Esculetin, a coumarin derivative, exerts in vitro and in vivo antiproliferative activity against hepatocellular carcinoma by initiating a mitochondrial-dependent apoptosis pathway

This study investigated the in vitro and in vivo antiproliferative activity of esculetin against hepatocellular carcinoma, and clarified its potential molecular mechanisms. Cell viability was determined by the MTT (tetrazolium) colorimetric assay. In vivoantitumor activity of esculetin was evaluated in a hepatocellular carcinoma mouse model. Seventy-five C57BL/6J mice were implanted with Hepa1-6 cells and randomized into five groups (n=15 each) given daily intraperitoneal injections of vehicle (physiological saline), esculetin (200, 400, or 700 mg·kg-1·day-1), or 5-Fu (200 mg·kg-1·day-1) for 15 days. Esculetin significantly decreased tumor growth in mice bearing Hepa1-6 cells. Tumor weight was decreased by 20.33, 40.37, and 55.42% with increasing doses of esculetin. Esculetin significantly inhibited proliferation of HCC cells in a concentration- and time-dependent manner and with an IC50 value of 2.24 mM. It blocked the cell cycle at S phase and induced apoptosis in SMMC-7721 cells with significant elevation of caspase-3 and caspase-9 activity, but did not affect caspase-8 activity. Moreover, esculetin treatment resulted in the collapse of mitochondrial membrane potential in vitro and in vivo accompanied by increased Bax expression and decreased Bcl-2 expression at both transcriptional and translational levels. Thus, esculetin exerted in vitro and in vivo antiproliferative activity in hepatocellular carcinoma, and its mechanisms involved initiation of a mitochondrial-mediated, caspase-dependent apoptosis pathway.

Characterization of new sources of derivative starches as wall materials of essential oil by spray drying

Starch derivatives of taro (Colocasia esculenta L. Schott) and rice were characterized as wall materials of orange oil (d-limonene) by spray drying. Native starches were initially hydrolyzed with HCl and then esterified. Succinylated starches were modified using a conventional method in a slurry and were extruded; whereas, the phosphorylated starches were modified using the extrusion process. Viscosity and solubility of starches reduced after acid hydrolysis, derivatization, and extrusion. The particle size of the wall materials ranged between 20.05 and 31.81 µm. The encapsulation efficiency of the phosphorylated taro, rice, and waxy corn starches was 96.9, 96.8 and 97.1% respectively, and 98.6, 98.1, and 98.8% for succynilated taro, rice, and waxy corn starches, respectively. Starch derivatives of taro and rice could potentially be used as wall materials of orange oil d-limonene.

The effects of derivative use on equity fund performance

Investing in mutual funds has become more popular than ever and the amount of money invested in mutual funds registered in Finland has hit its all-time high. Mutual funds provide a relatively low-cost method for private investors to invest in stock market and achieve diversified portfolios. In finance there is always a tradeoff between risk and return, where higher expected returns can usually be achieved only by taking higher risks. Diversifying the portfolio gets rid some of the risk but systematic risk cannot be diversified away. These risks can be managed by hedging the investments with derivatives. The use of derivatives should improve the performance of the portfolios using them compared to the funds that don’t. However, previous studies have shown that the risk exposure and return performance of derivative users does not considerably differ from nonusers. The purpose of this study is to examine how the use of derivatives affects the performance of equity funds. The funds studied were 155 equity funds registered in Finland in 2013. Empirical research was done by studying the derivative use of the funds during a 6-year period between 2008–2013. The performance of the funds was studied quantitatively by using several different performance measures used in mutual fund industry; Sharpe Ratio, Treynor Ratio, Jensen's alpha, Sortino Ratio, M2 and Omega Ratio. The effect of derivative use on funds' performance was studied by using a dummy variable and comparing performance measures of derivative-users and nonusers. The differences in performance measures between the two groups were analyzed with statistical tests. The hypothesis was that funds' derivative use should improve their performance relative to the funds that don't use them. The results of this study are in line with previous studies that state that the use of derivatives does not improve mutual funds' performance. When performance was measured with Jensen's alpha, funds that did not use derivatives performed better than the ones that used them. When measured with other performance measures, the results didn’t differ between two groups.

