Genetic analysis of Pitx2 in left -right asymmetry and cardiovascular development

Pitx2, a paired-related homeobox gene that is mutated in human Rieger Syndrome, plays a key role in transferring the early asymmetric signals to individual organs. Pitx2 encodes three isoforms, Pitx2a, Pitx2b and Pitx2c. I found that Pitx2c was the Pitx2 isoform for regulating left-right asymmetry in heart, lung and the predominant isoform in guts. Previous studies suggested that the generation of left-right asymmetry within individual organs is an all or none, random event. Phenotypic analysis of various Pitx2 allelic combinations, that encode graded levels of Pitx2c, reveals an organ-intrinsic mechanism for regulating left-right asymmetric morphogenesis based on differential response to Pitx2c levels. The heart needs low Pitx2c levels, while the lungs and duodenum require higher doses of Pitx2c. In addition, the duodenal rotation is under strict control of Pitx2c activity. Left-right asymmetry development for aortic arch arteries involves complex vascular remodeling. Left-sided expression of Pitx2c in these developing vessels implied its potential function in this process. In order to determine if Pitx2c also can regulate the left-right asymmetry of the aortic arch arteries, a Pitx2c-specific loss of function mutation is generated. Although in wild type mice, the direction of the aortic arch is always oriented toward the left side, the directions of the aortic arches in the mutants were randomized, showing that Pitx2c also determined the left-right asymmetry of these vessels. I have further showed that the cardiac neural crest wasn't involved in this vascular remodeling process. In addition, all mutant embryos had Double Outlet Right Ventricle (DORV), a common congenital heart disease. This study provided insight into the mechanism of Pitx2c-mediated late stages of left-right asymmetry development and identified the roles of Pitx2c in regulation of aortic arch remodeling and heart development. ^

Development Resource Planning: Complexity of Product Development and the Capacity to Launch New Products

Overcommitment of development capacity or development resource deficiencies are important problems in new product development (NPD). Existing approaches to development resource planning have largely neglected the issue of resource magnitude required for NPD. This research aims to fill the void by developing a simple higher-level aggregate model based on an intuitive idea: The number of new product families that a firm can effectively undertake is bound by the complexity of its products or systems and the total amount of resources allocated to NPD. This study examines three manufacturing companies to verify the proposed model. The empirical results confirm the study`s initial hypothesis: The more complex the product family, the smaller the number of product families that are launched per unit of revenue. Several suggestions and implications for managing NPD resources are discussed, such as how this study`s model can establish an upper limit for the capacity to develop and launch new product families.

Policies to improve the lives of Slum Dwellers – from international agreements to local contexts. The Brazilian case-study

Last decades economic development induced massive international and regional migration flows directed to the urban spaces. The magnitude and swiftness of these processes determined that several cities’ authorities would fail to respond to the increasing demands of many social services. The right to an “adequate housing” emerged as a political concern, leading governments and institutions to develop housing programmes directed to improve the lives of slum dwellers. This paper presents a diachronic evolution of these specific housing policies in the paradigmatic case-study of Brazil, critically analysing the evolving roles played by the multiple levels of decision (from international institutions to local communities) in the development and implementation of such measures.

Neither dashboard nor 'mashup' indices: an empirical wealth approach as a pathway to a comprehensive measure of development

The article is composed of two sections. The first one is a critical review of the three main alternative indices to GDP which were proposed in the last decades – the Human Development Index (HDI), the Genuine Progress Indicator (GPI), and the Happy Planet Index (HPI) – which is made on the basis of conceptual foundations, rather than looking at issues of statistical consistency or mathematical refinement as most of the literature does. The pars construens aims to propose an alternative measure, the composite wealth index, consistent with an approach to development based on the notion of composite wealth, which is in turn derived from an empirical common sense criterion. Arguably, this approach is suitable to be conveyed into an easily understandable and coherent indicator, and thus appropriate to track development in its various dimensions: simple in its formulation, the wealth approach can incorporate social and ecological goals without significant alterations in conceptual foundations, while reducing to a minimum arbitrary weighting.

