A calcineurin inhibitory protein overexpressed in Down's syndrome interacts with the product of a ubiquitously expressed transcript

The Down's syndrome candidate region 1 (DSCR1) protein, encoded by a gene located in the human chromosome 21, interacts with calcineurin and is overexpressed in Down's syndrome patients. As an approach to clarifying a putative function for this protein, in the present study we used the yeast two-hybrid system to identify DSCR1 partners. The two-hybrid system is a method that allows the identification of protein-protein interactions through reconstitution of the activity of the yeast GAL 4 transcriptional activator. The gene DSCR1 fused to the GAL 4 binding domain (BD) was used to screen a human fetal brain cDNA library cloned in fusion with the GAL 4 activation domain (AD). Three positive clones were found and sequence analysis revealed that all the plasmids coded for the ubiquitously expressed transcript (UXT). UXT, which is encoded in human Xp11, is a 157-amino acid protein present in both cytosol and nucleus of the cells. This positive interaction of DSCR1 and UXT was confirmed in vivo by mating the yeast strain AH109 (MATa)expressing AD-UXT with the strain Y187 (MATalpha) expressing BD-DSCR1, and in vitro by co-immunoprecipitation experiments. These results may help elucidate a new function for DSCR1 and its participation in Down's syndrome pathogenesis.

Service product internationalisation : market selection for new service products in a multinational financial service firm

The significance and impact of services in the modern global economy has become greater and there has been more demand for decades in the academic community of international business for further research into better understanding internationalisation of services. Theories based on the internationalisation of manufacturing firms have been long questioned for their applicability to services. This study aims at contributing to understanding internationalisation of services by examining how market selection decisions are made for new service products within the existing markets of a multinational financial service provider. The study focused on the factors influencing market selection and the study was conducted as a case study on a multinational financial service firm and two of its new service products. Two directors responsible for the development and internationalisation of the case service products were interviewed in guided semi-structured interviews based on themes adopted from the literature review and the outcome theoretical framework. The main empirical findings of the study suggest that the most significant factors influencing the market selection for new service products within a multinational financial service firm’s existing markets are: commitment to the new service products by both the management and the rest of the product related organisation; capability and competence by the local country organisations to adopt new services; market potential which combines market size, market structure and competitive environment; product fit to the market requirements; and enabling partnerships. Based on the empirical findings, this study suggests a framework of factors influencing market selection for new service products, and proposes further research issues and methods to test and extend the findings of this research.

Inventive design and product development of a mechanical element

The thesis is dedicated to enhancement and development of a Mechanism in Company X in order to increase its key parameters and approve its workability. Current Mechanism model is described in details. The basis of various analysis, models and theories that are reflecting the working process of the Mechanism are included in the thesis. According to these three directions of enhancements are chosen: from mechanical, tribological and conceptual points of view. As the result the list of improvements is presented. The new models of Mechanism are built. The efficiency and lifetime value are obtained in accordance with corresponding estimations. The comparative analysis confirms the necessity of conducted changes. Recommendations for the Company X specialists are represented in the thesis. Proposals for deeper research are also suggested.

Operant serial feature-positive conditional discrimination with composite features and different topography responses

In a serial feature-positive conditional discrimination procedure the properties of a target stimulus A are defined by the presence or not of a feature stimulus X preceding it. In the present experiment, composite features preceded targets associated with two different topography operant responses (right and left bar pressing); matching and non-matching-to-sample arrangements were also used. Five water-deprived Wistar rats were trained in 6 different trials: X-R®Ar and X-L®Al, in which X and A were same modality visual stimuli and the reinforcement was contingent to pressing either the right (r) or left (l) bar that had the light on during the feature (matching-to-sample); Y-R®Bl and Y-L®Br, in which Y and B were same modality auditory stimuli and the reinforcement was contingent to pressing the bar that had the light off during the feature (non-matching-to-sample); A- and B- alone. After 100 training sessions, the animals were submitted to transfer tests with the targets used plus a new one (auditory click). Average percentages of stimuli with a response were measured. Acquisition occurred completely only for Y-L®Br+; however, complex associations were established along training. Transfer was not complete during the tests since concurrent effects of extinction and response generalization also occurred. Results suggest the use of both simple conditioning and configurational strategies, favoring the most recent theories of conditional discrimination learning. The implications of the use of complex arrangements for discussing these theories are considered.

ABCB1 C1236T, G2677T/A and C3435T polymorphisms in systemic lupus erythematosus patients

P-glycoprotein (Pgp), the ABCB1 gene product, acts as an efflux pump that transports a large variety of substrates and is a mechanism of cell protection against xenobiotics. An increasing number of studies have shown that some ABCB1 polymorphisms may affect Pgp expression and activity, as well as affecting the development and susceptibility to diseases and pharmacological response. High activity of Pgp has been detected in systemic lupus erythematosus (SLE) patients. The C1236T, G2677T/A, and C3435T are the most commonly studied single nucleotide polymorphisms in the ABCB1 gene. Therefore, their frequencies were determined in Brazilian individuals with European ancestry (N = 143) and in SLE patients (N = 137). Genotyping was performed by PCR-RFLP analysis using specific primers followed by incubation with the appropriate restriction enzymes. The resulting DNA fragments were visualized on agarose or polyacrylamide gels. No statistically significant differences were observed in allelic and genotypic frequencies between SLE and healthy subjects (Fisher exact test). Nevertheless, the 2677A allelic frequency was lower in SLE patients with malar rash (0.007) compared with patients without this feature (0.04; P = 0.0054), while the frequency of this variant was higher in SLE patients with pleuritis (0.07) compared with patients without this feature (0.01; P = 0.0156). We suggest that although the ABCB1 polymorphisms do not directly interfere in SLE susceptibility, their evaluation, especially the 2677A allele, in other immunological processes may be interesting since they can interfere in clinical features of this disease.

