Vyra enie obob čёnno-ličnogo značenija v russkom jazyke

Expressing generalized-personal meaning in Russian Based on data from Russian, this doctoral dissertation examines generalized-personal meaning that is, generic expressions referring to all human beings, people in general, each or any person (e.g. S vozrastom načinae cenit prostye ve či With age you start to appreciate simple things ). The study shares its basic theoretical orientation with functional approaches going from meaning to form . The objective of the thesis is to determine and describe the various linguistic means which can be used by the speaker to express generalized-personal meaning. The main material of the study consists of 2,000 examples collected from modern Russian literature, newspapers, and magazines. The linguistic means of expressing generalized-personal meaning are divided into three main classes. Morphological and lexico-grammatical means (22% of the material) include the use of personal pronouns and personal verbal endings. In Russian, all personal forms except the 3rd person singular can be used in a generalized-personal meaning. Lexical means (14% of the material) involve, above all, pronouns like vse all , ka dyj everyone , nikto no one , as well as the nouns čelovek man and ljudi people . In emotional speech, generalized-personal meaning can also be conveyed lexically by using utterances like da e idiot znaet even an idiot knows . In rhetorical questions the pronoun kto who can appear in this meaning (cf. Kto ne ljubit moro enoe?! Who doesn t like ice cream?! ). The third main class, syntactic means (64% of the material), consists of constructions in which the generic person is not expressed at the surface level. This class mainly includes two-component structures in which the infinitive relates to a modal predicative adverb (e.g. mo no can, be allowed to , nado must ), modal verb (e.g. stoit be worth(while) , sleduet must, be obliged to ), or predicative adverb ending in -о (e.g. trudno it is hard to , neprilično is not appropriate ). Other syntactic means are: one-component infinitive structures, so-called embedded structures, structures with a processual noun, passive constructions, and gerund constructions. The different forms of expression available in Russian are not interchangeable in all contexts. Even if a given context tolerates the substitution of one construction for another, the two expressions are never entirely synonymous. In addition to determining the range of forms which can express generalized-personal meaning, the study aims to compare these forms and to specify the conditions and possible restrictions (contextual, semantic, syntactic, stylistic, etc.) associated with the use of each construction. In Russian linguistics, the generalized-personal meaning has not been extensively studied from a functional perspective. The advantage of a meaning-based functional approach is that it gives a comprehensive picture of the diversity and distribution of the phenomenon.

Studies on Matrix Metalloproteinase (MMP-2, -9 and -14) and β2 Integrin Targeting as Potential Anticancer Therapeutics

Proteolytic enzymes, such as matrix metalloproteinases (MMP), are associated to the progression of several cancers. They degrade extracellular components, which helps tumors to expand and cancer cells to escape from the primary site. Of all MMPs, gelatinases (MMP-2 and -9) and membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14), in particular, are often associated to more aggressive types of head and neck carcinomas as well as to a poorer outcome in patient survival. Although therapies during the last decades have advanced, the mortality of the disease is still rather high and adjuvant therapies are searched for continuously. MMP-9 and MT1-MMP are also involved in neo-angiogenesis, which is necessary for tumor expansion. For this reason, we have identified synthetic peptides-targeting gelatinases and MT1-MMP, and have also evaluated their anticancer effects in vitro and in vivo. Antigelatinolytic peptides effectively inhibited tongue-carcinoma cell invasion and reduced the growth of xenografted tumors. In tumor samples of mice that were treated with antigelatinolytic peptides, the micro-vessel density was significantly reduced. We also identified a novel MT1-MMP targeting peptide and demonstrated that it exerted anticancer effects against several malignant cell lines in vitro. The effects of MT1-MMP inhibition on tongue-squamous cell carcinomas were evaluated by using xenograft tumors, which it effectively inhibited. Tranexamic acid was also demonstrated to inhibit tongue-squamous cell carcinoma invasion, most probably due to its ability to prevent the plasmin-mediated activation of proMMP-9. Leukocyte β2 integrins are another interesting option when evaluating targets for the therapeutic intervention of inflammatory conditions or malignancies of hematopoietic origin, since β2 integrins are expressed mainly by leukocytes. We identified a novel technique for screening small-molecule libraries against β2 integrins, and by using this technique we identified a novel αMβ2 integrin-binding chemical (IMB-10). IMB-10 significantly enhances leukocyte adhesion and inhibits their motility. We also demonstrated that IMB-10 can be used to inhibit inflammation and lymphoma growth in vivo. Interestingly, IMB-10 also reduced leukocyte tumor infiltration and inhibited tumor invasion.

