Using Push and Pull Principles to Improve Non-Linear Level Navigation

This thesis studies the Player’s habits of navigation when they are in an open-world environment. It incorporates assumptions of best practices utilizing the Push and Pull level design theory that guides the Player in a free-flowing, exploratory environment and utilizes these practices in an open-world level in The Elder Scrolls V: Skyrim

Design of lysine-free epidermal growth factor mutants for development of anti-cancer nanoconjugates

早稲田大学博士(理学)早大学位記番号:新9340doctoral thesi

The Growth of Industry Web Portals: A Case Study

With the development of the Internet, professionals in different industries or specialized areas have an increasing need forinformation exchange and social support. Therefore, industry or specialized web portals present a new opportunity in theInternet business. This paper presents a growth model for industry web portals. The model contains five stages: preparationstage, attraction stage, contagion stage, entrenchment stage, and defense stage. The model also gives the actions andstrategies to be taken and used in each stage. An industry web portal for engineering supervision, testing, and inspectionprofessionals in China is analyzed. This paper contributes to the industry web portals practice by a set of guidelines that canbe applied by practitioners in the industry web portals business

Inactivation of the MDM2 RING domain enhances p53 transcriptional activity in mice

The MDM2 RING domain harbors E3 ubiquitin ligase activity critical for regulating the degradation of tumor suppressor p53, which controls many cellular pathways. The MDM2 RING domain also is required for an interaction with MDMX. Mice containing a substitution in the MDM2 RING domain, MDM2C462A, disrupting MDM2 E3 function and the MDMX interaction, die during early embryogenesis that can be rescued by p53 deletion. To investigate whether MDM2C462A, which retains p53 binding, has p53-suppressing activity, we generated Mdm2C462A/C462A;p53ER/- mice, in which we replaced the endogenous p53 alleles with an inducible p53ER/- allele, and compared survival with that of similarly generated Mdm2-/-;p53ER/- mice. Adult Mdm2-null mice died ~7 days after tamoxifen-induced p53 activation, indicating that in the absence of MDM2, MDMX cannot suppress p53. Surprisingly, Mdm2C462A/C462A;p53ER/- mice died ~5 days after tamoxifen injection, suggesting that p53 activity is higher in the presence of MDM2C462A than in the absence of MDM2. Indeed, in MDM2C462A-expressing mouse tissues and embryonic fibroblasts, p53 exhibited higher transcriptional activity than in those expressing no MDM2 or no MDM2 and MDMX. This observation indicated that MDM2C462A not only is unable to suppress p53 but may have gained the ability to enhance p53 activity. We also found that p53 acetylation, a measure of p53 transcriptional activity, was higher in the presence of MDM2C462A than in the absence of MDM2. These results reveal an unexpected role of MDM2C462A in enhancing p53 activity and suggest the possibility that compounds targeting MDM2 RING domain function could produce even more robust p53 activation

Biosynthesis, characterization, and antifungal activity of plant-mediated silver nanoparticles using Cnidium monnieri fruit extract

The present study describes a novel method for green synthesis of silver nanoparticles using Cnidium monnieri (CM-AgNPs). Cnidium monnieri fruit is an excellent anti tinea drug that can be used externally to treat superficial fungal infections in the human body. The aqueous ethanolic extract of Cnidium monnieri fruit was prepared and employed in the synthesis of stable silver nanoparticles via biological reduction method. The synthesis conditions of CM-AgNPs was systematically optimized using Box–Behnken design. CM-AgNPs were well characterized by UV-spectroscopy and X-ray powder diffraction (XRD), and it was confirmed that the synthesized particles were AgNPs. The possible functional groups required for the reduction and stabilization of CM-AgNPs in the extract were identified through FTIR spectrum. The size of CM-AgNPs structure was confirmed to be approximately 44.6 nm in polydisperse spherical shape through scanning electron microscopy (SEM), transmission electron microscopy (TEM), and laser dynamic light scattering (DLS). Further, the minimum inhibitory concentration 90% (MIC90) ratios values of Cm-AgNPs against Trichophyton rubrum (7 d), T. mentagrophytes (7 d) and Candida albicans (24 h) were 3.125, 3.125, and 0.78125 μg/mL, respectively, determined by the broth micro dilution method. Finally, the result was concluded that the synthesized AgNPs could be further evaluated in large scale as a potential human topical antifungal agent

Vision-based displacement test method for high-rise building shaking table test

The vision-based displacement measurement system was developed, which using digital video camcorder to test the deformation of high-rise structures. It is more economical than contact and contact-less displacement sensors. A series of tests were conducted to investigate the precision, serviceability, and stability of the vision-based displacement method. The results show that, the proposed method can effectively test the dynamic displacement, moreover, the method can be effectively applied to test the displacement caused by vibration which contains various frequency components. Based on the system, the deformation of high-rise building structure was tested. The results show that, the displacement obtained by vision-based can illustrate the free-vibration characteristics of structure well, meanwhile, this method can test bidirectional displacement in shaking table test and practical engineering

p32 heterozygosity protects against age- and diet-induced obesity by increasing energy expenditure

Obesity is increasing in prevalence and has become a global public health problem. The main cause of obesity is a perturbation in energy homeostasis, whereby energy intake exceeds energy expenditure. Although mitochondrial dysfunction has been linked to the deregulation of energy homeostasis, the precise mechanism is poorly understood. Here, we identify mitochondrial p32 (also known as C1QBP) as an important regulator of lipid homeostasis that regulates both aerobic and anaerobic energy metabolism. We show that while whole-body deletion of the p32 results in an embryonic lethal phenotype, mice heterozygous for p32 are resistant to age- and high-fat diet-induced ailments, including obesity, hyperglycemia, and hepatosteatosis. Notably, p32 +/- mice are apparently healthy, demonstrate an increased lean-to-fat ratio, and show dramatically improved insulin sensitivity despite prolonged high-fat diet feeding. The p32 +/- mice show increased oxygen consumption and heat production, indicating that they expend more energy. Our analysis revealed that haploinsufficiency for p32 impairs glucose oxidation, which results in a compensatory increase in fatty acid oxidation and glycolysis. These metabolic alterations increase both aerobic and anaerobic energy expenditure. Collectively, our data show that p32 plays a critical role in energy homeostasis and represents a potential novel target for the development of anti-obesity drugs

Regulation of p53 by Mdm2 E3 Ligase Function Is Dispensable in Embryogenesis and Development, but Essential in Response to DNA Damage

Mdm2 E3 ubiquitin ligase-mediated p53 degradation is generally accepted as the major mechanism for p53 regulation; nevertheless, the in vivo significance of this function has not been unequivocally established. Here, we have generated an Mdm2Y487A knock-in mouse; Mdm2Y487A mutation inactivates Mdm2 E3 ligase function without affecting its ability to bind its homologue MdmX. Unexpectedly, Mdm2Y487A/Y487A mice were viable and developed normally into adulthood. While disruption of Mdm2 E3 ligase function resulted in p53 accumulation, p53 transcriptional activity remained low; however, exposure to sub-lethal stress resulted in hyperactive p53 and p53-dependent mortality in Mdm2Y487A/Y487A mice. These findings reveal a potentially dispensable nature for Mdm2 E3 ligase function in p53 regulation, providing insight that may affect how this pathway is targeted therapeutically