A Ca2+-sensitive cyclic-3',5'-nucleotide phosphodiesterase from sheep lung modulated by a tightly bound endogenous calmodulin.

Highly purified sheep lung cyclic-3',5'-nucleotide phosphodiesterase was sensitive to Ca2+/EGTA but insensitive to exogenous calmodulin. The Ca2+-sensitivity was inhibited by trifluoperazine. Heat-treated enzyme could activate a calmodulin-deficient phosphodiesterase, suggesting the presence of endogenous calmodulin in sheep lung cyclic-3',5'-nucleotide phosphodiesterase, possibly associated with the enzyme in a Ca2+-independent manner.

Crystal Structure of Staphylococcus aureus Metallopeptidase (Sapep) Reveals Large Domain Motions between the Manganese-bound and Apo-states

Proteases belonging to the M20 family are characterized by diverse substrate specificity and participate in several metabolic pathways. The Staphylococcus aureus metallopeptidase, Sapep, is a member of the aminoacylase-I/M20 protein family. This protein is a Mn2+-dependent dipeptidase. The crystal structure of this protein in the Mn2+-bound form and in the open, metal-free state suggests that large interdomain movements could potentially regulate the activity of this enzyme. We note that the extended inactive conformation is stabilized by a disulfide bond in the vicinity of the active site. Although these cysteines, Cys(155) and Cys(178), are not active site residues, the reduced form of this enzyme is substantially more active as a dipeptidase. These findings acquire further relevance given a recent observation that this enzyme is only active in methicillin-resistant S. aureus. The structural and biochemical features of this enzyme provide a template for the design of novel methicillin-resistant S. aureus-specific therapeutics.

Elämänmuutoksen, jännityksen ja asiantuntijuuden representointi Veikkaus Oy:n mainonnassa vuosina 1970— 2006

Aim of this master's thesis paper for consumer economics, is to research gambling advertisements in Finland over a period of 35 years, from 1970 to 2006. Veikkaus Oy (later Veikkaus), was founded in 1940, as one of the three licensed gambling organizations in Finland. Material for the current research comprised 1494 advertisements published by Veikkaus in newspapers and magazines at that time. Veikkaus has the exclusive licence to organize lotto games, sport games, instant games and other draw games in Finland. The other two operators, The Finnish Slot Machine Association RAY and Fintoto (on-track horse betting), were not included in the current analysis. This study has been completed according to research contract and grand by the Finnish Foundation for Gaming Research (Pelitoiminnan tutkimussäätiö). In general, advertisements reflect surrounding culture and time, and their message is built on stratified meanings, symbols and codes. Advertising draws the viewer's attention, introduces the advertised subject, and finally, affects the individual's consumption habits. However, advertisements not only work on individual level, but also influence public perception of the advertised product. Firstly, in order to assess gambling as a phenomenon, this paper discusses gambling as consumer behaviour, and also reviews history of gambling in Finland. Winning is a major feature of gambling, and dreaming about positive change of life is a centre of most gambling ads. However, perceived excitement through risk of losing can also be featured in gambling ads. Secondly, this study utilizes Veikkaus’ large advertising archives, were advertising data is analyzed by content analysis and the semiotic analysis. Two methods have been employed to support analyzing outcome in a synergistic way. Content analysis helps to achieve accuracy and comprehensiveness. Semiotic analysis allows deeper and more sensitive analysis to emerged findings and occurrences. It is important to understand the advertised product, as advertising is bound to the culture and time. Hence, to analyze advertising, it is important to understand the environment where the ads appear. Content analysis of Veikkaus data discovered the main gambling and principal advertisement style for each.period. Interestingly, nearly half of Veikkaus’ advertisements promoted topic other than “just winning the bet”. Games of change, like Lotto, typically advertised indirectly represented dreams about winning. In the category of skill gambling, features were represented as investment, and the excitement of sporting expertise was emphasized. In addition, there were a number of gambling ads that emphasize social responsibility of Veikkaus as a government guided organization. Semiotic methods were employed to further elaborate on findings of content analysis. Dreaming in the advertisements was represented by the product of symbols, (e.g. cars and homes) that were found to have significance connection with each other. Thus, advertising represents change of life obtained by the winning. Interestingly, gambling ads promoting jackpots were often representing religious symbolisms. Ads promoting social responsibility were found to be the most common during economical depression of the 90’s. Deeper analysis showed that at that time, advertisements frequently represented depression-related meanings, such as unemployment and bank loans. Skill gaming ads were often represented by sports expertise – late 90’s, their number started sky rocketing, and continued increasing until 2006 (when this study ended). One may conclude that sport betting draws its meanings from the relevant consumer culture, and from the rules and features of the betted sport.

