Protein folding: a perspective for biology, medicine and biotechnology

At the present time, protein folding is an extremely active field of research including aspects of biology, chemistry, biochemistry, computer science and physics. The fundamental principles have practical applications in the exploitation of the advances in genome research, in the understanding of different pathologies and in the design of novel proteins with special functions. Although the detailed mechanisms of folding are not completely known, significant advances have been made in the understanding of this complex process through both experimental and theoretical approaches. In this review, the evolution of concepts from Anfinsen's postulate to the "new view" emphasizing the concept of the energy landscape of folding is presented. The main rules of protein folding have been established from in vitro experiments. It has been long accepted that the in vitro refolding process is a good model for understanding the mechanisms by which a nascent polypeptide chain reaches its native conformation in the cellular environment. Indeed, many denatured proteins, even those whose disulfide bridges have been disrupted, are able to refold spontaneously. Although this assumption was challenged by the discovery of molecular chaperones, from the amount of both structural and functional information now available, it has been clearly established that the main rules of protein folding deduced from in vitro experiments are also valid in the cellular environment. This modern view of protein folding permits a better understanding of the aggregation processes that play a role in several pathologies, including those induced by prions and Alzheimer's disease. Drug design and de novo protein design with the aim of creating proteins with novel functions by application of protein folding rules are making significant progress and offer perspectives for practical applications in the development of pharmaceuticals and medical diagnostics.

The advantages and disadvantages of logistics centralization and decentralization from employee’s perspective

Tämän tutkimuksen tarkoituksena on havainnoida keskittämisen ja hajauttamisen hyötyjä ja haittoja logistiikassa, ja selventää mitä tekijöidä tulee huomioida näiden kahden rakenteen väliltä valitessa. Tutkimus kokoaa molempien rakenteiden hyödyt ja haitat hyödyntämällä sekä haastateltujen työntekijöiden osaamista ja mielipiteitä että aiheeseen liittyvää kirjallisuutta. Päätavoitteena on lisätä ymmärrystä siitä, miten organisaatiorakenne vaikuttaa logistiseen toimintaan.

New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

Panic disorder patients are vulnerable to recurrent panic attacks. Two neurochemical hypotheses have been proposed to explain this susceptibility. The first assumes that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organize defensive reactions to cope with proximal threats and of sympathomotor control areas of the rostral ventrolateral medulla that generate most of the neurovegetative symptoms of the panic attack. The second suggests that endogenous opioids buffer normal subjects from the behavioral and physiological manifestations of the panic attack, and their deficit brings about heightened suffocation sensitivity and separation anxiety in panic patients, making them more vulnerable to panic attacks. Experimental results obtained in rats performing one-way escape in the elevated T-maze, an animal model of panic, indicate that the inhibitory action of serotonin on defense is connected with activation of endogenous opioids in the periaqueductal gray. This allows reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the fulcrum of serotonin-opioid interaction.

Biochemical adaptations of mammalian hibernation: exploring squirrels as a perspective model for naturally induced reversible insulin resistance

An important disease among human metabolic disorders is type 2 diabetes mellitus. This disorder involves multiple physiological defects that result from high blood glucose content and eventually lead to the onset of insulin resistance. The combination of insulin resistance, increased glucose production, and decreased insulin secretion creates a diabetic metabolic environment that leads to a lifetime of management. Appropriate models are critical for the success of research. As such, a unique model providing insight into the mechanisms of reversible insulin resistance is mammalian hibernation. Hibernators, such as ground squirrels and bats, are excellent examples of animals exhibiting reversible insulin resistance, for which a rapid increase in body weight is required prior to entry into dormancy. Hibernator studies have shown differential regulation of specific molecular pathways involved in reversible resistance to insulin. The present review focuses on this growing area of research and the molecular mechanisms that regulate glucose homeostasis, and explores the roles of the Akt signaling pathway during hibernation. Here, we propose a link between hibernation, a well-documented response to periods of environmental stress, and reversible insulin resistance, potentially facilitated by key alterations in the Akt signaling network, PPAR-γ/PGC-1α regulation, and non-coding RNA expression. Coincidentally, many of the same pathways are frequently found to be dysregulated during insulin resistance in human type 2 diabetes. Hence, the molecular networks that may regulate reversible insulin resistance in hibernating mammals represent a novel approach by providing insight into medical treatment of insulin resistance in humans.

