The evolution of alternative splicing patterns and regulatory mechanisms

Alternative splicing produces multiple isoforms from the same gene, thus increasing the number of transcripts of the species. Alternative splicing is a virtually ubiquitous mechanism in eukaryotes, for example more than 90% of protein-coding genes in human are alternatively spliced. Recent evolutionary studies showed that alternative splicing is a fast evolving and highly species- specific mechanism. The rapid evolution of alternative splicing was considered as a contribution to the phenotypic diversity between species. However, the function of many isoforms produced by alternative splicing remains unclear and they might be the result of noisy splicing. Thus, the functional relevance of alternative splicing and the evolutionary mechanisms of its rapid divergence among species are still poorly understood. During my thesis, I performed a large-scale analysis of the regulatory mechanisms that drive the rapid evolution of alternative splicing. To study the evolution of alternative splicing regulatory mechanisms, I used an extensive RNA-sequencing dataset comprising 12 tetrapod species (human, chimpanzee and bonobo, gorilla, orangutan, macaque, marmoset, mouse, opossum, platypus, chicken and frog) and 8 tissues (cerebellum, brain, heart, kidney, liver, testis, placenta and ovary). To identify the catalogue of alternative splicing eis-acting regulatory elements in the different tetrapod species, I used a previously defined computational approach. This approach is a statistical analysis of exons/introns and splice sites composition and relies on a principle of compensation between splice sites strength and the presence of additional regulators. With an evolutionary comparative analysis of the exonic eis-acting regulators, I showed that these regulatory elements are generally shared among primates and more conserved than non-regulatory elements. In addition, I showed that the usage of these regulatory elements is also more conserved than expected by chance. In addition to the identification of species- specific eis-acting regulators, these results may explain the rapid evolution of alternative splicing. I also developed a new approach based on evolutionary sequence changes and corresponding alternative splicing changes to identify potential splicing eis-acting regulators in primates. The identification of lineage-specific substitutions and corresponding lineage-specific alternative splicing changes, allowed me to annotate the genomic sequences that might have played a role in the alternative splicing pattern differences among primates. Finally, I showed that the identified splicing eis-acting regulator datasets are enriched in human disease-causing mutations, thus confirming their biological relevance.

Nonsurgical treatment of cyclic esotropia.

Cyclic esotropia is characterized by a 24-hour period of straight eye position followed by 24 hours of large-angle esotropia. Possible mechanisms include notably progressive loss of compensation of a latent strabismus. The classic treatment is surgical correction of the angle measured on the days with manifest deviation. We report the first case of cyclic esotropia successfully treated by prismatic correction of the latent strabismus present on "straight" days.

The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.

Routinely collected health data, obtained for administrative and clinical purposes without specific a priori research goals, are increasingly used for research. The rapid evolution and availability of these data have revealed issues not addressed by existing reporting guidelines, such as Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). The REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement was created to fill these gaps. RECORD was created as an extension to the STROBE statement to address reporting items specific to observational studies using routinely collected health data. RECORD consists of a checklist of 13 items related to the title, abstract, introduction, methods, results, and discussion section of articles, and other information required for inclusion in such research reports. This document contains the checklist and explanatory and elaboration information to enhance the use of the checklist. Examples of good reporting for each RECORD checklist item are also included herein. This document, as well as the accompanying website and message board (http://www.record-statement.org), will enhance the implementation and understanding of RECORD. Through implementation of RECORD, authors, journals editors, and peer reviewers can encourage transparency of research reporting.

