Copper-doped mesoporous silica nanospheres, a promising immunomodulatory agent for inducing osteogenesis

The application of mesoporous silica nanospheres (MSNs) loaded with drugs/growth factors to induce osteogenic differentiation of stem cells has been trialed by a number of researchers recently. However, limitations such as high cost, complex fabrication and unintended side effects from supraphysiological concentrations of the drugs/growth factors represent major obstacles to any potential clinical application in the near term. In this study we reported an in situ one-pot synthesis strategy of MSNs doped with hypoxia-inducing copper ions and systematically evaluated the nanospheres by in vitro biological assessments. The Cu-containing mesoporous silica nanospheres (Cu-MSNs) had uniform spherical morphology (∼100 nm), ordered mesoporous channels (∼2 nm) and homogeneous Cu distribution. Cu-MSNs demonstrated sustained release of both silicon (Si) and Cu ions and controlled degradability. The Cu-MSNs were phagocytized by immune cells and appeared to modulate a favorable immune environment by initiating proper pro-inflammatory cytokines, inducing osteogenic/angiogenic factors and suppressing osteoclastogenic factors by the immune cells. The immune microenvironment induced by the Cu-MSNs led to robust osteogenic differentiation of bone mesenchymal stem cells (BMSCs) via the activation of Oncostation M (OSM) pathway. These results suggest that the novel Cu-MSNs could be used as an immunomodulatory agent with osteostimulatory capacity for bone regeneration/therapy application. Statement of significance In order to stimulate both osteogenesis and angiogenesis of stem cells for further bone regeneration, a new kind of hypoxia-inducing copper doped mesoporous silica nanospheres (Cu-MSNs) were prepared via one-pot synthesis. Biological assessments under immune environment which better reflect the in vivo response revealed that the nanospheres possessed osteostimulatory capacity and had potential as immunomodulatory agent for bone regeneration/therapy application. The strategy of introducing controllable amount of therapeutic ions instead of loading expensive drugs/growth factors in mesoporous silica nanosphere provides new options for bioactive nanomaterial functionalization.

An extension of the continual reassessment method using decision theory

The primary goal of a phase I trial is to find the maximally tolerated dose (MTD) of a treatment. The MTD is usually defined in terms of a tolerable probability, q*, of toxicity. Our objective is to find the highest dose with toxicity risk that does not exceed q*, a criterion that is often desired in designing phase I trials. This criterion differs from that of finding the dose with toxicity risk closest to q*, that is used in methods such as the continual reassessment method. We use the theory of decision processes to find optimal sequential designs that maximize the expected number of patients within the trial allocated to the highest dose with toxicity not exceeding q*, among the doses under consideration. The proposed method is very general in the sense that criteria other than the one considered here can be optimized and that optimal dose assignment can be defined in terms of patients within or outside the trial. It includes as an important special case the continual reassessment method. Numerical study indicates the strategy compares favourably with other phase I designs.

Reading the Texture of Reality : Chaos Theory, Literature and the Humanist Perspective

