The key role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: Ranging from non-cytotoxic to highly cytotoxic compounds

A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulfur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be unstable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [5: HSA] and [6: HSA] adducts (HSA = human serum albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and density functional theory calculations allowed us to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands toward an increased cytotoxic effect. X-ray structure analysis of compound [Ru(eta(5)-C5H5)(bipy)(PPh3)][PF6] (7; bipy = bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(eta(5)-C5H5)(bipy)(PPh3)](+) cation complex in the racemic crystal packing. (C) 2015 Elsevier Inc All rights reserved.

The key role of coligands in novel ruthenium(II)-cyclopentadienyl bipyridine derivatives: ranging from non-cytotoxic to highly cytotoxic compounds

A new family of eight ruthenium(II)-cyclopentadienyl bipyridine derivatives, bearing nitrogen, sulfur, phosphorous and carbonyl sigma bonded coligands, has been synthesized. Compounds bearing nitrogen bonded coligands were found to be unstable in aqueous solution, while the others presented appropriate stabilities for the biologic assays and pursued for determination of IC50 values in ovarian (A2780) and breast (MCF7 and MDAMB231) human cancer cell lines. These studies were also carried out for the [5: HSA] and [6: HSA] adducts (HSA=human serum albumin) and a better performance was found for the first case. Spectroscopic, electrochemical studies by cyclic voltammetry and density functional theory calculations allowed us to get some understanding on the electronic flow directions within the molecules and to find a possible clue concerning the structural features of coligands that can activate bipyridyl ligands toward an increased cytotoxic effect. X-ray structure analysis of compound [Ru(η(5)-C5H5)(bipy)(PPh3)][PF6] (7; bipy=bipyridine) showed crystallization on C2/c space group with two enantiomers of the [Ru(η(5)-C5H5)(bipy)(PPh3)](+) cation complex in the racemic crystal packing.

Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism (MUSIASEM): an outline of rationale and theory

This paper presents an outline of rationale and theory of the MuSIASEM scheme (Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism). First, three points of the rationale behind our MuSIASEM scheme are discussed: (i) endosomatic and exosomatic metabolism in relation to Georgescu-Roegen’s flow-fund scheme; (2) the bioeconomic analogy of hypercycle and dissipative parts in ecosystems; (3) the dramatic reallocation of human time and land use patterns in various sectors of modern economy. Next, a flow-fund representation of the MUSIASEM scheme on three levels (the whole national level, the paid work sectors level, and the agricultural sector level) is illustrated to look at the structure of the human economy in relation to two primary factors: (i) human time - a fund; and (ii) exosomatic energy - a flow. The three levels representation uses extensive and intensive variables simultaneously. Key conceptual tools of the MuSIASEM scheme - mosaic effects and impredicative loop analysis - are explained using the three level flow-fund representation. Finally, we claim that the MuSIASEM scheme can be seen as a multi-purpose grammar useful to deal with sustainability issues.

The Teggiolo zone: a key to the Helvetic-Penninic connection (stratigraphy and tectonics in the Val Bavona, Ticino, Central Alps)

The Teggiolo zone is the sedimentary cover of the Antigorio nappe, one of the lowest tectonic units of the Penninic Central Alps. Detailed mapping, stratigraphic and structural analyses, and comparisons with less metamorphic series in several well-studied domains of the Alps, provide a new stratigraphic interpretation. The Teggiolo zone is comprised of several sedimentary cycles, separated by erosive surfaces and large stratigraphic gaps, which cover the time span from Triassic to Eocene. At Mid-Jurassic times it appears as an uplifted, partially emergent block, marking the southern limit of the main Helvetic basin (the Limiting South-Helvetic Rise LSHR). The main mass of the Teggiolo calcschists, whose base truncates the Triassic-Jurassic cycles and can erode the Antigorio basement, consists of fine-grained clastic sediments analogous to the deep-water flyschoid deposits of Late Cretaceous to Eocene age in the North-Penninic (or Valais s.l.) basins. Thus the Antigorio-Teggiolo domain occupies a crucial paleogeographic position, on the boundary between the Helvetic and Penninic realms: from Triassic to Early Cretaceous its affinity is with the Helvetic; at the end of Cretaceous it is incorporated into the North-Penninic basins. An unexpected result is the discovery of the important role played by complex formations of wildflysch type at the top of the Teggiolo zone. They contain blocks of various sizes. According to their nature, three different associations are distinguished that have specific vertical and lateral distributions. These blocks give clues to the existence of territories that have disappeared from the present-day level of observation and impose constraints on the kinematics of early folding and embryonic nappe emplacement. Tectonics produced several phases of superimposed folds and schistosities, more in the metasediments than in the gneissic basement. Older deformations that predate the amplification of the frontal hinge of the nappe generated the dominant schistosity and the km-wide Vanzèla isoclinal fold.

