Direct Measurement of the W Production Charge Asymmetry in pp̅ Collisions at √s=1.96 TeV

We present the first direct measurement of the $W$ production charge asymmetry as a function of the $W$ boson rapidity $\yW$ in $\ppbar$ collisions at $\sqrt{s} = 1.96$ $\TeV$. We use a sample of $\wenu$ events in data from 1 $\ifb$ of integrated luminosity collected using the CDF II detector. In the region $|\yW|

Consumption in Rural Bangladesh : Households, Lifestyles, and Identities

Bangladesh, often better known to the outside world as a country of natural calamities, is one of the most densely populated countries in the world. Despite rapid urbanization, more than 75% of the people still live in rural areas. The density of the rural population is also one of the highest in the world. Being a poor and low-income country, its main challenge is to eradicate poverty through increasing equitable income. Since its independence in 1971, Bangladesh has experienced many ups and downs, but over the past three decades, its gross domestic product (GDP) has grown at an impressive rate. Consequently, the country s economy is developing and the country has outperformed many low-income countries in terms of several social indicators. Bangladesh has achieved the Millennium Development Goal (MDG) of eliminating gender disparity in primary and secondary school enrollment. A sharp decline in child and infant mortality rates, increased per capita income, and improved food security have placed Bangladesh on the track to achieving in the near future the status of a middle-income country. All these developments have influenced the consumption pattern of the country. This study explores the consumption scenario of rural Bangladesh, its changing consumption patterns, the relationship between technology and consumption in rural Bangladesh, cultural consumption in rural Bangladesh, and the myriad reasons why consumers nevertheless feel compelled to consume chemically treated foods. Data were collected in two phases in the summers of 2006 and 2008. In 2006, the empirical data were collected from the following three sources: interviews with consumers, producers/sellers, and doctors and pharmacists; observations of sellers/producers; and reviews of articles published in the national English and Bengali (the national language of Bangladesh) daily newspapers. A total of 110 consumers, 25 sellers/producers, 7 doctors, and 7 pharmacists were interviewed and observed. In 2008, data were collected through semi-structured in-depth qualitative interviews, ethnography, and unstructured conversations substantiated by secondary sources and photographs; the total number of persons interviewed was 22. -- Data were also collected on the consumption of food, clothing, housing, education, medical facilities, marriage and dowry, the division of labor, household decision making, different festivals such as Eid (for Muslims), the Bengali New Year, and Durga puja (for Hindus), and leisure. Qualitative methods were applied to the data analysis and were supported by secondary quantitative data. The findings of this study suggest that the consumption patterns of rural Bangladeshis are changing over time along with economic and social development, and that technology has rendered aspects of daily life more convenient. This study identified the perceptions and experiences of rural people regarding technologies in use and explored how culture is associated with consumption. This study identified the reasons behind the use of hazardous chemicals (e.g. calcium carbide, sodium cyclamate, cyanide and formalin, etc.) in foods as well as the extent to which food producers/sellers used such chemicals. In addition, this study assessed consumer perceptions of and attitudes toward these contaminated food items and explored how adulterated foods and food stuffs affect consumer health. This study also showed that consumers were aware that various foods and food stuffs contained hazardous chemicals, and that these adulterated foods and food stuffs were harmful to their health.

ISO 13567 - The Proposed International Standard for Structuring Layers in Computer Aided Building Design