Tutkimuksessa analysoidaan kaaosteorian vaikutusta kaunokirjallisuudessa ja kirjallisuudentutkimuksessa ja esitetään, että kaaosteorian roolia kirjallisuuden kentällä voidaan parhaiten ymmärtää sen avaamien käsitteiden kautta. Suoran soveltamisen sijaan kaaosteorian avulla on käyty uudenlaisia keskusteluja vanhoista aiheista ja luonnontieteestä ammennetut käsitteet ovat johtaneet aiemmin tukkeutuneiden argumenttien avaamiseen uudesta näkökulmasta käsin. Väitöskirjassa keskitytään kolmeen osa-alueeseen: kaunokirjallisen teoksen rakenteen teoretisointiin, ihmisen (erityisesti tekijän) identiteetin hahmottamiseen ja kuvailemiseen sekä fiktion ja todellisuuden suhteen pohdintaan. Tutkimuksen tarkoituksena on osoittaa, kuinka kaaosteorian kautta näitä aiheita on lähestytty niin kirjallisuustieteessä kuin kaunokirjallisissa teoksissakin. Väitöskirjan keskiössä ovat romaanikirjailija John Barthin, dramatisti Tom Stoppardin ja runoilija Jorie Grahamin teosten analyysit. Nämä kirjailijat ammentavat kaaosteoriasta keinoja käsitteellistää rakenteita, jotka ovat yhtä aikaa dynaamisia prosesseja ja hahmotettavia muotoja. Kaunokirjallisina teemoina nousevat esiin myös ihmisen paradoksaalisesti tunnistettava ja aina muuttuva identiteetti sekä lopullista haltuunottoa pakeneva, mutta silti kiehtova ja tavoiteltava todellisuus. Näiden kirjailijoiden teosten analyysin sekä teoreettisen keskustelun kautta väitöskirjassa tuodaan esiin aiemmassa tutkimuksessa varjoon jäänyt, koherenssia, ymmärrettävyyttä ja realismia painottava humanistinen näkökulma kaaosteorian merkityksestä kirjallisuudessa.

Contributions to the Theory of Finite-State Based Grammars

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

4th International Workshop on Theory and Application of Visualizations and Human-centric Aspects in Processes

This is the fourth TAProViz workshop being run at the 13th International Conference on Business Process Management (BPM). The intention this year is to consolidate on the results of the previous successful workshops by further developing this important topic, identifying the key research topics of interest to the BPM visualization community. Towards this goal, the workshop topics were extended to human computer interaction and related domains. Submitted papers were evaluated by at least three program committee members, in a double blind manner, on the basis of significance, originality, technical quality and exposition. Three full and one position papers were accepted for presentation at the workshop. In addition, we invited a keynote speaker, Jakob Pinggera, a postdoctoral researcher at the Business Process Management Research Cluster at the University of Innsbruck, Austria.

Is one-parameter scaling theory of localisation consistent? Comment on Schuh's comment

It is maintained that the one-parameter scaling theory is inconsistent with the physics of Anderson localisation.

Agent-based modelling of worker interactions and related impacts on workplace dynamics

This study uses agent based modelling to simulate the worker interactions within a workplace and to investigate how the interactions can have impact on the workplace dynamics. Two new models (Bounded Confidence with Bias model and Relative Agreement with Bias model) are built based on the theoretical foundation of two existing models. A new factor, namely bias, is added into the new models which raises several issues to be studied.

Space in Musical Semiosis : An Abductive Theory of the Musical Composition Process

Space in musical semiosis is a study of musical meaning, spatiality and composition. Earlier studies on musical composition have not adequately treated the problems of musical signification. Here, composition is considered an epitomic process of musical signification. Hence the core problems of composition theory are core problems of musical semiotics. The study employs a framework of naturalist pragmatism, based on C. S. Peirce’s philosophy. It operates on concepts such as subject, experience, mind and inquiry, and incorporates relevant ideas of Aristotle, Peirce and John Dewey into a synthetic view of esthetic, practic, and semiotic for the benefit of grasping musical signification process as a case of semiosis in general. Based on expert accounts, music is depicted as real, communicative, representational, useful, embodied and non-arbitrary. These describe how music and the musical composition process are mental processes. Peirce’s theories are combined with current morphological theories of cognition into a view of mind, in which space is central. This requires an analysis of space, and the acceptance of a relativist understanding of spatiality. This approach to signification suggests that mental processes are spatially embodied, by virtue of hard facts of the world, literal representations of objects, as well as primary and complex metaphors each sharing identities of spatial structures. Consequently, music and the musical composition process are spatially embodied. Composing music appears as a process of constructing metaphors—as a praxis of shaping and reshaping features of sound, representable from simple quality dimensions to complex domains. In principle, any conceptual space, metaphorical or literal, may set off and steer elaboration, depending on the practical bearings on the habits of feeling, thinking and action, induced in musical communication. In this sense, it is evident that music helps us to reorganize our habits of feeling, thinking, and action. These habits, in turn, constitute our existence. The combination of Peirce and morphological approaches to cognition serves well for understanding musical and general signification. It appears both possible and worthwhile to address a variety of issues central to musicological inquiry in the framework of naturalist pragmatism. The study may also contribute to the development of Peircean semiotics.

