519 resultados para Phage display and peptide inhibitor
Resumo:
Concepts, models, or theories that end up shaping practices, whether those practices fall in the domains of science, technology, social movements, or business, always emerge through a change in language use. First, communities begin to talk differently, incorporating new vocabularies (Rorty, 1989), in their narratives. Whether the community’s new narratives respond to perceived anomalies or failures of the existing ones (Kuhn, 1962) or actually reveal inadequacies by addressing previously unrecognized practices (Fleck, 1979; Rorty, 1989) is less important here than the very phenomena that they introduce differences. Then, if the new language proves to be useful, for example, because it helps the community solve a problem or create a possibility that existing narratives do not, the new narrative will begin circulating more broadly throughout the community. If other communities learn of the usefulness of these new narratives, and find them sufficiently persuasive, they may be compelled to test, modify, and eventually adopt them. Of primary importance is the idea that a new concept or narrative perceived as useful is more likely to be adopted. We can expect that business concepts emerge through a similar pattern. Concepts such as “competitive advantage,” “disruption,” and the “resource based view,” now broadly known and accepted, were each at some point first introduced by a community. This community experimented with the concepts they introduced and found them useful. The concept “competitive advantage,” for example, helped researchers better explain why some firm’s outperformed others and helped practitioners more clearly understand what choices to make to improve the profit and growth prospects of their firms. The benefits of using these terms compelled other communities to consider, apply, and eventually adopt them as well. Were these terms not viewed as useful, they would not likely have been adopted. This thesis attempts to observe and anticipate new business concepts that may be emerging. It does so by seeking to observe a community of business practitioners that are using different language and appear to be more successful than a similar community of practitioners that are have not yet begun using this different language as extensively. It argues that if the community that is adopting new types of narratives is perceived as being more successful, their success will attract the attention of other communities who may then seek to adopt the same narratives. Specifically, this thesis compares the narratives used by a set of firms that are considered to be performing well (called Winners) with those of set of less-successful peers (called Losers). It does so with the aim of addressing two questions: - How do the strategic narratives that circulate within “winning” companies and their leaders differ from those circulating within “losing” companies and their leaders? - Given the answer to the first question: what new business strategy concepts are likely to emerge in the business community at large? I expected to observe “winning” companies shifting their language, abandoning an older set of narratives for newer ones. However the analysis indicates a more interesting dynamic: “winning” companies adopt the same core narratives as their “losing” peers with equal frequency yet they go beyond these. Both “winners” and “losers” seem to pursue economies of scale, customer captivity, best practices, and securing preferential access to resources with similar vigor. But “winners” seem to go further, applying three additional narratives in their pursuits of competitive advantage. They speak of coordinating what is uncoordinated, adopting what this thesis calls “exchanging the role of guest for that of host,” and “forcing a two-front battle” more frequently than their “loser” peers. Since these “winning” companies are likely perceived as being more successful, the unique narratives they use are more likely to be emulated and adopted. Understanding in what ways winners speak differently, therefore, gives us a glimpse into the possible future evolution of business concepts.
Resumo:
The decreasing fossil fuel resources combined with an increasing world energy demand has raised an interest in renewable energy sources. The alternatives can be solar, wind and geothermal energies, but only biomass can be a substitute for the carbon–based feedstock, which is suitable for the production of transportation fuels and chemicals. However, a high oxygen content of the biomass creates challenges for the future chemical industry, forcing the development of new processes which allow a complete or selective oxygen removal without any significant carbon loss. Therefore, understanding and optimization of biomass deoxygenation processes are crucial for the future bio–based chemical industry. In this work, deoxygenation of fatty acids and their derivatives was studied over Pd/C and TiO2 supported noble metal catalysts (Pt, Pt–Re, Re and Ru) to obtain future fuel components. The 5 % Pd/C catalyst was investigated in semibatch and fixed bed reactors at 300 °C and 1.7–2 MPa of inert and hydrogen–containing atmospheres. Based on extensive kinetic studies, plausible reaction mechanisms and pathways were proposed. The influence of the unsaturation in the deoxygenation of model compounds and industrial feedstock – tall oil fatty acids – over a Pd/C catalyst was demonstrated. The optimization of the reaction conditions suppressed the formation of by–products, hence high yields and selectivities towards linear hydrocarbons and catalyst stability were achieved. Experiments in a fixed bed reactor filled with a 2 % Pd/C catalyst were performed with stearic acid as a model compound at different hydrogen–containing gas atmospheres to understand the catalyst stability under various conditions. Moreover, prolonged experiments were carried out with concentrated model compounds to reveal the catalyst deactivation. New materials were proposed for the selective deoxygenation process at lower temperatures (~200 °C) with a tunable selectivity to hydrodeoxygenation by using 4 % Pt/TiO2 or decarboxylation/decarbonylation over 4 % Ru/TiO2 catalysts. A new method for selective hydrogenation of fatty acids to fatty alcohols was demonstrated with a 4 % Re/TiO2 catalyst. A reaction pathway and mechanism for TiO2 supported metal catalysts was proposed and an optimization of the process conditions led to an increase in the formation of the desired products.
