Impfung gegen humane Papillomaviren (HPV) zur Prävention HPV 16/18 induzierter Zervixkarzinome und derer Vorstufen

Einleitung: Notwendige Voraussetzung für die Entstehung von Zervixkarzinomen ist eine persistierende Infektion mit humanen Papillomaviren (HPV). Die HPV-Typen 16 und 18 verursachen mit etwa 70% den überwiegenden Teil der Zervixkarzinome. Seit 2006/2007 stehen zwei Impfstoffe gegen HPV 16 und 18 zur Verfügung. Fragestellung: Wie effektiv ist die HPV-Impfung hinsichtlich der Reduktion von Zervixkarzinomen bzw. ihren Vorstufen (CIN)? Stellt die HPV-Impfung eine kosteneffektive Ergänzung zur derzeitigen Screeningpraxis dar? Gibt es Unterschiede bezüglich der Kosten-Effektivität zwischen den beiden verfügbaren Impfstoffen? Sollte aus gesundheitsökonomischer Perspektive eine Empfehlung für den Einsatz der HPV-Impfung gegeben werden? Falls ja, welche Empfehlungen bezüglich der Ausgestaltung einer Impfstrategie lassen sich ableiten? Welche ethischen, sozialen und juristischen Implikationen sind zu berücksichtigen? Methoden: Basierend auf einer systematischen Literaturrecherche werden randomisierte kontrollierte Studien zur Wirksamkeit der HPV-Impfungen für die Prävention von Zervixkarzinomen bzw. deren Vorstufen, den zervikalen intraepithelialen Neoplasien, identifiziert. Gesundheitsökonomische Modellierungen werden zur Beantwortung der ökonomischen Fragestellungen herangezogen. Die Beurteilung der Qualität der medizinischen und ökonomischen Studien erfolgt mittels anerkannter Standards zur systematischen Bewertung wissenschaftlicher Studien Ergebnisse: Bei zu Studienbeginn HPV 16/18 negativen Frauen, die alle Impfdosen erhalten haben, liegt die Wirksamkeit der Impfungen gegen HPV 16/18-induzierten CIN 2 oder höher bei 98% bis 100%. Nebenwirkungen der Impfung sind vor allem mit der Injektion assoziierte Beschwerden (Rötungen, Schwellungen, Schmerzen). Es gibt keine signifikanten Unterschiede für schwerwiegende unerwünschte Ereignisse zwischen Impf- und Placebogruppe. Die Ergebnisse der Basisfallanalysen der gesundheitsökonomischen Modellierungen reichen bei ausschließlicher Berücksichtigung direkter Kostenkomponenten von ca. 3.000 Euro bis ca. 40.000 Euro pro QALY (QALY = Qualitätskorrigiertes Lebensjahr), bzw. von ca. 9.000 Euro bis ca. 65.000 Euro pro LYG (LYG = Gewonnenes Lebensjahr). Diskussion: Nach den Ergebnissen der eingeschlossenen Studien sind die verfügbaren HPV-Impfstoffe wirksam zur Prävention gegen durch HPV 16/18 verursachte prämaligne Läsionen der Zervix. Unklar ist derzeit noch die Dauer des Impfschutzes. Hinsichtlich der Nebenwirkungen ist die Impfung als sicher einzustufen. Allerdings ist die Fallzahl der Studien nicht ausreichend groß, um das Auftreten sehr seltener Nebenwirkungen zuverlässig zu bestimmen. Inwieweit die HPV-Impfung zur Reduktion der Inzidenz und Mortalität des Zervixkarzinoms in Deutschland führen wird, hängt nicht allein von der klinischen Wirksamkeit der Impfstoffe ab, sondern wird von einer Reihe weiterer Faktoren wie der Impfquote oder den Auswirkungen der Impfungen auf die Teilnahmerate an den bestehenden Screeningprogrammen determiniert. Infolge der Heterogenität der methodischen Rahmenbedingungen und Inputparameter variieren die Ergebnisse der gesundheitsökonomischen Modellierungen erheblich. Fast alle Modellanalysen lassen jedoch den Schluss zu, dass die Einführung einer Impfung mit lebenslanger Schutzdauer bei Fortführung der derzeitigen Screeningpraxis als kosteneffektiv zu bewerten ist. Eine Gegenüberstellung der beiden verschiedenen Impfstoffe ergab, dass die Modellierung der tetravalenten Impfung bei der Berücksichtigung von QALY als Ergebnisparameter in der Regel mit einem niedrigeren (besseren) Kosten-Effektivitäts-Verhältnis einhergeht als die Modellierung der bivalenten Impfung, da auch Genitalwarzen berücksichtigt werden. In Sensitivitätsanalysen stellten sich sowohl die Schutzdauer der Impfung als auch die Höhe der Diskontierungsrate als wesentliche Einflussparameter der Kosten-Effektivität heraus. Schlussfolgerung: Die Einführung der HPV-Impfung kann zu einem verringerten Auftreten von Zervixkarzinomen bei geimpften Frauen führen. Jedoch sollten die Impfprogramme von weiteren Evaluationen begleitet werden, um die langfristige Wirksamkeit und Sicherheit beurteilen sowie die Umsetzung der Impfprogramme optimieren zu können. Von zentraler Bedeutung sind hohe Teilnahmeraten sowohl an den Impfprogrammen als auch - auch bei geimpften Frauen - an den Früherkennungsuntersuchungen. Da die Kosten-Effektivität entscheidend von der Schutzdauer, die bislang ungewiss ist, beeinflusst wird, ist eine abschließende Beurteilung der Kosten-Effektivität der HPV-Impfung nicht möglich. Eine langfristige Schutzdauer ist eine bedeutende Vorraussetzung für die Kosten-Effektivität der Impfung. Der Abschluss einer Risk-Sharing-Vereinbarung zwischen Kostenträgern und Herstellerfirmen stellt eine Option dar, um die Auswirkungen der Unsicherheit der Schutzdauer auf die Kosten-Effektivität zu begrenzen.