Growth differentiation factor 9 signalling in the ovary

In the ovary, two new members of the large TGF-beta superfamily of growth factors were discovered in the 1990s. The oocyte was shown to express two closely related growth factors that were named growth differentiation factor 9 (GDF-9) and growth differentiation factor 9B (GDF-9B). Both of these proteins are required for normal ovarian follicle development although their individual significance varies between species. GDF-9 and GDF-9B mRNAs are expressed in the human oocytes from the primary follicle stage onwards. This thesis project was aimed to define the signalling mechanisms utilized by the oocyte secreted GDF-9. We used primary cultures of human granulosa luteal cells (hGL) as our cell model, and recombinant adenovirus-mediated gene transfer in manipulating the TGF-b family signalling cascade molecules in these cells. Overexpression of the constitutively active forms of the seven type I receptors, the activin receptor-like kinases 1-7 (ALK1-7), using recombinant adenoviruses caused a specific activation of either the Smad1 or Smad2 pathway proteins depending on the ALK used. Activation of both Smad1 and Smad2 proteins also stimulated the expression of dimeric inhibin B protein in hGL cells. Treatment with recombinant GDF-9 protein induced the specific activation of the Smad2 pathway and stimulated the expression of inhibin betaB subunit mRNA as well as inhibin B protein secretion in our cell model. Recombinant GDF-9 also activated the Smad3-responsive CAGA-luciferase reported construct, and the GDF-9 response in hGL cells was markedly potentiated upon the overexpression of Alk5 by adenoviral gene transduction. Alk5 overexpression also enhanced the GDF-9 induced inhibin B secretion by these cells. Similarly, in a mouse teratocarcinoma cell line P19, GDF-9 could activate the Smad2/3 pathway, and overexpression of ALK5 in COS7 cells rendered them responsive to GDF-9. Furthermore, transfection of rat granulosa cells with small interfering RNA for ALK5 or overexpression of the inhibitory Smad7 resulted in dose-dependent suppression of GDF-9 effects. In conclusion, this thesis shows that both Smad1 and Smad2 pathways are involved in controlling the regulation of inhibin B secretion. Therefore, in addition to endocrine control of inhibin production by the pituitary gonadotropins, also local paracrine factors within in the ovary, like the oocyte-derived growth factors, may contribute to controlling inhibin secretion. This thesis shows as well that like other TGF-beta family ligands, also GDF-9 signalling is mediated by the canonical type I and type II receptors with serine/threonine kinase activity, and the intracellular transcription factors, the Smads. Although GDF-9 binds to the BMP type II receptor, its downstream actions are specifically mediated by the type I receptor, ALK5, and the Smad2 and Smad3 proteins.

Controls on trace metals in urban stream sediments : implications for pollution monitoring using sediment chemistry data

Contamination of urban streams is a rising topic worldwide, but the assessment and investigation of stormwater induced contamination is limited by the high amount of water quality data needed to obtain reliable results. In this study, stream bed sediments were studied to determine their contamination degree and their applicability in monitoring aquatic metal contamination in urban areas. The interpretation of sedimentary metal concentrations is, however, not straightforward, since the concentrations commonly show spatial and temporal variations as a response to natural processes. The variations of and controls on metal concentrations were examined at different scales to increase the understanding of the usefulness of sediment metal concentrations in detecting anthropogenic metal contamination patterns. The acid extractable concentrations of Zn, Cu, Pb and Cd were determined from the surface sediments and water of small streams in the Helsinki Metropolitan region, southern Finland. The data consists of two datasets: sediment samples from 53 sites located in the catchment of the Stream Gräsanoja and sediment and water samples from 67 independent catchments scattered around the metropolitan region. Moreover, the sediment samples were analyzed for their physical and chemical composition (e.g. total organic carbon, clay-%, Al, Li, Fe, Mn) and the speciation of metals (in the dataset of the Stream Gräsanoja). The metal concentrations revealed that the stream sediments were moderately contaminated and caused no immediate threat to the biota. However, at some sites the sediments appeared to be polluted with Cu or Zn. The metal concentrations increased with increasing intensity of urbanization, but site specific factors, such as point sources, were responsible for the occurrence of the highest metal concentrations. The sediment analyses revealed, thus a need for more detailed studies on the processes and factors that cause the hot spot metal concentrations. The sediment composition and metal speciation analyses indicated that organic matter is a very strong indirect control on metal concentrations, and it should be accounted for when studying anthropogenic metal contamination patterns. The fine-scale spatial and temporal variations of metal concentrations were low enough to allow meaningful interpretation of substantial metal concentration differences between sites. Furthermore, the metal concentrations in the stream bed sediments were correlated with the urbanization of the catchment better than the total metal concentrations in the water phase. These results suggest that stream sediments show true potential for wider use in detecting the spatial differences in metal contamination of urban streams. Consequently, using the sediment approach regional estimates of the stormwater related metal contamination could be obtained fairly cost-effectively, and the stability and reliability of results would be higher compared to analyses of single water samples. Nevertheless, water samples are essential in analysing the dissolved concentrations of metals, momentary discharges from point sources in particular.

