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Ursolic acid (UA) is a potent triterpenoid compound found in plants and fruits with activities modulating key cell signaling pathways involving STATs, NF-κB, and TRAIL. But it's highly hydrophobic and very poorly soluble in nature. It had been prepared as nanocrystals, solid dispersion and loaded in nanoparticles but the achieved systemic exposure and circulation half-life were not ideal. We reported the development of UA-liposomes made by HPβCD assisted active loading. Compared to lipid suspensions of UA (Lipid-UA) with similar lipid composition, the novel process enabled the formation of UA-Ca crystalline structures inside the liposomes and therefore sustained release of UA in vivo. While the UA-liposomes were not generally toxic towards 4T1 triple negative breast cancer cells, they could effectively modulate CD4+CD25+Foxp3+ T cells from 4T1 tumor bearing mouse by inhibiting STAT5 phosphorylation and IL-10 secretion. In vivo administration of UA-liposomes at 10 mg/kg dose led to reduced numbers of myeloid derived suppressor cells (MDSCs) and regulatory T cells (Tregs) residing in tumor tissues. These changes signified the correction of the tumor mediated immune-suppressive microenvironment. The UA-liposomes treatment alone was already effective in deterring tumor growth. Such a formulation may be highly promising as an immunotherapy agent and be combined with chemotherapeutics or targeted drugs.

Drug encapsulated liposomes and monoclonal antibodies (Mabs) are two distinctively different classes of therapeutics, but both aim to become the ultimate "magic bullet". While PEGylated liposomes rely on the enhanced permeability and retention (EPR) effect for accumulation in solid tumor tissues, Mabs are designed to bind tightly to specific surface antigens on target cells to exert effector functions. Immunoliposome (IL) refers to the structural combination of liposomes and antibodies, whereas the antibodies are usually decorated on the liposome surface. ILs can therefore take advantage of interactions between antibodies and cancer cells for more efficient endocytosis and intracellular drug delivery. The antibody structure, affinity, density, as well as the liposome surface properties and drug to lipid ratios all contribute to the IL pharmacokinetic(PK) and pharmacodynamic(PD) behaviors. The optimal formulation parameters may vary for different target cells and tissues. Furthermore, besides the delivery of cytotoxic drugs to cancer cells, new ILs are being developed to interact with multiple target receptors, multiple target cells and trigger multiple therapeutic effects. We envision that the IL format can be a great platform for the molecular engineering of multi-valent, multi-specific interactions to achieve complex biological functions for therapeutic benefits, especially in the area of cancer immunotherapy.

Cell-based drug delivery systems (DDSs) have received attention recently because of their unique biological properties and self-powered functions, such as excellent biocompatibility, low immunogenicity, long circulation time, tissue-homingcharacteristics, and ability to cross biological barriers. A variety of cells, including erythrocytes, stem cells, and lymphocytes, have been explored as functional vectors for the loading and delivery of various therapeutic payloads (e.g., small-molecule and nucleic acid drugs) for subsequent disease treatment. These cell-based DDSs have their own unique in vivo fates, which are attributed to various factors, including their biological properties and functions, the loaded drugs and loading process, physiological and pathological circumstances, and the body's response to these carrier cells, which result in differences in drug delivery efficiency and therapeutic effect. In this review, we summarize the main cell-based DDSs and their biological properties and functions, applications in drug delivery and disease treatment, and in vivo fate and influencing factors. We envision that the unique biological properties, combined with continuing research, will enable development of cell-based DDSs as friendly drug vectors for the safe, effective, and even personalized treatment of diseases.

We developed an anticancer siRNA delivery system (named HLPR) through modular assembly of endogenous molecules. The structure of HLPR was a tightly condensed siRNA-peptide inner core in turn surrounded by the disordered lipid layer and thin HA coating from which the EGFR-targeted amino acid sequences of YHWYGYTPQNVI partially protrude outside of cell surfaces. Both HA and YHWYGYTPQNVI anchored on HLPR were responsible for targeting CD44 and EGFR overexpressed on the tumor cell surfaces, respectively. HLPR was relatively stable in the blood circulation and reached the tumor tissue in vivo through passive and active targeting. Then HLPR entered tumor cells mainly through EGFR-mediated pathway followed by the separation of HA from the remaining parts of nanocomplexes. The HA-uncoated complexes escaped the endosome through the membrane fusion function of DOPE and released cargoes (siRNA and peptide/siRNA) in the cytoplasm. HLPR significantly inhibited the growth of implanted subcutaneous liver tumors without toxicity.

