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Using a panel of democracies from 1987 to 2016, this study examines the effect of a defective democracy on the political budget cycle. To separate defective democracies from embedded democracies, we apply cluster analysis to the central elements of democracy. We find that the political budget cycle is significant only in defective democracies. Our finding indicates that the electoral cycle can persist even though democracies become old and economies become advanced. We also find that, of the central elements of democracy, weak rule of law and an ineffective government mainly explain the political budget cycle in defective democracies.

A high level of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2) upregulates pro-inflammatory cytokines and inhibits the osteogenic differentiation of mesenchymal stem cells (MSCs), which are key factors in bone regeneration. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has antioxidant and anti-inflammatory activities and also plays beneficial roles in bone regeneration by stimulating the osteogenic differentiation of MSCs while suppressing their adipogenic differentiation. Despite its remarkable capacity for bone regeneration, multiple injections of UDCA induce adverse side effects such as mechanical stress and contamination in bone defects. To fully exploit the beneficial roles of UDCA, a concept polymeric prodrug was developed based on the hypothesis that removal of overproduced H2O2 will potentiate the osteogenic functions of UDCA. In this work, we report bone regenerative nanoparticles (NPs) formulated from a polymeric prodrug of UDCA (PUDCA) with UDCA incorporated in its backbone through H2O2-responsive peroxalate linkages. The PUDCA NPs displayed potent antioxidant and anti-inflammatory activities in MSCs and induced osteogenic rather than adipogenic differentiation of the MSCs. In rat models of bone defect, the PUDCA NPs exhibited significantly better bone regeneration capacity and anti-inflammatory effects than equivalent amounts of UDCA. We anticipate that PUDCA NPs have tremendous translational potential as bone regenerative agents.

Inflammatory responses associated with ischemia/reperfusion injury (IRI) play a central role in alloimmunity and transplant outcomes. A key event driving these inflammatory responses is the burst of reactive oxygen species, with hydrogen peroxide (H(2)O(2)) as the most abundant form that occurs as a result of surgical implantation of the donor organ. Here, we used a syngeneic rat renal transplant and IRI model to evaluate the therapeutic properties of APP-103, a copolyoxalate molecule containing vanillyl alcohol (VA) that exhibits high sensitivity and specificity towards the production of H(2)O(2). We show that APP-103 is safe, effectively promotes kidney function following IRI, and survival of renal transplants. APP-103 reduces tissue injury and IRI-associated inflammatory responses in models of both warm ischemia (kidney clamping) and prolonged cold ischemia (syngeneic renal transplant). Mechanistically, we demonstrate that APP-103 exerts protective effects by specifically targeting the production of reactive oxygen species (ROS). Our data introduce APP-103 as a novel, non-toxic and site-activating therapeutic approach that effectively ameliorates the consequences of IRI in solid organ transplantation.

Because various stimuli can affect living organisms, substances that response to stimuli, such as H2O2, have been studied for biomaterials. To synthesize a biocompatible H2O2-responsive ionic cross-linker, we synthesized a water-soluble H2O2-responsive diselenide compounds containing both sulfate end groups (diSe-SO4). The synthesis of diSe-SO4 was evaluated by 1H NMR and FT-IR. H2O2 responsiveness was evaluated by UV–vis spectra, FT-IR, and XPS. The optical density at 303 nm due to diselenide in diSe-SO4 was decreased in the H2O2 concentration increased. FT-IR and XPS results showed new peaks at 880 cm and 3500 cm−1, and at 63.0 eV, respectively, due to oxidized Se, which indicated the cleavage of the diselenide bond in diSe-SO4 as the H2O2 concentration increased. The ionic binding efficiency of diSe-SO4 to cationic materials was confirmed by measuring the zeta-potential difference (from –15.6 mV to 10.3 mV) before and after mixing with chitosan. MRC-5 cell viability and apoptosis in the presence of diSe-SO4 was evaluated using a CCK-8 assay and FACS, respectively. A high cell viability exceeding 95% was observed at 500 μM diSe-SO4 over 48 h of culture. In conclusion, the synthesized water-soluble diSe-SO4 provides a H2O2-responsive ionic cross-linking material with a high cell affinity.

This study investigated the thermal performance of an independent dedicated outdoor air system integrated with thermal energy storage (TES) used in a childcare center located in the eco-friendly energy town of Jincheon. During the cooling season, chilled water from the TES served buildings based on the use of a thermal network. To thermally charge the TES, a ground source heat pump was operated during off-peak periods (i.e., overnight). Based on the monitoring data for the childcare center and building leakage test results, the required sensible and latent cooling loads were estimated through simulations. The potential for operational energy savings in the proposed system was investigated and compared with the existing heat pump system, which was integrated with the TES and a dehumidifier. It was found that the proposed system could save up to 38% of the operating energy consumption compared with existing systems.

