1,214 research outputs found
Families versus Machines: On how a startup can improve digital well-being in the family life
No full textThe goal of this project was to find a way to improve digital well-being in family life through design for the startup Unpluq. In this thesis, the designer combined a design approach called Value Sensitive Design with the list of requirements methodology taught at Industrial Design Engineering. This resulted in a new methodology that allowed the designer to develop a concrete list of requirements and wishes for improving well-being through design. To establish this list of requirements, the design student performed a detailed literature review on positive psychology, behavioural economics and digital parenting literature. In addition to this, he interviewed both parents and children to empathise with their world views. Lastly, he performed a market analysis to understand how the context and available resources could affect Unpluq’s capacity to take up a role in this new market. Based on this research, the answer found is that improving digital well-being in the family life requires the design of a choice architecture that helps parents and children take more conscious control of their time and attention (both transactional values). Doing so should allow them to spend these transactional values on activities that align with things they intrinsically value. This choice architecture should help rearrange actors, artefacts, and stimuli within the family home environment so that time is less easily spent without intentional consent. Based on this list of requirements, the design student initiated a design process to translate these insights into a physical design concept that Unpluq could bring to the market to help families rearrange this choice architecture. This design process was executed by iteratively evaluating design concepts with both the client, potential end-users, experts, and professionals from different psychology and pedagogics fields. In the end, the designer delivered a concept that stimulates reflective thinking about what users find intrinsically valuable and provides tips, tools and challenges that push them to try and change habits. This is done by focusing on conversations that help raise awareness of the critical issues and stimulating the iterative goal setting that the family should engage in to start solving these issues for themselves. The way that time can and should be allocated for intrinsically valued activities was so unique for each individual and family that it is hard to find one solution to help everyone. Therefore, the core insight of this project for Unpluq is that if they would be interested in entering this market, their focus should be on helping families reimagine the way they use their environments within their own family homes. This should be done both individually and together through reflection and iteration and supported in that journey by scientific and expert information.https://unpluq.com/graduation-niels/ Presentation webpageStrategic Product Desig
Investigation of the molecular disease causing mechanism by the two pore domain channcel TASK-4 gain-of-function mutation G88R in progressive cardiac conduction disorder
No full textMutationen in Zwei-Porendomänen Kalium (K2P) -Kanälen konnten bereits mit verschiedenen Erkrankungen in Verbindung gebracht werden. Dazu zählt beispielsweise die dominant-negative Mutation im TRESK-Kanal (KCNK18), welche mit einer Form von familiärer Migräne mit Aura assoziiert ist (Lafrenière et al., 2010). Eine Mutation im TASK-3-Kanal (KCNK9) kann zu dem Birk Barel Syndrom mit mentaler Retardierung führen (Barel et al., 2008). Eine hereditäre pulmonale Hypertension kann durch verschiedene TASK-1 (KCNK3) Mutationen verursacht sein, die einen Funktionsverlust des Kanals verursachen (Ma et al., 2013). Eine heterozygote Punktmutation im Selektivitätsfilter des TREK-1-Kanals (KCNK2) kann ursächlich für eine RVOT-Tachykardie (Tachykardie aus dem rechten ventrikulären Ausflusstrakt; right ventricular outflow tract = RVOT) sein. Die Mutation führt bei TREK-1 zu einer erhöhen Na+-Permeabilität und einer gesteigerten Aktivierung durch eine erhöhte Sensibilität für mechanische Dehnung (Decher et al., 2017). In dem pH-sensitiven K2P-Kanal TASK-4 (KCNK17) konnte 2014 durch Friedrich et al. eine Genmutation identifiziert werden, welche ebenfalls eine krankheitsauslösende Rolle bei Arrhythmien spielt. In dieser Studie war die Grundlage für die genetischen Untersuchungen der Phänotyp einer
