Steady-state global optimization of metabolic non-linear dynamic models through recasting into power-law canonical models

Background: Design of newly engineered microbial strains for biotechnological purposes would greatly benefit from the development of realistic mathematical models for the processes to be optimized. Such models can then be analyzed and, with the development and application of appropriate optimization techniques, one could identify the modifications that need to be made to the organism in order to achieve the desired biotechnological goal. As appropriate models to perform such an analysis are necessarily non-linear and typically non-convex, finding their global optimum is a challenging task. Canonical modeling techniques, such as Generalized Mass Action (GMA) models based on the power-law formalism, offer a possible solution to this problem because they have a mathematical structure that enables the development of specific algorithms for global optimization. Results: Based on the GMA canonical representation, we have developed in previous works a highly efficient optimization algorithm and a set of related strategies for understanding the evolution of adaptive responses in cellular metabolism. Here, we explore the possibility of recasting kinetic non-linear models into an equivalent GMA model, so that global optimization on the recast GMA model can be performed. With this technique, optimization is greatly facilitated and the results are transposable to the original non-linear problem. This procedure is straightforward for a particular class of non-linear models known as Saturable and Cooperative (SC) models that extend the power-law formalism to deal with saturation and cooperativity. Conclusions: Our results show that recasting non-linear kinetic models into GMA models is indeed an appropriate strategy that helps overcoming some of the numerical difficulties that arise during the global optimization task.

Impact of the Spanish smoking control law on exposure to second-hand smoke and respiratory health in hospitality workers: a cohort study

A smoke-free law came into effect in Spain on 1st January 2006, affecting all enclosed workplaces except hospitality venues, whose proprietors can choose among totally a smoke-free policy, a partial restriction with designated smoking areas, or no restriction on smoking on the premises. We aimed to evaluate the impact of the law among hospitality workers by assessing second-hand smoke (SHS) exposure and the frequency of respiratory symptoms before and one year after the ban.

The scope of Baker's law.

656 I. 657 II. 658 III. 660 IV. 661 V. 663 VI. 663 VII. 664 VIII. 664 665 References 665 SUMMARY: Baker's law refers to the tendency for species that establish on islands by long-distance dispersal to show an increased capacity for self-fertilization because of the advantage of self-compatibility when colonizing new habitat. Despite its intuitive appeal and broad empirical support, it has received substantial criticism over the years since it was proclaimed in the 1950s, not least because it seemed to be contradicted by the high frequency of dioecy on islands. Recent theoretical work has again questioned the generality and scope of Baker's law. Here, we attempt to discern where the idea is useful to apply and where it is not. We conclude that several of the perceived problems with Baker's law fall away when a narrower perspective is adopted on how it should be circumscribed. We emphasize that Baker's law should be read in terms of an enrichment of a capacity for uniparental reproduction in colonizing situations, rather than of high selfing rates. We suggest that Baker's law might be tested in four different contexts, which set the breadth of its scope: the colonization of oceanic islands, metapopulation dynamics with recurrent colonization, range expansions with recurrent colonization, and colonization through species invasions.

Treaty shopping in international investment law

Is "treaty shopping" in international investment law "legitimate nationality planning" or "treaty abuse"? This is the question investment arbitral tribunals have been increasingly faced with over past years. This PhD thesis will examine in a systematic and comprehensive manner investment arbitral decisions that have attempted to draw this line. It will show that while some legal approaches taken by arbitral tribunals have started to consolidate, others remain unsettled, contributing to the picture of an overall inconsistent jurisprudence. The thesis will also make proposals de lege ferenda on how States could reform their international investment agreements in order to make them less susceptible to the practice of treaty shopping.

Challenges and Opportunities of Online Entertainment. Proceedings of the 7th International Conference on Internet, Law & Politics. Universitat Oberta de Catalunya, Barcelona, 9-10 July, 2012.

El VIII Congrés Internacional Internet, Dret i Política (IDP 2012) que s'ha dut a terme a Barcelona els dies 9 i 10 de juliol de 2012 sota el títol genèric de "Reptes i oportunitats de l'entreteniment en línia", ha abordat alguns dels principals reptes als que s'enfronta la societat de la informació des de la perspectiva jurídica i politològica. Concretament, els temes centrals han estat el debat sobre l'entreteniment a la xarxa, així com altres qüestions relacionades amb Internet i els drets de propietat intel·lectual, la privacitat, la seguretat o la llibertat d'expressió.

Internet, Law and Politics. A decade of transformations.

Proceedings of Internet, Law and Politics. A decade of transformations.

Catalan law in the European context

The article provides an overview of the Catalan law at the European context. How the Catalan institutions can tackle on the Spanish Government policies and decisions in front of the European Union. And how the European Union Law and policies are implemented in a decentralized country such Spain where Autonomous Communities have their own Governments and Parliaments. There is also examined how this Spanish territorial decentralized structure affects the implementation of such EU norms and its control. Finally, there is exposed how Catalan institutions manage to participate in front of the European Union institutions. Which are the instruments that can guarantee this participation and which are the EU responses to them.

Prescription in the proposal for a common european sales law

The rules on prescription in Part VIII, Chapter 18, of the Proposal for a Common European Sales Law (CESL) follow the provisions of the Principles of European Contract Law (PECL) and the Draft Common Frame of Reference (DCFR), which, in general, have deserved favourable comments. Yet, a number of rules contained in those texts have been omitted. It is necessary to ascertain whether the CESL rules only apply to provisions on rights and claims resulting from sales or related services contracts, or whether they are also applicable to any other contractual right or claim and also to rights or claims of non-contractual origin. One of the most problematic issues concerns general prescription periods: firstly, because there are two general periods, a short one and a long one, without any specification about the claims or rights covered by each one of them; secondly, because neither period is suitable in case of non-conformity. There are also some interpretation problems due to missing, ambiguous or defective definitions. The systematic approach demands clarification too.

Oncobiguanides: Paracelsus" law and nonconventional routes for administering diabetobiguanides for cancer treatment

The dose makes the poison, the common motto of toxicology first expressed by Paracelsus more than 400 years ago, may effectively serve to guide potential applications for metformin and related biguanides in oncology. While Paracelsus' law for the dose-response effect has been commonly exploited for the use of some anti-cancer drugs at lower doses in non-neoplastic diseases (e.g., methotrexate), the opposite scenario also holds true; in other words, higher doses of non-oncology drugs, such as anti-diabetic biguanides, might exert direct anti-neoplastic effects. Here, we propose that, as for any drug, there is a dose range for biguanides that is without any effect, one corresponding to"diabetobiguanides" with a pharmacological effect (e.g., insulin sensitization in type 2 diabetes, prevention of insulin-dependent carcinogenesis, indirect inhibition of insulin and growth factor-dependent cancer growth) but with minimal toxicity and another corresponding to 'oncobiguanides' with pharmacological (i.e., direct and strong anticancer activity against cancer cells) as well as toxic effects. Considering that biguanides demonstrate a better safety profile than most oncology drugs in current use, we should contemplate the possibility of administering biguanides through non-conventional routes (e.g., inhaled for carcinomas of the lung, topical for skin cancers, intravenous as an adjunctive therapy, rectal suppositories for rectal cancer) to unambiguously investigate the therapeutic value of high-dose transient biguanide exposure in cancer. Perhaps then, the oncobiguanides, as we call them here, could be viewed as a mechanistically different type of anti-cancer drugs employed at doses notably higher than those used chronically when functioning as diabetobiguanides