We develop a theoretical model to study investors' trading behavior in the presence of large shareholders' influence on a firm's equity. We show that, for a good stock, large shareholders may invest a higher proportion of their wealth in the firm than smart small investors, although they predict the same equity return. Insight is also cast into the impacts of board structure on the firm's equity when the firm possesses several large influential shareholders: (i) the large shareholders collude in trading, and each tends to invest more aggressively as other large shareholders do, and (ii) firms with sole ownership can outperform those with dispersed ownership, if the impact coefficient of the former case exceeds or coincides with the aggregated impact coefficients of the latter.

Compared with extensive empirical literature on contrarian strategy, we build a dynamic mean-variance model with geometric mean reversion stock price which implies a contrarian strategy. Our model suggests that the investor should buy distressed stocks, and sell them after the company recovers. Simulation and empirical test demonstrate that our model often yields a significant return in a volatile market.

In contrast to traditional financial advising, robo-advising needs to elicit investors’ risk profile via several simple online questions and provide advice consistent with conventional investment wisdom, e.g., rich and young people should invest more in risky assets. To meet the two challenges, we propose to do the asset allocation part of robo- advising using a dynamic mean-variance criterion over the the portfolio’s log-returns. The model yields analytical and time-consistent optimal portfolio policies under jump-diffusion models and regime-switching models.

The optimal growth of a wealth process toward a goal is studied under ambiguous markets with first- and second-order moment uncertainties relating to stock returns. Optimal strategies and value functions are solved explicitly. A verification theorem is proved to show that the results solve the original stochastic control problem. Quantitative analyses of the investment strategies indicate that a rational individual with ambiguity aversion reduces market participation when return and volatility are uncorrelated, while there is an exception for synchronous return and volatility. The welfare of shorting a discounted reward is computed, which demonstrates that in an ambiguous pricing economy, investors can generate a positive premium via appropriate asset allocations.

In this work, the O impurity particle adsorption on the Cs/Mo(110) surface, to determine the influence of O on Cs stability on Mo(110) surface and also the work function of Cs/O/Mo(110) surface, has been investigated by performing density functional theory (DFT). There are four independent adsorption sites on Cs/Mo(110) surface for O atom. No matter which adsorption site O was adsorbed, the surface adsorption energy of Cs increased. O atoms attract more charges due to the difference in electronegativity. Although this weakens the interaction between the Cs and Mo atoms, the O atom does connect them like a bridge, resulting in enhanced adsorption of Cs atom. In our model, the surface work function of Cs/Mo(110) is calculated as 1.835 eV. In some cases, the adsorption of O can dramatically reduce the surface work function to 1.633 eV. Conversely, O may also increase it, but this increase is not pronounced. This result suggests that the appropriate addition of O atoms may be beneficial to the development of high-efficiency negative ion sources.

A direct metal-free method for the synthesis of perfluoroalkylated indolizines by means of DIPEA-promoted tandem C N/C C bond formation was developed. Various substituted pyridines and bromoacetyl derivatives with methyl perfluoroalk-2-ynoates proceeded smoothly in this mild transformation, and the desired products were obtained in good to excellent yields under air.

In this note, we consider the pricing problem for a type of real option, which gives the right to switch investment modes and abandon the investment project before its maturity. The value of this option can be characterized by solutions to multidimensional backward stochastic differential equations (BSDEs) with both normal and oblique reflections, whose coefficients are of linear growth and are left-Lipschitz with respect to (w.r.t) y and Lipschitz w.r.t. z. We provide an existence theorem of minimal solutions for BSDEs in this framework.

In order to support the design and manufacture the cesium (Cs) oven for the prototype negative ion source in the Chinese Fusion Engineering Test Reactor-Negative Ion Based Neutral Beam Injection (CFETR-NNBI) system, an advanced cesium oven is being set up at IFS. The design scheme is proposed based on the characteristics of the prototype negative ion source in the CFETR-NNBI system and combined with the international frontier research related to this aspect. Based on the reference to the Padova cesium oven, this article has designed a dedicated nozzle for the cesium oven and a transport channel more conducive to steam transport. A corrosion-resistant Cs reservoir and delivery tube is utilized. Precise control of cesium flux is achieved via remotely controlled switching valves and heating systems. The surface ionization detector is used to detect the cesium flux of the nozzle. And the thermal stability analysis, thermal transient analysis, thermal stress analysis and thermal deformation analysis were carried out on the design. The feasibility of the design is demonstrated through finite element analysis, which provides a theoretical basis for the next step of manufacturing. The cesium flux of oven is simulated and calculated, which provides reference for the subsequent device testing.

