Search

We examine the epistemic disjunction between economic and legal scholarship with respect to the concept of the contract. While economics continues to tendto treat the “contract” as a single,unified concept, legal studies, increasingly, acknowledges wide institutional variation in contracts in different contexts. Based on extensive analysis of the empirical evidence on contracting practices, we take a radical step in the direction of challenging a unitary theory of contract. We propose that there exist patterns of contracting across three different sectors: the high, medium and low levels of sophistication of the market economy and tease out, so far unnoticed, similarities in the high and low ends of the spectrum, i.e., instances where uncertainty is particularly salient. We argue that economic theory would provide a more accurate analysis of contracting practices, and, indeed, contracts, if these different variations, and their implications, were foregrounded.

L'objectiu principal del projecte és el desenvolupament d'un prototip funcional per a un sistema de gestió i visualització d'excedents fotovoltaics basat en la integració de tecnologies ja existents. En termes més concrets, implica la implementació d'una solució software capaç de gestionar els excedents d'energia d'una casa intel·ligent o instal·lació similar (seguiment de l'ús de l'energia importada/exportada, decidir quan i com utilitzar l'excés d'energia, etc.), així com visualitzar-lo (consum de diferents dispositius, càlcul de potènciacostos/beneficis, recursos hardware, etc.) The project's main objective is the development of a working prototype for a photovoltaic excess management and visualization system based on the integration of already existing technologies. In more concrete terms, this means the implementation of a software-based solution capable of managing excess power from a smart home or similar installation (tracking use of imported/exported power, deciding when and how to use excess power, etc.), as well as visualizing it (consumption of different devices, computation of power costs/benefits, hardware resources, etc.)

Collaborative inter-firm innovation in the frontiers of the knowledge economy: preliminary remarks towards rethinking private law for the new economy Inovação interfirma colaborativa nas fronteiras da economia do conhecimento: considerações preliminares para repensar o direito privado na nova economia Innovación colaborativa interfirma en las fronteras de la economía del conocimiento: consideraciones preliminares para repensar o derecho privado en la nueva economía Pablo Marcello Baquero* RESUMO: Este artigo se propõe a examinar a questão da inovação colaborativa entre empresas em quatro etapas. Primeiro, analiso as principais características do paradigma de produção da “Nova Economia”, onde as empresas são cada vez mais obrigadas a estabelecer relações de colaboração para se manterem competitivas no mercado. Segundo, examino as principais formas de colaboração entre empresas estabelecidas e as formas correspondentes de desenho legal das transações. Terceiro, descrevo os principais desafios legais de coordenação para que essas colaborações sejam eficazes. Quarto, concluo mencionando as formas potenciais pelas quais as regras de comércio internacional ou guias legislativos podem contribuir para facilitar e encorajar colaborações inovadoras entre empresas legalmente independentes para inovar. PALAVRAS-CHAVE: Nova Economia. Colaboração entre empresas. Inovação. RESUMEN: Este artículo propone examinar el tema de la innovación colaborativa entre empresas en cuatro etapas. En primer lugar, analizo las principales características del paradigma productivo de la “Nueva Economía”, donde las empresas se ven cada vez más obligadas a establecer relaciones de colaboración para seguir siendo competitivas en el mercado. En segundo lugar, examino las principales formas de colaboración entre empresas establecidas y las correspondientes formas de diseño de transacciones legales. En tercer lugar, describo los principales desafíos legales de la coordinación para que estas colaboraciones sean efectivas. En cuarto lugar, concluyo mencionando las posibles formas en que las reglas de comercio internacional o las directrices legislativas pueden contribuir a facilitar y fomentar colaboraciones innovadoras entre empresas legalmente independientes para innovar. PALABRAS-CLAVE: Nueva Economía. Colaboración entre empresas. Innovación ABSTRACT: This paper proposes to examine the issue of collaborative inter-firm innovation in four steps. In the first, I analyze the main features of the “New Economy” production paradigm, where companies increasingly are required to establish collaborative relationships to remain competitive in the market. Second, I examine the main forms of inter-firm collaborations established and the corresponding forms of legal design of the transactions. Third, I describe the main legal challenges of coordination for these collaborations to be effective. Fourth, I conclude mentioning the potential ways through which international trade rules or legislative guides could contribute to facilitating and encouraging innovative collaborations between legally independent companies to innovate. KEYWORDS: New Economy. Inter-firm collaboration. Inovation. SUMÁRIO: Introduction. 1 The “new economy” production paradigm: de-verticalization, globalization, problem-solving. 2 Models of inter-firm cooperation: relational, modular, co-design. 3 Legal issues regarding collaborative innovative projects: beyond the traditional legal categories. 4 Challenges to be overcome in the coordination of collaborative inter-firm projects. 5 Potential areas of study for international trade organizations. 5.1 Governance mechanisms and legal design. 5.2 Legal doctrine. References. * Professor Assistente na École des hautes études commerciales de Paris, na França (HEC Paris). Doutor em Direito pela Universidade de Cambridge, na Inglaterra. E-mail: baquero@hec.fr