A Producer Theory with Business Risks

In this paper, we consider a producer who faces uninsurable business risks due to incomplete spanning of asset markets over stochastic goods market outcomes, and examine how the presence of the uninsurable business risks affects the producer's optimal pricing and production behaviours. Three key (inter-related) results we find are: (1) optimal prices in goods markets comprise ‘markup’ to the extent of market power and ‘premium’ by shadow price of the risks; (2) price inertia as we observe in data can be explained by a joint work of risk neutralization motive and marginal cost equalization condition; (3) the relative responsiveness of risk neutralization motive and marginal cost equalization at optimum is central to the cyclical variation of markups, providing a consistent explanation for procyclical and countercyclical movements. By these results, the proposed theory of producer leaves important implications both micro and macro, and both empirical and theoretical.

A Theory of Wage Setting Behavior

Concerns for fairness, workers' morale and reciprocity infuence firms' wage setting policy. In this paper we formalize a theory of wage setting behavior in a simple and tractable model that explicitly considers these behavioral aspects. A worker is assumed to have reference-dependent preferences and displays loss aversion when evaluating the fairness of a wage contract. The theory establishes a wage-effort relationship that captures the worker's reference-dependent reciprocity, which in turn in uences the firm's optimal wage policy. The paper makes two key contributions: it identifies loss aversion as an explanation for a worker's asymmetric reciprocity; and it provides realistic and generalized microfoundation for downward wage rigidity. We further illustrate the implications of our theory for both wage setting and hiring behavior. Downward wage rigidity generates several implications for the outcome of the initial employment contract. The worker's reference wage, his extent of negative reciprocity and the firms expectations are key drivers of the propositions derived.

Migration and trade: Theory with an Application to the Eastern- Western European Integration

The remarkable increase in trade flows and in migratory flows of highly educated people are two important features of globalization of the last decades. This paper extends a two-country model of inter- and intraindustry trade to a rich environment featuring technological differences, skill differences and the possibility of international labor mobility. The model is used to explain the patterns of trade and migration as countries remove barriers to trade and to labor mobility. We parameterize the model to match the features of the Western and Eastern European members of the EU and analyze first the effects of the trade liberalization which occured between 1989 and 2004, and then the gains and losses from migration which are expected to occur if legal barriers to labor mobility are substantially reduced. The lower barriers to migration would result in significant migration of skilled workers from Eastern European countries. Interestingly, this would not only benefit the migrants and most Western European workers but, via trade, it would also benefit the workers remaining in Eastern Europe. Key Words: Skilled Migration, Gains from Variety, Real Wages, Eastern-Western Europe. JEL Codes: F12, F22, J61.

Merging the hypothetical extraction method and the classical multiplier approach: a hybrid possibility for identifying key distributive sectors

The two main alternative methods used to identify key sectors within the input-output approach, the Classical Multiplier method (CMM) and the Hypothetical Extraction method (HEM), are formally and empirically compared in this paper. Our findings indicate that the main distinction between the two approaches stems from the role of the internal effects. These internal effects are quantified under the CMM while under the HEM only external impacts are considered. In our comparison, we find, however that CMM backward measures are more influenced by within-block effects than the proposed forward indices under this approach. The conclusions of this comparison allow us to develop a hybrid proposal that combines these two existing approaches. This hybrid model has the advantage of making it possible to distinguish and disaggregate external effects from those that a purely internal. This proposal has also an additional interest in terms of policy implications. Indeed, the hybrid approach may provide useful information for the design of ''second best'' stimulus policies that aim at a more balanced perspective between overall economy-wide impacts and their sectoral distribution.