Aplicación de administración con Angular, Node y Express para una aplicación Django

En este trabajo de fin de grado se ha desarrollado una aplicación de administración que sustituye a las que ofrecen por defecto las aplicaciones creadas con el framework de desarrollo web Django. La aplicación está compuesta por dos partes: un servidor, desarrollado con Node y Express, que ataca a la base de datos MySQL de la aplicación Django (es el nexo de unión entre ambas), y expone una API que es utilizada por la otra parte que compone la aplicación, la parte del cliente. La API es totalmente privada, siendo necesario un token de autenticación válido para poder obtener una respuesta satisfactoria de la misma. La generación del token también es tarea del servidor. El cliente, que es la parte que ve el usuario final, está desarrollada usando el framework Angular. La interfaz de usuario utiliza Bootstrap, por lo que su visualización es correcta en cualquier tipo de dispositivo, tanto de escritorio como móvil. En definitiva, se ha desarrollado una aplicación JavaScript End-to-End, empleando las últimas tecnologías web, mejorando ostensiblemente, las prestaciones que ofrece un panel de administración generado automáticamente por una aplicación Django.

Papel do turista na conservação do património cultural e natural

Resumo O estudo realizado no âmbito deste relatório centra-se numa análise do papel do turista na conservação do património natural e cultural, em particular do Parque Nacional da Tijuca, no Rio de Janeiro. Os objetivos definidos para este trabalho são dilucidar o conceito de turismo cultural nas suas inter-relações com o ecoturismo; compreender o estado da arte em relação à intervenção do terceiro setor (ONG associações, fundações) e do turista particular na conservação do património; caracterizar o Parque Nacional da Tijuca; caracterizar a Amigos do Parque; e por fim indagar sobre a predisposição do turista para se associar à Associação dos Amigos do Parque Nacional da Tijuca. Para isso foi concebido um inquérito, realizado pela estagiária aos turistas que visitavam o parque, fazendo assim uma recolha de dados que serviram de base para as conclusões deste trabalho, levando no fim à proposta de algumas estratégias e diretivas a seguir para atrair novos associados, em particular turistas. Os resultados levam a concluir que no geral o turista não está predisposto a contribuir para a conservação e associar-se à Amigos do Parque. A percentagem de turistas que afirmaram estar predispostos a associarem-se foi de apenas 5%, sendo maioritariamente de turistas com idades entre os 25 e os 44 anos, com formação superior e provenientes dos países da América do Sul. O turista foi também questionado quanto à predisposição para fazer uma doação pontual, para a qual a taxa de respostas positiva foi mais elevada com 22%, com a contribuição também de turistas europeus. Apesar destes valores, o número de visitantes anuais do Parque Nacional da Tijuca aumenta a cada ano (prevendo-se que continue a aumentar), sendo que em 2014 foi de 3.086.207 de pessoas, e destes, cerca de 72% foram turistas. É importante conseguir o apoio destes turistas através da associação e através de doação, já que é relevante não só a nível financeiro, como também a nível de internacionalização e reconhecimento da associação e do parque, o que levará a uma maior rede de associados. Palavras-chave: ecoturismo; terceiro setor; conservação; Associação dos Amigos do Parque Nacional da Tijuca vii Abstract The study in this report focuses on an analysis of the tourist role in the conservation of natural and cultural heritage, in particular of the Tijuca National Park in Rio de Janeiro. The