Computational studies on new chemical species in the gas-phase and the solid-state.

There is intense activity in the area of theoretical chemistry of gold. It is now possible to predict new molecular species, and more recently, solids by combining relativistic methodology with isoelectronic thinking. In this thesis we predict a series of solid sheet-type crystals for Group-11 cyanides, MCN (M=Cu, Ag, Au), and Group-2 and 12 carbides MC2 (M=Be-Ba, Zn-Hg). The idea of sheets is then extended to nanostrips which can be bent to nanorings. The bending energies and deformation frequencies can be systematized by treating these molecules as an elastic bodies. In these species Au atoms act as an 'intermolecular glue'. Further suggested molecular species are the new uncongested aurocarbons, and the neutral Au_nHg_m clusters. Many of the suggested species are expected to be stabilized by aurophilic interactions. We also estimate the MP2 basis-set limit of the aurophilicity for the model compounds [ClAuPH_3]_2 and [P(AuPH_3)_4]^+. Beside investigating the size of the basis-set applied, our research confirms that the 19-VE TZVP+2f level, used a decade ago, already produced 74 % of the present aurophilic attraction energy for the [ClAuPH_3]_2 dimer. Likewise we verify the preferred C4v structure for the [P(AuPH_3)_4]^+ cation at the MP2 level. We also perform the first calculation on model aurophilic systems using the SCS-MP2 method and compare the results to high-accuracy CCSD(T) ones. The recently obtained high-resolution microwave spectra on MCN molecules (M=Cu, Ag, Au) provide an excellent testing ground for quantum chemistry. MP2 or CCSD(T) calculations, correlating all 19 valence electrons of Au and including BSSE and SO corrections, are able to give bond lengths to 0.6 pm, or better. Our calculated vibrational frequencies are expected to be better than the currently available experimental estimates. Qualitative evidence for multiple Au-C bonding in triatomic AuCN is also found.

Regional Integration and the State : The Changing Nature of Sovereignty in Southern Africa and Europe

The study explores the role of the state in regional integration processes. The question is approached through theoretical discussion and two case-studies - SADC (Southern African Development Community) and the EU. The main research question of the study is, what are the possibilities and problems of the integration process in Southern Africa and how do they differ from the possibilities and problems of the integration process in Europe. The undelrying question of the study is why do states decide to participate in an integration process where they have to limit their sovereignty. Review of the theoretical discussion of the integration studies shows that the integration process is affected by several factors on different levels of the international system. But the state plays a central role in integration processes - integration processes are inititated and carried on by the participatig states. The European integration process shows that the interests of the state can change over time. At the beginning of the integration process, the objective was to strengthen participating states. Later EU member states have decided that it is in their interest to deepen the process even if it has meant limitation of their sovereignty. The determinant factor has been that the member states have considered it to be in their interst to deepen the process. In Southern Africa the integration process is only at the beginning. SADC aims to establish a free trade area by 2008. The biggest challenge is how to implement the integration process so that it benefits all member states in a region that is economically dominated by South Africa. In practice this can be achieved through establishment of corrective mechanisms, which ensure equitable distribution of benefits. This would require deeper integration and South Africa to adapt responsibility towards its regional partners. African integration processes in general have not been as successful as for example the EU. African states have been reluctant to limit their sovereignty in favour of regional organisations.This can be explained by the differences between European and African states. The EU member states have been democracies while African states have been characterised by concentration of power in the executive branch. Furthermore the political systems in Africa have been characterised by vertical clientelist reltionships. As a result it has not been in the interest of the political elite to limit the state sovereignty in favour of regional organisations. In recent years SADC has been relatively succesful in its integration process and reforms, but a lot remains to be done before the implementation of the free trade area can be succesful. The institutional structure and treaties of SADC differ from the structures of the EU. Member states are the main actors of the integration processes. Their differences are reflected in the process and produce different kinds of integration in different parts of the world.

Search for WW and WZ production in lepton plus jets final state at CDF

We present a search for WW and WZ production in final states that contain a charged lepton (electron or muon) and at least two jets, produced in sqrt(s) = 1.96 TeV ppbar collisions at the Fermilab Tevatron, using data corresponding to 1.2 fb-1 of integrated luminosity collected with the CDF II detector. Diboson production in this decay channel has yet to be observed at hadron colliders due to the large single W plus jets background. An artificial neural network has been developed to increase signal sensitivity, as compared with an event selection based on conventional cuts. We set a 95% confidence level upper limit of sigma_{WW}* BR(W->lnu,W->jets)+ sigma_{WZ}*BR(W->lnu,Z->jets)

