Novel Mass Spectrometric Analysis Methods for Anabolic Androgenic Steroids in Sports Drug Testing

The feasibility of different modern analytical techniques for the mass spectrometric detection of anabolic androgenic steroids (AAS) in human urine was examined in order to enhance the prevalent analytics and to find reasonable strategies for effective sports drug testing. A comparative study of the sensitivity and specificity between gas chromatography (GC) combined with low (LRMS) and high resolution mass spectrometry (HRMS) in screening of AAS was carried out with four metabolites of methandienone. Measurements were done in selected ion monitoring mode with HRMS using a mass resolution of 5000. With HRMS the detection limits were considerably lower than with LRMS, enabling detection of steroids at low 0.2-0.5 ng/ml levels. However, also with HRMS, the biological background hampered the detection of some steroids. The applicability of liquid-phase microextraction (LPME) was studied with metabolites of fluoxymesterone, 4-chlorodehydromethyltestosterone, stanozolol and danazol. Factors affecting the extraction process were studied and a novel LPME method with in-fiber silylation was developed and validated for GC/MS analysis of the danazol metabolite. The method allowed precise, selective and sensitive analysis of the metabolite and enabled simultaneous filtration, extraction, enrichment and derivatization of the analyte from urine without any other steps in sample preparation. Liquid chromatographic/tandem mass spectrometric (LC/MS/MS) methods utilizing electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) were developed and applied for detection of oxandrolone and metabolites of stanozolol and 4-chlorodehydromethyltestosterone in urine. All methods exhibited high sensitivity and specificity. ESI showed, however, the best applicability, and a LC/ESI-MS/MS method for routine screening of nine 17-alkyl-substituted AAS was thus developed enabling fast and precise measurement of all analytes with detection limits below 2 ng/ml. The potential of chemometrics to resolve complex GC/MS data was demonstrated with samples prepared for AAS screening. Acquired full scan spectral data (m/z 40-700) were processed by the OSCAR algorithm (Optimization by Stepwise Constraints of Alternating Regression). The deconvolution process was able to dig out from a GC/MS run more than the double number of components as compared with the number of visible chromatographic peaks. Severely overlapping components, as well as components hidden in the chromatographic background could be isolated successfully. All studied techniques proved to be useful analytical tools to improve detection of AAS in urine. Superiority of different procedures is, however, compound-dependent and different techniques complement each other.

Medicines information sources and services for consumers : A special focus on the Internet and people with depression

The range of consumer health and medicines information sources has diversified along with the increased use of the Internet. This has led to a drive to develop medicines information services and to better incorporate the Internet and e-mail into routine practice in health care and in community pharmacies. To support the development of such services more information is needed about the use of online information by consumers, particularly of those who may be the most likely to use and to benefit from the new sources and modes of medicines communication. This study explored the role and utilization of the Internet-based medicines information and information services in the context of a wider network of information sources accessible to the public in Finland. The overall aim was to gather information to develop better and more accessible sources of information for consumers and services to better meet the needs of consumers. Special focus was on the needs and information behavior among people with depression and using antidepressant medicines. This study applied both qualitative and quantitative methods. Consumer medicines information needs and sources were identified by analyzing the utilization of the University Pharmacy operated national drug information call center (Study I) and surveying Finnish adults (n=2348) use of the different medicines information sources (Study II). The utilization of the Internet as a source of antidepressant information among people with depression was explored by focus group discussions among people with depression and with current or past use of the antidepressant(s) (n=29, Studies III & IV). Pharmacy response to the needs of consumers in term of providing e-mail counseling was assessed by conducting a virtual pseudo customer study among the Finnish community pharmacies (n=161, Study V). Physicians and pharmacists were the primary sources of medicines information. People with mental disorders were more frequent users of telephone- and Internet-based medicines information sources and patient information leaflets than people without mental disorders. These sources were used to complement rather than replace information provided face-to-face by health professionals. People with depression used the Internet to seek facts about antidepressants, to share experiences with peers, and for the curiosity. They described that the access to online drug information was empowering. Some people reported lacking the skills necessary to assess the quality of online information. E-mail medication counseling services provided by community pharmacies were rare and varied in quality. Study results suggest that rather than discouraging the use of the Internet, health professionals should direct patients to use accurate and reliable sources of online medicines information. Health care providers, including community pharmacies should also seek to develop new ways of communicating information about medicines with consumers. This study determined that people with depression and using antidepressants need services enabling interactive communication not only with health care professionals, but also with peers. Further research should be focused on developing medicines information service facilitating communication among different patient and consumer groups.

