962 resultados para conformational transition
Resumo:
The business logic in the manufacturing industry has changed in the 21st century. In the current industrial market, manufacturers are driven to provide more comprehensive offerings that go beyond the traditional product-orientation by providing capacity and availability for their customers. From incidental merchandise, services have become the core of manufacturers’ offerings with long-lasting service agreements over the life-cycles of their products. This change is driven both by the need of providers to grow and gain competitive advantage and by increased customer demand caused by customers’ outsourcing trends. The three key drivers for manufacturers’ service strategies are outsourcing trends, saturation of the installed base, and commoditization in product markets. Thus, manufacturers focus on providing industrial solutions which are delivered through relational processes with customers by using solution-driven business models. In the management of marketing activities, this can be regarded as closer customer relationships, service-dominant business logic, and collaboration in solving customers’ problems. However, there are few studies on comprehensive conceptualizations of a solution offering that include different elements and their roles, especially in the context of capital goods industry. Also the transition process needs further studies in a real life context. This study explores the transition process of an industrial company from product to solution business and, as an aid to managing the solution business, explicates the structure and management of an industrial solution offering. There are two themes, the industrial transition process and industrial solution offering. Regarding the industrial transition process, the aim is to understand the supplier view on the process and its execution and to determine the challenges related to the transition process. The industrial solution offering is discussed by its elements and characteristics, as well as management. Furthermore, a special type of build-own-operate-transfer business model is presented and its suitability in the industrial context analyzed. The study includes findings achieved by qualitative methods and from four case companies. Based on the results, it is tentatively suggested that in the industrial solution business, the transition from product to solution business is not a linear project but an evolving process that varies according to customer needs, which suggests that companies need to possess an ability to develop new business models for different customer needs. The industrial solution offering is dynamic as it evolves in collaboration according to the prevailing and latent customer needs, which suggest restructuring of the organization from a product-centric to a customer-centric one. Furthermore, based on the findings, the concept of industrial solutions is defined as an ongoing relational process to satisfy a customer’s particular business or operational requirements, and the concept of industrial solution offering as an entity comprising the customized goods, services, collaboration, and finance needed to fulfill the industrial solution. Finally, the study offers several managerial implications for industrial managers involved in the transition and management of the solution business and its offering.
Resumo:
Ambitious energy targets set by EU put pressures to increase share of renewable electricity supply in this and next decades and therefore, some EU member countries have boosted increasing renewable energy generation capacity by implementing subsidy schemes on national level. In this study, two different change approaches to increase renewable energy supply and increase self-sufficiency of supply are assessed with respect to their impacts on power system, electricity market and electricity generation costs in Finland. It is obtained that the current electricity generation costs are high compared to opportunities of earnings from present-day investor’s perspective. In addition, the growth expectations of consumptions and the price forecasts do not stimulate investing in new generation capacity. Revolutionary transition path is driven by administrative and political interventions to achieve the energy targets. Evolutionary transition path is driven by market-based mechanisms, such as market itself and emission trading scheme. It is obtained in this study that in the revolutionary transition path operation of market-based mechanisms is distorted to some extent and it is likely that this path requires providing more public financial resources compared to evolutionary transition path. In the evolutionary transition path the energy targets are not achieved as quickly but market-based mechanisms function better and investment environment endures more stable compared to revolutionary transition path.
Resumo:
Breast cancer in families with germ line mutations in the TP53 gene has been described in the medical literature. Mutation screening for susceptibility genes should allow effective prophylactic and preventive measures. Using single-strand conformational polymorphism, we screened for mutations in exons 5, 6, 7 and 8 of gene TP53 in the peripheral blood of 8 young non-affected members (17 to 36 years old) of families with a history of breast cancer. Studies of this type on young patients (mean age, 25 years) are very rare in the literature. The identification of these mutations would contribute to genetic counseling of members of families with predisposition to breast cancer. The results obtained did not show any polymorphism indicating mutation. In our sample, the familial tumorigenesis is probably related to other gene etiologies.
