The multiple phenotypes of allosteric receptor mutants.

Channel-linked neurotransmitter receptors are membrane-bound heterooligomers made up of distinct, although homologous, subunits. They mediate chemo-electrical signal transduction and its regulation via interconversion between multiple conformations that exhibit distinct pharmacological properties and biological activities. The large diversity of functional properties and the widely pleiotropic phenotypes, which arise from point mutations in their subunits (or from subunit substitutions), are interpreted in terms of an allosteric model that incorporates multiple discrete conformational states. The model predicts that three main categories of phenotypes may result from point mutations, altering selectively one (or more) of the following features: (i) the properties of individual binding sites (K phenotype), (ii) the biological activity of the ion channel (gamma phenotype) of individual conformations, or (iii) the isomerization constants between receptor conformations (L phenotype). Several nicotinic acetylcholine and glycine receptor mutants with complex phenotypes are quantitatively analyzed in terms of the model, and the analogies among phenotypes are discussed.

Mutations in the MSH3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae.

Eukaryotic genomes contain tracts of DNA in which a single base or a small number of bases are repeated (microsatellites). Mutations in the yeast DNA mismatch repair genes MSH2, PMS1, and MLH1 increase the frequency of mutations for normal DNA sequences and destabilize microsatellites. Mutations of human homologs of MSH2, PMS1, and MLH1 also cause microsatellite instability and result in certain types of cancer. We find that a mutation in the yeast gene MSH3 that does not substantially affect the rate of spontaneous mutations at several loci increases microsatellite instability about 40-fold, preferentially causing deletions. We suggest that MSH3 has different substrate specificities than the other mismatch repair proteins and that the human MSH3 homolog (MRP1) may be mutated in some tumors with microsatellite instability.

Validation of the Item-Attribute Matrix in TIMSS-Mathematics Using Multiple Regression and the LSDM

The purposes of this study were (1) to validate of the item-attribute matrix using two levels of attributes (Level 1 attributes and Level 2 sub-attributes), and (2) through retrofitting the diagnostic models to the mathematics test of the Trends in International Mathematics and Science Study (TIMSS), to evaluate the construct validity of TIMSS mathematics assessment by comparing the results of two assessment booklets. Item data were extracted from Booklets 2 and 3 for the 8th grade in TIMSS 2007, which included a total of 49 mathematics items and every student's response to every item. The study developed three categories of attributes at two levels: content, cognitive process (TIMSS or new), and comprehensive cognitive process (or IT) based on the TIMSS assessment framework, cognitive procedures, and item type. At level one, there were 4 content attributes (number, algebra, geometry, and data and chance), 3 TIMSS process attributes (knowing, applying, and reasoning), and 4 new process attributes (identifying, computing, judging, and reasoning). At level two, the level 1 attributes were further divided into 32 sub-attributes. There was only one level of IT attributes (multiple steps/responses, complexity, and constructed-response). Twelve Q-matrices (4 originally specified, 4 random, and 4 revised) were investigated with eleven Q-matrix models (QM1 ~ QM11) using multiple regression and the least squares distance method (LSDM). Comprehensive analyses indicated that the proposed Q-matrices explained most of the variance in item difficulty (i.e., 64% to 81%). The cognitive process attributes contributed to the item difficulties more than the content attributes, and the IT attributes contributed much more than both the content and process attributes. The new retrofitted process attributes explained the items better than the TIMSS process attributes. Results generated from the level 1 attributes and the level 2 attributes were consistent. Most attributes could be used to recover students' performance, but some attributes' probabilities showed unreasonable patterns. The analysis approaches could not demonstrate if the same construct validity was supported across booklets. The proposed attributes and Q-matrices explained the items of Booklet 2 better than the items of Booklet 3. The specified Q-matrices explained the items better than the random Q-matrices.

Prevalence of exposure to occupational risks during preganancy in Spain

Objectives. We describe reported exposures to main categories of occupational agents and conditions in Spanish pregnant workers. Methods. Women were recruited at 12th week of pregnancy from main public gynaecological consults to be included in the INMA Spanish cohorts study (n = 2,058). Through personal interviews with structured questionnaires, information on working situation and working conditions during pregnancy was obtained. Results. Fifty percent of the women reported frequent exposure to physical load (standing, heavy lifting) and 45 % reported exposure to three or more indicators of job strain. Exposure to at least one physical agent (noise, vibrations, etc.) affected 25 % of the women. Exposure to chemicals was reported by 20 % of the women, mostly including solvents and cleaning products. Eight percent of the women worked at night shifts. Job strain was more prevalent in office workers and industrial operators. Industrial workers showed the highest prevalence of exposure to chemical and physical pollutants. Conclusions. Our data suggest that working conditions of pregnant women may need increased control in Spain.