Structural and functional roles of KCC2 in developing cortex

Cation chloride cotransporters (CCCs) are critical for controlling intracellular chloride homeostasis. The CCC family is composed of four isoforms of K-Cl cotransporters (KCC1-4), two isoforms of Na-K-2Cl cotransporters (NKCC1-2), one Na-Cl cotransporter (NCC) and two the structurally related proteins with unknown function, CCC8 also known as cation-chloride cotransporter interaction protein, CIP, and CCC9. KCC2 is a neuron-specific isoform, which plays a prominent role in controlling the intracellular Cl- concentration in neurons and is responsible for producing the negative shift of GABAA responses from depolarizing to hyperpolarizing during neuronal maturation. In the present studies we first used in situ hybridization to examine the developmental expression patterns of the cation-chloride cotransporters KCC1-4 and NKCC1. We found that they display complementary expression patterns during embryonic brain development. Most interestingly, KCC2 expression in the embryonic central nervous system strictly follows neuronal maturation. In vitro data obtained from primary and organotypic neuronal cultures support this finding and revealed a temporal correlation between the expression of KCC2 and synaptogenesis. We found that KCC2 is highly expressed in filopodia and mature spines as well as dendritic shaft and investigated the role of KCC2 in spine formation by analyzing KCC2-/- neurons in vitro. Our studies revealed that KCC2 is a key factor in the maturation of dendritic spines. Interestingly, the effect of KCC2 in spine formation is not due to Cl- transport activity, but mediated through the interaction between KCC2 C-terminal and intracellular protein associated with cytoskeleton. The interacting protein we found is protein 4.1N by immunoprecipitation. Our results indicate a structural role for KCC2 in the development of functional glutamatergic synapses and suggest KCC2 as a synchronizer for the functional development of glutamatergic and GABAergic synapses in neuronal network. Studies on the regulatory mechanisms of KCC2 expression during development and plasticity revealed that synaptic activity of both the glutamatergic and GABAergic system is not required for up-regulation of KCC2 during development, whereas in acute mature hippocampal slices which undergo continuous synchronous activity induced by the absence of Mg2+ solution, KCC2 mRNA and protein expression were down-regulated in CA1 pyramidal neurons subsequently leading to a reduced capacity for neuronal Cl- extrusion. This effect is mediated by endogenous BDNF-TrkB down-stream cascades involving both Shc/FRS-2 and PLCγ-CREB signaling. BDNF mediated changes in KCC2 expression indicate that KCC2 is significantly involved in the complex mechanisms of neuronal plasticity during development and pathophysiological conditions.

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.

Search for the Production of Narrow tb̅ Resonances in 1.9 fb-1 of pp̅ Collisions at √s=1.96 TeV

We present new limits on resonant tb production in proton-antiproton collisions at 1.96 TeV, using 1.9 fb^-1 of data recorded with the CDF II detector at the Fermilab Tevatron. We reconstruct a candidate mass in events with a lepton, neutrino candidate, and two or three jets, and search for anomalous tb production as modeled by W'->tb. We set a new limit on a right-handed W' with standard model-like coupling, excluding any mass below 800 GeV at 95% C.L. The cross-section for any narrow, resonant tb production between 750 and 950 GeV is found to be less than 0.28 pb at 95% C.L. We also present an exclusion of the W' coupling strength versus W' mass over the range 300 to 950 GeV.

