Psychophysiology of flow experience : An explorative study

This study explored the possibilities the psychophysiological methodology offer to flow research. Facial electromyography has often been used to index valence, and electrodermal activity to index arousal, the two basic dimensions of emotion. It was hypothesized that these measures can also be used to examine enjoyment, a basic component of flow experiment. A digital game was used to induce flow, and physiological activity of 32 subjects was measured continuously. Flow State Scale was used to assess flow. Activity of corrugator supercilii muscle, an index of negative valence, was negatively correlated with flow reports, as hypothesized. Contrary to hypothesis, skin conductance level, an index of arousal, was unrelated to self-reported flow. The results for association between flow and zygomaticus major and orbicularis oculi muscle activities, indices of positive valence, were inconclusive, possibly due to experimental design where only tonic measures were available. Psychophysiological methods are recommended for future studies of flow. Specifically, the time series approach may be particularly viable in examining the temporal aspects of flow, an area currently unexplored. Furthermore, it is suggested that digital game research would benefit from psychophysiological study of game-related flow.

Nonverbal predication in Erzya : Studies on morphosyntactic variation and part of speech distinctions

This dissertation consists of four articles and an introduction. The five parts address the same topic, nonverbal predication in Erzya, from different perspectives. The work is at the same time linguistic typology and Uralic studies. The findings based on a large corpus of empirical Erzya data, which was collected using several different methods and included recordings of the spoken language, made it possible for the present study to apply, then test and finally discuss the previous theories based on cross-linguistic data. Erzya makes use of multiple predication patterns which vary from totally analytic to the morphologically very complex. Nonverbal predicate clause types are classified on the basis of propositional acts in clauses denoting class-membership, identity, property and location. The predicates of these clauses are nouns, adjectives and locational expressions, respectively. The following three predication strategies in Erzya nonverbal predication can be identified: i. the zero-copula construction, ii. the predicative suffix construction and iii. the copula construction. It has been suggested that verbs and nouns cannot be clearly distinguished on morphological grounds when functioning as predicates in Erzya. This study shows that even though predicativity must not be considered a sufficient tool for defining parts of speech in any language, the Erzya lexical classes of adjective, noun and verb can be distinguished from each other also in predicate position. The relative frequency and degree of obligation for using the predicative suffix construction decreases when moving left to right on the scale verb adjective/locative noun ( identificational statement). The predicative suffix is the main pattern in the present tense over the whole domain of nonverbal predication in Standard Erzya, but if it is replaced it is most likely to be with a zero-copula construction in a nominal predication. This study exploits the theory of (a)symmetry for the first time in order to describe verbal vs. nonverbal predication. It is shown that the asymmetry of paradigms and constructions differentiates the lexical classes. Asymmetrical structures are motivated by functional level asymmetry. Variation in predication as such adds to the complexity of the grammar. When symmetric structures are employed, the functional complexity of grammar decreases, even though morphological complexity increases. The genre affects the employment of predication strategies in Erzya. There are differences in the relative frequency of the patterns, and some patterns are totally lacking from some of the data. The clearest difference is that the past tense predicative suffix construction occurs relatively frequently in Standard Erzya, while it occurs infrequently in the other data. Also, the predicative suffixes of the present tense are used more regularly in written Standard Erzya than in any other genre. The genre also affects the incidence of the translative in uľ(ń)ems copula constructions. In translations from Russian to Erzya the translative case is employed relatively frequently in comparison to other data. This study reveals differences between the two Mordvinic languages Erzya and Moksha. The predicative suffixes (bound person markers) of the present tense are used more regularly in Moksha in all kinds of nonverbal predicate clauses compared to Erzya. It should further be observed that identificational statements are encoded with a predicative suffix in Moksha, but seldom in Erzya. Erzya clauses are more frequently encoded using zero-constructions, displaying agreement in number only.