The design activity on the CFQS quasi-axisymmetric stellarator which is conducted as a joint international project is ongoing by National Institute for Fusion Science (NIFS) in Japan and Southwest Jiaotong University (SWJTU) in China. The CFQS magnetic field generating coils consist of sixteen modular coils (MCs) in total with four different types, four poloidal field coils (PFCs), and twelve toroidal field coils (TFCs). In designing fusion devices, eddy currents and electromagnetic (EM) forces on the vacuum vessel (VV) have to be evaluated to verify the mechanical confidence and reliability. In this work, we consider the following three issues, (1) Influence of eddy current induced by external coil current change on the CFQS magnetic confinement, (2) Evaluation of EM force on VV by eddy current under a typical current of the MC and the PFC, and (3) Feasibility check of whether it is possible to heat the CFQS VV by using induction current.

Trivalent cerium (Ce(Ⅲ)) was demonstrated to have great potential for phosphate (P) removal. Besides the valence states, the relationship of nano-structure and adsorption capacity needs further study to explore more efficient adsorbents. Herein, a series of Ce(Ⅲ)-terephthalate (BDC) metal-organic framework (MOF) with linker deficiencies are fabricated to achieve excellent P capture. The defective density can be increased by decreasing the reaction time and the ratio of organic linkers/metal. TGA reveals Ce-BDC-48 synthesized with BDC:Ce ratio of 1:1 for 48 h possessed 2.5 missing linkers per inorganic node. And the P uptake of Ce-BDC-48 was 35% higher than that of Ce-BDC-72 without defects. The maximum adsorption capacity of Ce-BDC-48 was 278.8 mg/g for P and 128.0 mg/g for fluoride (F), respectively. The adsorption mechanism illustrates that both P and F mainly focus on the Ce(Ⅲ) active sites to achieve ligand exchange. The competing adsorption of P and F at the lower concentration of F (50 mg/L) indicates that the interference of F for P removal is insignificant on account of the selective preferential order of P. However, with the increment of F concentration (100 mg/L), amount of F with small sizes gathering around the adsorbent surface enlarge the steric hindrance to hinder the access of P, leading to the sharp decline of P uptake. This study not only provides promising candidate by the design of structural defects for the P removal in practical application but also give a deep analysis on the adsorption mechanism of P with competing F surrounded.

As sucrose esters (SEs) are natural and biodegradable excipients with excellent drug dissolution and drug absorption/permeation in controlled release systems, we firstly incorporated SE into liposomes for gene delivery in this article. A peptide-based lipid (CDO14), Gemini-based quaternary ammonium-based lipid (CTA14), and mono-head quaternary ammonium lipid (CPA14), and SE as helper lipid, were prepared into liposomes which could enhance the interactions between liposomes and pDNA. Most importantly, the liposomes with helper lipid SE showed higher transfection and lower cytotoxicity than those without SE in Hela and A549 cells. It was also found that the transfection efficiency increased with the increase of SE content. The selected liposome, CDO14/SE, was able to deliver siRNA against luciferase for silencing gene in lung tumors of mice, with little in vivo toxicity. The results convincingly demonstrated SEs could be highly desirable candidates for gene delivery systems.

The electronic structure and associated chemical characteristics of metal-based adsorbent are directly relevant to the selectivity and efficiency of phosphate uptake. However, few studies focus on the nature of metal centers’ electronic orbit (i.e., the coordination number and valence state). Herein, we report a coordinatively unsaturated Ce(III)-based materials, which exhibits excellent potential in effective phosphate removal. Via controlled partial thermolysis and the following reduction process, the valence state and coordination number of original Ce(III)-MOF (denoted as CM) can be tuned and optimized. The manufacture of more coordination vacancy was fulfilled through total release of solvent molecules under annealing at 300 °C in air. Meanwhile, the reduction procedure could precisely tuned the ratio of Ce(III)/Ce(IV). The result shows that samples only annealed induce a sharp decrease of the phosphate capacity due to the high amount of Ce(IV) state. After the reduction process, the XPS spectra reveal the growth of oxygen vacancy content calculated as 11.6% and the increase of Ce(III)/Ce(IV) values from 0.79:1 to 1.36:1. Based on those great improvement of the unsaturated coordination numbers and the recovery of Ce(III) content for metal centers, the maximum capacity of CM-300(R) to adsorb phosphate is up to 273 mg/g, 2.6 times larger than that of pristine CM. Those new insights provide a novel strategy for synthesizing a highly active adsorbent by controlling the electronic structure of metal centers for efficient phosphate removal.