Search for the Higgs boson in the all-hadronic final state using the CDF II detector

We report on a search for the production of the Higgs boson decaying to two bottom quarks accompanied by two additional quarks. The data sample used corresponds to an integrated luminosity of approximately 4  fb-1 of pp̅ collisions at √s=1.96  TeV recorded by the CDF II experiment. This search includes twice the integrated luminosity of the previous published result, uses analysis techniques to distinguish jets originating from light flavor quarks and those from gluon radiation, and adds sensitivity to a Higgs boson produced by vector boson fusion. We find no evidence of the Higgs boson and place limits on the Higgs boson production cross section for Higgs boson masses between 100  GeV/c2 and 150  GeV/c2 at the 95% confidence level. For a Higgs boson mass of 120  GeV/c2, the observed (expected) limit is 10.5 (20.0) times the predicted standard model cross section.

Understanding solid-state transformations during dehydration: new insights using vibrational spectroscopy and multivariate modelling

Many active pharmaceutical ingredients (APIs) have both anhydrate and hydrate forms. Due to the different physicochemical properties of solid forms, the changes in solid-state may result in therapeutic, pharmaceutical, legal and commercial problems. In order to obtain good solid dosage form quality and performance, there is a constant need to understand and control these phase transitions during manufacturing and storage. Thus it is important to detect and also quantify the possible transitions between the different forms. In recent years, vibrational spectroscopy has become an increasingly popular tool to characterise the solid-state forms and their phase transitions. It offers several advantages over other characterisation techniques including an ability to obtain molecular level information, minimal sample preparation, and the possibility of monitoring changes non-destructively in-line. Dehydration is the phase transition of hydrates which is frequently encountered during the dosage form production and storage. The aim of the present thesis was to investigate the dehydration behaviour of diverse pharmaceutical hydrates by near infrared (NIR), Raman and terahertz pulsed spectroscopic (TPS) monitoring together with multivariate data analysis. The goal was to reveal new perspectives for investigation of the dehydration at the molecular level. Solid-state transformations were monitored during dehydration of diverse hydrates on hot-stage. The results obtained from qualitative experiments were used to develop a method and perform the quantification of the solid-state forms during process induced dehydration in a fluidised bed dryer. Both in situ and in-line process monitoring and quantification was performed. This thesis demonstrated the utility of vibrational spectroscopy techniques and multivariate modelling to monitor and investigate dehydration behaviour in situ and during fluidised bed drying. All three spectroscopic methods proved complementary in the study of dehydration. NIR spectroscopy models could quantify the solid-state forms in the binary system, but were unable to quantify all the forms in the quaternary system. Raman spectroscopy models on the other hand could quantify all four solid-state forms that appeared upon isothermal dehydration. The speed of spectroscopic methods makes them applicable for monitoring dehydration and the quantification of multiple forms was performed during phase transition. Thus the solid-state structure information at the molecular level was directly obtained. TPS detected the intermolecular phonon modes and Raman spectroscopy detected mostly the changes in intramolecular vibrations. Both techniques revealed information about the crystal structure changes. NIR spectroscopy, on the other hand was more sensitive to water content and hydrogen bonding environment of water molecules. This study provides a basis for real time process monitoring using vibrational spectroscopy during pharmaceutical manufacturing.

Contributions to the Theory of Finite-State Based Grammars

This dissertation is a theoretical study of finite-state based grammars used in natural language processing. The study is concerned with certain varieties of finite-state intersection grammars (FSIG) whose parsers define regular relations between surface strings and annotated surface strings. The study focuses on the following three aspects of FSIGs: (i) Computational complexity of grammars under limiting parameters In the study, the computational complexity in practical natural language processing is approached through performance-motivated parameters on structural complexity. Each parameter splits some grammars in the Chomsky hierarchy into an infinite set of subset approximations. When the approximations are regular, they seem to fall into the logarithmic-time hierarchyand the dot-depth hierarchy of star-free regular languages. This theoretical result is important and possibly relevant to grammar induction. (ii) Linguistically applicable structural representations Related to the linguistically applicable representations of syntactic entities, the study contains new bracketing schemes that cope with dependency links, left- and right branching, crossing dependencies and spurious ambiguity. New grammar representations that resemble the Chomsky-Schützenberger representation of context-free languages are presented in the study, and they include, in particular, representations for mildly context-sensitive non-projective dependency grammars whose performance-motivated approximations are linear time parseable. (iii) Compilation and simplification of linguistic constraints Efficient compilation methods for certain regular operations such as generalized restriction are presented. These include an elegant algorithm that has already been adopted as the approach in a proprietary finite-state tool. In addition to the compilation methods, an approach to on-the-fly simplifications of finite-state representations for parse forests is sketched. These findings are tightly coupled with each other under the theme of locality. I argue that the findings help us to develop better, linguistically oriented formalisms for finite-state parsing and to develop more efficient parsers for natural language processing. Avainsanat: syntactic parsing, finite-state automata, dependency grammar, first-order logic, linguistic performance, star-free regular approximations, mildly context-sensitive grammars

