In this study, we collected 18 plasma samples from NPC patients, and 10 plasma samples from healthy person for plasma proteomic analysis. We classified these samples into 3 groups: treatment, pretreatment and recurrent. Two-dimensional electrophoresis (2-DE) and MALDI-TOF were performed followed by comparative and statistic analysis. In conclusions, we totally identified 30 proteins in Nasopharyngeal carcinoma (NPC) plasma, and found 10 proteins with expression level down regulated (p<0.001). These proteins were characterized to be Serotransferrin, Vitamin D-binding protein (VDB), alpha-1 antitrypsin (AAT), Haptoglobin, Apolipoprotein B fragment, Syntaxin-7, Apolipoprotein, A-I, PRO1779, Transthyrin, MDN1 protein, respectively. Consequently, we established a protocol to remove high abundant proteins (e.g., albumin, immunoglobin etc.) in plasma. We are especially interested in ATT and VDB. Western blotting assay was performed to confirm ATT and VDB expression. Furthermore, the quantity of ATT and VDB were measured by ELISA to obtain the threshold value of these proteins. Finally, we want to realize the relationship between these down regulation proteins and clinical parameters in NPC malignancy and tumor progression. Since there are few protein expression research of NPC in clinical studies, our works will provide insights in NPC studies for tumor progression with potential to elevate treatment efficiency.

Epstein-Barr virus, or EBV, is a human herpesvirus that is nearly universally present in most of the human population. The infection rate in adults is quickly approaching an astonishing 95% worldwide. While the most common clinical manifestation of EBV infection is infectious mononucleosis, there are multiple malignancies strongly associated with the virus, such as nasopharyngeal carcinoma (NPC). A contemporary problem in public health is the scarcity of markers to predict the development of EBV-associated malignancies, which prevents a possible cure or a suitable treatment. Of the approximately 85 proteins that the virus expresses, EBV serological tests rely on detection of antibodies against only three antigens: BFRF3 (viral capsid antigen or VCA), BMRF1 (early antigen or EA), and BKRF1 (nuclear antigen or NA). Antibodies against two of these antigens, VCA and NA, are produced by almost all EBV carriers for their entire lifetime, and so detection of these antibodies can make it difficult to differentiate between non-cancerous EBV carriers and EBV-associated cancer patients. To address this problem, the project aimed to identify a set of markers to diagnose NPC and treat it. To test this, 3 EBV genes were cloned with a 3X FLAG-tag into a mammalian expression vector, then expressed and detected by immunoblotting with a monoclonal FLAG antibody and each of the 9 human serum samples used in this study. Our results were generally inconclusive, and further studies are warranted to explore possible diagnostic and prognostic biomarkers.

The traditional roles of the tumor suppressor protein, p53, in transcriptional regulation are mostly defined in cancer or stressed cells and are centered on control of the cell cycle, DNA repair or senescence. In this thesis, data is presented demonstrating that the p53-regulated transcriptome is highly context-dependent as illustrated using the developing kidney as a model system. To this end, we utilized whole genome transcriptome and ChIP-Seq (chromatin immunoprecipitation-high throughput sequencing) analyses in p53+/+ and p53-/- mice to identify p53 regulated pathways in the embryonic kidney. This integrated approach allowed identification of novel genes that are direct p53 targets in the developing nephron. This approach was further refined using RNA-Seq analysis of lineage-tagged FACS-isolated nephron progenitors. We find that the p53-regulated transcriptome in the embryonic kidney is mostly involved in development, morphogenesis, and metabolic pathways. Interestingly, traditional targets of p53, such as DNA repair, cell cycle and apoptosis, accounted for < 5% of differentially expressed genes. The majority of 7,893 p53-binding genomic regions contain consensus p53 binding sites. Unlike a cancer cell line in which 7% of p53 binding sites lie within proximal promoters, 78% of p53 peaks in the developing kidney overlies the promoter. Moreover, 25% of the differentially expressed p53-bound genes belong to nephron progenitors and nascent nephrons, including key transcriptional regulators, components of Fgf, Wnt, Bmp, and Notch pathways, and ciliogenesis genes. RNA-Seq of nephron progenitors from wild-type and mutant p53 mice demonstrated repression of the nephron stem cell marker, Cited1, but not Six2. Moreover, cytoskeleton, cell adhesion, and energy metabolism genes were downregulated in mutant progenitors consistent with the loosely organized cap mesenchyme and disrupted mesenchyme-to-epithelium transition of p53-/- progenitors. In conclusion, our studies demonstrate that p53 genomic occupancy and regulated transcriptome are distinctly different in development and cancer. p53 is a key regulator of transcriptional programs that maintain nephron niche integrity, nephron progenitor cell renewal and differentiation. / acase@tulane.edu