We propose adjusted quasi score (AQS) tests for testing the existence of temporal heterogeneity in slope and spatial parameters in spatial panel data (SPD) models, allowing for the presence of individual-specific and/or time-specific fixed effects (or in general intercept heterogeneity). The SPD model with spatial lag is treated in detail by first considering the model with individual fixed effects only, and then extending it to the model with both individual and time fixed effects. Two types of AQS tests (naive and robust) are proposed, and their asymptotic properties are presented. These tests are then fully extended to SPD models with both spatial lag and spatial error. Monte Carlo results show that the robust tests have much superior finite and large sample properties than the naive tests. Thus, the proposed robust tests provide reliable tools for identifying possible existence of temporal heterogeneity in regression and spatial coefficients. Empirical applications of the proposed tests are given.

The structural, elastic constants, mechanical properties and thermodynamic properties of WTi, WV, W2Zr, WVTi and WVZr alloys were investigated in this paper by using first-principles calculation based on density functional theory(DFT). Bulk modulus, shear modulus, radio B/G, Poisson's ratio and Young’s were derived from elastic data Cij. And the Debye temperature, melting point and minimum thermal conductivity can be obtained by empirical formulas. The Vickers hardness and Cauchy pressure of WTi, WV, W2Zr, WVTi and WVZr alloys were also calculated in this work. This work provides a theoretical basis for employing and further developing WTi, WV, W2Zr, WVTi and WVZr alloys.

A series of hierarchical micro/nano Ce-based composites were derived from Ce-MOF via thermal treatment in N2 atmosphere. Different from conventional complete decomposed materials, forming cerium oxide in air, Ce-MOF that calcinated in N2 at lower temperatures (400 °C or 500 °C) showed a partial thermal decomposition with high percent content of Ce(III). Even though the complete decomposed products held higher surface areas, the partial decomposed samples exhibited extremely higher phosphate uptake, with working capacity 2–4 times higher than that of ceria. The results implied a predominant effect of different valence states on phosphate removal by Ce-based materials, in which Ce(III) species were demonstrated playing the major role to form binding with phosphate. The maximum adsorption capacity (189.4 mg/g) was achieved by Ce-MOF-500(S) with wide applicable scope of pH ranging from 2 to 12 and great selectivity for phosphate in the presence of competing anions. Remarkably, Ce-MOF-500(S) described obvious enhanced phosphate adsorption ability under alkaline condition. This was due to the fact that the hydrolyzed Ce(III) species brought more active sites in the form of hydroxyl groups for ligand exchange with phosphate. Furthermore, based on the analysis of FTIR, XPS, XRD and zeta potential, electrostatic attraction, ligand exchange and surface precipitation were confirmed as the main adsorption mechanisms for partial decomposed samples, while electrostatic attraction was the main mechanism for complete decomposed samples.

Brown adipose tissue (BAT) plays important roles in regulating energy homeostasis and combating obesity. Accordingly, increasing the abundance and/or activating BAT would be effective and promising approaches to combat obesity and obesity-relative diseases. Our previous data in vitro have shown that osteopontin (OPN) induces the brown adipogenesis in 3T3-L1 cells via a phosphatidylinositol 3 kinase (PI3K)-AKT pathway. However, it is currently unknown whether OPN exerts such an effect on animals in vivo. Therefore, in the study we sought to investigate the pro-browning effects of OPN and to explore its underlying mechanisms by transfecting with Ad-GFP-aP2-OPN-shRNA to specifically down-regulate the OPN of white adipose tissue (WAT) in mice. Our present results show that downregulation of OPN in WAT exacerbates obesity and inhibits WAT-browning. Moreover, immunohistochemical results also exhibit that the downregulation of OPN significantly diminishes the expression and sub-cellular localization of UCP-1, PRDM16 and PGC-1α. Besides, the western blotting results reveal that the expression levels of PI3K, AKT-pS473 and PPARγ markedly reduce. Consequently, we conclude that the downregulation of OPN inhibits the browning of WAT through inhibiting the expression of PPARγ mediated by the PI3K-AKT pathway. The findings suggest that OPN is involved in regulation of WAT-browning and regulating its expression would become a potential strategy to combat obesity and obesity-relative metabolic diseases.

