Thermogenic effect of the new beta-adrenoreceptor agonist Ro 16-8714 in healthy male volunteers.

Previous investigations in experimental animals have shown that a new type of beta-adrenoceptor agonist (Ro 16-8714) possesses both thermogenic and antihyperglycemic properties. The aim of the study was to assess the thermogenic capacity of the compound in man after acute administration. Following an overnight fast three different doses (5, 10 and 20 mg) and a placebo were given per os to six normal-weight young men. The rate of energy expenditure (EE) and substrate utilization were determined by indirect calorimetry (hood system) before and for 6 h following the drug administration. Heart rate and blood pressure as well as plasma glucose, insulin and free fatty acid (FFA) concentrations were also measured at regular intervals throughout the study. The increment relative to base-line (mean +/- s.e.m.) in EE with placebo, 5, 10 and 20 mg was 4 +/- 3, 10 +/- 2, 11 +/- 2 and 21 +/- 2 percent respectively whereas heart rate was enhanced by 2 +/- 2, 8 +/- 3, 22 +/- 2, and 49 +/- 8 percent. Systolic blood pressure increased less (1 +/- 2, 8 +/- 1, 11 +/- 1 and 13 +/- 2 percent), and diastolic blood pressure did not change significantly. Simultaneously we observed a slight and transient increase in blood glucose, insulin and FFA concentrations. It is concluded that in lean individuals Ro 16-8714 is a potent thermogenic agent; however, new beta-adrenoceptor agonists should be developed in order to avoid the tachycardia associated with the thermogenic effect.

La contraception d'urgence chez les adolescents en Suisse: une étude sur la sexualité des 16-20 ans

Objectifs: Faire le point sur les connaissances concernant la contraception post-coïtale (CPC) et son utilisation par les adolescentes, et réunir les recommandations utiles aux médecins prescripteurs. Matériel et méthodes: La revue de littérature concernant la CPC et les résultats d'une enquête concernant les comportements sexuels des adolescents de 16-20 ans en Suisse sont utilisés. Résultats: Plusieurs méthodes peuvent être utilisées incluant les oestroprogestatifs et les progestatifs seuls. C'est surtout à l'occasion de rupture de préservatif, d'oubli de pilule ou d'absence de contraception que la CPC peut être utile. Les adolescents sexuellement actifs semblent connaître l'existence de la CPC et 20% des jeunes filles y ont eu recours en Suisse. Mais les obstacles qui limitent l'accès à la CPC sont nombreux au niveau de l'information et de la qualité des services dans cette situation d'urgence. Discussion et conclusion: La sensibilisation des adolescents et des jeunes aux conditions d'utilisation de la CPC est nécessaire, et doit être associée à un effort de formation des professionnels et de qualité des services pour faciliter l'accès à la CPC. Mots-clefs: contraception d?urgence, contraception post-coïtale, pilule du lendemain, adolescents.<br/><br/>Purpose: To describe and analyze emergency contraception (EC) awareness and use among sexually active Swiss teenagers. Methods: Anonymous computerized questionnaires were distributed to a national representative sample of 4283 in-school adolescents (aged 16 to 20 years) in high schools and professional centers. Young people who were sexually active (51.5% of the sample: 1058 girls and 1073 boys) responded to questions on EC awareness and use and on sexual perception, attitude and behaviors. Univariate analyses and multiple regression analyses were used to describe EC awareness and use and their correlates. Results: Most of the sexually active girls (89.3%) and boys (75.2%) knew of the existence of EC. Of girls, 20% reported having used EC, and the majority of them used it only once (64.1%) or twice (18.5%). EC awareness was positively associated with the father's level of education (girls: odds ratio:5.18), and the scholastic curriculum of the respondent. Gender differences in the correlates of EC awareness demonstrate that girls who had a confidant, or a group of friends or boys of Swiss nationality and those who have had the opportunity to discuss the issue of contraception declare greater awareness of EC. EC use was higher among girls who lived in urban areas (odds ratio: 1.91) and occasionally had unprotected intercourse. We did not find any significant difference in the profile of multiple vs. one-time users. Conclusion: EC awareness and use should be improved through better information and accessibility, especially among teenagers who place themselves in at-risk situations. Keywords: Adolescents, Emergency contraception, Gender differences, Teenage pregnancy prevention, Switzerland.

