937 resultados para ryanodine channel
Resumo:
The importance of after-sales service or service in general can be seen and experienced by customers every day with industrial as well as other non-industrial services or products. This dissertation, drawing on theory and experience, focuses on practical engineering implications, specifically the management of customer issues in the after-sales phase in the mobile phone arena. The main objective of this doctoral dissertation is to investigate customer after-sales issue management, specifically regarding mobile phones. The case studies focus on issue resolution time and the issue of corrective actions. This dissertation consists of a main body and four peer-reviewed journal articles and one manuscript currently under review by a peer-reviewed journal. The main body of this dissertation examines the elements of customer satisfaction, loyalty, and retention with respect to corrective actions to address customer issues and issue resolution time through literature and empirical studies. The five independent works are case studies supporting the thesis research questions. This study examines four questions: 1) What are the factors affecting corrective actions for customers? 2) How can customer issue resolution time be controlled? 3) What are the factors affecting processes in the service chain? and 4) How can communication be measured in a service chain? In this work, both quantitative and qualitative analysis methods are used. The main body of the thesis reviews the literature regarding the elements that bridge the five case studies. The case studies of the articles and surveys lean more toward the methodology of critical positivism and then apply the interpretive approach in interpreting the results. The case study articles employ various statistical methods to analyze and to interpret the empirical and survey data. The statistical methods were used to create a model that is useful for significantly optimizing issue resolution time. Moreover, it was found that samples for verifying issues provided by the customer neither improve the perceived quality of corrective actions nor the perceived quality of issue resolution time. The term “service” in this work is limited to the technical services that are provided by product manufacturers and after-sales authorized service vendors. On the basis of this research work, it has been observed that corrective actions and issue resolution time are associated with customer satisfaction and hence, according to induction theory, to customer loyalty and retention. This thesis utilizes knowledge of marketing and customer relationships to contribute to the existing body of knowledge concerning information and communication technology for after-sales service recovery of mobile terminals. The established models in the thesis contribute to the existing knowledge of the after-sales process of dealing with customer issues in the field of mobile phones. The findings suggest that process managers could focus more on communication and training provided to the staff as new technology evolves rapidly. The study also suggest the managers formulate strategies for how customers can be kept informed on a regular basis of the status of issues that have been escalated for corrective action. The findings also lay the foundation for the comprehensive objective to control the entire product development process, starting with conceptualization. This implies that robust design should be applied to the new products so that problems affecting customer service quality are not repeated. The objective will be achieved when the entire service chain from product development to the final user can be modeled and this model can be used to support the organization at all levels.
Resumo:
The aim of this master’s thesis was to make a qualitative marketing research and on the basis of this to develop a distribution plan for the case company Finnish 3M Ltd.’s wound care products. The literature review includes three important parts: distribution channel planning, the buying behavior of seniors, and special characteristics of health care products’ marketing. The empirical part of this thesis comprises two different parts. The first part is a marketing research, in which the buying behavior of wound care products is studied in Espoo. The research aim was to examine, in which distribution channels the wound care patients under home care would most preferably buy wound care products during the time period, when municipalities will not yet provide the products for free. The data was collected through semi-structured phone interviews and regular interviews, and was treated qualitatively and anonymously. The study revealed that the recommendations of nurses and doctors influenced most the buying behavior of wound care customers. In the second part of the thesis a distribution channel plan for wound care products was made for the case company 3M Finland Ltd. based on the results. 3M Finland Ltd. should focus on pharmacies, online-stores and municipal health centers as their main distributors.