Resumo:
The cell is continuously subjected to various forms of external and intrinsic proteindamaging stresses, including hyperthermia, pathophysiological states, as well as cell differentiation and proliferation. Proteindamaging stresses result in denaturation and improper folding of proteins, leading to the formation of toxic aggregates that are detrimental for various pathological conditions, including Alzheimer’s and Huntington’s diseases. In order to maintain protein homeostasis, cells have developed different cytoprotective mechanisms, one of which is the evolutionary well-conserved heat shock response. The heat shock response results in the expression of heat shock proteins (Hsps), which act as molecular chaperones that bind to misfolded proteins, facilitate their refolding and prevent the formation of protein aggregates. Stress-induced expression of Hsps is mediated by a family of transcription factors, the heat shock factors, HSFs. Of the four HSFs found in vertebrates, HSF1-4, HSF1 is the major stress-responsive factor that is required for the induction of the heat shock response. HSF2 cannot alone induce Hsps, but modulates the heat shock response by forming heterotrimers with HSF1. HSFs are not only involved in the heat shock response, but they have also been found to have a function in development, neurodegenerative disorders, cancer, and longevity. Therefore, insight into how HSFs are regulated is important for the understanding of both normal physiological and disease processes. The activity of HSF1 is mainly regulated by intricate post-translational modifications, whereas the activity of HSF2 is concentrationdependent. However, there is only limited understanding of how the abundance of HSF2 is regulated. This study describes two different means of how HSF2 levels are regulated. In the first study it was shown that microRNA miR-18, a member of the miR-17~92 cluster, directly regulates Hsf2 mRNA stability and thus protein levels. HSF2 has earlier been shown to play a profound role in the regulation of male germ cell maturation during the spermatogenesis. The effect on miR-18 on HSF2 was examined in vivo by transfecting intact seminiferous tubules, and it was found that inhibition of miR-18 resulted in increased HSF2 levels and modified expression of the HSF2 targets Ssty2 and Speer4a. HSF2 has earlier been reported to modulate the heat shock response by forming heterotrimers with HSF1. In the second study, it was shown that HSF2 is cleared off the Hsp70 promoter and degraded by the ubiquitinproteasome pathway upon acute stress. By silencing components of the anaphase promoting complex/cyclosome (APC/C), including the co-activators Cdc20 and Cdh1, it was shown that APC/C mediates the heatinduced ubiquitylation of HSF2. Furthermore, down-regulation of Cdc20 was shown to alter the expression of heat shock-responsive genes. Next, we studied if APC/C-Cdc20, which controls cell cycle progression, also regulates HSF2 during the cell cycle. We found that both HSF2 mRNA and protein levels decreased during mitosis in several but not all human cell lines, indicating that HSF2 has a function in mitotic cells. Interestingly, although transcription is globally repressed during mitosis, mainly due to the displacement of RNA polymerase II and transcription factors, including HSF1, from the mitotic chromatin, HSF2 is capable of binding DNA during mitosis. Thus, during mitosis the heat shock response is impaired, leaving mitotic cells vulnerable to proteotoxic stress. However, in HSF2-deficient mitotic cells the Hsp70 promoter is accessible to both HSF1 and RNA polymerase II, allowing for stress-inducible Hsp expression to occur. As a consequence HSF2-deficient mitotic cells have a survival advantage upon acute heat stress. The results, presented in this thesis contribute to the understanding of the regulatory mechanisms of HSF2 and its function in the heat shock response in both interphase and mitotic cells.
Resumo:
One of the main challenges in Software Engineering is to cope with the transition from an industry based on software as a product to software as a service. The field of Software Engineering should provide the necessary methods and tools to develop and deploy new cost-efficient and scalable digital services. In this thesis, we focus on deployment platforms to ensure cost-efficient scalability of multi-tier web applications and on-demand video transcoding service for different types of load conditions. Infrastructure as a Service (IaaS) clouds provide Virtual Machines (VMs) under the pay-per-use business model. Dynamically provisioning VMs on demand allows service providers to cope with fluctuations on the number of service users. However, VM provisioning must be done carefully, because over-provisioning results in an increased operational cost, while underprovisioning leads to a subpar service. Therefore, our main focus in this thesis is on cost-efficient VM provisioning for multi-tier web applications and on-demand video transcoding. Moreover, to prevent provisioned VMs from becoming overloaded, we augment VM provisioning with an admission control mechanism. Similarly, to ensure efficient use of provisioned VMs, web applications on the under-utilized VMs are consolidated periodically. Thus, the main problem that we address is cost-efficient VM provisioning augmented with server consolidation and admission control on the provisioned VMs. We seek solutions for two types of applications: multi-tier web applications that follow the request-response paradigm and on-demand video transcoding that is based on video streams with soft realtime constraints. Our first contribution is a cost-efficient VM provisioning approach for multi-tier web applications. The proposed approach comprises two subapproaches: a reactive VM provisioning approach called ARVUE and a hybrid reactive-proactive VM provisioning approach called Cost-efficient Resource Allocation for Multiple web applications with Proactive scaling. Our second contribution is a prediction-based VM provisioning approach for on-demand video transcoding in the cloud. Moreover, to prevent virtualized servers from becoming overloaded, the proposed VM provisioning approaches are augmented with admission control approaches. Therefore, our third contribution is a session-based admission control approach for multi-tier web applications called adaptive Admission Control for Virtualized Application Servers. Similarly, the fourth contribution in this thesis is a stream-based admission control and scheduling approach for on-demand video transcoding called Stream-Based Admission Control and Scheduling. Our fifth contribution is a computation and storage trade-o strategy for cost-efficient video transcoding in cloud computing. Finally, the sixth and the last contribution is a web application consolidation approach, which uses Ant Colony System to minimize the under-utilization of the virtualized application servers.
