published_or_final_version / Language Studies / Master / Master of Arts

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [48]-59).

This study aims to analyse the interconnection between human memory and digital media technology, and its relation to forgetting and deletion. The main focus area is related to short messages (SMS) as a form of digital memory and mobile application Delete by Haiku that assists the user in creating poetry out of stored messages. The reception analysis approach was chosen and individual in-depth interview method was combined with focus group interview. The collected data regarding human memory and media indicates similarities between theoretical claims and respondents’ views; memory could be perceived as a narrative, storytelling, fading away. Informants’ relation to memorabilia and their deleting practices are very dependent on the personal and professional characteristics. Besides, deleting practices could be related to organization of a physical space. Delete by Haiku app could be seen as an invitation to engage into playful process of creation through deletion, however mostly for the people attached to memorabilia.

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Date: 2023-06-04 Title: Identifying the product deletion decision-making process at a large multinational company Level: Master thesis in Industrial Engineering and Management, Product and Process development - 30 ECTS Institution: School of Innovation Design and Engineering, Mälardalen University Authors: Alan Abdulrahman & Johan Glenne Tutor: Angelina Sundström Keywords: Product deletion process; Product deletion decision-making; Product portfolio management - product deletion Aim: The purpose of this study is to identify how a large multinational company is managing its product portfolios, specifically how they conduct product deletion, and examine to what extent those decisions are influenced by external actors Research question: How does a large multinational company manage its product deletion decision-making and what role do external actors’ influences play? Methodology: This study is qualitative and utilizes an abductive approach where a theoretical framework has been created based on gatherings from a literature study combined with the empirical results based on five semi-structured interviews conducted with both local and global product managers at a large multinational company. Conclusion: This study has successfully identified how a large multinational company works with product deletion decision-making. The conclusion of this study is that the studied company has no formal ways of working with product deletion and that there is currently no way of evaluating a product deletion decision. This study has also identified that the influence that external actors have varies greatly depending on the actor, and the precise amount of influence is impossible to measure.

Chromosomal anomaly is an abnormality of the number or structure of the chromosome. Based on this, they are classified as either numerical or structural. These anomalies can have a mild or severe effect on the phenotype of the carrier which depends on the chromosomal region involved and the genes implicated. They can be sporadic or inherited. Thus, it is essential to investigate such anomalies both prenatally and postnatally alike. In a standard cytogenetic lab, these anomalies can be detected using low-resolution or high-resolution karyotype, usually by performing GTG (G-bands by trypsin using Giemsa) on chromosomes undergoing mitosis, derived from blood. If higher resolution is required, there are various other molecular cytogenetic techniques available like FISH and microsatellite analysis. More recently, microarrays have opened a new era in the field of molecular genetics by greatly increasing the resolution of screening for copy number gains and losses. Using these techniques, we characterized deletions in the long arm of chromosome 7 in three clinical cases, identified the breakpoint, studied the inheritance pattern and compared our cases with the other cases carrying similar deletion in the literature. It was observed that the deletion was located at 7q36.2, 7q35 and 7q36.1 for cases 1, 2 and 3 respectively. Case 3 also carried a duplication of Xq28.

