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The Story
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Well first, you are right "we" isn't everyone; i was only speaking for most gamers, who have a limited amount of disposable income and thus can only purchase a few titles and like to get their money's worth with multiple DIFFERENT play thrus.
Second, uh withholding content seems to be the best way to extend the games life. In fact it's the only way i can think of. Whether it is keeping guns locked in muti-players like COD, or different characters like in WOW, or different story arcs like in DA:2. Personally i played L4D thousands of times without anything being withheld, but that was cuz i REALLY REALLY liked that gameplay, which is only personal preference, and cannot really be accounted for in game design.
Finally, dumb attempted cheap shot. Try to stay on point it u have something with some substance to say.
I'm kind of surprised they didn't mention Heavy Rain. Yahtzee seems to allude to their setup when he gets into the bit about timed responses, and the story is the gameplay. The dialogue tree is the gameplay for that matter.
While I wouldn't be so pretentious as to assume my opinion stands for anyone but myself, I have to agree with Neogeta in that, even though I -rarely- give a game more than a single playthrough, I actually take a great amount of pleasure in the fact that the choices I make have consequences and that those consequences are helping to shape and form not only a story, but a world around me. Just as in real life, I make mistakes, sometimes big ones, these mistakes have consequences (Poor Thane, you will be missed) and those consequences are folded into the tapestry that becomes, in the case of my above example, my story of Commander Shepard.
Fair opinion i suppose, except i don't know who Moviebob is. I know he does videos and articles but i don't read/watch um. But quick, so because he excuses himself, my opinion is somehow wrong?
I kinda want to reference the way Enslaved did things. You interacted while other characters were doing their thing. It may not have been the best example, but it felt more natural to see them getting along and working together with all they went through than Dragon Age 2's radial menu of blank face for two minutes while I get up for a piss.
yeah maybe they do that because cutscence can be skipped. in Half-Life 2 you will have talks (some longer then other) and some people will not care about and there is no way to skip them
ehm aren't you thinking of a Bioware game there?
Anyone else find "extra consideration" a bit boring? I only really read it because I like yahtzee's videos and articles. It's a nice idea, and if you're really into analysing video games, then it might be for you; but I just can't get much entertainment out of it. Yahtzee is only good when he's abusing people/games/objects. And I don't know who the rest of the people are, but they seem....meh.
i was wondering why shamus, and indeed graham werent part of the first one, i think like someone else mentioned a rotation of everyone each week would be awesome, because everyone involved in extra consideration so far, is pretty much everyone who i visit the escapist for
It's not uncommon to hear people say stuff like 'stories were better ten years ago' or something similar, but they often can't put the finger on why they think that. The unreasonable will make up crazy reasons whereas the less crazy try to pick out details that appealed to them personally.
But, I think it goes deeper than that and if we focus on RPGs I have two things to suggest.
1: Voice acting sucks!
I'm not saying game voice acting is doomed to suck from now 'till eternity, but as a general rule it's just not that good for various reasons. Even if the actors are capable they're simply handed a heavy binder full of words to be read into a microphone. As long as that tasks is completely things like characterization, shifts in emotion depending on the situation and that unshakable feeling that they're not talking to you so much as reading a list to you aren't important enough to get right.
In games like Torment and the Baldur's Gates there was very little acting. Most characterization was done through text where shifts in mood and expression were described for you to imagine rather than implied and not really followed up on by the actor/character model. Basically, we remember the stories and characters as better because we were left to, for the most part, imagine them rather than have a bland performance forced upon us.
Still, I think the craziest part is the gamers of today who claim to love the acting in games like Dragon Age and Mass Effect, standards fallen so low that they would be blown away by some random soap opera on tv. The procedures for voice acting need to improve a lot before they can compete with our imaginations.
2: The main character could be smart.
In the more recent BioWare games I get the feeling the people who claimed Inception could never be successful because of its complexity have a hand in the game of modern video games. Most responses in BioWare's more recent titles results in the NPC calling you a moron and disproving sort of brushing the protagonist like a dumb child. And often that's what the dialog feels like. Even the 'power'-responses that you gain through influence or good/evil-levels seem flimsy and of no higher consideration than any other words one could've chosen. But the jesus-touch of the protagonist makes even the most ineffectual argument seems Ciceronian if backed up by enough paragon points. It heals the addicts, it stops the ruthless murderers hand, it scares the fearless warrior races.
