Therapeutic target discovery using Boolean network attractors: improvements of kali

In a previous article, an algorithm for identifying therapeutic targets in Boolean networks modeling pathological mechanisms was introduced. In the present article, the improvements made on this algorithm, named kali, are described. These improvements are i) the possibility to work on asynchronous Boolean networks, ii) a finer assessment of therapeutic targets and iii) the possibility to use multivalued logic. kali assumes that the attractors of a dynamical system, such as a Boolean network, are associated with the phenotypes of the modeled biological system. Given a logic-based model of pathological mechanisms, kali searches for therapeutic targets able to reduce the reachability of the attractors associated with pathological phenotypes, thus reducing their likeliness. kali is illustrated on an example network and used on a biological case study. The case study is a published logic-based model of bladder tumorigenesis from which kali returns consistent results. However, like any computational tool, kali can predict but can not replace human expertise: it is a supporting tool for coping with the complexity of biological systems in the field of drug discovery

Therapeutic target discovery using Boolean network attractors: avoiding pathological phenotypes

Target identification, one of the steps of drug discovery, aims at identifying biomolecules whose function should be therapeutically altered in order to cure the considered pathology. This work proposes an algorithm for in silico target identification using Boolean network attractors. It assumes that attractors of dynamical systems, such as Boolean networks, correspond to phenotypes produced by the modeled biological system. Under this assumption, and given a Boolean network modeling a pathophysiology, the algorithm identifies target combinations able to remove attractors associated with pathological phenotypes. It is tested on a Boolean model of the mammalian cell cycle bearing a constitutive inactivation of the retinoblastoma protein, as seen in cancers, and its applications are illustrated on a Boolean model of Fanconi anemia. The results show that the algorithm returns target combinations able to remove attractors associated with pathological phenotypes and then succeeds in performing the proposed in silico target identification. However, as with any in silico evidence, there is a bridge to cross between theory and practice, thus requiring it to be used in combination with wet lab experiments. Nevertheless, it is expected that the algorithm is of interest for target identification, notably by exploiting the inexpensiveness and predictive power of computational approaches to optimize the efficiency of costly wet lab experiments.Comment: Since the publication of this article and among the possible improvements mentioned in the Conclusion, two improvements have been done: extending the algorithm for multivalued logic and considering the basins of attraction of the pathological attractors for selecting the therapeutic bullet

Fair Trade Contracts for Some, an Insurance for Others

This article analyzes the impact of Fair Trade contracts between sub-groups of farmers and a Fair Trade organization on the spot market price. We analyze a three level vertical chain gathering perfectly competitive farmers upstream who offer their raw product on a spot market to manufacturers who then sell finished products to a downstream retailer. Absent Fair Trade, the entire raw product is sold on the spot market. When a Fair Trade organization offers a Fair Trade contract to a sub-group of farmers, it gathers a Guaranteed Minimum Price clause and a straight relationship between the sub-group of farmers and the retailer. This article highlights several conditions such that a snowball effect exists, i.e farmers outside of the Fair Trade contract also benefit from a higher spot market price.Guaranteed Minimum Price Contracts, Disintermediation, Fair Trade, Vertical Chain, Two-part Tariff Contracts

Fair Trade: In or Out the Market?

Cet article s'intéresse à l'évolution du concept de commerce équitable. Nous proposons un modèle simple en vue de donner des arguments théoriques dans le débat sur la vente de produits équitables dans la grande distribution. L'hypothèse principale est que certains consommateurs sont prêts à payer un prix plus élevé pour acheter un produit équitable. Nous mettons en évidence que les produits équitables ont plus de chance d'être dans les rayons des supermarchés si le certificateur du label équitable a pour objectif de maximiser les quantités certifiées plutôt que le prix payé aux producteurs. Nous soulignons également que la variable clé dans le choix du revendeur de vendre ou non des produits équitables n'est pas le pourcentage de consommateurs prêts à payer pour un bien équitable, mais combien ces consommateurs sont prêts à payer pour ce type de produit.Différentiation des produits;Discrimination en prix;Revente

Les défis du commerce équitable dans l'hémisphère Nord

The fair trade born fifty years ago defines itself as an alternative approach to conventional trade. In the late 1980s, fair trade organizations began labelling fair products to facilitate their entry into the large-scale distribution. This article presents the concept and its evolution, as well as the debate on the introducion of fair products into the large-scale distribution. It also evaluates the situation of the legislation introduced in France.Le commerce équitable connaît depuis quelques années un intérêt grandissant de la part des industriels et de la grande distribution grâce à sa filière labellisée. Cet article présente le commerce équitable et son évolution, ainsi que le débat sur l'introduction de produits équitables dans la grande distribution. Il fait également le point sur la législation mise en place en France

Guaranteed Minimum Price Contracts for Some, an Insurance for Others?

