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

Characterization of cytokines, matrix metalloproteinases and toll-like receptors in human periodontal tissue destruction

Periodontal Disease affects the supporting structures of the teeth and is initiated by a microbial biofilm called dental plaque. Severity ranges from superficial inflammation of the gingiva (gingivitis) to extensive destruction of connective tissue and bone leading to tooth loss (periodontitis). In periodontitis the destruction of tissue is caused by a cascade of microbial and host factors together with proteolytic enzymes. Matrix metalloproteinases (MMPs) are known to be central mediators of the pathologic destruction in periodontitis. Initially plaque bacteria provide pathogen-associated molecular patterns (PAMPs) which are sensed by Toll-like receptors (TLRs), and initiate intracellular signaling cascades leading to host inflammation. Our aim was to characterize TNF-α (tumor necrosis factor-alpha) and its type I and II receptors in periodontal tissues, as well as, the effects of TNF-α, IL-1β (interleukin-1beta) and IL-17 on the production and/or activation of MMP-3, MMP-8 and MMP-9. Furthermore we mapped the TLRs in periodontal tissues and assessed how some of the PAMPs binding to the key TLRs found in periodontal tissues affect production of TNF-α and IL-1β by gingival epithelial cells with or without combination of IL-17. TNF-α and its receptors were detected in pericoronitis. Furthermore, increased expression of interleukin-1β and vascular cell adhesion molecule-1 was found as a biological indicator of TNF-α ligand-receptor interaction. MMP-3, -8, and 9 were investigated in periodontitis affected human gingival crevicular fluid and gingival fibroblasts produced pro-MMP-3. Following that, the effect of IL-17 was studied on MMP and pro-inflammatory cytokine production. IL-17 was increased in periodontitis and up-regulated IL-1β, TNF-α, MMP-1 and MMP-3. We continued by demonstrating TLRs in gingival tissues, in which significant differences between patients with periodontitis and healthy controls were found. Finally, enzyme-linked immunosorbent assays were performed to show that the gingival cells response to inflammatory responses in a TLR-dependent manner. Briefly, this thesis demonstrates that TLRs are present in periodontal tissues and present differences in periodontitis compared to healthy controls. The cells of gingival tissues respond to inflammatory process in a TLR-dependent manner by producing pro-inflammatory cytokines. During the destruction of periodontal tissues, the release (IL-1β and TNF-α) and co-operation with other pro-inflammatory cytokines (IL-17), which in turn increase the inflammation and thus be more harmful to the host with the increased presence of MMPs (MMP-1, MMP-3, MMP-8, MMP-9) in diseased over healthy sites.

NMR Spectroscopy of Multi-domain Proteins : Immunoglobulin-like Domains of Human Filamin A

Proteins are complex biomacromolecules playing fundamental roles in the physiological processes of all living organisms. They function as structural units, enzymes, transporters, process regulators, and signal transducers. Defects in protein functions often derive from genetic mutations altering the protein structure, and impairment of essential protein functions manifests itself as pathological conditions. Proteins operate through interactions, and all protein functions depend on protein structure. In order to understand biological mechanisms at the molecular level, one has to know the structures of the proteins involved. This thesis covers structural and functional characterization of human filamins. Filamins are actin-binding and -bundling proteins that have numerous interaction partners. In addition to their actin-organizing functions, filamins are also known to have roles in cell adhesion and locomotion, and to participate in the logistics of cell membrane receptors, and in the coordination of intracellular signaling pathways. Filamin mutations in humans induce severe pathological conditions affecting the brain, bones, limbs, and the cardiovascular system. Filamins are large modular proteins composed of an N-terminal actin-binding domain and 24 consecutive immunoglobulin-like domains (IgFLNs). Nuclear magnetic resonance (NMR) spectroscopy is a versatile method of gaining insight into protein structure, dynamics and interactions. NMR spectroscopy was employed in this thesis to study the atomic structure and interaction mechanisms of C-terminal IgFLNs, which are known to house the majority of the filamin interaction sites. The structures of IgFLN single-domains 17 and 23 and IgFLN domain pairs 16-17 and 18-19 were determined using NMR spectroscopy. The structures of domain pairs 16 17 and 18 19 both revealed novel domain domain interaction modes of IgFLNs. NMR titrations were employed to characterize the interactions of filamins with glycoprotein Ibα, FilGAP, integrin β7 and dopamine receptors. Domain packing of IgFLN domain sextet 16 21 was further characterized using residual dipolar couplings and NMR relaxation analysis. This thesis demonstrates the versatility and potential of NMR spectroscopy in structural and functional studies of multi-domain proteins.