Resumo:
Initially identified as stress activated protein kinases (SAPKs), the c-Jun Nterminal kinases (JNKs) are currently accepted as potent regulators of various physiologically important cellular events. Named after their competence to phosphorylate transcription factor c-Jun in response to UVtreatment, JNKs play a key role in cell proliferation, cell death or cell migration. Interestingly, these functions are crucial for proper brain formation. The family consists of three JNK isoforms, JNK1, JNK2 and JNK3. Unlike brain specific JNK3 isoform, JNK1 and JNK2 are ubiquitously expressed. It is estimated that ten splice variants exist. However, the detailed cellular functions of these remain undetermined. In addition, physiological conditions keep the activities of JNK2 and JNK3 low in comparison with JNK1, whereas cellular stress raises the activity of these isoforms dramatically. Importantly, JNK1 activity is constitutively high in neurons, yet it does not stimulate cell death. This suggests a valuable role for JNK1 in brain development, but also as an important mediator of cell wellbeing. The aim of this thesis was to characterize the functional relationship between JNK1 and SCG10. We found that SCG10 is a bona fide target for JNK. By employing differential centrifugation we showed that SCG10 co-localized with active JNK, MKK7 and JIP1 in a fraction containing endosomes and Golgi vesicles. Investigation of JNK knockout tissues using phosphospecific antibodies recognizing JNK-specific phosphorylation sites on SCG10 (Ser 62/Ser 73) showed that phosphorylation of endogenous SCG10 was dramatically decreased in Jnk1-/- brains. Moreover, we found that JNK and SCG10 co-express during early embryonic days in brain regions that undergo extensive neuronal migration. Our study revealed that selective inhibition of JNK in the cytoplasm significantly increased both the frequency of exit from the multipolar stage and radial migration rate. However, as a consequence, it led to ill-defined cellular organization. Furthermore, we found that multipolar exit and radial migration in Jnk1 deficient mice can be connected to changes in phosphorylation state of SCG10. Also, the expression of a pseudo-phosphorylated mutant form of SCG10, mimicking the JNK1- phopshorylated form, brings migration rate back to normal in Jnk1 knockout mouse embryos. Furthermore, we investigated the role of SCG10 and JNK in regulation of Golgi apparatus (GA) biogenesis and whether pathological JNK action could be discernible by its deregulation. We found that SCG10 maintains GA integrity as with the absence of SCG10 neurons present more compact fragmented GA structure, as shown by the knockdown approach. Interestingly, neurons isolated from Jnk1-/- mice show similar characteristics. Block of ER to GA is believed to be involved in development of Parkinson's disease. Hence, by using a pharmacological approach (Brefeldin A treatment), we showed that GA recovery is delayed upon removal of the drug in Jnk1-/- neurons to an extent similar to the shRNA SCG10-treated cells. Finally, we investigated the role of the JNK1-SCG10 duo in the maintenance of GA biogenesis following excitotoxic insult. Although the GA underwent fragmentation in response to NMDA treatment, we observed a substantial delay in GA disintegration in neurons lacking either JNK1 or SCG10.
Resumo:
Technological innovations, the development of the internet, and globalization have increased the number and complexity of web applications. As a result, keeping web user interfaces understandable and usable (in terms of ease-of-use, effectiveness, and satisfaction) is a challenge. As part of this, designing userintuitive interface signs (i.e., the small elements of web user interface, e.g., navigational link, command buttons, icons, small images, thumbnails, etc.) is an issue for designers. Interface signs are key elements of web user interfaces because ‘interface signs’ act as a communication artefact to convey web content and system functionality, and because users interact with systems by means of interface signs. In the light of the above, applying semiotic (i.e., the study of signs) concepts on web interface signs will contribute to discover new and important perspectives on web user interface design and evaluation. The thesis mainly focuses on web interface signs and uses the theory of semiotic as a background theory. The underlying aim of this thesis is to provide valuable insights to design and evaluate web user interfaces from a semiotic perspective in order to improve overall web usability. The fundamental research question is formulated as What do practitioners and researchers need to be aware of from a semiotic perspective when designing or evaluating web user interfaces to improve web usability? From a methodological perspective, the thesis follows a design science research (DSR) approach. A systematic literature review and six empirical studies are carried out in this thesis. The empirical studies are carried out with a total of 74 participants in Finland. The steps of a design science research process are followed while the studies were designed and conducted; that includes (a) problem identification and motivation, (b) definition of objectives of a solution, (c) design and development, (d) demonstration, (e) evaluation, and (f) communication. The data is collected using observations in a usability testing lab, by analytical (expert) inspection, with questionnaires, and in structured and semi-structured interviews. User behaviour analysis, qualitative analysis and statistics are used to analyze the study data. The results are summarized as follows and have lead to the following contributions. Firstly, the results present the current status of semiotic research in UI design and evaluation and highlight the importance of considering semiotic concepts in UI design and evaluation. Secondly, the thesis explores interface sign ontologies (i.e., sets of concepts and skills that a user should know to interpret the meaning of interface signs) by providing a set of ontologies used to interpret the meaning of interface signs, and by providing a set of features related to ontology mapping in interpreting the meaning of interface signs. Thirdly, the thesis explores the value of integrating semiotic concepts in usability testing. Fourthly, the thesis proposes a semiotic framework (Semiotic Interface sign Design and Evaluation – SIDE) for interface sign design and evaluation in order to make them intuitive for end users and to improve web usability. The SIDE framework includes a set of determinants and attributes of user-intuitive interface signs, and a set of semiotic heuristics to design and evaluate interface signs. Finally, the thesis assesses (a) the quality of the SIDE framework in terms of performance metrics (e.g., thoroughness, validity, effectiveness, reliability, etc.) and (b) the contributions of the SIDE framework from the evaluators’ perspective.