We have constructed Herceptin-conjugated, paclitaxel (PTX) loaded, PCL-PEG worm-like nanocrystal micelles (PTX@PCL-PEG-Herceptin) for the combinatorial therapy of HER2-positive breast cancer that exploit the specific targeting of Herceptin to HER2-positive breast cancer cells. Firstly, amphiphilic PCL2000-MPEG2000 and PCL5000-PEG2000-CHO were selected as the optimized matrix to wrap PTX that self-assembled into worm-like micelles with internal nanocrystal structures (PTX@PCL-PEG). Then the aldehydes of PCL5000-PEG2000-CHO exposed on the outside surface of PTX@PCL-PEG were utilized to react with the primary amines of Herceptin and formed stable, carbon-nitrogen single linkers (–C–N–) between the antibodies and nanoparticles. This study shows PTX@PCL-PEG-Herceptin remained relatively stable in the circulation and in the tumor microenvironment, and rapidly targeted and entered into the HER2-overexpressing tumor cells while sparing normal tissues from the toxic effects. PTX@PCL-PEG-Herceptin shrank the tumors and prolonged survival time in a SKBR-3-tumor-xenograft, nude mice model more effectively than TAXOL®, PTX@PCL-PEG, Herceptin+TAXOL® and Herceptin+PTX@PCL-PEG. Mechanistic studies showed that PTX@PCL-PEG-Herceptin entered into the HER2-positive tumor cells through the caveolin-mediated pathway. The conjugated Herceptin greatly enhanced the binding ability of the nanoparticle to the targeted SKBR-3 cells. This novel strategy provides a rational and simple antibody-conjugated-nanoparticle platform for the clinical application of combinatorial anticancer treatment.

We propose a dynamic portfolio choice model with the mean-variance criterion for log-returns. The model yields time-consistent portfolio policies and is analytically tractable even under some incomplete market settings. The portfolio policies conform with conventional investment wisdom (e.g. richer people should invest more absolute amount of money in risky assets; the longer investment time horizon, the more proportional amount of money should be invested in risky assets; and for long-term investment, people should not short sell major stock indices whose returns are higher than the risk-free rate), and the model provides a direct link with the CRRA utility maximization in a complete market.

A kind of worst-case value-at-risk, GVaR, is defined to measure risk incorporating model uncertainty. Compared with most extant notions of worst-case VaR, GVaR can be computed by an explicit formula, and can be applied to large portfolios of several hundreds dimensions with low computational cost. It is robust for, but not limited to a set of VaRs based on normal distributions. We also reveal connections to robust portfolio optimization, which provides a tractable way to give optimal allocations under market ambiguity. Empirical analysis demonstrates that GVaR is a reliably robust risk measure.

A practical and economical process for the synthesis of perfluoroalkylated biphenyl derivatives has been developed. The three-component reaction of aromatic ketones, malononitrile and methyl perfluoroalk-2-ynoates gave the desired products in good to excellent yields via a one-pot two-step process.

The necessary condition is derived for optimal control with multiple priors which are mutually singular. The tool we use is the theory of G -expectation.

The angiopoietin–Tie2 binding and related signal transduction pathways are crucial for vascular angiogenesis, blood vessel integrity and maturation. In this study, we preformed a virtual screening of small molecules targeting to Tie2. The binding site was selected at the extracellular ligand binding region of Tie2, rather than its conventional endocellular ATP binding region. It was found that loperamide, a widely-used antidiarrhea drug, was among the top hits. The binding between loperamide and Tie2 was confirmed by surface plasmon resonance (SPR) assay. Loperamide competitively inhibited the binding of both angiopoietin1 and angiopoietin2. These results indicate that loperamide is an antagonist of angiopoietin1 and angiopoietin2.

Loperamide, an antidiarrhea drug, is a peripheral opiate agonist. Some other opiate agonists have been shown to promote cell apoptosis. In this research, we studied the apoptosis-inducing and cytotoxic activities of loperamide. MTT assay was used to determine its cytotoxicity on nine established human tumor cell lines. Cell apoptosis was detected by flow cytometry. Hypodiploid cells and cell cycles were analyzed by propidium iodide (PI) staining, while early apoptotic cells were detected by annexin V-FITC/PI staining. It was found that loperamide could inhibit the proliferation of the tested tumor cell lines. The IC₅₀ values for SMMC7721, MCF7, SPC-A1, SKOV3-DDP, H460, HepG2, SGC7901, U2OS, and ACHN cells were 24.2±2.1 μM, 23.6±2.5 μM, 25.9±3.1 μM, 27.1±2.5 μM, 41.4±2.1 μM, 23.7±1.3 μM, 35.4±3.5 μM, 11.8±2.8 μM, and 28.5±3.4 μM, respectively. Loperamide was more effective to the human osteosarcoma U2OS cells with an IC₅₀ value of 11.8±2.8 μM. Meanwhile, it could induce cell apoptosis and cause G2/M-phase cell cycle arrest. The apoptotic cells could be found when treating with loperamide for 6h and most of them belonged to early apoptosis. In loperamide-treated cells, activation of caspase-3 was found, namely that caspase-3 was involved in the loperamide-induced apoptosis. The results of these studies indicate that loperamide is a potential antitumor agent. To our knowledge, this is the first report on antitumor activity of loperamide.