Wind drift of snowfall between the radar volume and ground

This study evaluates how the advection of precipitation, or wind drift, between the radar volume and ground affects radar measurements of precipitation. Normally precipitation is assumed to fall vertically to the ground from the contributing volume, and thus the radar measurement represents the geographical location immediately below. In this study radar measurements are corrected using hydrometeor trajectories calculated from measured and forecasted winds, and the effect of trajectory-correction on the radar measurements is evaluated. Wind drift statistics for Finland are compiled using sounding data from two weather stations spanning two years. For each sounding, the hydrometeor phase at ground level is estimated and drift distance calculated using different originating level heights. This way the drift statistics are constructed as a function of range from radar and elevation angle. On average, wind drift of 1 km was exceeded at approximately 60 km distance, while drift of 10 km was exceeded at 100 km distance. Trajectories were calculated using model winds in order to produce a trajectory-corrected ground field from radar PPI images. It was found that at the upwind side from the radar the effective measuring area was reduced as some trajectories exited the radar volume scan. In the downwind side areas near the edge of the radar measuring area experience improved precipitation detection. The effect of trajectory-correction is most prominent in instant measurements and diminishes when accumulating over longer time periods. Furthermore, measurements of intensive and small scale precipitation patterns benefit most from wind drift correction. The contribution of wind drift on the uncertainty of estimated Ze (S) - relationship was studied by simulating the effect of different error sources to the uncertainty in the relationship coefficients a and b. The overall uncertainty was assumed to consist of systematic errors of both the radar and the gauge, as well as errors by turbulence at the gauge orifice and by wind drift of precipitation. The focus of the analysis is error associated with wind drift, which was determined by describing the spatial structure of the reflectivity field using spatial autocovariance (or variogram). This spatial structure was then used with calculated drift distances to estimate the variance in radar measurement produced by precipitation drift, relative to the other error sources. It was found that error by wind drift was of similar magnitude with error by turbulence at gauge orifice at all ranges from radar, with systematic errors of the instruments being a minor issue. The correction method presented in the study could be used in radar nowcasting products to improve the estimation of visibility and local precipitation intensities. The method however only considers pure snow, and for operational purposes some improvements are desirable, such as melting layer detection, VPR correction and taking solid state hydrometeor type into account, which would improve the estimation of vertical velocities of the hydrometeors.

On linear order and computation : The expressiveness of interactive computations on linear orders and computations indexed by ordinals

We solve the Dynamic Ehrenfeucht-Fra\"iss\'e Game on linear orders for both players, yielding a normal form for quantifier-rank equivalence classes of linear orders in first-order logic, infinitary logic, and generalized-infinitary logics with linearly ordered clocks. We show that Scott Sentences can be manipulated quickly, classified into local information, and consistency can be decided effectively in the length of the Scott Sentence. We describe a finite set of linked automata moving continuously on a linear order. Running them on ordinals, we compute the ordinal truth predicate and compute truth in the constructible universe of set-theory. Among the corollaries are a study of semi-models as efficient database of both model-theoretic and formulaic information, and a new proof of the atomicity of the Boolean algebra of sentences consistent with the theory of linear order -- i.e., that the finitely axiomatized theories of linear order are dense.

Homogeneous model theory of metric structures

This thesis studies homogeneous classes of complete metric spaces. Over the past few decades model theory has been extended to cover a variety of nonelementary frameworks. Shelah introduced the abstact elementary classes (AEC) in the 1980s as a common framework for the study of nonelementary classes. Another direction of extension has been the development of model theory for metric structures. This thesis takes a step in the direction of combining these two by introducing an AEC-like setting for studying metric structures. To find balance between generality and the possibility to develop stability theoretic tools, we work in a homogeneous context, thus extending the usual compact approach. The homogeneous context enables the application of stability theoretic tools developed in discrete homogeneous model theory. Using these we prove categoricity transfer theorems for homogeneous metric structures with respect to isometric isomorphisms. We also show how generalized isomorphisms can be added to the class, giving a model theoretic approach to, e.g., Banach space isomorphisms or operator approximations. The novelty is the built-in treatment of these generalized isomorphisms making, e.g., stability up to perturbation the natural stability notion. With respect to these generalized isomorphisms we develop a notion of independence. It behaves well already for structures which are omega-stable up to perturbation and coincides with the one from classical homogeneous model theory over saturated enough models. We also introduce a notion of isolation and prove dominance for it.