Resumo:
I denna avhandling analyserar jag både offentliga och privata företag och organisationer, inklusive universitet, särskilt när det existerar potentiell inre motivation. Jag behandlar både industriell produktion, inklusive infrastruktursektorer med vertikala relationer, och tjänstesektorn. Man tänker sig att ägandet kan påverka kostnadseffektiviteten dels genom olika storlek hos lönetillägg och andra förmåner för de anställda (eng. Internal Rent Capture), och dels via asymmetrisk information. Jag frågar dessutom om det finns andra faktorer än ägande och konkurrens som kan påverka prestandan hos kommersiella företag och ideella organisationer. Dessa frågeställningar aktualiseras av pågående reformer inom den offentliga sektorn, särskilt i samband med den så kallade nya offentliga förvaltningen (eng. New Public Management). Jag analyserar reformernas inverkan på hur bra en organisation fungerar och på den sociala välfärden. Analysen i denna avhandling är teoretisk, men resultaten är relaterade också till den empiriska litteraturen. Avhandlingen är uppdelad i del I och II. I del I sammanfattar jag avhandlingen och sätter den i ett sammanhang, medan del II består av fem redan publicerade essäer. De två första (I–II) är mera traditionella, i och med att de baserar sig på homo economicus (eng. the economic man), utan att beakta den inre motivationen. I essä I (publicerad 2008) bedömer vi fördelar och nackdelar av privatisering och avreglering innanför en sådan ram, men med en betoning också på icke återvinningsbara fasta kostnader och vertikala relationer. I essä II (publicerad 2012) fokuserar vi oss på vertikal separation, och konkurrensutsättning och privatisering i nätverksindustrier. I essäerna III–V vidgas perspektivet genom att införa potentiell inre motivation i en agentmodell. Analysen i essä III (publicerad 2014) tillämpas på offentligt ägande och privatisering. I essäerna IV och V (publicerade 2009 respektive 2013) utvidgas analysen till att även gälla kreativa branscher, särskilt arbete inom universiteten, där den inre motivationen hos de anställda kan tänkas vara avgörande. I dessa essäer tillämpas en analys som inbegriper ett intra-personellt spel inom ramen för en agentmodell med potentiell inre motivation. Vi analyserar sålunda avvägningen mellan ekonomiska incitament och inre motivation.
Resumo:
The purpose of this thesis is to study how and to which extent Finland, Sweden and Norway have adapted their alcohol policies to the framework imposed to them by the EU and the European Economic Area (EEA) since the mid-1990s. This is done by studying the underlying mechanisms that have influenced the formation of alcohol policy in the Nordic countries in that period. As a part of this analysis main differences in alcohol policies and alcohol consumption between the three countries are assessed and the phenomenon of cross-border trade with alcohol is discussed. The study examines also the development of Finnish, Norwegian and Swedish alcohol policies between 1994 and 2012 and compares the Nordic alcohol policies with other alcohol policies in Europe as the situation was in 2012. The time frame of the study spans from the mid-1990s to the end of 2013 and is divided into three phases. Studying the role of the Europeanisation process on the formation of alcohol policies has a key role in the analysis. Besides alcohol policies, the analyses comprise the development of alcohol consumption and cross-border trade with alcohol. In addition, a quantitative scale constructed to measure the strictness of alcohol policies is utilised in the analyses. The results from the scale are used to substantiate the qualitative analysis and to test whether the stereotypical view of a strict Nordic alcohol policy is still true. The results from the study clearly corroborate earlier findings on the significance of Europeanisation and the Single Market for the development of alcohol policies in the Nordic countries. Free movement of goods and unhindered competition have challenged the principle of disinterest and enabled private profit seeking in alcohol trade. The Single Market has also contributed to the increase in availability of alcohol and made it more difficult for the Nordic EU member states to maintain restrictive alcohol policies. All in all, alcohol policies in the Nordic countries are more liberal in 2013 than they were in 1994. Norway, being outside the EU has, however, managed to maintain a stricter alcohol policy than Finland and Sweden. Norway has also been spared from several EU directives that have affected Finland and Sweden, the most remarkable being the abolishment of the travellers’ import quotas for alcohol within the EU. Due to its position as a non-EU country Norway has been able to maintain high alcohol taxes without being subjected to a ”race to the bottom” regarding alcohol taxes the same way as Finland and Sweden. Finland distinguishes as the country that has liberalised its alcohol policy most during the study period. The changes in alcohol policies were not only induced by Europeanisation and the Single Market, but also by autonomous decision-making and political processes in the individual countries. Furthermore, the study shows that alcohol policy measures are implemented more widely in Europe than before and that there is a slow process of convergence going on regarding alcohol policy in Europe. Despite this, alcohol policies in the Nordic countries are still by far the strictest in all of Europe. From a Europeanisation perspective, the Nordic countries were clearly on the receiving end during the first two study phases (1994–2007), having more to adjust to rules from the EU and the Single Market than having success in uploading and shaping alcohol policy on the European and international field. During the third and final study phase (2008–2013), however, the Nordic countries have increasingly succeeded in contributing to shape the alcohol policy arena in the EU and also more widely through the WHOs global alcohol strategy. The restrictive Nordic policy tradition on which the current alcohol policies in Finland, Sweden and Norway were built on has still quite a solid evidence base. Although the basis of the restrictive alcohol policy has crumbled somewhat during the past twenty years and the policies have become less effective, nothing prevents it from being the base for alcohol policy in the Nordic countries even in the long term. In the future, all that is needed for an effective and successful alcohol policy is a solid evidence base, enough political will and support from the general public.