Traditional phosphodiester lipid vesicles (liposomes) are not stable and could be easily degraded in the gastrointestinal (GI) tract. We prepared a novel lipid based oral delivery system: archaeosomes, made of the polar lipid fraction E (PLFE) extracted from Sulfolobus acidocaldarius, and tested their immunogenic potentials as oral vaccine delivery vehicles. Our study showed that the archaeosomes had significant superior stability in simulated gastric and intestinal fluids, and would help fluorescent labeled antigens to reside longer time in the GI tract after oral administration. The resulted immune responses against model antigen ovalbumin (OVA) were greatly improved, eliciting substantial IgG response systemically as well as IgA response mucosally. In addition, the archaeosomes also facilitated antigen specific CD8(+) T cell proliferation. These data indicate that archaeosomes may be a potential vaccine carrier and adjuvant for effective oral immunization.

Silicon electrode with sandwich structure as anode of lithium ion batteries is fabricated by adding a carbon layer between current collector and active coating. The prepared silicon electrode with the sandwich structure can exhibit high reversible capacity of 2500 mAh g −1 for 30 cycles, which is much higher than that of bare silicon electrode with normal structure. The electrochemical impedance spectroscopy and electrode morphologies characterizations show that the improved performance of sandwich electrode is attributed to the carbon layer, which not only enhances the electric conductivity at the current collector/active coating interface but also releases the rigid stress caused by volume change of silicon. The results demonstrate that such sandwich structure is a potential facile method for performance improvement of silicon-based anode compared with the previous reports.

The nano-silicon connected by a nest-like polyaniline (PANi) was simply synthesized by a chemical polymerization process. The cycle stability and rate performance of the Si/PANi composite were greatly enhanced compared with the pristine nano-silicon. The improved electrochemical characteristics are attributed to the volume buffering effect as well as effective electronic conductivity of the nest-like polyaniline, and lower aggregation of the nano-silicon. Keywords: Lithium ion battery, Anode, Nano-silicon, Polyaniline, Rate performance

An annealing method has been reported for silicon anode based on polyvinylidene fluoride (PVDF) binder. High initial coulombic efficiency of 75.6% and a stable reversible capacity of 715.6 mAh g−1 for 50 cycles have been obtained after annealing process. Such improvements are attributed to the enhanced cohesive ability of PVDF and the compact morphology of the electrode reconstructed by annealing, which improves the electronic contacts of silicon particles and stabilizes the electrode structure effectively. It is demonstrated that such annealing method is very economic and effective for performance improvement of silicon anode.

Oral administration of peptide and protein drugs faces a big challenge partly due to the hostile gastrointestinal (GI) environment. Lipid-based delivery systems are attractive because they offer some protection for peptides and proteins. In this context, we prepared a special lipid-based oral delivery system: archaeosomes, made of the polar lipid fraction E (PLFE) extracted from Sulfolobus acidocaldarius, and explored its potential as an oral drug delivery vehicle. Our study demonstrates that archaeosomes have superior stability in simulated GI fluids, and enable fluorescent labeled peptides to reside for longer periods in the GI tract after oral administration. Although archaeosomes have little effect on the transport of insulin across the Caco-2 cell monolayers, the in vivo experiments indicated that archaeosomes containing insulin induced lower levels of blood glucose than a conventional liposome formulation. These data indicate that archaeosomes could be a potential carrier for effective oral delivery of peptide drugs.

How to reconstruct the scene (a visible surface) from a set of scattered, noisy and possibly sparse range data is a challenging problem in robotic navigation and computer graphics. As most real scenes can be modeled by piecewise smooth surfaces, traditional surface fitting techniques (e.g. smoothing spline) generally can not preserve sharp discontinuities of surfaces. Based on sparse approximation of piecewise smooth functions in frame domain, we propose a new tight frame based formulation for reconstructing a piecewise smooth surface from a sparse range data set, which is robust to both additive noise and outliers. Furthermore, the resulting minimization problem from our formulation can be efficiently solved by the split Bregman method [1] , [2] . The numerical experiments show that the proposed approach is capable of reconstructing a piecewise smooth surface with sharp edges from sparse range data corrupted with noise and outliers.

Integrins play critical roles in the process of angiogenesis and are attractive targets for anticancer therapies. It is desirable to develop new types of small-molecule inhibitors of integrin. Herein, the binding features of several inhibitors to integrin alpha(v)beta(3) have been studied by surface plasmon resonance (SPR) biosensor technology and molecular docking analyses. The SPR results indicated that the equilibrium dissociation constant (K(D)) values are evaluated for the inhibitors and showed that the K(D) value of cyclopeptide c-Lys is much lower than the reference molecule. In addition, the 3D structural model of integrin alpha(v)beta(3) was generated according to the crystal structure of the integrin alpha(v)beta(3) complex, and the molecular docking simulation analyses revealed that the predicted binding sites for the most active cyclopeptide c-Lys were consistent with the reported structure. These results thus implied that cyclopeptide c-Lys could be developed as a novel inhibitor for integrin alpha(v)beta(3). The current work has potential for application in structure-based integrin alpha(v)beta(3) inhibitor discovery.