Analyzing the Background Information of an Activity-Based Costing System

The aim of this thesis was to analyze the background information of an activity-based costing system, which is being used in a domestic forest industry company. The reports produced by the system have not been reliable, and this has caused the utilization of the system to diminish. The study was initiated by examining the theory of activity-based costing. It was also discovered, that the system produces management accounting information and therefore also that theory was introduced briefly. Next the possible sources of errors were examined. The significance of these errors was evaluated and waste handling was chosen as a subject of further study. The problem regarding waste handling was that there is no waste compensation in current model. When paper or board machine produces waste, it can be used as raw material in the process. However, at the moment the product, which is being produced, at the time does not get any compensation. The use of compensation has not been possible due to not knowing the quantity of process waste. As a result of the study a calculatory model, which enables calculating the quantity of process waste based on the data from the mill system, was introduced. This, for one, enables starting to use waste compensation in the future.

The progress and obstacles of implementing and improving e-government in Islamic Republic of Iran

To improving efficiency and transparency of government services, government authorities may increase the frequency of interaction between citizens and government as well as improving the quality of the government services and trust. Electronic Government (E-Government) in definition is the delivery of government services to citizens, businesses, and government organizations through the use of internet, web based applications, and Information and Communication Technologies (ICTs) is the solution to build more reliable and efficient contact with citizens. Like the developing and developed countries, Iran also has been processing the various aspects of ICT, IT, and e-Government. Though, in order to implement and improve e-Government; Iran has faced with some obstacles. Therefore, the purpose of this thesis is to study progress of e- Government and identify obstacles of implementing and improving e Government in Iran. In this thesis, based on the literature review, the progress of e-Government in Iran was studied and various obstacles were identified. Therefore, as a result, e- Government of Iran is said to be in the transactional stage of the United Nations’ e-Government maturity stages. In addition, establishing more reliable, efficient, and accurate e-Government initiatives, plans, guidelines, and strategies will extremely enhance e-Government status of Iran. On the other hand, the needs of the citizens should always be under consideration when implementing and improving e-Government services; because citizens are considered to be at the core of every e-Government services and the responsibilities of the authorities.

The consequences of e-HRM on line managers

The purpose of this research was to provide a deeper insight into the consequences of electronic human resource management (e-HRM) for line managers. The consequences are viewed as used information system (IS) potentials pertaining to the moderate voluntaristic category of consequences. Due to the need to contextualize the research and draw on line managers’ personal experiences, a qualitative approach in a case study setting was selected. The empirical part of the research is loosely based on literature on HRM and e-HRM and it was conducted in an industrial private sector company. In this thesis, method triangulation was utilized, as nine semi-structured interviews, conducted in a European setting, created the main method for data collection and analysis. Other complementary data such as HRM documentation and statistics of e-HRM system usage were utilized as background information to help to put the results into context. E-HRM has partly been taken into use in the case study company. Line managers tend to use e-HRM when a particular task requires it, but they are not familiar with all the features and possibilities which e-HRM has to offer. The advantages of e-HRM are in line with the company’s goals. The advantages are e.g. an transparency of data, process consistency, and having an efficient and easy-to-use tool at one’s disposal. However, several unintended, even contradictory, and mainly negative outcomes can also be identified, such as over-complicated processes, in-security in use of the tool, and the lack of co-operation with HR professionals. The use of e-HRM and managers’ perceptions regarding e-HRM affect the way in which managers perceive the consequences of e-HRM on their work. Overall, the consequences of e-HRM are divergent, even contradictory. The managers who considered e-HRM mostly beneficial to their work found that e-HRM affects their work by providing information and increasing efficiency. Those managers who mostly perceived challenges in e-HRM did not think that e-HRM had affected their role or their work. Even though the perceptions regarding e-HRM and its consequences might reflect the strategies, the distribution of work, and the ways of working in all HRM in general and can’t be generalized as such, this research contributed to the field of e-HRM and it provides new perspectives to e-HRM in the case study organization and in the academic field in general.