Resumo:
The aim of this caring science thesis is to deepen the understanding for the long-term ill adolescents care. In particular it aims to reach a better understanding of transition in health care, with a focus on how young people perceive health care. The goal is to build a model, a consistent theoretical framework that makes it possible to listen to the adolescent´s own voice, providing a better understanding of what good care consists in from their point of view. This Master's thesis consists of a literature overview on the concept of transition and a themed interview with young patients regarding transition of health care. The overall issue is 1. What is good care during the transition according to the adolescents themselves? 2. How does transition affect the young people's health and lives? The theoretical perspective of this thesis lies in the caring science tradition that has been developed at the Åbo Akademi University department of caring science with the caritative nursing theory as a basis. The epistemological and ontological assumptions are based on the caritative nursing theory, which in itself is ethical. Understanding of the concept of transition is based on A. Meleis transitions theory. The methodological approach is hermeneutical. The theme interview has been analyzed by using S. Kvales method. The material consists of a thematic interview with 10 long-term ill adolescents, about their views of the care received. This thesis research even in how NOBABs standards appears in the litterature as well as how they are implemented from the point of view of young people. The findings of this thesis shows that good care for the adolescent is a true presence with the young and an understanding of the direction in which the young move toward during the transition of care. Good care for an adolescent consists in being recognized as a person who is seen, known, appreciated and understood. Good care for the young involves recognizing her strength and joy of life including the contrast she experiences between health and suffering. To recognize their personal strength and courage supports the adolescents during the process of transitions of care Good care for the young involves responsibility for the individual person and humility in approaching her, giving attention to her view of life and aspirations. Openness and humility in the approach lays the foundation for a trusting relation during the transition of care. A unified theoretical framework is needed to promote the long-term ill adolescents care during transition of care. When the young and her individual needs is the centerpiece of healthcare creates this the basis for empowering care that supports the young in her quest for health. This master thesis adds a given model to the long-term ill adolescents` healthcare.
Resumo:
The objective of this Master’s Thesis is to find individuals’ inducements that assist innovation adoption in the framework of sustainable food system. The purpose of the thesis is to examine the reasons why individuals adopt sustainable approaches, and furthermore, to see by what means the transition to the more sustainable food system could be accelerated. The study’s focal point is on the micro level, even if the wider purpose is to accelerate the holistic change of food system in the near future. The study consists of a literature review and a qualitative research, which is actualized with semi-structured interviews. The results indicate that individuals adopt innovations based on their strong intrinsic motivation. The main inducements were environment-related and health-related aspects, and individual’s deep connection to the countryside. The effect of social circle and doing good actions with the consuming behavior were also highlighted. Strongest barriers to innovation adoption seem to be price sensitivity, lack of easiness, and lack of interest in food. The findings indicate also that the most significant means that could ease the individuals’ decision to adopt an innovation are health-related aspects, educating and learning, environmental aspects, and decreasing the prices. Although the theoretical part of the study highlights the effect of positive reinforcement, the empirical part neglects it.
Resumo:
Tämä työ tutkii ja tarkastelee transitio-kokeilua ravinnetaloudessa. Transitio-kokeilu on toimintatutkimusprojekti, joka toteutetaan systeemisen muutoksen ajattelun mukaisesti alhaalta ylöspäin. Ravinnetalous määritetään tarkemmin työn kautta sekä analysoidaan monitaso-perspektiivin näkökulmasta. Ravinnetalous on terminä varsin tuntematon ja tarvitsee enemmän tunnettavuutta laajemman yleisön edessä. Transitio-areenan ja transitio-visioiden kehittäminen ovat työn keskipisteessä, koska ne ovat tärkeimpiä vaiheita transition alkuvaiheessa. Joukko sidosryhmätoimijoita osallistuu transitio areenaan sekä visioiden jatkokehittelyyn. Visio(t) luodaan ensisijaisesti backcasting-menetelmällä, jota myös täydennetään tavanomaisella ennustamisella. Backcasting- menetelmä on osin osallistava ja siinä käytetään ravinteiden planeettarajoja kvantitatiivisina pääperiaatteina, minkä tuloksena myös visiot ovat osin kvantitatiivisia. Transitio areenan kokoaminen ja fasilitointi aiheuttavat hankalia kysymyksiä, jotka tarvitsevat jatko-tutkimusta. Alhaalta-ylöspäin organisoitu transitio-arena houkuttelee niche-toimijoita, mutta epäonnistuu sitouttamaan julkisen vallan toimijoita. Toimintamallin voimasuhteet, politiikka ja transition vakiinnuttaminen tulisivat olla jatko-toimenpiteinä niin tutkimuksessa kuin toiminnassakin.