Use-dependent block of the voltage-gated Na+ channel by tetrodotoxin and saxitoxin: Effect of pore mutations that change ionic selectivity.

Voltage-gated Na(+) channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca(2+) permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca(2+) or Na(+) ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca(2+) permeability, suggesting that ion-toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation.

A key role of TRPC channels in the regulation of electromechanical activity of the developing heart.

Aims It is well established that dysfunction of voltage-dependent ion channels results in arrhythmias and conduction disturbances in the foetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC (transient receptor potential canonical) channels remains unclear. We assessed the hypothesis that TRPC channels play a crucial role in the spontaneous activity of the developing heart.Methods and results TRPC isoforms were investigated in isolated hearts obtained from 4-day-old chick embryos. Using RT-PCR, western blotting and co-immunoprecipitation, we report for the first time that TRPC1, 3, 4, 5, 6, and 7 isoforms are expressed at the mRNA and protein levels and that they can form a macromolecular complex with the alpha 1C subunit of the L-type voltage-gated calcium channel (Cav1.2) in atria and ventricle. Using ex vivo electrocardiograms, electrograms of isolated atria and ventricle and ventricular mechanograms, we found that inhibition of TRPC channels by SKF-96365 leads to negative chrono-, dromo-, and inotropic effects, prolongs the QT interval, and provokes first-and second-degree atrioventricular blocks. Pyr3, a specific antagonist of TRPC3, affected essentially atrioventricular conduction. On the other hand, specific blockade of the L-type calcium channel with nifedipine rapidly stopped ventricular contractile activity without affecting rhythmic electrical activity.Conclusions These results give new insights into the key role that TRPC channels, via interaction with the Cav1.2 channel, play in regulation of cardiac pacemaking, conduction, ventricular activity, and contractility during cardiogenesis.

Full diversity product codes for block erasure and block fading channels

We show how to build full-diversity product codes under both iterative encoding and decoding over non-ergodic channels, in presence of block erasure and block fading. The concept of a rootcheck or a root subcode is introduced by generalizing the same principle recently invented for low-density parity-check codes. We also describe some channel related graphical properties of the new family of product codes, a familyreferred to as root product codes.

What is the value of joint processing of pilots and data in block-fading channels?

The spectral efficiency achievable with joint processing of pilot and data symbol observations is compared with that achievable through the conventional (separate) approach of first estimating the channel on the basis of the pilot symbols alone, and subsequently detecting the datasymbols. Studied on the basis of a mutual information lower bound, joint processing is found to provide a non-negligible advantage relative to separate processing, particularly for fast fading. It is shown that, regardless of the fading rate, only a very small number of pilot symbols (at most one per transmit antenna and per channel coherence interval) shouldbe transmitted if joint processing is allowed.

Capital, Wages, and Growth: Theory and Evidence

Returns to scale to capital and the strength of capital externalities play a key role for the empirical predictions and policy implications of different growth theories. We show that both can be identified with individual wage data and implement our approach at the city-level using US Census data on individuals in 173 cities for 1970, 1980, and 1990. Estimation takes into account fixed effects, endogeneity of capital accumulation, and measurement error. We find no evidence for human or physical capital externalities and decreasing aggregate returns to capital. Returns to scale to physical and human capital are around 80 percent. We also find strong complementarities between human capital and labor and substantial total employment externalities.

Capital, wages and growth: Theory and evidence

Returns to scale to capital and the strength of capital externalities play a key role for the empirical predictions and policy implications of different growth theories. We show that both can be identified with individual wage data and implement our approach at the city-level using US Census data on individuals in 173 cities for 1970, 1980, and 1990. Estimation takes into account fixed effects, endogeneity of capital accumulation, and measurement error. We find no evidence for human or physical capital externalities and decreasing aggregate returns to capital. Returns to scale to physical and human capital are around 80 percent. We also find strong complementarities between human capital and labor and substantial total employment externalities.