Of course there are plenty of examples of this in earlier works from various companies, but there's one thing that's slightly different. As long as there were intelligence and/or wisdom stats there was room for longer, more convincing arguments, not seldom something that extended past one exchange. The extended conversation you have with Dak'kon in Planescape Torment is a pretty good example of this, were you actually start shattering a man's perception of reality. It's not quick, it's not badly underbuilt and it's not something that has immediate effect on the character.
All in all, I think it's time to do something with the 'intelligence'-tool again, because playing as a idiot space marine or medival moron isn't really that flattering since it suggests the player isn't smart enough to figure things out past what you can put into the character's mouth. If you're constantly several steps ahead so to speak it just feels frustrating, and you can't adapt by for instance maxing out the intelligence stat :(
edit: As for Alpha Protocol, your choices can change the story monumentally. What is this dude talking about?
The average gamer US gamer is 34 years old so time is more likely to be the more limited resource than income. Your "we" still may not be most gamers.
You are right, games unlock more content as you play. It still feels like it is a cheap way to make your game go further by locking out a large chunk of content on your first play through. I don't just get to drop into the remaining content on the second play through, I have to go through all of the things I've already seen and done. If we are talking Bioware then that is a lot of text and cut scene that needs to be skipped.
You said that the game design for L4D doesn't account for the replay value. I disagree. It was designed to be played through over and over again without withholding any content. It is also nice how the story is in the back ground with visual cues, messages on walls etc. If you want to take your time and drink the game in you gather the story in a much more engaging way than the mountains of cut scenes used by other games. You can also blast through it and shoot zombies if you are not interested. That, to me, is good story telling in videogames. Not unskippable monologues from super soldiers.
But how would one make turn based, more traditional RPGs more seamless in regards to story telling? Would there have to be a change in gameplay to make that happen, or would the environment tell more while dialogue became more fluid. I suppose traditional RPGs don't have that same problem, since it's an expected outcome of the genre and the narrative can be treated in a book like manner at some points, but it doesn't mean there can't be improvements. SMT does some interesting things at times with this, such as the final battles in Persona 3 and 4, but otherwise there arn't many leaps and bounds for the RPG genre.
I wish there had been a bit more exchange between everyone but it was cool to let some different people in to the discussion. Hopefully Shamus and Graham will be in this again because I both appreciate their opinions as well as thinking that adding more intelligent opinions to this is always good.
Comment to Graham about Fallout and Mass Effect arbitrary conversation options locking out things: I don't know about Fallout but I know in Mass Effect that this rarely happens (I can think of once and it is more a talk too long leads to death then anything else). I know this particularly because I was worried about missing out on cool experiences or cool characters so I looked in to it previous to my playing and found that while your choices have effects, they so far have not locked out anything (especially within the game the decision is made). These decisions probably will lock out things in the third game but what it keeps you from doing should not be surprises (such as collector base decision or geth decision)
Couple things. First, I'm in the same boat as many others here where, if a game gives me the chance to make choices, I want those choices to mean something. I want to be locked out of certain things if I choose Option A instead of Option B. It allows the developers to tell a much richer story that rewards player interaction as opposed to laughing at it and games that offer the illusion of a choice with no impact at all are little better than old JRPGs that used the infinite YES?/NO? loop. If you feel robbed of your play experience by not "winning" the game the way you wanted then you were probably approaching the game with the wrong intention.
Secondly, I'm one of those who doesn't like the Half Life way of storytelling (or, more particularly, conversations). I don't want the NPCs to talk at me while I'm running around the room jumping on the architecture. Scenarios like that, or even the possibility of them existing should you choose to sit there and be a good boy, make me feel like the game world doesn't even care if I'm there or not. That sort of thing works for world events, but it's the complete opposite of immersion when interaction is assumed. Next time you are having a conversation with someone in real life try to run around the room and rifle through their drawers. Approximately no one in the world would just continue their conversation as normal under those circumstances.
Hey look, it's Graham! Cartoon Graham! Welcome, Cartoon Graham!