Das Hauptziel der medizinischen Genetik ist es, die Ursachen für genetisch hervorgerufene Krankheiten zu finden, um eine bessere Behandlung der Patienten zu gewährleisten, sei es um die Medikamente auf den Metabolismus des Individuums anzupassen oder natürlich dazu, um die Krankheit selbst zu behandeln und in Zukunft auch heilen zu können. Um dieses Ziel zu erreichen werden immer neue Technologien entwickelt, die mit Hilfe von bereits etablierten Methoden auf ihre Eignung hin überprüft werden müssen. Eine der neuesten Entwicklungen stellt die Array-Technologie dar. In dieser Studie wurde versucht zu überprüfen, inwieweit diese neue Methode zur Analyse von einzelnen bis wenigen Patienten mit bestimmten Syndromen geeignet ist. Dafür wurden mehrere Patienten mir sehr unterschiedlichen Phänotypen ausgesucht, die verschiedene Ursachen und Entstehungsmechanismen der genetischen und phänotypischen Veränderung vermuten ließen. Die erste hier dargestellte Publikation beschreibt einen Fall mit einer einseitigen Schalleitungsschwerhörigkeit, der mit einer Translokation der(18)t(18;22) mit der involvierten Deletion 22pter→q11.21, sowie den darin enthaltenden Genen der CES-Region, erklärt wurde. Der in der zweiten Publikation beschriebene Fall mit MR und Verhaltensauffälligkeiten wurde mit einer intragenischen Mikrodeletion im Gen IL1RAPL1 korreliert. Zwei Fälle autoimmunbedingten Leberversagens bei einem Phelan-McDermid Syndrom wurden in der dritten Publikation primär auf eine Deletion des Gens PIM3 zurückgeführt. Ein autistischer Junge mit einer Entwicklungsverzögerung und gewalttätigen Ausbrüchen zeigte in der vierten Publikation ein sehr komplexes Rearrangement mit mehreren Brüchen im Gen CNTNAP2 und Deletionen anderer Gene, die zusammen für den Phänotyp verantwortlich sein können. Keine Mikrodeletion, sondern eine Epimutation in Chromosom 14q32.2 war die Ursache für die Adipositas mit einer Sprachentwicklungsverzögerung bei einem Jungen, der in der fünften Publikation beschrieben ist. Um die o. g. genetischen Veränderungen zu finden, wurden verschiedene Methoden wie die GTG-Bänderung, FISH, MLPA und verschiedene Array-Systeme verwendet. Mit jeder von diesen Methoden konnten neue und einander ergänzende Daten zu den genetischen Veränderungen eines Individuums gewonnen werden. Keine der Methoden konnte für sich allein ein vollständiges Bild liefern. Die GTG-Bänderung zeigt zwar das ganze Genom, hat aber die Limitierung der niedrigen Auflösung. Sie konnte dennoch Anhaltspunkte für höherauflösende Untersuchungsmethoden geben. Dazu gehörte die FISH, die entweder zur feineren Auflösung der Bänderungsdaten oder zur Bestätigung von Array-Befunden verwendet wurde. Die MLPA wurde unterstützend auf der Suche nach sehr kleinen Veränderungen in eingegrenzten Regionen eingesetzt. In einigen der beschriebenen Fälle wurden trotz eines negativen Bänderungsbefundes aufgrund des auffälligen Phänotyps genetische Ursachen vermutet, und daher feiner auflösende Methoden eingesetzt. Die am höchsten auflösenden Array-basierten Methoden wurden eingesetzt, wenn ansonsten keine Ergebnisse zu erzielen waren, oder eine feinere Auflösung der vorhandenen Daten erreicht werden sollte. Anschließend konnten die Erkenntnisse über die Veränderungen mit dem Phänotyp korreliert werden, um ein Kandidatengen oder eine Kandidatengenregion zu ermitteln. Aufgrund der großen Datenmenge aus den Array-Experimenten, waren zur Entscheidung über die Relevanz der Daten bezüglich der Entstehung des Phänotyps umfassende Datenbank- und Literatur-Recherchen notwendig. Zusammenfassend kann gesagt werden, dass die Array-Technologie einen großen Fortschritt darstellt, in der Suche nach Ursachen für genetische Erkrankungen. Sie hat aber technische Limitierungen und um das Problem der Phänotyp-Genotyp-Korrelation zu vereinfachen, werden weltweit noch viele Daten gesammelt werden müssen. Das ist eine Frage der Zeit und der Weiterentwicklung geeigneter Technologien. / The major aim of medical genetics is to find the reasons for genetic diseases, to ensure better treatment of patients, for example to better adapt medication to the patient’s metabolism or to treat and in the future also to cure the illness. To reach this goal new technologies are developed, which have to be tested for their applicability by already established methods. One of the newest developments is constituted by the array-technology. In this study it has been tried to find out to which extent this new method is suited for testing individual or few patients with certain syndromes. To do that several patients have been chosen with very different phenotypes, for which different mechanisms underlying the genetic and phenotypic changes were presumed. The first paper presented here describes a case with unilateral conductive hearing loss, which was explained by the translocation der(18)t(18;22) including the deletion of the region 22pter→q11.21 and the genes of the CES region. The case with MR and behavioral abnormalities described in the second paper was associated with an intragenic deletion of IL1RAPL1. Two cases of hepatic failure caused by an autoimmune reaction in patients with the Phelan-McDermid syndrome were explained by the deletion of PIM3 in the third paper. In the fourth paper an autistic boy with a developmental delay and violent outbursts had a very complex rearrangement containing many breaking points in CNTNAP2 and deletion of other genes, which altogether explain the phenotype. Not a microdeletion, but an epimutation in 14q32.2 was the cause for the obesity with a speech delay in a boy described in the fifth paper. Different methods were used to find the above mentioned genetic changes, i.e. GTG-banding, FISH, MLPA and several array-systems. Each of these methods revealed new and complementing data about the genetic changes of an individual. None of the methods alone could provide a complete picture. GTG-banding shows the entire genome, but has the limitation of a low resolution. This banding method provided candidate regions for further investigations with higher resolving methods. FISH was used for this cause or to confirm array data. MLPA was used to search for very small changes in specific regions. In some of the described cases with negative findings in the GTG-banding but a noticeable phenotype, genetic cause was assumed and higher resolving methods were used. The method with the highest resolution were the array-based technologies, which were used as screening method if no information could be obtained by any other method. Finally, the findings on the genetic changes were correlated with the phenotype to determine the candidate gene or a candidate gene region. Due to the large amount of data obtained from the array-experiments, the correlation required a decision about the relevance of the data for the development of the phenotype based on thorough database research. Collectively, it can be said that the array-technology is a useful technique for searching for reasons of genetic diseases. But it has its technical limitations. To facilitate the problem of the phenotype-genotype-correlation, data has to be accumulated worldwide. It is a question of time and further development of adequate technologies.