Derivative hedging strategies for bitumen price risk

The objective of the study is to extend the existing hedging literature of the commodity price risks by investigating what kind of hedging strategies can be used in companies using bitumen as raw material in their production. Five different alternative swap hedging strategies in bitumen markets are empirically tested. Strategies tested are full hedge strategy, simple, conservative, and aggressive term structure strategies, and implied volatility strategy. The effectiveness of the alternative strategies is measured by excess returns compared to no hedge strategy. In addition, the downside risk of each strategy is measured with target absolute semi-deviation. Results indicate that any of the tested strategies does not outperform the no hedge strategy in terms of excess returns in all maturities. The best-performing aggressive term structure strategy succeeds to create positive excess returns only in short maturities. However, risk seems to increase hand-in-hand with the excess returns so that the best-performing strategies get the highest risk metrics as well. This implicates that the company willing to gain from favorable price movements must be ready to bear a greater risk. Thus, no superior hedging strategy over the others is found.

Does friendship give us non-derivative partial reasons ?

Une des façons d’approcher la question de l’existence de raisons partiales non-dérivatives d’une quelconque sorte consiste à expliquer ce que sont les raisons partiales et ensuite à chercher à savoir s’il y a des raisons de cette sorte. Si de telles raisons existent, alors il est au moins possible qu’il y ait des raisons partiales d’amitié. C’est cette approche que j’adopterai ici, et elle produit des résultats intéressants. Le premier a trait à la structure des raisons partiales. C’est au moins une condition nécessaire pour qu’une raison soit partiale qu’elle aie une composante relationnelle explicite. Cette composante, techniquement parlant, est un relatum dans la relation d’être une raison qui elle-même est une relation entre la personne à qui la raison s’applique et la personne concernée par l’action pour laquelle il y a une raison. La deuxième conclusion de ce texte est que cette composante relationnelle est aussi requise dans de nombreuses sortes de raisons admises comme impartiales. Afin d’éviter de banaliser la distinction entre raisons partiales et impartiales nous devons appliquer une condition suffisante additionnelle. Finalement, bien qu’il pourrait s’avérer possible de distinguer les raisons impartiales ayant une composante relationnelle des raisons partiales, cette approche suggère que la question de savoir si l’éthique est partiale ou impartiale devra se régler au niveau de l’éthique normative, ou à tout le moins, qu’elle ne pourra se régler au niveau du discours sur la nature des raisons d’agir.

A PVC Plasticized Sensor for Ni(II) Ion Based on a Simple Ethylenediamine Derivative

new PVC membrane ion selective electrode which is highly selective towards Ni(II) ions was constructed using a Schiff base containing a binaphthyl moiety as the ionophore. The sensor exhibited a good Nernstian response for nickel ions over the concentration range 1.0 × 10–1 – 5.0 × 10–6 M with a lower limit of detection of 1.3 × 10–6 M. It has a fast response time and can be used for a period of 4 months with a good reproducibility. The sensor is suitable for use in aqueous solutions in a wide pH range of 3.6 – 7.4 and works satisfactorily in the presence of 25% (v/v) methanol or ethanol. The sensor shows high selectivity to nickel ions over a wide variety of cations. It has been successfully used as an indicator electrode in the potentiometric titration of nickel ions against EDTA and also for the direct determination of nickel content in real samples: effluent samples, chocolates and hydrogenated oils.

A Nonparametric Approach to Pricing and Hedging Derivative Securities via Learning Networks

We propose a nonparametric method for estimating derivative financial asset pricing formulae using learning networks. To demonstrate feasibility, we first simulate Black-Scholes option prices and show that learning networks can recover the Black-Scholes formula from a two-year training set of daily options prices, and that the resulting network formula can be used successfully to both price and delta-hedge options out-of-sample. For comparison, we estimate models using four popular methods: ordinary least squares, radial basis functions, multilayer perceptrons, and projection pursuit. To illustrate practical relevance, we also apply our approach to S&P 500 futures options data from 1987 to 1991.

Atmosphere feedbacks during ENSO in a coupled GCM with a modified atmospheric convection scheme

The too diverse representation of ENSO in a coupled GCM limits one’s ability to describe future change of its properties. Several studies pointed to the key role of atmosphere feedbacks in contributing to this diversity. These feedbacks are analyzed here in two simulations of a coupled GCM that differ only by the parameterization of deep atmospheric convection and the associated clouds. Using the Kerry–Emanuel (KE) scheme in the L’Institut Pierre-Simon Laplace Coupled Model, version 4 (IPSL CM4; KE simulation), ENSO has about the right amplitude, whereas it is almost suppressed when using the Tiedke (TI) scheme. Quantifying both the dynamical Bjerknes feedback and the heat flux feedback in KE, TI, and the corresponding Atmospheric Model Intercomparison Project (AMIP) atmosphere-only simulations, it is shown that the suppression of ENSO in TI is due to a doubling of the damping via heat flux feedback. Because the Bjerknes positive feedback is weak in both simulations, the KE simulation exhibits the right ENSO amplitude owing to an error compensation between a too weak heat flux feedback and a too weak Bjerknes feedback. In TI, the heat flux feedback strength is closer to estimates from observations and reanalysis, leading to ENSO suppression. The shortwave heat flux and, to a lesser extent, the latent heat flux feedbacks are the dominant contributors to the change between TI and KE. The shortwave heat flux feedback differences are traced back to a modified distribution of the large-scale regimes of deep convection (negative feedback) and subsidence (positive feedback) in the east Pacific. These are further associated with the model systematic errors. It is argued that a systematic and detailed evaluation of atmosphere feedbacks during ENSO is a necessary step to fully understand its simulation in coupled GCMs.

