mRNA decay is an important step in gene regulation, environmental responsiveness, and mRNA quality control. One such quality control pathway, Nonsense-mediated mRNA Decay (NMD), targets transcripts whose translation terminates prematurely. However, the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we re-evaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1, UPF2, or UPF3 genes. The vast majority of NMD-regulated transcripts are normal-looking protein-coding mRNAs. Our bioinformatics analyses reveal that this set of NMD-regulated transcripts generally have lower translational efficiency, lower average codon optimality scores, and higher ratios of out-of-frame translation. General mRNA decay is predominantly mediated by decapping by the Dcp1-Dcp2 complex and 5' to 3' decay by Xrn1, but the exact mechanism of decapping regulation has remained largely unknown. Several in vitro and in vivo studies have revealed the importance of the C-terminal extension of Dcp2 and the identities of many decapping regulators that interact with the decapping complex. To better understand how decapping regulation is achieved by the C-terminal extension of Dcp2 we generated RNA-Seq libraries from a Dcp2 allele that lacks this portion of Dcp2 along with libraries from strains that contain single deletions of several decapping activators. Our transcriptome-wide results indicate that the C-terminal extension of Dcp2 is crucial for efficient regulation of decapping, and different decapping activators are responsible for targeting different sets of mRNAs. Considering the limited pool of Dcp1-Dcp2 in the cell decapping activators might be in competition for decapping complex binding. Collectively, our results yield valuable insights into the mechanism of substrate selection for mRNA quality control and decay in yeast.

Att en spelare lever sig in i ett spel kan ses som en av de viktigaste delarna av ett bra spel och spelare vill ständigt ha spel där dom känner mer och mer inlevelse. Tidigare forskning visar på att inlevelse i digitala spel inte är ett enkelt område och för att kunna forska på det så krävs det att man delar upp det i mindre, mer hanterbara, delområden som kan undersökas både som enskilda områden och i relation till andra. Denna uppsats bryter ut tre delområden som alla bidrar till inlevelse i spel för att utforska, testa och utvärdera. De valda delområdena används för att skapa en artefakt i form av ett spel där delområdena är implementerade och kan testas. De resultat som presenteras i detta arbete visar på att olika delområden inom inlevelse påverkar inlevelsen i ett spel olika mycket. Vidare visar även denna uppsats på hur vissa av dessa delområden relaterar till varandra och hur de tillsammans påverkar inlevelsen i ett spel som helhet. / Immersion can be considered as an essential part in digital games and developers are constantly challenged when trying to create immersive game experiences to an ever growing demand. However, as previous work suggests, immersion is not an easy concept to grasp and the area must be divided into smaller sub-areas. The sub-areas can then be investigated both individually and in relation to one another. This thesis breaks out three sub-areas (immersive features), that contribute to the overall feeling of immersion, to explore and test. The immersive features are used to create an artifact in the form of a game where all features can be tested. The data presented in this thesis shows that the three features have different amounts of impact on immersion. Furthermore, this thesis shows how the selected features relate to each other and how they together affect the overall game.

The ways film can be studied are many. The academic area of film science is very fragmented due to a lack of unity in its consensus and the overarching understanding of what its field entails. This situation warrants the evaluation of alternative pathways and tools for students to better understand the field of film science. The usage of gamification, an alternative approach to academic study, was chosen for this work due to its growing in interest, potential and usage. The method used to determine the validity of this concept was based on principles and methodology found in design science. The produced prototype showcased the concept of a gamified platform for film students to use in their studies. The study performed was an interactive lesson and test of the prototype where twelve participants used and experienced its intended purpose, with additional data collected using qualitative interviews and a questionnaire. The results of this work found that gamified interfaces can aid students but cannot be the sole source for an academic course or program. Partial aspects were found to be effective, but more research is necessary to fully see the effects of its implementation.

Git is a distributed version control system that tracks changes to a project overtime and is used to save these changes. Today it is being used by millions of people and is becoming a demand on the job market. For this reason it has become important to learn the version control system. Learning Git however may be difficult for beginners and learning it through tutorials may not always be effective. Learning it through a serious educational game (SEG) may be more effective as a SEG can provide motivation and feedback which are two factors for successful learning. This study seeks to assess how effective a SEG is in teaching Git by looking at the amount of knowledge gained from playing a SEG. This study also seeks to assess how much participants learned Git using a tutorial compared to participants who used a serious educational game. From the results, the study found that the SEG expanded the understanding of Git. The study also found that there was no significant difference in the amount of understanding gained from the SEG and the tutorial.