There are four phenomena that are particularly troublesome for theories of ellipsis: <br>the existence of sloppy readings when the relevant pronouns cannot possibly be bound; an ellipsis being resolved in such a way that an ellipsis site in the antecedent is not understood in the way it was there; an ellipsis site drawing material from two or more separate antecedents; and ellipsis with no linguistic antecedent. <br>These cases are accounted for by means of a new theory that involves copying syntactically incomplete antecedent material and an analysis of silent VPs and NPs that makes them into higher order definite descriptions that can be bound into.

Transposable elements (TEs) are one major force of genome evolution thanks to theirability to create genetic variation. TEs are ubiquitous and their proportion is variable between species and also populations, suggesting that a tight relationship exists between genomes and TEs. The model system composed of the natural populations of the twin sisters Drosophila melanogaster and D. simulans is interesting to compare host/TE relationship, since both species harbour different amounts of TE copies. The helena element is nearly silenced in D.simulans natural populations despite a very high copy number. Such repression is associated to abundant internally deleted copies suggesting a regulatory mechanism of TEs based on DNA deletion. Another pathway of TE regulation is through epigenetics where the host genome is able to keep intact the DNA sequences of TEs and still silence their activities.Chromatin remodelling is well known in drosophila and specific histone modifications can be associated to specific chromatin domains. We observed an important variation on H3K27me3and H3K9me2, two heterochromatic marks, on TE copies in D. melanogaster and D. simulans natural populations. Also, we show that derepressed lines of D. simulans exist for specific elements, have high TE transcription rates and are highly associated to non constitutive heterochromatic marks. TEs are therefore controlled by the host genome through DNA deletion and a possible chromatin remodelling mechanism. Not only genetic variability is enhanced by TEs but also epigenetic variability, allowing the host genome to be partitioned into chromatin domains. TEs are therefore mandatory to gene network regulation through their ability of "jumping epigenetics".