The Use of Dolls and Figures in Therapy: A Literature Review

Therapists utilize various means to treat clients, which includes the use of toys, games, dolls, and other media. By reviewing existing literature on therapeutic uses of dolls, I wish to shed light on the potential benefit of using dolls and figurines in the therapeutic setting. The use of dolls in therapy has been utilized in various ways, aligning with themes of narrative, drama, play, and expression. Through a review of existing literature and case study, the use of dolls as a therapeutic intervention will be explored through examining their use in multiple populations and age groups. By highlighting their wide range of applications, dolls demonstrate to be useful objects in the therapeutic context. Existing literature outlines dolls as a means of expression through interaction and play as well as through the act of making a doll or figure. The potential benefits and practical uses of dolls in therapy are summarized and explored through literature review

Essays on Institutional Investor Trading

This dissertation consists of three chapters that examine the role of institutional investors in stock market efficiency. Institutions are important and influential market participants. This study aims to analyze whether institutional investor trading is consistent with higher attention and better skill, what is the impact of institutional trading on future asset prices and how does institutional trading relate to the liquidity in the market. The first chapter of the dissertation analyzes institutional investors’ response to stock level liquidity shocks. I find that institutions, especially the transient ones, buy stocks that experience positive liquidity shocks and sell those that experience negative ones. High-low decile portfolios representing difference between stocks with positive and negative liquidity shocks are related to future increase in institutional trading 53% higher than the amount of average monthly institutional trading. Changes in ownership induced by the high-low liquidity shocks positively predict 5.03% annualized return in the subsequent month. This trading activity further amplifies the liquidity shocks through feedback effects. The results suggest that institutional investors help improve market efficiency by exploiting the mispricing associated with liquidity shocks, although their trading exacerbates stock level liquidity uncertainty. The second chapter examines trading behavior of institutional investors in attention grabbing stocks. I find that institutions increase their trading volume on high attention days, both buys and sells. Both liquidity demanding and supplying institutions are abnormally active on those days, despite significantly higher transaction costs. I document outstanding demand for liquidity by institutional investors on high attention days. Those findings suggest that institutional trades are consistent with limited attention theory. Institutions’ trading decisions result in poor performance, especially following demand buys, and even more so on high attention days. Professional money managers who supply liquidity enjoy positive long-term performance, particularly those trading on high attention days, and they benefit from higher transaction costs. Overall the study contributes to the discussion on the role of institutional investors in the stock market, pointing to their low sophistication and poor trading decisions, which may lead to exacerbation of the mispricing in the market. On the other hand, some of them serve a positive and stabilizing role as liquidity suppliers. The third chapter studies aggregate herding behavior of institutional investors over 35 years. I find significant evidence of aggregate herding over that time period, based on Sias (2004) dynamic herding measure. Interestingly, I observe large shocks to herding activity during the dot com bubble in 2000-2001, in times of high uncertainty regarding the valuations of new companies. There is a positive relation between herding and aggregate market uncertainty as measured by the average stock correlation. The analysis of relation between herding and future returns does not however point to the distorting impact of herding on information incorporation into stock prices. I document a positive relationship between herding activity and next quarter aggregate market return. There is no reversal in the following 3 quarters, contributing to the view that herding may in fact enhance overall pricing efficiency in the market

Outcrop-Based Gamma-Ray Characterization of the Woodford Shale of South-Central Oklahoma

The late Devonian (Frasnian, Fammenian) and basal Mississippian (Tournasian) in age Woodford Shale was studied in Murray, Carter, and Pontotoc Counties, Oklahoma. The purpose of this study was to determine if a relationship exists between outcrop lithofacies and gamma-ray response and if ultimately this relationship can be extended into the subsurface. Over 500 gamma-ray readings were collected from five studied outcrops to complete this work. Thin-section analysis, total organic carbon, x-ray diffraction and vitrinite reflectance data were also integrated in this study.Boone Pickens School of Geolog

Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89.: Activation of Aurora-A by Nucleophosmin

International audienceAurora A (AurA) is a major mitotic protein kinase involved in centrosome maturation and spindle assembly. Nucleophosmin/B23 (NPM) is a pleiotropic nucleolar protein involved in a variety of cellular processes including centrosome maturation. In the present study, we report that NPM is a strong activator of AurA kinase activity. NPM and AurA coimmunoprecipitate and colocalize to centrosomes in G2 phase, where AurA becomes active. In contrast with previously characterized AurA activators, NPM does not trigger autophosphorylation of AurA on threonine 288. NPM induces phosphorylation of AurA on serine 89, and this phosphorylation is necessary for activation of AurA. These data were confirmed in vivo, as depletion of NPM by ribonucleic acid interference eliminated phosphorylation of CDC25B on S353 at the centrosome, indicating a local loss of AurA activity. Our data demonstrate that NPM is a strong activator of AurA kinase activity at the centrosome and support a novel mechanism of activation for AurA

Understanding interactions in face-to-face and remote undergraduate science laboratories

This paper reviews the ways in which interactions have been studied, and the findings of such studies, in science education in both face-to-face and remote laboratories. Guided by a systematic selection process, 27 directly relevant articles were analysed based on three categories: the instruments used for measuring interactions, the research findings on student interactions, and the theoretical frameworks used in the studies of student interactions. In face-to-face laboratories, instruments for measuring interactions and the characterisation of the nature of interactions were prominent. For remote laboratories, the analysis of direct interactions was found to be lacking. Instead, studies of remote laboratories were mainly concerned with their practical scope. In addition, it is found that only a limited number of theoretical frameworks have been developed and applied in the research design. Existent theories are summarised and possible theoretical frameworks that may be implemented in studies of interactions in undergraduate laboratories are proposed. Finally, future directions for research on the interrelationship between student interactions and laboratory learning are suggested

Science teachers’ experiences of inquiry-based learning through a serious game:a phenomenographic perspective

This study employed a phenomenographic approach to investigate science teachers’ conceptions of inquiry-based learning through a serious game. Simaula is a prototype game designed and used as a virtual practicum for eliciting understandings on how in-game inquiry was appeared to, or experienced by, the participating teachers. Group interviews with 20 secondary education science teachers revealed four qualitatively different ways of experiencing inquiry-based learning through Simaula: (a) as uncovering insights about student’s learning needs, interests and emotions; (b) as generating ideas and concepts for meaningful inquiry; (c) as a set of operations for designing and carrying out scientific research; and (d) as authentic inquiry for enabling knowledge building processes. Seven dimensions of variation have been identified viewed as contextual influences on conceptions of in-game inquiry constituting discernment of: epistemic inquiry-based learning modes; role of teacher; role of student; game-play focus; core mechanics focus; feedback and progress mechanics and game uncertainty. The results illuminated a partial in-game inquiry approach with distinct epistemic modes from developing empathy and meaning making to knowledge construction and knowledge building. The findings also indicated that game design elements played central role in shaping conceptions of in-game inquiry from focusing on rules and logic as means to completing the game’s level to understanding the complexity of core mechanics for developing and transferring in-game inquiry to the real classroom. This insinuates that distinct game design properties may be considered in terms of extending intrinsic in-game inquiry experiences to actual in-class inquiry practice

