The Structural Basis for inorganic Pyrophosphatase Catalysis and Regulation

Inorganic pyrophosphatases (PPases) are essential enzymes for every living cell. PPases provide the necessary thermodynamic pull for many biosynthetic reactions by hydrolyzing pyrophosphate. There are two types of PPases: integral membrane-bound and soluble enzymes. The latter type is divided into two non-homologous protein families, I and II. Family I PPases are present in all kingdoms of life, whereas family II PPases are only found in prokaryotes, including archae. Family I PPases, particularly that from Saccharomyces cerevisiae, are among the most extensively characterized phosphoryl transfer enzymes. In the present study, we have solved the structures of wild-type and seven active site variants of S. cerevisiae PPase bound to its natural metal cofactor, magnesium ion. These structures have facilitated derivation of the complete enzyme reaction scheme for PPase, fulfilling structures of all the reaction intermediates. The main focus in this study was on a novel subfamily of family II PPases (CBSPPase) containing a large insert formed by two CBS domains and a DRTGG domain within the catalytic domain. The CBS domain (named after cystathionine beta-synthase in which it was initially identified) usually occurs as tandem pairs with two or four copies in many proteins in all kingdoms of life. The structure formed by a pair of CBS domains is also known as a Bateman domain. CBS domains function as regulatory units, with adenylate ligands as the main effectors. The DRTGG domain (designated based on its most conserved residues) occurs less frequently and only in prokaryotes. Often, the domain co-exists with CBS domains, but its function remains unknown. The key objective of the current study was to explore the structural rearrangements in the CBS domains induced by regulatory adenylate ligands and their functional consequences. Two CBS-PPases were investigated, one from Clostridium perfringens (cpCBS-PPase) containing both CBS and DRTGG domains in its regulatory region and the other from Moorella thermoacetica (mt CBS-PPase) lacking the DRTGG domain. We additionally constructed a separate regulatory region of cpCBS-PPase (cpCBS). Both full-length enzymes and cpCBS formed homodimers. Two structures of the regulatory region of cpCBS-PPase complexed with the inhibitor, AMP, and activator, diadenosine tetraphosphate, were solved. The structures were significantly different, providing information on the structural pathway from bound adenylates to the interface between the regulatory and catalytic parts. To our knowledge, these are the first reported structures of a regulated CBS enzyme, which reveal large conformational changes upon regulator binding. The activator-bound structure was more open, consistent with the different thermostabilities of the activator- and inhibitor-bound forms of cpCBS-PPase. The results of the functional studies on wild-type and variant CBS-PPases provide support for inferences made on the basis of structural analyses. Moreover, these findings indicate that CBS-PPase activity is highly sensitive to adenine nucleotide distribution between AMP, ADP and ATP, and hence to the energy level of the cell. CBS-PPase activity is markedly inhibited at low energy levels, allowing PPi energy to be used for cell survival instead of being converted into heat.