Layering is a widely used method for structuring data in CAD-models. During the last few years national standardisation organisations, professional associations, user groups for particular CAD-systems, individual companies etc. have issued numerous standards and guidelines for the naming and structuring of layers in building design. In order to increase the integration of CAD data in the industry as a whole ISO recently decided to define an international standard for layer usage. The resulting standard proposal, ISO 13567, is a rather complex framework standard which strives to be more of a union than the least common denominator of the capabilities of existing guidelines. A number of principles have been followed in the design of the proposal. The first one is the separation of the conceptual organisation of information (semantics) from the way this information is coded (syntax). The second one is orthogonality - the fact that many ways of classifying information are independent of each other and can be applied in combinations. The third overriding principle is the reuse of existing national or international standards whenever appropriate. The fourth principle allows users to apply well-defined subsets of the overall superset of possible layernames. This article describes the semantic organisation of the standard proposal as well as its default syntax. Important information categories deal with the party responsible for the information, the type of building element shown, whether a layer contains the direct graphical description of a building part or additional information needed in an output drawing etc. Non-mandatory information categories facilitate the structuring of information in rebuilding projects, use of layers for spatial grouping in large multi-storey projects, and storing multiple representations intended for different drawing scales in the same model. Pilot testing of ISO 13567 is currently being carried out in a number of countries which have been involved in the definition of the standard. In the article two implementations, which have been carried out independently in Sweden and Finland, are described. The article concludes with a discussion of the benefits and possible drawbacks of the standard. Incremental development within the industry, (where ”best practice” can become ”common practice” via a standard such as ISO 13567), is contrasted with the more idealistic scenario of building product models. The relationship between CAD-layering, document management product modelling and building element classification is also discussed.

'... the walls fell down but the blokes just coded ...' - Varieties of stability in software product development during organizational restructurings

Many Finnish IT companies have gone through numerous organizational changes over the past decades. This book draws attention to how stability may be central to software product development experts and IT workers more generally, who continuously have to cope with such change in their workplaces. It does so by analyzing and theorizing change and stability as intertwined and co-existent, thus throwing light on how it is possible that, for example, even if ‘the walls fall down the blokes just code’ and maintain a sense of stability in their daily work. Rather than reproducing the picture of software product development as exciting cutting edge activities and organizational change as dramatic episodes, the study takes the reader beyond the myths surrounding these phenomena to the mundane practices, routines and organizings in product development during organizational change. An analysis of these ordinary practices offers insights into how software product development experts actively engage in constructing stability during organizational change through a variety of practices, including solidarity, homosociality, close relations to products, instrumental or functional views on products, preoccupations with certain tasks and humble obedience. Consequently, the study shows that it may be more appropriate to talk about varieties of stability, characterized by a multitude of practices of stabilizing rather than states of stagnation. Looking at different practices of stability in depth shows the creation of software as an arena for micro-politics, power relations and increasing pressures for order and formalization. The thesis gives particular attention to power relations and processes of positioning following organizational change: how social actors come to understand themselves in the context of ongoing organizational change, how they comply with and/or contest dominant meanings, how they identify and dis-identify with formalization, and how power relations often are reproduced despite dis-identification. Related to processes of positioning, the reader is also given a glimpse into what being at work in a male-dominated and relatively homogeneous work environment looks like. It shows how the strong presence of men or “blokes” of a particular age and education seems to become invisible in workplace talk that appears ‘non-conscious’ of gender.

Direct detection of atmospheric particle formation using the Neutral cluster and Air Ion Spectrometer

Aerosol particles play an important role in the Earth s atmosphere and in the climate system: they scatter and absorb solar radiation, facilitate chemical processes, and serve as seeds for cloud formation. Secondary new particle formation (NPF) is a globally important source of these particles. Currently, the mechanisms of particle formation and the vapors participating in this process are, however, not truly understood. In order to fully explain atmospheric NPF and subsequent growth, we need to measure directly the very initial steps of the formation processes. This thesis investigates the possibility to study atmospheric particle formation using a recently developed Neutral cluster and Air Ion Spectrometer (NAIS). First, the NAIS was calibrated and intercompared, and found to be in good agreement with the reference instruments both in the laboratory and in the field. It was concluded that NAIS can be reliably used to measure small atmospheric ions and particles directly at the sizes where NPF begins. Second, several NAIS systems were deployed simultaneously at 12 European measurement sites to quantify the spatial and temporal distribution of particle formation events. The sites represented a variety of geographical and atmospheric conditions. The NPF events were detected using NAIS systems at all of the sites during the year-long measurement period. Various particle formation characteristics, such as formation and growth rates, were used as indicators of the relevant processes and participating compounds in the initial formation. In a case of parallel ion and neutral cluster measurements, we also estimated the relative contribution of ion-induced and neutral nucleation to the total particle formation. At most sites, the particle growth rate increased with the increasing particle size indicating that different condensing vapors are participating in the growth of different-sized particles. The results suggest that, in addition to sulfuric acid, organic vapors contribute to the initial steps of NPF and to the subsequent growth, not just later steps of the particle growth. As a significant new result, we found out that the total particle formation rate varied much more between the different sites than the formation rate of charged particles. The results infer that the ion-induced nucleation has a minor contribution to particle formation in the boundary layer in most of the environments. These results give tools to better quantify the aerosol source provided by secondary NPF in various environments. The particle formation characteristics determined in this thesis can be used in global models to assess NPF s climatic effects.