Involvement of the mitotic kinase Aurora A in DNA damage response

Die Hauptaufgabe der Zellteilung ist die korrekte und komplette Verdoppelung des Genoms und die folgende gleichmässige Aufteilung der Chromosomen auf die beiden Tochterzellen. Dieser Prozess wird durch eine Familie von Cyclin-abhängigen Kinasen dirigiert. Jede Kinase verbindet sich mit einer eigenen Klasse von Cyclinen, welche benötigt werden, um die verschiedenen Stadien des Zellzyklus zu durchlaufen. In höheren Eukaryoten sind der Übergang von der G2- zur M-Phase und der Abschluss der Mitose abhängig von der Aktivität eines Komplexes aus Cylin B und Cdk1. Die Aktivität von Cdk1 ist sehr straff reguliert durch Phoshorylierung und Dephosphorylierung. Die volle Aktivierung von Cyclin B/Cdk1 leitet die Mitose ein. Aktuelle Studien haben das Wissen über die Zellteilung erweitert und aufgezeigt, dass neben Cdk1 auch weitere Proteinkinasen wichtige Funktionen haben. Die Centrosomen-Reifung und die Aufteilung der Chromosomen erfordert die Beteiligung von Polo-ählichen Kinasen. Die Aufteilung der Chromosomen scheint dahingegen von Nek2 reguliert zu sein. Eine weitere wichtige Rolle in der Aufteilung der Chromosomen, der Orientierung der Chromosomen und der Cytokinese ist für Mitglieder der Aurora Familie postuliert worden. Die genomische Stabilität wird nicht nur durch den normalen Metabolismus, sondern auch durch verschiedenste Chemikalien und Strahlung ständig gefährdet. Um die korrekte Zellteilung auch in solchen Fällen zu gewährleisten, bremsen Zellzyklus Kontrollpunkte den Zellzyklus ab oder stoppen ihn ganz. Dadurch wird eine Reparatur des Schadens möglich. Falls das Ausmass des Schadens zu gross ist, wird die Apoptose eingeleitet. Der G2-Kontrollpunkt verhindert, dass Zellen die Mitose beginnen, falls DNS Schäden vorhanden sind. Diese Schäden können während der G2-, oder früher in der S- oder sogar in der G1-Phase entstanden sein, falls die Schäden dann nicht repariert worden sind. Phosphatasen der Cdc25-Familie, welche normalerweise Cdk1 an der G2/M-Grenze aktivieren, werden in solchen Fällen inhibiert und degradiert. Ausserdem vermitteln ATM/ATR und Chk1/Chk2 ein Signal, welches zu einer Sequestrierung des Cyclin B/Cdk1 Komplexes in verschiedenen subzellulären Kompartimente führt. Kürzlich wurde gezeigt, dass Kinasen, wie Plk1, Nek2 und Aurora B, welche in die normale Spindel Formation involviert sind, auch eine wichtige Rolle in der Zellantwort auf DNA Schäden spielen. In dieser Dissertation wurde Etoposid, ein Topoisomerase II Inhibitor, benutzt, um Doppelstrangbrüche zu erzeugen, um die Rolle von Aurora A in der DNS-Schadensantwort zu untersuchen. Wir haben herausgefunden, dass die Aktivität von Aurora A durch die Zellantwort auf Doppelstrangbrüche in der G2/M-Phase reguliert wird (Krystyniak A. et al, 2006). Nach Behandlung mit Etoposid war die Kinaseaktivität des Enzyms inhibiert und sein Proteinlevel stieg an. Die Frage war, ob Aurora A abhängig ist von Cdk1 oder umgekehrt. Wir haben herausgefunden, dass die Inhibition von Aurora A und Cdk1 unabhängig voneinander auftritt. Dass die Deaktivierung von Aurora A durch die ATM/ATR Kinasen bewerkstelligt wird, konnten wir durch den ATM/ATR Inhibitor Koffein zeigen. Ausserdem konnten wir durch Blockierung von Chk1 mit dessen Inhibitor UCN01 und siRNA zeigen, dass das Signal an Aurora A über einen Chk1-abhängigen Signalweg geleitet wird. Diese Resultate wurden zusätzlich durch Experimente mit einer Zelllinie, welche defizient ist in Chk2 (HCT15), verifiziert. Eine Punktmutation in Aurora A, S342 zu A, führt zu einem aktiven Enzym, das nicht mehr durch DNS-Schäden deaktiviert werden kann. Die S342 Phosphorylierungsstelle wurde bereits früher als eine negative Regulationsstelle postuliert. Diese Stelle liegt direkt neben einem der Bindemotive für PP1, einem Aurora A Interaktionspartner. Nach Behandlung mit Etoposid verringert sich die Interaktion zwischen diesen zwei Proteinen sehr stark (Krystyniak A. et al, manuscript submitted). Die S342 Mutation zu Alanin, das nicht phosphoryliert werden kann, verhindert die Ablösung der Phosphatase vom Komplex. Auf der anderen Seite haben wir herausgefunden, dass eine Mutation an derselben Stelle zu einem Aspartat, welches eine ständige Phosphorylierung imitiert, die Bildung des Komplexes aus PP1 und Aurora A verhindert. Zwei verschiedene Ansätze wurden gewählt um die Frage