Water-in-oil Microemulsions and Hydrogel Nanoparticles in Water-in-Oil Microemulsions for Local Intestinal Delivery of Peptides and Proteins

The objectives of the present studies were to develop water-in-oil (W/O) microemulsions (MEs) and hydrogel nanoparticles in W/O MEs for effective local intestinal delivery of peptide and protein drugs. Water-in-oil MEs consisting of Miglyol 812, Capmul MCM, Tween 80 and water were developed and characterized. Selected W/O MEs containing a model peptide, 5-(and-6)-carboxytetramethylrhodamine labeled HIV transactivator protein TAT (TAMRA-TAT), were evaluated both in vitro and in vivo. In vitro enzymatic stability studies showed the half-life (t?1/2?) of TAMRA-TAT in ME was enhanced nearly three-fold compared to that in the water solution when challenged by modified simulated intestinal fluid. In vivo studies in mice showed TAMRA-TAT ME resulted in greater fluorescence intensity in all intestinal sections (duodenum, jejunum, ileum and colon) compared to controls after oral administration. The in vitro and in vivo studies together demonstrated that TAMRA-TAT was better protected in the W/O ME in an enzyme-containing environment, suggesting the W/O MEs developed in this study may serve as a delivery vehicle for local intestinal delivery of peptides or proteins. To further improve the current W/O ME formulations, a thermoreversible gelling polymer Pluronic F127 (PF127) was explored to engineer hydrogel nanoparticles in the W/O MEs. Water-in-oil MEs with 14% PF127 were developed based on viscosity studies and construction of phase diagrams, and then physically characterized at different temperatures. After physical characterization, TAMRA-TAT loaded W/O MEs with 8% and 14% PF127, were evaluated in vitro in enzymatic stability studies. The results showed the t?1/2? of TAMRA-TAT in the W/O ME with 14% PF127 was shorter than that in the W/O ME without PF127. In contrast, the t?1/2? of TAMRA-TAT in the W/O ME with 8% PF127 was almost the same as that in the W/O ME without PF127. This observation was explained by the large increase in droplet diameter, polydispersity index and turbidity of the ME with 14% PF127, which indicated a possible aggregation and precipitation of PF127 from the ME at 37°C. Consequently, the aggregation and precipitation of PF127 might have exposed more TAMRA-TAT associated with it to enzymes, resulting in faster TAMRA-TAT degradation. The formation of hydrogel nanoparticles in the W/O MEs was not completely achieved; further research is necessary to better understand and improve the formulation. In summary, the use of W/O ME systems proposed in this work is an attractive strategy to deliver peptides and proteins orally for the treatment of local intestinal pathologies such as inflammatory bowel diseases.Doctor of Philosoph

Freeze-thaw damage evaluation and model creation for concrete exposed to freeze–thaw cycles at early-age

Concrete subjected to freeze–thaw cycles action at early-age will suffer serious physical damage, resulting in degradation of the concrete’s performance. The subsequent curing conditions after early-age freeze–thaw cycles (E-FTCs) are critical to the development of the properties of frost-damaged concrete. Four test environments were set up for this study, based on different numbers of E-FTCs and subsequent curing conditions. The later-age resistance to freeze–thaw of concrete exposed to E-FTCs was evaluated by analysing the influence of precuring times and curing conditions. Results show that the earlier the FTCs occur, the worse the later-age freeze–thaw resistance is. In particular, for the frost-damaged concrete with a pre-curing time of 18 h, its freeze–thaw resistance is significantlypublishedVersio

Lists of Selected Full-text Databases by Subscription in East Asian Studies

Compilation of e-book, e-journal, and multi-media databases by subscription for East Asian studies and their contents for purpose of annual CEAL Statistics collection assessment.A list of e-book, e-journal, and multi-media databases for East Asian studies compiled by CEAL Statistics for database subscription statisticsCouncil on East Asian Libraries (CEAL) Statistics Committe

Profile-based Maximum Penalised Likelihood Trajectory Estimation from Space-borne LOS Measurements

Estimating the boost-phase trajectory of a ballistic missile using line of sight measurements from space-borne passive sensors is an important issue in missile defense. A well-known difficulty of this issue is the poor-observability of the target motion. A profile-based maximum penalised likelihood estimator is presented, which is expected to work in poor-observability scenarios. Firstly, a more adaptable boost-phase profile is proposed by introducing unknown parameters. Then, the estimator is given based on the Bayesian paradigm. After that, a special penalty for box constraint is constructed based on a mixed distribution. Numerical results for some typical scenarios and sensitivity with respect to a priori information are reported to show that the proposed estimator is promising

Mechanical and durability properties of concrete subjected to early-age freeze–thaw cycles