Resumo:
Cholesterol (Chol) is an important lipid in cellular membranes functioning both as a membrane fluidity regulator, permeability regulator and co-factor for some membrane proteins, e.g. G-protein coupled receptors. It also participates in the formation of signaling platforms and gives the membrane more mechanical strenght to prevent osmotic lysis of the cell. The sterol structure is very conserved and already minor structural modifications can completely abolish its membrane functions. The right interaction with adjacent lipids and the preference of certain lipid structures over others are also key factors in determining the membrane properties of cholesterol. Because of the many important properties of cholesterol it is of value to understand the forces and structural properties that govern the membrane behavior of this sterol. In this thesis we have used established fluorescence spectroscopy methods to study the membrane behavior of both cholesterol and some of its 3β-modified analogs. Using several fluorescent probes we have established how the acyl chain order of the two main lipid species, sphingomyelin (SM) and phosphatidylcholine (PC) affect sterol partitioning as well as characterized the membrane properties of 3β-aminocholesterol and cholesteryl phosphocholine. We concluded that cholesterol prefers SM over PC at equal acyl chain order, indicating that other structural properties besides the acyl chain order are important for sphingomyelin-sterol interactions. A positive charge at the 3β position only caused minor changes in the sterol membrane behavior compared to cholesterol. A large phosphocholine head group caused a disruption in membrane packing together with other membrane lipids with large head groups, but was also able to form stable fluid bilayers together with ceramide and cholesterol. The Ability of the large head group sterol to form bilayers together with ceramide was further explored in the last paper where cholesteryl phosphocholine/ceramide (Chol-PC/Cer) complexes were successfully used to transfer ceramide into cultured cells.
Resumo:
Online sexual solicitation (solicitation) of youth has received widespread media and research attention during the last decade. The prevalence rates of youth who have experienced solicitation or solicitation attempts vary between studies depending on the methodology used (e.g., whether youth or adults are the target study group). In studies focusing on youth victims, the prevalence of solicitation attempts made by adults during the past year is typically reported to be between 5 and 9%. Adults who solicit youth online have been found to use deception and other manipulative behaviors to gain access to sexual activities with youth. However, previous studies have lacked a control group of adults who solicit other adults online. Without this comparison, one could argue that deceiving others online about one’s identity, and engaging in manipulative behaviors, is an inherent part of most online sexual interactions with strangers. Additionally, little is known about the associations between manipulative behaviors and the solicitation outcomes. In research concerning offline sexual behaviors, it has been noted that situational factors, such as sexual arousal, may alter both sexual interest and behavior. The effects of situational factors on online sexual behaviors have been less extensively studied (especially so with a quantitative approach); no studies have to date focused on adults’ solicitation of youth. Investigating the role of a lowered sexual age preference and the role of situational factors in the soliciting adults could be an important step in order to receive deeper knowledge of the role of traits and states in the context of solicitation. Additionally, there is a lack of knowledge of the effect of the age of the youth. Although previous studies on solicitation has found that older youth, compared with younger youth and children, are more often solicited, the possible reasons for this have not been investigated. Are adults who solicit youth affected by legal deterrence (through the legal age of consent), is it because older youth are more available online, or are the adults’ age preferences merely a product of a normally distributed age preference in the population? The purpose of the present thesis was fivefold: 1) to obtain an estimate of the frequency of adults’ solicitation of youth as self-reported and observed in actual behavior; 2) to explore whether the legal age of consent (LAC) affects solicitation frequency, or whether a normally distributed sexual age preference more accurately describe the proportion of solicited youth of different ages; 3) to investigate the associations of both traits (e.g., lower sexual age preference) and states (immediate situational factors, such as alcohol intoxication), and the solicitation target; 4) to explore whether adults who solicit youth and adults who solicit adults are equally deceitful and manipulative online, and whether the different solicitation outcomes are as common in both groups; and 5) to investigate whether the deceitful and manipulative behaviors engaged in had different associations with the solicitation outcomes depending on the age of the solicited. In the survey study, a convenience sample of 1393 adult participants (aged 18 years or older) self-reported any online communication with strangers during the past year. Of these, 56% (776 respondents) reported that they had solicited or attempted to solicit at least one stranger. Of the respondents, 453 (58.4%) were men, and 323 (41.6%) were women. Participants with only adult contacts (18 years or older) constituted the majority (640 respondents). In contrast, 136 individuals reported a youth contact (a 13 year old or younger, or a 14 to 17-year old). Approximately half of the participants were men in the adult contact group, while 75% of the participants were men in the youth contact group. Approximately 60% of the participants with youth contacts were recruited from two websites associated with a pedophilic sexual interest. In an online quasi-experimental study, with researchers impersonating youth of different ages (10–18 year olds) in chat rooms, 251 online conversations with chat room visitors made up the entire sample. All chat room visitors alleged to be men. The self-reported frequency of having solicited youth (0–17-year olds) during the past year was approximately 10% in our sample of adults who reported communicating with any strangers online. When we observed this behavior in chat rooms, we found that approximately 30% of the chat room visitors who believed they interacted with a 10 to 14 year old attempted to solicit the youth. We found that solicitation attempts increased equally much when increasing the age of the impersonated youth from 14 to 16, as from 16 to 18. Thus, we concluded that a normally distributed age preference in the population was a more plausible explanation to the effect of the age of the solicited, rather than the LAC (here; 15 and 16). If the chat room visitors would have been deterred only by the LAC, we would have expected that the change in amount of solicitation attempts from an illegal age group to a legal age group would have been significantly stronger than changes between age groups within illegal-illegal and legal-legal groups. Our subsample of survey participants from the pedophilia-related websites expectedly reported that they had solicited youth more often in comparison to the sample gathered through general (i.e., not associated with any particular sexual preference) websites. We also found that participants with a youth contact reported higher levels of sexual arousal and shame before the sexual interaction with their online contact, compared with participants with an adult contact. Additionally, the participants with youth contacts who reported consumption of child- and adolescent pornography also reported being more sexually aroused before the interaction, compared to the participants with youth contacts who did not report consumption of these kinds of pornography. We also found clear indications that the online sexual interaction had an alleviatory effect on reported levels of sadness, boredom and stress, independent of the age of the contact. Generally, the participants with youth and adult contacts reported deceiving their contacts as often and suggesting keeping the communication a secret from someone as often. Participants with a youth contact, however, reported using more persuasion techniques for online sexual purposes or for the purpose of an offline meeting, compared to those with an adult contact. In the chat rooms, we found that more indirect ways of future sexual communication (e.g., continuing chatting) was suggested by the chat room visitors that were under the assumption of interacting with youth aged 10 to 14, compared with more direct means (e.g., meeting offline). Survey participants with youth contacts who had used deception, suggested keeping the interactions a secret, and/or persuaded their contact by appealing to the contacts feelings of love and attachment for the participant had also more often engaged in cybersex with the contact. No other manipulative behaviors were associated with the other investigated solicitation outcomes (receiving a sexual picture, meeting offline, and engaging in sexual contact offline) within this group of participants. However, using deception, suggesting secrecy and using persuasion was also positively associated with certain solicitation outcomes within participants with an adult contact. In summary, adults’ solicitation of youth is much more frequent when observed in chat rooms than self-reported. Additionally, an underlying lowered sexual age preference seems to be a motivating factor on a group level in adults who solicit youth. We concluded that directed prevention efforts should be made on pedophiliarelated websites. Additionally, the role of situational factors, especially sexual arousal in persons with a pedo- or hebephilic sexual interest should be investigated further in the context of online sexual solicitation.
