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

The impact of the law 10,267/2001 in the brazilian rural registration

The publication of the Law 10,267 of 08/28/2001 changed the paradigm of rural registration in Brazil, because this law known as the "Law of Georeferencing" has created the National Registration of Rural Property, that unifies in a common basis different registrations present in several government agencies, such as the National Institute for Colonization and Agrarian Reform (INCRA), the Secretariat of Federal Revenue, the Brazilian Institute of Environment and Natural Resources, and the National Indian Foundation. Also, this new registration system has a graphical component which has not existed until such date, where the boundaries of rural property are georeferenced to the Brazilian Geodetic System. This new paradigm has resulted in a standardization of the survey and its representation of rural properties according to the Technical Standard for Georeferencing of Rural Properties, published by INCRA in compliance with the new legislation. Due to the georeferencing, the creation of a public GIS of free access on the Internet was possible. Among the difficulties found it may be observed the great Brazilian territory, the need for specialized professionals, and especially the certification process that INCRA has to perform for each georeferenced property. It is hoped that this last difficulty is solved with the implementation of the Land Management System that will allow automated and online certification, making the process more transparent, agile and fast.

In Search for the European solidarity: The rule of law within the European Union in the framework of constitutional pluralism

The dissertation examines the rule of law within the European Union in the theoretical framework of constitutional pluralism. The leading lines of constitutional pluralism are examined with relation to the traditional and prevailing, monistic and hierarchical conceptions on how to perceive legal orders in Europe. The theoretical part offers also historical perspective by highlighting some of the turning points for the Union constitutional legal order in the framework of European integration. The concept of rule of law is examined in legal terms and its meaning to the Union constitutional constellation as a constitutional principle and a common value is observed. The realization of the rule of law at supranational and national level is explored with a view to discover that recent developments in some of the Member States give rise to concern about the viability of the rule of law within the European Union. It is recognized that the inobservance of the rule of law at national level causes a threat to the supranational constitutional legal order. The relationship between the supranational and national legal orders is significant in this respect and therefore particularly the interaction between the Court of Justice of the European Union (hereinafter the ECJ) and the Member States’ (constitutional/supreme) courts takes focus. It is observed that functioning dialogue between the supranational and national courts based on mutual respect and judicial deference is an important prerequisite for the realization of the rule of law within Europe. In order to afford a concrete example, a recent case C-62/14 Gauweiler v Deutscher Bundestag is introduced and analysed in relation to the notorious relationship between the Federal Constitutional Court of Germany and the ECJ. The implications of the ECJ’s decision in Gauweiler v Deutscher Bundestag is assessed with reference to some of the pressing issues of constitutionalism within Europe and some institutional aspects are also brought forward. Lastly, the feasibility of constitutional pluralism as a theoretical setting is measured against the legal reality of today’s Europe and its many constitutions. The hierarchical idea of one ultimate source of power, stemming from the traditional approaches to legal systems, is then assessed with relation to the requirement of the realization of the rule of law within the European Union from the supranational and national point of view.

By-Law no. 12

A by-law begins: "It was then moved by R.S. Kinner and Seconded by George Barnes that by Law No. 12 be read. Whereas by Identure bearing date thirteenth day of August A.D. 1873 made between one George Barnes of the first part thereof and Andrew S. Kinner and Charles Robert Murray of the second part thereof which said Identure was duly registered in the Registry Office for Lands for the said County of Lincoln on the 14th day of August A.D. 1880 in Book 4 for the Township of Louth as No. 1534 the said George Barnes granted and conveyed the Lands and premises therein described to the said Andrew S. Kinner and Charles Robert Murray and their heirs and assigns as joint tenants and not as tenants as common upon the trusts and for the purposes therein expressed. And Whereas the said Andrew S. Kinner died on about the 13th day of June 1877 A.D. without having made any appointment under the provisions of the said in part recited Identure.."