Changes in cortical and sub-cortical patterns of activity associated with aging during the performance of a lexical set-shifting task

Bien que le passage du temps altère le cerveau, la cognition ne suit pas nécessairement le même destin. En effet, il existe des mécanismes compensatoires qui permettent de préserver la cognition (réserve cognitive) malgré le vieillissement. Les personnes âgées peuvent utiliser de nouveaux circuits neuronaux (compensation neuronale) ou des circuits existants moins susceptibles aux effets du vieillissement (réserve neuronale) pour maintenir un haut niveau de performance cognitive. Toutefois, la façon dont ces mécanismes affectent l’activité corticale et striatale lors de tâches impliquant des changements de règles (set-shifting) et durant le traitement sémantique et phonologique n’a pas été extensivement explorée. Le but de cette thèse est d’explorer comment le vieillissement affecte les patrons d’activité cérébrale dans les processus exécutifs d’une part et dans l’utilisation de règles lexicales d’autre part. Pour cela nous avons utilisé l’imagerie par résonance magnétique fonctionnelle (IRMf) lors de la performance d’une tâche lexicale analogue à celle du Wisconsin. Cette tâche a été fortement liée à de l’activité fronto-stritale lors des changements de règles, ainsi qu’à la mobilisation de régions associées au traitement sémantique et phonologique lors de décisions sémantiques et phonologiques, respectivement. Par conséquent, nous avons comparé l’activité cérébrale de jeunes individus (18 à 35 ans) à celle d’individus âgés (55 à 75 ans) lors de l’exécution de cette tâche. Les deux groupes ont montré l’implication de boucles fronto-striatales associées à la planification et à l’exécution de changements de règle. Toutefois, alors que les jeunes semblaient activer une « boucle cognitive » (cortex préfrontal ventrolatéral, noyau caudé et thalamus) lorsqu’ils se voyaient indiquer qu’un changement de règle était requis, et une « boucle motrice » (cortex postérieur préfrontal et putamen) lorsqu’ils devaient effectuer le changement, les participants âgés montraient une activation des deux boucles lors de l’exécution des changements de règle seulement. Les jeunes adultes tendaient à présenter une augmentation de l’activité du cortex préfrontal ventrolatéral, du gyrus fusiforme, du lobe ventral temporale et du noyau caudé lors des décisions sémantiques, ainsi que de l’activité au niveau de l’aire de Broca postérieur, de la junction temporopariétale et du cortex moteur lors de décisions phonologiques. Les participants âgés ont montré de l’activité au niveau du cortex préfrontal latéral et moteur durant les deux types de décisions lexicales. De plus, lorsque les décisions sémantiques et phonologiques ont été comparées entre elles, les jeunes ont montré des différences significatives au niveau de plusieurs régions cérébrales, mais pas les âgés. En conclusion, notre première étude a montré, lors du set-shifting, un délai de l’activité cérébrale chez les personnes âgées. Cela nous a permis de conceptualiser l’Hypothèse Temporelle de Compensation (troisième manuscrit) qui consiste en l’existence d’un mécanisme compensatoire caractérisé par un délai d’activité cérébrale lié au vieillissement permettant de préserver la cognition au détriment de la vitesse d’exécution. En ce qui concerne les processus langagiers (deuxième étude), les circuits sémantiques et phonologiques semblent se fusionner dans un seul circuit chez les individus âgés, cela représente vraisemblablement des mécanismes de réserve et de compensation neuronales qui permettent de préserver les habilités langagières.

Highly conductive and transparent ZnO thin film using Chemical Spray Pyrolysis technique: Effect of doping and deposition parameters

In the present work we report the preparation details studies on ZnO thin films. ZnO thin films are prepared using cost effective deposition technique viz., Chemical Spray Pyrolysis (CSP). The method is very effective for large area preparation of the ZnO thin film. A new post-deposition process could also be developed to avoid the adsorption of oxygen that usually occurs after the spraying process i.e., while cooling. Studies were done by changing the various deposition parameters for optimizing the properties of ZnO thin film. Moreover, different methods of doping using various elements are also tried to enhance the conductivity and transparency of the film to make these suitable for various optoelectronic applications.