Resumo:
Outward current oscillations associated with transient membrane hyperpolarizations were induced in murine macrophage polykaryons by membrane depolarization in the absence of external Na+. Oscillations corresponded to a cyclic activation of Ca2+-dependent K+ currents (IKCa) probably correlated with variations in intracellular Ca2+ concentration. Addition of external Na+ (8 mM) immediately abolished the outward current oscillations, suggesting that the absence of the cation is necessary not only for their induction but also for their maintenance. Oscillations were completely blocked by nisoldipine. Ruthenium red and ryanodine reduced the number of outward current cycles in each episode, whereas quercetin prolonged the hyperpolarization 2- to 15-fold. Neither low molecular weight heparin nor the absence of a Na+ gradient across the membrane had any influence on oscillations. The evidence suggests that Ca2+ entry through a pathway sensitive to Ca2+ channel blockers is elicited by membrane depolarization in Na+-free medium and is essential to initiate oscillations, which are also dependent on the cyclic release of Ca2+ from intracellular Ca2+-sensitive stores; Ca2+ ATPase acts by reducing intracellular Ca2+, thus allowing slow deactivation of IKCa. Evidence is presented that neither a Na+/Ca2+ antiporter nor Ca2+ release from IP3-sensitive Ca2+ stores participate directly in the mechanism of oscillation
Resumo:
Evidence has indicated that the sarcoplasmic reticulum (SR) might be involved in the generation of spontaneous electrical activity in atrial pacemaker cells. We report the effect of disabling the SR with ryanodine (0.1 µM) on the sinus node recovery time (SNRT) measured in isolated right atria from 4-6-month-old male Wistar rats. Electrogram and isometric force were recorded at 36.5oC. Two methods for sinus node resetting were used: a) pulse: a single stimulus pulse interpolated at coupling intervals of 50, 65 or 80% of the regular spontaneous cycle length (RCL), and b) train: a 2-min train of pulses at intervals of 50, 65 or 80% of RCL. Corrected SNRT (cSNRT) was calculated as the difference between SNRT (first spontaneous cycle length after stimulation interruption) and RCL. Ryanodine only slightly increased RCL (<10%), but decreased developed force by 90%. When the pulse method was used, cSNRT (~40 ms), which represents intranodal/atrial conduction time, was independent of the coupling interval and unaffected by ryanodine. However, cSNRT obtained by the train method was significantly higher for shorter intervals between pulses, indicating the occurrence of overdrive suppression. In this case, ryanodine prolonged cSNRT in a rate-dependent fashion, with a greater effect at shorter intervals. These results indicate that: a) a functional SR, albeit important for force development, does not seem to play a major role in atrial automaticity in the rat; b) disruption of cell Ca2+ homeostasis by inhibition of SR function does not appear to affect conduction; however, it enhances overdrive-induced depression of sinusal automaticity.
Resumo:
Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.
Resumo:
The vasorelaxant effects of SR 47063 (4-(2-cyanimino-1,2-dihydropyrid-1-yl)-2,2-dimethyl-6-nitrochromene), a new K+-channel opener structurally related to levcromakalim, were examined in isolated human saphenous vein (HSV) and rat aorta (RA). HSV or RA rings were precontracted with either KCl or noradrenaline and cumulative relaxant concentration-response curves were obtained for SR 47063 (0.1 nM to 1 µM) in the presence or absence of 3 µM glibenclamide. SR 47063 potently relaxed HSV and RA precontracted with 20 mM (but not 60 mM) KCl or 10 µM noradrenaline in a concentration-dependent manner, showing slightly greater activity in the aorta. The potency of the effect of SR 47063 on HSV and RA was 12- and 58-fold greater, respectively, than that reported for the structurally related K+-channel opener levcromakalim. The vasorelaxant action of SR 47063 in both blood vessels was strongly inhibited by 3 µM glibenclamide, consistent with a mechanism of action involving ATP-dependent K+-channels.
Resumo:
Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.
Resumo:
Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (~40%) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia.