Resumo:
Terpenes are a valuable natural resource for the production of fine chemicals. Turpentine, obtained from biomass and also as a side product of softwood industry, is rich in monoterpenes such as α-pinene and β-pinene, which are widely used as raw materials in the synthesis of flavors, fragrances and pharmaceutical compounds. The rearrangement of their epoxides has been thoroughly studied in recent years, as a method to obtain compounds which are further used in the fine chemical industry. The industrially most desired products of α-pinene oxide isomerization are campholenic aldehyde and trans-carveol. Campholenic aldehyde is an intermediate for the manufacture of sandalwood-like fragrances such as santalol. Trans-carveol is an expensive constituent of the Valencia orange essence oil used in perfume bases and food flavor composition. Furthermore it has been found to exhibit chemoprevention of mammary carcinogenesis. A wide range of iron and ceria supported catalysts were prepared, characterized and tested for α-pinene oxide isomerization in order to selective synthesis of above mentioned products. The highest catalytic activity in the preparation of campholenic aldehyde over iron modified catalysts using toluene as a solvent at 70 °C (total conversion of α-pinene oxide with a selectivity of 66 % to the desired aldehyde) was achieved in the presence of Fe-MCM-41. Furthermore, Fe-MCM-41 catalyst was successfully regenerated without deterioration of catalytic activity and selectivity. The most active catalysts in the synthesis of trans-carveol from α-pinene oxide over iron and ceria modified catalysts in N,N-dimethylacetamide as a solvent at 140 °C (total conversion of α-pinene oxide with selectivity 43 % to trans-carveol) were Fe-Beta-300 and Ce-Si-MCM-41. These catalysts were further tested for an analogous reaction, namely verbenol oxide isomerization. Verbenone is another natural organic compound which can be found in a variety of plants or synthesized by allylic oxidation of α-pinene. An interesting product which is synthesized from verbenone is (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol. It has been discovered that this diol possesses potent anti-Parkinson activity. The most effective way leading to desired diol starts from verbenone and includes three stages: epoxidation of verbenone to verbenone oxide, reduction of verbenone oxide and subsequent isomerization of obtained verbenol oxide, which is analogous to isomerization of α-pinene oxide. In the research focused on the last step of these synthesis, high selectivity (82 %) to desired diol was achieved in the isomerization of verbenol oxide at a conversion level of 96 % in N,N-dimethylacetamide at 140 °C using iron modified zeolite, Fe-Beta-300. This reaction displayed surprisingly high selectivity, which has not been achieved yet. The possibility of the reuse of heterogeneous catalysts without activity loss was demonstrated.
Resumo:
The emergence of the idea of multiculturalism in Swedish public discourse and social science in the latter half of the 1960s and introduction of official multiculturalism in 1975 constituted a major intellectual and political shift in the post-war history of Sweden. The ambition of the 1975 immigrant and minority policy to enable the preservation of ethno-cultural minorities and to create a positive attitude towards the new multicultural society among the majority population was also incorporated into Swedish cultural, educational and media policies. The rejection of assimilationism and the new commitment to ethno-cultural diversity, the multicultural moment, has earned Sweden a place on the list of the early adopters of official multiculturalism, together with Canada and Australia. This compilation thesis examines the origins and early post-war history of the idea of multiculturalism as well as the interplay between idea and politics in the shift from a public ideal of homogeneity to an ideal of multiculturalism in Sweden. It does so from a range of conceptual, comparative, transnational, and biographical perspectives. The thesis consists of an introduction (Part I) and four previously published studies (Part II). The primary research result of the thesis concerns the agency involved in the break-through and formal establishment of the idea of multiculturalism in Sweden. Actors such as ethnic activists, experts and officials were instrumental in the introduction and establishment of multiculturalism in Sweden, as they also had been in Canada and in Australia. These actors have, however, not previously been recognized and analysed as significant idea-makers and political agents in the case of Sweden. The intertwined connections between activists, social scientists, linguists, and officials facilitated the transfer of the idea of multiculturalism from a publically contested idea to public policy via the way of The Swedish Trade Union Confederation, academia and the Royal Commission of Immigration. The thesis furthermore shows that the political success of the idea of multiculturalism, such as it was within the limits of the universalist social democratic welfare state, was dependent on whom the claims-makers were, the status and positions they held, and the way the idea of multiculturalism was conceptualised and used. It was also dependent on the migratory context of labour immigration in the 1960s and 1970s and on whose behalf the advocates of multiculturalism made their claims. The majority of the labour immigrants were Finnish citizens from the former eastern half of the kingdom of Sweden who were net contributors to the Swedish welfare state. This facilitated the recognition of their ethno-cultural difference, and, following the logic of universalism, the ethno-cultural difference of other minority groups in Sweden. The historical significance of the multicultural moment is still evident in the contemporary immigration and integration policies of Sweden. The affirmation of diversity continues to set Sweden apart from the rest of Europe, now more so than in the 1970s, even though the migratory context has changed radically in the last 40 years.