Curcumin is a major active phenolic component of turmeric and has gained great attention in pharmaceutics due to its potent antioxidant, anti-inflammatory and anticancer activity. Here, we developed poly(oxalate-co-curcumin) (POC) as a hydrogen peroxide (H2O2)-activatable polymeric prodrug of curcumin by incorporating curcumin in the backbone of H2O2-responsive polyoxalate. POC particles effectively scavenged H2O2 and released curcumin in a H2O2-triggered manner. POC particles exhibited excellent antioxidant and anti-inflammatory activity in activated cells. POC particles intravenously administrated into acetaminophen-intoxicated mice remarkably suppressed the level of alanine transaminase and inhibited apoptotic cell death in liver. Interestingly, POC particles could also enhance the ultrasound contrast in the intoxicated liver due to CO2 bubble generation through H2O2-triggered oxidation of peroxalate esters. Given their H2O2-responsiveness and highly potent antioxidant activity, POC particles hold great translational potential as theranostic agents for H2O2-associated diseases.

Stimulus-responsive self-assembling prodrug-based nanomedicine has emerged as a novel paradigm in controlled drug delivery. All-trans retinoic acid (RA), one of vitamin A metabolites, induces apoptotic cancer cell death, but its clinical applications are limited by weak anticancer efficacy. To fully maximize the therapeutic potential of RA, we exploited the unique chemistry of arylboronic acid which undergoes hydrogen peroxide (H

We use Nielsen Homescan data to examine whether the incidence of excise taxes on menthol cigarettes varies with race. We find that taxes are shifted at significantly lower rates to Black smokers of menthol cigarettes than any other smokers. A potential explanation is that Black menthol smokers have lower search cost owing to targeted marketing and promotions. We find evidence that Black smokers receive significantly more price discounts for menthol products than white menthol smokers. Our results are robust across product types (packs and cartons), product qualities (generic and premium cigarettes), and cross-state tax avoidance. Our findings indicate that increasing cigarette taxes may be ineffective in reducing racial disparities in menthol cigarette use and smoking-related diseases, and that restricting the sale of menthol cigarettes may provide an alternative to cigarette taxation.

The past decade has witnessed explosive growth in the segment of information technology (IT) professionals who work in the offshore business process outsourcing (BPO) industry. BPO positions are highly regimented and standardized with coercive and normative controls to deter employees from deviating from prescribed work procedures and exercising independent judgment. Coping with these challenges requires a different set of skills than human capital and technical competencies that are discussed in most prior information systems (IS) research. This paper develops theory on the role of social support in employee compensation, and tests the theory using a unique data set of 8,000+ Indian BPO professionals during the 2006–2011 time period. Co-worker social support has a larger impact at higher levels of time stress and supervisor stress, while supervisor social support plays a larger role for senior-level positions than for junior-level positions. We discuss implications of our theory and findings for research and practice.

Using a panel of OECD countries, we show that immigration systematically alters the composition of public spending in the destination country. To mitigate the bias from endogenous sorting of immigrants, we use an IV estimation strategy. The instrument is constructed by estimating a bilateral migration model for 24 destination and 208 source countries. We find that the host country responds to the increase in immigrants by adjusting various expenditures — for instance, reallocating resources from social welfare to national defense and public order. Our findings imply that: (1) immigration affects policy outcomes in areas with little ethnic or re-distributive dimension, and (2) the impact of immigration on the total size of government may not be substantial.

The ‘commodity currency’ literature highlights the robust exchange rate response to fluctuations in global commodity prices that occurs for major commodity exporters. The magnitude of the response, however, varies widely across countries and over time horizons. This paper examines the real exchange rates of 51 commodity exporters over the period from 1980 to 2010, and finds that in the long-run, a higher degree of market power in the world commodity trade can reduce the exchange rate response, while in the short-run, an inflation targeting regime can amplify it. These differential impacts across countries and horizons are of particular relevance for monetary policy-making and for trade strategy in commodity-abundant economies.

Experiments and simulations are performed to study the interaction of solitary waves in a granular crystal with a plastically compressible and rate-sensitive test medium in the form of rigid polyurethane (PU) foam. We study the effects of the foam's compressive strength and elastic modulus on the nonlinear wave dynamics near the interface and on the formation of reflected solitary waves. Experiments are conducted using a granular crystal composed of a vertical array of spherical steel particles, directly contacting the foamed polyurethane samples. Single solitary waves are generated in the chain through striker particle impact, and the temporal profiles of the incident and reflected solitary waves are recorded by placing an instrumented sensor particle in the chain. The measurements show that travel time and wave amplitude of the reflected solitary waves are highly sensitive to the elasto-plastic properties of the inspection medium, particularly when the intensity of the incident solitary waves is increased. The measurements were compared to the predictions obtained with a coupled discrete/finite element model and good agreement was reported. The predictions show that when the amplitude of the incident solitary wave increases, the response transitions from an elastic regime to a regime dominated by plastic compression.