Esiopetuskirjojen harjoitukset kielellisen tietoisuuden kehittäjinä

Tutkimus oli kasvatustieteellinen varhaiskasvatuksen alan tutkimus, jossa hyödynnettiin kielitieteellistä käsitteistöä. Tutkimuksen kohteena olivat esiopetuskirjojen kielellisen tietoisuuden harjoitukset. Aineistona oli 12 esiopetuksen harjoituskirjaa ja opettajan opasta. Kirjoissa oli yhteensä yli 2000 sivua ja yli 1300 harjoitusta. Tarkemmassa analyysissä olleiden harjoitusten määrä oli noin 460. Analyysimenetelmänä käytettiin sisällönanalyysiä, jonka avulla tutkittiin, millaisia kielellisen tietoisuuden harjoituksia esiopetuskirjoissa oli ja miten harjoitukset etenivät. Kielellisen tietoisuuden harjoitukset luokiteltiin fonologisen, morfologisen ja syntaktisen tietoisuuden harjoituksiin. Fonologinen tietoisuus käsitettiin lapsen kyvyksi havaita ja käsitellä kielen äännerakennetta. Morfologisella tietoisuudella tarkoitettiin kykyä havaita ja käsitellä kielen morfeemeja eli pienimpiä merkityksellisiä osia. Syntaktisella tietoisuudella tarkoitettiin lapsen tietoisuutta siitä, miten lauseet rakentuvat. Olennaisiksi piirteiksi fonologisen tietoisuuden harjoituksissa identifioituivat harjoitusten edellyttämä tai harjoittama tietoisuuden taso, harjoitusten kohteena olevien lingvististen yksiköiden taso ja harjoitustyyppi sekä morfologisen ja syntaktisen tietoisuuden harjoituksissa tietoisuuden taso ja harjoitustyyppi. Tutkimuksessa luotiin aikaisempien tutkimusten pohjalta mallit siitä, miten eri harjoitukset etenisivät optimaalisesti lapsen kielellisen tietoisuuden kehittymisen kannalta. Eri harjoituskirjojen harjoitusten etenemistä verrattiin näihin malleihin. Fonologisen tietoisuuden harjoituksista voitiin tunnistaa viisi päätyyppiä, joista useat jakautuivat vielä alatyypeiksi. Harjoitusten alatyypit ilmaisivat yleensä harjoituksissa käytettävän kognitiivisen operaation – käytettiinkö harjoituksessa tunnistamista, yhdistämistä vai osiin jakamista. Tämä samoin kuin harjoituksessa käytetty lingvistinen yksikkö (sana, loppusointu, tavu tai äänne) ja tietoisuuden taso olivat yhteydessä harjoituksen vaikeuteen. Tutkimuksissa ja interventioissa esiopetusikäisilläkin käytettyjä muunteluharjoituksia, joissa sanasta tai tavusta poistetaan osa, siihen lisätään osa tai osaa siirretään, harjoituskirjoissa ei ollut. Morfologisen tietoisuuden harjoitukset kohdistuivat yhdyssanoihin, taivutuspäätteisiin tai johdoksiin. Syntaktisen tietoisuuden harjoituksista identifioitui yhdentoista harjoituslajin alatyypin kautta kuusi päätyyppiä. Tutkimusta voidaan hyödyntää esiopetuskirjojen arvioinnissa ja laatimisessa sekä varhaiskasvatus- ja esiopetuspedagogiikassa.

Tekijännimet Mikael Agricolan teosten kielessä. Henkilötarkoitteisten johdosten merkitykset, funktiot ja rakenteet

My research deals with agent nouns in the language of the works of Mikael Agricola (ca. 1510–1557). The main tasks addressed in my thesis have been to describe individual agent noun types, to provide a comprehensive picture of the category of agent nouns and to clarify the relations between different types of agent nouns. My research material consists of all the agent nouns referring to persons in the language of Agricola’s works, together with their context. The language studied is for the most part translated language. Agent nouns play an important role both in the vocabulary of natural language and in broader sentence structures, since in a text it is constantly necessary to refer to actors re-ferring to persons in the text. As a concept and a phenomenon, the agent noun is widely known in languages. It is a word formed with a certain derivational affixes, which typical-ly refers to a person. In my research the agent noun category includes both deverbal and denominal derivatives referring to persons, e.g. kirjoittaa > kirjoittaja (to write > writer), asua > asuva (to inhabit > inhabitant), imeä > imeväinen (to suck > suckling), juopua > juopunut (to drink > drunkard), pelätä > pelkuri (to fear > one who fears ‘a coward’), apu > apulainen (help/to help > helper); lammas > lampuri (sheep > shepherd). Besides original Finnish expressions, agent noun derivatives taken as such from foreign languages form a word group of central importance for the research (e.g. nikkari, porvari, ryöväri, based on the German/Swedish for carpenter, burgher, robber). Especially important for the formation of agent nouns in Finnish are the models offered by foreign languages. The starting point for my work is predominantly semantic, as both the criteria for collecting the material and the categorisation underlying the analysis of the material are based on semantic criteria. When examining derivatives, aspects relating to structure are also inevitably of central importance, as form and meaning are closely associated with each other in this type of vocabulary. The alliance of structure and meaning can be described in an illustrative manner with the help of structural schemata. The examination of agent nouns comprises on the one hand analysis of syntactic elements and on the other, study of cultural words in their most typical form. The latter aspect offers a research object in which language and the extralinguistic world, referents, their designations and cultural-historical reality are in concrete terms one and the same. Thus both the agent noun types that follow the word formation principles of the Finn-ish language and those of foreign origin borrowed as a whole into Finnish illustrate very well how an expression of a certain origin and formed according to a certain structural model is inseparably bound up with the background of its referent and in general with semantic factors. This becomes evident both on the level of the connection between cer-tain linguistic features and text genre and in relation to cultural words referring to per-sons. For example, the model for the designations of God based on agent nouns goes back thousands of years and is still closely linked in 16th century literature with certain text genres. This brings out the link between the linguistic feature and the genre in a very con-crete manner. A good example of the connection between language and the extralinguistic world is provided by the cultural vocabulary referring to persons. Originally Finnish agent noun derivatives are associated with an agrarian society, while the vocabulary relat-ing to mediaeval urbanisation, the Hansa trade and specialisation by trade or profession is borrowed and originates in its entirety from vocabulary that was originally German.