Japanese Video Game Localization : A Case Study of Sony's Sairen Series

This thesis is a comparative case study in Japanese video game localization for the video games Sairen, Sairen 2 and Sairen Nyûtoransurêshon, and English-language localized versions of the same games as published in Scandinavia and Australia/New Zealand. All games are developed by Sony Computer Entertainment Inc. and published exclusively for Playstation2 and Playstation3 consoles. The fictional world of the Sairen games draws much influence from Japanese history, as well as from popular and contemporary culture, and in doing so caters mainly to a Japanese audience. For localization, i.e. the adaptation of a product to make it accessible to users outside the original market it was intended for in the first place, this is a challenging issue. Video games are media of entertainment, and therefore localization practice must preserve the games’ effects on the players’ emotions. Further, video games are digital products that are comprised of a multitude of distinct elements, some of which are part of the game world, while others regulate the connection between the player as part of the real world and the game as digital medium. As a result, video game localization is also a practice that has to cope with the technical restrictions that are inherent to the medium. The main theory used throughout the thesis is Anthony Pym’s framework for localization studies that considers the user of the localized product as a defining part of the localization process. This concept presupposes that localization is an adaptation that is performed to make a product better suited for use during a specific reception situation. Pym also addresses the factor that certain products may resist distribution into certain reception situations because of their content, and that certain aspects of localization aim to reduce this resistance through significant alterations of the original product. While Pym developed his ideas with mainly regular software in mind, they can also be adapted well to study video games from a localization angle. Since modern video games are highly complex entities that often switch between interactive and non-interactive modes, Pym’s ideas are adapted throughout the thesis to suit the particular elements being studied. Instances analyzed in this thesis include menu screens, video clips, in-game action and websites. The main research questions focus on how the games’ rules influence localization, and how the games’ fictional domain influences localization. Because there are so many peculiarities inherent to the medium of the video game, other theories are introduced as well to complement the research at hand. These include Lawrence Venuti’s discussions of foreiginizing and domesticating translation methods for literary translation, and Jesper Juul’s definition of games. Additionally, knowledge gathered from interviews with video game localization professionals in Japan during September and October 2009 is also utilized for this study. Apart from answering the aforementioned research questions, one of this thesis’ aims is to enrich the still rather small field of game localization studies, and the study of Japanese video games in particular, one of Japan’s most successful cultural exports.

Zur Sättigung der Valenz in den Kleinen Meldungen des Typus Notiz : Eine pragmatisch fundierte Analyse

Valency Realization in Short Excerpts of News Text. A Pragmatics-funded analysis This dissertation is a study of the so-called pragmatic valency. The aim of the study is to examine the phenomenon both theoretically by discussing the research literature and empirically based on evidence from a text corpus consisting of 218 short excerpts of news text from the German newspaper Frankfurter Allgemeine Zeitung. In the theoretical part of the study, the central concepts of the valency and the pragmatic valency are discussed. In the research literature, the valency denotes the relation among the verb and its obligatory and optional complements. The pragmatic valency can be defined as modification of the so-called system valency in the parole, including non-realization of an obligatory complement, non- realization of an optional complement and realization of an optional complement. Furthermore, the investigation of the pragmatic valency includes the role of the adjuncts, elements that are not defined by the valency, in the concrete valency realization. The corpus study investigates the valency behaviour of German verbs in a corpus of about 1500 sentences combining the methodology and concepts of valency theory, semantics and text linguistics. The analysis is focused on the about 600 sentences which show deviations from the system valency, providing over 800 examples for the modification of the system valency as codified in the (valency) dictionaries. The study attempts to answer the following primary question: Why is the system valency modified in the parole? To answer the question, the concept of modification types is entered. The modification types are recognized using distinctive feature bundles in which each feature with a negative or a positive value refers to one reason for the modification treated in the research literature. For example, the features of irrelevance and relevance, focus, world and text type knowledge, text theme, theme-rheme structure and cohesive chains are applied. The valency approach appears in a new light when explored through corpus-based investigation; both the optionality of complements and the distinction between complements and adjuncts as defined in the present valency approach seem in some respects defective. Furthermore, the analysis indicates that the adjuncts outside the valency domain play a central role in the concrete realization of the valency. Finally, the study suggests a definition of pragmatic valency, based on the modification types introduced in the study and tested in the corpus analysis.