Resumo:
JNK1 is a MAP-kinase that has proven a significant player in the central nervous system. It regulates brain development and the maintenance of dendrites and axons. Several novel phosphorylation targets of JNK1 were identified in a screen performed in the Coffey lab. These proteins were mainly involved in the regulation of neuronal cytoskeleton, influencing the dynamics and stability of microtubules and actin. These structural proteins form the dynamic backbone for the elaborate architecture of the dendritic tree of a neuron. The initiation and branching of the dendrites requires a dynamic interplay between the cytoskeletal building blocks. Both microtubules and actin are decorated by associated proteins which regulate their dynamics. The dendrite-specific, high molecular weight microtubule associated protein 2 (MAP2) is an abundant protein in the brain, the binding of which stabilizes microtubules and influences their bundling. Its expression in non-neuronal cells induces the formation of neurite-like processes from the cell body, and its function is highly regulated by phosphorylation. JNK1 was shown to phosphorylate the proline-rich domain of MAP2 in vivo in a previous study performed in the group. Here we verify three threonine residues (T1619, T1622 and T1625) as JNK1 targets, the phosphorylation of which increases the binding of MAP2 to microtubules. This binding stabilizes the microtubules and increases process formation in non-neuronal cells. Phosphorylation-site mutants were engineered in the lab. The non-phosphorylatable mutant of MAP2 (MAP2- T1619A, T1622A, T1625A) in these residues fails to bind microtubules, while the pseudo-phosphorylated form, MAP2- T1619D, T1622D, Thr1625D, efficiently binds and induces process formation even without the presence of active JNK1. Ectopic expression of the MAP2- T1619D, T1622D, Thr1625D in vivo in mouse brain led to a striking increase in the branching of cortical layer 2/3 (L2/3) pyramidal neurons, compared to MAP2-WT. The dendritic complexity defines the receptive field of a neuron and dictates the output to the postsynaptic cells. Previous studies in the group indicated altered dendrite architecture of the pyramidal neurons in the Jnk1-/- mouse motor cortex. Here, we used Lucifer Yellow loading and Sholl analysis of neurons in order to study the dendritic branching in more detail. We report a striking, opposing effect in the absence of Jnk1 in the cortical layers 2/3 and 5 of the primary motor cortex. The basal dendrites of pyramidal neurons close to the pial surface at L2/3 show a reduced complexity. In contrast, the L5 neurons, which receive massive input from the L2/3 neurons, show greatly increased branching. Another novel substrate identified for JNK1 was MARCKSL1, a protein that regulates actin dynamics. It is highly expressed in neurons, but also in various cancer tissues. Three phosphorylation target residues for JNK1 were identified, and it was demonstrated that their phosphorylation reduces actin turnover and retards migration of these cells. Actin is the main cytoskeletal component in dendritic spines, the site of most excitatory synapses in pyramidal neurons. The density and gross morphology of the Lucifer Yellow filled dendrites were characterized and we show reduced density and altered morphology of spines in the motor cortex and in the hippocampal area CA3. The dynamic dendritic spines are widely considered to function as the cellular correlate during learning. We used a Morris water maze to test spatial memory. Here, the wild-type mice outperformed the knock-out mice during the acquisition phase of the experiment indicating impaired special memory. The L5 pyramidal neurons of the motor cortex project to the spinal cord and regulate the movement of distinct muscle groups. Thus the altered dendrite morphology in the motor cortex was expected to have an effect on the input-output balance in the signaling from the cortex to the lower motor circuits. A battery of behavioral tests were conducted for the wild-type and Jnk1-/- mice, and the knock-outs performed poorly compared to wild-type mice in tests assessing balance and fine motor movements. This study expands our knowledge of JNK1 as an important regulator of the dendritic fields of neurons and their manifestations in behavior.