Echogenic bubble formulations have wide applications in both disease diagnosis and therapy. In the current study, nanobubbles were prepared and the contrast agent function was evaluated in order to study the nanosized bubble's property for ultrasonic imaging. Coumarin-6 as a model drug was loaded into nanobubbles to investigate the drug delivery potential to cells. The results showed that the nanobubbles composed of 1% of Tween 80, and 3 mg/ml of lipid worked well as an ultrasonic contrast agent by presenting a contrast effect in the liver region in vivo. The drug-loaded nanobubbles could enhance drug delivery to cells significantly, and the process was analyzed by sigmoidally fitting the pharmacokinetic curve. It can be concluded that the nanobubble formulation is a promising approach for both ultrasound imaging and drug delivery enhancing.

The problem of fitting a nice curve or surface to scattered, possibly noisy, data arises in many applications in science and engineering. In this paper we solve the problem using a standard regularized least square framework in an approximation space spanned by the shifts and dilates of a single compactly supported function ϕ. We first provide an error analysis to our approach which, roughly speaking, states that the error between the exact (probably unknown) data function and the obtained fitting function is small whenever the scattered samples have a high sampling density and a low noise level. We then give a computational formulation in the univariate case when ϕ is a uniform B-spline and in the bivariate case when ϕ is the tensor product of uniform B-splines. Though sparse, the arising system of linear equations is ill-conditioned; however, when written in terms of a short support wavelet basis with a well-chosen normalization, the resulting system, which is symmetric positive definite, appears to be well-conditioned, as evidenced by the fast convergence of the conjugate gradient iteration. Finally, our method is compared with the classical cubic/thin-plate smoothing spline methods via numerical experiments, where it is seen that the quality of the obtained fitting function is very much equivalent to that of the classical methods, but our method offers advantages in terms of numerical efficiency. We expect that our method remains numerically feasible even when the number of samples in the given data is very large.

The geometric and electronic structure of Li15Si4 is studied as the full-lithiated phase of Si anode by first principle calculations within the framework of the density functional theory. The results reveal that the volume change of Si host after Li-intercalation is 269.3%. Besides, the Si host shows metallic properties with the Fermi level crossing the partial-occupied bands after Li intercalation and the chemical bands of Li–Si are found to be polar covalence with some ionicity caused by the partial electron transfer from Li to Si atoms. Further, the deterioration factor of Si anode is analyzed theoretically to be the flaking of active Si off the current collector, which is in agreement with the experimental knowledge. The average intercalation voltage is also calculated to be 0.304 V which is close to the experimental value 0.1–0.2 V. Moreover, the results demonstrate that the theoretical quantum computations could be a meaningful tool in the research field of Si-based anode.

A simple and mild synthesis of a new family of cyclopeptide analogues cyclo[-Arg-Gly-Asp-Ψ(triazole)-Gly-Xaa-] that is obtained by cyclization with click chemistry was investigated. In addition, the method was also successfully expanded to the synthesis of their analogues of different ring sizes. The result supports the potential utility of click chemistry in the preparation of novel integrin domain-binding antagonists and other cyclopeptide analogues.

Cationic polymers including polylysine (PLL) and polyethylenimine are being widely tested as gene delivery vectors in various gene therapy applications. In many cases, the polymers were further modified by hydrophilic polymer grafting or ligand conjugation, which had been shown to greatly affect the vector stability, delivery efficiency and specificity. The characterization of modified polycation is particularly critical for quality control and vector development. Here several different separation modes using capillary electrophoresis for the analytical characterization of the modified polymers are described. PLL molecules were grafted with poly(ethylene glycol) (PEG) chain or conjugated with epidermal growth factor and analyzed under various analytical conditions. Poly(N,N'-dimethylacrylamide)-coated capillary was used to analyze the modified PLL to reduce the interaction between the samples and the capillary wall. PLLs containing different numbers of conjugated ligands were well separated with the coating method but, for PLL-g-PEG, the separation was poor under the same conditions. A method using low buffer pH and hydroxypropylmethyl cellulose additive was developed. These methods are useful to characterize various polycations and important for the quality control and application of potential gene delivery vectors.