Early-age frost damage to concrete used in winter construction or in cold environments negatively affects the development of the hydration process and the performance of the concrete, thereby reducing the service life of the building structure. Experimental research was carried out to investigate the compressive strength,resistance to chloride penetration and resistance to freeze–thaw of concrete specimens subjected to earlyage freeze–thaw cycles (E-FTCs). The effects that different pre-curing times of concrete and mineral admixtures have on the properties of early-age frostaffected concrete were also analyzed. Results show that the earlier the freeze–thaw cycles (FTCs), the poorer the later-age performance. Later-age water-curing cannot completely restore the damage that E-FTCs do to concrete. In the same conditions used in this study, the effects of E-FTCs on later-age mechanical and durability properties of ordinary Portland cement concrete (OPC)are small. The incorporation of fly ash significantly reduces the resistance to freeze–thaw of concrete during early-age and later-age. The presence of silica fumes has an adverse effect on the later-age resistance to freeze–thaw. In general, the recovery percentage of later-age durability indexes of concrete subjected to E-FTCs is lower than that of compressive strength. For concrete subjected to E-FTCs, it is more important to ensure the recovery of later-age durability.publishedVersio

BCL11B is required for positive selection and survival of double-positive thymocytes

Transcriptional control of gene expression in double-positive (DP) thymocytes remains poorly understood. We show that the transcription factor BCL11B plays a critical role in DP thymocytes by controlling positive selection of both CD4 and CD8 lineages. BCL11B-deficient DP thymocytes rearrange T cell receptor (TCR) α; however, they display impaired proximal TCR signaling and attenuated extracellular signal-regulated kinase phosphorylation and calcium flux, which are all required for initiation of positive selection. Further, provision of transgenic TCRs did not improve positive selection of BCL11B-deficient DP thymocytes. BCL11B-deficient DP thymocytes have altered expression of genes with a role in positive selection, TCR signaling, and other signaling pathways intersecting the TCR, which may account for the defect. BCL11B-deficient DP thymocytes also presented increased susceptibility to spontaneous apoptosis associated with high levels of cleaved caspase-3 and an altered balance of proapoptotic/prosurvival factors. This latter susceptibility was manifested even in the absence of TCR signaling and was only partially rescued by provision of the BCL2 transgene, indicating that control of DP thymocyte survival by BCL11B is nonredundant and, at least in part, independent of BCL2 prosurvival factors

IKKβ programs to turn on the GADD45α–MKK4–JNK apoptotic cascade specifically via p50 NF-κB in arsenite response

Cross talk between NF-κB and c-Jun N-terminal kinases (JNKs) has been implicated in the cell life and death decision under various stresses. Functional suppression of JNK activation by NF-κB has recently been proposed as a key cellular survival mechanism and contributes to cancer cells escaping from apoptosis. We provide a novel scenario of the proapoptotic role of IκB kinase β (IKKβ)–NF-κB, which can act as the activator of the JNK pathway through the induction of GADD45α for triggering MKK4/JNK activation, in response to the stimulation of arsenite, a cancer therapeutic reagent. This effect of IKKβ–NF-κB is dependent on p50 but not the p65/relA NF-κB subunit, which can increase the stability of GADD45α protein through suppressing its ubiquitination and proteasome-dependent degradation. IKKβ–NF-κB can therefore either activate or suppress the JNK cascade and consequently mediate pro- or antiapoptotic effects, depending on the manner of its induction. Furthermore, the NF-κB p50 subunit can exert a novel regulatory function on protein modification independent of the classical NF-κB transcriptional activity

Root Growth, Water and Nitrogen Use Efficiencies in Winter Wheat Under Different Irrigation and Nitrogen Regimes in North China Plain

Excessive nitrogen (N) application combined with water shortage has a negative effect on crop production, particularly wheat (Triticum aestivum L.) production in the North China Plain. This study examined root growth and water and nitrogen use efficiencies in wheat grown on loam soil in the North China Plain, from 2012 to 2014 using a fixed-position experiment initiated in 2010. The experiment followed a completely randomized split-plot design with four replications, taking irrigation [no irrigation (W0) versus irrigation at jointing plus flowering (W2)] as the main plot and N treatment (0, 180, 240, and 300 kg N ha-1) as the subplot. Compared with W0, W2 increased grain yield and root weight density (RWD) by up to 91.3 and 57.7% in 2012–2013, and 15.5 and 43.0% in 2013–2014, respectively, across all N application rates. Irrigation had no effect on grain water use efficiency (WUEY), but caused a decrease in biomass WUE at vegetative growth stage (WUEF) and at grain-filling stage (WUEM). Significant improvements in grain yield and biomass WUE during vegetative growth stage, and reductions in nitrogen-use efficiency (NUE) and RWD, were observed with increasing N application. Compared with non-N treatment, N treatment increased yield by up to 98.9 and 93.7% in 2012–2013 and 2013–2014, respectively, decreasing RWD by 12.0 and 16.9%. Correlation analysis further revealed that RWD was positively correlated with grain yield, evapotranspiration (ET) and NUE. NUE was also positively correlated with nitrogen uptake efficiency (UPE). Overall, the findings suggest that optimal N application improves NUE by increasing above–ground nitrogen uptake as a result of optimized RWD and a synchronous increase in WUE, thus increasing yield. Under the experimental conditions, an N application rate of 240 kg N ha-1 plus irrigation at jointing and flowering is recommended