Vitronectin is not essential for normal mammalian development and fertility.

Vitronectin (VN) is an abundant glycoprotein present in plasma and the extracellular matrix of most tissues. Though the precise function of VN in vivo is unknown, it has been implicated as a participant in diverse biological processes, including cell attachment and spreading, complement activation, and regulation of hemostasis. The major site of synthesis appears to be the liver, though VN is also found in the brain at an early stage of mouse organogenesis, suggesting that it may play an important role in mouse development. Genetic deficiency of VN has not been reported in humans or in other higher organisms. To examine the biologic function of VN within the context of the intact animal, we have established a murine model for VN deficiency through targeted disruption of the murine VN gene. Southern blot analysis of DNA obtained from homozygous null mice demonstrates deletion of all VN coding sequences, and immunological analysis confirms the complete absence of VN protein expression in plasma. However, heterozygous mice carrying one normal and one null VN allele and homozygous null mice completely deficient in VN demonstrate normal development, fertility, and survival. Sera obtained from VN-deficient mice are completely deficient in "serum spreading factor" and plasminogen activator inhibitor 1 binding activities. These observations demonstrate that VN is not essential for cell adhesion and migration during normal mouse development and suggest that its role in these processes may partially overlap with other adhesive matrix components.

Hybrid simulation-optimization based approach for the optimal design of single-product biotechnological processes

In this work, we present a systematic method for the optimal development of bioprocesses that relies on the combined use of simulation packages and optimization tools. One of the main advantages of our method is that it allows for the simultaneous optimization of all the individual components of a bioprocess, including the main upstream and downstream units. The design task is mathematically formulated as a mixed-integer dynamic optimization (MIDO) problem, which is solved by a decomposition method that iterates between primal and master sub-problems. The primal dynamic optimization problem optimizes the operating conditions, bioreactor kinetics and equipment sizes, whereas the master levels entails the solution of a tailored mixed-integer linear programming (MILP) model that decides on the values of the integer variables (i.e., number of equipments in parallel and topological decisions). The dynamic optimization primal sub-problems are solved via a sequential approach that integrates the process simulator SuperPro Designer® with an external NLP solver implemented in Matlab®. The capabilities of the proposed methodology are illustrated through its application to a typical fermentation process and to the production of the amino acid L-lysine.

Spherical carbons: Synthesis, characterization and activation processes

Spherical carbons have been prepared through hydrothermal treatment of three carbohydrates (glucose, saccharose and cellulose). Preparation variables such as treatment time, treatment temperature and concentration of carbohydrate have been analyzed to obtain spherical carbons. These spherical carbons can be prepared with particle sizes larger than 10 μm, especially from saccharose, and have subsequently been activated using different activation processes (H3PO4, NaOH, KOH or physical activation with CO2) to develop their textural properties. All these spherical carbons maintained their spherical morphology after the activation process, except when KOH/carbon ratios higher than 4/1 were used, which caused partial destruction of the spheres. The spherical activated carbons develop interesting textural properties with the four activating agents employed, reaching surface areas up to 3100 m2/g. Comparison of spherical activated carbons obtained with the different activating agents, taking into account the yields obtained after the activation process, shows that phosphoric acid activation produces spherical activated carbons with higher developed surface areas. Also, the spherical activated carbons present different oxygen groups’ content depending on the activating agent employed (higher surface oxygen groups content for chemical activation than for physical activation).

Development of multidisciplinary workshops between different subjects as an innovative teaching methodology for the acquisition of professional skills of the future architect

The implantation of the new Architecture Degree and the important normative changes in the building sector imply the need to use new teaching methodologies that enhance skills and competences in order to response to the increasing requirements demanded by society to the future architect. The aim of this paper is to present, analyze and discuss the development of multidisciplinary workshops as a new teaching methodology used in several Construction subjects of the Architecture Degree in the University of Alicante. Workshops conceived with the aim to synthesize and complement the technical knowledge acquired by the students during the Degree and to enhance the skills and competencies necessary for the professional practice. With that purpose, we decided to experiment on current subjects of the degree during this academic year, by applying the requirements defined in the future Architecture Degree in a practical way, through workshops between different subjects, superposing the technical knowledge with the resolution of constructive problems in the development of an architectural project. Developing these workshops between subjects we can dissolve the traditional boundaries between different areas of the Degree. This multidisciplinary workshop methodology allows the use of all the global knowledge acquired by students during their studies and at the same time, it enhances students’ ability to communicate and discuss their ideas and solutions in public. It also increases their capacity of self-criticism, and it foments their ability to undertake learning strategies and research in an autonomous way. The used methodology is based on the development of a practical work common to several subjects of different knowledge areas within the "Technology Block" of the future Architecture Degree. Thus, students work approaching the problem in a global way discussing simultaneously with teachers from different areas. By using these new workshops we stimulate an interactive class versus a traditional lecture. Work is evaluated continuously, valuing the participative pupil´s attitude, working in groups in class time, reaching weekly objectives and stimulating the individual responsibility and positive interdependence of the pupil inside the working group. The exercises are designed to improve students’ ability to transmit their ideas and solutions in public, knowing how to discuss and defend their technical resolutions to peers and teachers (Peer Reviewing), their capacity for self-criticism and their capacity to undertake strategies and autonomous learning processes at the same time they develop a personal research into new technologies, systems and materials. Students have shown their majority preference for this teaching methodology by the multidisciplinary workshops offered in the last years, with very satisfactory academic results. In conclusion, it can be verified nowadays the viability of the introduction of new contents and new teaching methodologies necessary for the acquisition of the skills in the future Architecture Degree, through workshops between several subjects that have had a great acceptance in students and positive contrasted academic results.

Seeding a Profession: The Intersection of the State, International Interests, and the Early Development of Brazilian Nursing

State and international entities can have profound effects on the development of a country’s nursing profession. Through a global health governance lens, this paper explores the development of nursing in Brazil during the early twentieth century, and its intersections with national and international interests. Accordingly, we will show how state policies established an environment that fostered the institutionalization of nursing as a profession in Brazil and supported it as a means to increase the presence of females in nation building processes. The State focused on recruiting elite women for nursing, in part due to the Rockefeller Foundation’s involvement in the country. Nurses who worked for Rockefeller came from well-educated classes within US society with specific ideas about who should be a nurse and the roles of nurses in a healthcare system. These women served as the primary vehicles for interacting with Brazilian health authorities responsible for health system development. Their early efforts did not, however, ensure a system capable of producing nursing human resources at a rate that, in present day Brazil, could meet the health needs of the country. Findings from this paper offer new avenues for historians to explore the early roots of professional nursing through a global health governance lens, improve the understanding of the intersection between international politics and professionalization, and highlight how these factors may impact nursing human resources production in the long term.

Role of the cotransporter KCC2 in cortical excitatory synapse development and febrile seizure susceptibility

Le co-transporteur KCC2 spécifique au potassium et chlore a pour rôle principal de réduire la concentration intracellulaire de chlore, entraînant l’hyperpolarisation des courants GABAergic l’autorisant ainsi à devenir inhibiteur dans le cerveau mature. De plus, il est aussi impliqué dans le développement des synapses excitatrices, nommées aussi les épines dendritiques. Le but de notre projet est d’étudier l’effet des modifications concernant l'expression et la fonction de KCC2 dans le cortex du cerveau en développement dans un contexte de convulsions précoces. Les convulsions fébriles affectent environ 5% des enfants, et ce dès la première année de vie. Les enfants atteints de convulsions fébriles prolongées et atypiques sont plus susceptibles à développer l’épilepsie. De plus, la présence d’une malformation cérébrale prédispose au développement de convulsions fébriles atypiques, et d’épilepsie du lobe temporal. Ceci suggère que ces pathologies néonatales peuvent altérer le développement des circuits neuronaux irréversiblement. Cependant, les mécanismes qui sous-tendent ces effets ne sont pas encore compris. Nous avons pour but de comprendre l'impact des altérations de KCC2 sur la survenue des convulsions et dans la formation des épines dendritiques. Nous avons étudié KCC2 dans un modèle animal de convulsions précédemment validé, qui combine une lésion corticale à P1 (premier jour de vie postnatale), suivie d'une convulsion induite par hyperthermie à P10 (nommés rats LHS). À la suite de ces insultes, 86% des rats mâles LHS développent l’épilepsie à l’âge adulte, au même titre que des troubles d’apprentissage. À P20, ces animaux presentent une augmentation de l'expression de KCC2 associée à une hyperpolarisation du potentiel de réversion de GABA. De plus, nous avons observé des réductions dans la taille des épines dendritiques et l'amplitude des courants post-synaptiques excitateurs miniatures, ainsi qu’un déficit de mémoire spatial, et ce avant le développement des convulsions spontanées. Dans le but de rétablir les déficits observés chez les rats LHS, nous avons alors réalisé un knock-down de KCC2 par shARN spécifique par électroporation in utero. Nos résultats ont montré une diminution de la susceptibilité aux convulsions due à la lésion corticale, ainsi qu'une restauration de la taille des épines. Ainsi, l’augmentation de KCC2 à la suite d'une convulsion précoce, augmente la susceptibilité aux convulsions modifiant la morphologie des épines dendritiques, probable facteur contribuant à l’atrophie de l’hippocampe et l’occurrence des déficits cognitifs. Le deuxième objectif a été d'inspecter l’effet de la surexpression précoce de KCC2 dans le développement des épines dendritiques de l’hippocampe. Nous avons ainsi surexprimé KCC2 aussi bien in vitro dans des cultures organotypiques d’hippocampe, qu' in vivo par électroporation in utero. À l'inverse des résultats publiés dans le cortex, nous avons observé une diminution de la densité d’épines dendritiques et une augmentation de la taille des épines. Afin de confirmer la spécificité du rôle de KCC2 face à la région néocorticale étudiée, nous avons surexprimé KCC2 dans le cortex par électroporation in utero. Cette manipulation a eu pour conséquences d’augmenter la densité et la longueur des épines synaptiques de l’arbre dendritique des cellules glutamatergiques. En conséquent, ces résultats ont démontré pour la première fois, que les modifications de l’expression de KCC2 sont spécifiques à la région affectée. Ceci souligne les obstacles auxquels nous faisons face dans le développement de thérapie adéquat pour l’épilepsie ayant pour but de moduler l’expression de KCC2 de façon spécifique.

Sustainable Development and Collective Learning: Theory and a European Case Study. Bruges European Economic Policy (BEEP) Briefing 7/2004

Network governance of collective learning processes is an essential approach to sustainable development. The first section of the article briefly refers to recent theories about both market and government failures that express scepticism about the way framework conditions for market actors are set. For this reason, the development of networks for collective learning processes seems advantageous if new solutions are to be developed in policy areas concerned with long-term changes and a stepwise internalisation of externalities. With regard to corporate actors’ interests, the article shows recent insights from theories about the knowledge-based firm, where the creation of new knowledge is based on the absorption of societal views. This concept shifts the focus towards knowledge generation as an essential element in the evolution of sustainable markets. This involves at the same time the development of new policies. In this context innovation-inducing regulation is suggested and discussed. The evolution of the Swedish, German and Dutch wind turbine industries are analysed based on the approach of governance put forward in this article. We conclude that these coevolutionary mechanisms may take for granted some of the stabilising and orientating functions previously exercised by basic regulatory activities of the state. In this context, the main function of the governments is to facilitate learning processes that depart from the government functions suggested by welfare economics.

Applications of thermal processing in pharmaceutical drug product development

Dissertação para obtenção do grau de Mestre no Instituto Superior de Ciências da Saúde Egas Moniz

'Going Public': The Mediatization of Decision-Making Processes

In most Western countries, the media are said to exert an increasing influence on the political game. This development, which has been described variably as a shift towards an 'audience democracy' (Manin 1995) or the 'mediatization of politics' (Mazzoleni and Schulz 1999), emphasizes the increasing importance of the media for political actors and political decision-making. In such a context, political actors need to communicate with both the media and the public in order to gain support for their policy plans and to influence decision-making. The media were noticeably absent from Kriesi's (1980) in-depth analysis of political decision-making in Switzerland. This suggests that in the early 1970s, the media did not matter or mattered far less than they do today.

Measuring the Social Identity of Entrepreneurs: Scale Development and International Validation

Recent research indicates that social identity theory offers an important lens to improve our understanding of founders as enterprising individuals, the venture creation process, and its outcomes. Yet, further advances are hindered by the lack of a valid scale that could be used to measure founders' social identities - a problem that is particularly severe because social identity is a multidimensional construct that needs to be assessed properly so that organizational phenomena can be understood. Drawing on social identity theory and the systematic classification of founders' social identities (Darwinians, Communitarians, Missionaries) provided in Fauchart and Gruber (2011), this study develops and empirically validates a 12-item scale that allows scholars to capture the multidimensional nature of social identities of entrepreneurs. Our validation tests are unusually comprehensive and solid, as we not only validate the developed scale in the Alpine region (where it was originally conceived), but also in 12 additional countries and the Anglo-American region. Scholars can use the scale to identify founders' social identities and to relate these identities to micro-level processes and outcomes in new firm creation. Scholars may also link founders' social identities to other levels of analysis such as industries (e.g., industry evolution) or whole economies (e.g., economic growth).

Role of the cotransporter KCC2 in cortical excitatory synapse development and febrile seizure susceptibility

Le co-transporteur KCC2 spécifique au potassium et chlore a pour rôle principal de réduire la concentration intracellulaire de chlore, entraînant l’hyperpolarisation des courants GABAergic l’autorisant ainsi à devenir inhibiteur dans le cerveau mature. De plus, il est aussi impliqué dans le développement des synapses excitatrices, nommées aussi les épines dendritiques. Le but de notre projet est d’étudier l’effet des modifications concernant l'expression et la fonction de KCC2 dans le cortex du cerveau en développement dans un contexte de convulsions précoces. Les convulsions fébriles affectent environ 5% des enfants, et ce dès la première année de vie. Les enfants atteints de convulsions fébriles prolongées et atypiques sont plus susceptibles à développer l’épilepsie. De plus, la présence d’une malformation cérébrale prédispose au développement de convulsions fébriles atypiques, et d’épilepsie du lobe temporal. Ceci suggère que ces pathologies néonatales peuvent altérer le développement des circuits neuronaux irréversiblement. Cependant, les mécanismes qui sous-tendent ces effets ne sont pas encore compris. Nous avons pour but de comprendre l'impact des altérations de KCC2 sur la survenue des convulsions et dans la formation des épines dendritiques. Nous avons étudié KCC2 dans un modèle animal de convulsions précédemment validé, qui combine une lésion corticale à P1 (premier jour de vie postnatale), suivie d'une convulsion induite par hyperthermie à P10 (nommés rats LHS). À la suite de ces insultes, 86% des rats mâles LHS développent l’épilepsie à l’âge adulte, au même titre que des troubles d’apprentissage. À P20, ces animaux presentent une augmentation de l'expression de KCC2 associée à une hyperpolarisation du potentiel de réversion de GABA. De plus, nous avons observé des réductions dans la taille des épines dendritiques et l'amplitude des courants post-synaptiques excitateurs miniatures, ainsi qu’un déficit de mémoire spatial, et ce avant le développement des convulsions spontanées. Dans le but de rétablir les déficits observés chez les rats LHS, nous avons alors réalisé un knock-down de KCC2 par shARN spécifique par électroporation in utero. Nos résultats ont montré une diminution de la susceptibilité aux convulsions due à la lésion corticale, ainsi qu'une restauration de la taille des épines. Ainsi, l’augmentation de KCC2 à la suite d'une convulsion précoce, augmente la susceptibilité aux convulsions modifiant la morphologie des épines dendritiques, probable facteur contribuant à l’atrophie de l’hippocampe et l’occurrence des déficits cognitifs. Le deuxième objectif a été d'inspecter l’effet de la surexpression précoce de KCC2 dans le développement des épines dendritiques de l’hippocampe. Nous avons ainsi surexprimé KCC2 aussi bien in vitro dans des cultures organotypiques d’hippocampe, qu' in vivo par électroporation in utero. À l'inverse des résultats publiés dans le cortex, nous avons observé une diminution de la densité d’épines dendritiques et une augmentation de la taille des épines. Afin de confirmer la spécificité du rôle de KCC2 face à la région néocorticale étudiée, nous avons surexprimé KCC2 dans le cortex par électroporation in utero. Cette manipulation a eu pour conséquences d’augmenter la densité et la longueur des épines synaptiques de l’arbre dendritique des cellules glutamatergiques. En conséquent, ces résultats ont démontré pour la première fois, que les modifications de l’expression de KCC2 sont spécifiques à la région affectée. Ceci souligne les obstacles auxquels nous faisons face dans le développement de thérapie adéquat pour l’épilepsie ayant pour but de moduler l’expression de KCC2 de façon spécifique.

Measuring the Social Identity of Entrepreneurs: Scale Development and International Validation

Social identity theory offers an important lens to improve understanding of founders as enterprising individuals, the venture creation process, and its outcomes. Yet, further advances are hindered by the lack of valid scales to measure founders’ social identities. Drawing on social identity theory and a systematic classification of founders’ social identities (Darwinians, Communitarians, and Missionaries), we develop and test a corresponding 15-item scale in the Alpine region and validate it in 13 additional countries and regions. The scale allows identifying founders’ social identities and relating them to processes and outcomes in entrepreneurship. The scale is available online in 15 languages.

A comparison of oxidation ditch plants to competing processes for secondary and advanced treatment of municipal wastes /

Mode of access: Internet.

Automotive manufacturing processes. Volume V - manufacturing processes and equipment for the mass production and assembly of motor vehicles. Final report.

National Highway Traffic Safety Administration, Office of Research and Development, Washington, D.C.

Processes affecting subsurface transport of leaking underground tank fluids /

"CR 810052."