STRATEGIES TO SURPASS THE VULNERABILITY OF THE SMALL ISLAND STATES WITH FEW RESOURCES: THE CASE OF CAPE VERDE

The problem of small Island Developing States (SIDS) is quite recent, end of the 80s and 90s, still looking for a theoretical consolidation. SIDS, as small states in development, formed by one or several islands geographically dispersed, present reduced population, market, territory, natural resources, including drinkable water, and, in great number of the cases, low level of economic activity, factors that together, hinder the gathering of scale economies. To these diseconomies they come to join the more elevated costs in transports and communications which, allies to lower productivities, to a smaller quality and diversification of its productions, which difficult its integration in the world economy. In some SIDS these factors are not dissociating of the few investments in infrastructures, in the formation of human resources and in productive investments, just as it happens in most of the developing countries. In ecological terms, many of them with shortage of natural resources, but integrating important ecosystems in national and world terms, but with great fragility relatively to the pollution action, of excessive fishing, of uncontrolled development of tourism, factors that, conjugated and associated to the stove effect, condition the climate and the slope of the medium level of the sea water and therefore could put in cause the own survival of some of them. The drive to the awareness of the international community towards its problems summed up with the accomplishment by the United Nations in the Barbados’s Conference, 1994 where the right to the development was emphasized, through the going up the appropriate strategies and the Programme of Action for the Sustainable Development of the SIDS. The orientation of the regional and international cooperation in that sense, sharing technology (namely clean technology and control and administration environmental technology), information and creation of capacity-building, supplying means, including financial resources, creating non discriminatory and just trade rules, it would drive to the establishment of a world system economically more equal, in which the production, the consumption, the pollution levels, the demographic politics were guided towards the sustainability. It constituted an important step for the recognition for the international community on the specificities of those states and it allowed the definition of a group of norms and politics to implement at the national, regional and international level and it was important that they continued in the sense of the sustainable development. But this Conference had in its origin previous summits: the Summit of Rio de Janeiro about Environment and Development, accomplished in 1992, which left an important document - the Agenda 21, in the Conference of Stockholm at 1972 and even in the Conference of Ramsar, 1971 about “Wetlands.” CENTRO DE ESTUDOS AFRICANOS Occasional Papers © CEA - Centro de Estudos Africanos 4 Later, the Valletta Declaration, Malta, 1998, the Forum of Small States, 2002, get the international community's attention for the problems of SIDS again, in the sense that they act to increase its resilience. If the definition of “vulnerability” was the inability of the countries to resist economical, ecological and socially to the external shocks and “resilience” as the potential for them to absorb and minimize the impact of those shocks, presenting a structure that allows them to be little affected by them, a part of the available studies, dated of the 90s, indicate that the SIDS are more vulnerable than the other developing countries. The vulnerability of SIDS results from the fact the they present an assemblage of characteristics that turns them less capable of resisting or they advance strategies that allow a larger resilience to the external shocks, either anthropogenic (economical, financial, environmental) or even natural, connected with the vicissitudes of the nature. If these vulnerability factors were grouped with the expansion of the economic capitalist system at world level, the economic and financial globalisation, the incessant search of growing profits on the part of the multinational enterprises, the technological accelerated evolution drives to a situation of disfavour of the more poor. The creation of the resilience to the external shocks, to the process of globalisation, demands from SIDS and of many other developing countries the endogen definition of strategies and solid but flexible programs of integrated development. These must be assumed by the instituted power, but also by the other stakeholders, including companies and organizations of the civil society and for the population in general. But that demands strong investment in the formation of human resources, in infrastructures, in investigation centres; it demands the creation capacity not only to produce, but also to produce differently and do international marketing. It demands institutional capacity. Cape Verde is on its way to this stage.