Finitary Abstract Elementary Classes

The research in model theory has extended from the study of elementary classes to non-elementary classes, i.e. to classes which are not completely axiomatizable in elementary logic. The main theme has been the attempt to generalize tools from elementary stability theory to cover more applications arising in other branches of mathematics. In this doctoral thesis we introduce finitary abstract elementary classes, a non-elementary framework of model theory. These classes are a special case of abstract elementary classes (AEC), introduced by Saharon Shelah in the 1980's. We have collected a set of properties for classes of structures, which enable us to develop a 'geometric' approach to stability theory, including an independence calculus, in a very general framework. The thesis studies AEC's with amalgamation, joint embedding, arbitrarily large models, countable Löwenheim-Skolem number and finite character. The novel idea is the property of finite character, which enables the use of a notion of a weak type instead of the usual Galois type. Notions of simplicity, superstability, Lascar strong type, primary model and U-rank are inroduced for finitary classes. A categoricity transfer result is proved for simple, tame finitary classes: categoricity in any uncountable cardinal transfers upwards and to all cardinals above the Hanf number. Unlike the previous categoricity transfer results of equal generality the theorem does not assume the categoricity cardinal being a successor. The thesis consists of three independent papers. All three papers are joint work with Tapani Hyttinen.

Type III Secretion System of Phytopathogenic Bacterium Pseudomonas syringae:From Gene to Function

The type III secretion system (T3SS) is an essential requirement for the virulence of many Gram-negative bacteria which infect plants, animals and men. Pathogens use the T3SS to deliver effector proteins from the bacterial cytoplasm to the eukaryotic host cells, where the effectors subvert host defenses. The best candidates for directing effector protein traffic are the bacterial type III-associated appendages, called needles or pili. In plant pathogenic bacteria, the best characterized example of a T3SS-associated appendage is the HrpA pilus of the plant pathogen Pseudomonas syringae pv. tomato DC3000. The components of the T3SS in plant pathogens are encoded by a cluster of hrp (hypersensitive reaction and pathogenicity) genes. Two major classes of T3SS-secreted proteins are: harpin proteins such as HrpZ which are exported into extracellular space, and avirulence (Avr) proteins such as AvrPto which are translocated directly to the plant cytoplasm. This study deals with the structural and functional characterization of the T3SS-associated HrpA pilus and the T3SS-secreted harpins. By insertional mutagenesis analysis of HrpA, we located the optimal epitope insertion site in the amino-terminus of HrpA, and revealed the potential application of the HrpA pilus as a carrier of antigenic determinants for vaccination. By pulse-expression of proteins combined with immuno-electron microscopy, we discovered the Hrp pilus assembly strategy as addition of HrpA subunits to the distal end of the growing pilus, and we showed for the first time that secretion of HrpZ occurs at the tip of the pilus. The pilus thus functions as a conduit delivering proteins to the extracellular milieu. By using phage-display and scanning-insertion mutagenesis methods we identified a conserved HrpZ-binding peptide and localized the peptide-binding site to the central domain of HrpZ. We also found that the HrpZ specifically interacts with a host bean protein. Taken together, the current results provide deeper insight into the molecular mechanism of T3SS-associated pilus assembly and effector protein translocation, which will be helpful for further studies on the pathogenic mechanisms of Gram-negative bacteria and for developing new strategies to prevent bacterial infection.