Mauwake reference grammar

This dissertation provides a synchronic grammatical description of Mauwake, a Papuan (Trans-New Guinea) language of about 2000 speakers on the North Coast of the Madang Province in Papua New Guinea. The theoretical background is that of Basic Linguistic Theory (BLT), used extensively in analysing and writing descriptive grammars. The chapters from morphology to clause level are described from form to function; in the later chapters the function is taken more often as the starting point. Any theory-specific terminology is kept to the minimum and formalisms have been avoided in accordance with BLT principles. Mauwake has a classic 5-vowel system and 14 consonant phonemes. With its simple phonology it is a typical representative of the Madang North Coast languages. For a Papuan language there are relatively few morphophonological alternations. Nouns are either alienably or inalienably possessed. There is no obligatory number marking in nouns or noun phrases. Pronouns have several different forms: five for case and three for other functions. The dative pronouns are treated as [+human] locatives, and they have also grammaticalised as possessives. The verbal morphology is agglutinative and mainly suffixal. Unusual features include two distributive suffixes, and the interaction of the derivational benefactive and the inflectional beneficiary suffixes. The applicative suffix has either transitivising or causative but not benefactive function. The switch-reference system distinguishes between simultaneous and sequential action, as well as same or different subject in relation to the following clause. There are several verbs denoting coming and going, and they may combine with one of three prefixes to indicate bringing and taking. Mauwake is a nominative-accusative type language, and the basic constituent order in a clause is SOV. Subject and object are the only syntactic arguments. There is no indirect object, but a clause can have two or even three objects. A nominalised clause with a finite verb functions as a relative clause or a complement clause; one with a nominalised verb has several different functions. Functional domains described include modality, negation, deixis, quantification, possession and comparison. As there are four negators, Mauwake has more variation in negative expressions than is usual in Papuan languages. Clause chaining is the preferred strategy for joining clauses into sentences, but coordination and subordination of finite clauses are also common. The form of a complement clause depends on whether it is of the fact, action or potential type. Tail-head linkage is used as a cohesive device between sentences. The discourse-level features described are topic and focus.

Getting value out of your sensory testing - the difference from control test

Non-parametric difference tests such as triangle and duo-trio tests traditionally are used to establish differences or similarities between products. However they only supply the researcher with partial answers and often further testing is required to establish the nature, size and direction of differences. This paper looks at the advantages of the difference from control (DFC) test (also known as degree of difference test) and discusses appropriate applications of the test. The scope and principle of the test, panel composition and analysis of results are presented with the aid of suitable examples. Two of the major uses of the DFC test are in quality control and shelf-life testing. The role DFC takes in these areas and the use of other tests to complement the testing is discussed. Controls or standards are important in both these areas and the use of standard products, mental and written standards and blind controls are highlighted. The DFC test has applications in products where the duo-trio and triangle tests cannot be used because of the normal heterogeneity of the product. While the DFC test is a simple difference test it can be structured to give the researcher more valuable data and scope to make informed decisions about their product.

Hantzsch 1,4-dihydropyridine esters and analogs: candidates for generating reproducible one-dimensional packing motifs

Examination of the symmetric Hantzsch 1,4-dihydropyridine ester derivatives of the prototypical nifedipine molecule indicates the tendency of this class of molecule to form a common packing motif. Crystal structure analysis of 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic diesters and analogs reveals that they form extended chains, characterized as the C(6) packing motif, via intermolecular (amine) N-H...O=C (C3,C5 carbonyl) hydrogen bonds. In addition, all the prepared derivatives also satisfy the basic structural requirements for their high binding efficiency to the receptor. The reproducible C(6) packing motif observed among these compounds has a use in the design of solid-state materials.