The role of network competence and international business competence in multinational corporations: Subsidiary perspective

On-going process of globalization makes companies all over the world to go beyond the national markets and internationalize. Organizational form of multinational corporation (MNC) has capabilities for establishing the affiliate companies in several countries. Thus, the relocation of resources occurs and particularly, the cross-border transfer of knowledge which possesses the competitive advantage. However, differences in countries` business environments and cultures may constrain this capability. The research aim of this thesis is to investigate the role of subsidiary’s network competence (ability to build and manage the relationships with other local business units) and international business competence in relation to the benefits that MNC receives from a subsidiary. Additionally, subsidiary’s business adaptation, partnerships and knowledge transfer mechanism with parent company and external partners are investigated. This research, conducted in the Finnish-Russian context, consists of theoretical and empirical parts. The qualitative approach in the form of multiple case studies is employed. The empirical data incorporated primary and secondary data in the form of interviews collected in 2013 and 2015 years. Interviews were collected from four Finnish case companies in Saint-Petersburg and Kaluga region and five Russian partner companies. Results are drawn from two cases from Saint-Petersburg. The abductive research approach for the results analysis is adopted. The results indicate that both competencies lead to the subsidiary’s local embeddedness in the form of mutual business activities with local business partners and product adaptation for the local market needs. In addition to the monetary benefits in form of payments or turnover share, local embeddedness brings the knowledge of the local environment which is utilized by an MNC in the long-term planning. Another found tacit benefit is the access to the national market. This is strategically useful benefit not only for parent MNC but also for the subsidiary’s partners, i.e. international suppliers.

The Utilization of Chinese Social Media in Internationalization into China: Perspective of a Western Company

The purpose of this qualitative research is to analyze western-based companies’ social media usage in internationalization into China and to identify social media presence’ impact on the internationalization process. Additionally, the benefits and challenges a western company may face while using social media in China will be illustrated. Competitive advantages, knowledge, networks and relations, and costs and risks could be identified as the key antecedents for successful internationalization. A great social media presence could create a competitive advantage for a western company while competitive advantages may be communicated in social media marketing, knowledge and networks can be enhanced and utilized in internationalization via social media two-way communication. The biggest benefit for internationalization resulted from decreased marketing costs due to cost-effectiveness of social media. The results revealed that cost effective brand awareness was the main benefit from the social media usage in internationalization into China. However, companies struggled with the limited resources and despite of understanding the importance of Chinese social media, lacked sufficient resources for the social media operations. Companies should determine clear strategy and goals that they are willing to achieve via social media in internationalization process, and allocate required resources according to the social media strategy. Localization of the social media operations is important in China, and business-to-consumer companies tend to benefit more from the social media presence. Business-to-business companies may increase the brand’s credibility by successful Chinese social media operations.