goals set for this work are to elucidate the concept of cultural tourism in its interrelations with ecotourism; to understand the state of the art concerning the third sector (NGO associations, foundations) and private tourist in heritage conservation; to characterize the Tijuca National Park; to characterize the Friends of the Park; and finally to inquire about the willingness of the tourist to join the Association of Friends of the Tijuca National Park. For this a survey was designed and conducted by the intern to the tourists visiting the park, thus allowing for a collection of data that formed the basis to the conclusions of this work, leading at the end to the proposal of some strategies and policies to attract new members, particularly tourists. The results lead to the conclusion that as a rule the tourist is not willing to contribute to the conservation and join the Friends of the Park. The percentage of tourists who assumed they were willing to join the association was only 5%, and mostly tourists aged 25 and 44, with higher education, and from the South American countries. Tourists were also asked about their willingness for giving donations, for which the rate of positive responses was higher 22%, with the contribution of European tourists. Despite these numbers, the number of annual visitors to the Tijuca National Park increases every year (and it is expected to continue to increase). In 2014 ir received 3,086,207 visitors, and of these, about 72% were tourists. It is important to get the support of these tourists through association and through donation, since it is relevant not only financially, but also as a tool of the internationalization and recognition of the association and the park, which will lead to a larger network of associates. Keywords: ecotourism; third sector; conservation; Association of Friends of the Tijuca National Park

Extraction, identification, fractionation and isolation of phenolic compounds in plants with hepatoprotective effects

The liver is one of the most important organs of human body, being involved in several vital functions and regulation of physiological processes. Given its pivotal role in the excretion of waste metabolites and drugs detoxification, the liver is often subjected to oxidative stress that leads to lipid peroxidation and severe cellular damage. The conventional treatments of liver diseases such as cirrhosis, fatty liver and chronic hepatitis are frequently inadequate due to side effects caused by hepatotoxic chemical drugs. To overcome this problematic paradox, medicinal plants, owing to their natural richness in phenolic compounds, have been intensively exploited concerning their extracts and fraction composition in order to find bioactive compounds that could be isolated and applied in the treatment of liver ailments. The present review aimed to collect the main results of recent studies carried out in this field and systematize the information for a better understanding of the hepatoprotective capacity of medicinal plants in in vitro and in vivo systems. Generally, the assessed plant extracts revealed good hepatoprotective properties, justifying the fractionation and further isolation of phenolic compounds from different parts of the plant. Twenty-five phenolic compounds, including flavonoids, lignan compounds, phenolic acids and other phenolic compounds, have been isolated and identified, and proved to be effective in the prevention and/or treatment of chemically induced liver damage. In this perspective, the use of medicinal plant extracts, fractions and phenolic compounds seems to be a promising strategy to avoid side effects caused by hepatotoxic chemicals.