The kinetics and reactivity of several polyatomic free radicals in reactions with NO2, O2, Cl2, and HCl

In this thesis, the kinetics of several alkyl, halogenated alkyl, and alkenyl free radical reactions with NO2, O2, Cl2, and HCl reactants were studied over a wide temperature range in time resolved conditions. Laser photolysis photoionisation mass spectrometer coupled to a flow reactor was the experimental method employed and this thesis present the first measurements performed with the experimental system constructed. During this thesis a great amount of work was devoted to the designing, building, testing, and improving the experimental apparatus. Carbon-centred free radicals were generated by the pulsed 193 or 248 nm photolysis of suitable precursors along the tubular reactor. The kinetics was studied under pseudo-first-order conditions using either He or N2 buffer gas. The temperature and pressure ranges employed were between 190 and 500 K, and 0.5 45 torr, respectively. The possible role of heterogeneous wall reactions was investigated employing reactor tubes with different sizes, i.e. to significantly vary the surface to volume ratio. In this thesis, significant new contributions to the kinetics of carbon-centred free radical reactions with nitrogen dioxide were obtained. Altogether eight substituted alkyl (CH2Cl, CHCl2, CCl3, CH2I, CH2Br, CHBr2, CHBrCl, and CHBrCH3) and two alkenyl (C2H3, C3H3) free radical reactions with NO2 were investigated as a function of temperature. The bimolecular rate coefficients of all these reactions were observed to possess negative temperature dependencies, while pressure dependencies were not noticed for any of these reactions. Halogen substitution was observed to moderately reduce the reactivity of substituted alkyl radicals in the reaction with NO2, while the resonance stabilisation of the alkenyl radical lowers its reactivity with respect to NO2 only slightly. Two reactions relevant to atmospheric chemistry, CH2Br + O2 and CH2I + O2, were also investigated. It was noticed that while CH2Br + O2 reaction shows pronounced pressure dependence, characteristic of peroxy radical formation, no such dependence was observed for the CH2I + O2 reaction. Observed primary products of the CH2I + O2 reaction were the I-atom and the IO radical. Kinetics of CH3 + HCl, CD3 + HCl, CH3 + DCl, and CD3 + DCl reactions were also studied. While all these reactions possess positive activation energies, in contrast to the other systems investigated in this thesis, the CH3 + HCl and CD3 + HCl reactions show a non-linear temperature dependency on the Arrhenius plot. The reactivity of substituted methyl radicals toward NO2 was observed to increase with decreasing electron affinity of the radical. The same trend was observed for the reactions of substituted methyl radicals with Cl2. It is proposed that interactions of frontier orbitals are responsible to these observations and Frontier Orbital Theory could be used to explain the observed reactivity trends of these highly exothermic reactions having reactant-like transition states.

A Soul for Europe? : Contributions of European Churches to the Forum of the Convention on the Future of Europe

The aim of this research was to study how European churches contributed to the shaping of the Constitutional Treaty during the work of the Convention on the future of Europe through the public discussion forum, established by the Convention for this specific purpose in the years 2002 2003. In particular, this study sought to uncover the areas of interest brought up by the churches in their contributions, the objectives they pursued, and the approaches and arguments they employed to reach those objectives. The data for this study comprised all official submissions by European churches and church alliances to the Forum, totalling 21 contributions. A central criterion for inclusion of the data was that the organization can reasonably be assumed to represent the official position of one or more Christian churches within the European Union before the 2004 expansion. The contributing churches and organizations represent the vast majority of Christians in Europe. The data was analyzed using primarily qualitative content analysis. The research approach was a combination of abductive and inductive inference. Based on the analysis a two-fold theoretical framework was adopted, focusing on theories of public religion, secularization and deprivatization of religion, and of legitimation and collective identity. The main areas of interest found in the contributions of the churches were the value foundation of the European Union, which is demanded to coherently permeate all policies and actions of the EU, and the social dimension of Europe, which must be given equal status to the political and economic dimensions. In both areas the churches claim significant experience and expertise, which they want to see recognized in the Constituional Treaty through a formally guaranteed status for churches and religious communities in the EU. In their contributions the churches show a strong determination to secure a significant role for both religion and religious communities in the public life of Europe. As for the role of religion, they point out to its potential as a motivating and cohesive force in society and as a building block for a collective European identity, which is still missing. Churches also pursue a substantial public role for themselves beyond the spiritual dimension, permeating the secular areas of the social, political and economic dimensions. The arguments in suppport of such role are embedded in their interest and expertise in spiritual and other fundamental values and their broad involvement in providing social services. In this context churches use expressions inclusive of all religions and convictions, albeit clearly advocating the primacy of Europe's Christian heritage. Based on their historical role, their social involvement and their spiritual mission they use the public debate on the Constitutional Treaty to gain formal legitimacy for the public status of religion and religious communities, both nationally and on a European level, through appropriate provisions in the constitutional text. In return they offer the European Union ways of improving its own legitimacy by reducing the democratic and ideological deficit of the EU and advancing the development a collective European identity.