Effects of unilateral vocal fold paralysis treatment with fascia augmentation on airflow mechanics, tracheal sounds and voice acoustics

Data on the influence of unilateral vocal fold paralysis on breathing, especially other than information obtained by spirometry, are relatively scarce. Even less is known about the effect of its treatment by vocal fold medialization. Consequently, there was a need to study the issue by combining multiple instruments capable of assessing airflow dynamics and voice. This need was emphasized by a recently developed medialization technique, autologous fascia injection; its effects on breathing have not previously been investigated. A cohort of ten patients with unilateral vocal fold paralysis was studied before and after autologous fascia injection by using flow-volume spirometry, body plethysmography and acoustic analysis of breathing and voice. Preoperative results were compared with those of ten healthy controls. A second cohort of 11 subjects with unilateral vocal fold paralysis was studied pre- and postoperatively by using flow-volume spirometry, impulse oscillometry, acoustic analysis of voice, voice handicap index and subjective assessment of dyspnoea. Preoperative peak inspiratory flow and specific airway conductance were significantly lower and airway resistance was significantly higher in the patients than in the healthy controls (78% vs. 107%, 73% vs. 116% and 182% vs. 125% of predicted; p = 0.004, p = 0.004 and p = 0.026, respectively). Patients had a higher root mean square of spectral power of tracheal sounds than controls, and three of them had wheezes as opposed to no wheezing in healthy subjects. Autologous fascia injection significantly improved acoustic parameters of the voice in both cohorts and voice handicap index in the latter cohort, indicating that this procedure successfully improved voice in unilateral vocal fold paralysis. Peak inspiratory flow decreased significantly as a consequence of this procedure (from 4.54 ± 1.68 l to 4.21 ± 1.26 l, p = 0.03, in pooled data of both cohorts), but no change occurred in the other variables of flow-volume spirometry, body-plethysmography and impulse oscillometry. Eight of the ten patients studied by acoustic analysis of breathing had wheezes after vocal fold medialization compared with only three patients before the procedure, and the numbers of wheezes per recorded inspirium and expirium increased significantly (from 0.02 to 0.42 and from 0.03 to 0.36; p = 0.028 and p = 0.043, respectively). In conclusion, unilateral vocal fold paralysis was observed to disturb forced breathing and also to cause some signs of disturbed tidal breathing. Findings of flow volume spirometry were consistent with variable extra-thoracic obstruction. Vocal fold medialization by autologous fascia injection improved the quality of the voice in patients with unilateral vocal fold paralysis, but also decreased peak inspiratory flow and induced wheezing during tidal breathing. However, these airflow changes did not appear to cause significant symptoms in patients.

Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) : Identification of novel TNFRSF1A mutations and intracellular signalling defects