Energy Cooperation in Energy Harvesting Communication Systems

In energy harvesting communications, users transmit messages using energy harvested from nature. In such systems, transmission policies of the users need to be carefully designed according to the energy arrival profiles. When the energy management policies are optimized, the resulting performance of the system depends only on the energy arrival profiles. In this dissertation, we introduce and analyze the notion of energy cooperation in energy harvesting communications where users can share a portion of their harvested energy with the other users via wireless energy transfer. This energy cooperation enables us to control and optimize the energy arrivals at users to the extent possible. In the classical setting of cooperation, users help each other in the transmission of their data by exploiting the broadcast nature of wireless communications and the resulting overheard information. In contrast to the usual notion of cooperation, which is at the signal level, energy cooperation we introduce here is at the battery energy level. In a multi-user setting, energy may be abundant in one user in which case the loss incurred by transferring it to another user may be less than the gain it yields for the other user. It is this cooperation that we explore in this dissertation for several multi-user scenarios, where energy can be transferred from one user to another through a separate wireless energy transfer unit. We first consider the offline optimal energy management problem for several basic multi-user network structures with energy harvesting transmitters and one-way wireless energy transfer. In energy harvesting transmitters, energy arrivals in time impose energy causality constraints on the transmission policies of the users. In the presence of wireless energy transfer, energy causality constraints take a new form: energy can flow in time from the past to the future for each user, and from one user to the other at each time. This requires a careful joint management of energy flow in two separate dimensions, and different management policies are required depending on how users share the common wireless medium and interact over it. In this context, we analyze several basic multi-user energy harvesting network structures with wireless energy transfer. To capture the main trade-offs and insights that arise due to wireless energy transfer, we focus our attention on simple two- and three-user communication systems, such as the relay channel, multiple access channel and the two-way channel. Next, we focus on the delay minimization problem for networks. We consider a general network topology of energy harvesting and energy cooperating nodes. Each node harvests energy from nature and all nodes may share a portion of their harvested energies with neighboring nodes through energy cooperation. We consider the joint data routing and capacity assignment problem for this setting under fixed data and energy routing topologies. We determine the joint routing of energy and data in a general multi-user scenario with data and energy transfer. Next, we consider the cooperative energy harvesting diamond channel, where the source and two relays harvest energy from nature and the physical layer is modeled as a concatenation of a broadcast and a multiple access channel. Since the broadcast channel is degraded, one of the relays has the message of the other relay. Therefore, the multiple access channel is an extended multiple access channel with common data. We determine the optimum power and rate allocation policies of the users in order to maximize the end-to-end throughput of this system. Finally, we consider the two-user cooperative multiple access channel with energy harvesting users. The users cooperate at the physical layer (data cooperation) by establishing common messages through overheard signals and then cooperatively sending them. For this channel model, we investigate the effect of intermittent data arrivals to the users. We find the optimal offline transmit power and rate allocation policy that maximize the departure region. When the users can further cooperate at the battery level (energy cooperation), we find the jointly optimal offline transmit power and rate allocation policy together with the energy transfer policy that maximize the departure region.

Managing Fisheries in the context of an integrated policy: the importance of spatial issues

A variety of conservation policies now frame the management of fishing activity and so do also the spatial planning of different sectorial activities. These framework policies are additional to classical fishery management. There is a risk that the policies applying on the marine system are not coherent from a fisheries point of view. The spatial management of fishing activity at regional scale has the potential to meet multiple management objectives, on a habitat basis. Here we consider how to integrate multiple objectives of different policies into integrated ocean management scenarios. In the EU, European Directives and the CFP are now implementing the ecosystem approach to the management of human activity at sea. In this context, we further identify three research needs: • Develop Management Strategy Evaluation (MSE) for multiple-objective and multiple-sector spatial management schemes • Improve knowledge on and evaluation of functional habitats • Develop spatially-explicit end-to-end models with appropriate complexity for spatial MSE The contribution is based on the results of a workshop of the EraNet COFASP.

