An overview about erythrocyte membrane

© 2010 – IOS Press and the authors. All rights reservedIn the sixties and seventies, erythrocytes or red blood cells (RBCs) were extensively studied. Much has been learnt particularly concerning their metabolism and gas transporter function. In the past decade, the use of new approaches and methodologies, such as proteomic analysis, has contributed for a renewed interest on the erythrocyte. Recent studies have provided us with a more detailed and comprehensive picture on the composition and organization of its cellular membrane that will be the main subject of this minireview. Unexpectedly, it has been recognized that this cell expresses several adhesion molecules on its surface, like other cellular types such blood circulating cells or endothelial cells. Taking into consideration the cellular functions of the erythrocyte, the clarification of the role of those adhesion molecules may in the future open new horizons for the biological significance of this cellular player.Fundação para a Ciência e Tecnologia (FCT) for the financial support(PTDC/SAU-OSM/73449/2006)

Efficient Haplotype Inference with Pseudo-Boolean Optimization

Abstract. Haplotype inference from genotype data is a key computational problem in bioinformatics, since retrieving directly haplotype information from DNA samples is not feasible using existing technology. One of the methods for solving this problem uses the pure parsimony criterion, an approach known as Haplotype Inference by Pure Parsimony (HIPP). Initial work in this area was based on a number of different Integer Linear Programming (ILP) models and branch and bound algorithms. Recent work has shown that the utilization of a Boolean Satisfiability (SAT) formulation and state of the art SAT solvers represents the most efficient approach for solving the HIPP problem. Motivated by the promising results obtained using SAT techniques, this paper investigates the utilization of modern Pseudo-Boolean Optimization (PBO) algorithms for solving the HIPP problem. The paper starts by applying PBO to existing ILP models. The results are promising, and motivate the development of a new PBO model (RPoly) for the HIPP problem, which has a compact representation and eliminates key symmetries. Experimental results indicate that RPoly outperforms the SAT-based approach on most problem instances, being, in general, significantly more efficient

Novel Excipient Candidates for RNA Stabilization

Until recently, the study of therapies using the RNA molecule as a therapeutic agent was considerably low when compared to therapies using DNA and proteins. For a long time, the RNA molecule was considered as a mere intermediary in the production of proteins. More recently, the study of the RNA molecule has led to a better understanding of its function, thus bringing a new perspective to potential therapeutic applications of this molecule. The use of therapeutic RNAs namely, mRNAs and microRNAs has been increasing, especially due to the recent use of mRNA in vaccination against COVID-19. One of the limitations in the use of mRNA vaccines, which has seen a lot of discussion, is the temperature at which they have to be stored, in order to maintain vaccine stability and effectiveness. This reveals the importance and urgency in identifying compounds capable of stabilizing the RNA molecule in order to facilitate, the storage and handling, while maintaining its biological activity. Taking into account the growing research in the therapeutic RNAs field, identifying stabilizers might have an impact when working with other RNA molecules with different applications. In the present work, Circular Dichroism (CD) assays were performed to assess the stability of the RNA structure, after incubation with different categories of excipients, namely amino acids (arginine and glycine), ionic liquids (N-acetyl amino acid N-alkyl cholinium-based ILs), sugars (glucose, sucrose and trehalose) and Deep Eutectic Solvents (DES) (glucose-based DES and trehalose-based DES). These studies also involved the assessment of stability over time (0, 7, 15, 30 and 60 days) at different storage temperatures (4 ° C and room temperature). In general, the results obtained demonstrate the potential of amino acids to stabilize RNA, for 60 days of storage at both temperatures. Moreover, the samples stabilized by the new excipient candidates also demonstrated great potential, taking into account that the samples stabilized by trehalose-based DES not only maintained their stability after 60 days at both temperatures, but also increased the melting temperature by around 18 °C. Data gathered by molecular docking simulations allowed for a better understanding of the interactions that happen between DES and RNA and which of the compounds might have a higher contribution for the RNA stabilization. Results using amino acid-based ionic liquids as stabilizers were also very encouraging, as most of the samples tested maintained stability over the testing period at both temperatures. Considering the results obtained, these confirm the stabilizing capacity of the classes already used as excipients and the potential of new classes as RNA stabilizers. Thus opening the door to new possibilities for formulating therapeutic products.Até recentemente, o estudo de terapias usando a molécula de RNA como agente terapêutico era consideravelmente reduzido, quando comparado com terapias usando DNA e proteínas. A molécula de RNA era considerada como um mero intermediário na produção de proteínas. Mais recentemente, o estudo da molécula de RNA levou à identificação de outras funções, trazendo uma nova perspetiva para a potencial aplicação terapêutica desta molécula. A utilização de RNAs terapêuticos nomeadamente, os mRNAs e microRNAs tem vindo a aumentar, especialmente devido ao uso recente do mRNA na vacinação contra a COVID-19. Uma das principais limitações na distribuição global e utilização das vacinas de mRNA, que muito tem sido discutida, é a temperatura de armazenamento necessária à manutenção de estabilidade e eficácia da vacina. Isto revela a importância e urgência na identificação de compostos capazes de estabilizar a molécula de RNA de modo a facilitar, o seu armazenamento e distribuição, garantindo a sua atividade biológica. Considerando a crescente investigação na área dos RNAs terapêuticos, a identificação de estabilizadores pode ter um impacto transversal e alargado a outras moléculas de RNA, com diferentes aplicações. No presente trabalho foram realizados ensaios de Dicroísmo Circular (CD) para avaliar a estabilidade da estrutura do RNA, após a incubação com diferentes categorias de excipientes, nomeadamente aminoácidos (arginina e glicina), líquidos iónicos (Nacetyl amino acid N-alkyl cholinium-based), açúcares (glucose, sacarose e trealose) e Deep Eutectic Solvents (DES) (glucose-based DES e trehalose-based DES). Os estudos de estabilidade envolveram também a avaliação da estabilidade de um RNA modelo ao longo do tempo (0, 7, 15, 30 e 60 dias) e também quando armazenado a diferentes temperaturas (4°C e temperatura ambiente). De uma maneira geral os resultados obtidos demonstraram a possibilidade de estabilizar o RNA na presença de aminoácidos, durante os 60 dias de armazenamento, quer a 4°C quer à temperatura ambiente. As novas classes de estabilizadores também demonstraram grande potencial, tendo em conta que as amostras estabilizadas por DES composto por trehalose e colina mantiveram a sua estabilidade após os 60 dias de armazenamento, a ambas as temperaturas, com um aumento da temperatura de melting de cerca de 18 °C. Os resultados obtidos por docking molecular permitiram um melhor entendimento das interações estabelecidas entre os DES e a molécula de RNA, permitindo estimar qual dos componentes do DES é que apresenta uma maior contribuição para a estabilização global da molécula de RNA. Outra das novas classes estudadas foram os líquidos iónicos com aminoácidos acetilados que também demonstraram resultados encorajadores. Neste caso, grande parte das amostras de RNA manteve a estabilidade ao longo do tempo, para ambas as temperaturas, demonstrando assim uma melhoria relativamente à amostra de RNA sem estabilizadores. Considerando os resultados obtidos, foi possível confirmar a possibilidade de estabilizar RNA usando alguns excipientes já estabelecidos e verificar o potencial de novas classes na indução da estabilidade desta molécula por um tempo médio de armazenamento à temperatura ambiente ou em refrigeração a 4 °C. Com este trabalho, criam-se novas perspetivas e novas possibilidades de formulação de produtos terapêuticos de base génica