Functions of the human papillomavirus type 16 E4 protein

1. Abstract Cervical cancer is thought to be the consequence of infection by human papillomaviruses (HPV). In the majority of cases, DNA from HPV type 16 (HPV16) is found in malignant cervical lesions. The initial steps leading to transformation of an infected cell are not clearly understood but in most cases, disruption and integration of the episomal viral DNA must take place. As a consequence, the E2 and E4 genes are usually not expressed whereas the E6 and E7 oncogenes are highly expressed. However, in a normal infection in which the viral DNA is maintained as an episome, all viral genes are expressed. The pattern according to which the viral proteins are made, and therefore the life cycle of the virus, is tightly linked to the differentiation process of the host keratinocyte. The study of the viral oncogenes E6 and E7 has revealed crucial functions in the process of malignant transformation such as degradation of the p53 tumor suppressor protein, deregulation of the Retinoblastoma protein pathway and activation of the telomerase ribonucleoprotein. All these steps are necessary for cancerous lesions to develop. However, the loss of the E2 gene product seems to be necessary for sufficient expression of E6 and E7 in order to achieve such effects. In normal infections, the E4 protein is made abundantly in the later stages of the viral life cycle. Though extensive amounts of work have been carried out to define the function of E4, it still remains unclear. In this study, several approaches have been used to try and determine the functions of E4. First, a cell-penetrating fusion protein was designed and produced in order to circumvent the chronic difficulties of expressing E4 in mammalian cells. Unfortunately, this approach was not successful due to precipitation of the purified fusion protein. Second, the observation that E4 accumulates in cells having modified their adhesion properties led to the hypothesis that E4 might be involved in the differentiation process of keratinocytes. Preliminary results suggest that E4 triggers differentiation. Last, as E4 has been reported to collapse the cytokeratin network of keratinocytes, a direct approach using atomic force microscopy has allowed us to test the potential modification of mechanical properties of cells harboring reorganized cytokeratin networks. If so, a potential role for E4 in viral particle release could be hypothesized. 2. Résumé Il a été établi que le cancer du col de l'utérus se développe essentiellement à la suite d'une infection par le virus du papillome humain (HPV). Dans la majorité des cas analysés, de l'ADN du HPV de type 16 (HPV16) est détecté. Les étapes initiales de la transformation d'une cellule infectée sont mal connues mais il semble qu'une rupture du génome viral, normalement épisomal, suivi d'une intégration dans le génome de la cellule hôte soient des étapes nécessaires dans la plupart des cas. Or il semble qu'il y ait une sélection pour les cas où l'expression des oncogènes viraux E6 et E7 soit favorisée alors que l'expression des gènes E2 et E4 est en général impossible. Par contre, dans une infection dite normale où le génome viral n'est pas rompu, il n'y pas développement de cancer et tous les gènes viraux sont exprimés. L'ordre dans lequel les protéines virales sont produites, et donc le cycle de réplication du virus, est intimement lié au processus de différentiation de la cellule hôte. L'étude des protéines oncogènes E6 et E7 a révélé des fonctions clés dans le processus de transformation des cellules infectées telles que la dégradation du suppresseur de tumeur p53, la dérégulation de la voie de signalisation Rb ainsi que l'activation de la télomérase. Toutes ces activités sont nécessaires au développement de lésions cancéreuses. Toutefois, il semble que l'expression du gène E2 doit être empêchée afin que suffisamment des protéines E6 et E7 soient produites. Lorsque le gène E2 est exprimé, et donc lorsque le génome viral n'est pas rompu, les protéines E6 et E7 n'entraînent pas de telles conséquences. Le gène E4, qui se trouve dans la séquence codante de E2, a aussi besoin d'un génome viral intact pour être exprimé. Dans une infection normale, le gène E4 est exprimé abondamment dans les dernières étapes de la réplication du virus. Bien que de nombreuses études aient été menées afin de déterminer la fonction virale à E4, aucun résultat n'apparaît évident. Dans ce travail, plusieurs approches ont été utilisées afin d'adresser cette question. Premièrement, une protéine de fusion TAT-E4 a été produite et purifiée. Cette protéine, pouvant entrer dans les cellules vivantes par diffusion au travers de la membrane plasmique, aurait permis d'éviter ainsi les problèmes chroniques rencontrés lors de l'expression de E4 dans les cellules mammifères. Malheureusement, cette stratégie n'a pas pu être utilisée à cause de la précipitation de la protéine purifiée. Ensuite, l'observation que E4 s'accumule dans les cellules ayant modifié leurs propriétés d'adhésion a suggéré que E4 pourrait être impliqué dans le procédé de différentiation des kératinocytes. Des résultats préliminaires supportent cette possibilité. Enfin, il a été montré que E4 pouvait induire une réorganisation du réseau des cytokératines. Une approche directe utilisant le microscope à force atomique nous a ainsi permis de tester une potentielle modification des propriétés mécaniques de cellules ayant modifié leur réseau de cytokératines en présence de E4. Si tel est le cas, un rôle dans la libération de particules virales peut être proposé pour E4.

In Search of Corporate Renewal: How to Benefit from Corporate Venturing?