Resumo:
The aims of the study were to assess the validity of a clinical dental fear question (Short Dental Fear Question, SDFQ) and an instrument measuring interaction between adolescents and dental staff (Patient Dental Staff Interaction Questionnaire, PDSIQ). Also, adolescents’ subjective perception of interaction with dental staff, the association with adolescents’ dental fear and sense of coherence as well as a multi-professional small-group intervention model for decreasing high dental fear were assessed. The study sample comprised Finnish adolescents in transition to early adulthood, aged 18–26 years (n = 777, n = 773, n = 5), except for a sample of 15-year-old adolescents (n = 27). Dental fear, sense of coherence (SOC) and the adolescents’ perceived interaction with dental staff were assessed with questionnaires. The principles of fear treatment such as gradual exposure, relaxation, encouragement and cornerstones of the reteaming method based on a solution-focused framework to maintain motivation and peer support were used to decrease fear in the intervention study. The SDFQ was found to be a valid dental fear instrument and the PDSIQ a valid interaction instrument with five factors of interaction retrieved: ‘kind atmosphere and mutual communication’, ‘roughness’, ‘insecurity’, ‘trust and safety’, and ‘shame and guilt’. Highly fearful young adults more often perceived their interaction with dental staff as negative, more often felt insecure and had a weaker sense of coherence compared to their peers with no to moderate dental fear. The results of the intervention study showed that young adults’ high dental fear decreased and their commitment to dental treatment increased. The SDFQ is clinically feasible and informative instrument in measuring dental fear. Knowledge of the level of fear enables dental staff to better consider an adolescent’s fear. Dental staff should be aware that a supportive interaction style, creating trust and safety, is especially beneficial for highly dentally fearful young adults. A weak SOC may affect young adults’ high dental fear in that they would not have enough tools to manage their fear. A multi-professional small therapeutic group seems to increase fearful young adults’ resources for confronting dental treatment.
Resumo:
The pressure behavior of proteins may be summarized as a the pressure-induced disordering of their structures. This thermodynamic parameter has effects on proteins that are similar but not identical to those induced by temperature, the other thermodynamic parameter. Of particular importance are the intermolecular interactions that follow partial protein unfolding and that give rise to the formation of fibrils. Because some proteins do not form fibrils under pressure, these observations can be related to the shape of the stability diagram. Weak interactions which are differently affected by hydrostatic pressure or temperature play a determinant role in protein stability. Pressure acts on the 2º, 3º and 4º structures of proteins which are maintained by electrostatic and hydrophobic interactions and by hydrogen bonds. We present some typical examples of how pressure affects the tertiary structure of proteins (the case of prion proteins), induces unfolding (ataxin), is a convenient tool to study enzyme dissociation (enolase), and provides arguments to understand the role of the partial volume of an enzyme (butyrylcholinesterase). This approach may have important implications for the understanding of the basic mechanism of protein diseases and for the development of preventive and therapeutic measures.
Resumo:
Pressure-induced dissociation of a turbid solution of casein micelles was studied in situ in static and dynamic light scattering experiments. We show that at high pressure casein micelles decompose into small fragments comparable in size to casein monomers. At intermediate pressure we observe particles measuring 15 to 20 nm in diameter. The stability against pressure dissociation increased with temperature, suggesting enhanced hydrophobic contacts. The pressure transition curves are biphasic, compatible with a temperature (but not pressure)-dependent conformational equilibrium of two micelle species. Our thermodynamic model predicts an increase in structural entropy with temperature.
Resumo:
Pharmacological evidence indicates that the basolateral nucleus of the amygdala (BLA) is involved in the mediation of inhibitory avoidance but not of escape behavior in the elevated T-maze test. These defensive responses have been associated with generalized anxiety disorder (GAD) and panic disorder, respectively. In the present study, we determined whether the BLA plays a differential role in the control of inhibitory avoidance and escape responses in the elevated T-maze. Male Wistar rats (250-280 g, N = 9-10 in each treatment group) were pre-exposed to one of the open arms of the maze for 30 min and 24 h later tested in the model after inactivation of the BLA by a local injection of the GABA A receptor agonist muscimol (8 nmol in 0.2 µL). It has been shown that a prior forced exposure to one of the open arms of the maze, by shortening latencies to withdrawal from the open arm during the test, improves the escape task as a behavioral index of panic. The effects of muscimol in the elevated T-maze were compared to those caused by this GABA agonist in the avoidance reaction generated in the light/dark transition test. This defensive behavior has also been associated with GAD. In the elevated T-maze, intra-BLA injection of muscimol impaired inhibitory avoidance (control: 187.70 ± 14.90 s, muscimol: 37.10 ± 2.63 s), indicating an anxiolytic effect, without interfering with escape performance. The drug also showed an anxiolytic effect in the light/dark transition test as indicated by the increase in the time spent in the lighted compartment (control: 23.50 ± 2.45 s, muscimol: 47.30 ± 4.48 s). The present findings point to involvement of the BLA in the modulation of defensive responses that have been associated with GAD.
