Understanding solid-state transformations during dehydration: new insights using vibrational spectroscopy and multivariate modelling

Many active pharmaceutical ingredients (APIs) have both anhydrate and hydrate forms. Due to the different physicochemical properties of solid forms, the changes in solid-state may result in therapeutic, pharmaceutical, legal and commercial problems. In order to obtain good solid dosage form quality and performance, there is a constant need to understand and control these phase transitions during manufacturing and storage. Thus it is important to detect and also quantify the possible transitions between the different forms. In recent years, vibrational spectroscopy has become an increasingly popular tool to characterise the solid-state forms and their phase transitions. It offers several advantages over other characterisation techniques including an ability to obtain molecular level information, minimal sample preparation, and the possibility of monitoring changes non-destructively in-line. Dehydration is the phase transition of hydrates which is frequently encountered during the dosage form production and storage. The aim of the present thesis was to investigate the dehydration behaviour of diverse pharmaceutical hydrates by near infrared (NIR), Raman and terahertz pulsed spectroscopic (TPS) monitoring together with multivariate data analysis. The goal was to reveal new perspectives for investigation of the dehydration at the molecular level. Solid-state transformations were monitored during dehydration of diverse hydrates on hot-stage. The results obtained from qualitative experiments were used to develop a method and perform the quantification of the solid-state forms during process induced dehydration in a fluidised bed dryer. Both in situ and in-line process monitoring and quantification was performed. This thesis demonstrated the utility of vibrational spectroscopy techniques and multivariate modelling to monitor and investigate dehydration behaviour in situ and during fluidised bed drying. All three spectroscopic methods proved complementary in the study of dehydration. NIR spectroscopy models could quantify the solid-state forms in the binary system, but were unable to quantify all the forms in the quaternary system. Raman spectroscopy models on the other hand could quantify all four solid-state forms that appeared upon isothermal dehydration. The speed of spectroscopic methods makes them applicable for monitoring dehydration and the quantification of multiple forms was performed during phase transition. Thus the solid-state structure information at the molecular level was directly obtained. TPS detected the intermolecular phonon modes and Raman spectroscopy detected mostly the changes in intramolecular vibrations. Both techniques revealed information about the crystal structure changes. NIR spectroscopy, on the other hand was more sensitive to water content and hydrogen bonding environment of water molecules. This study provides a basis for real time process monitoring using vibrational spectroscopy during pharmaceutical manufacturing.

The Vexing Case of Igor Shafarevich, a Russian Political Thinker

The Russian mathematician, academician and former dissident Igor Shafarevich (b. 1923) is commonly mentioned in Western scholarly studies on perestroika and post-perestroika-era Russian politics as one of the most notable anti-Semites and extreme nationalists of the country. This notoriety owes to Shafarevich’s old samizdat article Russophobia, which was published in 1988. The scandal surrounding Russophobia came to a head when the president of The National Academy of Sciences in the United States asked Shafarevich, its honorary member, to resign. Nothing like this had ever happened in the academy’s history. The present dissertation discusses Shafarevich’s political activities, his texts and ideas as well as their reception. Particular attention is given to Russophobia, whose detailed examination proves very clearly that its reputation as an anti-Semitic text is groundless. The reasons for Russophobia’s hasty but fierce condemnation were many, but only one was that when the Soviet system began to tumble, it was commonly assumed that a vigorous rise in anti-Semitism and extreme nationalism in the Soviet Union/Russia would be just a matter of time. Many observers were highly sensitised to detecting its signs and symptoms. The dissertation also shows that most of those to write the first criticisms of Russophobia and to liken Shafarevich to the ideologues of Nazi Germany were the same people he had criticised in Russophobia for their deterministic view of history and irrational manner of connecting things for the purpose of fanning the flames of distrust between Russia’s Jews and Russians. In retrospect, it is fairly evident that Shafarevich actually managed to effectively “neutralise” the message of many of those obsessed with the Jews among his Russian contemporaries and contributed to the fact that anti-Jewish sentiments have been a great deal less popular in post-communist Russia than so many had feared and expected. The thesis also thoroughly discusses Shafarevich’s other texts and activities before Russophobia’s appearance and after it. In the 1970s, Shafarevich was one of the best-known dissidents in the Soviet Union. He worked together with academician Andrei Sakharov in a dissidents’ unofficial human rights committee and co-operated closely with Aleksandr Solzhenitsyn before Solzhenitsyn’s exile. Then, during the chaotic years of perestroika, Shafarevich defended the basic rights of ordinary citizens and warned that the hype concerning democracy could become counterproductive if the most palpable result of the reforms was the disappearance of citizens’ basic security and elementary social justice. One of the conclusions of the thesis is that even if the world around Shafarevich has changed considerably, his views have remained essentially the same since the late 1960s and early 1970s.