zu untersuchen, ob Aurora A in vorhergehend geschädigten Zellen eine mitotische Zellteilung einleiten kann. Transiente Transfektion von Zellen mit aktiven Formen von Aurora A (Wildtyp oder S342A, aber nicht mit dem kinase-inaktiven S342D Aurora A) hat den Zellen nicht erlaubt die Zellzyklusblockade, welche durch DNS Schäden induziert wurde, zu überwinden und mit der Mitose fortzufahren. Da eine Transfektion auch experimentelle Nachteile mit sich bringt, wie lange Transkriptions- und Translationszeiten oder eine Überexpression des Proteins, wurden direkt aktives Protein in Zellen transduziert, welche in der G2 Phase arretiert waren, gleich nachdem Doppelstrangbrüche induziert wurden. Dies hat den Zellen ermöglicht sogleich mit der Mitose zu beginnen, obwohl die Schäden noch nicht repariert worden waren. Molekular betrachtet ergibt sich, dass aktives Aurora A die Wiederaufnahme des Zellzyklus über eine Reaktivierung von Cdk1 erwirkt. Daher spielt Aurora A eine Schlüsselrolle im Signalweg oberhalb von Cdk1 - mindestens solange DNS Schäden bestehen. Aurora A wird ebenso wie andere Mitglieder dieser Proteinfamilie durch Phosphorylierung reguliert. Die Phosphorylierung einer konservierten Aminosäure von Aurora A, Threonin 288, ergibt eine beträchtliche Steigerung der Kinaseaktivität. Dieser Baustein befindet sich in einer Schlaufe in der katalytischen Domäne. Wir konnten zeigen, dass die Phosphorylierung von T288 möglicherweise durch einen intermolekularen Autophosphorylierungsmechanismus stattfindet. Ausserdem konnten wir zeigen, dass PKA in vivo nicht involviert ist in die Phosphorylierung von T288, obwohl diese Kinase früher in vitro als dafür verantwortlich befunden wurde. Wie niemand gedacht hätte, wurde eine Phosphorylierung dieser Stelle auch in DNS geschädigten Zellen gefunden. Das Ausmass der Phosphorylierung war dasselbe wie in mitotischen Zellen. Da Aurora A unter solchen Umständen nicht aktiv ist, wie wir durch unsere Kinase Tests zeigen konnten, müssen auch andere Mechanismen in der Steuerung der Aktivität eine Rolle spielen. The major mission of the cell division is a faithful and complete duplication of the genome with equal partition of chromosomes into subsequent cell generations. Progression through different stages of the cell cycle is governed by the activity of several members of the Cyclin-dependent kinase family, each pairing with the separate class of Cyclin. In higher eukaryotes, transition from G2 to M phase and completion of mitosis requires action of Cyclin B paired with Cdk1. Cdk1 is tightly regulated by phosphorylation/dephosphorylation processes and only full activation of Cyclin B/Cdk1 complex triggers the initiation of mitosis. Although the role of Cdk1 is crucial and Cdk1 remains the major regulator of mitosis, recent studies have broadened our knowledge of cell division, revealing the presence and importance of other protein kinases. Centrosome maturation and chromosome segregation require the action of Polo-like kinases, whereas separation of centrosomes seems to be regulated by the kinase Nek2. An important role in centrosome separation, chromosome bi-orientation and cytokinesis has been postulated for Aurora family members. Genomic stability is under constant threat not only from the products of normal cellular metabolism, but also from radiation and chemicals present in the environment. To ensure proper cell division upon the occurrence damage to DNA, checkpoints are triggered and result in slowing or stopping cell cycle transitions. This, in turn, enables the repair of damage or, when it is too extensive, facilitate the triggering of cell death. Normal cells possess a full complement of cell cycle checkpoints, whereas cancer cells, in most cases, acquire mutations that result in bypass of the checkpoints. Nonetheless, the G2 checkpoint is operative also in cancer cells, since division with incompletely duplicated or damaged DNA is incompatible with life. At the molecular level the G2 checkpoint prevents cells from entering mitosis through inactivation of Cyclin B/Cdk1. This occurs in an ATM/ATR-dependent manner and involves Chk1/Chk2-mediated sub-cellular sequestration and inhibition or degradation of members of the Cdc25 family of phosphatases, which normally activate Cdk1 at the G2/M boundary. It has been recently discovered that kinases involved in spindle formation, like Plk1, Nek2 and