Resumo:
In this thesis, stepwise titration with hydrochloric acid was used to obtain chemical reactivities and dissolution rates of ground limestones and dolostones of varying geological backgrounds (sedimentary, metamorphic or magmatic). Two different ways of conducting the calculations were used: 1) a first order mathematical model was used to calculate extrapolated initial reactivities (and dissolution rates) at pH 4, and 2) a second order mathematical model was used to acquire integrated mean specific chemical reaction constants (and dissolution rates) at pH 5. The calculations of the reactivities and dissolution rates were based on rate of change of pH and particle size distributions of the sample powders obtained by laser diffraction. The initial dissolution rates at pH 4 were repeatedly higher than previously reported literature values, whereas the dissolution rates at pH 5 were consistent with former observations. Reactivities and dissolution rates varied substantially for dolostones, whereas for limestones and calcareous rocks, the variation can be primarily explained by relatively large sample standard deviations. A list of the dolostone samples in a decreasing order of initial reactivity at pH 4 is: 1) metamorphic dolostones with calcite/dolomite ratio higher than about 6% 2) sedimentary dolostones without calcite 3) metamorphic dolostones with calcite/dolomite ratio lower than about 6% The reactivities and dissolution rates were accompanied by a wide range of experimental techniques to characterise the samples, to reveal how different rocks changed during the dissolution process, and to find out which factors had an influence on their chemical reactivities. An emphasis was put on chemical and morphological changes taking place at the surfaces of the particles via X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Supporting chemical information was obtained with X-Ray Fluorescence (XRF) measurements of the samples, and Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) and Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) measurements of the solutions used in the reactivity experiments. Information on mineral (modal) compositions and their occurrence was provided by X-Ray Diffraction (XRD), Energy Dispersive X-ray analysis (EDX) and studying thin sections with a petrographic microscope. BET (Brunauer, Emmet, Teller) surface areas were determined from nitrogen physisorption data. Factors increasing chemical reactivity of dolostones and calcareous rocks were found to be sedimentary origin, higher calcite concentration and smaller quartz concentration. Also, it is assumed that finer grain size and larger BET surface areas increase the reactivity although no certain correlation was found in this thesis. Atomic concentrations did not correlate with the reactivities. Sedimentary dolostones, unlike metamorphic ones, were found to have porous surface structures after dissolution. In addition, conventional (XPS) and synchrotron based (HRXPS) X-ray Photoelectron Spectroscopy were used to study bonding environments on calcite and dolomite surfaces. Both samples are insulators, which is why neutralisation measures such as electron flood gun and a conductive mask were used. Surface core level shifts of 0.7 ± 0.1 eV for Ca 2p spectrum of calcite and 0.75 ± 0.05 eV for Mg 2p and Ca 3s spectra of dolomite were obtained. Some satellite features of Ca 2p, C 1s and O 1s spectra have been suggested to be bulk plasmons. The origin of carbide bonds was suggested to be beam assisted interaction with hydrocarbons found on the surface. The results presented in this thesis are of particular importance for choosing raw materials for wet Flue Gas Desulphurisation (FGD) and construction industry. Wet FGD benefits from high reactivity, whereas construction industry can take advantage of slow reactivity of carbonate rocks often used in the facades of fine buildings. Information on chemical bonding environments may help to create more accurate models for water-rock interactions of carbonates.
Resumo:
Acid sulfate (a.s.) soils constitute a major environmental issue. Severe ecological damage results from the considerable amounts of acidity and metals leached by these soils in the recipient watercourses. As even small hot spots may affect large areas of coastal waters, mapping represents a fundamental step in the management and mitigation of a.s. soil environmental risks (i.e. to target strategic areas). Traditional mapping in the field is time-consuming and therefore expensive. Additional more cost-effective techniques have, thus, to be developed in order to narrow down and define in detail the areas of interest. The primary aim of this thesis was to assess different spatial modeling techniques for a.s. soil mapping, and the characterization of soil properties relevant for a.s. soil environmental risk management, using all available data: soil and water samples, as well as datalayers (e.g. geological and geophysical). Different spatial modeling techniques were applied at catchment or regional scale. Two artificial neural networks were assessed on the Sirppujoki River catchment (c. 440 km2) located in southwestern Finland, while fuzzy logic was assessed on several areas along the Finnish coast. Quaternary geology, aerogeophysics and slope data (derived from a digital elevation model) were utilized as evidential datalayers. The methods also required the use of point datasets (i.e. soil profiles corresponding to known a.s. or non-a.s. soil occurrences) for training and/or validation within the modeling processes. Applying these methods, various maps were generated: probability maps for a.s. soil occurrence, as well as predictive maps for different soil properties (sulfur content, organic matter content and critical sulfide depth). The two assessed artificial neural networks (ANNs) demonstrated good classification abilities for a.s. soil probability mapping at catchment scale. Slightly better results were achieved using a Radial Basis Function (RBF) -based ANN than a Radial Basis Functional Link Net (RBFLN) method, narrowing down more accurately the most probable areas for a.s. soil occurrence and defining more properly the least probable areas. The RBF-based ANN also demonstrated promising results for the characterization of different soil properties in the most probable a.s. soil areas at catchment scale. Since a.s. soil areas constitute highly productive lands for agricultural purpose, the combination of a probability map with more specific soil property predictive maps offers a valuable toolset to more precisely target strategic areas for subsequent environmental risk management. Notably, the use of laser scanning (i.e. Light Detection And Ranging, LiDAR) data enabled a more precise definition of a.s. soil probability areas, as well as the soil property modeling classes for sulfur content and the critical sulfide depth. Given suitable training/validation points, ANNs can be trained to yield a more precise modeling of the occurrence of a.s. soils and their properties. By contrast, fuzzy logic represents a simple, fast and objective alternative to carry out preliminary surveys, at catchment or regional scale, in areas offering a limited amount of data. This method enables delimiting and prioritizing the most probable areas for a.s soil occurrence, which can be particularly useful in the field. Being easily transferable from area to area, fuzzy logic modeling can be carried out at regional scale. Mapping at this scale would be extremely time-consuming through manual assessment. The use of spatial modeling techniques enables the creation of valid and comparable maps, which represents an important development within the a.s. soil mapping process. The a.s. soil mapping was also assessed using water chemistry data for 24 different catchments along the Finnish coast (in all, covering c. 21,300 km2) which were mapped with different methods (i.e. conventional mapping, fuzzy logic and an artificial neural network). Two a.s. soil related indicators measured in the river water (sulfate content and sulfate/chloride ratio) were compared to the extent of the most probable areas for a.s. soils in the surveyed catchments. High sulfate contents and sulfate/chloride ratios measured in most of the rivers demonstrated the presence of a.s. soils in the corresponding catchments. The calculated extent of the most probable a.s. soil areas is supported by independent data on water chemistry, suggesting that the a.s. soil probability maps created with different methods are reliable and comparable.