progressiven kardialen Reizleitungsstörung (progressive cardiac conduction disorder = PCCD) in Kombination mit einem idiopathischen Kammerflimmern. Die hierbei identifizierte Mutation, TASK-4G88R, verursachte eine erhebliche Funktionssteigerung des Kanals. Bei demselben Patienten konnte neben der Mutation im TASK-4-Kanal eine Mutation im prädisponierenden SCN5A-Gen identifiziert werden, welches für den spannungsabhängigen Natriumkanal Nav1.5 kodiert. Eine Mutation in der gleichen Spleißstelle, welche zum Überspringen eines Exons führte, wurde bereitszuvor von Probst et al. (2003) im Rahmen von Untersuchungen von Mitgliedern einer französischen Familie, in welcher eine kardiale Reizleitungsstörung autosomal-dominant vererbt wurde, als krankheitsauslösend beschrieben. In den „whole cell“ Patch-Clamp-Messungen zeigte sich hier ein Funktionsverlust des Nav1.5-Kanals, welcher zu einer herabgesetzten Reizleitungsgeschwindigkeit führte. Die Kombination aus diesem Funktionsverlust des Nav1.5-Kanals und einer verstärkten Hyperpolarisation von Zellen des Reizleitungssystems durch die TASK-4G88R Funktionsgewinn-Mutation könnte die Reizleitung in diesen Patienten noch einmal zusätzlich verlangsamen und den ungewöhnlichen Phänotyp aus Kammerflimmern und PCCD erklären (Friedrich et al., 2014). Der molekulare Mechanismus, welcher der veränderten Kanalfunktion von TASK-4G88R zu Grunde liegt, blieb ungeklärt. Das Ziel dieser Arbeit war es, diesen Mechanismus weitergehend zu untersuchen. Zu diesem Zwecke wurden elektrophysiologische Experimente an Xenopus laevis Oozyten mittels der Zwei-Elektroden-Spannungsklemme durchgeführt. Messungen der Ionenströme, nach systematischer Einführung aller 20 verschiedenen natürlichen Aminosäuren an Position 88 im TASK-4-Protein durch positionsgerichtete Mutagenese, ergaben, dass eine normale Kanalfunktion vermutlich über die Hydrophobizität des an dieser Position lokalisierten Aminosäurerestes vermittelt wird. Ein weiterer wichtiger Fokus war die Frage, ob die pH-Sensitivät des TASK-4-Kanals ebenfalls durch die Aminosäure an Position 88 beeinflusst wird. Anhand vorheriger elektrophysiologischer Untersuchungen von Niemeyer et al. (2007) wurde postuliert, dass ein Lysin-Rest an Position 242, in unmittelbarer Nähe der Kanalpore gelegen, als pH-Sensor von TASK-4 fungieren könnte. Eine Neutralisierung von K242 führte zu erhöhten Stromamplituden bei einem neutralen pH-Wert im Vergleich zum TASK-4WT. G88 befindet sich direkt oberhalb des Selektivitätsfilters, also in unmittelbarer Nähe zum pH-Sensor. In dieser Arbeit konnte ich bestätigen, dass der Lysin-Rest an Position 242 zwar die pH-Sensitivität vermittelt, jedoch nicht in Zusammenhang mit dem Mechanismus steht, der die Funktionssteigerung in TASK-4G88R begründet. Dies konnte anhand von Doppelmutationen gezeigt werden, in denen sowohl die Aminosäure an Position 242 als auch an Position 88 ausgetauscht wurde. Ableitungen auf Einzelkanalebene mittels der Patch-Clamp�Technik zeigten eine erhöhte Einzelkanal-Leitfähigkeit von TASK-4G88R. Eine Hypothese für den kausalen Mechanismus ist eine komplexe Aminosäure-Interaktion des hydrophilen Arginin-Restes an Position 88 mit Aminosäuren des nahe gelegenen Selektivitätsfilters. Eine solche Interaktion könnte durch die Ausbildung einer „hydrophilen Wolke“ einen starken elektrostatischen Effekt erzielen und so die Ionenpermeation gezielt regulieren.A variety of mutations in two-pore domain potassium (K2P)- channels have been linked to various diseases. Examples include the dominant-negative mutation in the TRESK channel (KCNK18),which is associated with a form of familial migraine with aura (Lafrenière et al., 2010) and a mutation in the TASK-3 channel (KCNK9) leading to Birk Barel syndrome with mental retardation (Barel et al., 2008). Hereditary pulmonary hypertension can be caused by various loss of function mutations in the TASK-1 channel (KCNK3) (Ma et al., 2013). A tachycardia of the right ventricular outflow tract (RVOT) can be caused by a heterozygous point mutation in the selectivity filter sequence of the TREK-1 channel (KCNK2), which leads to an increased sodium permeability and stretch-sensibility (Decher et al., 2017). In 2014, Friedrich et al. identified a novel mutation in the pH-sensitive K2P -channel TASK-4 (KCNK17) in a patient with a progressive cardiac conduction disorder (PCCD) in combination with idiopathic ventricular fibrillation. This TASK-4G88R mutation causes a significant gain of function. Interestingly, in the same patient, an additional mutation in the predisposing SCN5A gene was identified, which codes for the voltage-dependent sodium channel Nav1.5. Probst et al. (2003) previously described a disease-causing mutation affecting the same splice site, which resulted in an exon skipping, in several members of a French family with an autosomal-dominant cardiac conduction disorder. Data from "whole cell" patch-clamp measurements showed a loss of function of the Nav1.5-channel leading to a lengthening of conduction times. Therefore, the combination of the loss of function mutation in the Nav1.5 channel and the increased cellular hyperpolarization due to the TASK-4G88R mutation in the same patient may exert additive effects slowing down cardiac conductivity. This could explain the unusual phenotype of ventricular fibrillation and PCCD (Friedrich et al., 2014). The molecular mechanism underlying the altered channel function of TASK-4G88R has not been clarified yet. The main focus of this thesis was to further