Aurora B, play important roles in the cellular response to DNA damage. In the studies presented in this dissertation I used etoposide, a topoisomerase II poison, to create double strand breaks in DNA, in order to elucidate the role of Aurora A in the DNA damage response. I found that Aurora A indeed is one of the targets of the double-strand break response in G2/M phase (Krystyniak A. et al, 2006). The kinase activity of the enzyme was actively inhibited upon etoposide treatment and this was accompanied by prolonged accumulation of the protein. I also addressed the issue of dependence between Aurora A and Cdk1, showing that the former is not downstream of the latter, but rather inhibition of Aurora A and Cdk1 by DNA damage occurs independently. By using caffeine, an ATM/ATR inhibitor, I showed that Aurora A de-activation in response to DNA damage was dependent on those kinases. More precisely, using cell lines deficient in ATM or conditionally expressing kinase-dead ATR, I was able to confirm that signalling to Aurora A was mediated through ATM. Further, by means of specifically blocking Chk1 with its inhibitor UCN01 or by using siRNA to Chk1, I showed that the signals were delivered to Aurora A via a Chk1-dependent pathway. Those results were additionally confirmed by experiments with cells functionally deficient in Chk2 (HCT15). Looking for the mechanism responsible for Aurora A inhibition, I found that the point mutation S342 to A resulted in a mutant that was active and could not be inhibited by DNA damage. S342 was already postulated as a negative site and it is located directly next to one of the binding motifs for PP1 – a known Aurora A interaction partner. Upon etoposide treatment, however, the interaction between Aurora A and PP1 is highly diminished (Krystyniak A. et al, manuscript submitted). Using the point mutant A342 of Aurora A I found that mutation to non-phosphorylable alanine prevents releasing of the phosphatase from the complex. On the contrary, mutation of the same site to aspartic acid, to mimick constitutive phosphorylation, resulted in complete abolishment of binding, irrespective of the presence of DNA damage. Finally, I took advantage of two independent approaches to examine the possibility that reconstitution of Aurora A activity in DNA damaged cells may trigger mitotic cell division. Transient transfection of cells with active (wild-type or S342A) but not with inactive (kinase-dead or S342D) forms of Aurora A, enabled them to bypass the DNA damage-induced cell cycle arrest and proceed to mitosis. To avoid large overexpression of proteins in transfection assays and given that such method requires time for the protein to be expressed, I used a more appropriate approach. This allows rapid transduction of proteins in the cell in a manner compatible with the kinetic of the G2 arrest in response to DNA damage. To this end, I directly transduced active AuroraA isoforms into G2-arrested cells, immediately after inducing double-strand breaks in DNA. This resulted in mitotic entry, despite the unrepaired damage. A closer look to the molecular mechanism underlying progression to mitosis in these conditions revealed that active Aurora A promoted reactivation of Cdk1, thus indicating that Aurora A plays a key role upstream of Cdk1, at least under DNA damage conditions. Aurora A, similarly to other members of the family, is known to be regulated by phosphorylation. Phosphorylation of a conserved residue, T288, localized in the activation loop of the catalytic domain of the kinase, results in significant increase of Aurora A kinase activity. I was able to show that phosphorylation of T288 may occur through an intermolecular autophosphorylation mechanism. Moreover, I found that PKA, previously claimed to be the kinase responsible for this event in vitro, was not involved in T288 phosphorylation in vivo. Surprisingly phosphorylation of this site, which is a direct indicator of the activity of the kinase, was found also in DNA-damaged cells to an extent comparable, or even higher than in mitotic cells. This situation is reminding of Cdk1, where phosphorylation at the T-loop residue T161 is hierarchically less important than inhibitory phosphorylation at the ATP-binding site. This finding points to presence of other, maybe structural, mechanisms responsible for the activity of Aurora A that remain to be discovered

