Grow! is a game where player gets to enjoy in the perspective of grass, an object which is though to have passive stance in daily lives. Its' main aesthetic is to tweak norms of puzzle game just a little bit to let users enjoy a new sense of fun from it.  Grow! is no different from usual puzzle games, except for the fact that it has always more than 2 protagonists running at the same time. The items, such as holes and soil, and the enemies, represented as deer, are so common features of normal puzzle games. I wanted user to have a fresh experience, but not a strange experience where everything is new with never exited rules of chaos. I was astonished by the game "Yami" (from the last semester) and "Baba is You" and learned how important it is to think out of box when making games. The "multiple protagonist" concept is the answer I came up with, and I've figured out that it was pretty successful while play testing the game.  Grow! has another core concept. Grass merges. Grass grows in 4 steps in the overall game. They are able to do different things when they have grown to certain level. On the design stage, I wanted to make a game where players could feel the distinctive difference in available options they could make according to the different states of grass, but due to time limitations and 45 event limitations I ended up having just one effect where grass grows to state 3, the sand on the map is broken.  Grow! takes a lot of concepts learned from class active. The mechanics are simple, making 80 pixels of move works fairly for all objects in the game. Everything is under control and rules, you don't have to worry about objects or deer sliding down in different speeds with their own positions. It is relatively easy and intuitive to learn, easy to control yet has variety of options that we could make the game through.  "Cool!" was one of the most frequent comment I've heard while play testing this game. It was for sure, had independent logic and feature among the games made this semester. I've played all the Construct games from last semester posted on board. Some of them were normal, some of them were fun, and some of them were astonishing. It was not only the effort they've put into the game that surprised me, but also how much they have thought about the game itself, really surprised me. For instance, "Yami" had its unique feature of turning the light off, making the game a totally different from usual Mario games. Although the idea itself might sound simple, it is never easy to come up with a brilliant idea like that. I've spent a lot of time, focusing on what could be distinctive in our games that would be fresh and unique. I've came up with an idea of Maze Sprinter first, where acceleration matters in a maze game, protagonist could break the wall if they have enough speed, but due to logical issues (both programming logic and gaming logic) I've discarded the idea.  30 seconds describable and 15 minutes playable are difficult conditions to match. This literally means that your game should be simple but fun. You really need a sparking idea to achieve those goals. Therefore I was proud, since people really enjoyed playing the last 2 stages of Grow! The average time taken for people to play Grow! was 10 mins, and the worst case (who had no previous experience in playing games) took 17 mins to complete. Even for the game lovers, it took 6 mins to clear the game. Considering the fact that the game could be physically cleared in a minute and a half if played perfectly, we could assure that there is a challenge which players had to overcome, eventually generating fun and continuous retries.  Developing Grow! would be an unforgettable experience. I've achieved confidence in making games or logic that people could actually enjoy and be engaged in. I've got a sense of developer's perspective, which was totally different from that of a normal player. In my future life, both as a player and as a developer, this experience would help in understanding and exploring games for more good. I would like to thank Tad and hard working TAs for introducing a wonderful chance to have the game developed, tested and published with evaluation.  The soul of Grow! will grow on, even after all class schedules are over.

I wanted the user to engage into the game, exploring each story, piece by piece, to see the whole story like a puzzle. The story not only continues on the chamber(imaginary) side but impacts how things are going to happen in real world too in the endings. All endings have meanings, but true ending is meant to be hard and go through repetitive steps, for users who like the game can have longer experience and in each loop different flashbacks could be visited so covers the entire story. After all these steps, I wanted user to feel katharsis from how the deer actually played a role and what deer actually was to me.

MicroRNA (miRNA)-mediated gene regulation is of critical functional importance in animals and is thought to be largely constrained during evolution. However, little is known regarding evolutionary changes of the miRNA network and their role in human evolution. Here we show that a number of miRNA binding sites display high levels of population differentiation in humans and thus are likely targets of local adaptation. In a subset we demonstrate that allelic differences modulate miRNA regulation in mammalian cells, including an interaction between miR-155 and TYRP1, an important melanosomal enzyme associated with human pigmentary differences. We identify alternate alleles of TYRP1 that induce or disrupt miR-155 regulation and demonstrate that these alleles are selected with different modes among human populations, causing a strong negative correlation between the frequency of miR-155 regulation of TYRP1 in human populations and their latitude of residence. We propose that local adaptation of microRNA regulation acts as a rheostat to optimize TYRP1 expression in response to differential UV radiation. Our findings illustrate the evolutionary plasticity of the microRNA regulatory network in recent human evolution.

Objective

To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD.

Methods

GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer's disease (AD) and 10 healthy controls (HCs) of similar age.

Results

In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98).

Conclusions

Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.