Sairaanhoitajaksi kasvattaminen : Sairaanhoitajakoulutus ja siinä käytetyt oppikirjat Suomessa vuoteen 1967 asti

The historical development of Finnish nursing textbooks from the late 1880s to 1967: the training of nurses in the Foucauldian perspective. This study aims, first, to analyse the historical development of Finnish nursing textbooks in the training of nurses and in nursing education: what Foucauldian power processes operate in the writing and publishing processes? What picture of nursing did early nursing books portray and who were the decision makers? Second, this study also aims to analyse the processes of power in nurse training processes. The time frame extends from the early stages of nurse training in the late 1880s to 1967. This present study is a part of textbook research and of the history of professional education in Finland. This study seeks to explain how, who or what contributed the power processes involved in the writing of nursing textbooks and through textbooks. Did someone use these books as a tool to influence nursing education? The third aim of this study is to define and analyse the purpose of nurse training. Michel Foucault´s concept of power served as an explanatory framework for this study. A very central part of power is the assembling of data, the supplying of information and messages, and the creation of discourses. When applied to the training of nurses, power dictates what information is taught in the training and contained in the books. Thus, the textbook holds an influential position as a power user in these processes. Other processes in which such power is exercised include school discipline and all other normalizing processes. One of most powerful ways of adapting is the hall of residence, where nursing pupils were required to live. Trained nurses desired to separate themselves from their untrained predecessors and from those with less training by wearing different uniforms and living in separate housing units. The state supported the registration of trained nurses by legislation. With this decision the state made it illegal to work as a nurse without an authorised education, and use these regulations to limit and confirm the professional knowledge and power of nurses. Nurses, physicians and government authorities used textbooks in nursing education as tools to achieve their own purposes and principles. With these books all three groups attempted to confirm their own professional power and knowledge while at the same time limit the power and expertise of others. Public authorities sought to unify the training of nurses and the basis of knowledge in all nursing schools in Finland with similar and obligatory textbooks. This standardisation started 20 years before the government unified nursing training in 1930. The textbooks also served as data assemblers in unifying nursing practices in Finnish hospitals, because the Medical Board required all training hospitals to attach the textbooks to units with nursing pupils. For the nurses, and especially for the associations of Finnish nurses, making and publishing their own textbooks for the training of nurses was a part of their professional projects. With these textbooks, the nursing elite and the teachers tended to prepare nursing pupils’ identities for nursing’s very special mission. From the 1960s, nursing was no longer understood as a mission, but as a normal vocation. Nurses and doctors disputed this view throughout the period studied, which was the optimal relationship between theory and practice in nursing textbooks and in nurse education. The discussion of medical knowledge in nursing textbooks took place in the 1930s and 1940s. Nurses were very confused about their own professional knowledge and expertise, which explains why they could not create a new nursing textbook despite the urgency. A brand new nursing textbook was published in 1967, about 30 years after the predecessor. Keyword: nurse, nurse training, nursing education, power, textbook, Michel Foucault

Markers of systemic inflammation in diagnostics and in prediction of outcome of community-acquired infection