The six-minute walk test and body weight-walk distance product in healthy Brazilian subjects

We assessed the 6-min walk distance (6MWD) and body weight x distance product (6MWw) in healthy Brazilian subjects and compared measured 6MWD with values predicted in five reference equations developed for other populations. Anthropometry, spirometry, reported physical activity, and two walk tests in a 30-m corridor were evaluated in 134 subjects (73 females, 13-84 years). Mean 6MWD and 6MWw were significantly greater in males than in females (622 ± 80 m, 46,322 ± 10,539 kg.m vs 551 ± 71 m, 36,356 ± 8,289 kg.m, P < 0.05). Four equations significantly overestimated measured 6MWD (range, 32 ± 71 to 137 ± 74 m; P < 0.001), and one significantly underestimated it (-36 ± 86 m; P < 0.001). 6MWD significantly correlated with age (r = -0.39), height (r = 0.44), body mass index (r = -0.24), and reported physical activity (r = 0.25). 6MWw significantly correlated with age (r = -0.21), height (r = 0.66) and reported physical activity (r = 0.25). The reference equation devised for walk distance was 6MWDm = 622.461 - (1.846 x Ageyears) + (61.503 x Gendermales = 1; females = 0); r2 = 0.300. In an additional group of 85 subjects prospectively studied, the difference between measured and the 6MWD predicted with the equation proposed here was not significant (-3 ± 68 m; P = 0.938). The measured 6MWD represented 99.6 ± 11.9% of the predicted value. We conclude that 6MWD and 6MWw variances were adequately explained by demographic and anthropometric attributes. This reference equation is probably most appropriate for evaluating the exercise capacity of Brazilian patients with chronic diseases.

Scalable Feature Selection Applications for Genome-Wide Association Studies of Complex Diseases

Personalized medicine will revolutionize our capabilities to combat disease. Working toward this goal, a fundamental task is the deciphering of geneticvariants that are predictive of complex diseases. Modern studies, in the formof genome-wide association studies (GWAS) have afforded researchers with the opportunity to reveal new genotype-phenotype relationships through the extensive scanning of genetic variants. These studies typically contain over half a million genetic features for thousands of individuals. Examining this with methods other than univariate statistics is a challenging task requiring advanced algorithms that are scalable to the genome-wide level. In the future, next-generation sequencing studies (NGS) will contain an even larger number of common and rare variants. Machine learning-based feature selection algorithms have been shown to have the ability to effectively create predictive models for various genotype-phenotype relationships. This work explores the problem of selecting genetic variant subsets that are the most predictive of complex disease phenotypes through various feature selection methodologies, including filter, wrapper and embedded algorithms. The examined machine learning algorithms were demonstrated to not only be effective at predicting the disease phenotypes, but also doing so efficiently through the use of computational shortcuts. While much of the work was able to be run on high-end desktops, some work was further extended so that it could be implemented on parallel computers helping to assure that they will also scale to the NGS data sets. Further, these studies analyzed the relationships between various feature selection methods and demonstrated the need for careful testing when selecting an algorithm. It was shown that there is no universally optimal algorithm for variant selection in GWAS, but rather methodologies need to be selected based on the desired outcome, such as the number of features to be included in the prediction model. It was also demonstrated that without proper model validation, for example using nested cross-validation, the models can result in overly-optimistic prediction accuracies and decreased generalization ability. It is through the implementation and application of machine learning methods that one can extract predictive genotype–phenotype relationships and biological insights from genetic data sets.

Impact of increased environmental awareness on product marketing

This Bachelor thesis studies how companies use a variety of different sustainable marketing approaches to sell their green products. Empirical part is done by researching and interviewing two B2B furniture companies.

Integration of marketing research data in new product development. Case study: Food industry company

The aim of this master’s thesis is to provide a real life example of how marketing research data is used by different functions in the NPD process. In order to achieve this goal, a case study in a company was implemented where gathering, analysis, distribution and synthesis of marketing research data in NPD were studied. The main research question was formulated as follows: How is marketing research data integrated and used by different company functions in the NPD process? The theory part of the master’s thesis was focused on the discussion of the marketing function role in NPD, use of marketing research particularly in the food industry, as well as issues related to the marketing/R&D interface during the NPD process. The empirical part of the master’s thesis was based on qualitative explanatory case study research. Individual in-depth interviews with company representatives, company documents and online research were used for data collection and analyzed through triangulation method. The empirical findings advocate that the most important marketing data sources at the concept generation stage of NPD are: global trends monitoring, retailing audit and consumers insights. These data sets are crucial for establishing the potential of the product on the market and defining the desired features for the new product to be developed. The findings also suggest the example of successful crossfunctional communication during the NPD process with formal and informal communication patterns. General managerial recommendations are given on the integration in NPD of a strategy, process, continuous improvement, and motivated cross-functional product development teams.

Theoretical modelling of Staphylococcus aureus growth in a cooked meat product kept at ambient temperature using temperature profiles of selected Mexican cities

A theoretical model is used to predict the growth of Staphylococcus aureus in a pasteurized meat product kept at ambient temperatures for several hours. For this purpose, the temperature profiles of some cities of Mexico were combined with literature data on the kinetics of S. aureus growth. As shown by theoretical predictions, if the food is kept at ambient temperature, the average daily temperature may not give accurate predictions.