Phylogeny of a taxonomically difficult group and evolution of host location mechanism

The parasitic wasps are one of the largest insect groups and their life histories are remarkably variable. Common to all parasitic wasps is that they kill their hosts, which are usually beetles, butterflies and sometimes spiders. Hosts are often at a larval or pupal stage and live in concealed conditions, such as in plant tissue. Parasitic wasps have two main ways of finding their host. 1) They can detect chemical compounds emitted by damaged plant material or released by larvae living in plant tissue, and 2) detect the larvae by sound vibrations. Even though pupae are immobile and silent, and therefore do not cause vibration, parasitoids have, however, adapted to find passive developmental stages by producing vibration themselves by knocking the substrate with their antennae, and then detecting the echoes with their legs. This echolocation allows a parasitoid to locate its potential hosts that are deeply buried in wood. This study focuses on the relationships of the subfamily Cryptinae (Hymenoptera: Ichneumonidae) and related taxa, and the evolution of host location mechanism. There are no earlier studies of the phylogeny of the Cryptinae, and the position of related taxa are unclear. According to the earlier classification, which is entirely intuitional, the Cryptinae is divided into three tribes: Cryptini, Hemigasterini and Phygadeuontini. Further, these tribes are subdiveded into numerous subtribes. This work, based on molecular characters, shows that the cryptine tribes Cryptini, Phygadeuon¬tini and Hemigasterini come out largely as monophyletic groups, thus agreeing with the earlier classification. The earlier subtribal classification had no support. In addition, it is shown that modified antennal structures are associated with host usage of wood-boring coleopteran hosts. The cryptines have a clear modification series on their antennal tips from a simply tip to a hammer-like structure. The species with strongly modified antennae belong mostly to the tribe Cryptini and they utilise wood-boring beetles as hosts. Also, field observations on insect behaviour support this result.

Kuka kasvattaa, kuka opettaa? : Genealoginen tutkimus perheen ja koulun välisen kasvatusvastuun politiikasta

FAMILIES AND SCHOOLS AND THE POLITICS OF RESPONSIBILITIES - a genealogical study on family and school as carers and educators of the child population in modern society This study aims to uncover the politics behind such discourses in the media which have claimed the family to be totally responsible for children and which ignore the various responsibilities accorded to the state in matters concerning the child population. Using Max Weber s and Michael Mann s theorizing on the history of power relationships, feminist social history on patriarchy and Foucauldian power analytic concept of dispositif the study traces two competing child policies which have influenced the historical formation of modern generational order in Western societies. One of them is based on the interests of the hegemonic bourgeois elite and the other on the interests of the non-elite population, which were expressed during the phase of building the welfare state in Finland in the 1960 1980 s. The central strategies of the bourgeois child policy are 1) to construct the childhood years as a time for preparation and formation of the individual according to the interests of the elite, 2) to construct the family as the sole site of holistic care and responsibility of children in society, and 3) compulsory schooling of children of the non-elite population in state organized schools. To implement these strategies the elite uses strategically patriarchal cultural formations/dispositifs in modernized versions. The result has been the formation of a sexually divided and hierarchical order of care and education, where, on the one hand, there is the less important feminine care of children done by mothers at home and, on the other, the real education of the school, where children are made the object of authoritarian shaping and where the needs and the personal experiences of the child are ignored. The welfare order of care and education is based on the ethos of welfare society, where the state and the families are seen to share the responsibility for the child population. In this vein, families and schools are seen as partners who both have a caring attitude to children s welfare and learning. The study shows that discourses and terminology in the mainstream educational policy texts in Finland create a chaotic linguistic game which makes it difficult to have a rational discussion about the roles of family and school in the holistic care and education of children. This has opened the door to political discourses where familist interpretations of the question of responsibility are claimed to be based on law.

Ihmissalakuljetus ja ihmiskauppa Helsingin Sanomissa ja Dagens Nyheterissä

Human smuggling and trafficking in human beings are phenomena that are often represented as global and growing problems. Human smuggling means that a person is taken to a country illegally which means that smuggling does not exist without states. Trafficking in human beings by contrast means the exploitation of persons which makes it a human rights violation. The news coverage about both phenomena, especially about human trafficking, has grown rapidly during the last decade. However, there has not been research on the news coverage about phenomena in Finland and the news coverage on trafficking in human beings is little researched even in European countries. In this thesis I am comparing critically the newspaper content on the phenomena in Finland and in Sweden from the viewpoint of political and moral geography. Besides the contexts of the news, I paid attention to how identities in different scales, including the scale of the body, were represented in the news and how the boundaries between different identities were drawn in the news. As a methodology I used content analysis to classify the context of the news and discourse analysis to analyze how the different scales and boundaries between them were represented. The results address that in Finland especially the human smuggling is considered as a border issue and Finland´s location between East and West is emphasized, which points out that Finland´s location is a crucial part of the Finnish identity. In addition the linkages between human trafficking and prostitution are often debated in the news from different aspects. In Sweden meanwhile its´ political activeness in the fight against trafficking in human beings and international crime especially in the EU level are emphasized. Trafficking in human beings likewise prostitution according to Swedish law is seen as violence against women and the news are strongly against buying of sex as well. The states themselves, the state authorities and the EU are represented as active actors in both countries whereas international crime is represented as a threat and regions outside EU as chaotic. Additionally, illegal immigrants and the victims of trafficking are stigmatised. According to the results, the news coverage of both phenomena are used in constructing a more integrated national and European identity.