Patents in the Information and Communications Technology Sector - Development Trends, Problem Areas and Pressures for Change

The patent system was created for the purpose of promoting innovation by granting the inventors a legally defined right to exclude others in return for public disclosure. Today, patents are being applied and granted in greater numbers than ever, particularly in new areas such as biotechnology and information andcommunications technology (ICT), in which research and development (R&D) investments are also high. At the same time, the patent system has been heavily criticized. It has been claimed that it discourages rather than encourages the introduction of new products and processes, particularly in areas that develop quickly, lack one-product-one-patent correlation, and in which theemergence of patent thickets is characteristic. A further concern, which is particularly acute in the U.S., is the granting of so-called 'bad patents', i.e. patents that do not factually fulfil the patentability criteria. From the perspective of technology-intensive companies, patents could,irrespective of the above, be described as the most significant intellectual property right (IPR), having the potential of being used to protect products and processes from imitation, to limit competitors' freedom-to-operate, to provide such freedom to the company in question, and to exchange ideas with others. In fact, patents define the boundaries of ownership in relation to certain technologies. They may be sold or licensed on their ownor they may be components of all sorts of technology acquisition and licensing arrangements. Moreover, with the possibility of patenting business-method inventions in the U.S., patents are becoming increasingly important for companies basing their businesses on services. The value of patents is dependent on the value of the invention it claims, and how it is commercialized. Thus, most of them are worth very little, and most inventions are not worth patenting: it may be possible to protect them in other ways, and the costs of protection may exceed the benefits. Moreover, instead of making all inventions proprietary and seeking to appropriate as highreturns on investments as possible through patent enforcement, it is sometimes better to allow some of them to be disseminated freely in order to maximize market penetration. In fact, the ideology of openness is well established in the software sector, which has been the breeding ground for the open-source movement, for instance. Furthermore, industries, such as ICT, that benefit from network effects do not shun the idea of setting open standards or opening up their proprietary interfaces to allow everyone todesign products and services that are interoperable with theirs. The problem is that even though patents do not, strictly speaking, prevent access to protected technologies, they have the potential of doing so, and conflicts of interest are not rare. The primary aim of this dissertation is to increase understanding of the dynamics and controversies of the U.S. and European patent systems, with the focus on the ICT sector. The study consists of three parts. The first part introduces the research topic and the overall results of the dissertation. The second part comprises a publication in which academic, political, legal and business developments that concern software and business-method patents are investigated, and contentiousareas are identified. The third part examines the problems with patents and open standards both of which carry significant economic weight inthe ICT sector. Here, the focus is on so-called submarine patents, i.e. patentsthat remain unnoticed during the standardization process and then emerge after the standard has been set. The factors that contribute to the problems are documented and the practical and juridical options for alleviating them are assessed. In total, the dissertation provides a good overview of the challenges and pressures for change the patent system is facing,and of how these challenges are reflected in standard setting.

Database Rights in Safe European Home: The Path to More Rigorous Protection of Information