Interior Medial Axis Transform computation of 3D objects bound by free-form surfaces

This paper presents an algorithm for generating the Interior Medial Axis Transform (iMAT) of 3D objects with free-form boundaries. The algorithm proposed uses the exact representation of the part and generates an approximate rational spline description of the iMAT. The algorithm generates the iMAT by a tracing technique that marches along the object's boundary. The level of approximation is controlled by the choice of the step size in the tracing procedure. Criteria based on distance and local curvature of boundary entities are used to identify the junction points and the search for these junction points is done in an efficient way. The algorithm works for multiply-connected objects as well. Results of the implementation are provided. (C) 2010 Elsevier Ltd. All rights reserved.

A Direct Approach to the Problem of Diffraction by a Half-Plane under Mixed Boundary Conditions

A general direct technique of solving a mixed boundary value problem in the theory of diffraction by a semi-infinite plane is presented. Taking account of the correct edge-conditions, the unique solution of the problem is derived, by means of Jones' method in the theory of Wiener-Hopf technique, in the case of incident plane wave. The solution of the half-plane problem is found out in exact form. (The far-field is derived by the method of steepest descent.) It is observed that it is not the Wiener-Hopf technique which really needs any modification but a new technique is certainly required to handle the peculiar type of coupled integral equations which the Wiener-Hopf technique leads to. Eine allgemeine direkte Technik zur Lösung eines gemischten Randwertproblems in der Theorie der Beugung an einer halbunendlichen Ebene wird vorgestellt. Unter Berücksichtigung der korrekten Eckbedingungen wird mit der Methode von Jones aus der Theorie der Wiener-Hopf-Technik die eindeutige Lösung für den Fall der einfallenden ebenen Welle hergeleitet. Die Lösung des Halbebenenproblems wird in exakter Form angegeben. (Das Fernfeld wurde mit der Methode des steilsten Abstiegs bestimmt.) Es wurde bemerkt, daß es nicht die Wiener-Hopf-Technik ist, die wirklich irgend welcher Modifikationen bedurfte. Gewiß aber wird eine neue Technik zur Behandlung des besonderen Typs gekoppelter Integralgleichungen benötigt, auf die die Wiener-Hopf-Technik führt.

Diffraction of a cylindrical pulse by a half plane under mixed boundary conditions

The general time dependent source problem has been solved by the method of transforms (Laplace, Lebedev–Kontorovich in succession) and the solution is obtained in the form of an infinite series involving Legendre functions. The solutions in the case of harmonic time dependence and the incident plane wave have been derived from the above solution and are presented in the form of an infinite series. In the case of an incident plane wave, the series has been summed and the final solution involves an improper integral which behaves like a complementary error function for large values of the argument. Finally, the far field evaluation has been shown. The results are compared with those of Sommerfeld's half-plane diffraction problem with unmixed boundary conditions.

Mechanistic Aspects of Nucleophilic Substitution at Half-Sandwich Metal Complexes

The hydrolysis reactions of organometallic ruthenium(II) piano-stool complexes of the type Ru-II(eta(6)-cymene)(L)Cl](0/+) (1-5, where L = kappa(1)- or kappa(2)-1,1-bis(diphenylphosphino)methane,1,1bis-(diphenylphosphino)methane oxide, kappa(1)-mercaptobenzothiazole) have been studied using density functional theory at the B3LYP level. In addition to considering a syn attack in an associative fashion, where the nucleophile approaches from the same side as the leaving group, we have explored alternative paths such as an anti attack in an associative manner, where the nucleophile attacks from the opposite side of the leaving group. During the anti attack, an intermediate is formed and there is a coordination mode change of the arene ring from eta(6) to eta(2) along with its rotation. When the intermediate goes to the product, the arene ring slips back from eta(2) to eta(6) coordination. This coordinated movement of the arene ring makes the associative anti attack an accessible pathway for the substitution process. Our calculations predict very similar activation barriers for both syn and anti attacks. In the dissociative path, the rate-determining step is the generation of a coordinatively unsaturated 16-electron ruthenium species. This turns out to be viable once solvent effects are included. The large size of the ancillary ligands on Ru makes the dissociative process as favorable as the associative process. Activation energy calculations reveal that although the dissociative path is favorable for kappa(1) complexes, both dissociative and associative processes can have significant contribution to the hydrolysis reaction in kappa(2) complexes. Once activated by hydrolysis, these complexes react with guanine and adenine bases of DNA. The thermodynamic stabilities of complexes formed with the nucleobases are also presented.