Trustworthy context dependency in ubiquitous systems

The modern society is getting increasingly dependent on software applications. These run on processors, use memory and account for controlling functionalities that are often taken for granted. Typically, applications adjust the functionality in response to a certain context that is provided or derived from the informal environment with various qualities. To rigorously model the dependence of an application on a context, the details of the context are abstracted and the environment is assumed stable and fixed. However, in a context-aware ubiquitous computing environment populated by autonomous agents, a context and its quality parameters may change at any time. This raises the need to derive the current context and its qualities at runtime. It also implies that a context is never certain and may be subjective, issues captured by the context’s quality parameter of experience-based trustworthiness. Given this, the research question of this thesis is: In what logical topology and by what means may context provided by autonomous agents be derived and formally modelled to serve the context-awareness requirements of an application? This research question also stipulates that the context derivation needs to incorporate the quality of the context. In this thesis, we focus on the quality of context parameter of trustworthiness based on experiences having a level of certainty and referral experiences, thus making trustworthiness reputation based. Hence, in this thesis we seek a basis on which to reason and analyse the inherently inaccurate context derived by autonomous agents populating a ubiquitous computing environment in order to formally model context-awareness. More specifically, the contribution of this thesis is threefold: (i) we propose a logical topology of context derivation and a method of calculating its trustworthiness, (ii) we provide a general model for storing experiences and (iii) we formalise the dependence between the logical topology of context derivation and its experience-based trustworthiness. These contributions enable abstraction of a context and its quality parameters to a Boolean decision at runtime that may be formally reasoned with. We employ the Action Systems framework for modelling this. The thesis is a compendium of the author’s scientific papers, which are republished in Part II. Part I introduces the field of research by providing the mending elements for the thesis to be a coherent introduction for addressing the research question. In Part I we also review a significant body of related literature in order to better illustrate our contributions to the research field.

Adaptive control of Hydraulic Drive

Adaptive control systems are one of the most significant research directions of modern control theory. It is well known that every mechanical appliance’s behavior noticeably depends on environmental changes, functioning-mode parameter changes and changes in technical characteristics of internal functional devices. An adaptive controller involved in control process allows reducing an influence of such changes. In spite of this such type of control methods is applied seldom due to specifics of a controller designing. The work presented in this paper shows the design process of the adaptive controller built by Lyapunov’s function method for the Hydraulic Drive. The calculation needed and the modeling were conducting with MATLAB® software including Simulink® and Symbolic Math Toolbox™ etc. In the work there was applied the Jacobi matrix linearization of the object’s mathematical model and derivation of the suitable reference models based on Newton’s characteristic polynomial. The intelligent adaptive to nonlinearities algorithm for solving Lyapunov’s equation was developed. Developed algorithm works properly but considered plant is not met requirement of functioning with. The results showed confirmation that adaptive systems application significantly increases possibilities in use devices and might be used for correction a system’s behavior dynamics.