Is the date of birth an advantage/ally to excel in handball?

The Relative Age Effect (RAE) has been analyzed in a population of Spanish international handball players (n=161) divided into four different levels: Senior, Junior, Juvenile and Promising Talents. The variables registered were quarter, half year and year of birth using the initial information of their date of birth. The data were collected from the Royal Spanish Handball Federation on-line data base. The statistical method used was the χ2 and the minimum level of significance was set at p<0.05. The total results on distribution by quarter show a significant difference (χ2= 21.68; p<0.01) with a greater frequency of players born in the first quarter (40.37%) compared to those born in the second (22.36%), third (16.15%) and fourth quarter (21.12%). The total results on the distribution of birth date by half year show a significant difference (χ2= 10.44; p<0.01) with a greater frequency of players born in the first half of the year (62.73%). With regard to the rate of births registered in an even numbered or odd numbered year there are significant differences when the rates for an even numbered year (64.60%) and an odd numbered year (35.40%) are compared with those of the general population (χ2= 13.72; p<0.001). Based on the data collected and analyzed it can be concluded that there is a RAE in the basic categories of the Spanish national men’s handball teams according to quarter, half year and year of birth (even or odd numbered), but there exists little knowledge about the causes and consequence which may be produced by, or derive from, this effect.

The effect of smoking on visceral fat accumulation in Czech men and women

Many studies indicate that smoking is one of risk factors influencing the accumulation of visceral fat (VFA). The mechanism by which smoking contributes to the accumulation of visceral fat is not yet fully understood, but it is assumed that smoking increases the level of plasma cortisol, causes imbalance between male and female sex hormones in women, and decreases testosterone levels in men (Chiolero et al., 2008). The objection of this study was to evaluate the effect of smoking on the accumulation of VFA in the population of the Czech Republic. The research included 1,412 individuals of both genders divided into categories of smokers vs nonsmokers and physically active vs. physically inactive. VFA was measured by the device InBody 720 and information about physical activity and smoking was collected via a questionnaire. We supposed that smokers would have a higher percentage of VFA than non-smokers. The results showed that smokers had a higher amount of VFA, but the difference was not statistically significant. In contrast, statistically significant differences were found in the waist-to-hip ratio (WHR) and total % body fat. Physically active individuals had a much more favourable results than physically inactive individuals. Remarkably, the amount of VFA, WHR and % body fat tended to be smaller in smoking men than in non-smoking men, but higher in smoking women than in non-smoking women.

An ethnopharmacological and historical analysis of “Dictamnus”, a European traditional herbal medicine

Ethnopharmacological relevance and background: “Dictamnus” was a popular name for a group of medicinal herbaceous plant species of the Rutaceae and Lamiaceae, which since the 4th century have been used for gynaecological problems and other illnesses BCE and still appear in numerous ethnobotanical records. Aims: This research has as four overarching aims: Determining the historical evolution of medical preparations labelled “Dictamnus” and the different factors affecting this long-standing herbal tradition. Deciphering and differentiating those medicinal uses of “Dictamnus” which strictly correspond to Dictamnus (Rutaceae), from those of Origanum dictamnus and other Lamiaceae species. Quantitatively assessing the dependence from herbal books, and pharmaceutical tradition, of modern Dictamnus ethnobotanical records. Determining whether differences between Western and Eastern Europe exist with regards to the Dictamnus albus uses in ethnopharmacology and ethnomedicine. Methods: An exhaustive review of herbals, classical pharmacopoeias, ethnobotanical and ethnopharmacological literature was conducted. Systematic analysis of uses reported which were standardized according to International Classification of Diseases – 10 and multivariate analysis using factorial, hierarchical and neighbour joining methods was undertaken. Results and discussion: The popular concept “Dictamnus” includes Origanum dictamnus L., Ballota pseudodictamnus (L.) Benth. and B. acetabulosa (L.) Benth. (Lamiaceae), as well as Dictamnus albus L. and D. hispanicus Webb ex Willk. (Rutaceae), with 86 different types of uses. Between 1000 and 1700 CE numerous complex preparations with “Dictamnus” were used in the treatment of 35 different pathologies. On biogeographical grounds the widespread D. albus is a far more likely prototypical “Dictamnus” than the Cretan endemic Origanum dictamnus. However both form integral parts of the “Dictamnus” complex. Evidence exists for a sufficiently long and coherent tradition for D. albus and D. hispanicus, use to treat 47 different categories of diseases. Conclusions: This approach is a model for understanding the cultural history of plants and their role as resources for health care. “Dictamnus” shows how transmission of traditional knowledge about materia medica, over 26 centuries, represents remarkable levels of development and innovation. All this lead us to call attention to D. albus and D. hispanicus which are highly promising as potential herbal drug leads. The next steps of research should be to systematically analyse phytochemical, pharmacological and clinical evidence and to develop safety, pharmacology and toxicology profiles of the traditional preparations.