Resumo:
In this work emission, optical, electrical and magnetic properties of the d- and f- elements doped zinc selenide crystals were investigated within a wide temperature range. Doping was performed in various technological processes: during the growth by chemical vapor transport method; by thermal diffusion from the Bi or Zn melt. Concentration of the doping impurity in the crystals was controlled by amount of the dopant in the source material or by its concentration in the doping media. Special interest in the work was paid to the influence of the different concentrations of Cr and Yb impurities on ZnSe crystals’ properties, correlations between observed effects and similarities with the Ni, Mn and Gd dopants are analysed. Possibility of formation of the excitons bound to the doping d-ions was shown. In contrast to this, it was observed that f-elements do not bound excitons, but prevent formation of excitons bound to some uncontrolled impurities. A mechanism of Cr doping impurity interaction with background impurities and zinc selenide structural defects was proposed based on experimental data. An assumption about resonant energy transfer between double charged chromium ions and complexes based on crystals’ vacancy defects was made. A correlation between emission and magnetic properties of the d- ions doped samples was established. Based on this correlation a mechanism explaining the concentration quench of the emission was proposed. It was found that f-ions bind electrically active shallow and deep donor and acceptor states of background impurity to electrically neutral complexes. This may be observed as “purification” of ZnSe crystals by doping with the rare-earth elements, resulting i tendency of the properties of f-ion doped crystals to the properties of intrinsic crystals, but with smaller concentration of uncontrolled native and impurity defects. A possible interpretation of this effect was proposed. It was shown that selenium substituting impurities decrease efficiency of the Yb doping. Based on this experimental results an attempt to determine ytterbium ion surroundings in the crystal lattice was made. It was shown that co-doping of zinc selenide crystals with the d- and f- ions leads to the combination of the impurities influence on the material’s properties. On the basis of obtained data an interaction mechanism of the d- and f-elements co-dopants was proposed. Guided by the model of the ytterbium ion incorporation in the selenide sublattice of the ZnSe crystals, an assumption about stabilization of single charged chromium ions in the zinc sublattice crystal nodes, by means of formation of the local charge compensating clusters, was made.
Resumo:
Mitochondria increase their outer and inner membrane permeability to solutes, protons and metabolites in response to a variety of extrinsic and intrinsic signaling events. The maintenance of cellular and intraorganelle ionic homeostasis, particularly for Ca2+, can determine cell survival or death. Mitochondrial death decision is centered on two processes: inner membrane permeabilization, such as that promoted by the mitochondrial permeability transition pore, formed across inner membranes when Ca2+ reaches a critical threshold, and mitochondrial outer membrane permeabilization, in which the pro-apoptotic proteins BID, BAX, and BAK play active roles. Membrane permeabilization leads to the release of apoptogenic proteins: cytochrome c, apoptosis-inducing factor, Smac/Diablo, HtrA2/Omi, and endonuclease G. Cytochrome c initiates the proteolytic activation of caspases, which in turn cleave hundreds of proteins to produce the morphological and biochemical changes of apoptosis. Voltage-dependent anion channel, cyclophilin D, adenine nucleotide translocase, and the pro-apoptotic proteins BID, BAX, and BAK may be part of the molecular composition of membrane pores leading to mitochondrial permeabilization, but this remains a central question to be resolved. Other transporting pores and channels, including the ceramide channel, the mitochondrial apoptosis-induced channel, as well as a non-specific outer membrane rupture may also be potential release pathways for these apoptogenic factors. In this review, we discuss the mechanistic models by which reactive oxygen species and caspases, via structural and conformational changes of membrane lipids and proteins, promote conditions for inner/outer membrane permeabilization, which may be followed by either opening of pores or a rupture of the outer mitochondrial membrane.
Resumo:
The microenvironment of the tumor plays an important role in facilitating cancer progression and activating dormant cancer cells. Most tumors are infiltrated with inflammatory cells which secrete cytokines such as tumor necrosis factor-a (TNF-a). To evaluate the role of TNF-a in the development of cancer we studied its effects on cell migration with a migration assay. The migrating cell number in TNF-a -treated group is about 2-fold of that of the control group. Accordingly, the expression of E-cadherin was decreased and the expression of vimentin was increased upon TNF-a treatment. These results showed that TNF-a can promote epithelial-mesenchymal transition (EMT) of MCF-7 cells. Further, we found that the expression of Snail, an important transcription factor in EMT, was increased in this process, which is inhibited by the nuclear factor kappa B (NFkB) inhibitor aspirin while not affected by the reactive oxygen species (ROS) scavenger N-acetyl cysteine. Consistently, specific inhibition of NFkB by the mutant IkBa also blocked the TNF-a-induced upregulation of Snail promoter activity. Thus, the activation of NFkB, which causes an increase in the expression of the transcription factor Snail is essential in the TNF-a-induced EMT. ROS caused by TNF-a seemed to play a minor role in the TNF-a-induced EMT of MCF-7 cells, though ROS per se can promote EMT. These findings suggest that different mechanisms might be responsible for TNF-a - and ROS-induced EMT, indicating the need for different strategies for the prevention of tumor metastasis induced by different stimuli.