Transverse momentum and pseudorapidity distributions of charged hadrons in pp collisions at sqrt(s) = 0.9 and 2.36 TeV

Measurements of inclusive charged-hadron transverse-momentum and pseudorapidity distributions are presented for proton-proton collisions at sqrt(s) = 0.9 and 2.36 TeV. The data were collected with the CMS detector during the LHC commissioning in December 2009. For non-single-diffractive interactions, the average charged-hadron transverse momentum is measured to be 0.46 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 0.9 TeV and 0.50 +/- 0.01 (stat.) +/- 0.01 (syst.) GeV/c at 2.36 TeV, for pseudorapidities between -2.4 and +2.4. At these energies, the measured pseudorapidity densities in the central region, dN(charged)/d(eta) for |eta|

Conditional Moments in Asset Pricing

A better understanding of stock price changes is important in guiding many economic activities. Since prices often do not change without good reasons, searching for related explanatory variables has involved many enthusiasts. This book seeks answers from prices per se by relating price changes to their conditional moments. This is based on the belief that prices are the products of a complex psychological and economic process and their conditional moments derive ultimately from these psychological and economic shocks. Utilizing information about conditional moments hence makes it an attractive alternative to using other selective financial variables in explaining price changes. The first paper examines the relation between the conditional mean and the conditional variance using information about moments in three types of conditional distributions; it finds that the significance of the estimated mean and variance ratio can be affected by the assumed distributions and the time variations in skewness. The second paper decomposes the conditional industry volatility into a concurrent market component and an industry specific component; it finds that market volatility is on average responsible for a rather small share of total industry volatility — 6 to 9 percent in UK and 2 to 3 percent in Germany. The third paper looks at the heteroskedasticity in stock returns through an ARCH process supplemented with a set of conditioning information variables; it finds that the heteroskedasticity in stock returns allows for several forms of heteroskedasticity that include deterministic changes in variances due to seasonal factors, random adjustments in variances due to market and macro factors, and ARCH processes with past information. The fourth paper examines the role of higher moments — especially skewness and kurtosis — in determining the expected returns; it finds that total skewness and total kurtosis are more relevant non-beta risk measures and that they are costly to be diversified due either to the possible eliminations of their desirable parts or to the unsustainability of diversification strategies based on them.

"Musiikki merkitsee minulle paljon" : Asennetutkimus musiikin opiskelun merkityksellisyydestä peruskoulun 9. luokkalaisille

The main purpose of the Master Thesis was to find out what kind of attitudes the pupils in the 9th grade of Finnish comprehensive school have towards music as a school subject and compare it to the attitudes of the principals at a school level. The theoretical context of the research is based on the former studies of the significance of music education in the comprehensive school, the connection between learning and attitudes and the motivational factors towards the study motivation of music. In addition to this, I have analysed the role of the evaluation and the assessment from the point of view of developing the educational system and what is the role of management and leadership in relation to the pupils` behaviour and attitudes. The data of the research is the Finnish National Board of Education`s collected data of the assessment of the learning outcomes of arts education and it is nationally representative (N=5056 I phase and n=1570 II phase), both the Finnish-language and the Swedish-language pupil data. I have especially concentrated on the items of measuring the attitudes, the certain background variables and the questionnaire of the principals. The numerical data was analyzed using the multivariate statistical methods. The results of the research prove that in general the pupils and the principals think that music is quite significant as a school subject. The girls valued music on average more than the boys when comparing all the dimensions. The differences were systematic but the effect sizes were under 10 %. There were not statistically significant differences between the Finnish-language and the Swedish-language pupils. Comparing the grades of music in the 7th grade, the differences were growing linearly and the effect size was 15.7 %. There was a positive statistically significant correlation between the Significance of music and music as a hobby (Active interest in music, Informal interest in music, Taking part of music activities in the school) during free time. The strongest correlation were with the Active interest in music variable (r= 0.53, p= .000). Also the principals thought that music is important as a school subject considering the development of the pupil and the function of the school. The answers of the pupils were not clustering at a school level and there were no strong correlations between the attitudes of the pupils and the principals. A statistically nearly significant and a slight correlation (r= 0.21, p= .011) was found between the principals valuing the Significance of the music for school function and the pupils valuing the Benefits and hobbyism. The role of a well-motivated and active music teacher can be important from this point of view. The most important conclusion of the research was that the significance of music is a very personal individual level phenomenon. The results highlight also that in the pupils` opinion the most important thing about music lessons is to musical activity and learning as an experience.

Silva Fennica Vol. 9, 1975.

Julkaistu Silva Fennica Vol. 9(4) -numeron liitteenä.