Diffraction of a cylindrical pulse by a metallic half plane

A direct transform technique is applied to the initial and boundary value problem involving diffraction of a cylindrical pulse by a half plane, on which impedance type of boundary conditions must be met by the total field. The solution to the time harmonic incident plane wave is deduced as a particular case of the general time-dependent problem considered here and we avoid the Wiener–Hopf technique which leads to very complicated factorization and which masks the role of the impedance factor Z′ (a small quantity) in the expression for the scattered field.

Nafion®-bound carbon electrodes containing transitionmetal phthalocyanines for oxygen reduction in solid-polymer-electrolyte fuel cells

Catalytic activities of some transition metal-phthalocyanine complexes towards electroreduction of molecular oxygen are examined on Nafion®-bound and bare porous carbon electrodes in 2.5 M H2SO4 electrolyte. It is found that these metal complexes exhibit better catalytic activities towards oxygen reduction with the Nafion®-bound electrodes.

Importance of COMT in the regulation of prefrontal dopamine

The prefrontal cortex (PFC), located in the anterior region of the frontal lobe, is considered to have several key roles in higher cognitive and executive functions. In general, the PFC can be seen as a coordinator of thought and action allowing subjects to behave in a goal-directed manner. Due to its anatomical connections with a variety of cortical and subcortical structures, several neurotransmitters, including dopamine, are involved in the regulation of PFC activity. In general, the majority of released dopamine is cleared by the dopamine transporter (DAT). In the PFC however, the number of presynaptic DAT is diminished, emphasizing the relative importance of catechol-O-methyltransferase (COMT) in dopamine metabolism. As a result, the role of COMT in the etiology of psychotic disorders is under constant debate. The present study investigated the role of COMT in prefrontal cortical dopamine metabolism by different neurochemical methods in COMT knockout (COMT-KO) mice. Pharmacological tools to inhibit other dopamine clearing mechanisms were also used for a more comprehensive and collective picture. In addition, this study investigated how a lack of the soluble (S-) COMT isoform affects the total COMT activity as well as the pharmacokinetics of orally administered L-dopa using mutant mice expressing only the membrane-bound (MB-) COMT isoform. Also the role of COMT in striatal and accumbal dopamine turnover during Δ9-tetrahydrocannabinol (THC) challenge was studied. We found markedly increased basal dopamine concentrations in the PFC, but not the striatum or nucleus accumbens (NAcc), of mice lacking COMT. Pharmacological inhibition of the noradrenaline transporter (NET) and monoamine oxidase (MAO) elevated prefrontal cortical dopamine levels several-fold, whereas inhibition of DAT did not. The lack of COMT doubled the dopamine raising effects of NET and MAO inhibition. No compensatory expression of either DAT or NET was found in the COMT-KO mice. The lack of S-COMT decreased the total COMT activity by 50-70 % and modified dopamine transmission and the pharmacokinetics of exogenous Ldopa in a sex and tissue specific manner. Finally, we found that subsequent tolcapone and THC increased dopamine levels in the NAcc, but not in the striatum. Conclusively, this study presents neurochemical evidence for the important role of COMT in the PFC and shows that COMT is responsible for about half of prefrontal cortical dopamine metabolism. This study also highlights the previously underestimated proportional role of MB-COMT and supports the clinical evidence of a gene x environment interaction between COMT and cannabis.

'South-South' Remittance - Poverty reduction nexus. The Case of 'Hadiya' immigrants in South Africa, as Agents of 'Constituence development' in Ethiopia, and the policy implications of their 'remittance instrument'