The systemic autoinflammatory disorders are a group of rare diseases characterized by periodically recurring episodes of acute inflammation and a rise in serum acute phase proteins, but with no signs of autoimmunity. At present eight hereditary syndromes are categorized as autoinflammatory, although the definition has also occasionally been extended to other inflammatory disorders, such as Crohn s disease. One of the autoinflammatory disorders is the autosomally dominantly inherited tumour necrosis factor receptor-associated periodic syndrome (TRAPS), which is caused by mutations in the gene encoding the tumour necrosis factor type 1 receptor (TNFRSF1A). In patients of Nordic descent, cases of TRAPS and of three other hereditary fevers, hyperimmunoglobulinemia D with periodic fever syndrome (HIDS), chronic infantile neurologic, cutaneous and articular syndrome (CINCA) and familial cold autoinflammatory syndrome (FCAS), have been reported, TRAPS being the most common of the four. Clinical characteristics of TRAPS are recurrent attacks of high spiking fever, associated with inflammation of serosal membranes and joints, myalgia, migratory rash and conjunctivitis or periorbital cellulitis. Systemic AA amyloidosis may occur as a sequel of the systemic inflammation. The aim of this study was to investigate the genetic background of hereditary periodically occurring fever syndromes in Finnish patients, to explore the reliability of determining serum concentrations of soluble TNFRSF1A and metalloproteinase-induced TNFRSF1A shedding as helpful tools in differential diagnostics, as well as to study intracellular NF-κB signalling in an attempt to widen the knowledge of the pathomechanisms underlying TRAPS. Genomic sequencing revealed two novel TNFRSF1A mutations, F112I and C73R, in two Finnish families. F112I was the first TNFRSF1A mutation to be reported in the third extracellular cysteine-rich domain of the gene and C73R was the third novel mutation to be reported in a Finnish family, with only one other TNFRSF1A mutation having been reported in the Nordic countries. We also presented a differential diagnostic problem in a TRAPS patient, emphasizing for the clinician the importance of differential diagnostic vigiliance in dealing with rare hereditary disorders. The underlying genetic disease of the patient both served as a misleading factor, which possibly postponed arrival at the correct diagnosis, but may also have predisposed to the pathologic condition, which led to a critical state of the patient. Using a method of flow cytometric analysis modified for the use on fresh whole blood, we studied intracellular signalling pathways in three Finnish TRAPS families with the F112I, C73R and the previously reported C88Y mutations. Evaluation of TNF-induced phosphorylation of NF-κB and p38, revealed low phosphorylation profiles in nine out of ten TRAPS patients in comparison to healthy control subjects. This study shows that TRAPS is a diagnostic possibility in patients of Nordic descent, with symptoms of periodically recurring fever and inflammation of the serosa and joints. In particular in the case of a family history of febrile episodes, the possibility of TRAPS should be considered, if an etiology of autoimmune or infectious nature is excluded. The discovery of three different mutations in a population as small as the Finnish, reinforces the notion that the extracellular domain of TNFRSF1A is prone to be mutated at the entire stretch of its cysteine-rich domains and not only at a limited number of sites, suggesting the absence of a founder effect in TRAPS. This study also demonstrates the challenges of clinical work in differentiating the symptoms of rare genetic disorders from those of other pathologic conditions and presents the possibility of an autoinflammatory disorder as being the underlying cause of severe clinical complications. Furthermore, functional studies of fresh blood leukocytes show that TRAPS is often associated with a low NF-κB and p38 phosphorylation profile, although low phosphorylation levels are not a requirement for the development of TRAPS. The aberrant signalling would suggest that the hyperinflammatory phenotype of TRAPS is the result of compensatory NF-κB-mediated regulatory mechanisms triggered by a deficiency of the innate immune response.

A Historical Approach to Children s Physics Education : Modelling of DC-circuit Phenomena in a Small Group