Muscles of peripheral artery disease (PAD) patients are under oxidative stress associated with a significantly elevated level of reactive oxygen species (ROS) including hydrogen peroxide (H2O2). Curcumin is a major active constituent of turmeric and is well known for its highly potent antioxidant, anti-inflammatory and angiogenic effects. We previously reported antioxidant vanillyl alcohol-incorporated copolyoxalate (PVAX) which is designed to rapidly scavenge H2O2 and release bioactive vanillyl alcohol and CO2 in a H2O2-triggered manner. In this work, we developed curcumin-loaded PVAX (CUR-PVAX) nanoparticles as contrast-enhanced ultrasound imaging agents as well as on-demand therapeutic agents for ischemic injuries based on the hypothesis that PVAX nanoparticles generate echogenic CO2 bubbles through H2O2-triggered oxidation of peroxalate esters and the merger of curcumin and PVAX exerts H2O2-activatable synergistic therapeutic actions. CUR-PVAX nanoparticles also displayed the drastic ultrasound signal in ischemic areas by generating CO2 bubbles. CUR-PVAX nanoparticles exhibited significantly higher antioxidant and anti-inflammatory activities than empty PVAX nanoparticles and equivalent curcumin in vascular endothelial cells. A mouse model of ischemic injury was used to evaluate the potential of CUR-PVAX nanoparticles as ultrasound imaging agents and on-demand therapeutic agents. CUR-PVAX nanoparticles significantly suppressed the expression of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Moreover, CUR-PVAX nanoparticles significantly enhanced the level of vascular endothelial growth factor (VEGF) and platelet endothelial cell adhesion molecule-1 (PECAM-1, also known as CD31), leading to blood perfusion into ischemic tissues. We, therefore, believe that CUR-PVAX nanoparticles hold great translational potential as novel theranostic agents for ischemic diseases such as PAD.

The recent advances in nanotechnology have led to the development of smart nanomaterials that combine diagnostic and therapeutic functions and provide synergistic anticancer effects through the combination of different treatment modalities. Here, we report a promising theranostic nanoconstruct that can translate into multiple functionalities: fluorescence/photoacoustic imaging, acid-triggered generation of ROS (reactive oxygen species), heat and singlet oxygen production under near infrared (NIR) laser irradiation, and coupling oxidative anticancer therapy to dual imaging-guided photothermal/photodynamic therapy. An NIR dye-conjugated hydroxyl radical generating biodegradable polymer (HRGP-IR) is employed as a theranostic nanoplatform. HRGP-IR could self-assemble to form micelles and elevate oxidative stress by generating hydrogen peroxide and hydroxyl radical. Under the NIR (808 nm) laser irradiation, HRGP-IR micelles also generate heat and singlet oxygen to induce cancer cell death. In mouse xenograft models, HRGP-IR micelles accumulated in tumors preferentially and the tumor could be detected by dual imaging. Effective tumor ablation was achieved by HRGP-IR micelles (5 mg/kg) combined with NIR laser irradiation, demonstrating the synergistic anticancer effects of oxidative stress with photothermal heating. Given their dual imaging capability, anticancer phototherapy and highly potent synergistic anticancer activity with NIR laser irradiation, HRGP-IR micelles hold great potential as a nanotheranostic agent for cancer treatment.

Drug delivery systems have been extensively developed to enhance the therapeutic efficacy of drugs by altering their pharmacokinetics and biodistribution. However, the use of high quantities of drug delivery systems can cause toxicity due to their poor metabolism and elimination. In this study, we developed polysaccharide-based drug delivery systems which exert potent therapeutic effects and could display synergistic therapeutic effects with drug payloads, leading to dose reduction. Cinnamaldehyde, a major component of cinnamon is known to induce anticancer activity by generating ROS (reactive oxygen species). We developed cinnamaldehyde-conjugated maltodextrin (CMD) as a polymeric prodrug of cinnamaldehyde and a drug carrier. Cinnamaldehyde was conjugated to the hydroxyl groups of maltodextrin via acid-cleavable acetal linkages, allowing facile formulation of nanoparticles and drug encapsulation. CMD nanoparticles induced acid-triggered ROS generation to induce apoptotic cell death. Camptothecin (CPT) was used as a model drug to investigate the potential of CMD nanoparticles as a drug carrier and also evaluate the synergistic anticancer effects with CMD nanoparticles. CPT-loaded CMD nanoparticles exhibited significantly higher anticancer activity than empty CMD nanoparticles and CPT alone in the study of mouse xenograft models, demonstrating the synergistic therapeutic effects of CMD with CPT. Taken together, we believe that CMD nanoparticles hold tremendous potential as a polymeric prodrug of cinnamaldehyde and a drug carrier in anticancer therapy.