FUTURES OF FINNISH FOOD SYSTEM BY 2050. The perspective of resilience

Modern food systems face complex global challenges such as climate change, resource scarcities, population growth, concentration and globalization. It is not possible to forecast how all these challenges will affect food systems, but futures research methods provide possibilities to enable better understanding of possible futures and that way increases futures awareness. In this thesis, the two-round online Delphi method was utilized to research experts’ opinions about the present and the future resilience of the Finnish food system up to 2050. The first round questionnaire was constructed based on the resilience indicators developed for agroecosystems. Sub-systems in the study were primary production (main focus), food industry, retail and consumption. Based on the results from the first round, the future images were constructed for primary production and food industry sub-sections. The second round asked experts’ opinion about the future images’ probability and desirability. In addition, panarchy scenarios were constructed by using the adaptive cycle and panarchy frameworks. Furthermore, a new approach to general resilience indicators was developed combining “categories” of the social ecological systems (structure, behaviors and governance) and general resilience parameters (tightness of feedbacks, modularity, diversity, the amount of change a system can withstand, capacity of learning and self- organizing behavior). The results indicate that there are strengths in the Finnish food system for building resilience. According to experts organic farms and larger farms are perceived as socially self-organized, which can promote innovations and new experimentations for adaptation to changing circumstances. In addition, organic farms are currently seen as the most ecologically self-regulated farms. There are also weaknesses in the Finnish food system restricting resilience building. It is important to reach optimal redundancy, in which efficiency and resilience are in balance. In the whole food system, retail sector will probably face the most dramatic changes in the future, especially, when panarchy scenarios and the future images are reflected. The profitability of farms is and will be a critical cornerstone of the overall resilience in primary production. All in all, the food system experts have very positive views concerning the resilience development of the Finnish food system in the future. Sometimes small and local is beautiful, sometimes large and international is more resilient. However, when probabilities and desirability of the future images were questioned, there were significant deviations. It appears that experts do not always believe desirable futures to materialize.

Standing before a sentence : Moore’s paradox and a perspective from within language

Med avstamp i ett satsbegrepp som inspirerats av Ludwig Wittgenstein, där sats och kontext betraktas som internt förbundna och där den verkliga användningen av en sats är central för dess mening, visar avhandlingen hur filosofers olika uppfattning om den filosofiska terminologins roll och möjligheter har följder för deras sätt att uppfatta och behandla filosofiska frågeställningar. Moores paradox fungerar som testfall. Denna kända filosofiska frågeställning har diskuterats sedan 1940-talet och kretsar kring hävdandet av satsen ”Jag tror att det regnar och det regnar inte”. Problemet är att det vore märkligt för en talare att hävda satsen om sig själv: det verkar finnas ett logiskt hinder för att hävda en sats även om den är välformad, kunde vara sann och inte på ett entydigt sätt innehåller en kontradiktion. Moores paradox behandlas genom att granska några lösningsförslag (framförda av bl.a. G.E. Moore, J. L. Austin, J. Searle) och de uppfattningar om språket som de förutsätter. Genom att kontrastera dessa med ett användarperspektiv där språkets användning i meningsfulla sammanhang förväntas spela en central roll i behandlingen av paradoxen visar författaren hur också den intellektuella kontext inom vilken en filosof betraktar paradoxen spelar en avgörande roll för vilka mått som krävs för att upplösa den. Istället för att föreslå en egen lösning presenteras en behandling av paradoxen genom en diskussion och utredning av de grundvillkor som leder till att den uppstår. Här intar satsbegreppet en central plats. Avhandlingen är författad inom traditionen efter den senare Wittgenstein (närmare bestämt den gren som ansluter sig till en s.k. terapeutisk filosofisyn) men går i dialog med filosofiskt arbete som ligger utanför traditionen. Författaren strävar både till att medla mellan, sammanföra och särskilja olika temata som behandlats på ett sätt inom traditionen och på andra sätt utanför den och använder sig här av metaforen att filosofera inifrån i kontrast till utanför språket. Avhandlingens huvudsakliga bidrag är till metafilosofin genom dess fokus på filosofins metod. ------------------------------------------------------------ Mooren paradoksi on tunnettu filosofinen ongelma, josta on keskusteltu 1940-luvulta alkaen. Paradoksin keskeisenä osana esiintyy väitelause ”Uskon, että ulkona sataa, mutta ulkona ei sada”. Ongelman lähtökohta on, että olisi merkillistä jos puhuja esittäisi lauseen itseään koskevana väitteenä: väite näyttää olevan loogisesti mahdoton esittää, vaikka se on hyvinmuodostettu, mahdollisesti tosi, eikä yksiselitteisellä tavalla sisällä kontradiktiota. Tässä väitöskirjassa Mooren paradoksi esiintyy esimerkkinä filosofisesta ongelmasta, jossa mm. lausekäsitteellä on keskeinen rooli ja jonka avulla voidaan muodostella ns. kielensisäinen filosofinen näkökulma. Mooren paradoksia käsitellään tarkastelemalla muutamia ratkaisuehdotuksia (mm. G.E. Mooren, J.L. Austinin, J. Searlen esittämät) ja niitä kielikäsityksiä joita nämä ratkaisuehdotukset edellyttävät. Asettamalla vastakkain ratkaisuehdotukset ja käyttäjänäkymä, jossa kielenkäyttö mielekkäissä konteksteissa asetetaan keskeiseen asemaan paradoksin käsittelyssä, kirjoittaja osoittaa miten myös paradoksin filosofisen tarkastelun intellektuaalinen konteksti on hyväksyttävien toimenpiteiden löytämisen kannalta ratkaisevaa. Uuden ratkaisun sijaan kirjoittaja ehdottaa paradoksin terapeuttista käsittelyä: keskustelua ja selontekoa niistä perusehdoista, jotka johtavat sen syntyyn. Tässä käsittelyssä lausekäsite on keskipisteenä – erityisesti Ludwig Wittgensteinin inspiroima lausekäsitys, jossa lauseen mielekkyyden kannalta sen todellinen käyttö mielekkäässä kontekstissa on ratkaiseva tekijä. Väitöskirja liittyy myöhäisiwittgensteinilaiseen perinteeseen, johon kuuluu ns. terapeuttinen filosofiankäsitys, mutta teos keskustelee myös tradition ulkopuolisten ajattelijoiden kanssa yrittäen yhdistää, sovitella ja myös eritellä teemoja, joita käsitellään yhdellä tavalla tradition sisällä ja toisella tavalla sen ulkopuolella. Väitöskirjan pääasiallinen panos sijoittuu metafilosofiaan, koska sen mielenkiinnon kohteena ovat erityisesti filosofian menetelmät.