Tackling the Eyjafjallajökull Volcanic Ash Crisis: How the EU influenced the International Civil Aviation Organization

The goal of this single-case study is to contribute to understanding of the Eyjafjallajökull volcanic ash crisis from the institutional perspective. The Eyjafjallajökull eruption in April 2010 and the subsequent volcanic ash crisis grounding the flights across Europe demonstrated certain procedural inadequacies in the international aviation regime. This prompted the two institutions responsible in the area of civil aviation - the EU and ICAO - to interact with each other in order to tackle the crisis. The EU, supported by the expertise of the European aviation bodies adopted an approach to volcanic ash that allowed resuming the flight operations in Europe. This approach was afterwards incorporated by ICAO into its amended volcanic ash procedures. Process-tracing technique is employed in order to analyze the EU - ICAO interaction by examining all their initiatives undertaken in the context of the crisis. As a result it is concluded that the EU exerted causal influence on ICAO in adoption of the new procedures through causal mechanism based on commitment. The theoretical framework, constructed on the basis of the approaches that complement each other: regime theory, epistemic communities, normative institutionalism and the conceptual framework of institutional interaction, provide interpretations for the case analysis

Inhibition of Aurora A in response to DNA damage

Mitotic kinases are the ultimate target of pathways sensing genotoxic damage and impinging on the cell cycle machinery. Here, we provide evidence that Aurora A (AurA) was inhibited upon generation of double-strand breaks in DNA. We demonstrate that AurA was not downstream of CDK1 and that inhibition of AurA and CDK1 by DNA damage occurred independently. Using a cell line functionally deficient in Chk2, a selective Chk1 inhibitor and siRNA to Chk1, we show that DNA-damage signals were delivered to AurA through a Chk1-dependent pathway. With regard to the molecular mechanism of AurA inhibition, we found that the point mutation Ser(342)>Ala rendered AurA resistant to inhibition by DNA damage. By means of two distinct approaches we examined the impact of reconstitution of AurA activity in DNA-damaged cells: (i) transient expression of wild-type and Ser(342)>Ala mutant, but not kinase-dead, AurA led to bypass of the DNA damage block; (ii) direct transduction of highly active wt-AurA into G2 arrested cells precisely after induction of DNA damage resulted in mitotic entry. We show that the mechanism through which AurA allowed entry into mitosis was reactivation of CDK1, thus indicating that AurA plays a key role upstream of CDK1. A model depicting the possible role of AurA at the onset of mitosis and upon DNA damage is presented