Communication strategy affects consumer online purchase channel choice behavior.Consumer fixate the channel which they inflow.Time invariant of mobile channel use is observed, while others not.Goods such as experience/credence goods tend to be purchased via mobile.Substitution (cannibalization) effects are mostly observed between online channels. With the rapid diffusion of smart devices, retailers provide new forms of interactive communication channels, enabling their consumers to access through the mobile channel. The retailers recognize the importance of the mobile channel as an efficient sales channel and as a tool for CRM (Customer Relationship Management). However, CRM has become increasingly complex after adopting it to the mobile channel. It is imperative for retailers to understand consumer behavior in an omni-channel circumstance. Using the four-year transaction data obtained from the online home-shopping provider that expanded its online service (telephone, ARS, Internet website) onto a mobile platform, this research analyzes the consumer channel choice behavior in the perspectives of consumer sociodemographic information, consumer behavior, and corporate communication strategies. To explain channel choices in the omni-channel environment, we use multivariate probit model with sociodemographic variables, communication strategies, order hour, and product categories. Our empirical results indicate that age and gender have significant influences on channel choice behavior. Consumer fixates their inflow channel. Communication strategies such as SMS and app push alarm significantly influence consumer channel choice. Consumers using mobile channel are making purchases without time constraints, while others not. We observed that products that have characteristics of experience goods or credence goods tend to be purchased via mobile and Internet channels that provide detailed and additive information like consumer reviews. Finally, the results revealed substitution effect between most of the channels, except for the Internet and telephone. Our investigation contributes to omni-channel online shopping literature by empirically testing the choice behavior, cross-channel effects, and also by providing insights for online retailers.

Ta metal is frequently used as a raw material in the production of military hardware and electromagnetic components; therefore, obtaining high-purity tantalum is emerging as an important goal. Here, Ta metal powder was successfully prepared by reduction of Mg gas with tantalum pentoxide (Ta2O5). The reduction behavior was studied kinetically using Ta2O5 with different initial particle sizes (0.3 and 1.2 μm). Reduction temperature varied in the range from 1073 to 1273 K. In the X-ray diffraction patterns of reduced powders, pure Ta peaks appear above 1123 K when using the 0.3 μm initial powder, and at 1173 K when using the 1.2 μm initial powder. With increasing reduction temperature, reduction rates were higher with the use of the 0.3 μm powder than with the coarser 1.2 μm powder. This behavior resulted in different activation energies for Mg-reduction (5.234 and 8.695 kJ/mol for the 0.3 and 1.2 μm powder, respectively). In the powder reduced at 1273 K, the oxygen content was lowered to 0.66 and 0.88 wt% for the 1.2 and 0.3 μm powders, respectively; this is explained by differences in the specific surface area according to particle size.

In recent years, crowdsourcing has emerged as a new computing paradigm for bridging the gap between human- and machine-based computation. As one of the core operations in data retrieval, we study top- k queries with crowdsourcing, namely crowd-enabled top- k queries . This problem is formulated with three key factors, latency, monetary cost , and quality of answers . We first aim to design a novel framework that minimizes monetary cost when latency is constrained. Toward this goal, we employ a two-phase parameterized framework with two parameters, called buckets and ranges . On top of this framework, we develop three methods: greedy, equi-sized , and dynamic programming , to determine the buckets and ranges. By combining the three methods at each phase, we propose four algorithms: GdyBucket , EquiBucket , EquiRange , and CrowdK . When the crowd answers are imprecise, we also address improving the accuracy of the top- k answers. Lastly, using both simulated crowds and real crowds at Amazon Mechanical Turk, we evaluate the trade-off between our proposals with respect to monetary cost, accuracy of answers, and running time. Compared to other competitive algorithms, it is found that CrowdK reduces monetary cost up to 20 times, without sacrificing the accuracy of the top- k answers.