Editorial

info:eu-repo/semantics/publishedVersio

Editorial

info:eu-repo/semantics/publishedVersio

The Huawei case and its aftermath: a new test for a new type of abuse

Competition law sets limits on the exercise of intellectual property rights by dominant companies, namely in cases involving standard essential patents (SEPs). This article will examine the framework for SEP owners’ right to seek an injunction, discussing competitive problems that such situations may cause as well as the solutions adopted by the European Institutions, comparing them with the US and Japanese approach, and finally reflecting upon the opportunity for a new test for a new type of abuse. Although the three legal orders – US, EU and Japan – apply different laws establishing a general presumption against injunctions in SEPs encumbered with FRAND commitments, their goal is the same: to protect the interest of the SEP holder to obtain a remuneration without an abusive recourse to injunctions. I will argue that, in the EU, the Huaweicase created a new test for a new type of abuse, improving the comprehensibility and certainty for the companies involved in standardization across Europe and allowing the harmonization of national judicial solutions regarding the seeking of injunctions in the SEPs context. In spite of some uncertainties, the new test clarifies the role that competition rules should play in cases of abuses by SEPs owners.Le droit de la concurrence fixe des limites à l’exercice des droits de propriété intellectuelle par les entreprises dominantes, notamment dans les affaires concernant des brevets essentiels standard (standard essential patents, SEPs). Cet article examinera le cadre du droit des propriétaires de SEP de demander une injonction en discutant des problèmes de la concurrence que de telles situations peuvent causer ainsi que des solutions adoptées par les institutions européennes. Ces solutions seront ensuite comparées avec l’approche américaine et japonaise. Enfin, l’auteur réfléchira à l’opportunité d’un nouveau test pour un nouveau type d’abus. Bien que les trois ordres juridiques – les États-Unis, l’UE et le Japon – appliquent des lois différentes établissant une présomption générale contre les injonctions dans des SEP grevés d’engagements FRAND, leur objectif est le même: protéger l’intérêt du titulaire du SEP d’obtenir une rémunération sans recours abusif aux injonctions. Je soutiendrai que, dans l’UE, l’affaire Huawei a créé un nouveau test pour un nouveau type d’abus, améliorant la compréhensibilité et la certitude pour les entreprises impliquées dans la normalisation en Europe et permettant l’harmonisation de solutions judiciaires nationales concernant la recherche d’injonctions dans le contexte des SEP. Malgré quelques incertitudes, le nouveau test clarifie le rôle que les règles de la concurrence devraient jouer dans les cas d’abus par des propriétaires de SEP.info:eu-repo/semantics/publishedVersio

Editorial

info:eu-repo/semantics/publishedVersio

The Lundbeck case through the lens of probabilistic patents

On Topic - The Lundbeck case and the concept of potential competitioninfo:eu-repo/semantics/acceptedVersio

Editorial

info:eu-repo/semantics/publishedVersio

National human rights institutions in the EU : Spanish and Portuguese experiences

The multilevel protection of human rights, through national Constitutions, European and International Conventions, is nowadays a fundamental goal at national and transnational levels. To achieve that goal, strengthening the role of the National Human Rights Institutions (NHRIs) is a priority. This article will focus a particular type of NHRIs – the Ombudsman – and will assess the Portuguese and Spanish experience in that domain, taking into account their advantages and the problems that have emerged in the national contexts.peer-reviewe