Photobiological studies of Baltic Sea phytoplankton

Phytoplankton ecology and productivity is one of the main branches of contemporary oceanographic research. Research groups in this branch have increasingly started to utilise bio-optical applications. My main research objective was to critically investigate the advantages and deficiencies of the fast repetition rate (FRR) fluorometry for studies of productivity of phytoplankton, and the responses of phytoplankton towards varying environmental stress. Second, I aimed to clarify the applicability of the FRR system to the optical environment of the Baltic Sea. The FRR system offers a highly dynamic tool for studies of phytoplankton photophysiology and productivity both in the field and in a controlled environment. The FRR metrics obtain high-frequency in situ determinations of the light-acclimative and photosynthetic parameters of intact phytoplankton communities. The measurement protocol is relatively easy to use without phases requiring analytical determinations. The most notable application of the FRR system lies in its potential for making primary productivity (PP) estimations. However, the realisation of this scheme is not straightforward. The FRR-PP, based on the photosynthetic electron flow (PEF) rate, are linearly related to the photosynthetic gas exchange (fixation of 14C) PP only in environments where the photosynthesis is light-limited. If the light limitation is not present, as is usually the case in the near-surface layers of the water column, the two PP approaches will deviate. The prompt response of the PEF rate to the short-term variability in the natural light field makes the field comparisons between the PEF-PP and the 14C-PP difficult to interpret, because this variability is averaged out in the 14C-incubations. Furthermore, the FRR based PP models are tuned to closely follow the vertical pattern of the underwater irradiance. Due to the photoacclimational plasticity of phytoplankton, this easily leads to overestimates of water column PP, if precautionary measures are not taken. Natural phytoplankton is subject to broad-waveband light. Active non-spectral bio-optical instruments, like the FRR fluorometer, emit light in a relatively narrow waveband, which by its nature does not represent the in situ light field. Thus, the spectrally-dependent parameters provided by the FRR system need to be spectrally scaled to the natural light field of the Baltic Sea. In general, the requirement of spectral scaling in the water bodies under terrestrial impact concerns all light-adaptive parameters provided by any active non-spectral bio-optical technique. The FRR system can be adopted to studies of all phytoplankton that possess efficient light harvesting in the waveband matching the bluish FRR excitation. Although these taxa cover the large bulk of all the phytoplankton taxa, one exception with a pronounced ecological significance is found in the Baltic Sea. The FRR system cannot be used to monitor the photophysiology of the cyanobacterial taxa harvesting light in the yellow-red waveband. These taxa include the ecologically-significant bloom-forming cyanobacterial taxa in the Baltic Sea.

Structure and Dynamics of Coil-like Molecules by Residual Dipolar Couplings

Nuclear magnetic resonance (NMR) spectroscopy provides us with many means to study biological macromolecules in solution. Proteins in particular are the most intriguing targets for NMR studies. Protein functions are usually ascribed to specific three-dimensional structures but more recently tails, long loops and non-structural polypeptides have also been shown to be biologically active. Examples include prions, -synuclein, amylin and the NEF HIV-protein. However, conformational preferences in coil-like molecules are difficult to study by traditional methods. Residual dipolar couplings (RDCs) have opened up new opportunities; however their analysis is not trivial. Here we show how to interpret RDCs from these weakly structured molecules. The most notable residual dipolar couplings arise from steric obstruction effects. In dilute liquid crystalline media as well as in anisotropic gels polypeptides encounter nematogens. The shape of a polypeptide conformation limits the encounter with the nematogen. The most elongated conformations may come closest whereas the most compact remain furthest away. As a result there is slightly more room in the solution for the extended than for the compact conformations. This conformation-dependent concentration effect leads to a bias in the measured data. The measured values are not arithmetic averages but essentially weighted averages over conformations. The overall effect can be calculated for random flight chains and simulated for more realistic molecular models. Earlier there was an implicit thought that weakly structured or non-structural molecules would not yield to any observable residual dipolar couplings. However, in the pioneering study by Shortle and Ackerman RDCs were clearly observed. We repeated the study for urea-denatured protein at high temperature and also observed indisputably RDCs. This was very convincing to us but we could not possibly accept the proposed reason for the non-zero RDCs, namely that there would be some residual structure left in the protein that to our understanding was fully denatured. We proceeded to gain understanding via simulations and elementary experiments. In measurements we used simple homopolymers with only two labelled residues and we simulated the data to learn more about the origin of RDCs. We realized that RDCs depend on the position of the residue as well as on the length of the polypeptide. Investigations resulted in a theoretical model for RDCs from coil-like molecules. Later we extended the studies by molecular dynamics. Somewhat surprisingly the effects are small for non-structured molecules whereas the bias may be large for a small compact protein. All in all the work gave clear and unambiguous results on how to interpret RDCs as structural and dynamic parameters of weakly structured proteins.