Despite the therapeutic effects of resveratrol, its clinical application is restricted by its poor oral bioavailability and low water solubility. To overcome these physicochemical and pharmacokinetic limitations, encapsulation of resveratrol (RV) into nanodevices has been explored. Resveratrol cross-linked chitosan nanoparticles modified with phospholipids (RVC-lipid) were synthesized using a double emulsion technique. The surface morphology of RVC-lipid nanoparticles was evaluated with field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM). Particle size was measured using dynamic light scattering technique (DLS), X-ray diffraction (XRD) was performed to identify the crystallographic nature and Fourier transform infrared spectroscopy (FTIR) was used to measure changes in the chemical structures of the resveratrol and RVC-lipid nanoparticles. Results showed RVC-lipid nanoparticle had a characteristic amorphous structure, a mean particle sizes of 570 nm in DI water and 950 nm in ethanol, and an encapsulation efficiency of 63.82% in aqueous medium and 85.59% in ethanol medium. In-vitro release studies demonstrated a slow and sustained release of resveratrol governed by diffusion. Based on assays of antioxidant activity the scavenging activity of RVC-lipid nanoparticles was inferior to that of resveratrol due to its prolonged release. We concluded that phospholipids are the potential carriers for resveratrol.

Using de facto financial market integration estimated based on an international CAPM, this paper finds that while emerging markets can keep monetary autonomy under the trilemma constraint, advanced economies have limited autonomy due to tight financial integration in recent decades.

This study examines the determinants of member customers' decision to redeem versus accumulate loyalty program (LP) points by focusing on the effects of the different transaction channels (online versus offline) and the demographic information of member customers. This study finds that transactions that occur through online channels and those made by younger customers demonstrate a greater tendency of redeeming LP points as opposed to accumulating them. This study also finds that online channels show a moderating role by mitigating the demographic effects on member customers' point redemption behavior. These findings allow LP providers to predict future LP point balances by analyzing their main transaction channels and the demographic profiles of member customers.

In this paper, we study the problem of retrieving a ranked list of top-N items to a target user in recommender systems. We first develop a novel preference model by distinguishing different rating patterns of users, and then apply it to existing collaborative filtering (CF) algorithms. Our preference model, which is inspired by a voting method, is well-suited for representing qualitative user preferences. In particular, it can be easily implemented with less than 100 lines of codes on top of existing CF algorithms such as user-based, item-based, and matrix-factorization-based algorithms. When our preference model is combined to three kinds of CF algorithms, experimental results demonstrate that the preference model can improve the accuracy of all existing CF algorithms such as ATOP and [email protected] by 3-24% and 6-98%, respectively.

Kinin B1 receptors are implicated in asthmatic airway inflammation. Here we tested this hypothesis by examining the anti-inflammatory effects of BI113823, a novel non-peptide orally active kinin B1 receptor antagonist in mice sensitized to ovalbumin (OVA). Male Balb-c mice were randomly assigned to four study groups: (1) control, (2) OVA+vehicle, (3) OVA+BI113823, (4) OVA+dexamethasone. Mice were sensitized intraperitoneally with 75μg ovalbumin on days 1 and 8. On days 15-17, mice were challenged intranasally with 50μg of ovalbumin. Mice received vehicle, BI113823, or dexamethasone (positive control) on days 16-18. On day 19, bronchoalveolar lavage (BAL) and lung tissue were collected for biochemical and immuno-histological analysis. Compared to controls treatment with BI113823 significantly reduced the numbers of BAL eosinophils, macrophages, neutrophils and lymphocytes by 58.3%, 61.1%, 66.4% and 56.0%, respectively. Mice treated with dexamethasone showed similar reductions in BAL cells. Treatment with BI113823 and dexamethasone also significantly reduced total protein content, IgE, TNF-α and IL-1β in lavage fluid, reduced myeloperoxidase activity, mucus secretion in lung tissues, and reduced the expression of B1 receptors, matrix metalloproteinase (MMP)-2 and cyclooxygenase (COX)-2 compared to vehicle-treated mice. Only BI113823 reduced MMP-9 and inducible nitric oxide synthase (iNOS). BI113823 effectively reduced OVA-induced inflammatory cell, mediator and signaling pathways equal to or greater than that seen with steroids in a mouse asthma model. BI113823 might be useful in modulating inflammation in asthma.

Reactive oxygen species (ROS) produced by host phagocytes exert antibacterial action against a variety of pathogens and ROS-induced oxidative stress is the governing mechanism for the antibacterial activity of major bactericidal antibiotics. In particular, hydroxyl radical is a strong and nonselective oxidant which can damage biomolecules such as DNA, proteins and lipids. Ferrous ion is known to convert mild oxidant hydrogen peroxide (H2O2) into highly reactive and toxic hydroxyl radicals, referred to as Fenton reaction. Herein, we report a new class of antibacterial agents based on Fenton reaction-performing nanostructures, composed of H2O2-generating polymer (PCAE) and iron-containing ferrocene. Amphiphilic PCAE was designed to incorporate H2O2-generating cinnamaldehyde through acid-cleavable linkages and self-assemble to form thermodynamically stable micelles which could encapsulate ferrocene in their hydrophobic core. All the experiments in vitro display that ferrocene-loaded PCAE micelles produce hydroxyl radicals to kill Escherichia coli and Pseudomonas aeruginosa through membrane damages. Intraperitoneally injected ferrocene-loaded PCAE micelles significantly reduced the lung damages and therefore increased the survival rate of mice infected with drug resistant P. aeruginosa. Given their potent antibacterial activity, ferrocene-loaded PCAE micelles hold great potential as a new class of ROS-manipulating antibacterial agents.