I largely agree with what was discussed; most games today want to have a pretence of a story, but you shouldn't bother if you don't think you can deliver an experience like that. The problem is that most people don't think of stories the way they are presented in videogames, which is why people don't follow the HL lead - they think of stories as linear things, not exploratory things. I remember one of the Deus Ex devs talking about how his team complained when he said not all things would be available to the player depending on the path they took, because they didn't want to work on a major scenario or cutscene the player might skip; likewise, there's the railroading DM who treats her players as video game characters and merely sets up a story for them to drive through without input. Perhaps a good video game writer is not one who is otherwise a good writer, but one who is a good GM.
Too true. The need to voice everything and to have HD visuals to go with it has really hurt story telling. It is so obvious that voice work and "acting" (facial expressions, body language, casually doing paper work while talking...) are done seperately. It really kills it for me. We have worlds populated by stationary, staring, socially aukward, zombies impersonating real charecters in video games. at what point will we be able to have actors controlling body movement, face, body language and voice at the same time? It will really help story telling and charecterisation... if the actors and script are good.
I agree that at its core, gaming is about interactivity and player agency. It's true that the "purest" game story will be one where a player stays in control except where it's important to the story that they lose that control.
At the same time, there is no one "right" way to tell a story in games. There is only what's fun, entertaining, enjoyable. I find BioWare games to be immensely entertaining, despite their reliance on cutscenes and dialog wheels. These things are part of the experience and make it what it is.
Too often, I feel that opponents of cutscenes and cinematic storytelling in games would prefer a world in which no games tell stories in that way and I think that would be an incredibly tragic loss. There are many ways to tell a story and gaming is one medium for doing so. We shouldn't be trying to exclude certain methods just because they don't fit into our idea of a pure game.
"I'd like an NPC to start talking to me as soon as I come close to them, rather than staring mutely at me until I hit the context-sensitive prompt flashing over their heads. I'd then like to still be in control of my character throughout the conversation, walking around,"
You've played the Darkness Yahtzee and that offers a flowing form of reralistic dialog that doesn't limit control between ingame playing... they call to you as you move towards them, they curse at you for moving away, the communication is both witty and gritty adding to the story or to the mini quest you're currently doing, the camera does switch postitions so you can see a perspective where you see yourself and you can still move as freely as you would...
Small Spoiler Alert
... Having said that besides being an awesomely layed out game... Jackie Estacado is a sort of Keanu Reeves of an actor showing as little emotion as possible... Even though he ain't a pussy and like most of us would rather rage at Paulie than cry over your girl he just murdered in front of you.
Oh and great comments about Saints Row Graham... You're right on the money!
How about a discussion regarding moral choice in games some other time??
I think everyone should get the cartoon avatar treatment, Yahtzee, Bob, and James included. I really freakin' like them. Whoever drew them should get many cookies.
...or just money
I completely disagree with this. If your choice is meaningless aside from deciding if you fill the good or evil bar, what is the point? This was one of the biggest disappointments about Mass Effect 2 for me. I played both paragon and renegade and I was rather let down by the fact that neither choice seemed to have an immediate impact on your interaction with the world. Aside from one choice about a minor character (I'm sorry but Morinth and Samara are the same character with a pallet swap), your crew accepts your decisions regardless. I found that it took the immersion quality out of the game when I realized that it didn't matter what I did, sense the journey would be the same.
An example of this choice done well is from a previous Bioware game: KOTOR. At the end of the game, if you chose the dark side, characters in your party will not accept your decision and fight you. It made the story much better when you realized that your party members would stick to their principles and you could lose them if you made the wrong decisions. It added a whole new element to the game where you not only considered game mechanics like whether decision A got you more experience than decision B but also if your decisions could lose you party members.
Well it's obviously the voice acting, not the physical acting that impresses people. A lot can be conveyed through the tone of the voice with simple visual cues in the body. What we see in recent BioWare games isn't as good as say, what we're seeing from L.A. Noire, but it does the job. Just as a person can become immersed in a classic sprite-based RPG, where simple visuals imply detail and invite the player to imagine how it might "really look," physical acting in BioWare games--when coupled with the top-notch voice acting--suggests enough of the reality of the scene to tell the story and let our mind fill in the blanks.
So it's not high-quality body motion, but it's a significant step up from static NPCs and text boxes (which would feel very out of place in their games). It's a trade-off really. BioWare could probably give us much better physical acting in their characters, but at the cost of all the different dialogue options. They use a modular approach where specific clips are strung together to get the right feel instead of one continuous scene. I compare it to Red Dead Redemption, which has noticeably better character animation in its cutscenes, but nowhere near the level of choice.