Studies on diamond-like carbon and novel diamond-like carbon polymer hybrid coatings deposited with filtered pulsed arc discharge method

The main obstacle for the application of high quality diamond-like carbon (DLC) coatings has been the lack of adhesion to the substrate as the coating thickness is increased. The aim of this study was to improve the filtered pulsed arc discharge (FPAD) method. With this method it is possible to achieve high DLC coating thicknesses necessary for practical applications. The energy of the carbon ions was measured with an optoelectronic time-of-flight method. An in situ cathode polishing system used for stabilizing the process yield and the carbon ion energies is presented. Simultaneously the quality of the coatings can be controlled. To optimise the quality of the deposition process a simple, fast and inexpensive method using silicon wafers as test substrates was developed. This method was used for evaluating the suitability of a simplified arc-discharge set-up for the deposition of the adhesion layer of DLC coatings. A whole new group of materials discovered by our research group, the diamond-like carbon polymer hybrid (DLC-p-h) coatings, is also presented. The parent polymers used in these novel coatings were polydimethylsiloxane (PDMS) and polytetrafluoroethylene (PTFE). The energy of the plasma ions was found to increase when the anode-cathode distance and the arc voltage were increased. A constant deposition rate for continuous coating runs was obtained with an in situ cathode polishing system. The novel DLC-p-h coatings were found to be water and oil repellent and harder than any polymers. The lowest sliding angle ever measured from a solid surface, 0.15 ± 0.03°, was measured on a DLC-PDMS-h coating. In the FPAD system carbon ions can be accelerated to high energies (≈ 1 keV) necessary for the optimal adhesion (the substrate is broken in the adhesion and quality test) of ultra thick (up to 200 µm) DLC coatings by increasing the anode-cathode distance and using high voltages (up to 4 kV). An excellent adhesion can also be obtained with the simplified arc-discharge device. To maintain high process yield (5µm/h over a surface area of 150 cm2) and to stabilize the carbon ion energies and the high quality (sp3 fraction up to 85%) of the resulting coating, an in situ cathode polishing system must be used. DLC-PDMS-h coating is the superior candidate coating material for anti-soiling applications where also hardness is required.

Preterm delivery and selected biomarkers : phosphorylated insulin-like growth factor-binding protein-1 and matrix metalloproteinase-8 – in cervical fluid

Premature delivery is a major cause of neonatal morbidity and mortality. The incidence of premature deliveries has increased around the world. In Finland 5.3%, or about 3,000 children per year are born prematurely, before 37 weeks of gestation. The corresponding figure in the United States is about 13%. The morbidity and mortality are highest among infants delivered before 32 weeks of gestation - about 600 children each year in Finland. Approximately 70% of premature deliveries are unexplained. Preterm delivery can be caused by an asympto-matic infection between uterus and the fetal membranes, such can begin already in early pregnancy. It is difficult to predict preterm delivery, and many patients are therefore unnecessarily admitted to hospital for observation and exposed to medical treatments. On the other hand, the high risk women should be identified early for the best treatment of the mother and preterm infant. --- In the prospective study conducted at the Department of Obstetric and Gynecology, Helsinki University Central Hospital two biochemical inflammation related markers were measured in the lower genital tract fluids of asymp-tomatic women in early and mid pregnancy in an order to see whether these markers could identify women with an increased risk of preterm delivery. These biomarkers were phosphorylated insulin-like growth factor binding protein-1 (phIGFBP-1) and matrix metalloproteinase-8 (MMP-8). The study involved 5180 asymptomatic pregnant women, examined during the first and second ultrasound screening visits. The study samples were taken from the vagina and cervicix. In addition, 246 symptomatic women were studied (pregnancy weeks 22 – 34). The study showed that increased phIGFBP-1 concentration in cervical canal fluid in early pregnancy increased the risk for preterm delivery. The risk for very premature birth (before 32 weeks of gestation) was nearly four-fold. Low MMP-8 concentration in mid pregnancy increased the risk of subsequent premature preterm rupture of fetal membranes (PPROM). Significantly high MMP-8 concentrations in the cervical fluid increased the risk for prema-ture delivery initiated by preterm labour with intact membranes. Among women with preterm contractions the shortened cervical length measured by ultrasound and elevated cervical fluid phIGFBP-1 both predicted premature delivery. In summary, because of the relatively low sensitivity of cervical fluid phIGFBP-1 this biomarker is not suitable for routine screening, but provides an additional tool in assessing the risk of preterm delivery. Cervical fluid MMP-8 is not useful in early or mid pregnancy in predicting premature delivery because of its dual role. Further studies on the role of MMP-8 are therefore needed. Our study confirms that phIGFBP-1 testing is useful in predicting pre-term delivery.