CSR in forest industry – Case study of reporting and implementation of social responsibility in three international companies

Corporate Social Responsibility (CSR) has become increasingly important topic in forest industries, and other global companies, in recent years. Globalisation, faster information delivery and demand for sustainable development have set new challenges for global companies in their business operations. Also the importance of stakeholder relations, and pressure to become more transparent has increased in the forest industries. Three dimensions of corporate responsibility economic, environmental and social, are often included in the concept of CSR. Global companies mostly claim that these dimensions are equally important. This study analyses CSR in forest industry and has focus on reporting and implementation of social responsibility in three international companies. These case-companies are Stora Enso, SCA and Sappi, and they have different geographical base, product portfolios and therefore present interesting differences about forest industry strategy and CSR. Global Reporting Initiative (GRI) has created the most known and used reporting framework in CSR reporting. GRI Guidelines have made CSR reporting a uniform function, which can also be measured between companies and different sectors. GRI Guidelines have also made it possible to record and control CSR data in the companies. In recent years the use of GRI Guidelines has increased substantially. Typically CSR reporting on economic and environmental responsibility have been systematic in the global companies and often driven by legistlation and other regulations. However the social responsibility has been less regulated and more difficult to compare. Therefore it has previously been often less focused in the CSR reporting of the global companies. The implementation and use of GRI Guidelines have also increased dialogue on social responsibility issues and stakeholder management in global companies. This study analyses the use of GRI´s framework in the forest industry companies´ CSR reporting. This is a qualitative study and the disclosure of data is empricially analysed using content analysis. Content analysis has been selected as a method for this study because it makes it possible to use different sources of information. The data of this study consists of existing academic literature of CSR, sustainability reports of thecase-companies during 2005-2009, and the semi-structured interviews with company representatives. Different sources provide the possibility to look at specific subject from more than one viewpoint. The results of the study show that all case-companies have relatively common themes in their CSR disclosure, and the differences rise mainly from their product-portfolios, and geographic base. Social impacts to local communities, in the CSR of the companies, were mainly dominated by issues concerning creating wealth to the society and impacting communities through creation of work. The comparability of the CSR reporting, and especially social indicators increased significally from 2007 onwards in all case-companies. Even though the companies claim that three dimensions of CSR economic, environmental and social are equally important economic issues and profit improvement still seem to drive most of the operations in the global companies. Many issues that are covered by laws and regulations are still essentially presented as social responsibility in CSR. However often the unwelcome issues in companies like closing operations are covered just briefly, and without adequate explanation. To make social responsibility equally important in the CSR it would demand more emphasis from all the case-companies. A lot of emphasis should be put especially on the detail and extensiveness of the social reponsibility content in the CSR.