1. Introduction "The one that has compiled ... a database, the collection, securing the validity or presentation of which has required an essential investment, has the sole right to control the content over the whole work or over either a qualitatively or quantitatively substantial part of the work both by means of reproduction and by making them available to the public", Finnish Copyright Act, section 49.1 These are the laconic words that implemented the much-awaited and hotly debated European Community Directive on the legal protection of databases,2 the EDD, into Finnish Copyright legislation in 1998. Now in the year 2005, after more than half a decade of the domestic implementation it is yet uncertain as to the proper meaning and construction of the convoluted qualitative criteria the current legislation employs as a prerequisite for the database protection both in Finland and within the European Union. Further, this opaque Pan-European instrument has the potential of bringing about a number of far-reaching economic and cultural ramifications, which have remained largely uncharted or unobserved. Thus the task of understanding this particular and currently peculiarly European new intellectual property regime is twofold: first, to understand the mechanics and functioning of the EDD and second, to realise the potential and risks inherent in the new legislation in economic, cultural and societal dimensions. 2. Subject-matter of the study: basic issues The first part of the task mentioned above is straightforward: questions such as what is meant by the key concepts triggering the functioning of the EDD such as presentation of independent information, what constitutes an essential investment in acquiring data and when the reproduction of a given database reaches either qualitatively or quantitatively the threshold of substantiality before the right-holder of a database can avail himself of the remedies provided by the statutory framework remain unclear and call for a careful analysis. As for second task, it is already obvious that the practical importance of the legal protection providedby the database right is in the rapid increase. The accelerating transformationof information into digital form is an existing fact, not merely a reflection of a shape of things to come in the future. To take a simple example, the digitisation of a map, traditionally in paper format and protected by copyright, can provide the consumer a markedly easier and faster access to the wanted material and the price can be, depending on the current state of the marketplace, cheaper than that of the traditional form or even free by means of public lending libraries providing access to the information online. This also renders it possible for authors and publishers to make available and sell their products to markedly larger, international markets while the production and distribution costs can be kept at minimum due to the new electronic production, marketing and distributionmechanisms to mention a few. The troublesome side is for authors and publishers the vastly enhanced potential for illegal copying by electronic means, producing numerous virtually identical copies at speed. The fear of illegal copying canlead to stark technical protection that in turn can dampen down the demand for information goods and services and furthermore, efficiently hamper the right of access to the materials available lawfully in electronic form and thus weaken the possibility of access to information, education and the cultural heritage of anation or nations, a condition precedent for a functioning democracy. 3. Particular issues in Digital Economy and Information Networks All what is said above applies a fortiori to the databases. As a result of the ubiquity of the Internet and the pending breakthrough of Mobile Internet, peer-to-peer Networks, Localand Wide Local Area Networks, a rapidly increasing amount of information not protected by traditional copyright, such as various lists, catalogues and tables,3previously protected partially by the old section 49 of the Finnish Copyright act are available free or for consideration in the Internet, and by the same token importantly, numerous databases are collected in order to enable the marketing, tendering and selling products and services in above mentioned networks. Databases and the information embedded therein constitutes a pivotal element in virtually any commercial operation including product and service development, scientific research and education. A poignant but not instantaneously an obvious example of this is a database consisting of physical coordinates of a certain selected group of customers for marketing purposes through cellular phones, laptops and several handheld or vehicle-based devices connected online. These practical needs call for answer to a plethora of questions already outlined above: Has thecollection and securing the validity of this information required an essential input? What qualifies as a quantitatively or qualitatively significant investment? According to the Directive, the database comprises works, information and other independent materials, which are arranged in systematic or methodical way andare individually accessible by electronic or other means. Under what circumstances then, are the materials regarded as arranged in systematic or methodical way? Only when the protected elements of a database are established, the question concerning the scope of protection becomes acute. In digital context, the traditional notions of reproduction and making available to the public of digital materials seem to fit ill or lead into interpretations that are at variance with analogous domain as regards the lawful and illegal uses of information. This may well interfere with or rework the way in which the commercial and other operators have to establish themselves and function in the existing value networks of information products and services. 4. International sphere After the expiry of the implementation period for the European Community Directive on legal protection of databases, the goals of the Directive must have been consolidated into the domestic legislations of the current twenty-five Member States within the European Union. On one hand, these fundamental questions readily imply that the problemsrelated to correct construction of the Directive underlying the domestic legislation transpire the national boundaries. On the other hand, the disputes arisingon account of the implementation and interpretation of the Directive on the European level attract significance domestically. Consequently, the guidelines on correct interpretation of the Directive importing the practical, business-oriented solutions may well have application on European level. This underlines the exigency for a thorough analysis on the implications of the meaning and potential scope of Database protection in Finland and the European Union. This position hasto be contrasted with the larger, international sphere, which in early 2005 does differ markedly from European Union stance, directly having a negative effect on international trade particularly in digital content. A particular case in point is the USA, a database producer primus inter pares, not at least yet having aSui Generis database regime or its kin, while both the political and academic discourse on the matter abounds. 5. The objectives of the study The above mentioned background with its several open issues calls for the detailed study of thefollowing questions: -What is a database-at-law and when is a database protected by intellectual property rights, particularly by the European database regime?What is the international situation? -How is a database protected and what is its relation with other intellectual property regimes, particularly in the Digital context? -The opportunities and threats provided by current protection to creators, users and the society as a whole, including the commercial and cultural implications? -The difficult question on relation of the Database protection and protection of factual information as such. 6. Dsiposition The Study, in purporting to analyse and cast light on the questions above, is divided into three mainparts. The first part has the purpose of introducing the political and rationalbackground and subsequent legislative evolution path of the European database protection, reflected against the international backdrop on the issue. An introduction to databases, originally a vehicle of modern computing and information andcommunication technology, is also incorporated. The second part sets out the chosen and existing two-tier model of the database protection, reviewing both itscopyright and Sui Generis right facets in detail together with the emergent application of the machinery in real-life societal and particularly commercial context. Furthermore, a general outline of copyright, relevant in context of copyright databases is provided. For purposes of further comparison, a chapter on the precursor of Sui Generi, database right, the Nordic catalogue rule also ensues. The third and final part analyses the positive and negative impact of the database protection system and attempts to scrutinize the implications further in the future with some caveats and tentative recommendations, in particular as regards the convoluted issue concerning the IPR protection of information per se, a new tenet in the domain of copyright and related rights.