A Literary Turn : Rethinking the Roles of Generalization and Theory in Anglo-American Moral Philosophy

This work investigates the role of narrative literature in late-20th century and contemporary Anglo-American moral philosophy. It aims to show the trend of reading narrative literature for purposes of moral philosophy from the 1970 s and early 80 s to the present day as a part of a larger movement in Anglo-American moral philosophy, and to present a view of its significance for moral philosophy overall. Chapter 1 provides some preliminaries concerning the view of narrative literature which my discussion builds on. In chapter 2 I give an outline of how narrative literature is considered in contemporary Anglo-American moral philosophy, and connect this use to the broad trend of neo-Aristotelian ethics in this context. In chapter 3 I connect the use of literature to the idea of the non-generalizability of moral perception and judgment, which is central to the neo-Aristotelian trend, as well as to a range of moral particularisms and anti-theoretical positions of late 20th century and contemporary ethics. The joint task of chapters 2 and 3 is to situate the trend of reading narrative literature for the purposes of moral philosophy in the present context of moral philosophy. In the following two chapters, 4 and 5, I move on from the particularizing power of narrative literature, which is emphasized by neo-Aristotelians and particularists alike, to a broader under-standing of the intellectual potential of narrative literature. In chapter 4 I argue that narrative literature has its own forms of generalization which are enriching for our understanding of the workings of ethical generalizations in philosophy. In chapter 5 I discuss Iris Murdoch s and Martha Nussbaum s respective ways of combining ethical generality and particularity in a philosophical framework where both systematic moral theory and narrative literature are taken seriously. In chapter 6 I analyse the controversy between contemporary anti-theoretical conceptions of ethics and Nussbaum s refutation of these. I present my suggestion for how the significance of the ethics/literature discussion for moral philosophy can be understood if one wants to overcome the limitations of both Nussbaum s theory-centred, equilibrium-seeking perspective, and the anti-theorists repudiation of theory. I call my position the inclusive approach .

A simplified approach to a three-part Wiener-Hopf problem arising in diffraction theory

A direct and simple approach, utilizing Watson's lemma, is presented for obtaining an approximate solution of a three-part Wiener-Hopf problem associated with the problem of diffraction of a plane wave by a soft strip.

Theory and Analysis of Classic Heavy Metal Harmony

This thesis explores melodic and harmonic features of heavy metal, and while doing so, explores various methods of music analysis; their applicability and limitations regarding the study of heavy metal music. The study is built on three general hypotheses according to which 1) acoustic characteristics play a significant role for chord constructing in heavy metal, 2) heavy metal has strong ties and similarities with other Western musical styles, and 3) theories and analytical methods of Western art music may be applied to heavy metal. It seems evident that in heavy metal some chord structures appear far more frequently than others. It is suggested here that the fundamental reason for this is the use of guitar distortion effect. Subsequently, theories as to how and under what principles heavy metal is constructed need to be put under discussion; analytical models regarding the classification of consonance and dissonance and chord categorization are here revised to meet the common practices of this music. It is evident that heavy metal is not an isolated style of music; it is seen here as a cultural fusion of various musical styles. Moreover, it is suggested that the theoretical background to the construction of Western music and its analysis can offer invaluable insights to heavy metal. However, the analytical methods need to be reformed to some extent to meet the characteristics of the music. This reformation includes an accommodation of linear and functional theories that has been found rather rarely in music theory and musicology.