Analysis of physical and physiological requirements in soccer trainings in young soccer players (under -10 years)

The aim of this study is to analyse the physical and physiological factors in soccer training at different categories of training. The participants were 30 soccer players of 8-aside soccer in the under 10’s age group (9.93±0.25 years) who participated in the under 10 Provincial Tournament in Alicante. During training, the variables of covered distance, heart rate, speed (average and maximum values) as well as the methodology used and position were registered. After the statistical analysis and its related discussion, it was concluded that the players do not show differences in the covered total distance in relation to the category. Notwithstanding, there are differences with regards to speed and heart rate, which are caused by the greater physical development of the players in comparison to the under10’s age group category. Regarding the methodology employed, it is worth stressing that the coaches used, to a greater extend, the global method, followed by the mixed method.

The Impact of BIM on the Distribution of Cost and Return on Investment in UK Construction Projects

It has been widely documented that when Building Information Modelling (BIM) is used, there is a shift in effort to the design phase. Little investigation into the impact of this shift in effort has been done and how it impacts on costs. It can be difficult to justify the increased expenditure on BIM in a market that is heavily driven by costs. There are currently studies attempting to quantify the return on investment (ROI) for BIM for which these returns can be seen to balance out the shift in efforts and costs to the design phase. The studies however quantify the ROI based on the individual stakeholder’s investment without consideration for the impact that the use of BIM from their project partners may have on their own profitability. In this study, a questionnaire investigated opinions and experience of construction professionals, representing clients, consultants, designers and contractors, to determine fluctuations in costs by their magnitude and when they occur. These factors were examined more closely by interviewing senior members representing each of the stakeholder categories and comparing their experience in using BIM within environments where their project partners were also using BIM and when they were not. This determined the differences in how the use and the investment in BIM impacts on others and how costs are redistributed. This redistribution is not just through time but also between stakeholders and categories of costs. Some of these cost fluctuations and how the cost of BIM is currently financed are also highlighted in several case studies. The results show that the current distribution of costs set for traditional 2D delivery is hindering the potential success of BIM. There is also evidence that stakeholders who don’t use BIM may benefit financially from the BIM use of others and that collaborative BIM is significantly different to the use of ‘lonely’ BIM in terms of benefits and profitability.

Towards a Definition of Excellence in Sport Coaching

In this paper,we propose different definitions of coaching excellence based on two principles. First,the application of coaching skill,as in any other domain of excellence,is context-dependent. Second, excellent coaches are knowledgeable and constantly assemble mental models that enable them to meet their athletes' needs and to effectively manage the central duties of coaching - organization, training, and competition. Four categories of coaches and corresponding definitions are proposed based on the characteristics of athletes and the developmentally-appropriate sport contexts: 1) participation coaches for children, 2) participation coaches for teens and adults, 3) performance coaches for young adolescents, 4) performance coaches for older adolescents and adults.