Efeito do GQ-02, derivado de tiazolidinadionas, sobre a aquisição de fenótipo termogênico pelo adipócito in vivo e em cultura de células

Dissertação (mestrado)—Universidade de Brasília, Faculdade em Ciências da Saúde, Programa de Pós-Graduação em Ciências da Saúde, 2016.

Deflazacort Versus Prednisolone: Randomized Controlled Trial in Treatment of Children With Idiopathic Nephrotic Syndrome

Background: Corticosteroids are the main therapy of nephrotic syndrome and goal of corticosteroid therapy is to obtain maximum clinical benefit with minimum adverse effects. Children are more vulnerable to side effects of corticosteroids related to growth and adrenal suppression, so a search for an alternative steroid with fewer side-effects is underway. Deflazacort is an oxazoline derivative and preliminary data suggest reduced osteoporosis, lesser growth retardation and weight gain with deflazacort. Objectives: This study was done to compare the effectiveness and safety of deflazacort in idiopathic nephrotic syndrome. Patients and Methods: Twenty five children with age between 2 to 12 years, with idiopathic nephrotic syndrome were enrolled. They were randomly assigned to receive deflazacort (Group A, n = 12) or prednisolone (Group B, n = 13) and were followed up for six months. Results: All children of group A and 11 of group B had remission. Two children from group B were steroid resistant. Mean time taken to induce remission was significantly (P = 0.012) less in group A (10.25 ± 2.41 days) than group B (12.55 ± 1.44 days). One patient in group A had relapse on follow up as compared to 3 in group B (P = 0.58). Statistically significant difference (P = 0.03) in change in mean height was found between group A (2.13 ± 0.50cm) and B (1.44 ± 0.45 cm), with group B gaining less height. Conclusions: Remission rate in both groups was comparable although time taken to induce remission was shorter in deflazacort group and there was a significant difference in change of mean height on follow up with prednisolone group gaining lesser height.

Un modèle rétroactif de réconciliation utilité-confidentialité sur les données d’assurance

Le partage des données de façon confidentielle préoccupe un bon nombre d’acteurs, peu importe le domaine. La recherche évolue rapidement, mais le manque de solutions adaptées à la réalité d’une entreprise freine l’adoption de bonnes pratiques d’affaires quant à la protection des renseignements sensibles. Nous proposons dans ce mémoire une solution modulaire, évolutive et complète nommée PEPS, paramétrée pour une utilisation dans le domaine de l’assurance. Nous évaluons le cycle entier d’un partage confidentiel, de la gestion des données à la divulgation, en passant par la gestion des forces externes et l’anonymisation. PEPS se démarque du fait qu’il utilise la contextualisation du problème rencontré et l’information propre au domaine afin de s’ajuster et de maximiser l’utilisation de l’ensemble anonymisé. À cette fin, nous présentons un algorithme d’anonymat fortement contextualisé ainsi que des mesures de performances ajustées aux analyses d’expérience.

De la maltraitance à l’enfance aux comportements d’agression à l’âge adulte : quel est le rôle de la réactivité émotionnelle et comportementale?

En dépit des efforts déployés pour diminuer la prévalence de la maltraitance à l’enfance, celle-ci serait associée à des difficultés non négligeables, dont la manifestation d’agression. La réactivité émotionnelle et comportementale, incluant la colère, la peur et l’évitement, est proposée comme mécanisme expliquant la relation unissant la maltraitance à l’agression. Quatre objectifs sont poursuivis à cette fin, soit d’examiner la relation notée entre: (1) la maltraitance et l’agression, (2) la maltraitance et la colère, la peur, ainsi que l’évitement, (3) la colère, la peur, ainsi que l’évitement et l’agression et (4) tester formellement le rôle médiateur et modérateur de la colère, la peur et l’évitement à cette relation. Les données de 160 hommes âgés de 18 à 35 ans ayant été exposés ou non à de la maltraitance ont été colligées par le biais de questionnaires et d’une tâche de provocation sociale permettant de mesurer les expressions faciales de colère et de peur, ainsi que les comportements d’évitement. Les résultats suggèrent que la maltraitance et les comportements d’évitement sont associés à l’agression. La maltraitance ne serait toutefois pas liée à la colère, à la peur et à l’évitement. Alors que les résultats suggèrent que ces indices n’aient pas de rôles médiateurs dans la relation entre la maltraitance et l’agression, la réactivité aux plans de la colère et de l’évitement magnifierait cette relation. Ainsi, les résultats invitent à prendre en compte les expériences de maltraitance et l’intensité de la réactivité émotionnelle et comportementale dans les interventions afin de cibler les individus plus à risque d’avoir recours à l’agression.