FUTURES OF FINNISH FOOD SYSTEM BY 2050. The perspective of resilience

Modern food systems face complex global challenges such as climate change, resource scarcities, population growth, concentration and globalization. It is not possible to forecast how all these challenges will affect food systems, but futures research methods provide possibilities to enable better understanding of possible futures and that way increases futures awareness. In this thesis, the two-round online Delphi method was utilized to research experts’ opinions about the present and the future resilience of the Finnish food system up to 2050. The first round questionnaire was constructed based on the resilience indicators developed for agroecosystems. Sub-systems in the study were primary production (main focus), food industry, retail and consumption. Based on the results from the first round, the future images were constructed for primary production and food industry sub-sections. The second round asked experts’ opinion about the future images’ probability and desirability. In addition, panarchy scenarios were constructed by using the adaptive cycle and panarchy frameworks. Furthermore, a new approach to general resilience indicators was developed combining “categories” of the social ecological systems (structure, behaviors and governance) and general resilience parameters (tightness of feedbacks, modularity, diversity, the amount of change a system can withstand, capacity of learning and self- organizing behavior). The results indicate that there are strengths in the Finnish food system for building resilience. According to experts organic farms and larger farms are perceived as socially self-organized, which can promote innovations and new experimentations for adaptation to changing circumstances. In addition, organic farms are currently seen as the most ecologically self-regulated farms. There are also weaknesses in the Finnish food system restricting resilience building. It is important to reach optimal redundancy, in which efficiency and resilience are in balance. In the whole food system, retail sector will probably face the most dramatic changes in the future, especially, when panarchy scenarios and the future images are reflected. The profitability of farms is and will be a critical cornerstone of the overall resilience in primary production. All in all, the food system experts have very positive views concerning the resilience development of the Finnish food system in the future. Sometimes small and local is beautiful, sometimes large and international is more resilient. However, when probabilities and desirability of the future images were questioned, there were significant deviations. It appears that experts do not always believe desirable futures to materialize.