El Sistema Ventricular Cerebral se desarrolla de forma paralela al resto del Sistema Nervioso Central, facilitando la circulación del Líquido Cefalorraquídeo, desde su separación del líquido amniótico a nivel embrionario. Este desarrollo es necesario para entender correctamente la anatomía ventricular y facilitar el abordaje para patologías intraventriculares. El objetivo de esta revisión es reconocer los puntos más importantes en la embriología ventricular para facilitar el aprendizaje de la anatomía quirúrgica ventricular The cerebral ventricular system is developed in parallel with the rest of the central nervous system, facilitating the circulation of cerebrospinal fluid, from the amniotic fluid separation in the embryonic phases. This development is necessary to correctly understand the ventricular anatomy and facilitate approach to intraventricular pathologies. The objective of this review is to recognize the most important points in the ventricular embryology and in the intraventricular endoscopic vision to facilitate learning of the ventricular surgical anatomy

Despite the development of selective BCR‐ABL‐targeting tyrosine kinase inhibitors (TKIs) transforming the management of chronic myeloid leukaemia (CML), therapy‐resistant leukaemic stem cells (LSCs) persist after TKI treatment and present an obstacle to a CML cure. Recently, we and others have made significant contributions to the field by unravelling survival dependencies in LSCs to work towards the goal of eradicating LSCs in CML patients. In this review, we describe these findings focusing on autophagy and mitochondrial metabolism, which have recently been uncovered as two essential processes for LSCs quiescence and survival, respectively. In addition, we discuss the therapeutic potential of autophagy and mitochondrial metabolism inhibition as a strategy to eliminate CML cells in patients where the resistance to TKI is driven by BCR‐ABL‐independent mechanism(s).

This paper proposes that societal constitutionalism, as elaborated by Gunther Teubner, provides a potential legal approach to understand the structure of the EU, one that can provide valuable insights into how to deal with some of the problems generating its identity crisis. The theory of societal constitutionalism provides a perspective of the EU as a flexible, malleable organization, able to maintain a certain coherence while remaining open for adaptation to different circumstances. This structure, combining flexibility with coherence, could serve as a guideline in rethinking or reforming an EU that can overcome/survive the current crisis. The paper is structured in six parts, each of them examining an issue of EU law, proposing how it would be examined in the light of Teubner’s theory of societal constitutionalism. This analysis intends to reveal the EU legal persona that emerges from the viewpoint of social systems theory, in the context of examples that have been discussed in the scholarly legal literature on the EU crisis.

This thesis analyses whether and what adaptations the Law of Contract and Contract Governance require to deal with inter-firm relationships to collaboratively co-create advanced innovation in the comparative context of English and Brazilian law. It asks how inter-firm practices to generate advanced innovation are contractually structured and whether there is a need to rethink the legal doctrine to facilitate these kinds of relationships. The hypotheses proposed in this thesis are the following. First, legal experimentalism is the most adequate approach to deal with these highly uncertain relationships – through the development of a procedural framework for the continuous and collaborative revision of the obligations of the parties involved in the project. Second, legal experimentalism in contracts to innovate is instrumentalised through the braiding (intertwining) of formal and informal (relational) contracting to propel cooperation and undermine opportunism. Third, the “low-powered enforcement” approach towards these transactions (rejecting expectation damages or specific performance but granting reliance damages for violations of the agreement), suggested in the relevant literature, requires further clarification of what constitutes substantial violations of cooperation duties. The thesis provides an original contribution in four levels. First, by surveying legal concepts of contractual networks available in the comparative legal scholarship with the potential to govern advanced innovation projects. Second, by systematising and expanding the repertoire of governance mechanisms available for coordinating these transactions, considering the comparative legal scholarship and empirical studies from different jurisdictions on this subject. Third, by undertaking an empirical assessment examining the tenets of braiding theory in the Brazilian context. Fourth, by refining the concept and applications of a duty of loyalty to the network (or to the collaborative project) as an interpretative parameter to legally regulate these relationships, identifying potential violations of duties to cooperate., CAPES Cambridge Trust