Holy Cow, Yahtzee's seen the Plinkett reviews! They're awesome, for those who haven't seen it.
I remember the bit I played through of GTA 4 being really jarring. Unlike previos games they set up this likable character who has a troubled past and who they were trying to make a fleshed out three dimensional person. The problem is that this guy who keeps saying "I don't want to kill any more people" is in a GTA game where the reason you are playing it is to drive around, cause mayhem, and slaughter vast amounts of people. And if he doesn't want to kill people any more, why can I only choose jobs that involve killing people. Personally, I felt like a dick playing it and stopped, while I had no problems with GTA 3.
To a comment graham made to Shamus at the end, I think that video games leaving more of the story to out imagination did make them better. Sure they didn't have a choice, but games today do, and more should choose it. Personally, when I played Half-life 2 I hadn't played the first one so I filled in the gaps myself and while I knew the plot I was constructing wasn't correct it was still fun. Just try playing through half-life 2 while rationalizing Freeman's muteness, I found it really fun. Every time I came to a radio in a resistance base calling for someone to respond I pictured Freeman tortured over his inability to respond and tell them that all of their friends are dead and that they should probably watch out for soldiers..
They used that System again in the Dragon Age games didn't they?
and the setting of Mass Effect is different then that of KOTOR
I could never stand more then 30 second of that guys voice
and if I got it right then Yahtzee complained that all they where doing was just sitting there and talk? Didn't they do that in 12 Angry Men as well?
Different stroke for different folks.
Me i love a great epic cut scene like the final confrontation in mass effect 1, i love the interactive movie aspects of the metal gear series, not just because the story is so bat crap crazy but because the parts you do play are fun to play.
Older rpgs like fallout 1 and 2 get to be more varied in their dialogue simply cause it is just text, no voice actors to hire to sit in a booth for 12 hours a day for weeks on end recutting the same lines over and over to get the proper feel for a 2 min conversation branch in a game.
Lots of people love their stories, lots of people just want to shoot things and blow things up. It is very hard to please both camps.
Hence to put it in a mmo perspective many people do not even bother to read or listen to the quests, many of them do not want to sit through a cutscene no matter how well done it is, why tor could be sink or swim depending how they handle the dialogue and cutscenes since some people are not going to want to be arsed about them while other will want to listen and watch and pick their choices carefully. Granted many mmos standard dialogues boil down to go kill XX x, y, and zs for XXXX reward and X plus x. TOR better be a tad more creative in their quests if each and every quest giver is going to be spoken and in cutscene form.
Half life 2 in and of itself was just pure epic because the gameplay and the story are great. Not many games nail one or the other or both. Bioware does a decent job in many of it's games of lest giving us characters and events that seem to matter and therefore your choices matter.
ANd yea for your 50 to 60 dollars do you want a wholly linear rpg that lasts 25 to 40 hours and then your done with it or would you rather have the option to play things out a different way, bring different characters to your side, make events happen differently. Sadly the one thing that does fail pretty hard in those cases is those branching events do not mean a ton to the overall story. Picking dragon age and the like where the choice events seem to have a tiny bit to do with the story especuially since bioware has an official canon story for the outcome no matter if you do everything differently from what they want you to do.
Like you can piss all over the ashes of andraste in dao and kill leandria right then and there but by da2 she is a fairly key is background figure in the da2 story. Half tempted to go back to dao and kill here just to see what the hell happens in da2 if she is dead.
But it does fly in the face of choices matter when there is an official canon ending rather than the canon ending of the games is what you make of it. And if they do have a canon ending why even allow you options to kill certain npcs and etc.
What? There is only one function of dialogue within a story? Do you not find that idea somewhat limiting?
Eh, this wasn't a great one for me because there were no disagreement. I would have wanted to see someone taking an alternate opinion from someone else to drive the discussion, this one was more just brief and saying "A is good. I agree. B is good. I agree."
Which will happen when people are being honest about games and the issue ends up being not especially contentious, but still.
As for game stories, I think an issue that people should touch on is the problem of dialogue trees making characters too vague...I mean, take a bioware game, because it gives you all these options of reacting as good or evil it forces the game to make the character blank enough that any of these character options still work in the game. It inevitably ends up that your character becomes at best a sort of background observer who just ends up watching other people react to things and make decisions and occasionally chiming in with hitting something or saying "Yes, that sounds great"
Which makes the whole story less interactive feeling because it feels like everyone else is leading you around and it is really really hard to care about or connect with my character when they're just a blank slate.