The role of atmosphere feedbacks during ENSO in the CMIP3 models

Several studies using ocean-atmosphere GCMs suggest that the atmospheric component plays a dominant role in the modelled ENSO. To help elucidate these findings, the two main atmosphere feedbacks relevant to ENSO, the Bjerknes positive feedback (µ) and the heat flux negative feedback (), are analysed here in 12 coupled GCMs. We find that the models generally underestimate both feedbacks, leading to an error compensation. The strength of is inversely related to the ENSO amplitude in the models and the latent heat and shortwave flux components of this feedback dominate. Furthermore, the shortwave component could help explain the model diversity in both overall and ENSO amplitude.

Quantifying carbon-cycle feedbacks

Perturbations to the carbon cycle could constitute large feedbacks on future changes in atmospheric CO2 concentration and climate. This paper demonstrates how carbon cycle feedback can be expressed in formally similar ways to climate feedback, and thus compares their magnitudes. The carbon cycle gives rise to two climate feedback terms: the concentration–carbon feedback, resulting from the uptake of carbon by land and ocean as a biogeochemical response to the atmospheric CO2 concentration, and the climate–carbon feedback, resulting from the effect of climate change on carbon fluxes. In the earth system models of the Coupled Climate–Carbon Cycle Model Intercomparison Project (C4MIP), climate–carbon feedback on warming is positive and of a similar size to the cloud feedback. The concentration–carbon feedback is negative; it has generally received less attention in the literature, but in magnitude it is 4 times larger than the climate–carbon feedback and more uncertain. The concentration–carbon feedback is the dominant uncertainty in the allowable CO2 emissions that are consistent with a given CO2 concentration scenario. In modeling the climate response to a scenario of CO2 emissions, the net carbon cycle feedback is of comparable size and uncertainty to the noncarbon–climate response. To quantify simulated carbon cycle feedbacks satisfactorily, a radiatively coupled experiment is needed, in addition to the fully coupled and biogeochemically coupled experiments, which are referred to as coupled and uncoupled in C4MIP. The concentration–carbon and climate–carbon feedbacks do not combine linearly, and the concentration–carbon feedback is dependent on scenario and time.

General derivative relations for anharmonic force fields

The brace notation, introduced by Allen and Csaszar (1993, J. chem. Phys., 98, 2983), provides a simple and compact way to deal with derivatives of arbitrary non-tensorial quantities. One of its main advantages is that it builds the permutational symmetry of the derivatives directly into the formalism. The brace notation is applied to formulate the general nth-order Cartesian derivatives of internal coordinates, and to provide closed forms for general, nth-order transformation equations of anharmonic force fields, expressed as Taylor series, from internal to Cartesian or normal coordinate spaces.

Optimality analysis of Th1/Th2 immune responses during microparasite-macroparasite co-infection, with epidemiological feedbacks

Individuals are typically co-infected by a diverse community of microparasites (e.g. viruses or protozoa) and macroparasites (e.g. helminths). Vertebrates respond to these parasites differently, typically mounting T helper type 1 (Th1) responses against microparasites and Th2 responses against macroparasites. These two responses may be antagonistic such that hosts face a 'decision' of how to allocate potentially limiting resources. Such decisions at the individual host level will influence parasite abundance at the population level which, in turn, will feed back upon the individual level. We take a first step towards a complete theoretical framework by placing an analysis of optimal immune responses under microparasite-macroparasite co-infection within an epidemiological framework. We show that the optimal immune allocation is quantitatively sensitive to the shape of the trade-off curve and qualitatively sensitive to life-history traits of the host, microparasite and macroparasite. This model represents an important first step in placing optimality models of the immune response to co-infection into an epidemiological framework. Ultimately, however, a more complete framework is needed to bring together the optimal strategy at the individual level and the population-level consequences of those responses, before we can truly understand the evolution of host immune responses under parasite co-infection.

X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)(2) molecules by a bis(9-aminoacridine-4-carboxamide) derivative

Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 angstrom resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)(2) molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation.