Accurate 3D protein structure prediction is one of the most challenging problems facing bioinformaticians today. This thesis develops and examines an evaluation module for ranking predicted super-secondary structures – specifically a-helix pairs – as part of a case-based reasoning system. The proposed module is part of the Triptych project, which aims at the accurate prediction of the three-dimensional structure of proteins from contact maps. Triptych is an advanced case-based reasoning system that utilizes a library of existing protein structures and motifs to help predict the structure of a known polypeptide chain of amino acids that represents a target a-helix pair. The proposed module evaluates possible solutions by integrating multiple strategies, learning methods and sources of knowledge in the form of expert advisors. It uses advisors which integrate knowledge from the fields of biology, biochemistry, classical physics, and statistical data analysis obtained from pre-determined structures. Lastly, the proposed evaluation module would allow for the integration of more sources of knowledge, in the form of expert advisors, as well as serve as a framework for evaluating other structural motifs in future. / Thesis (Master, Computing) -- Queen's University, 2007-09-09 19:42:59.094

Rapid changes in the global economy forces Industry to continuously seek competitive advantages; the University on the other hand pursue additional funding. Both Industry and University are trying to keep up with the accelerating pace of change, therefore partnership become critical in achieving key objectives. Research collaborations become essential and offer direct benefits for University and company participants. The impact extends well beyond the direct partners. When potential partners have the resources and knowledge to accomplish individual goals, working with outside experts can improve the quality of the research and help to reduce costs. Industry-sponsored research allows the University to obtain financial support as well as Industry exposure for its educational and research missions. The Technology and Human Resources for Industry Programme (THRIP) aims to boost South African Industry by supporting research and technology development, and by enhancing the quality and quantity of appropriately skilled people. THRIP brings together the best of South Africa's researchers, academics and industry players in funding partnerships that enable participants to improve the quality of their products, services and people. In 13 years it has become a powerful formula for stimulating innovation in South Africa - innovation leads to competitiveness and competition leads to growth. There are many difficulties in managing projects across organisational boundaries; their cultures and their mission differ. The goal and the prime objective of the industries are to make a profit and build-value for shareholders. The universities‟ missions are to develop new knowledge and educate the next generation. Factors that may prevent research collaboration with Industry from being successfully accomplished are: • The practical difficulties of managing a collaboration, • Deleterious effects on faculty and students, • Impact on the mission, • Reputation and financing of the University. Industry needs to overcome the following hurdles in order to foster greater collaboration: • Respect the value of research collaboration, • Incorporate University research into product development, • Management barriers. / Thesis (MBA)--North-West University, Potchefstroom Campus, 2013.

Rapid changes in the global economy forces Industry to continuously seek competitive advantages; the University on the other hand pursue additional funding. Both Industry and University are trying to keep up with the accelerating pace of change, therefore partnership become critical in achieving key objectives. Research collaborations become essential and offer direct benefits for University and company participants. The impact extends well beyond the direct partners. When potential partners have the resources and knowledge to accomplish individual goals, working with outside experts can improve the quality of the research and help to reduce costs. Industry-sponsored research allows the University to obtain financial support as well as Industry exposure for its educational and research missions. The Technology and Human Resources for Industry Programme (THRIP) aims to boost South African Industry by supporting research and technology development, and by enhancing the quality and quantity of appropriately skilled people. THRIP brings together the best of South Africa's researchers, academics and industry players in funding partnerships that enable participants to improve the quality of their products, services and people. In 13 years it has become a powerful formula for stimulating innovation in South Africa - innovation leads to competitiveness and competition leads to growth. There are many difficulties in managing projects across organisational boundaries; their cultures and their mission differ. The goal and the prime objective of the industries are to make a profit and build-value for shareholders. The universities‟ missions are to develop new knowledge and educate the next generation. Factors that may prevent research collaboration with Industry from being successfully accomplished are: • The practical difficulties of managing a collaboration, • Deleterious effects on faculty and students, • Impact on the mission, • Reputation and financing of the University. Industry needs to overcome the following hurdles in order to foster greater collaboration: • Respect the value of research collaboration, • Incorporate University research into product development, • Management barriers. / Thesis (MBA)--North-West University, Potchefstroom Campus, 2013.

The host adaptive immune response to a pathogen infection comprises both cell mediated and antibody dependent components. Antibody mediated neutralization is a key component of protection against viruses and is the primary focus of this thesis. Antibodies recognize structurally defined epitopes within the context of native proteins. These may be represented by a simple linear sequence of amino acids or a discontinuous sequence of residues brought together by the conformational constraints of the protein. Many protein epitopes recognized by antibodies have been shown to be short α-helices of 3-5 turns. However corresponding synthetic peptides of this length have no structure in water because solvent competes strongly for the hydrogen bonding amides otherwise required to hydrogen bond one another to define an α-helix. This thesis is aimed primarily at (1) synthetically constraining short peptide sequences (9-13 residues) into stable α-helices of 3-4 turns; (2) structurally characterizing such constrained α-helical structures by circular dichroism and 1D and 2D NMR spectroscopy; and (3) evaluating these helix mimetics for serum stability, immunogenicity, antigenicity as well as the biological relevance of the antibodies they induce. The overall aim was to demonstrate that constrained short peptides more effectively structurally and functionally mimic known α-helical B cell epitopes from native proteins than unconstrained short peptides of the same lengths. The primary focus of Chapter 2 was to optimize in vitro ELISA conditions and immunization protocols for potentially assessing antibody responses in mice to short peptides corresponding to segments of important dengue virus proteins (NS1 and the envelope fusion protein, E). The NS1 peptide investigated had been suggested to be an α-helical epitope, but my investigations reveal that it is more likely a turn rather than a helix. While the E protein epitope chosen was not a viable epitope for testing a helix-constraining strategy, it was evaluated as a constrained turn mimic of a viral fusion epitope. Although the constrained peptides from both proteins (NS1 and E) elicited stronger antibody responses in mice than their unconstrained analogues, they still induced relatively poor antibody levels. Interestingly, mouse antibodies raised to the constrained peptide (β-turn analogue) from NS1 protein also reacted with the native protein. To evaluate a helix-constraining strategy for short peptides (less than 15 residues) that have no helix structure in water, an epitope of the HPV E7 protein was selected for mimicry. A short peptide sequence corresponding to this B cell epitope had previously been reported to have α-helical propensity but only in trifluoroethanol-water mixtures, and my initial work showed that it had no detectable helical structure at all in water. Chapter 3 presents an example of a short helical peptide as a B cell epitope, constrained into an α-helix by a side chain to side chain lactam bridge. The constraint involved cyclizing the peptide by specifically linking together side chains of lysine and aspartic acid inserted in the sequence three amino acids apart. CD and NMR structural studies highlighted significant α-helicity in the constrained short peptide, whereas the corresponding unconstrained short peptide had no structure in water. Both unconstrained and constrained short peptide epitopes were injected into mice and antibodies raised were quantified ex vivo by peptide ELISA. The helix-constrained epitope elicited higher antibody titres than the unconstrained peptide which was relatively non-immunogenic. Importantly, antibodies raised to the constrained synthetic α-helical peptide also reacted with the native E7 protein, suggesting that the helical constraint conferred on the peptide a structure analogous to that seen in the protein. In Chapter 4 a constrained α-helical peptide corresponding to a crystallographically defined α-helical sequence in the fusion, F protein of respiratory syncitial virus (RSV) was investigated for its potential to induce an antibody response. Again, while the helix-constrained peptide clearly had α-helicity by CD and NMR studies, the unconstrained short peptide had no detectable helical structure in water. To potentially boost antibody responses, relative to those generated against the dengue virus peptides examined in Chapter 3, both unconstrained and constrained peptides were coupled to the carrier protein KLH before immunizing mice. Significant levels of peptide reactive antibody were generated to both the unconstrained and constrained peptides. However, when investigated in a viral neutralization assay, the antibodies raised to the unconstrained peptide showed a higher neutralization potential than those raised to the constrained peptide. We attribute this unexpected difference to the fact that the region of the F protein corresponding to the epitope chosen, undergoes dramatic conformational changes during the viral fusion process and it is only in its post-fusion form that this helix has been observed. It is possible that the inherent flexibility of the linear, unconstrained counterpart of this epitope may more effectively mimic the conformational intermediates of the native structure on presentation to the immune system. Chapter 5 began an examination of the effects of three different adjuvants on antibody induction by short peptides. They were compared using a candidate peptide vaccine for malaria as a model system. As before, a helix-constrained peptide was compared with its unconstrained peptide sequence in immunization experiments. Higher titres of antibodies were raised to the constrained versus unconstrained peptides. In the second part of this chapter, a putative cancer vaccine peptide was similarly constrained via an ester linkage or a helix-inducing lactam bridge but both methods induced only low T-cell responses compared to their corresponding unconstrained sequences, possibly because the incorrect structure had been stabilized. The focus of this thesis was to evaluate a helix stabilization strategy for its possible application to short peptide vaccines. Using extensive circular dichroism and NMR spectroscopy measurements, we have shown in all cases that helix-constrained peptides were much more α-helical in solution than their corresponding unconstrained short peptide sequences that tended to have no or negligible α-helix structure in water. In some examples, we have compared serum stability and found that constrained peptides have higher serum stability than unconstrained peptides, a difference attributed to their greater stability towards proteolytic degradation – proteases being unable to recognize helices. We have also proven that the helix-constrained peptides induced higher mouse antibody titres than unconstrained peptides. Several attempts were made to boost antibody responses to the peptides by varying either immunization protocols, adjuvant or by attaching a carrier molecule. Further work is needed to optimize this promising new approach to short peptide vaccines.

Universiẗat, Diss., 2003--Frankfurt (Main).

Universiẗat, Diss., 2003--Dortmund.

The aim is to evaluate the involvement of the three spheres of innovation in innovative projects funded by the EU, taking place in South Bohemia. From a methodological point of view of scientific inquiry is used in our study, the logical method, including analysis and synthesis, which in this case means a set of design measures to improve cooperation within the South Bohemia, pro-innovation projects. Own work prior to the study of literature addressed the issue, developing literature search related to the issue. Subsequently, within each sector analyzed three selected projects. These were chosen to implement them in the most studied reflected cooperation spheres. Selection of suitable projects had to precede the analysis of grant programs that currently support such cooperation and support included. The analysis of the subsidized projects followed separate survey, which is again from a different perspective to reveal how much the projects are implemented between the spheres together or separately. The present study demonstrated that the involvement of three basic spheres in innovation projects is not ideal. Not only are projects implemented by at least two spheres, often shows that the innovative project is designed rather isolated and only executor, that the applicant for the grant. The result of this work is a set of measures based on research that will improve the coherence of three spheres in the implementation of pro-innovation projects.

This thesis investigates the municipality of Linkopings role in the development project Ebbepark. How an innovative business-environment can facilitate trilateral networks in the Triple-Helix. The thesis aims to compare intentions and outcome of the development project. The theory of the Triple-Helix constitutes the theoretical framework, of which the study relates to. With the use of a thematic analysis of qualitative data gathered from interviews, an insight is given to government officials own beliefs and convictions about Ebbepark. An additional document analysis of the development projects visionary- and general plan, generates an understanding of the projects initial intentions. A tangible difference in outcome, is Linkopings University involvement in Ebbepark. Initially the plan was to establish a physical presence in order to strengthen the innovative space. The University decided to centralize their operations on campus, which can be seen as limiting in regard to facilitating the Triple-Helix. / Studien undersöker hur Linköpings kommun har arbetet med projektet Ebbepark och hur en organisationsöverskridande samverkan, s.k.Triple-Helix, kan faciliteras. Uppsatsen ämnar undersöka och besvara hur projektets initiala intentioner skiljer sig från utfallet av Ebbepark. Teorin för Triple-Helix utgör det teoretiska ramverk som studien förhåller sig till. En tematisk analys av intervjuer ger insyn till tjänstemäns egna övertygelser angående projektet. Kompletterande dokumentanalys av projektets förarbete skapar förståelse för visionerna och Ebbeparks helhetsplan. Ett exempel på skillnader mellan planerade intentioner och utfallet, är Linköpings universitets roll. Från att vara engagerade om en fysisk närvaro i Ebbepark för ökat innovationsskpande, till att centralisera sin verksamhet inom campusområdet. Det leder till en minskad akademisk närvaro, något som kan minska möjligheterna för en Triple-Helixsamverkan.

grado de magíster en farmacología / Las condiciones de vida actuales, que incluyen nuevas características dietarías, nutricionales y comportamentales, han modificado el perfil epidemiológico en las últimas décadas, lo que incrementa la incidencia y prevalencia de las enfermedades crónicas no transmisibles, entre las que se encuentra la Diabetes Mellitus. El comportamiento de este grupo de patologías, cómo su nombre lo indica, tiende a la cronicidad, generando una serie de alteraciones en la fisiología y anatomía del paciente, que afecta considerablemente su calidad y expectativa de vida. Entre las múltiples complicaciones tardías que se manifiestan, tenemos el pie diabético, la cual es la consecuencia de los daños microangiopáticos, macroangiopáticos y neuropáticos de la Diabetes Mellitus. El problema clínico a resolver, es determinar la mejoría y aminorar en lo posible las altas tasas de hospitalización por infecciones en los grados avanzados de pie diabético, lo cual puede avanzar a situaciones complejas como la amputación. Se estima que la incidencia anual de esta complicación (pie diabético) está en alrededor del 2%, y su presencia, al menos una vez en la vida oscila entre el 15 y el 25% [1]. La Federación Internacional de Diabetes, hizo un llamado de atención al referirse que cada 30 segundos, una extremidad se pierde en algún lugar del mundo como consecuencia de la diabetes [1]. Un estimativo, según estudios de Kerr et al llevados a cabo en el Reino Unido, es que la tasa de progresión hacia la amputación es del 28% y ahonda en el tema, considerando que una persona con diabetes mellitus tiene 23 veces más posibilidades de sufrir una amputación por úlcera en comparación con una persona sin dicho diagnóstico [2]. Al respecto, se ha planteado el presente ensayo clínico, considerado de Fase I-II, (de evaluación de seguridad y eficacia), para una formulación de baba de caracol y extractos naturales, que persigue ser analizada en la evaluación de la mejoría clínica, de úlceras de los pacientes afectados con pié diabético, además de demostrar un perfil de seguridad. El estudio clínico en mención, será controlado, abierto y aleatorizado. La formulación en estudio, llamada MUCIDERM® (contenida en parches), será complementada al tratamiento convencional de pie diabético, indicado tanto en la Norma Clínica del manejo integral del pie diabético como en la Guía Clínica de curación avanzada de pie diabético del Ministerio de Salud (MINSAL) [3,4]. Los individuos en estudio fueron pacientes con Diabetes Mellitus tipo 2, que presentaron heridas ulcerosas de pie Grado 1 y 2 de la clasificación de Wagner y entre otros criterios de inclusión se consideraron: lesión unilateral, sin foco infeccioso a distancia (exceptuando onicomicosis), con condiciones higiénico-sanitarias adecuadas, con regularidad en sus controles, adecuado apoyo familiar, evidencia de cumplimiento de sus indicaciones terapéuticas y la consolidación del proceso de consentimiento informado. Se excluyeron quienes refirieron historia de alergia a alguno de los componentes de la formulación, pacientes con diagnóstico de cáncer o alguna otra situación medico quirúrgica que a juicio del investigador pudiese colocar al paciente en riesgo al participar en el estudio o haber recibido algún otro medicamento bajo investigación en el último mes. Se estimó incluir un total de 90 pacientes, divididos en dos grupos de 45 pacientes cada uno, tomándose uno como grupo control (A) y el otro (B) quién recibió el tratamiento innovador (MUCIDERM®), además se administró el producto en estudio en pie sano para evaluar seguridad. El periodo de reclutamiento estimado fue de 18 meses y el seguimiento de los pacientes se realizó durante 60 días aproximadamente. El presente trabajo se constituye en una Actividad Formativa Equivalente (A.F.E.) para obtener el grado de Magíster en Farmacología, en el que se desarrollan una serie de actividades en el marco del proyecto, que permiten obtener las competencias y capacidades requeridas para lograr el grado. En este caso, esta A.F.E. se ha circunscrito en un estudio clínico, cuyos aspectos fundamentales son descritos a continuación. / Current life conditions that include new dietary, nutritional and behavioral characteristics have modified the epidemiological profile in the last decades, which increases the incidence and prevalence of chronic non-communicable diseases, including Diabetes Mellitus. The behavior of this group of pathologies, as its name indicates, tends to the chronicity, generating a series of alterations in the physiology and anatomy of the patient that affects considerably its quality and life expectancy. Among the many late complications that are manifested we can find the diabetic foot, which is the consequence of the microangiopathic, macroangiopathic and neuropathic damages of Diabetes Mellitus. The clinical problem to be resolved is to determine the improvement and to reduce the high rates of hospitalization for infections in the advanced states of diabetic foot, which may lead to complex situations such as amputation. The annual incidence of this complication (diabetic foot) is estimated to be around 2%, and its presence at least once in life ranges from 15% to 25% [1]. The International Diabetes Federation drew attention to the fact that every 30 seconds, somewhere in the world a limb is lost as a result of diabetes [1]. An estimate, according to studies by Kerr et al carried out in the United Kingdom, the rate of progression of amputation is 28% and deepens the subject, considering that a person with diabetes mellitus is 23 times more likely to suffer an ulcer amputation compared to a person without such a diagnosis [2]. The present Phase I-II clinical trial (a safety and efficacy evaluation), for a formulation of snail slime and natural extracts, has been proposed, which aims to be analyzed in the evaluation of the clinical improvement of Ulcers of affected patients with diabetic foot, in addition to demonstrating a safety profile. The clinical study in question will be controlled, open and randomized. The formulation under study (contained in patches) will be complemented with the conventional diabetic foot treatment indicated both in the Clinical Standard of the integral management of the diabetic foot and in the Diabetes Foot Advanced Clinical Guide of the Ministry of Health (MINSAL) [3,4]. The individuals under study are patients with Type 2 Diabetes Mellitus who present Grade 1 and 2 foot ulcers of the Wagner classification and, among other inclusion criteria, will be: unilateral lesion, with no infectious focus at a distance (except for onychomycosis), with conditions Hygienic-sanitary, with regular checks, adequate family support, evidence of compliance with their therapeutic indications and consolidation of the informed consent process. Those who reported a history of allergy to any of the components of the formulation, patients with a diagnosis of cancer or any other surgical medical situation were excluded, which in the opinion of the investigator could put the patient at risk when participating in the study or having received any medication under research in the last month. It is estimated that a total of 90 patients will be divided into 2 groups of 45 patients each, one being taken as the control group (A) and the other (B) receiving the innovative treatment, and the study product will be administered in healthy foot to evaluate security. The estimated recruitment period will be 18 months and the patients will be monitored for approximately 60 days. The present work is constituted in an Equivalent Formative Activity (A.F.E.) to obtain the Master's degree in Pharmacology and that constitute a series of activities within the framework of the project that allow to obtain the competences and capacities required to achieve the degree. In this case, this A.F.E has been circumscribed in a clinical study, whose fundamental aspects are described below.

No description available.