The Narrative Turn in the French Novel of the 1970s

The most important French literary movement of the 1950s and 1960s, the nouveau roman, radically questioned the idea of the novel as storytelling, claiming that narratives create a false illusion of the world’s intelligibility. However, in the 1970s storytelling finds its way back into the French novel – a shift that has been characterized as the “return of the narrative”. In my article, I argue that the “narrative turn” in the French novel of the 1970s can be seen as a turn towards a fundamentally hermeneutic view of the narrative mediatedness of our relation to the world. From a hermeneutic perspective, the nouveaux romanciers – insofar as they reject the narrative in order to disclose the discontinuous, fragmentary and chaotic nature of reality – hang onto the positivistic idea that “real” is only that which is independent of human meaning-giving processes. By contrast, the hermeneutists, such as Paul Ricoeur, consider also the human experience of the world to be real, and largely narrative in form. This view is shared by the principal novelists associated with the narrative turn, such as Michel Tournier to whom man is a “mythological animal”. However, after the nouveau roman , narratives have lost their innocence: they no longer appear as “natural” but are conscious of their own narrativity, historicity, and the way they represent only one possible – inevitably ethically and politically charged – perspective into reality. By making storytelling thematic and by telling “counter-stories” that question prevailing models of sense-making, Tournier and other “new storytellers” strive to promote critical reflection on the stories on the basis of which we orient to the world and narrate our lives – both as individuals and as communities.

The Far Eastern Question at the Washington Conference (1921-1922) with an outline of its implications for internal politics in China

This dissertation is a narrative account of the negotiations concerning the question of the Far East and the Shandong issue at the Washington Conference, leading to treaties, agreements and resolutions. In this dissertation, a certain stress is laid on the interaction between the Conference and the internal situation in China, particularly concerning the question of the implications of the Conference for Cabinet politics in Peking. Through the narrative account of the Conference, the general aim is an attempt to reassess the achievements of the Washington Conference. Too often the Washington Conference has been viewed negatively. The political aim behind the legal framework was to open the door to China as a sovereign State member of the international community whose territorial integrity was internationally recognized, despite its chaotic internal situation. It is undeniable that the Washington Conference opened a new chapter in modern Chinese history. The violations of the agreements concerning China that occurred in the 1930s should not lead to the belief that these agreements were of no value. Peace may not be lasting and evolves according to circumstances; agreements are transitory, and new situations need new arrangements. This dissertation tries to demonstrate that the agreements in themselves were not the cause of their failure, but the failure was due to the lack of determination on the part of the Signatories Powers to defend them.

Theorizing the Nature of Reflection

For the past decades reflection has been the buzzword of adult and higher education. Reflection is facilitated in many practices and there is abundant research on the issue. Despite the popularity of the concept, the reasons why bringing about reflection in educational practices is difficult remain unclear. The prevailing theories inform of the process in its ideal form. However, to a great extent, they fail to offer conceptual tools for understanding and working with the actualities of reflection. The aim of the doctoral thesis was to explore the challenges and prerequisites of reflection in order to theorize the nature of reflection. By the term reflection it is here referred to becoming aware of and questioning the assumptions that orient our thinking, feelings and actions. The doctoral thesis consists of five studies that approach these questions from different viewpoints and within different contexts. The methods involve both a philosophical and an empirical approach. This multifaceted approach embodies the aim of both gaining a more thorough grasp of the phenomenon and to develop the methodology of researching reflection. The theory building is based on conceptual analysis and rational reconstruction (see Davia 1998; Habermas 1979; Rorty1984) of Mezirow s (1981; 1991; 2000; 2009) theory of transformative learning. In order to explore the aspects which, based on the analysis, appeared insufficiently considered within Mezirow s theory, Damasio s (1994; 1999; 2003; 2010) theory on emotions and consciousness as well as Clausewitz s (1985) view on friction are used as complementary theories. Empirical analyses are used in dialogue with the theoretical, in order to challenge and refine the emerging theorization. Reflection is examined in three different contexts; regarding university teachers pedagogical growth, involuntarily childless women recovering from a life-event crisis, and soldiers preparing to act in chaotic situations of the battlefield as well as recovering from it. The choice of these contexts is based on Mezirow s notion of disorienting dilemma as a trigger for reflection. This notion indicates that reflection may more naturally emerge in association to life-event crises or other cumulative sets of instances, which bring our worldview and beliefs under question. Nevertheless, reflection is often being promoted in educational contexts in which the trigger conditions may not readily prevail. These contextual issues as well as the differences between the facilitated and non-facilitated contexts have not, however, been considered in detail within the research on reflection (or transformative learning). The doctoral thesis offers a new perspective into reflection which, as a further development on Mezirow s transformative learning theory, theorizes the nature of reflection. The developed theory explicates the prerequisites and challenges to reflection. The theory suggests that the challenges of reflection are fundamentally connected to the way the biological life-support system affects our thinking through emotions. While depicting the mechanisms that function as a counterforce to reflection, the developed theory also opens a perspective for considering possibilities for carrying out reflection, and suggests ways to locate and deal with the assumptions to be reflected on. The basic dynamic of the challenges to reflection was explicated by conceptually bridging the gap between Mezirow s and Damasio s theories, through exploring the connections between the meaning perspective and the biological functions of emotions. The concepts of comfort zone and edge-emotions were formed so as to depict the emotional orientation of our thinking, as part of the explanation of the nature of reflection.