investigate this mechanism. For this purpose, electrophysiological experiments were carried out on Xenopus laevis oocytes using the two-electrode voltage clamp. Measurements of the ion currents after systematic introduction of all 20 different natural amino acids at position 88 in the TASK-4 protein by position-directed mutagenesis showed that normal channel function is probably mediated by the hydrophobicity of the amino acid residue located at this position. Another important focus was the question of whether the pH-sensitivity of TASK-4 is influenced by the amino acid at position 88. Based on previous electrophysiological investigations by Niemeyer et al. (2007), who postulated, that a lysine residue at position 242, located in the immediate vicinity of the channel pore, could act as the pH
sensor of TASK-4. A neutralization of K242 resulted in increased current amplitudes at a neutral pH-value compared to the TASK-4WT. G88 is located directly above the selectivity filter, in the immediate vicinity of the pH sensor. In this study, I provide evidence, that the lysine residue at position 242 mediates the pH-sensitivity, but this is not related to the additional gain of function mechanism due to TASK-4G88R mutation. This could be shown by double mutations in which both the amino acid at position 242 and at position 88 were exchanged. Investigations on single-channel level using patch clamp showed an increased single-channel conductance of TASK-4G88R. Finally, I hypothesize a complex interaction of the hydrophilic arginine residue at position 88 with amino acids of the selectivity filter nearby. Such an interaction could achieve a strong electrostatic effect through the formation of a "hydrophilic cloud" and thus regulate the ion permeation in a targeted manner
Modul 8: Manuskriptredigering - Copyediting
No full textFølg hele manuskriptredigeringsprocessen.
Kevin Stranack (Forfatter) Niels Erik Frederiksen (Redaktør)Copyediting
Kevin Stranack (Author) Niels Erik Frederiksen (Editor
Module 3: Submitting an Article
No full textSådan indsender forfatteren en artikel til OJS-tidsskriftets redaktion.
Kevin Stranack (Forfatter) Niels Erik Frederiksen (Redaktør)Submitting an Article
Kevin Stranack (Author) Niels Erik Frederiksen (Editor
Module 5: Assigning a Reviewer
No full textAssigning a Reviewer
Kevin Stranack (Author) Niels Erik Frederiksen (Editor)Sådan udvælger en sektionsredaktør en bedømmer.
Kevin Stranack (Forfatter) Niels Erik Frederiksen (Redaktør
Modul 6: Bedømmerens arbejde - The Reviewer's Steps
No full textSe hvordan bedømmeren udfører sit arbejde.
Kevin Stranack (Forfatter) Niels Erik Frederiksen (Redaktør)The Reviewer's Steps
Kevin Stranack (Author) Niels Erik Frederiksen (Editor
Module 10: Issue Management
No full textSe hvordan du opretter og efterfølgende tilretter et nummer.
Kevin Stranack (Forfatter) Niels Erik Frederiksen (Redaktør)Issue Management
Kevin Stranack (Author) Niels Erik Frederiksen (Editor
An Investigation of the Motivational Qualities of the Buddhist Concept of Merit in Thailand
No full textThe article describes the concept of merit or bun in Thai Buddhism and how it relates to the organization of the Thai government and educational systems.Mulder, J. A. Niels. "Merit; An Investigation of The Motivational Qualities of the Buddhist Concept of Merit in Thailand." Dept. of Sociology and Anthropology, Center for Southeast Asian Studies, Northern Illinois University, 1968 Novembe
Reviewing for an OJS Journal
No full textEn vejledning i hvordan OJS-Review-siden anvendes.
PKP-OJS (Forfatter) Niels Erik Frederiksen (Redaktør af dette tidsskrift)
En vejledning i hvordan OJS-Review-siden anvendes.
PKP-OJS (Author) Niels Erik Frederiksen (Editor of this Journal
Submitting to an OJS Journal
No full textVejledning i hvordan forfatteren uploader sit manuskript.
PKP-OJS (Author) Niels Erik Frederiksen (Editor of this Journal)Vejledning i hvordan forfatteren uploader sit manuskript.
PKP-OJS (Forfatter) Niels Erik Frederiksen (Redaktør af dette tidsskrift
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