In vivo plasmid DNA electroporation resulted in elevated and lasting transgene expression in skeletal muscles. But the nature of the cells that contributed to sustained gene expression remains unknown. We followed the fate of plasmid DNA delivered with electroporation and systematically investigated the time course and location of transgene expression in muscle tissues both with GFP and luciferase. Furthermore, satellite cell activation after electroporation was confirmed by RT-PCR and immunohistochemistry analysis. The activated satellite cells were shown to be able to uptake the injected plasmid DNA and express transgene products as regenerated myocytes. We found that cells with longer gene expression durations were mostly regenerated muscle fibers. In contrast, expression in pre-existing muscle fibers was rather transient. We also presented in this study that immune response to transgene products might hamper the lasting gene expression. Based on these observations, we proposed that the underlying mechanism for prolonged transgene expression in the muscles after electroporation is related to the activation and transfection of myogenic satellite cells which subsequently developed into regenerated muscle fibers.

The surface properties of the extracellular matrix play vital roles in cellular behavior such as adhesion, spreading, migration, proliferation and differentiation. While cell attachment and adhesion onto surfaces are mainly mediated by surface molecular interaction, cell morphology and orientation are significantly affected by the topographical cues of the substrate. We reported here the alignment of C6 glioma cells on polystyrene (PS) substrate containing periodic nanotopography. The ridge/groove type structures (210 nm in periodicity, and 30-40 nm in depth) were generated on polystyrene surface using Nd:YAG polarized laser radiation at 266 nm. The cultured cells were shown to align strictly along the direction of the ridges/grooves. And there were distinctive features such as elongated morphology and asymmetrical cell surface extensions, revealed by confocal laser scanning microscopy (CLSM), atomic force microscopy (AFM), and scanning electron microscopy (SEM). The results indicated that ordered and continuous nanostructures on substrates can pattern cell, and guide cell alignment and oriented growth along definite directions. The possible mechanism and significance of these observations were also discussed.

In this paper I investigate financial markets with drift and volatility uncertainties. Appropriate definitions of arbitrage for super and sub-hedging strategies are presented such that the super and sub-hedging prices are reasonable. Especially the condition of arbitrage for sub-hedging strategy fills the gap of the theory of arbitrage under model uncertainty. The Profit&Loss (P&L for short) of super(sub)-hedging is derived to be in fact the penalty term K with finite-variance arising in the super(sub)-hedging strategy. The ask-bid spread is hence an accumulation of the superhedging P&L and the subhedging P&L.Asset allocation under constant absolute risk aversion (CARA) utility is investigated with ambiguous volatility and subjective risk premium. I show that ambiguity aversion of a rational individual decreases her market participation. The aggregate premium is computed explicitly which is decomposed into three parts. Opposite signs between the rates of ambiguity premium and risk premium demonstrate that a decrease in ambiguity premium on volatility gives rise to an increase in risk premium.Kelly criterion for the wealth process to reach a goal is also studied under such ambiguous market. Ambiguity of stock appreciation rate results in investors' withdraw from markets whereas in a single-priced market, investors always trade with the market if no short-sale constraints and no transaction cost.

The Rho family of small GTP-binding proteins plays important roles in the regulation of actin cytoskeleton organization and cell growth. Activation of these GTPases involves the replacement of bound GDP with GTP, a process catalyzed by the Dbl-like guanine-nucleotide exchange factors, all of which seem to share a putative catalytic motif termed the Dbl homology (DH) domain, followed by a pleckstrin homology (PH) domain. Here we have examined the role of a Dbl-like molecule, the faciogenital dysplasia gene product (FGD1), which when mutated in its Dbl homology domain, cosegregates with the developmental disease Aarskog-Scott syndrome. We report that a polypeptide of FGD1 encompassing the DH and PH domains can bind specifically to the Rho family GTPase Cdc42Hs and stimulates the GDP-GTP exchange of the isoprenylated form of Cdc42Hs. Microinjection of this FGD1 polypeptide into Swiss 3T3 fibroblast cells induces the formation of peripheral actin microspikes, similar to that previously observed when cells were injected with a constitutively active form of Cdc42Hs. This effect of FGD1 on actin organization is readily inhibited by coinjection of a dominant-negative mutant of Cdc42Hs. Examination of NIH 3T3 cells expressing the FGD1 fragment revealed that similar to cells expressing Dbl, two independent elements downstream of Cdc42Hs, the Jun NH2-terminal kinase and the p70 S6 kinase, became activated. Hence, our results indicate that FGD1, through its DH and PH domains, acts as a Cdc42Hs-specific guanine-nucleotide exchange factor and suggest that the Cdc42Hs GTPase may have a role in mammalian development.