Adaptive edge analytics for distributed networked control of water systems

Over the last decade, there has been a trend where water utility companies aim to make water distribution networks more intelligent in order to improve their quality of service, reduce water waste, minimize maintenance costs etc., by incorporating IoT technologies. Current state of the art solutions use expensive power hungry deployments to monitor and transmit water network states periodically in order to detect anomalous behaviors such as water leakage and bursts. However, more than 97% of water network assets are remote away from power and are often in geographically remote underpopulated areas, facts that make current approaches unsuitable for next generation more dynamic adaptive water networks. Battery-driven wireless sensor/actuator based solutions are theoretically the perfect choice to support next generation water distribution. In this paper, we present an end-to-end water leak localization system, which exploits edge processing and enables the use of battery-driven sensor nodes. Our system combines a lightweight edge anomaly detection algorithm based on compression rates and an efficient localization algorithm based on graph theory. The edge anomaly detection and localization elements of the systems produce a timely and accurate localization result and reduce the communication by 99% compared to the traditional periodic communication. We evaluated our schemes by deploying non-intrusive sensors measuring vibrational data on a real-world water test rig that have had controlled leakage and burst scenarios implemented.

Un modèle rétroactif de réconciliation utilité-confidentialité sur les données d’assurance

Le partage des données de façon confidentielle préoccupe un bon nombre d’acteurs, peu importe le domaine. La recherche évolue rapidement, mais le manque de solutions adaptées à la réalité d’une entreprise freine l’adoption de bonnes pratiques d’affaires quant à la protection des renseignements sensibles. Nous proposons dans ce mémoire une solution modulaire, évolutive et complète nommée PEPS, paramétrée pour une utilisation dans le domaine de l’assurance. Nous évaluons le cycle entier d’un partage confidentiel, de la gestion des données à la divulgation, en passant par la gestion des forces externes et l’anonymisation. PEPS se démarque du fait qu’il utilise la contextualisation du problème rencontré et l’information propre au domaine afin de s’ajuster et de maximiser l’utilisation de l’ensemble anonymisé. À cette fin, nous présentons un algorithme d’anonymat fortement contextualisé ainsi que des mesures de performances ajustées aux analyses d’expérience.

De la maltraitance à l’enfance aux comportements d’agression à l’âge adulte : quel est le rôle de la réactivité émotionnelle et comportementale?

En dépit des efforts déployés pour diminuer la prévalence de la maltraitance à l’enfance, celle-ci serait associée à des difficultés non négligeables, dont la manifestation d’agression. La réactivité émotionnelle et comportementale, incluant la colère, la peur et l’évitement, est proposée comme mécanisme expliquant la relation unissant la maltraitance à l’agression. Quatre objectifs sont poursuivis à cette fin, soit d’examiner la relation notée entre: (1) la maltraitance et l’agression, (2) la maltraitance et la colère, la peur, ainsi que l’évitement, (3) la colère, la peur, ainsi que l’évitement et l’agression et (4) tester formellement le rôle médiateur et modérateur de la colère, la peur et l’évitement à cette relation. Les données de 160 hommes âgés de 18 à 35 ans ayant été exposés ou non à de la maltraitance ont été colligées par le biais de questionnaires et d’une tâche de provocation sociale permettant de mesurer les expressions faciales de colère et de peur, ainsi que les comportements d’évitement. Les résultats suggèrent que la maltraitance et les comportements d’évitement sont associés à l’agression. La maltraitance ne serait toutefois pas liée à la colère, à la peur et à l’évitement. Alors que les résultats suggèrent que ces indices n’aient pas de rôles médiateurs dans la relation entre la maltraitance et l’agression, la réactivité aux plans de la colère et de l’évitement magnifierait cette relation. Ainsi, les résultats invitent à prendre en compte les expériences de maltraitance et l’intensité de la réactivité émotionnelle et comportementale dans les interventions afin de cibler les individus plus à risque d’avoir recours à l’agression.