Denna uppsats har haft avsikten att studera hur NPC:ers agerande påverkar spelupplevelsen. NPC:er är de figurerna inom ett spel som inte är spelbara. Deras syfte är att skapa en trovärdig spelvärld och interagera med spelaren. Spelupplevelse innebär de känslor och tankar som spelare får under tiden de spelar. För att besvara uppsatsfrågan så studerades hur NPC:ers beteende påverkade spelarnas upplevelser genom observationer och enkäter. Under iakttagelserna så testades sex olika spel för att se hur deltagarna uppfattade NPC:ers olika agerande. Enkäten användes för att ge deltagarna utrymme att själva kunna tillföra sina egna tankar till hur de uppfattade de datorstyrda figurernas agerande. Överlag visade resultatet från både observationerna och enkäterna att det fanns delade meningar kring hur NPC:ernas agerande uppfattades. Testpersonernas uppfattningar skiljde sig åt både inom ett spel och mellan spelen. Samtidigt fanns det även beteenden som testgruppen hade samma åsikt kring. Exempelvis tyckte de flesta testpersoner att spelupplevelsen försämrades när NPC:erna inte försökte nå spelaren strategisk eller inte arbetade som en enhet. Uppsatsen visar att det är svårt att ta en fram en NPC som agerar på ett sätt som passar samtliga spelare. När ett nytt spel utvecklas läggs mycket fokus på att spelupplevelsen ska bli så bra som möjligt. Eftersom denna uppsats visar på att NPC:er har en inverkan på spelupplevelsen så är det viktigt att studera detta ämne vidare. / The purpose of this thesis is to analyze in what way the gaming experience for the gamer is affected by the NPC´s behaviour. NPCs are characters in a game that the gamer himself cannot control. The main purpose with adding NPCs into a game is to create a more realistic world and for them to interact with the gamer. Gaming experience is concerning the emotions and thoughts that the gamer has while playing the game. In order to be able to answer the questions posed in this thesis, questionnaires and observations was conducted to study how the NPCs behaviour affected the players´ gaming experience negatively or positively. During these observations, six different games were tested to see how the players reacted to the NPC´s behaviours and actions. The questionnaire was used as a tool for the players to be able to express their feelings and thoughts about the computer-controlled characters. The result from both the observation and the questionnaire shows that the participating people´s thoughts about the behaviours of the NPCs vary greatly. These differences could be found both concerning one specific game but also between games. On the other hand, there were specific behaviours that the participating people agreed upon. For example, a majority of the people thought that if NPCs did not try to get to the gamer in a more strategic way or if they did not work as a unit, lead to a negative gaming experience for the gamer. The conclusion of this thesis is that creating a NPC who has behaviour traits which suit all types of gamers is a very difficult task. The main focus of a new game in development is to create the best gaming experience possible for the gamer. This thesis shows the importance that the effect of the NPC´s behaviour has on the gaming experience and therefore it is a subject that is important to study more closely.

Detta är en studie vilken har undersökt spelares uppfattning av en NPC:s funktion i en fiktiv 1800-talskontext i relation till NPC:ens ansiktsbehåring. Människor har genom tiderna kategoriserat individer i form av stereotyper baserat på visuella aspekter, så som bland annat ansiktsbehåring. Stereotyper förväntas bete sig enligt specifika regler, och om en karaktär inte beter sig som dess publik förväntar sig uppstår dissonans (Loyall, 1997). Undersökningens artefakt bestod av en serie porträtt föreställandes en och samma NPC men med varierande uppsättningar ansiktsbehåring. Studiens respondenter ombads tilldela vart porträtt en NPC-funktion baserade på Bartles (2004) lista med NPC-funktioner. Resultatet visade på trender där ett fåtal funktioner föredrogs för var form av ansiktsbehåring. I framtida arbeten skulle andra kontexter kunna undersökas. Även mer avancerade undersökningar skulle kunna genomföras där NPC:erna placeras i en spelsimulation.

Niemann Pick Type C (NPC) disease is a fatal childhood neurological disease caused by mutations in the NPC-1 protein, resulting in cholesterol buildup in the late endosomes. StarD4 and StarD5 are cholesterol binding proteins that play a role in the intracellular cholesterol transport. In this study we overexpress StarD4 and StarD5 in in vitro and in vivo models, and find evidence of amelioration of the NPC phenotype. This study demonstrates that the overexpression of these proteins has the potential to be a therapeutic treatment for NPC disease.

The study is aimed to map the gestures of Non Player Characters to make it easier for developers in the future to find fitting gestures for their characters to make sure they retain their believability. By making a survey with open questions and animations of the different gestures, the respondents were asked what they thought the characters in the animation wanted to convey. By counting how many times the respondents used the same, or similar words, each question were summarized into a table. The results were that many of the gestures that were used to convey a feeling, were better suited to another type of gesture, and by mapping these the goal is to create a lexikon with gestures that makes it easier for future developers to apply the correct gesture in the right situation. / Studien avser att kartlägga gesterna hos Non Player Characters för att underlätta för framtida utvecklare att hitta passade gester för olika situationer som gör att karaktärerna i spelet bibehåller sin trovärdighet. Genom att formulera en enkät med öppna frågor och animeringar för att gestalta gesterna tillfrågades respondenterna vad de trodde att karaktären försökte förmedla. Genom att räkna hur många gånger respondenterna valde att beskriva gesterna i enkäten med samma eller liknande ord, sammanfattades varje fråga i en tabell. Resultatet blev att många gester som används i vissa syften passar bättre för att gestalta andra typer av känslor, och genom att kartlägga dessa gester är syftet att bygga upp ett lexikon med gester som utvecklare i framtiden kan använda för att applicera rätt typ av gest i rätt situation.

Nasopharyngeal carcinomas (NPC) is highly induced by Epstein-Barr virus (EBV). EBV infection encoded latent membrane protein 1 (LMP1) is expressed in latent stage II and III of EBV infection nasopharyngeal cells. LMP1 was reported to be associated with increased tumorigenesis, through the activation of nuclear factor-£eB (NF-£eB). In this study, LMP1 overexpressing NPC cell line (TW04) was used for assays of cell proliferation, apoptosis and migration under drug (Sodium Salicylate, Cisplatin and 5-Fluorouracil) treatment. Sodium Salicylate is one of non-steroidal anti-inflammatory (NSAID) drug, which inhibits the downstream of NF-£eB pathway, e.g., COX-1. Cisplatin and 5-Fluorouracil are traditional chemotherapy durgs used in many cancers. Our result shows that overexpression of LMP1 affects cell proliferation, apoptosis , invasion and migration ability. It indicates that LMP1-overexpression is an important marker for NPC therapy.

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