Changes in Beer Labels and their Meaning : A Holistic Approach to the Semiosic Process

The purpose of this study is to find a framework for a holistic approach to, and form a conceptual toolbox for, investigating changes in signs and in their interpretation. Charles S. Peirce s theory of signs in a communicative perspective is taken as a basis for the framework. The concern directing the study is the problem of a missing framework in analysing signs of visual artefacts from a holistic perspective as well as that of the missing conceptual tools. To discover the possibility of such a holistic approach to semiosic processes and to form a conceptual toolbox the following issues are discussed: i) how the many Objects with two aspects involved in Peirce s definition of sign-action, promote multiple semiosis arising from the same sign by the same Interpretant depending on the domination of the Objects; ii) in which way can the relation of the individual and society or group be made more apparent in the construction of the self since this construction is intertwined with the process of meaning-creation and interpretation; iii) how to account for the fundamental role of emotions in semiosis, and the relation of emotions with the often neglected topic of embodiment; iv) how to take into account the dynamic, mediating and processual nature of sign-action in analysing and understanding the changes in signs and in the interpretation of signs. An interdisciplinary approach is chosen for this dissertation. Concepts that developed within social psychology, developmental psychology, neurosciences and semiotics, are discussed. The common aspect of the approaches is that they in one way or another concentrate on mediation provided by signs in explaining human activity and cognition. The holistic approach and conceptual toolbox found are employed in a case study. This consists of an analysis of beer brands including a comparison of brands from two different cultures. It becomes clear that different theories and approaches have mutual affinities and do complement each other. In addition, the affinities in different disciplines somewhat provide credence to the various views. From the combined approach described, it becomes apparent that by the semiosic process, the emerging semiotic self intertwined with the Umwelt, including emotions, can be described. Seeing the interpretation and meaning-making through semiosis allows for the analysis of groups, taking into account the embodied and emotional component. It is concluded that emotions have a crucial role in all human activity, including so-called reflective thinking, and that emotions and embodiment should be consciously taken into account in analysing signs, the interpretation, and in changes of signs and interpretations from both the social and individual level. The analysis of the beer labels expresses well the intertwined nature of the relationship between signs, individual consumers and society. Many direct influences from society on the label design are found, and also some indirect attitude changes that become apparent from magazines, company reports, etc. In addition, the analysis brings up the issues of the unifying tendency of the visual artefacts of different cultures, but also demonstrates that the visual artefacts are able to hold the local signs and meanings, and sometimes are able to represent the local meanings although the signs have changed in the unifying process.

Connections not boundaries: Future learning and physical spaces

In the developed world, we feel the effects of "digital disruption" in our experiences of the spaces of retail, hospitality, entertainment, finance, arts and culture, and even healthcare. This disruption can take many forms: augmentation of physical experience with a digital complement such as the use of a bespoke mobile application to navigate an art museum, ordering food on digital tablets in a restaurant, recording our health data to share with a doctor. We also rate and review our experiences of a wide range of services and share these opinions with diverse others via the social web.

Stabilization of the Alleged 'Bishomoaromatic' Bicyclo[3.2.l]octa-2,6-dienyl Anion by Counterion Interactions and by Hyperconjugation

Hyperconjugation and inductive effects, rather than homoaromaticity, are responsible for the stabilization of the title anion in the gas phase; interaction of the double bond with the Li+ gegenion in the endo geometry contributes additionally in solution.

Development of a stable isotope index to assess decadal-scale vegetation change and application to woodlands of the Burdekin catchment, Australia