A comparative analysis of preprocessing techniques of cardiac event series for the study of heart rhythm variability using simulated signals

In the present study, using noise-free simulated signals, we performed a comparative examination of several preprocessing techniques that are used to transform the cardiac event series in a regularly sampled time series, appropriate for spectral analysis of heart rhythm variability (HRV). First, a group of noise-free simulated point event series, which represents a time series of heartbeats, was generated by an integral pulse frequency modulation model. In order to evaluate the performance of the preprocessing methods, the differences between the spectra of the preprocessed simulated signals and the true spectrum (spectrum of the model input modulating signals) were surveyed by visual analysis and by contrasting merit indices. It is desired that estimated spectra match the true spectrum as close as possible, showing a minimum of harmonic components and other artifacts. The merit indices proposed to quantify these mismatches were the leakage rate, defined as a measure of leakage components (located outside some narrow windows centered at frequencies of model input modulating signals) with respect to the whole spectral components, and the numbers of leakage components with amplitudes greater than 1%, 5% and 10% of the total spectral components. Our data, obtained from a noise-free simulation, indicate that the utilization of heart rate values instead of heart period values in the derivation of signals representative of heart rhythm results in more accurate spectra. Furthermore, our data support the efficiency of the widely used preprocessing technique based on the convolution of inverse interval function values with a rectangular window, and suggest the preprocessing technique based on a cubic polynomial interpolation of inverse interval function values and succeeding spectral analysis as another efficient and fast method for the analysis of HRV signals

A systematic mapping study of web services discovery mechanisms

Context: Web services have been gaining popularity due to the success of service oriented architecture and cloud computing. Web services offer tremendous opportunity for service developers to publish their services and applications over the boundaries of the organization or company. However, to fully exploit these opportunities it is necessary to find efficient discovery mechanism thus, Web services discovering mechanism has attracted a considerable attention in Semantic Web research, however, there have been no literature surveys that systematically map the present research result thus overall impact of these research efforts and level of maturity of their results are still unclear. This thesis aims at providing an overview of the current state of research into Web services discovering mechanism using systematic mapping. The work is based on the papers published 2004 to 2013, and attempts to elaborate various aspects of the analyzed literature including classifying them in terms of the architecture, frameworks and methods used for web services discovery mechanism. Objective: The objective if this work is to summarize the current knowledge that is available as regards to Web service discovery mechanisms as well as to systematically identify and analyze the current published research works in order to identify different approaches presented. Method: A systematic mapping study has been employed to assess the various Web Services discovery approaches presented in the literature. Systematic mapping studies are useful for categorizing and summarizing the level of maturity research area. Results: The result indicates that there are numerous approaches that are consistently being researched and published in this field. In terms of where these researches are published, conferences are major contributing publishing arena as 48% of the selected papers were conference published papers illustrating the level of maturity of the research topic. Additionally selected 52 papers are categorized into two broad segments namely functional and non-functional based approaches taking into consideration architectural aspects and information retrieval approaches, semantic matching, syntactic matching, behavior based matching as well as QOS and other constraints.

Altaica from Harrassowitz

Kirjallisuusarvostelu

Adaptive Dynamics of Resource Specialization

Ecological specialization in resource utilization has various facades ranging from nutritional resources via host use of parasites or phytophagous insects to local adaptation in different habitats. Therefore, the evolution of specialization affects the evolution of most other traits, which makes it one of the core issues in the theory of evolution. Hence, the evolution of specialization has gained enormous amounts of research interest, starting already from Darwin’s Origin of species in 1859. Vast majority of the theoretical studies has, however, focused on the mathematically most simple case with well-mixed populations and equilibrium dynamics. This thesis explores the possibilities to extend the evolutionary analysis of resource usage to spatially heterogeneous metapopulation models and to models with non-equilibrium dynamics. These extensions are enabled by the recent advances in the field of adaptive dynamics, which allows for a mechanistic derivation of the invasion-fitness function based on the ecological dynamics. In the evolutionary analyses, special focus is set to the case with two substitutable renewable resources. In this case, the most striking questions are, whether a generalist species is able to coexist with the two specialist species, and can such trimorphic coexistence be attained through natural selection starting from a monomorphic population. This is shown possible both due to spatial heterogeneity and due to non-equilibrium dynamics. In addition, it is shown that chaotic dynamics may sometimes inflict evolutionary suicide or cyclic evolutionary dynamics. Moreover, the relations between various ecological parameters and evolutionary dynamics are investigated. Especially, the relation between specialization and dispersal propensity turns out to be counter-intuitively non-monotonous. This observation served as inspiration to the analysis of joint evolution of dispersal and specialization, which may provide the most natural explanation to the observed coexistence of specialist and generalist species.