Sneutrino-antisneutrino oscillations at colliders

Modern elementary particle physics is based on quantum field theories. Currently, our understanding is that, on the one hand, the smallest structures of matter and, on the other hand, the composition of the universe are based on quantum field theories which present the observable phenomena by describing particles as vibrations of the fields. The Standard Model of particle physics is a quantum field theory describing the electromagnetic, weak, and strong interactions in terms of a gauge field theory. However, it is believed that the Standard Model describes physics properly only up to a certain energy scale. This scale cannot be much larger than the so-called electroweak scale, i.e., the masses of the gauge fields W^+- and Z^0. Beyond this scale, the Standard Model has to be modified. In this dissertation, supersymmetric theories are used to tackle the problems of the Standard Model. For example, the quadratic divergences, which plague the Higgs boson mass in the Standard model, cancel in supersymmetric theories. Experimental facts concerning the neutrino sector indicate that the lepton number is violated in Nature. On the other hand, the lepton number violating Majorana neutrino masses can induce sneutrino-antisneutrino oscillations in any supersymmetric model. In this dissertation, I present some viable signals for detecting the sneutrino-antisneutrino oscillation at colliders. At the e-gamma collider (at the International Linear Collider), the numbers of the electron-sneutrino-antisneutrino oscillation signal events are quite high, and the backgrounds are quite small. A similar study for the LHC shows that, even though there are several backrounds, the sneutrino-antisneutrino oscillations can be detected. A useful asymmetry observable is introduced and studied. Usually, the oscillation probability formula where the sneutrinos are produced at rest is used. However, here, we study a general oscillation probability. The Lorentz factor and the distance at which the measurement is made inside the detector can have effects, especially when the sneutrino decay width is very small. These effects are demonstrated for a certain scenario at the LHC.

Towards Understanding Powder Behavior Via Simulation

The aim of this study was to investigate powder and tablet behavior at the level of mechanical interactions between single particles. Various aspects of powder packing, mixing, compression, and bond formation were examined with the aid of computer simulations. The packing and mixing simulations were based on spring forces interacting between particles. Packing and breakage simulations included systems in which permanent bonds were formed and broken between particles, based on their interaction strengths. During the process, a new simulation environment based on Newtonian mechanics and elementary interactions between the particles was created, and a new method for evaluating mixing was developed. Powder behavior is a complicated process, and many of its aspects are still unclear. Powders as a whole exhibit some aspects of solids and others of liquids. Therefore, their physics is far from clear. However, using relatively simple models based on particle-particle interaction, many powder properties could be replicated during this work. Simulated packing densities were similar to values reported in the literature. The method developed for describing powder mixing correlated well with previous methods. The new method can be applied to determine mixing in completely homogeneous materials, without dividing them into different components. As such, it can describe the efficiency of the mixing method, regardless of the powder's initial setup. The mixing efficiency at different vibrations was examined, and we found that certain combinations of amplitude, direction, and frequencies resulted in better mixing while using less energy. Simulations using exponential force potentials between particles were able to explain the elementary compression behavior of tablets, and create force distributions that were similar to the pressure distributions reported in the literature. Tablet-breaking simulations resulted in breaking strengths that were similar to measured tablet breaking strengths. In general, many aspects of powder behavior can be explained with mechanical interactions at the particle level, and single particle properties can be reliably linked to powder behavior with accurate simulations.