Somatostatin Subtype‑2 Receptor-Targeted Metal-Based Anticancer Complexes

Conjugates of a dicarba analogue of octreotide, a potent somatostatin agonist whose receptors are overexpressed on tumor cells, with [PtCl2(dap)] (dap = 1-(carboxylic acid)-1,2-diaminoethane) (3), [(η6-bip)Os(4-CO2-pico)Cl] (bip = biphenyl, pico = picolinate) (4), [(η6-p-cym)RuCl(dap)]+ (p-cym = p-cymene) (5), and [(η6-p-cym)RuCl(imidazole-CO2H)(PPh3)]+ (6), were synthesized by using a solid-phase approach. Conjugates 35 readily underwent hydrolysis and DNA binding, whereas conjugate 6 was inert to ligand substitution. NMR spectroscopy and molecular dynamics calculations showed that conjugate formation does not perturb the overall peptide structure. Only 6 exhibited antiproliferative activity in human tumor cells (IC50 = 63 ± 2 μM in MCF-7 cells and IC50 = 26 ± 3 μM in DU-145 cells) with active participation of somatostatin receptors in cellular uptake. Similar cytotoxic activity was found in a normal cell line (IC50 = 45 ± 2.6 μM in CHO cells), which can be attributed to a similar level of expression of somatostatin subtype-2 receptor. These studies provide new insights into the effect of receptor-binding peptide conjugation on the activity of metal-based anticancer drugs, and demonstrate the potential of such hybrid compounds to target tumor cells specifically.

Invoking a cartesian product structure on social states: new resolutions of Sen's and Gibbard's impossibility theorems

The purpose of this article is to introduce a Cartesian product structure into the social choice theoretical framework and to examine if new possibility results to Gibbard's and Sen's paradoxes can be developed thanks to it. We believe that a Cartesian product structure is a pertinent way to describe individual rights in the social choice theory since it discriminates the personal features comprised in each social state. First we define some conceptual and formal tools related to the Cartesian product structure. We then apply these notions to Gibbard's paradox and to Sen's impossibility of a Paretian liberal. Finally we compare the advantages of our approach to other solutions proposed in the literature for both impossibility theorems.

Urban spatial structure and suburbanisation. The case of the Barcelona Metropolitan

The metropolitan spatial structure displays various patterns, sometimes monocentricity and sometimes multicentricity, which seems much more complicated than the exponential density function used in classic works such as Clark (1961), Muth (1969) or Mills (1973) among others, can effectively represent. It seems that a more flexible density function,such as cubic spline function (Anderson (1982), Zheng (1991), etc.) to describe the density-accessibility relationship is needed. Also, accessibility, the fundamental determinant of density variations, is only partly captured by the inclusion of distance to the city centre as an explanatory variable. Steen (1986) has proposed to correct that miss-especification by including an additional gradient for distance to the nearest transportation axis. In identifying the determinants of urban spatial structure in the context of inter-urban systems, some of the variables proposed by Muth (1969), Mills (1973) and Alperovich (1983) such as city age or population, make no sense in the case of a single urban system. All three criticism to the exponential density function and its determinants apply for the Barcelona Metropolitan Region, a polycentric conurbation structured on well defined transportation axes.

Airline competition and network structure

This paper characterizes the equilibria in airline networks and their welfare implications in an unregulated environment. Competing airlines may adopt either fully-connected (FC) or hub-and-spoke (HS) network structures; and passengers exhibiting low brand loyalty to their preferred carrier choose an outside option to travel so that markets are partially served by airlines. In this context, carriers adopt hubbing strategies when costs are sufficiently low, and asymmetric equilibria where one carrier chooses a FC strategy and the other chooses a HS strategy may arise. Quite interestingly, flight frequency can become excessive under HS network configurations.

Organisational structure, communication and group ethics

This paper investigates experimentally how organisational decision processes affect the moral motivations of actors inside a firm that must forego profits to reduce harming a third party. In a "vertical" treatment, one insider unilaterally sets the harm-reduction strategy; the other can only accept or quit. In a "horizontal" treatment, the insiders decide by consensus. Our 2-by-2 design also controls for communication effects. In our data, communication makes vertical firms more ethical; voice appears to mitigate "responsibility-alleviation" in that subordinates with voice feel responsible for what their firms do. Vertical firms are then more ethical than the horizontal firms for which our bargaining data reveal a dynamic form of responsibility-alleviation and our chat data indicate a strong "insider-outsider" effect.

Debt and deficit fluctuations and the structure of bond markets

We analyse the implications of optimal taxation for the stochastic behaviour of debt. We show that when a government pursues an optimal fiscal policy under complete markets, the value of debt has the same or less persistence than other variables in the economy and it declines in response to shocks that cause the deficit to increase. By contrast, under incomplete markets debt shows more persistence than other variables and it increases in response to shocks that cause a higher deficit. Data for US government debt reveals diametrically opposite results from those of complete markets and is much more supportive of bond market incompleteness.