Internet Law - An Attempt at a Polemic Retrospective

"Herbert Burket trace l’évolution des concepts reliés au ""droit de l’Internet"" dans le cadre du droit de l’Union Européenne. Initialement, ce domaine du droit était perçu comme une nouvelle discipline normative. Or, l’auteur soutient que le ""droit de l’Internet"" n’est pas un domaine normatif distinct, mais correspond aux domaines traditionnels auxquels il a été progressivement intégré. Le ""droit de l’Internet"" a amélioré notre compréhension du processus général d’évolution du droit. L’auteur souligne, entre autres, comment le législateur européen a réagi par diverses législations aux nouveaux impératifs technologiques. De plus, ce domaine offre une nouvelle perspective pour l’analyse de l’évolution des normes face aux innovations technologiques. Les tribunaux, les législateurs et les parties privées sont autant d’acteurs qui interviennent à différents moments et sur différents aspects du processus d’évolution du droit. Enfin, on s’attendait à ce que le droit de l’Internet conduise à la mondialisation des normes, à l’autorégulation des acteurs et à une architecture structurelle normative ouverte. L’auteur constate que la mondialisation des normes ne semble pas s’être réalisée. L’autorégulation, dans le domaine de l’Internet, fait référence aux normes de comportement établies par des acteurs privés et mixtes. Enfin, le concept d’architecture structurelle normative réfère au fait que les créateurs d’un système technologique imposent involontairement certaines règles aux utilisateurs, en dépit de l’affirmation qu’un tel système technologique est normativement neutre. L’auteur soutient que ces attentes, bien qu’elles soient toujours présentes au sein de l’activité normative, n’ont plus la même signification qu’au moment de leur formulation originale. Les concepts traditionnels de période normative, de juridiction, d’acteurs et de procédure ont aussi évolué parallèlement au développement du ""droit de l’Internet"", autant dans le cadre de l’environnement normatif de l’Union Européenne que dans celui du droit international en général. L’évolution de ces concepts modifie le processus de création du droit, ainsi que le rôle et les fonctions des intervenants impliqués dans ce processus.L’auteur conclut en soulignant que le concept même de droit a évolué en perdant ses représentations symboliques traditionnelles grâce au développement de l’accès généralisé à l’information, à l’évolution des technologies de l’information et à leur impact culturel."

The Legal Implications of Internet Marketing : Exploiting the Digital Marketplace Within the Boundaries of the Law

Au cours des dernières années, le domaine de la consommation a grandement évolué. Les agents de marketing ont commencé à utiliser l’Internet pour influencer les consommateurs en employant des tactiques originales et imaginatives qui ont rendus possible l’atteinte d'un niveau de communication interpersonnelle qui avait précédemment été insondable. Leurs interactions avec les consommateurs, en utilisant la technologie moderne, se manifeste sous plusieurs formes différentes qui sont toutes accompagnés de leur propre assortiment de problèmes juridiques. D’abord, il n'est pas rare pour les agents de marketing d’utiliser des outils qui leur permettent de suivre les actions des consommateurs dans le monde virtuel ainsi que dans le monde physique. Les renseignements personnels recueillis d'une telle manière sont souvent utilisés à des fins de publicité comportementale en ligne – une utilisation qui ne respecte pas toujours les limites du droit à la vie privée. Il est également devenu assez commun pour les agents de marketing d’utiliser les médias sociaux afin de converser avec les consommateurs. Ces forums ont aussi servi à la commission d’actes anticoncurrentiels, ainsi qu’à la diffusion de publicités fausses et trompeuses – deux pratiques qui sont interdites tant par la loi sur la concurrence que la loi sur la protection des consommateurs. Enfin, les agents de marketing utilisent diverses tactiques afin de joindre les consommateurs plus efficacement en utilisant diverses tactiques qui les rendent plus visible dans les moteurs de recherche sur Internet, dont certaines sont considérés comme malhonnêtes et pourraient présenter des problèmes dans les domaines du droit de la concurrence et du droit des marques de commerce. Ce mémoire offre une description détaillée des outils utilisés à des fins de marketing sur Internet, ainsi que de la manière dont ils sont utilisés. Il illustre par ailleurs les problèmes juridiques qui peuvent survenir à la suite de leur utilisation et définit le cadre législatif régissant l’utilisation de ces outils par les agents de marketing, pour enfin démontrer que les lois qui entrent en jeu dans de telles circonstances peuvent, en effet, se révéler bénéfiques pour ces derniers d'un point de vue économique.

Shari'a Commercial Law : "old wine in new bottles?"

Suite à la crise financière globale de 2008, ainsi qu’aux différents facteurs qui y ont mené, il est étonnant qu’une alternative éthique et juste pour une finance lucrative et stable n’existe toujours pas (ou du moins, demeure oubliée). Ayant décidé de contribuer au domaine pluri-centenaire du Droit Commercial de la Chari’a, nous avons été surpris par la découverte d’une problématique à l’origine de cette thèse. En France, nous avons suivi des débats doctrinaux intéressants dont les conclusions se rapprochent de la perception générale Occidentale quand à la nature de la finance Islamique, que ce soit au niveau de la finance basée sur le Droit de la Chari’a ou encore les exigences de sa pleine introduction dans le système juridique français de l’époque. Cet intérêt initial dans la finance islamique a ensuite mené à un intérêt dans la question des avantages d’éthique et de justice du Droit Commercial de la Chari’a dans son ensemble, qui est au coeur de cette thèse. Dans le monde moderne du commerce et de la finance d’aujourd’hui, les transactions sont marquées par une prise de risque excessive et un esprit de spéculation qui s’apparente aux jeux de hasard, et menant à des pertes colossales. Pire encore, ces pertes sont ensuite transférées à la collectivité. Par conséquent, y at-il des préceptes, des principes ou des règles éthiques et juridiques qui peuvent fournir une certaine forme de sécurité et de protection dans les marchés financiers d'aujourd'hui? Est-ce réalisable? Cette thèse soutient que la richesse de la jurisprudence islamique ainsi que ses règles dont les avantages n’ont pas encore été pleinement saisis et régénérés en réponse aux nouveaux défis d’aujourd'hui, peuvent encore fournir continuellement des solutions, et réformer des produits financiers de façon à refléter des principes de justice et d'équité. Dans ce processus, un éclairage nouveau sera apporté à certains sujets déjà connus dans le cadre de la contribution prévue de cette thèse, mais ne sera pas le principal objectif de la thèse.

