dependent environment. This situation has generally resulted in a smaller workforce confronted with voluminous information-processing requirements. Naturally, the focus has been on the design of organzations that will support effective and efficient learning processes. This specific study is on the contingency modely by Ouksel et al. (1997) on the impact of organizational structure on organizational learning and performance. It expands the empirical evaluation of the model to test its robustness. This is done by conducting extensive simulations with (a) a larger number of variables in the decision tasks, and (b) a larger set of numbers for each of the numeric variables, than has been used in the past. Overall, the validity of previous results achieved has been confirmed, but the selection of the most appropriate design, that which will indeed improve learning, is even more nuanced than past studies have concluded.     

GC–MS analysis of organic acids in rat urine: A protocol of direct ultrasound-assisted derivatization

The aim of the present study was to develop a novel ultrasound-assisted derivatization method for analysis of urine that can be used for preliminary screening and monitoring of metabolic disorders. Here we describe an ultrasound-assisted derivatization method followed by GC–MS analysis to quantify 26 organic acids in urine. The optimum levels of the variables affecting the yield of derivatization were investigated, including urease doses, derivatization reagents and derivatization conditions (duration time, reaction temperature and sonic power). The method exhibited the best results with 80 μl urease. The optimal reaction conditions were 100 μl BSTFA, 80% ultrasound power, 70°C and 40 min. This method showed satisfactory linearity, good reproducibility and an acceptable limit of detection and accuracy. Therefore, it could potentially be used to as a standard method to enable comparisons between laboratories. Finally, we applied our method to urine samples from pregnant rats administered 2 or 10 mg/kg folic acid supplementation.     

Control and recovery from rare congestion events in a large multi-server system

We develop deterministic fluid approximations to describe the recovery from rare congestion events in a large multi-server system in which customer holding times have a general distribution. There are two cases, depending on whether or not we exploit the age distribution (the distribution of elapsed holding times of customers in service). If we do not exploit the age distribution, then the rare congestion event is a large number of customers present. If we do exploit the age distribution, then the rare event is an unusual age distribution, possibly accompanied by a large number of customers present. As an approximation, we represent the large multi-server system as an M/G/∞ model. We prove that, under regularity conditions, the fluid approximations are asymptotically correct as the arrival rate increases. The fluid approximations show the impact upon the recovery time of the holding-time distribution beyond its mean. The recovery time may or not be affected by the holding-time distribution having a long tail, depending on the precise definition of recovery. The fluid approximations can be used to analyze various overload control schemes, such as reducing the arrival rate or interrupting services in progress. We also establish large deviations principles to show that the two kinds of rare events have the same exponentially small order. We give numerical examples showing the effect of the holding-time distribution and the age distribution, focusing especially on the consequences of long-tail distributions. This revised version was published online in June 2006 with corrections to the Cover Date.