Conformational states of HIV-1 reverse transcriptase for nucleotide incorporation vs. pyrophosphorolysis – binding of foscarnet

HIV-1 reverse transcriptase (RT) catalytically incorporates individual nucleotides into a viral DNA strand complementing an RNA or DNA template strand; the polymerase active site of RT adopts multiple conformational and structural states while performing this task. The states associated are dNTP binding at the N site, catalytic incorporation of a nucleotide, release of a pyrophosphate, and translocation of the primer 3′-end to the P site. Structural characterization of each of these states may help in understanding the molecular mechanisms of drug activity and resistance and in developing new RT inhibitors. Using a 38-mer DNA template-primer aptamer as the substrate mimic, we crystallized an RT/dsDNA complex that is catalytically active, yet translocation-incompetent in crystals. The ability of RT to perform dNTP binding and incorporation in crystals permitted obtaining a series of structures: (I) RT/DNA (P-site), (II) RT/DNA/AZTTP ternary, (III) RT/AZT-terminated DNA (N-site), and (IV) RT/AZT-terminated DNA (N-site)/foscarnet complexes. The stable N-site complex permitted the binding of foscarnet as a pyrophosphate mimic. The Mg2+ ions dissociated after catalytic addition of AZTMP in the pretranslocated structure III, whereas ions A and B had re-entered the active site to bind foscarnet in structure IV. The binding of foscarnet involves chelation with the Mg2+ (B) ion and interactions with K65 and R72. The analysis of interactions of foscarnet and the recently discovered nucleotide-competing RT inhibitor (NcRTI) α-T-CNP in two different conformational states of the enzyme provides insights for developing new classes of polymerase active site RT inhibitors.

The initial phase of sodium sulfite pulping of softwood : A comparison of different pulping options

Single stage and two-stage sodium sulfite cooking were carried out on either spruce, pine or pure pine heartwood chips to investigate the influence of several process parameters on the initial phase of such a cook down to about 60 % pulp yield. The cooking experiments were carried out in the laboratory with either a lab-prepared or a mill-prepared cooking acid and the temperature and time were varied. The influences of dissolved organic and inorganic components in the cooking liquor on the final pulp composition and on the extent of side reactions were investigated. Kinetic equations were developed and the activation energies for delignification and carbohydrate dissolution were calculated using the Arrhenius equation. A better understanding of the delignification mechanisms during bisulfite and acid sulfite cooking was obtained by analyzing the lignin carbohydrate complexes (LCC) present in the pulp when different cooking conditions were used. It was found that using a mill-prepared cooking acid beneficial effect with respect to side reactions, extractives removal and higher stability in pH during the cook were observed compared to a lab-prepared cooking acid. However, no significant difference in degrees of delignification or carbohydrate degradation was seen.  The cellulose yield was not affected in the initial phase of the cook however; temperature had an influence on the rates of both delignification and hemicellulose removal. It was also found that the  corresponding activation energies increased in the order:  xylan, glucomannan, lignin and cellulose. The cooking temperature could thus be used to control the cook to a given carbohydrate composition in the final pulp. Lignin condensation reactions were observed during acid sulfite cooking, especially at higher temperatures. The LCC studies indicated the existence of covalent bonds between lignin and hemicellulose components with respect to xylan and glucomannan. LCC in native wood showed the presence of phenyl glycosides, ϒ-esters and α-ethers; whereas the α-ethers  were affected during sulfite pulping. The existence of covalent bonds between lignin and wood polysaccharides might be the rate-limiting factor in sulfite pulping.