This three-phase design research describes the modelling processes for DC-circuit phenomena. The first phase presents an analysis of the development of the DC-circuit historical models in the context of constructing Volta s pile at the turn of the 18th century. The second phase involves the designing of a teaching experiment for comprehensive school third graders. Among other considerations, the design work utilises the results of the first phase and research literature of pupils mental models for DC-circuit phenomena. The third phase of the research was concerned with the realisation of the planned teaching experiment. The aim of this phase was to study the development of the external representations of DC-circuit phenomena in a small group of third graders. The aim of the study has been to search for new ways to guide pupils to learn DC-circuit phenomena while emphasing understanding at the qualitative level. Thus, electricity, which has been perceived as a difficult and abstract subject, could be learnt more comprehensively. Especially, the research of younger pupils learning of electricity concepts has not been of great interest at the international level, although DC-circuit phenomena are also taught in the lower classes of comprehensive schools. The results of this study are important, because there has tended to be more teaching of natural sciences in the lower classes of comprehensive schools, and attempts are being made to develop this trend in Finland. In the theoretical part of the research an Experimental-centred representation approach, which emphasises the role of experimentalism in the development of pupil s representations, is created. According to this approach learning at the qualitative level consists of empirical operations like experimenting, observations, perception, and prequantification of nature phenomena, and modelling operations like explaining and reasoning. Besides planning teaching, the new approach can be used as an analysis tool in describing both historical modelling and the development of pupils representations. In the first phase of the study, the research question was: How did the historical models of DC-circuit phenomena develop in Volta s time? The analysis uncovered three qualitative historical models associated with the historical concept formation process. The models include conceptions of the electric circuit as a scene in the DC-circuit phenomena, the comparative electric-current phenomenon as a cause of different observable effect phenomena, and the strength of the battery as a cause of the electric-current phenomenon. These models describe the concept formation process and its phases in Volta s time. The models are portrayed in the analysis using fragments of the models, where observation-based fragments and theoretical fragements are distinguished from each other. The results emphasise the significance of the qualitative concept formation and the meaning of language in the historical modelling of DC-circuit phenomena. For this reason these viewpoints are stressed in planning the teaching experiment in the second phase of the research. In addition, the design process utilised the experimentation behind the historical models of DC-circuit phenomena In the third phase of the study the research question is as follows: How will the small group s external representations of DC-circuit phenomena develop during the teaching experiment? The main question is divided into the following two sub questions: What kind of talk exists in the small group s learning? What kinds of external representations for DC-circuit phenomena exist in the small group discourse during the teaching experiment? The analysis revealed that the teaching experiment of the small group succeeded in its aim to activate talk in the small group. The designed connection cards proved especially successful in activating talk. The connection cards are cards that represent the components of the electric circuit. In the teaching experiment the pupils constructed different connections with the connection cards and discussed, what kinds of DC-circuit phenomena would take place in the corresponding real connections. The talk of the small group was analysed by comparing two situations, firstly, when the small group discussed using connections made with the connection cards and secondly with the same connections using real components. According to the results the talk of the small group included more higher-order thinking when using the connection cards than with similar real components. In order to answer the second sub question concerning the small group s external representations that appeared in the talk during the teaching experiment; student talk was visualised by the fragment maps which incorporate the electric circuit, the electric current and the source voltage. The fragment maps represent the gradual development of the external representations of DC-circuit phenomena in the small group during the teaching experiment. The results of the study challenge the results of previous research into the abstractness and difficulty of electricity concepts. According to this research, the external representations of DC-circuit phenomena clearly developed in the small group of third graders. Furthermore, the fragment maps uncover that although the theoretical explanations of DC-circuit phenomena, which have been obtained as results of typical mental model studies, remain undeveloped, learning at the qualitative level of understanding does take place.

On the homogeneous and heterogeneous nucleation of some organic compounds

The conversion of a metastable phase into a thermodynamically stable phase takes place via the formation of clusters. Clusters of different sizes are formed spontaneously within the metastable mother phase, but only those larger than a certain size, called the critical size, will end up growing into a new phase. There are two types of nucleation: homogeneous, where the clusters appear in a uniform phase, and heterogeneous, when pre-existing surfaces are available and clusters form on them. The nucleation of aerosol particles from gas-phase molecules is connected not only with inorganic compounds, but also with nonvolatile organic substances found in atmosphere. The question is which ones of the myriad of organic species have the right properties and are able to participate in nucleation phenomena. This thesis discusses both homogeneous and heterogeneous nucleation, having as theoretical tool the classical nucleation theory (CNT) based on thermodynamics. Different classes of organics are investigated. The members of the first class are four dicarboxylic acids (succinic, glutaric, malonic and adipic). They can be found in both the gas and particulate phases, and represent good candidates for the aerosol formation due to their low vapor pressure and solubility. Their influence on the nucleation process has not been largely investigated in the literature and it is not fully established. The accuracy of the CNT predictions for binary water-dicarboxylic acid systems depends significantly on the good knowledge of the thermophysical properties of the organics and their aqueous solutions. A large part of the thesis is dedicated to this issue. We have shown that homogeneous and heterogeneous nucleation of succinic, glutaric and malonic acids in combination with water is unlikely to happen in atmospheric conditions. However, it seems that adipic acid could participate in the nucleation process in conditions occurring in the upper troposphere. The second class of organics is represented by n-nonane and n-propanol. Their thermophysical properties are well established, and experiments on these substances have been performed. The experimental data of binary homogeneous and heterogeneous nucleation have been compared with the theoretical predictions. Although the n-nonane - n-propanol mixture is far from being ideal, CNT seems to behave fairly well, especially when calculating the cluster composition. In the case of heterogeneous nucleation, it has been found that better characterization of the substrate - liquid interaction by means of line tension and microscopic contact angle leads to a significant improvement of the CNT prediction. Unfortunately, this can not be achieved without well defined experimental data.