Background Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment. By modeling ponatinib resistance and testing samples from these CML patients, it is hoped that an alternative drug target can be identified and inhibited with a novel compound. Methods Two CML cell lines with acquired BCR-ABL-independent resistance were generated following culture in ponatinib. RNA sequencing and gene ontology (GO) enrichment were used to detect aberrant transcriptional response in ponatinib-resistant cells. A validated oncogene drug library was used to identify US Food and Drug Administration–approved drugs with activity against TKI-resistant cells. Validation was performed using bone marrow (BM)–derived cells from TKI-resistant patients (n = 4) and a human xenograft mouse model (n = 4–6 mice per group). All statistical tests were two-sided. Results We show that ponatinib-resistant CML cells can acquire BCR-ABL-independent resistance mediated through alternative activation of mTOR. Following transcriptomic analysis and drug screening, we highlight mTOR inhibition as an alternative therapeutic approach in TKI-resistant CML cells. Additionally, we show that catalytic mTOR inhibitors induce autophagy and demonstrate that genetic or pharmacological inhibition of autophagy sensitizes ponatinib-resistant CML cells to death induced by mTOR inhibition in vitro (% number of colonies of control[SD], NVP-BEZ235 vs NVP-BEZ235+HCQ: 45.0[17.9]% vs 24.0[8.4]%, P = .002) and in vivo (median survival of NVP-BEZ235- vs NVP-BEZ235+HCQ-treated mice: 38.5 days vs 47.0 days, P = .04). Conclusion Combined mTOR and autophagy inhibition may provide an attractive approach to target BCR-ABL-independent mechanism of resistance.

Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment. By modeling ponatinib resistance and testing samples from these CML patients, it is hoped that an alternative drug target can be identified and inhibited with a novel compound. Methods: Two CML cell lines with acquired BCR-ABL-independent resistance were generated following culture in ponatinib. RNA sequencing and gene ontology (GO) enrichment were used to detect aberrant transcriptional response in ponatinib-resistant cells. A validated oncogene drug library was used to identify US Food and Drug Administration-approved drugs with activity against TKI-resistant cells. Validation was performed using bone marrow (BM)-derived cells from TKI-resistant patients (n = 4) and a human xenograft mouse model (n = 4-6 mice per group). All statistical tests were two-sided. Results: We show that ponatinib-resistant CML cells can acquire BCR-ABL-independent resistance mediated through alternative activation of mTOR. Following transcriptomic analysis and drug screening, we highlight mTOR inhibition as an alternative therapeutic approach in TKI-resistant CML cells. Additionally, we show that catalytic mTOR inhibitors induce autophagy and demonstrate that genetic or pharmacological inhibition of autophagy sensitizes ponatinib-resistant CML cells to death induced by mTOR inhibition in vitro (% number of colonies of control[SD], NVP-BEZ235 vs NVP-BEZ235+HCQ: 45.0[17.9]% vs 24.0[8.4]%, P = .002) and in vivo (median survival of NVP-BEZ235- vs NVP-BEZ235+HCQ-treated mice: 38.5 days vs 47.0 days, P = .04). Conclusion: Combined mTOR and autophagy inhibition may provide an attractive approach to target BCR-ABL-independent mechanism of resistance.

El conocimiento de la anatomía de las estructuras cerebrales en relación con los ventrículos cerebrales representa la capacidad para poder respetarlas durante una tercer ventriculostomía endoscópica (TVE), lo cual es indispensable para evitar complicaciones relacionadas al procedimiento. El propósito de este trabajo es hacer una revisión sobre la anatomía ventricular endoscópica, tomas ventriculares y vías de acceso para hacer una TVE. Se revisaron los puntos relevantes de la técnica quirúrgica y de la anatomía ventricular en nuestra experiencia institucional con el fin de hacer una descripción gráfica de la anatomía ventricular endoscópica para fenestración del piso del tercer ventrículo. Se mostrarán imágenes y videos relacionados con este abordaje. Knowledge of anatomy of brain structu-res in relation to the cerebral ventricles represents the capacity to respect them during an Endoscopic Third Ventriculostomy (ETV), which is essential to prevent complications related to the procedure. The purpose of this paper is to review the ventri-cular endoscopic anatomy, ventricular outlets and access roads to make a successful ETV. The relevant points of the surgical technique and of the ventri-cular anatomy in our institutional experience in or-der to make a graphic description of the anatomy for endoscopic ventricular floor fenestration of the third ventricle were reviewed.