This paper analyzes the impact of guaranteed minimum price contracts between sub-groups of farmers and a fair trade manufacturer on the spot market price. We focus on the fair trade concept in the coffee supply chain as an example. We analyze a three level vertical chain gathering perfectly competitive farmers upstream who offer their raw product to manufacturers who then sell finished products to a downstream retailer. Without fair trade, all the raw product is sold on the spot market. When a sub-group of farmers benefit from a guaranteed minimum price contract offered by a fair trade certifier, we show that farmers outside of this fair trade agreement may also benefit from a higher spot market price in cases of a limited overproduction.Guaranteed Minimum Price Contracts, Fair Trade, Vertical Chain., Demand and Price Analysis, International Relations/Trade,

How do GM / non GM coexistence regulations affect markets and welfare?

This paper presents a theoretical economic model assessing the effect of the level of mandatory genetically modified (GM) / non-GM coexistence regulations on market and welfare outcome. We assume vertical differentiation of GM and non-GM goods on the consumer side. Producers are heterogeneous in their cost savings from GMO adoption. Producers of non-GM crops face a probability of having their harvest downgraded if gene flow from GM fields makes its GMO content above the labeling threshold. The government may impose to GMO producers mandatory ex ante isolation distances from non-GM fields in order to decrease the probability of non-GM harvest downgrading. It may also introduce an ex post compensation to non-GMO farmers for profit losses due to harvest downgrading, imposing GMO farmers’ participation to a compensation fund via a tax on GM seeds. Assuming endogenous crop choices and prices, we study the effects of ex ante regulation and ex post liability of GMO producers on market equilibrium as well as on global and interest group welfare.genetically modified organisms, coexistence, identity preservation, regulation, liability, vertical differentiation, law and economics, Marketing, Research and Development/Tech Change/Emerging Technologies,

Fair Trade Contracts for Some, an Insurance for Others

This article analyzes the impact of Fair Trade contracts between sub-groups of farmers and a Fair Trade organization on the spot market price. We analyze a three level vertical chain gathering perfectly competitive farmers upstream who offer their raw product on a spot market to manufacturers who then sell finished products to a downstream retailer. Absent Fair Trade, the entire raw product is sold on the spot market. When a Fair Trade organization offers a Fair Trade contract to a sub-group of farmers, it gathers a Guaranteed Minimum Price clause and a straight relationship between the sub-group of farmers and the retailer. This article highlights several conditions such that a snowball effect exists, i.e farmers outside of the Fair Trade contract also benefit from a higher spot market price

Fair Trade: In or Out the Market?

This paper focuses on a sustainable perspective of Fair Trade concept. We propose a simple model to provide some theoretical arguments in the debate about the sale of Fair Trade labelled goods in the large-scale distribution. The main hypothesis is related to the observation that some consumers are willing to pay a premium for Fair Trade products. We show that Fair Trade products are more likely to be on retailer's shelves if the Fair Trade certifier's objective is to maximize quantities labelled rather than the price paid to producers. We also underline that the key variable in the retailer's choice to sell the Fair Trade product is not the percentage of consumers who are willing to pay a Fair Trade good, but how much the Fair Trade likers are willing to pay for it.Cet article s'intéresse à l'évolution du concept de commerce équitable. Nous proposons un modèle simple en vue de donner des arguments théoriques dans le débat sur la vente de produits équitables dans la grande distribution. L'hypothèse principale est que certains consommateurs sont prêts à payer un prix plus élevé pour acheter un produit équitable. Nous mettons en évidence que les produits équitables ont plus de chance d'être dans les rayons des supermarchés si le certificateur du label équitable a pour objectif de maximiser les quantités certifiées plutôt que le prix payé aux producteurs. Nous soulignons également que la variable clé dans le choix du revendeur de vendre ou non des produits équitables n'est pas le pourcentage de consommateurs prêts à payer pour un bien équitable, mais combien ces consommateurs sont prêts à payer pour ce type de produit