Despite the rapid change in today's business environment there are relatively few studies about corporate renewal. This study aims for its part at filling that research gap by studying the concepts of strategy, corporate renewal, innovation and corporate venturing. Its purpose is to enhance our understanding of how established companies operating in dynamic and global environment can benefit from their corporate venturing activities. The theoretical part approaches the research problem in corporate and venture levels. Firstly, it focuses on mapping the determinants of strategy and suggests using industry, location, resources, knowledge, structure and culture, market, technology and business model to assess the environment and using these determinants to optimize speed and magnitude of change.Secondly, it concludes that the choice of innovation strategy is dependent on the type and dimensions of innovation and suggests assessing market, technology, business model as well as novelty and complexity related to each of them for choosing an optimal context for developing innovations further. Thirdly, it directsattention on processes through which corporate renewal takes place. On corporate level these processes are identified as strategy formulation, strategy formation and strategy implementation. On the venture level the renewal processes are identified as learning, leveraging and nesting. The theoretical contribution of this study, the framework of strategic corporate venturing, joins corporate and venture level management issues together and concludes that strategy processes and linking processes are the mechanism through which continuous corporate renewaltakes place. The framework of strategic corporate venturing proposed by this study is a new way to illustrate the role of corporate venturing as a purposefullybuilt, different view of a company's business environment. The empirical part extended the framework by enhancing our understanding of the link between corporate renewal and corporate venturing in its real life environment in three Finnish companies: Metso, Nokia and TeliaSonera. Characterizing companies' environmentwith the determinants of strategy identified in this study provided a structured way to analyze their competitive position and renewal challenges that they arefacing. More importantly the case studies confirmed that a link between corporate renewal and corporate venturing exists and found out that the link is not as straight forward as indicated by the theory. Furthermore, the case studies enhanced the framework by indicating a sequence according to which the processes work. Firstly, the induced strategy processes strategy formulation and strategy implementation set the scene for corporate venturing context and management processes and leave strategy formation for the venture. Only after that can strategies formed by ventures come back to the corporate level - and if found viable in the corporate level be formalized through formulation and implementation. With the help of the framework of strategic corporate venturing the link between corporaterenewal and corporate venturing can be found and managed. The suggested response to the continuous need for change is continuous renewal i.e. institutionalizing corporate renewal in the strategy processes of the company. As far as benefiting from venturing is concerned the answer lies in deliberately managing venturing in a context different to the mainstream businesses and establishing efficientlinking processes to exploit the renewal potential of individual ventures.

Analysis of the voltage source inverter with small DC-link capacitor

IIn electric drives, frequency converters are used to generatefor the electric motor the AC voltage with variable frequency and amplitude. When considering the annual sale of drives in values of money and units sold, the use of low-performance drives appears to be in predominant. These drives have tobe very cost effective to manufacture and use, while they are also expected to fulfill the harmonic distortion standards. One of the objectives has also been to extend the lifetime of the frequency converter. In a traditional frequency converter, a relatively large electrolytic DC-link capacitor is used. Electrolytic capacitors are large, heavy and rather expensive components. In many cases, the lifetime of the electrolytic capacitor is the main factor limiting the lifetime of the frequency converter. To overcome the problem, the electrolytic capacitor is replaced with a metallized polypropylene film capacitor (MPPF). The MPPF has improved properties when compared to the electrolytic capacitor. By replacing the electrolytic capacitor with a film capacitor the energy storage of the DC-linkwill be decreased. Thus, the instantaneous power supplied to the motor correlates with the instantaneous power taken from the network. This yields a continuousDC-link current fed by the diode rectifier bridge. As a consequence, the line current harmonics clearly decrease. Because of the decreased energy storage, the DC-link voltage fluctuates. This sets additional conditions to the controllers of the frequency converter to compensate the fluctuation from the supplied motor phase voltages. In this work three-phase and single-phase frequency converters with small DC-link capacitor are analyzed. The evaluation is obtained with simulations and laboratory measurements.

Produtividade e qualidade dos frutos da laranjeira 'Pêra' clone IAC em 16 porta-enxertos na região de Bebedouro-SP