Use of magnitude-squared coherence to identify the maximum driving response band of the somatosensory evoked potential

The present study proposes to apply magnitude-squared coherence (MSC) to the somatosensory evoked potential for identifying the maximum driving response band. EEG signals, leads [Fpz'-Cz'] and [C3'-C4'], were collected from two groups of normal volunteers, stimulated at the rate of 4.91 (G1: 26 volunteers) and 5.13 Hz (G2: 18 volunteers). About 1400 stimuli were applied to the right tibial nerve at the motor threshold level. After applying the anti-aliasing filter, the signals were digitized and then further low-pass filtered (200 Hz, 6th order Butterworth and zero-phase). Based on the rejection of the null hypothesis of response absence (MSC(f) > 0.0060 with 500 epochs and the level of significance set at a = 0.05), the beta and gamma bands, 15-66 Hz, were identified as the maximum driving response band. Taking both leads together ("logical-OR detector", with a false-alarm rate of a = 0.05, and hence a = 0.0253 for each derivation), the detection exceeded 70% for all multiples of the stimulation frequency within this range. Similar performance was achieved for MSC of both leads but at 15, 25, 35, and 40 Hz. Moreover, the response was detected in [C3'-C4'] at 35.9 Hz and in [Fpz'-Cz'] at 46.2 Hz for all members of G2. Using the "logical-OR detector" procedure, the response was detected at the 7th multiple of the stimulation frequency for the series as a whole (considering both groups). Based on these findings, the MSC technique may be used for monitoring purposes.

Capital investments planning and life cycle simulations for the new valves manufacturing facility in Russia

The focus of the research is on the derivation of the valid and reliable performance results regarding establishment and launching of the new full-scale industrial facility, considering the overall current conditions for the project realization in and out of Russia. The study demonstrates the process of the new facility concept development, with following perfor-mance calculation, comparative analyzes conduction, life-cycle simulations, performance indicators derivation and project`s sustainability evaluation. To unite and process the entire input parameters complexity, regards the interlacing between the project`s internal technical and commercial sides on the one hand, and consider all the specifics of the Russian conditions for doing business on the other hand, was developed the unique model for the project`s performance calculation, simulations and results representation. The complete research incorporates all corresponding data to substantiate the assigned facility`s design, sizing and output capacity for high quality and cost efficient ferrous pipe-line accessories manufacturing, as well as, demonstrates that this project could be suc-cessfully realized in current conditions in Russia and highlights the room for significant performance and sustainability improvements based on the indexes of the derived KPIs.

Notas críticas sobre a macroeconomia novo-Keynesiana

This article shows that, in spite of its great steps towards reality, new-Keynesian macroeconomics seems to be a non-systematic construction with problems originated from "ad hoc" hypothesis required to explain the non neutrality of money and the existence of disequilibria in the short run. In particular, it seems that prices and wages rigidities stand in sandy bases and that the derivation of the IS and LM curves from neoclassical fundamentals is problematic. Even disregarding the apparent difficulties of the neoclassical theory of value and distribution, the new-Keynesian connections between interest rate, money, and output do not seem fully consistent.