Narratives and counter-narratives on "marriage of convenience" : conjugality and (il)legality in portuguese migration policies and in couples’ experiences

Tese de doutoramento, Sociologia (Sociologia da Família, Juventude e das Relações do Género), Universidade de Lisboa, Instituto de Ciências Sociais, 2016

Determinants of Financial Capital Use: Review of theories and implications for rural businesses. Factor Markets Working Paper No. 19, February 2012

This paper presents a review of financial economics literature and offers a comprehensive discussion and systematisation of determinants of financial capital use. In congruence with modern financial literature, it is acknowledged here that real and financial capital decisions are interdependent. While the fundamental role of the (unconstrained) demand for real capital in the demand for finance is acknowledged, the deliverable focuses on three complementary categories of the determinants of financial capital use: i) capital market imperfections; ii) factors mitigating these imperfections or their impacts; and iii) firm- and sector-related factors, which alter the severity of financial constraints and their effects. To address the question of the optimal choice of financial instruments, theories of firm capital structure are reviewed. The deliverable concludes with theory-derived implications for agricultural and non-agricultural rural business’ finance.

Offshoring of Information-intensive Services: Structural Breaks in Industry Life Cycles. ACES Working Papers, August 2010

The emergence of widespread offshoring of information-intensive services is arguably one of the more impactful phenomena to transform business in the last ten years. A growing body of research has examined the firm-level drivers andlocation factors (i.e., the why's and where's) of services offshoring. However, little empirical research has examined the maturation sequencing (or when's) of services offshoring. Adopting industry life cycle theory as a framework, the key research questions examined in the paper are: when do different categories of offshoring services provision change from being emergent sectors to more mature ones, and how does the timing of this sequence relate to the type of service offshored. Using a database of 1420 offshore services FDI projects, we find that the value-add as well as the information sensitivity of the service category are related to when the service categories progress through the industry life cycle. Implications for future waves of service offshoring are discussed.

Extending Working Lives: A comparative analysis of how governments influence lifelong learning, CEPS Special Report No. 111, July 2015

This report offers a comparative policy study on adult learning within the scope of complementary research conducted by Beblavý et al. (2013) on how people upgrade their skills during their adult lifetimes. To achieve our objectives, we identified regulatory policies and financial support in 11 countries for two main categories of learning: formal higher education and employer-based training. Drawing upon the results of the country reports carried out by our partners in the MoPAct project, we found that in none of the countries examined is there an ‘older student’ policy. In most cases grants and financial support are awarded only up until a certain age. In all of the countries studied, standard undergraduate and post-graduate studies are available for part-time students. The distribution of full-time students and part-time students in tertiary education varies from one country to another as well as from one age group to another. The participation in full-time tertiary education programmes decreases with the age of students. In Lithuania, Latvia, Poland and the UK, there are no mandatory policies to ensure employer-based training. However, in Belgium, Czech Republic, Denmark, Estonia, Germany, Italy, the Netherlands and Spain, employer-based training is more clearly regulated and the employers might have obligations to provide training for their staff. Taking into consideration Beblavý et al. (2013), we observe that comparative differences across countries can be related to policy differences only in some cases. The policy framework seems to impact more the employer-based training than the educational attainment (upgrade of ISCED level). In Denmark, the Netherlands, Latvia, Lithuania, Czech Republic and Poland, we find a perfect match between policy outcomes and the results of Beblavý et al. (2013) related to employer-based training. This is not the case in the United Kingdom, where the two aspects observed are not correlated.

Three-Dimensional Structure and Disposition of the Air Conducting and Gas Exchange Conduits of the Avian Lung: The Domestic Duck (Cairina moschata)

The anatomy of the domestic duck lung was studied macroscopically, by casting and by light, transmission, and scanning electron microscopy. The lung had four categories of secondary bronchi (SB), namely, the medioventral (MV, 4-5), laterodorsal (LD, 6-10), lateroventral (LV, 2-4), and posterior secondary bronchi (PO, 36-44). The neopulmonic parabronchi formed an intricate feltwork on the ventral third of the lung and inosculated those from the other SB. The lung parenchyma was organized into cylindrical parabronchi separated by thin septa containing blood vessels. Atria were shallow and well-fortified by epithelial ridges reinforced by smooth muscle bundles and gave rise to 2-6 elongate infundibulae. Air capillaries arose either directly from the atria or from infundibulae and were tubular or globular in shape with thin interconnecting branches. The newly described spatial disposition of the conducting air conduits closely resembles that of the chicken. This remarkable similarity between the categories, numbers, and 3D arrangement of the SB in the duck and chicken points to a convergence in function-oriented design. To illuminate airflow dynamics in the avian lung, precise directions of airflow in the various categories of SB and parabronchi need to be characterized.