Corneal transplantation, a common surgical protocol for visual acuity improvement, is limited owing to shortage of high quality donor corneas and/or lack of accurate replication of structural and biochemical composition of native cornea in a scaffold. Construction of neo-corneas utilizing novel, biocompatible and biodegradable scaffold/film source, could possibly address such formidable challenges. Herein, we designed optically transparent, micro-structurally stable silk films surface-coated with collagen type-I (Col-I/SF) as an alternative scaffold source for bioengineering of neo-cornea. Morphological, structural characteristics and in vitro biological studies were performed using primary rabbit corneal endothelial cells (rCEnCs) as models. The Col-I/SF films demonstrated higher Ra (nm) values compared to the bare SF surfaces. In vitro biological studies showed a significant increment in initial cell attachment and proliferation of cultured rCEnCs on the Col-I/SF films with well-maintained characteristic polygonal shape of rCEnCs. Although any remarkable changes regarding the morphology, expression of ZO-1 and Na(+)/K(+)-ATPase were absent, however the cells were found to be capable of well-expressing their functional proteins which regulates functions of corneal endothelium. Collectively, these results strongly suggest Col-I/SF film for future corneal transplantation therapy.

Asthma is a common airway inflammatory disorder, characterized by increased infiltration of leukocytes and bronchoconstriction. Dexamethasone (DEX) has been widely used in the treatment of allergic asthma. However, long-term and frequent use of DEX has side effects. We therefore reasoned that if drug carriers have intrinsic anti-inflammatory and anti-asthmatic activity and synergize with drug payloads, a low dose of DEX could exert sufficient therapeutic effects. In this study, we developed DEX-loaded H2O2-activatable boronate maltodextrin (DEX-BM) nanoparticles. DEX-BM nanoparticles released DEX in a H2O2-triggered manner and remarkably suppressed the expression of pro-inflammatory cytokines in activated macrophages and lung epithelial cells. In the studies of a murine allergic asthma model, DEX-BM nanoparticles (5 mg/kg) effectively inhibited the inflammatory cell infiltration and airway inflammation than equivalent DEX and BM nanoparticles without noticeable side effects. We anticipate that DEX-BM nanoparticles hold great potential as therapeutic agents for various airway inflammatory diseases.

Neuropeptide-Y (NPY) leads to angiogenesis and remodeling of the ischemic myocardium. The objective of this study is to assess the therapeutic potential of NPY in a model of acute myocardial ischemia using a nanoparticles delivery system targeted to tissue with oxidative stress. NPY3-36 was loaded onto copolyoxalate containing vanillyl alcohol (PVAX) using a double emulsification strategy. Adult C57BL/J6 mice (n = 49) were randomly divided into PVAX-NPY3-36 (n = 22), Vehicle (Saline) (n = 16), and Sham (n = 11) groups. The ischemia to left anterior descending artery was induced in PVAX-NPY3-36 or vehicle groups. The tissue was collected at the end of two weeks after assessing the functional and echocardiographic data. There was a significant decrease in infarction size and mortality in PVAX-NPY3-36 group compared to the Vehicle group (P = 0.01 and P = 0.05). On echocardiography, there was significant improvement in contractility and diastolic parameters (P = 0.01). On pressure-volume loop there was significant increase in stroke volume (P = 0.01), cardiac output (P = 0.01) and ventricular stroke work (P = 0.01) in the PVAX-NPY3-36 group. On Western blot analysis, there was a significant increase in pro-angiogenic factors Ang-1, TGF-β, PDGF- β and its receptors and VEGF in the ischemic tissue treated with PVAX-NPY3-36 as compared to Vehicle ischemic tissue (P = 0.01, P = 0.0003, and P It may be possible to have targeted delivery of labile neurotransmitters NPY3-36 to the ischemic myocardium using nanoparticle PVAX and achieving angiogenesis and significant functional improvement.