Counterexample: Infinite Space (EXCELLENT storytelling)
Oh-ho, but you see, in 12 Angry Men, there was more to it than just standing and talking. The men moved around the room, , tested out theories, and above all, they actually showed some emotions in the movie. That, and the movie was WAY better-written than any of the Star Wars prequels. The problem with the Star Wars prequels is that they're just standing/sitting and talking to get expositionary dialogue out of the way so they can get to the CG-green screened action. Hell, even when they're talking there's a green screen, and it's through this that you can tell that these dialogue scenes are unnatural. You can just TELL that they're filling these talking scenes in an enclosed space, because there's little movement and all they do is say the lines they were supposed to say. There's nothing dynamic about any of it, and boring to boot. The review mainly uses the scene where Anakin reveals to Mace Windu that Palpatine is a Sith Lord as a primary example. This SHOULD be an exciting revelation, in which they learn that they're in trouble, but they just say they're lines and walk off screen at what can't even be called a brisk pace.
So yeah, even though his voice sounds weird, Plinkett makes SUCH good points throughout his reviews.
Oh thank goodness SOMEBODY has finally mentioned the story of GTA4. I honestly don't get why people were going around, giving it 10/10s, and saying the story was comparable to The Godfather when it just wasn't.
Sandbox games are probably the hardest games to write a story for because pacing goes completely out the window and it goes at the player's discretion. You need to keep the player's attention, so you give them a bunch of sidequests to do, but sometimes these sidequests don't fit with the whole story.
I'm pretty sure that Nico Belic was bipolar or schizophrenic or something. In one mission I had to keep a sniper watch over a "business meeting" with some mobsters and Nico eagerly accepted it and smiled, going "Alright, I'll do it." After that, I went around, did some stuff, went crazy with the police, and decided to go to another mission. I went to one of Nico's gay friends who wanted to take him on a relaxing boat ride, saying "It'll be fun!" to which Nico responded furiously with, "Fun? I'm trying to keep a low profile with mobsters and criminals going after me! I don't have time for your games!" and then he begrudgingly accepted, and somehow they ended up shooting some mobsters in the water.
Do you see the problem here? It's a huge inconsistency, and I can't really blame Rockstar for this (though I will) because it is pretty hard to keep a sandbox game with any form of consistency, let alone for the story. Red Dead Redemption was much better with this, but it still suffered from inconsistencies with John Marston (seriously, why did he need to go and help a revolution in Mexico? I had forgotten why I had come down there in the first place). Hopefully L.A. Noire will provide a better example of a story in a sandbox with consistent characterization, and consistent gameplay in general.
I love BioWare games but my replay of ME2 I'm doing right now (I just got it back from a friend) is really making it clear that the dialogue - while great for building a character - really does take you out of the game. It's really like ticknig a bunch of boxes. I'm doing an Renegade Femshep playthrough (in contrast to my first run of Paragon Manshep) and it's like Investigate > Option 1, Option 2, then move the analogue stick to the lower right to be a dick.
These are all things I'm thinking about when plotting out my character. On playthrough 1 all I did wasp ick paragon dialogue options, flirt with everyone, turn down Jack then invite Miranda back to my room. Granted, I probably would have gone the Paragon route anyway because that felt more natural to me, but I'm glad I'm deliberately doing a Renegade run because the contrast is quite interesting.
Fallout 3/New Vegas feel a lot more unnatural to me. Maybe it's the voice acting. Maybe it's the plastic look and feel of the people who are talking to me. Maybe it's the fact that I'm scrolling down a list of options and most combat is via VATS so it feels like my involvement is basically just walking around and mashing the stimpack hotkey when I get into trouble.
Mass Effect and Fallout 3 have great stories and let me make choices that shape my experience, but i'm very aware that I'm making those choices.
The most engaging games for me are the ones where they're aren't really any choices, but the game flows in a natural way that doesn't feel linear. It is linear, but the game design makes me not care. This is why while Mass Effect 2 is a better game, I enjoy playing Modern Warfare 2 and Halo Reach a bunch more.