A geochemical and petrological study of volcanic rocks in the Beardmore-Geraldton Archaean Greenstone Belt, Northwestern Ontario

Three repetitive sequences of northward youngIng, east striking, linear, volcano-sedimentary units are found in the late Archaean BeardmoreGeraldton greenstone belt, situated within the Wabigoon subprovince of the Superior Province of northwestern Ontario. The volcanic components are characterised by basaltic flows that are pillowed at the top and underlain by variably deformed massive flows which may In part be intrusive. Petrographic examination of the volcanic units indicates regional metamorphism up to greenschist facies (T=3250 C - 4500 C, P=2kbars) overprinted by a lower amphibolite facies thermal event (T=5750 C, P=2kbars) confined to the south-eastern portion of the belt. Chemical element results suggest olivine, plagioclase and pyroxene are the main fractionating mineral phases. Mobility studies on the varIOUS chemical elements indicate that K, Ca, Na and Sr are relatively mobile, while P, Zr, Ti, Fet (total iron = Fe203) and Mg are relatively immobile. Discriminant diagrams employing immobile element suggests that the majority of the samples are of oceanic affinity with a minor proportion displaying an island arc affinity. Such a transitional tectonic setting IS also refle.cted in REE data where two groups of volcanic samples are recognised. Oceanic tholeiites are LREE depleted with [La/Sm] N = 0.65 and a relatively flat HREE profile with [Sm/Yb] N = 1.2. Island arc type basalts (calc-alkaline) are LREE enriched, with a [La/Sm] N = 1.6, and a relatively higher fractionated HREE profile with [Sm/Yb] N = 1.9. Petrogenetic modelling performed on oceanIC tholeiites suggests derivation from a depleted spinel lherzolite source which undergoes 20% partial melting. Island arc type basalts can be derived by 10% partial melting of a hypothetical amphibolitised oceanic tholeiite source. The majority of the volcanic rocks in the Beardmore-Geraldton Belt are interpreted to represent fragments of oceanic crust trapped at a consuming plate margin. Subsequent post accretionary intrusion of gabbroic rocks (sensu lato) with calc-alkaline affinity is considered to result in the apparent hybrid tectonic setting recognized for the BGB.

A treatment of atomic mean square displacement in higher order perturbation theory

A general derivation of the anharmonic coefficients for a periodic lattice invoking the special case of the central force interaction is presented. All of the contributions to mean square displacement (MSD) to order 14 perturbation theory are enumerated. A direct correspondance is found between the high temperature limit MSD and high temperature limit free energy contributions up to and including 0(14). This correspondance follows from the detailed derivation of some of the contributions to MSD. Numerical results are obtained for all the MSD contributions to 0(14) using the Lennard-Jones potential for the lattice constants and temperatures for which the Monte Carlo results were calculated by Heiser, Shukla and Cowley. The Peierls approximation is also employed in order to simplify the numerical evaluation of the MSD contributions. The numerical results indicate the convergence of the perturbation expansion up to 75% of the melting temperature of the solid (TM) for the exact calculation; however, a better agreement with the Monte Carlo results is not obtained when the total of all 14 contributions is added to the 12 perturbation theory results. Using Peierls approximation the expansion converges up to 45% of TM• The MSD contributions arising in the Green's function method of Shukla and Hubschle are derived and enumerated up to and including 0(18). The total MSD from these selected contributions is in excellent agreement with their results at all temperatures. Theoretical values of the recoilless fraction for krypton are calculated from the MSD contributions for both the Lennard-Jones and Aziz potentials. The agreement with experimental values is quite good.

An Interactive Theorem Prover for First-Order Dynamic Logic

Dynamic logic is an extension of modal logic originally intended for reasoning about computer programs. The method of proving correctness of properties of a computer program using the well-known Hoare Logic can be implemented by utilizing the robustness of dynamic logic. For a very broad range of languages and applications in program veri cation, a theorem prover named KIV (Karlsruhe Interactive Veri er) Theorem Prover has already been developed. But a high degree of automation and its complexity make it di cult to use it for educational purposes. My research work is motivated towards the design and implementation of a similar interactive theorem prover with educational use as its main design criteria. As the key purpose of this system is to serve as an educational tool, it is a self-explanatory system that explains every step of creating a derivation, i.e., proving a theorem. This deductive system is implemented in the platform-independent programming language Java. In addition, a very popular combination of a lexical analyzer generator, JFlex, and the parser generator BYacc/J for parsing formulas and programs has been used.