Recently, Methylcrotonoyl-CoA carboxylase 2 (MCCC2) is reported to be involved in tumor formation and progression. However, MCCC2 has nerve been reported in colorectal cancer. In this study, we aimed to investigate the role of MCCC2 in colorectal cancer.118 colorectal cancer and matched adjacent normal tissues were enrolled in this study. The expression level of MCCC2 was measured by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The clinical significance of MCCC2 and its influence on cell proliferation was further analyzed.Results shown that the mRNA levels of MCCC2 in colorectal cancer tissues were significantly increased compared with those in normal tissues (P .0001). MCCC2 high-expression was observed in 56.8% colorectal cancer tissues, which was significantly higher than those in normal controls (9.3%, P .0001). MCCC2 high-expression correlated with tumor size, T stage, lymph node metastasis, distant metastasis, clinical stage and differentiation in colorectal cancer (P .05). Moreover, MCCC2 high-expression predicted poorer prognosis and could be as an independent prognostic factor. In addition, MCCC2 knockdown significantly inhibited cell proliferation compared with these controls, while MCCC2 overexpression could reverse the effect.These data indicate MCCC2 overexpression promotes cell proliferation and predicts poorer prognosis in colorectal cancer.

This paper studies equity mutual funds’ portfolio choices in emerging markets with different degrees of financial market integration. By examining the monthly holdings of 385 mutual funds from 1999 to 2017, we find that these funds generally engage in portfolio rebalancing strategies in response to equity return changes. Moreover, we show that the propensity to rebalance is greater in stock markets that are more financially integrated into the world market. High market liquidity and low regulatory barriers, which characterize financial integration, are found to be important drivers of active rebalancing in emerging markets.

We study the elastic interaction between strongly nonlinear solitary waves in lightly pre-compressed granular chains and laminated composite beams using experimental, analytical and numerical approaches. Experiments were conducted using a vertical array of 21 steel beads contacting a simply-supported composite beam at mid-span. A striker bead was dropped from a given height to initiate the propagation of a single solitary wave in the granular chain, whose interaction with the beam resulted in the propagation of multiple reflected solitary waves. The developed apparatus allowed measuring the delays and amplitudes of the reflected waves, and the obtained measurements were found in good agreement with numerical predictions based on a previously developed discrete element (DE) model. The numerical model was further simplified to derive a closed-form analytical solution for the delay of the primary reflected wave whose predictions showed no discernible differences to those obtained from the DE model. Experiments and predictions were performed on beams made of carbon fiber/epoxy and glass fiber/epoxy laminates, and the effects of beam thickness, width and flexural modulus on the characteristics of the reflected solitary waves were studied. We tested composite beams with thickness-to-length ratio in the range of 0.015

Curcumin, a primary active element of turmeric, has potent antioxidant and anti-inflammatory activity, but its low bioavailability is a major hurdle in its pharmaceutical applications. To enhance the therapeutic efficacy of curcumin, we exploited polymeric prodrug strategy. Here, we report rationally designed acid-activatable curcumin polymer (ACP), as a therapeutic prodrug of curcumin, in which curcumin was covalently incorporated in the backbone of amphiphilic polymer. ACP could self-assemble to form micelles that rapidly release curcumin under the acidic condition. The potential of ACP micelles as therapeutics for osteoarthritis was evaluated using a mouse model of monoidoacetic acid (MIA)-induced knee osteoarthritis. ACP micelles drastically protected the articular structures from arthritis through the suppression of tumor necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β). Given their pathological stimulus-responsiveness and potent antioxidant and anti-inflammatory activities, ACP micelles hold remarkable potential as a therapeutic agent for not only osteoarthritis but also various inflammatory diseases.

Therapeutic angiogenesis has achieved promising results for ischemic diseases or peripheral artery disease in preclinical and early-phase clinical studies. We examined the therapeutic angiogenic effects of HPOX, which is biodegradable polymer composing the antioxidant p -hydroxybenzyl alcohol (HBA), in a mouse model of hindlimb ischemia. HPOX effectively stimulated blood flow recovery, compared with its degraded compounds HBA and 1,4-cyclohexendimethanol, via promotion of capillary vessel density in the ischemic hindlimb. These effects were highly correlated with levels of angiogenic inducers, vascular endothelial cell growth factor (VEGF), heme oxygenase-1 (HO-1), and Akt/AMPK/endothelial nitric oxide synthase (eNOS) in ischemic mouse hindlimb muscle. Blood perfusion and neovascularization induced by HPOX were reduced in eNOS −/− and HO-1 +/− mice. HPOX also elevated the endothelial cell markers VEGF receptor-2, CD31, and eNOS mRNAs in the ischemic hindlimb, indicating that HPOX increases endothelial cell population and angiogenesis in the ischemic muscle. However, this nanoparticle suppressed expression levels of several inflammatory genes in ischemic tissues. These results suggest that HPOX significantly promotes angiogenesis and blood flow perfusion in the ischemic mouse hindlimb via increased angiogenic inducers, along with suppression of inflammatory gene expression. Thus, HPOX can be used potentially as a noninvasive drug intervention to facilitate therapeutic angiogenesis.