Development of foreign direct investment in Finland

During 1990 to 2009, Foreign Direct Investment (FDI henceforth) in Finland has fluctuated greatly. This paper focused on analyzing the overall development and basic characteristics of Foreign Direct Investment in Finland, covering the period from 1990 to present. By comparing FDI in Finland with FDI in other countries, the picture of Finland’s FDI position in the world market is clearer. A lot of statistical data, tables and figures are used to describe the trend of Foreign Direct Investment in Finland. All the data used in this study were obtained from Statistics Finland, UNCTAD, OECD, World Bank and International Labor Office, Investment map website and etc. It is also found that there is a big, long-lasting and increasing imbalance of the inward FDI and outward FDI in Finland, the performance of outward FDI is stronger than the inward FDI in Finland. Finland’s position of FDI in the world is rather modest. And based on existing theories, I tried to analyze the factors that might determine the size of the inflows of FDI in Finland. The econometric model of my thesis is based on time series data ranging from 1990 to 2007. A Log linear regression model is adopted to analyze the impact of each variable. The regression results showed that Labor Cost and Investment in Education have a negative influence on the FDI inflows into Finland. Too high labor cost is the main impediment of FDI in Finland, explaining the relative small size of FDI inflows into Finland. GDP and Economy openness have a significant positive impact on the inflows of FDI into Finland; other variables do not emerge as significant factor in affecting the size of FDI inflows in Finland as expected. Meanwhile, the impacts of the most recent financial and economic crisis on FDI in the world and in Finland are discussed as well. FDI inflows worldwide and in Finland have suffered from a big setback from the 2008 global crisis. The economic crisis has undoubtedly significant negative influence on the FDI flows in the world and in Finland. Nevertheless, apart from the negative impact, the crisis itself also brings in chances for policymakers to implement more efficient policies in order to create a pro-business and pro-investment climate for the recovery of FDI inflows. . The correspondent policies and measures aiming to accelerate the recovery of the falling FDI were discussed correspondently.

Trends in Pharmaceutical Product Development 2000-2010

Merkittävä osa alkuperäislääkevalmistajien tutkimus- ja tuotekehityskuluista näyttää olevan suunnattu olemassa olevien lääkkeiden kehittämiseen. Tämä voi oletettavasti johtaa kiinnostaviin formulaatiokehitysstrategioihin. Tutkimuksen tarkoituksena oli selvittää, voidaanko farmaseuttisen tuotekehityksen trendejä havaita myönnettyjen myyntilupien perusteella. Tutkimuksen mielenkiinnon kohteena olivat myös suurimpien lääkeyritysten käyttämät elinkaaren hallinnan keinot, joilla suojataan myyvimpiä tuotteita geneeriseltä kilpailulta ja varmistetaan markkinaosuus. Tutkimuksen painopiste oli kiinteissä oraalisissa lääkevalmisteissa. Laadullisten ja määrällisten menetelmien yhdistelmää käytettiin laajan näkökulman saamiseksi tutkittavaan aiheeseen. Suomalaisten myyntilupaviranomaisten haastatteluja käytettiin keräämään taustatietoa tutkimuksen määrällistä osaa varten. Määrällinen osa koostui myyntilupatietokannoista, jotka käsittivät kaikkien menettelyjen kautta Suomessa myönnetyt myyntiluvat, keskitetyn menettelyn kautta EU:ssa myönnetyt myyntiluvat ja maailman kymmenen suurinta lääkeyritystä USA:ssa. Tutkimustulosten perusteella rinnakkaislääkkeiden määrässä tapahtui merkittävä nousu Suomessa kaikkien menettelyjen kautta myönnetyissä myyntiluvissa ja EU:ssa keskitetyn menettelyn kautta myönnetyissä myyntiluvissa vuosina 2000-2010. Tämä muutos saattaa ainakin osaksi johtua lainsäädännöllisistä muutoksista, joilla luotiin kannustimia rinnakkaislääkkeiden käyttöön ja valmistukseen, kuten lääkevaihto ja viitehintajärjestelmä. USA:n tiedot osoittivat suurten lääkevalmistajien kiinnostuksen elinkaaren hallintaan: suurin osa maailman kymmenelle suurimmalle lääkeyritykselle myönnetyistä myyntiluvista vuosina 2005-2010 oli tähän tarkoitukseen. Elinkaaren hallinnan suhde uusiin lääkeaineisiin oli lähes 4:1. Kiinteä oraalinen lääkemuoto on kiistatta kaikista suosituin tapa annostella lääke, minkä vahvistivat sekä arvioijien haastattelut että myyntilupatiedot. Kiinteiden oraalisten rooli oli entistäkin korostuneempi rinnakkaislääkkeiden kohdalla. Kun innovatiivisuutta mitattiin epätyypillisten annosmuotojen määrällä, USA:n tiedot kiinteistä oraalisista lääkemuodoista osoittivat vahvaa innovatiivisuutta Suomen ja EU:n tietoihin verrattuna. Tämä saattaa heijastaa suurten lääkeyritysten innovatiivista tuotevalikoimaa. Epätyypillisten kiinteiden oraalisten annosmuotojen osuus oli huomattavasti pienempi rinnakkaislääkkeissä kuin alkuperäislääkkeissä kaikilla alueilla. Elinkaaren hallinnassa käytetyimmät strategiat olivat uusi formulaatio, uusi vahvuus ja uusi yhdistelmä olemassa olevasta valmisteesta. Kiinteiden oraalisten lääkemuotojen osalta kaksi kolmasosaa uusista elinkaaren hallinnan formulaatioista oli säädellysti vapauttavia valmisteita. Elinkaaren hallinta on olennainen osa suurten lääkeyritysten liiketoimintastrategiaa, ja sen tärkeyttä havainnollistettiin Coreg-tablettien tapausesimerkillä.