This thesis presents a design to route the spikes in a cognitive computing project called Systems of Neuromorphic Adaptive Plastic Scalable Electronics (SyNAPSE). SyNAPSE is a DARPA-funded program to develop electronic neuromorphic ma- chine technology that scales to biological levels. The basic computational block in the SyNAPSE system is the asynchronous spike processor (ASP) chip. This analog core contains the neurons and synapses in a neural fabric and performs the neural and synaptic computations.An ASP takes asynchronous pulses (spikes) as inputs and after some small delay produces asyn- chronous pulses as outputs.The ASP chips are organized in a nxn (where n [approximately equal to] 10) 2-dimensional grid with a dedicated node for each chip. This interconnected network is called Digital Fabric(DF) and the node is called Digital Fabric Node (DFN). The DF is a packet network that routes pulse (AER - Address event rep- resentation) packets between ASP's. This thesis also presents a technique for design implementation on a FPGA, perfor- mance testing of the network and validation of the network using various tools.

Augmented Reality (dt.: erweiterte Realität) und Virtual Reality (dt.: virtuelle Realität) ermöglichen die Erweiterung der Realität durch das Einblenden von visuellen Informationen in das Sichtfeld des Nutzenden bzw. den Ausschluss der Realität und das Eintauchen des Nutzenden in computergenerierte Simulationen mithilfe von Datenbrillen. Bestehende Arbeitswelten können durch diese Technologien nutzenstiftend erweitert werden oder vollständig neue Arbeitswelten abbilden. Damit eröffnen diese Technologien eine Vielzahl an Anwendungsfällen und diverse Nutzenpotenziale. Verschiedenste Barrieren hindern jedoch die Einführung der Technologien im unternehmerischen Bereich. Zur Entfaltung der Nutzenpotenziale und zur Minimierung der Adoptions- und Diffusionsbarrieren verfolgt die Dissertation einen gestaltungsorientierten Forschungsansatz der Wirtschaftsinformatik. Dabei wurden folgende Ergebnisse erzielt: (1) die Konzeption und Implementierung eines modellgetriebenen Softwareentwicklungsansatzes für erweiterte Arbeitswelten, (2) die Herleitung von Gestaltungsempfehlungen für erweiterte Arbeitswelten, (3) die Gestaltung von multiuserfähigen virtuellen Arbeitswelten als Prototyping- und Kreativitätsmedium sowie (4) die Entwicklung eines wirtschaftlichen Ökosystemmodells erweiterter und virtueller Arbeitswelten. Die im Forschungsprozess entwickelten IT-Artefakte wie Modelle, Methoden und Prototypen sowie das hergeleitete Gestaltungswissen leisten einen wesentlichen Beitrag zur Diffusion der Technologien, um nutzerseitig akzeptierte sowie im betrieblichen Umfeld nutzenstiftende erweiterte und virtuelle Arbeitswelten zu erzielen.

Units of measurement are needed in many of today’s software programs and datasets for describing physical concepts. Despite this, there are many issues regarding units of measurement in both code and data, such as inconsistent unit annotations, unit types being difficult to annotate and missing built-in unit support in tools and programming languages. Not least, is there a lack of examples of how to implement safe usage of units of measurement within an entire ecosystem consisting of code programs and data resources. Therefore, this thesis takes a design science approach to explore how a simple ecosystem of interconnected software and data components can be refactored to support safe usage of units of measurement, and whether the given solution shows it is possible to mitigate the burden of having to annotate types within the ecosystem. This has resulted in the development of an artifact that offers read/create, refactor and formatting capabilities, that can be used to implement units of measurement and unit checking into an ecosystem. The findings are that the artifact demonstrates how it is possible to implement safer usage of units, and at the same time being able to avoid the annotation burden to some extent.