We propose simplicity and interactivity as key determinants of usability.We examine the effects of usability on user satisfaction, trust, and brand loyalty.Increasing simplicity will increase interactivity and usability experience.Usability is a distal determinant of brand loyalty.Satisfaction and trust mediate the effects usability on brand loyalty. Usability is a central issue for mobile phone design and service because users need to access various functionalities via limited user interfaces (UI) often while they are on the road. In this paper, we propose simplicity and interactivity as the key determinants of mobile phone usability and assess their significance in an empirical setting. Furthermore, we examine the effects of mobile phone usability on user satisfaction, trust, and brand loyalty and provide a holistic view of the causal relationships between the proposed UI features and important organizational variables for building and maintaining long-term customer relationships. The study was conducted using survey questionnaire data collected from 310 mobile phone users in South Korea. The findings of the study confirm that simplicity and interactivity are two significant determinants of mobile phone usability and that interface simplicity is an important precondition for positive interactivity and usability experience. Our findings also show that usability is a distal determinant of brand loyalty, exerting its influence indirectly through the mediators of satisfaction and trust. We discuss the implications of the study findings for usability research and UI design.

Cancer cells are under oxidative stress due to a large production of reactive oxygen species (ROS), which involve in cell proliferation and cancer promotion and progression. On the other hand, ROS promotes cell death, depending on the rate of ROS production and the activity of antioxidant systems. Recently, "oxidation therapy" has arisen as a promising anticancer strategy, which can be achieved by inducing the generation of cytotoxic level of ROS or inhibiting the antioxidant systems in tumor cells. Here, we report oxidative stress amplifying nanoplatforms as novel anticancer therapeutics, which are able not only to suppress antioxidant but also to generate ROS simultaneously in acidic tumor microenvironments. The oxidative stress amplifying nanoplatforms are composed of dual pH-sensitive PBCAE copolymer, polymeric prodrug of BCA (benzoyloxycinnamaldehyde) and heme oxygenase-1 (HO-1) inhibiting zinc protoporphyrin (ZnPP). PBCAE was designed to incorporate ROS-generating BCA in its backbone via acid-cleavable acetal linkages and self-assemble to form micelles that encapsulate ZnPP. In vitro proof-of-concept studies revealed that ZnPP encapsulated in PBCAE micelles suppressed HO-1 to make cancer cells more vulnerable to BCA-induced ROS, leading to enhanced apoptotic cell death. In addition, ZnPP-loaded PBCAE micelles significantly suppressed the tumor growth in human cancer xenograft mouse models. We believe that oxidative stress amplifying micellar nanoparticles have a great potential as novel redox anticancer therapeutics.

Mobile devices are increasingly being used by non-profits and charitable organizations as an alternative channel for philanthropy. Specifically, organizations can construct fund-raising campaigns through mobile applications or through mobile services such as SMS messages to target individuals and incentivize charitable giving. Research studying how mobile devices may be used to enhance such campaigns is limited. In this paper, we study how charitable giving through mobile apps can be enhanced through the use of push notifications and economic incentives. Using a randomized field experiment conducted in partnership with a mobile service provider in the US, we examine the effects of push notifications, monetary subsidies, and intertemporal choices of rewards on donation outcomes by individual users. Even though the donated amounts are small, consistent with cause marketing campaigns, the campaigns are sustainable since the aggregate amounts received are significant over time. Our experiments provide three main findings. First, push notifications have a remarkably high effect on donation behavior in terms of the decision to donate as well as donation amounts, especially for idle users. Second, offering rebates as economic incentives are more effective than offering matching grants, in particular for male consumers. Finally, while users are indifferent between receiving their rewards now versus later, users that are offered a rebate respond with greater alacrity when rewarded immediately rather than later. Our findings have important implications for charitable organizations and application service providers as well as for the design of cause marketing campaigns using the mobile channel.

This paper examines how the financial globalization affects international equity mutual funds’ portfolio choices in emerging markets. By examining the monthly holdings of 155 international funds, we first show that these funds actively engage in a rebalancing strategy to maintain their risk preferences upon realization of excess return changes. We also document robust evidence that these funds’ propensity of rebalancing is larger in a country whose equity market is more strongly correlated with the global market. The results help understand how the financial globalization may raise the portfolio risk of the international funds’ equity holdings in emerging economies.

This study aims to investigate the economic value of cloud computing from the perspective of the stock market. More specifically, we conceptualize the relationship between the cloud computing initiatives of firms and the market reaction based on resource-based and extended resource-based views. For this study, we analyze 212 firm-level cloud computing announcements between 2006 and 2011 by employing the event study methodology. Our empirical results indicate that the market positively reacts to the cloud computing initiatives of firms. Moreover, the market reactions to cloud computing initiatives depend on three key characteristics of cloud computing, namely, firm-specific, resource-specific, and vendor-specific factors.