Effect of water vapour stabilization of raw materials on the quality of the inhalation product

Generation of raw materials for dry powder inhalers by different size reduction methods can be expected to influence physical and chemical properties of the powders. This can cause differences in particle size, size distribution, shape, crystalline properties, surface texture and energy. These physical properties of powders influence the behaviour of particles before and after inhalation. Materials with an amorphous surface have different surface energy compared to materials with crystalline surface. This can affect the adhesion and cohesion of particles. Changes in the surface nature of the drug particles results in a change in product performance. By stabilization of the raw materials the amorphous surfaces are converted into crystalline surfaces. The primary aim of the study was to investigate the influence of the surface properties of the inhalation particles on the quality of the product. The quality of the inhalation product is evaluated by measuring the fine particle dose (FPD). FDP is the total dose of particles with aerodynamic diameters smaller than 5,0 μm. The secondary aim of this study was to achieve the target level of the FPD and the stability of the FPD. This study was also used to evaluate the importance of the stabilization of the inhalation powders. The study included manufacturing and analysing drug substance 200 μg/dose inhalation powder batches using non-stabilized or stabilized raw materials. The inhaler formulation consisted of micronized drug substance, lactose <100μm and micronized lactose <10μm. The inhaler device was Easyhaler®. Stabilization of the raw materials was done in different relative humidity, temperature and time. Surface properties of the raw materials were studied by dynamic vapour sorption, scanning electron microscopy and three-point nitrogen adsorption technique. Particle size was studied by laser diffraction particle size analyzer. Aerodynamic particle size distribution from inhalers was measured by new generation impactor. Stabilization of all three raw materials was successful. A clear difference between nonstabilized and stabilized raw materials was achieved for drug substance and lactose <10μm. However for lactose <100μm the difference wasn’t as clear as wanted. The surface of the non-stabilized drug substance was more irregular and the particles had more roughness on the surface compared to the stabilized drug substances particles surface. The surface of the stabilized drug particles was more regular and smoother than non-stabilized. Even though a good difference between stabilized and non-stabilized raw materials was achieved, a clear evidence of the effect of the surface properties of the inhalation particles on the quality of the product was not observed. Stabilization of the raw materials didn’t lead to a higher FPD. Possible explanations for the unexpected result might be too rough conditions in the stabilization of the drug substance or smaller than wanted difference in the degree of stabilization of the main component of the product <100μm. Despite positive effects on the quality of the product were not seen there appears to be some evidence that stabilized drug substance results in smaller particle size of dry powder inhalers.

Local systems, global impacts : Using life cycle assessment to analyse the potential and constraints of industrial symbioses

Human activities extract and displace different substances and materials from the earth s crust, thus causing various environmental problems, such as climate change, acidification and eutrophication. As problems have become more complicated, more holistic measures that consider the origins and sources of pollutants have been called for. Industrial ecology is a field of science that forms a comprehensive framework for studying the interactions between the modern technological society and the environment. Industrial ecology considers humans and their technologies to be part of the natural environment, not separate from it. Industrial operations form natural systems that must also function as such within the constraints set by the biosphere. Industrial symbiosis (IS) is a central concept of industrial ecology. Industrial symbiosis studies look at the physical flows of materials and energy in local industrial systems. In an ideal IS, waste material and energy are exchanged by the actors of the system, thereby reducing the consumption of virgin material and energy inputs and the generation of waste and emissions. Companies are seen as part of the chains of suppliers and consumers that resemble those of natural ecosystems. The aim of this study was to analyse the environmental performance of an industrial symbiosis based on pulp and paper production, taking into account life cycle impacts as well. Life Cycle Assessment (LCA) is a tool for quantitatively and systematically evaluating the environmental aspects of a product, technology or service throughout its whole life cycle. Moreover, the Natural Step Sustainability Principles formed a conceptual framework for assessing the environmental performance of the case study symbiosis (Paper I). The environmental performance of the case study symbiosis was compared to four counterfactual reference scenarios in which the actors of the symbiosis operated on their own. The research methods used were process-based life cycle assessment (LCA) (Papers II and III) and hybrid LCA, which combines both process and input-output LCA (Paper IV). The results showed that the environmental impacts caused by the extraction and processing of the materials and the energy used by the symbiosis were considerable. If only the direct emissions and resource use of the symbiosis had been considered, less than half of the total environmental impacts of the system would have been taken into account. When the results were compared with the counterfactual reference scenarios, the net environmental impacts of the symbiosis were smaller than those of the reference scenarios. The reduction in environmental impacts was mainly due to changes in the way energy was produced. However, the results are sensitive to the way the reference scenarios are defined. LCA is a useful tool for assessing the overall environmental performance of industrial symbioses. It is recommended that in addition to the direct effects, the upstream impacts should be taken into account as well when assessing the environmental performance of industrial symbioses. Industrial symbiosis should be seen as part of the process of improving the environmental performance of a system. In some cases, it may be more efficient, from an environmental point of view, to focus on supply chain management instead.  

Development of radiosynthesis methods for 18F-labelled radiopharmaceuticals : General considerations and production of a dopamine transporter radioligand

Positron emission tomography (PET) is a molecular imaging technique that utilises radiopharmaceuticals (radiotracers) labelled with a positron-emitting radionuclide, such as fluorine-18 (18F). Development of a new radiotracer requires an appropriate radiosynthesis method: the most common of which with 18F is nucleophilic substitution with [18F]fluoride ion. The success of the labelling reaction is dependent on various factors such as the reactivity of [18F]fluoride, the structure of the target compound in addition to the chosen solvent. The overall radiosynthesis procedure must be optimised in terms of radiochemical yield and quality of the final product. Therefore, both quantitative and qualitative radioanalytical methods are essential in developing radiosynthesis methods. Furthermore, biological properties of the tracer candidate need to be evaluated by various pre-clinical studies in animal models. In this work, the feasibility of various nucleophilic 18F-fluorination strategies were studied and a labelling method for a novel radiotracer, N-3-[18F]fluoropropyl-2beta-carbomethoxy-3beta-4-fluorophenyl)nortropane ([18F]beta-CFT-FP), was optimised. The effect of solvent was studied by labelling a series of model compounds, 4-(R1-methyl)benzyl R2-benzoates. 18F-Fluorination reactions were carried out both in polar aprotic and protic solvents (tertiary alcohols). Assessment of the 18F-fluorinated products was studied by mass spectrometry (MS) in addition to conventional radiochromatographic methods, using radiosynthesis of 4-[18F]fluoro-N-[2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl-N-2-pyridinyl-benzamide (p-[18F]MPPF) as a model reaction. Labelling of [18F]beta-CFT-FP was studied using two 18F-fluoroalkylation reagents, [18F]fluoropropyl bromide and [18F]fluoropropyl tosylate, as well as by direct 18F-fluorination of sulfonate ester precursor. Subsequently, the suitability of [18F]beta-CFT-FP for imaging dopamine transporter (DAT) was evaluated by determining its biodistribution in rats. The results showed that protic solvents can be useful co-solvents in aliphatic 18F-fluorinations, especially in the labelling of sulfonate esters. Aromatic 18F-fluorination was not promoted in tert-alcohols. Sensitivity of the ion trap MS was sufficient for the qualitative analysis of the 18F-labelled products; p-[18F]MPPF was identified from the isolated product fraction with a mass-to-charge (m/z) ratio of 435 (i.e. protonated molecule [M+H]+). [18F]beta-CFT-FP was produced most efficiently via [18F]fluoropropyl tosylate, leading to sufficient radiochemical yield and specific radioactivity for PET studies. The ex vivo studies in rats showed fast kinetics as well as the specific uptake of [18F]beta-CFT-FP to the DAT rich brain regions. Thus, it was concluded that [18F]beta-CFT-FP has potential as a radiotracer for imaging DAT by PET.