One out of eight women in the United States will develop breast cancer during their lifetime. Ninety percent of cancer related deaths are due to metastasis. Metastasis is the biological process where individual or aggregate cancerous cells break away from the primary tumor site and colonize distant, non-adjacent locations throughout the body. It is my objectives to study how mechanical, topographical and biochemical cues affect metastatic breast cancer metastasis at an early developmental stage. ECM components have previously been shown to affect cell motility via ligand-receptor interactions, and physical cues, such as matrix stiffness and protein density. The primary tumor site significantly stiffens during tumor progression. The ability cells have to sense and respond to these matrix features influences and facilitates cell invasion. It is now widely accepted that mechanical properties of the ECM can regulate cell migration; however, presently, tissue modulus and stiffness have been used interchangeably. It is unknown if cell responses are sensitive to a bulk tissue modulus or stiffness on the geometric length scale of the cell. It is my objective to create tunable biomaterials from known materials to independently parse the roles of stiffness and modulus upon the migration of breast cancer cells. I have created a variety of tunable biomaterials which I can parse the roles of mechanical properties and observe their affect upon cell mechanosensing. All systems were coated with collagen I, which is the most abundant ECM protein during tumor development. I was able to quantify the migration along with other parameters of the metastatic breast cancer cell line MDA-MB-231. My results show that the highly metastatic MDA-MB-231 is stiffness sensitive among all biomaterial models. Cells maximum cell speeds are at high concentrations of collagen I on the polymer microlenses and show a biphasic response dependent on stiffness. On poly (ethylene glycol)- 2-Methacryloyloxyethyl phosphorylcholine (PEG-PC) hydrogels cells favor intermediate modulus and show stiffness dependency at low protein concentrations. Cells on Cd/Se and polydimethylsiloxane (PDMS) samples are influenced by the topographical cue more so than the stiffness or modulus of the material. By controlling mechanosensing via force transduction signaling pathways, and determining the appropriate length-scale by which mechanical properties regulate cancer metastasis, I hope to eventually uncover novel therapeutics to block cell invasion.

Breast cancer is the second leading cause of death of women in the United States, warranting further investigation into preventative therapies. It has been well documented that early pregnancy results in a lifetime decreased risk of breast cancer in humans and mounting evidence suggests that the retinoic acid pathway may play an important role in this protective effect. Cellular retinol binding protein-1 (CRBP1) is an essential component of the retinoic acid pathway and we propose that it plays an important role in pregnancy-induced protection against breast cancer. In order to investigate the role of CRBP1 in parity-induced protection against breast cancer, we utilized both mouse and human mammary epithelial cells. We examined the effect that pregnancy has on CRBP1 expression, how CRBP1 is regulated by growth promoting and inhibiting agents, if loss of CRBP1 is essential for the induction of the apoptotic pathway, and how CpG methylation of key breast cancer genes relates to known risk factors for the disease. Based on our study, CRBP1 is persistently upregulated in response to pregnancy in the mouse mammary gland at both the RNA and protein levels. Using a cell culture model, we established that CRBP1 is regulated by chemical agents that both promote and inhibit cellular growth. Utilizing CRBP1 knockout mice, we demonstrated that CRBP1 is not essential for induction of radiation induced apoptosis in parous mice. Finally, through methylation analysis, we examined how known breast cancer risk factors correlate to CpG methylation of three important genes for breast cancer and noted interesting trends that warrant future study.

Stretch activation (FSA) is the delayed increase in fiber specific tension (force per cross-sectional area) following a rapid stretch and can improve muscle performance during repetitive cyclical contractions. Historically considered minimal in skeletal muscle, our recent work showed the ratio ofstretch- to calcium-activated specific tension (FSA/F0) increased from 10 to 40% with greater inorganic phosphate (Pi) levels in soleus muscle fibers (Straight et al., 2019). Given Pi increases with muscle fatigue, we hypothesize that FSA helps maintain force generation during fatigue. To test this, FSA, induced by a stretch of 0.5% fiber length, was examined during Active (pCa 4.5 (pCa = -log([Ca2+]), pH 7.0, Pi 5 mM), High Ca2+ Fatigue (pCa 4.5, pH 6.2, Pi 30 mM) and Low Ca2+ Fatigue (pCa 5.1, pH 6.2, Pi 30 mM) in fibers expressing myosin heavy chain (MHC) I, IIA, IIX and IIB isoforms from soleus and extensor digitorum longus muscles of C57BL/6NJ mice. F0 of all MHC isoforms decreased from Active to High Ca2+ Fatigue to Low Ca2+ Fatigue, as expected. In MHC IIX and IIB fibers, FSA occurred under all conditions and FSA/F0 increased from Active (17-20%) to High Ca2+ Fatigue (32-35%) to Low Ca2+ Fatigue (42-44%). In MHC IIA fibers, FSA/F0 increased similarly to MHC IIX and IIB fibers from Active (14%) to High Ca2+ Fatigue (32%) but stayed elevated under Low Ca2+ Fatigue (35%). For MHC I fibers, no discernable FSA was apparent in either High – or Low Ca2+ Fatigue, leaving an FSA/F0 value in Active only ( 4%). These results show that FSA is a significant modulator of specific tension production under fatiguing conditions in fast-contracting muscle fibers. This mechanism could play an important physiological role during cyclical contractions, when the antagonistic muscle rapidly stretches the agonist muscle, by reducing the effect of fatigue on specific tension production.