Resumo:
Obesity is a complex multifactorial disorder that is often associated with cardiovascular diseases. Research on experimental models has suggested that cardiac dysfunction in obesity might be related to alterations in myocardial intracellular calcium (Ca2+) handling. However, information about the expression of Ca2+-related genes that lead to this abnormality is scarce. We evaluated the effects of obesity induced by a high-fat diet in the expression of Ca2+-related genes, focusing the L-type Ca2+ channel (Cacna1c), sarcolemmal Na+/Ca2+ exchanger (NCX), sarcoplasmic reticulum Ca2+ ATPase (SERCA2a), ryanodine receptor (RyR2), and phospholamban (PLB) mRNA in rat myocardium. Male 30-day-old Wistar rats were fed a standard (control) or high-fat diet (obese) for 15 weeks. Obesity was defined as increased percent of body fat in carcass. The mRNA expression of Ca2+-related genes in the left ventricle was measured by RT-PCR. Compared with control rats, the obese rats had increased percent of body fat, area under the curve for glucose, and leptin and insulin plasma concentrations. Obesity also caused an increase in the levels of SERCA2a, RyR2 and PLB mRNA (P < 0.05) but did not modify the mRNA levels of Cacna1c and NCX. These findings show that obesity induced by high-fat diet causes cardiac upregulation of Ca2+ transport_related genes in the sarcoplasmic reticulum.
Multigenerational Brazilian family with malignant hyperthermia and a novel mutation in the RYR1 gene
Resumo:
Malignant hyperthermia (MH) is a pharmacogenetic disease triggered in susceptible individuals by the administration of volatile halogenated anesthetics and/or succinylcholine, leading to the development of a hypermetabolic crisis, which is caused by abnormal release of Ca2+ from the sarcoplasmic reticulum, through the Ca2+ release channel ryanodine receptor 1 (RyR1). Mutations in the RYR1 gene are associated with MH in the majority of susceptible families. Genetic screening of a 5-generation Brazilian family with a history of MH-related deaths and a previous MH diagnosis by the caffeine halothane contracture test (CHCT) in some individuals was performed using restriction and sequencing analysis. A novel missense mutation, Gly4935Ser, was found in an important functional and conserved locus of this gene, the transmembrane region of RyR1. In this family, 2 MH-susceptible individuals previously diagnosed with CHCT carry this novel mutation and another 24 not previously diagnosed members also carry it. However, this same mutation was not found in another MH-susceptible individual whose CHCT was positive to the test with caffeine but not to the test with halothane. None of the 5 MH normal individuals of the family, previously diagnosed by CHCT, carry this mutation, nor do 100 controls from control Brazilian and USA populations. The Gly4932Ser variant is a candidate mutation for MH, based on its co-segregation with disease phenotype, absence among controls and its location within the protein.
Resumo:
Physical exercise triggers coordinated physiological responses to meet the augmented metabolic demand of contracting muscles. To provide adequate responses, the brain must receive sensory information about the physiological status of peripheral tissues and organs, such as changes in osmolality, temperature and pH. Most of the receptors involved in these afferent pathways express ion channels, including transient receptor potential (TRP) channels, which are usually activated by more than one type of stimulus and are therefore considered polymodal receptors. Among these TRP channels, the TRPV1 channel (transient receptor potential vanilloid type 1 or capsaicin receptor) has well-documented functions in the modulation of pain sensation and thermoregulatory responses. However, the TRPV1 channel is also expressed in non-neural tissues, suggesting that this channel may perform a broad range of functions. In this review, we first present a brief overview of the available tools for studying the physiological roles of the TRPV1 channel. Then, we present the relationship between the TRPV1 channel and spontaneous locomotor activity, physical performance, and modulation of several physiological responses, including water and electrolyte balance, muscle hypertrophy, and metabolic, cardiovascular, gastrointestinal, and inflammatory responses. Altogether, the data presented herein indicate that the TPRV1 channel modulates many physiological functions other than nociception and thermoregulation. In addition, these data open new possibilities for investigating the role of this channel in the acute effects induced by a single bout of physical exercise and in the chronic effects induced by physical training.