Forty-four study sites were established in remnant woodland in the Burdekin River catchment in tropical north-east Queensland, Australia, to assess recent (decadal) vegetation change. The aim of this study was further to evaluate whether wide-scale vegetation 'thickening' (proliferation of woody plants in formerly more open woodlands) had occurred during the last century, coinciding with significant changes in land management. Soil samples from several depth intervals were size separated into different soil organic carbon (SOC) fractions, which differed from one another by chemical composition and turnover times. Tropical (C4) grasses dominate in the Burdekin catchment, and thus δ13C analyses of SOC fractions with different turnover times can be used to assess whether the relative proportion of trees (C3) and grasses (C4) had changed over time. However, a method was required to permit standardized assessment of the δ13C data for the individual sites within the 13 Mha catchment, which varied in soil and vegetation characteristics. Thus, an index was developed using data from three detailed study sites and global literature to standardize individual isotopic data from different soil depths and SOC fractions to reflect only the changed proportion of trees (C3) to grasses (C3) over decadal timescales. When applied to the 44 individual sites distributed throughout the Burdekin catchment, 64% of the sites were shown to have experienced decadal vegetation thickening, while 29% had remained stable and the remaining 7% had thinned. Thus, the development of this index enabled regional scale assessment and comparison of decadal vegetation patterns without having to rely on prior knowledge of vegetation changes or aerial photography.

The three faces of Maxwell�s equations

In dealing with electromagnetic phenomena and in particular the phenomena of optics, despite the recognition of the quanta of light people tend to talk of the amplitudes and field strengths, as if the electromagnetic field were a classical field. For example we measure the wavelength of light by studying interference fringes. In this paper we study the inter-relationship of three ways of looking at the problem: in terms of classical wave fields, wave function of the photon; and the quantized wave field. The comparison and contrasts of these three modes of description are carefully analyzed in this paper. The ways in which these different modes complement our intuition and insight are also discussed.

A liquid biopsy for head and neck cancers

Head and neck cancer patients often present with advanced metastatic disease resulting in a poor 5-year survival. Therefore, there is a need for non-invasive diagnostic tools that could complement conventional imaging to inform clinicians of patient outcomes and treatment responses. A liquid biopsy addresses this unmet clinical need; a simple peripheral blood draw could provide information about the disseminated disease in terms of circulating tumor cells and circulating tumor DNA. Moreover, detectable tumor DNA in the saliva of head and neck cancer patients could signify the early signs of the disease and present an opportunity for clinical intervention. This review provides an overview of the current literature with regard to the feasibility of such a test in the head and neck cancer field and highlights the need for such a test.

Effect of Structural Modification on the Quantum-Size Effect in II-VI Semiconducting Nanocrystals

The electronic structure of group II-VI semiconductors in the stable wurtzite form is analyzed using state-of-the-art ab initio approaches to extract a simple and chemically transparent tight-binding model. This model can be used to understand the variation in the bandgap with size, for nanoclusters of these compounds. Results complement similar information already available for same systems in the zinc blende structure. A comparison with all available experimental data on quantum size effects in group II-VI semiconductor nanoclusters establishes a remarkable agreement between theory and experiment in both structure types, thereby verifying the predictive ability of our approach. The significant dependence of the quantum size effect on the structure type suggests that the experimental bandgap change at a given size compared to the bulk bandgap, may be used to indicate the structural form of the nanoclusters, particularly in the small size limit, where broadening of diffraction features often make it difficult to unambiguously determine the structure.

Decoration of Pasteurella multocida lipopolysaccharide with phosphocholine is important for virulence

Phosphocholine (PCho) is an important substituent of surface structures expressed by a number of bacterial pathogens. Its role in virulence has been investigated in several species, in which it has been shown to play a role in bacterial adhesion to mucosal surfaces, in resistance to antimicrobial peptides, or in sensitivity to complement-mediated killing. The lipopolysaccharide (LPS) structure of Pasteurella multocida strain Pm70, whose genome sequence is known, has recently been determined and does not contain PCho. However, LPS structures from the closely related, virulent P. multocida strains VP161 and X-73 were shown to contain PCho on their terminal galactose sugar residues. To determine if PCho was involved in the virulence of P. multocida, we used subtractive hybridization of the VP161 genome against the Pm70 genome to identify a four-gene locus (designated pcgDABC) which we show is required for the addition of the PCho residues to LPS. The proteins predicted to be encoded by pcgABC showed identity to proteins involved in choline uptake, phosphorylation, and nucleotide sugar activation of PCho. We constructed a P. multocida VP161 pcgC mutant and demonstrated that this strain produces LPS that lacks PCho on the terminal galactose residues. This pcgC mutant displayed reduced in vivo growth in a chicken infection model and was more sensitive to the chicken antimicrobial peptide fowlicidin-1 than the wild-type P. multocida strain