Avaliou-se a influência de 16 porta-enxertos na produtividade, nas características físicas e químicas (sólidos solúveis totais-°Brix; acidez; ratio; porcentagem de suco; índice tecnológico e tamanho dos frutos) dos frutos da laranjeira 'Pêra' [Citrus sinensis (L.) Osbeck] e na incidência e severidade da clorose variegada dos citros (CVC). O plantio do experimento foi realizado em julho de 1993, com espaçamento de 6,0 m entre linhas e 3,5 m entre plantas (476 plantas/ha). O experimento foi conduzido sem irrigação. O delineamento experimental foi em blocos ao acaso, duas plantas por parcela, três repetições e 16 tratamentos, constituídos pelas seguintes cultivares porta-enxertos: tangerineira 'Sun Chu Sha Kat' (Citrus reticulata Blanco), tangerineira 'Pectinífera' (C. reticulata), 'Shekwasha' (C. depressa Hayata), tangerineira 'Pectinífera/Shekwasha' (C. depressa Hayata), tangerineira 'Batangas' (C. reticulata), tangerineira 'Oneco' (C. reticulata), citrangor [citrange (Poncirus trifoliata Raf. x C. sinensis) x C. sinensis], citrandarin [C.sunki hort. Ex Tanaka) x Poncirus trifoliata (L.) Raf. cv. English, tangerineira 'Sunki' (C. sunki), tangerineira 'Suen-Kat' (C. sunki), tangerineira 'Nasnaran' (C. amblycarpa Ochse), tangerineira 'Venezuela' (C. reticulata), tangerineira Heen Naran (C. lycopersicaeformis hort. ex Tan. ), limoeiro 'Cravo' (C. limonia Osbeck) x tangerineira 'Cleópatra' (C. reshni hort ex Tanaka), limoeiro 'Cravo' (C. limonia), tangerineira 'Cleópatra' (C. reshni). A intensidade da clorose variegada dos citros variou em função dos porta-enxertos e não se relacionou com a produção de frutos até a quarta safra. Os porta-enxertos estudados, com exceção da tangerineira Nasnaran, proporcionaram qualidade e produções iniciais de frutos similares aos do limoeiro 'Cravo'.

Comportamento de 16 porta-enxertos para o tangor Murcott na região de Itirapina-SP

Foi monitorado o comportamento de 16 porta-enxertos para o tangor Murcott [Citrus reticulata Blanco x C. sinensis (L.) Osbeck], do clone nucelar J, em experimento instalado em 1990, na Fazenda Raio de Sol, Itirapina-SP. Os porta-enxertos foram: tangelo 'Orlando' (C. reticulata Blanco x C. paradisi Macf.), laranja 'Caipira DAC' [C. sinensis (L.) Osbeck], limão 'Cravo'(C. limonia Osbeck), os trifoliatas 'Kryder 8-5'e 'EEL'[Poncirus trifoliata (L.) Raf.] e as tangerinas 'Cleópatra' (C. reshni hort. ex. Tanaka), 'Sunki' [C. sunki (Hayata) hort. ex. Tanaka], 'Batangas', 'Oneco', 'Swatow', 'Szinkon', 'Satsuma', 'Cravo', 'Dancy', 'Suen Kat' e 'Pook Ling Ming' (C. reticulata Blanco). As produções foram avaliadas de 1996 a 2003 e as maiores médias foram proporcionadas pelas plantas enxertadas nas tangerinas 'Cleópatra', 'Suen Kat', 'Pook Ling Ming' e 'Sunki' (>40 kg planta-1). Dentre os porta-enxetos que induziram as mais baixas produções, estão os dois trifoliatas, a 'Caipira DAC' e a tangerina 'Cravo' (<25 kg planta-1). As características de qualidade apresentadas pelos frutos, referentes aos anos de 1998 e 2002, indicaram não existir diferenças expressivas entre os tratamentos.

Neuro-mechanical and metabolic adjustments to the repeated anaerobic sprint test in professional football players.

PURPOSE: This study aimed to determine the neuro-mechanical and metabolic adjustments in the lower limbs induced by the running anaerobic sprint test (the so-called RAST). METHODS: Eight professional football players performed 6 × 35 m sprints interspersed with 10 s of active recovery on artificial turf with their football shoes. Sprinting mechanics (plantar pressure insoles), root mean square activity of the vastus lateralis (VL), rectus femoris (RF), and biceps femoris (BF) muscles (surface electromyography, EMG) and VL muscle oxygenation (near-infrared spectroscopy) were monitored continuously. RESULTS: Sprint time, contact time and total stride duration increased from the first to the last repetition (+17.4, +20.0 and +16.6 %; all P < 0.05), while flight time and stride length remained constant. Stride frequency (-13.9 %; P < 0.001) and vertical stiffness decreased (-27.2 %; P < 0.001) across trials. Root mean square EMG activities of RF and BF (-18.7 and -18.1 %; P < 0.01 and 0.001, respectively), but not VL (-1.2 %; P > 0.05), decreased over sprint repetitions and were correlated with the increase in running time (r = -0.82 and -0.90; both P < 0.05). Together with a better maintenance of RF and BF muscles activation levels over sprint repetitions, players with a better repeated-sprint performance (lower cumulated times) also displayed faster muscle de- (during sprints) and re-oxygenation (during recovery) rates (r = -0.74 and -0.84; P < 0.05 and 0.01, respectively). CONCLUSION: The repeated anaerobic sprint test leads to substantial alterations in stride mechanics and leg-spring behaviour. Our results also strengthen the link between repeated-sprint ability and the change in neuromuscular activation as well as in muscle de- and re-oxygenation rates.