“Documentary Credit Law : An Indian Perspective"

This is a study in international trade law. Documentary credits are the most common method of payment for goods in international trade. In India also these instruments are used both in national and international trade. The law governing these transactions remains haphazard. This study identifies the deficiencies in the regulatory framework for documentary credits in India. It primarily focuses on those areas which exhibits a lack of equality and justice in its operation. An attempt has also been made to identify the rights and duties of parties involved in the transaction. The reasons for the increase of fraudulent activities associated with the documents executed in the documentary credit transactions are also examined. How far the law in India is sufficient to ensure fair business practice in international trade financing is also examined. Methodology adopted for the study is analytical. The statutory provisions, rules and case laws under these provisions have been examined. An empirical study by personal interview with the bankers is also made to ascertain the practice of bankers in India.

Human rights and mortgage repossession: beyond property law using Article 8

Following the Supreme Court decisions in Manchester CC v Pinnock and Hounslow CC v Powell, this article examines the possible impact of Article 8 of the European Convention on Human Rights and Fundamental Freedoms upon protection of the home in creditor repossession proceedings. The central argument advanced is that, although occupiers may not all be protected through property law, they may enjoy an independent right to respect for their home under Article 8, which should be acknowledged in the legal frameworks governing creditor's enforcement rights against the home. The article suggests that the most common creditor enforcement route, through mortgage repossession proceedings, falls short in this regard. It takes as its primary focus the treatment of children in such proceedings to provide an example of the potential for a human rights-based property protection heralded by these two Supreme Court decisions.

Construction contracts: law and management. 4th edition

This is a fully revised edition of the UK’s leading textbook on the law governing construction contracts and the management and administration of those contracts. Although the legal principles involved are an aspect of general contract law, the practical and commercial complexities of the construction industry have increasingly made this a specialist area. This new edition has been brought up to date with recent cases and developments in the law as it stands at March 2007. The basic approach of the book has been retained. Rather than provide a commentary on standard-form contracts, our approach is to introduce the general principles that underlie contracts in construction, illustrating them by reference to the most important standard forms currently in use. Some of the common standard-form contracts have been revised since the previous edition, and the text has been revised to take account of these changes. Practitioners (consultants, builders, clients and lawyers) will find this an extremely useful source of reference, providing in-depth explanations for all of the features found in contemporary construction contracts, with reasons. A unique feature of this book is the way that it brings together the relevant principles of law with the practical issues arising in construction cases. It is a key text for construction undergraduates and postgraduates as well as for those taking the RIBA Part III and CIOB Part II examinations.

Non-Refoulement between 'Common Article 1' and 'Common Article 3'

This article considers whether, in the context of armed conflicts, certain non-refoulement obligations of non-belligerent States can be derived from the 1949 Geneva Conventions. According to Common Article 1 (CA1) thereof, all High Contracting Parties (HCPs) undertake to ‘respect and to ensure respect’ for the four conventions ‘in all circumstances’. It is contended that CA1 applies both in international armed conflicts (IACs) and in non-international armed conflicts (NIACs). In turn, it is suggested that Common Article 3 (CA3) which regulates conduct in NIACs serves as a ‘minimum yardstick’ also applicable in IACs. It is widely (though not uniformly) acknowledged that the undertaking to ‘ensure respect’ in a given armed conflict extends to HCPs that are not parties to it; nevertheless, the precise scope of this undertaking is subject to scholarly debate. This article concerns situations where, in the course of an (international or non-international) armed conflict, persons ’taking no active part in hostilities’ flee from States where violations of CA3 are (likely to be) occurring to a non-belligerent State. Based on the undertaking in CA1, the central claim of this article is that, as long as risk of exposure to these violations persists, persons should not be refouled notwithstanding possible assessment of whether they qualify as refugees based on the 1951 Refugee Convention definition, or could be eligible for complementary or subsidiary forms of protection that are regulated in regional arrangements. The analysis does not affect the explicit protection from refoulement that the Fourth Geneva Convention accords to ‘protected persons’ (as defined in Article 4 thereof). It is submitted that CA1 should be read in tandem with other obligations of non-belligerent States under the 1949 Geneva Conventions. Most pertinently, all HCPs are required to take specific measures to repress ‘grave breaches’ and to take measures necessary for the suppression of all acts contrary to the 1949 Geneva Conventions other than the grave breaches. A HCP that is capable of protecting displaced persons from exposure to risks of violations of CA3 and nonetheless refoules them to face such risks is arguably failing to take lawful measures at its disposal in order to suppress acts contrary to the conventions and, consequently, fails to ‘ensure respect’ for the conventions. KEYWORDS Non-refoulement; International Armed Conflict; Non-International Armed Conflict; Common Article 1; Common Article 3