Society by Numbers : Studies on Model-Based Explanations in the Social Sciences

The aim of this dissertation is to provide conceptual tools for the social scientist for clarifying, evaluating and comparing explanations of social phenomena based on formal mathematical models. The focus is on relatively simple theoretical models and simulations, not statistical models. These studies apply a theory of explanation according to which explanation is about tracing objective relations of dependence, knowledge of which enables answers to contrastive why and how-questions. This theory is developed further by delineating criteria for evaluating competing explanations and by applying the theory to social scientific modelling practices and to the key concepts of equilibrium and mechanism. The dissertation is comprised of an introductory essay and six published original research articles. The main theses about model-based explanations in the social sciences argued for in the articles are the following. 1) The concept of explanatory power, often used to argue for the superiority of one explanation over another, compasses five dimensions which are partially independent and involve some systematic trade-offs. 2) All equilibrium explanations do not causally explain the obtaining of the end equilibrium state with the multiple possible initial states. Instead, they often constitutively explain the macro property of the system with the micro properties of the parts (together with their organization). 3) There is an important ambivalence in the concept mechanism used in many model-based explanations and this difference corresponds to a difference between two alternative research heuristics. 4) Whether unrealistic assumptions in a model (such as a rational choice model) are detrimental to an explanation provided by the model depends on whether the representation of the explanatory dependency in the model is itself dependent on the particular unrealistic assumptions. Thus evaluating whether a literally false assumption in a model is problematic requires specifying exactly what is supposed to be explained and by what. 5) The question of whether an explanatory relationship depends on particular false assumptions can be explored with the process of derivational robustness analysis and the importance of robustness analysis accounts for some of the puzzling features of the tradition of model-building in economics. 6) The fact that economists have been relatively reluctant to use true agent-based simulations to formulate explanations can partially be explained by the specific ideal of scientific understanding implicit in the practise of orthodox economics.

Makt, konst, elit - konstfältets positioner, relationer och resurser i 1940- och 1950-talens Helsingfors

The dissertation examines the power mechanisms and institutional power hierarchies of the 1940s-1950s era arts elite in Helsinki and their influence on issues of taste in the visual arts. For the purposes of this study, the elite is understood to consist mainly of the board members of the principal elected bodies in the field of the arts. The theoretical framework employed is based on Pierre Bourdieu s field theory and the network perspective. The author has examined what the key, pervasive valuations were that governed the exercising of power by the arts elite in issues of taste, involving determination of who was an acknowledged artist and what was good art. The dissertation demonstrates that this exercising of power was governed by certain collective practices which maintained the illusion that the exercising of power was democratic and based on artistic quality. These practices were the corporate system, using artistic arguments in issues of taste, and using networks in the exercising of power. The struggle in the field of the arts was about who ultimately was entitled to define the value of contemporary art; the issue did not arise regarding historical art. Artists managed to gain a leading position as gatekeepers in issues regarding contemporary art. The author discusses a number of conflicts in the field of the arts that highlight the institutional hierarchies and the capital held by the various players. The structural changes that occurred in administration in the field of cultural production in the 1950s led to the separation of bureaucratic competence on the one hand and aesthetic competence on the other. There was a hierarchy in the field of the arts between institutions, between instruments of legitimisation, and between the symbolic and social capital of players in the field. The hierarchy in the arts ultimately depended on how well the elite could influence tastes through the instruments at their disposal. The various instruments of legitimisation grants, purchases, etc. were ranked differently in the evaluation of acknowledged artists and good art. The dissertation discusses what values, in the form of types of symbolic capital, the arts elite embraced and what role these played in the elite s exercising of power, with particular focus on gender, language, region and economic capital. The aesthetic capital of an artist was of only minor importance in the exercising of power by the arts elite. The dissertation further discusses the points of contact between the arts elite and players in other fields, such as the economic, media and consumer fields. When the arts elite, through the Academy of Fine Arts, became an active player in the art market, this led to a hierarchy where the division between acknowledged and not-acknowledged galleries became sharper.