Compensation to Workmen for Industrial Injuries

This thesis Entitled compensation to workmen for industrial injuries.Evaluation of the different forms of liability for compensating industrial injuries makes it evident that the liability under the social insurance scheme is the most befitting one, as it eliminates the problem of evasion of liability by the employer by providing for sharing of liability. Liability for compensation under the workmen's Compensation Act, 1923 and the Employees' State Insurance Act, 1948 arises only in the case of accidents, arising in the course of and out of employment. Majority of the workers, covered by the workmen's Compensation Act, have supported lumpsum payment of compensation under the Act. It appears that workers are ignorant of the cemerits of lumpsum payment. So, the workers should be properly educated by the Inspectorate, proposed above, about the comparative advantages of periodical payments. It is suggested that the workmens Compensation Act, 1923 may be amended, imposing fee upon the parties for each adjournment. It is also suggested that provision may be made in the workmens Compensation Act, 1923 for the expeditious despatch of amendments of the Workmen's Compensation Act, 1923, the Workmens· Compensation Rules, 1924 and the Schedules, made from time to time, to the comrnissioners for workmens Compensation, This will help them mete out justice to an injured workman, as required by the changes in the law. The Employees' State Insurance Act, 1948 and the Rules may be amended, requiring the employers to provide the employees with necessary information, in the vernacular language, about the employment injury benefits available under the Employees' State Insurance Act, 1948 and the formalities for obtaining the same. This will help the illiterate employees, especially the casual ones, avail of employment injury benefits. Changes in the law, on the lines suggested above, are imperative to make the system of compensation for industrial injuries prove effective and beneficial to injured workmen.

The European organic food market - how to increase its transparency?

Der Europäische Markt für ökologische Lebensmittel ist seit den 1990er Jahren stark gewachsen. Begünstigt wurde dies durch die Einführung der EU-Richtlinie 2092/91 zur Zertifizierung ökologischer Produkte und durch die Zahlung von Subventionen an umstellungswillige Landwirte. Diese Maßnahmen führten am Ende der 1990er Jahre für einige ökologische Produkte zu einem Überangebot auf europäischer Ebene. Die Verbrauchernachfrage stieg nicht in gleichem Maße wie das Angebot, und die Notwendigkeit für eine Verbesserung des Marktgleichgewichts wurde offensichtlich. Dieser Bedarf wurde im Jahr 2004 von der Europäischen Kommission im ersten „Europäischen Aktionsplan für ökologisch erzeugte Lebensmittel und den ökologischen Landbau“ formuliert. Als Voraussetzung für ein gleichmäßigeres Marktwachstum wird in diesem Aktionsplan die Schaffung eines transparenteren Marktes durch die Erhebung statistischer Daten über Produktion und Verbrauch ökologischer Produkte gefordert. Die Umsetzung dieses Aktionsplans ist jedoch bislang nicht befriedigend, da es auf EU-Ebene noch immer keine einheitliche Datenerfassung für den Öko-Sektor gibt. Ziel dieser Studie ist es, angemessene Methoden für die Erhebung, Verarbeitung und Analyse von Öko-Marktdaten zu finden. Geeignete Datenquellen werden identifiziert und es wird untersucht, wie die erhobenen Daten auf Plausibilität untersucht werden können. Hierzu wird ein umfangreicher Datensatz zum Öko-Markt analysiert, der im Rahmen des EU-Forschungsprojektes „Organic Marketing Initiatives and Rural Development” (OMIaRD) erhoben wurde und alle EU-15-Länder sowie Tschechien, Slowenien, Norwegen und die Schweiz abdeckt. Daten für folgende Öko-Produktgruppen werden untersucht: Getreide, Kartoffeln, Gemüse, Obst, Milch, Rindfleisch, Schaf- und Ziegenfleisch, Schweinefleisch, Geflügelfleisch und Eier. Ein zentraler Ansatz dieser Studie ist das Aufstellen von Öko-Versorgungsbilanzen, die einen zusammenfassenden Überblick von Angebot und Nachfrage der jeweiligen Produktgruppen liefern. Folgende Schlüsselvariablen werden untersucht: Öko-Produktion, Öko-Verkäufe, Öko-Verbrauch, Öko-Außenhandel, Öko-Erzeugerpreise und Öko-Verbraucherpreise. Zudem werden die Öko-Marktdaten in Relation zu den entsprechenden Zahlen für den Gesamtmarkt (öko plus konventionell) gesetzt, um die Bedeutung des Öko-Sektors auf Produkt- und Länderebene beurteilen zu können. Für die Datenerhebung werden Primär- und Sekundärforschung eingesetzt. Als Sekundärquellen werden Publikationen von Marktforschungsinstituten, Öko-Erzeugerverbänden und wissenschaftlichen Instituten ausgewertet. Empirische Daten zum Öko-Markt werden im Rahmen von umfangreichen Interviews mit Marktexperten in allen beteiligten Ländern erhoben. Die Daten werden mit Korrelations- und Regressionsanalysen untersucht, und es werden Hypothesen über vermutete Zusammenhänge zwischen Schlüsselvariablen des Öko-Marktes getestet. Die Datenbasis dieser Studie bezieht sich auf ein einzelnes Jahr und stellt damit einen Schnappschuss der Öko-Marktsituation der EU dar. Um die Marktakteure in die Lage zu versetzen, zukünftige Markttrends voraussagen zu können, wird der Aufbau eines EU-weiten Öko-Marktdaten-Erfassungssystems gefordert. Hierzu wird eine harmonisierte Datenerfassung in allen EU-Ländern gemäß einheitlicher Standards benötigt. Die Zusammenstellung der Marktdaten für den Öko-Sektor sollte kompatibel sein mit den Methoden und Variablen der bereits existierenden Eurostat-Datenbank für den gesamten Agrarmarkt (öko plus konventionell). Eine jährlich aktualisierte Öko-Markt-Datenbank würde die Transparenz des Öko-Marktes erhöhen und die zukünftige Entwicklung des Öko-Sektors erleichtern. ---------------------------