Prognostic significance of cyclooxygenase-2 and associated molecules in gastric cancer

Background and aims: Low stage and curative surgery are established factors for improved survival in gastric cancer. However, not all low-stage patients have a good prognosis. Cyclooxygenase-2 (COX-2) is known to associate with reduced survival in several cancers, and has been shown to play an important role in gastric carcinogenesis. Since new and better prognostic markers are needed for gastric cancer, we studied the prognostic significance of COX-2 and of markers that associate with COX-2 expression. We also studied markers reflecting proliferation and apoptosis, and evaluated their association with COX-2. Our purpose was to construct an accurate prognostic model by combining tissue markers and clinicopathogical factors. Materials and methods: Of 342 consecutive patients who underwent surgery for gastric cancer at Meilahti Hospital, Helsinki University Central Hospital, 337 were included in this study. Low stages I to II were represented by 141 (42%) patients, and high stages III to IV by 196 (58%). Curative surgery was performed on 176 (52%) patients. Survival data were obtained from the national registers. Slides from archive tissue blocks were prepared for immunohistochemistry by use of COX-2, human antigen R (HuR), cyclin A, matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), and Ki-67 antibodies. Immunostainings were scored by microscopy, and scores were entered into a database. Associations of tumor markers with clinicopathological factors were calculated, as well as associations with p53, p21, and results of flow cytometry from earlier studies. Survival analysis was performed by the Kaplan-Meier method, and Cox multivariate models were reconstructed. Cell culture experiments were performed to explore the effect of small interfering (si)RNA of HuR on COX-2 expression in a TMK-1 gastric cancer cell line. Results: Overall 5-year survival was 35.1%. Study I showed that COX-2 was an independent prognostic factor, and that the prognostic impact of COX-2 was more pronounced in low-stage patients. Cytoplasmic HuR expression also associated with reduced survival in gastric cancer patients in a non-independent manner. Cell culture experiments showed that HuR can regulate COX-2 expression in TMK-1 cells in vitro, with an association also between COX-2 and HuR tissue expression in a clinical material. In Study II, cyclin A was an independent prognostic factor and was associated with HuR expression in the gastric cancer material. The results of Study III showed that epithelial MMP-2 associated with survival in univariate, but not in multivariate analysis. However, MMP-9 showed no prognostic value. MMP-2 expression was associated with COX-2 expression. In Study IV, the prognostic power of COX-2 was compared with that of all tested markers associated with survival in Studies I to III, as well as with p21, p53, and flow cytometry results. COX-2 and p53 were independent prognostic factors, and COX-2 expression was associated with that of p53 and Ki-67 and also with aneuploidy. Conclusions: COX-2 is an independent prognostic factor in gastric cancer, and its prognostic power emerges especially in low stage cancer. COX-2 is regulated by HuR, and is associated with factors reflecting invasion, proliferation, and apoptosis. In an extended multivariate model, COX-2 retained its position as an independent prognosticator. COX-2 can be considered a promising new prognostic marker in gastric cancer.