NGO Duties in Relation to Human Rights. A Closer Look at One Proposal

This paper investigates the moral duties that human rights NGOs, such as Amnesty International, and development NGOs, such as Oxfam, have in relation to human rights – especially in relation to the human right to a decent standard of living. The mentioned NGOs are powerful new agents on the global scene, and according to many they might be duty-bearers in relation to human rights. However, until now their moral duties have hardly been investigated. The present paper investigates NGO duties in relation to human rights by looking in particular to a moral theory recently proposed by Leif Wenar, a theory which has some similarities to utilitarianism. In applying this theory, a case for human-rights duties of NGOs is developed mainly by considering the indispensable role that civil society plays in protecting human rights. The paper concludes that, at least, NGOs bear duties with regard to human rights when, as in certain real-life cases, NGO involvement is the only way to achieve acceptable protection against standard threats to certain goods, such as a decent standard of living.

The ISSA Pedagogical Standards: a tool to influence quality in early childhood programs

The ISSA Pedagogical Standards were first published in 2001 as a network-developed tool that defined quality in teaching practices and the classroom environment and captured the changes that had occurred in the region since 1994 when the Step by Step Program, an initiative to promote democratic principles in early childhood development and education, was launched. The Program was built on belief that each child has the right to receive maximum support for the development of his or her full potential, and this work should be done in partnership and close cooperation with families, communities and professionals

Advances and limitations in the attention to the problems of housing and urban land in Mexico. An approach from the legal-institutional frame

In this work we analyze the reforms carried out by the Mexican state in the nineties of the 20th century, in the items concerning the policies of housing and urban land, based on an exhaustive review of the main actions, programs and changes in the legal and institutional frame that applies for each of these fields. The nineties represent a "breaking point" in the way the State considers the satisfaction of the right to the housing and attends the offer of urbanized land for a tidy and sustainable urban development. In this period of time, the approach of direct intervention in developing and financing housing and creation of land reserves has changed into another one, ruled by the logic of the market. The balance to the first decade of the 21st century is ambiguous, as neither the housing policy has solved the housing shortage for low-income population, nor the land policy has eliminated the illegal urban growth.