The Phosphorus Indicators Tool: a simple model of diffuse P loss from agricultural land to water

The Phosphorus Indicators Tool provides a catchment-scale estimation of diffuse phosphorus (P) loss from agricultural land to surface waters using the most appropriate indicators of P loss. The Tool provides a framework that may be applied across the UK to estimate P loss, which is sensitive not only to land use and management but also to environmental factors such as climate, soil type and topography. The model complexity incorporated in the P Indicators Tool has been adapted to the level of detail in the available data and the need to reflect the impact of changes in agriculture. Currently, the Tool runs on an annual timestep and at a 1 km(2) grid scale. We demonstrate that the P Indicators Tool works in principle and that its modular structure provides a means of accounting for P loss from one layer to the next, and ultimately to receiving waters. Trial runs of the Tool suggest that modelled P delivery to water approximates measured water quality records. The transparency of the structure of the P Indicators Tool means that identification of poorly performing coefficients is possible, and further refinements of the Tool can be made to ensure it is better calibrated and subsequently validated against empirical data, as it becomes available.

Comparative advantage in demand: Experimental evidence of preferences for genetically modified food in the United States and European Union

The United States (US) exports more than US$6 billion in agricultural commodities to the European Union (EU) each year, but one issue carries the potential to diminish this trade: use of biotechnology in food production. The EU has adopted more stringent policies towards biotechnology than the US. Understanding differences in European and American policies towards genetically modified (GM) foods requires a greater understanding of consumers' attitudes and preferences. This paper reports results from the first large-scale, cross-Atlantic study to analyse consumer demand for genetically modified food in a non-hypothetical market environment. We strongly reject the frequent if convenient assumption in trade theory that consumer preferences are identical across countries: the median level of compensation demanded by English and French consumers to consume a GM food is found to be more than twice that in any of the US locations. Results have important implications for trade theory, which typically focusses on differences in specialization, comparative advantage and factor endowments across countries, and for on-going trade disputes at the World Trade Organization.