Characterisation of antibiotic-resistant psychrotrophic bacteria in raw milk

Dynamics of raw milk associated bacteria during cold storage of raw milk and their antibiotic resistance was reviewed, with focus on psychrotrophic bacteria. This study aimed to investigate the significance of cold storage of raw milk on antibiotic-resistant bacterial population and analyse the antibiotic resistance of the Gram-negative antibiotic-resistant psychrotrophic bacteria isolated from the cold-stored raw milk samples. Twenty-four raw milk samples, six at a time, were obtained from lorries that collected milk from Finnish farms and were stored at 4°C/4 d, 6°C/3 d and 6°C/4 d. Antibiotics representing four classes of antibiotics (gentamicin, ceftazidime, levofloxacin and trimethoprim-sulfamethoxazole) were used to determine the antibiotic resistance of mesophilic and psychrotrophic bacteria during the storage period. A representative number of antibiotic-resistant Gram-negative isolates retrieved from the cold-stored raw milk samples were identified by the phenotypic API 20 NE system and a few isolates by the 16S rDNA gene sequencing. Some of the isolates were further evaluated for their antibiotic resistance by the ATB PSE 5 and HiComb system. The initial average mesophilic counts were found below 105 CFU/mL, suggesting that the raw milk samples were of good quality. However, the mesophilic and psychrotrophic population increased when stored at 4°C/4 d, 6°C/3 d and 6°C/4 d. Gentamicin- and levofloxacin-resistant bacteria increased moderately (P < 0.05) while there was a considerable rise (P < 0.05) of ceftazidime- and trimethoprim-sulfamethoxazole-resistant population during the cold storage. Of the 50.9 % (28) of resistant isolates (total 55) identified by API 20 NE, the majority were Sphingomonas paucimobilis (8), Pseudomonas putida (5), Sphingobacterium spiritivorum (3) and Acinetobacter baumanii (2). The analysis by ATB PSE 5 system suggested that 57.1% of the isolates (total 49) were multiresistant. This study showed that the dairy environment harbours multidrug-resistant Gramnegative psychrotrophic bacteria and the cold chain of raw milk storage amplifies the antibioticresistant psychrotrophic bacterial population.

Genetic polymorphisms and laboratory variables as predictors of blood pressure response to antihypertensive drugs

Hypertension is one of the major risk factors for cardiovascular morbidity. The advantages of antihypertensive therapy have been clearly demonstrated, but only about 30% of hypertensive patients have their blood pressure (BP) controlled by such treatment. One of the reasons for this poor BP control may lie in the difficulty in predicting BP response to antihypertensive treatment. The average BP reduction achieved is similar for each drug in the main classes of antihypertensive agents, but there is a marked individual variation in BP responses to any given drug. The purpose of the present study was to examine BP response to four different antihypertensive monotherapies with regard to demographic characteristics, laboratory test results and common genetic polymorphisms. The subjects of the present study are participants in the pharmacogenetic GENRES Study. A total of 208 subjects completed the whole study protocol including four drug treatment periods of four weeks, separated by four-week placebo periods. The study drugs were amlodipine, bisoprolol, hydrochlorothiazide and losartan. Both office (OBP) and 24-hour ambulatory blood pressure (ABP) measurements were carried out. BP response to study drugs were related to basic clinical characteristics, pretreatment laboratory test results and common polymorphisms in genes coding for components of the renin-angiotensin system, alpha-adducin (ADD1), beta1-adrenergic receptor (ADRB1) and beta2-adrenergic receptor (ADRB2). Age was positively correlated with BP responses to amlodipine and with OBP and systolic ABP responses to hydrochlorothiazide, while body mass index was negatively correlated with ABP responses to amlodipine. Of the laboratory test results, plasma renin activity (PRA) correlated positively with BP responses to losartan, with ABP responses to bisoprolol, and negatively with ABP responses to hydrochlorothiazide. Uniquely to this study, it was found that serum total calcium level was negatively correlated with BP responses to amlodipine, whilst serum total cholesterol level was negatively correlated with ABP responses to amlodipine. There were no significant associations of angiotensin II type I receptor 1166A/C, angiotensin converting enzyme I/D, angiotensinogen Met235Thr, ADD1 Gly460Trp, ADRB1 Ser49Gly and Gly389Arg and ADRB2 Arg16Gly and Gln27Glu polymorphisms with BP responses to the study drugs. In conclusion, this study confirmed the relationship between pretreatment PRA levels and response to three classes of antihypertensive drugs. This study is the first to note a significant inverse relation between serum calcium level and responsiveness to a calcium channel blocker. However, this study could not replicate the observations that common polymorphisms in angiotensin II type I receptor, angiotensin converting enzyme, angiotensinogen, ADD1, ADRB1, or ADRB2 genes can predict BP response to antihypertensive drugs.