Access to the countryside of England and Wales: popular leisure; commodified culture

Risk and uncertainty are, to say the least, poorly considered by most individuals involved in real estate analysis - in both development and investment appraisal. Surveyors continue to express 'uncertainty' about the value (risk) of using relatively objective methods of analysis to account for these factors. These methods attempt to identify the risk elements more explicitly. Conventionally this is done by deriving probability distributions for the uncontrolled variables in the system. A suggested 'new' way of "being able to express our uncertainty or slight vagueness about some of the qualitative judgements and not From its modern origins, associated with the urbanising effect of industrialisation, walking has remained a popular form of outdoor recreation. It has, furthermore, remained an important site of class struggle, with the 'landless' seeking to establish their moral 'citizen' right to roam over open country in contradistinction to the 'landed', who have successfully limited this right to legally-defined public rights of way. In the face of declining farm incomes, however, farmers and landowners have, apparently, modified their attitudes towards public access, but only in return for compensation and management payments under grant schemes such as Countryside Stewardship and the Countryside Premium Scheme. With the Ministry of Agriculture, Fisheries and Food now seeking to extend paid access arrangements to other grant schemes, as part of its response to the European Union's Agri-Environment Regulations, access 'rights' are assuming an increasingly commodified form, thereby questioning, if not undermining, the former citizen claims. For rather than being a benefit of citizenship, the existence of limited, often poorly maintained and inadequately signposted, public rights of way has tied inextricably the extension of legally-enforceable access to the needs of the landowners and farmers. At a time of falling prosperity in agriculture, therefore, they have now exercised their discretion by annexing the populism of consumer culture to reproduce the bourgeois liberal values of the market as a principal determinant of the extension of citizen rights of access to the countryside.

The Evolution of a Responsibility to Protect in Africa : The African Unions Emerging Peace and Security Regime

The thesis focuses on, and tries to evaluate, the role that the African Union (AU) plays in protecting the peace and security on the African continent. The thesis takes an interdisciplinary approach to the topic by both utilizing international relations and international law theories. The two disciplines are combined in an attempt to understand the evolution of the AU’s commitment to the pragmatist doctrine: responsibility to protect (R2P). The AU charter is considered to be the first international law document to cover R2P as it allows the AU to interfere in the internal affairs of its member states. The R2P doctrine was evolved around the notion of a need to arrive at a consensus in regard to the right to intervene in the face of humanitarian emergencies. A part of the post-Cold War shift in UN behaviour has been to support local solutions to local problems. Hereby the UN acts in collaboration with regional organizations, such as the AU, to achieve the shared aspirations to maintain international peace and security without getting directly involved on the ground. The R2P takes a more holistic and long-term approach to interventions by including an awareness of the need to address the root causes of the crisis in order to prevent future resurrections of conflicts. The doctrine also acknowledges the responsibility of the international community and the intervening parties to actively participate in the rebuilding of the post-conflict state. This requires sustained and well planned support to ensure the development of a stable society.While the AU is committed to implementing R2P, many of the AU’s members are struggling, both ideologically and practically, to uphold the foundations on which legitimate intervention rests, such as the protection of human rights and good governance. The fact that many members are also among the poorest countries in the world adds to the challenges facing the AU. A lack of human and material resources leads to a situation where few countries are willing, or able, to support a long-term commitment to humanitarian interventions. Bad planning and unclear mandates also limit the effectiveness of the interventions. This leaves the AU strongly dependent on regional powerbrokers such as Nigeria and South Africa, which in itself creates new problems in regard to the motivations behind interventions. The current AU charter does not provide sufficient checks and balances to ensure that national interests are not furthered through humanitarian interventions. The lack of resources within the AU also generates worries over what pressure foreign nations and other international actors apply through donor funding. It is impossible for the principle of “local solutions for local problems? to gain ground while this donor conditionality exists.The future of the AU peace and security regime is not established since it still is a work in progress. The direction that these developments will take depends on a wide verity of factors, many of which are beyond the immediate control of the AU.

Periapical tissue reactions to calcium hydroxide and MTA after external root resorption as a sequela of delayed tooth replantation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Women's contribution to equality in Latin America and the Caribbean

Includes bibliography