The influence of changing nicotine to tar ratios on human puffing behaviour and perceived sensory response

Rationale. Smokers modify their smoking behaviour when switching from their usual product to higher or lower tar and nicotine-yield cigarettes. Objective. The aims of the current study were to assess the influence of varying nicotine yields at constant tar yield on human puffing measures, nicotine deliveries under human smoking conditions and the sensory response to mainstream cigarette smoke. These assessments would allow an evaluation of the degree of compensation and the various possible causes of changes, if any. Methods. The participants were 13 regular smokers of commercial or hand-rolled cigarettes. They were tested with four cigarettes, which exhibited a wide range of nicotine to 'tar' ratios at a relatively constant 'tar' yield. Their smoking behaviour was monitored by placing the test cigarettes into an orifice-type holder/flowmeter attached to a custom-built smoker behaviour analyser. In addition, a comprehensive sensory evaluation of the products was carried out. Results. The differences in the nicotine to tar ratios of the samples did not significantly influence the puffing behaviour patterns, i.e. puff number and interval, total and average puff volume, integrated pressure and puff duration. Additionally the pre- to post-exhaled CO boosts were not significantly influenced by the experimental samples used in the study. However, the nicotine yields obtained by the smokers were significantly influenced by the machine-smoked nicotine yields or the nicotine to tar ratios of the samples. The machine-smoked nicotine yields were highly correlated with the nicotine yields obtained under human smoking conditions. For the sensory evaluation, there was only a significant difference between the samples in the intensity of the impact. Conclusion. These observations imply that these puffing variables are not controlled by the nicotine yield of the cigarette.

Properties of thick evaporated layers of PbTe

The changes in the optical transparency of PbTe monolayers induced by post-evaporation heat treatment are described. The monolayers are typically a few microns in thickness and heat treatment reduces the carrier density from about 1018 (n-type) per cm3 to 1017 per cm3 : the source material is 1019 (ptype) per cm3. The process seems to involve the diffusion of O2 at a reaction rate equivalent to an energy of 0.83 eV.

The 'veil' of control: exploring the attitudes and perceptions of UK design controllers

In the UK, architectural design is regulated through a system of design control for the public interest, which aims to secure and promote ‘quality’ in the built environment. Design control is primarily implemented by locally employed planning professionals with political oversight, and independent design review panels, staffed predominantly by design professionals. Design control has a lengthy and complex history, with the concept of ‘design’ offering a range of challenges for a regulatory system of governance. A simultaneously creative and emotive discipline, architectural design is a difficult issue to regulate objectively or consistently, often leading to policy that is regarded highly discretionary and flexible. This makes regulatory outcomes difficult to predict, as approaches undertaken by the ‘agents of control’ can vary according to the individual. The role of the design controller is therefore central, tasked with the responsibility of interpreting design policy and guidance, appraising design quality and passing professional judgment. However, little is really known about what influences the way design controllers approach their task, providing a ‘veil’ over design control, shrouding the basis of their decisions. This research engaged directly with the attitudes and perceptions of design controllers in the UK, lifting this ‘veil’. Using in-depth interviews and Q-Methodology, the thesis explores this hidden element of control, revealing a number of key differences in how controllers approach and implement policy and guidance, conceptualise design quality, and rationalise their evaluations and judgments. The research develops a conceptual framework for agency in design control – this consists of six variables (Regulation; Discretion; Skills; Design Quality; Aesthetics; and Evaluation) and it is suggested that this could act as a ‘heuristic’ instrument for UK controllers, prompting more reflexivity in relation to evaluating their own position, approaches, and attitudes, leading to better practice and increased transparency of control decisions.