This thesis explores the link between South-South remittance and development. It attempts to establish improved understanding about the role of immigrants as agents of constituency growth and development. By doing so, it illuminates the dark corners of the policy implications that the unconventional development agency of immigrants might have for countries in the Organization ft Economic Cooperation and Development (OECD). The thesis problematises the existence of state-centric international cooperation as providing the recipe for failed Aid in the face of global poverty menace. In the last half a century, the relative shi' of focus to non-state actors brought about the proliferation of NGOs. That, intrun, helped improve international access to crisis situations; however, their long-term remedial impacts on poverty and development have been contested. Major misgivings for non-governmental organizations (NGOs) are, on one hand, low level goal-bound expenditures and lack of independence from influence of the state, on the other. Therefore, the thesis enterprises to empirically verify its fundamental question whether remitting immigrants constitute an alternative development agency to the traditional players: the State and NGOs. Its main arguments are: due to state's failures in bringing sustainable development in many countries of the South, the future of poverty reduction and development also rests in immigrants' remittances. Nonetheless, in the last decade, remittance security-nexus dominated its discourse. Because of that remittance was viewed as something requiring global regime and restrictions. These temptations to tightly regulate remittance flows carry the danger of overlooking its trans-boundary nature and its strong link with livelihood of the poor. Therefore, to avoid unintended consequences of interventions, there need to be clear policy that bases itself on a discursive knowledge on the issues of North-South and South-South remittances The study involved both literature based and empirical research. It employed Discourse Analysis (C as main method for the former and snow-balling as its approach for the latter. For the first part the thesis constructed three conceptual models, these are: metrological model, police model and ecological model on remittance development-nexus. Through this modeling, the thesis achieved better deconstruction on the concepts remittance, immigrants and development agency. The protagonists of each model, the values and interests they represent, and their main arguments along various lines of dichotomies have been discussed. For instance, the main treats of meteorological model include: it sees remittance as transitional economic variable which require constant speculations and global management; it acts as meteorological station for following up or predicting the level, direction, flow and movement of global remittance. It focuses on official lines and considers the state as legitimate recipient of advic and positive consequence of remittance. On the other hand, police model views remittance as beir at best, development neutral or as an illicit activity requiring global regulations and tight control. Both immigrants and remittance viewed as subversive to establishments. It gives primacy to state stable agent of development and a partner for international cooperation. The anti-thesis to the police model is supplied by ecological model, which this thesis is a part. Ecological model on remittance and immigrants argues that, tight global regulations alone cannot be a panacea for possible abuse of informal remittance system. Ecological model, not only links remittance to poverty reduction, the main trust of development, but also considers the development agency of immigrants as critical factor for 21st century north-south development intervention. It sees immigrants as development conscious and their remittance instrument as most stable flow of finance to the developing countries. Besides, it sees remittance as effective poverty solutions than Foreign Direct Investment and international AID. This thesis focuses on the significance of South-South remittance and investigates the South Africa - Ethiopia remittance corridor, as case study; and empirically verifies the role of Ethiopian (Kembata and Hadiya) immigrants in South Africa as agents of local development back home. The study involved techniques of interview, group discussions, observations and investigative study. It also looked into the determinants of their migration to South Africa, and their remittance to Ethiopia. The theoretical models in the first part of the thesis have been operationalised throughout the empirical part to verify if the Kembata and Hadiya immigrants played the crucial role in their household poverty and local development in comparison with the Ethiopian state and the NGOs involved in the system. As evidenced by the research the thesis has made three distinct contributions to the discourse of remittance development-nexus. Fist, it systematized the debate about linkages between remittance, immigrants, development agency and policy of international cooperation by creating three conceptual models (school of thoughts); second, it singled out remitting immigrants as new agents of development in the South; third, it deconstructed concept of remittance and established South¬South remittance as additional sphere of academic investigation. In addition to the above contributions, the thesis finds that Kembata and Hadiya immigrants have engaged in various developmental activities in their locality than usually anticipated. Hence, it concludes that Ethiopian immigrants constitute an alternative development agency to the state and other non-state actors in their country, and the lesson can be applied to poverty reduction strategies in most developing countries.

Bearing capacity factors of circular foundations for a general c-phi soil using lower bound finite elements limit analysis

By using the lower bound limit analysis in conjunction with finite elements and linear programming, the bearing capacity factors due to cohesion, surcharge and unit weight, respectively, have been computed for a circular footing with different values of phi. The recent axisymmetric formulation proposed by the authors under phi = 0 condition, which is based on the concept that the magnitude of the hoop stress (sigma(theta)) remains closer to the least compressive normal stress (sigma(3)), is extended for a general c-phi soil. The computational results are found to compare quite well with the available numerical results from literature. It is expected that the study will be useful for solving various axisymmetric geotechnical stability problems. Copyright (C) 2010 John Wiley & Sons, Ltd.