Functional regulation of the Neurofibromatosis 2 tumor suppressor merlin

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder manifested by the formation of multiple benign tumors of the nervous system. Affected individuals typically develop bilateral vestibular schwannomas which lead to deafness and balance disorders. The syndrome is caused by inactivation of the NF2 tumor suppressor gene, and mutation or loss of the NF2 product, merlin, is sufficient for tumorigenesis in both hereditary and sporadic NF2-associated tumors. Merlin belongs to the band 4.1 superfamily of cytoskeletal proteins, which also contain the related ezrin, radixin, and moesin (ERM) proteins. The ERM members provide a link between the cell cytoskeleton and membrane by connecting membrane-associated proteins to actin filaments. By stabilizing complexes in the cell cortex, the ERMs modulate morphology, growth, and migration of cells. Despite their structural homology, overlapping subcellular distribution, direct molecular association, and partial overlap of molecular interactions, merlin and ezrin exert opposite effects on cell proliferation. Merlin suppresses cell proliferation, whereas ezrin expression is linked to oncogenic activity. We hypothesized that the regions which differ between the proteins might explain merlin s specificity as a tumor suppressor. We therefore analyzed the regions, which are most diverse between merlin and ezrin; the N-terminal tail and the C-terminus. To determine the properties of the C-terminal region, we studied the two most predominant merlin isoforms together with truncation variants similar to those found in patients. We also focused on the evolutionally conserved C-terminal residues, E545-E547, that harbor disease causing mutations in its corresponding DNA sequence. In addition to inhibiting cell proliferation, merlin regulates cytoskeletal organization. The morphogenic properties of merlin may play a role in tumor suppression, since patient-derived tumor cells demonstrate cytoskeletal abnormalities. We analyzed the mechanisms of merlin-induced extension formation and determined that the C-terminal region of amino acids 538-568 is particularly important for the morphogenic activity. We also characterized the role of C-terminal merlin residues in the regulation of proliferation, phosphorylation, and intramolecular associations. In contrast to previous reports, we demonstrated that both merlin isoforms are able to suppress cell proliferation, whereas C-terminally mutated merlin constructs showed reduced growth inhibition. Phosphorylation serves as a mechanism to regulate the tumor suppressive activity of merlin. The C-terminal serine 518 is phosphorylated in response to both p21-activated kinase (PAK) and protein kinase A (PKA), which inactivates the growth inhibitory function of merlin. However, at least three differentially phosphorylated forms of the protein exist. In this study we demonstrated that also the N-terminus of merlin is phosphorylated by AGC kinases, and that both PKA and Akt phosphorylate merlin at serine 10 (S10). We evaluated the impact of this N-terminal tail phosphorylation, and showed that the phosphorylation state of S10 is an important regulator of merlin s ability to modulate cytoskeletal organization but also regulates the stability of the protein. In summary, this study describes the functional effect of merlin specific regions. We demonstrate that both S10 in the N-terminal tail and residues E545-E547 in the C-terminus are essential for merlin activity and function.