Resumo:
The purpose of this study was to find out how a software company can successfully expand business to the Danish software market through distribution channel. The study was commissioned by a Finnish software company and it was conducted using a qualitative research method by analyzing external and internal business environment, and interviewing Danish ICT organizations and M-Files personnel. Interviews were semi-structured interviews, which were designed to collect comprehensive information on the existing ICT and software market in Denmark. The research used three external and internal analyzing frameworks; PEST analysis (market level), Porter´s Five Force analysis (industry level competition) and SWOT analysis (company level). Distribution channels theory was a base to understand why and what kind of distribution channels the case company uses, and what kind of channels target markets companies’ uses. Channel strategy and design were integrated to the industry level analysis. The empirical findings revealed that Denmark has very business friendly ICT environment. Several organizations have ranked Denmark´s information and communication technology as the best in the world. Denmark’s ICT and software market are relatively small, compared to many other countries in Europe. Danish software market is centralized. Largest software clusters are in the largest cities; Copenhagen, Aarhus, Odense and Aalborg. From these clusters, software companies can most likely find suitable resellers. The following growing trends are clearly seen in the software market: mobile and wireless applications, outsourcing, security solutions, cloud computing, social business solutions and e-business solutions. When expanding software business to the Danish market, it is important to take into account these trends. In Denmark distribution channels varies depending on the product or service. For many, a natural distribution channel is a local partner or internet. In the public sector solutions are purchased through a public procurement process. In the private sector the buying process is more straight forwarded. Danish companies are buying software from reliable suppliers. This means that they usually buy software direct from big software vendors or local partners. Some customers prefer to use professional consulting companies. These consulting companies can strongly influence on the selection of the supplier and products, and in this light, consulting companies can be important partners for software companies. Even though the competition is fierce in ECM and DMS solutions, Danish market offers opportunities for foreign companies. Penetration to the Danish market through reseller channel requires advanced solutions and objective selection criteria for channel partners. Based on the findings, Danish companies are interested in advanced and efficient software solutions. Interest towards M-Files solutions was clearly seen and the company has excellent opportunity to expand business to the Danish market through reseller channel. Since the research explored the Danish ICT and software market, the results of the study may offer valuable information also to the other software companies which are expanding their business to the Danish market.
Resumo:
This study discusses the evolution of an omni-channel model in managing customer experience. The purpose of this thesis is to expand the current academic literature available on omni-channel and offer suggestions for omni-channel creation. This is done by studying the features of an omni-channel approach into engaging with customers and through the sub-objectives of describing the process behind its initiation as well as the special features communication service providers need to take in consideration. Theories used as a background for this study are related to customer experience, channel management, omni-channel and finally change management. The empirical study of this thesis consists of seven expert interviews conducted in a case company. The interviews were held between March and November 2014. One of the interviewees is the manager of an omni-channel development team, whilst the rest were in charge of the management of the various customer channels of the company. The organization and analysis of the interview data was conducted topically. The use of themes related to major theories on the subject was utilized to create linkages between theory and practice. The responses were also organized in two groups based on the viewpoint to map responses related to the company perspective as well as the customers´ perspective. The findings in this study are that omni-channel is among the best tools for companies to respond to the challenge induced by changing customer needs and preferences, as well as intensifying competitive environment. The omni-channel model was found to promote excellent customer experience and thus to be a source of competition advantage and increasing financial returns by creating an omni-experience for the customer. Through omniexperience customers see all of the transactions with a company presenting one brand and providing ease and effortlessness in every encounter. The processes behind omni-channel formulation were identified as customer experience proclaimed as the most important strategic goal, mapping and establishing a unified brand experience in all (service) channels and empowering the first line personnel as the gate keepers of omniexperience. Further the tools, measurement and supporting strategies were to be in accordance with the omni-channel strategy and the customer needs to become a partner in a two way transaction with the firm. Based on these findings a model for omni-channel creation is offered. Future research is needed to firstly, further test these findings and expand the theoretical framework on omni-channel, as it is quite scarce to date and secondly, to increase the generalizability of the model suggested.