Sepsis is associated with a systemic inflammatory response. It is characterised by an early proinflammatory response and followed by a state of immunosuppression. In order to improve the outcome of patients with infection and sepsis, novel therapies that influence the systemic inflammatory response are being developed and utilised. Thus, an accurate and early diagnosis of infection and evaluation of immune state are crucial. In this thesis, various markers of systemic inflammation were studied with respect to enhancing the diagnostics of infection and of predicting outcome in patients with suspected community-acquired infection. A total of 1092 acutely ill patients admitted to a university hospital medical emergency department were evaluated, and 531 patients with a suspicion of community-acquired infection were included for the analysis. Markers of systemic inflammation were determined from a blood sample obtained simultaneously with a blood culture sample on admission to hospital. Levels of phagocyte CD11b/CD18 and CD14 expression were measured by whole blood flow cytometry. Concentrations of soluble CD14, interleukin (IL)-8, and soluble IL-2 receptor α (sIL-2Rα) were determined by ELISA, those of sIL-2R, IL-6, and IL-8 by a chemiluminescent immunoassay, that of procalcitonin by immunoluminometric assay, and that of C-reactive protein by immunoturbidimetric assay. Clinical data were collected retrospectively from the medical records. No marker of systemic inflammation, neither CRP, PCT, IL-6, IL-8, nor sIL-2R predicted bacteraemia better than did the clinical signs of infection, i.e., the presence of infectious focus or fever or both. IL-6 and PCT had the highest positive likelihood ratios to identify patients with hidden community-acquired infection. However, the use of a single marker failed to detect all patients with infection. A combination of markers including a fast-responding reactant (CD11b expression), a later-peaking reactant (CRP), and a reactant originating from inflamed tissues (IL-8) detected all patients with infection. The majority of patients (86.5%) with possible but not verified infection showed levels exceeding at least one cut-off limit of combination, supporting the view that infection was the cause of their acute illness. The 28-day mortality of patients with community-acquired infection was low (3.4%). On admission to hospital, the low expression of cell-associated lipopolysaccharide receptor CD14 (mCD14) was predictive for 28-day mortality. In the patients with severe forms of community-acquired infection, namely pneumonia and sepsis, high levels of soluble CD14 alone did not predict mortality, but a high sCD14 level measured simultaneously with a low mCD14 raised the possibility of poor prognosis. In conclusion, to further enhance the diagnostics of hidden community-acquired infection, a combination of inflammatory markers is useful; 28-day mortality is associated with low levels of mCD14 expression at an early phase of the disease.

Aspects and Applications of Pulse Sequence Design for Solution-State Nuclear Magnetic Resonance Spectroscopy

NMR spectroscopy enables the study of biomolecules from peptides and carbohydrates to proteins at atomic resolution. The technique uniquely allows for structure determination of molecules in solution-state. It also gives insights into dynamics and intermolecular interactions important for determining biological function. Detailed molecular information is entangled in the nuclear spin states. The information can be extracted by pulse sequences designed to measure the desired molecular parameters. Advancement of pulse sequence methodology therefore plays a key role in the development of biomolecular NMR spectroscopy. A range of novel pulse sequences for solution-state NMR spectroscopy are presented in this thesis. The pulse sequences are described in relation to the molecular information they provide. The pulse sequence experiments represent several advances in NMR spectroscopy with particular emphasis on applications for proteins. Some of the novel methods are focusing on methyl-containing amino acids which are pivotal for structure determination. Methyl-specific assignment schemes are introduced for increasing the size range of 13C,15N labeled proteins amenable to structure determination without resolving to more elaborate labeling schemes. Furthermore, cost-effective means are presented for monitoring amide and methyl correlations simultaneously. Residual dipolar couplings can be applied for structure refinement as well as for studying dynamics. Accurate methods for measuring residual dipolar couplings in small proteins are devised along with special techniques applicable when proteins require high pH or high temperature solvent conditions. Finally, a new technique is demonstrated to diminish strong-coupling induced artifacts in HMBC, a routine experiment for establishing long-range correlations in unlabeled molecules. The presented experiments facilitate structural studies of biomolecules by NMR spectroscopy.

From Francovich to Köbler and beyond : The evolution of a State liability regime for the EC

The aim of this paper is to present the evolution of the Francovich doctrine within the European legal order. The first part deals with the gradual development of the ECJ's case law on State liability in damages for breach of EC law. Starting from the seminal Francovich and Brasserie du Pêcheur, the clarification of the criteria set by the Court is attempted with reference to subsequent case law, whereas issues concerning the extent and form of the compensation owned are also mentioned. The second part concerns one of the more recent developments in the field, namely State liability for breaches of Community law attributed to national judiciary. The Court's ruling in Köbler is examined in connection with two other recent judgments, namely Commission v. Italy of 2003 and Kühne & Heitz, as an attempt of the ECJ to reframe its relationships with national supreme courts and appropriate for itself the position of the Supreme Court in the European legal order. The implications on State liability claims by the ruling in Commission v. France of 1997 constitute the theme of the third part, where it is submitted that Member States can also be held liable for disregard of Community law by private individuals within their respected territories. To this extent, Schmidberger is viewed as a manifestation of this opinion, with fundamental rights acquiring a new dimension, being invoked by the States, contra the individuals as a shield to liability claims. Finally, the third part examines the relationship between the Francovich doctrine and the principle of legal certainty and concludes that the solutions employed by the ECJ have been both predictable and acceptable by the national legal orders. Keywords: State liability, damages, Francovich, Köbler, Schmidberger