Did you just praise MW story while saying HL2's was inferior? Sir be thankful for free speech or i would be obliged to murder you.
On the more serious side, i read both your main points and it essentially boils down to "I'm not shooting stuff, something is wrong!" while it's perfectly fine for you to prefer that kind of gameplay, don't attempt to twist things to match your world view. MW story is mediocre (with the exception of the ending that provided a nice atmosphere, assuming we are talking about MW 1, MW 2 was just a steaming pile of shit story wise), while Half-Life story is much more engaging and with a much better atmosphere.
Simple check, try to separate by plot development the different areas you experienced in the game, this is a good way to tell a story impact. When you think MW you have a bunch of slightly different shooting locations that blend together in a horrible mess, while HF can easily (even by non-fans) be separated and have a clearly stronger impression. Boat section, beginning oppressive city 17, ravenholm, citadel, antlions, it is all much richer and distinct.
I think it's perfectly clear why Saint's Row 2 far surpasses GTA4. It doesn't take itself so damn seriously! It doesn't have "Cousin, it is your cousin! Want to go to a titty bar?" every FIVE GOD DAMN SECONDS!! >.<
You could do whatever you want, HOWEVER you want. I also didn't see ANY linearity in SR2.. You had plenty of side events to do OR 3-4 gangs to take down.. And it didn't drag on. In GTA4, not only was it horrendously dull and lacked any colour whatsoever.. SR2 was vibrant, the city was YOURS to do what you want and Volition really didn't hold back any insanity.. Oh, and let's not forget the brilliance that is playing the single-player storyline in co-op.
Anyway, I quite like this new segment of the site. I also hope it has a revolving cast of contributors, rather than just Yahtzee, Bob & James. Seeing Graham & Shamus contribute is great!
As for THIS particular article, I am in full agreement with Graham. I believe I've stated before my incredible distaste for the moral choice system in Western RPGs.. I can't stand Mass Effect or Dragon Age, gameplay OR story progression. I tolerate Fable III, but under immense suffering. I don't exactly mind a few personal decisions here and there, but when it drastically affects the story and forces me to choose between "right or wrong", with a major downside being that some quests have to be avoided or NPC's could just drop dead or hate you, etc.. It really annoys me. Prime example in Fable III's mercenary camp. The Dweller Camp's leader, Sabine, gives the forced quest to clear out the mercenary camp and kill the leader, Saker. You infiltrate their base and end up fighting the big man himself. After "defeating" him, you have two choices. The "good" option, sparing his life.. And the "bad" option, killing the vile bastard.
Now, let's go back a step. "The FORCED quest to clear out the mercenary camp and KILL THE LEADER, Saker." That's the outline of the quest Sabine gives you. Naturally, I choose to kill Saker.. I return to Sabine, heralded as their lord and savior and promise to help them as King. It is HOURS LATER IN THE GAME when I decide to read through some of the quests in the BradyGames Fable III guide and find out that SAKER CAN BECOME A "LOYAL FOLLOWER" on the Road to Rule. WHAT. THE. FUCK. The quest clearly stated to "KILL HIM, HE IS A VILE PIG".. Yet he counts as a follower if spared? What about Sabine's request? None of that makes ANY sense..
See, it's no wonder I choose to play more Japanese RPGs lately, even resorting to going back to my precious Final Fantasy IX and Final Fantasy X!
Boy am I glad these guy aren't in charge of gaming industry. I love cutscenes and I think free roaming games can have good stories. GTA, Assassin's Creed and MAFIA come to mind. Seriously, they didn't mention Mafia? The characters, the story progression and character development, the pacing slowly building up to a grand finale? And they didn't even mention it?!
Also, what half-life 2 did isn't quite unique. Bioshock did it too and it did it better in my opinion. I was more immersed in Bioshock then I ever was in Half Life 2 (as much as I love HL2).
And why hate the choices? If you don't like choices don't play RPG's. Simple as that. It seems they have forgotten some of the basic things about certain gaming genres. I loved Dragon Age Origins dialogues that lasted for hours. I wanted to know more about Ferelden and my companions. That kind of dialogue immerses you into the world of the game. And the more I know about it the more real it feels.
That Graham drawing is by the awesome Mike Lunsford, creator of the Supernormal Step webcomic. He also drew the massive Desert Bus for Hope IV poster!
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The father of the three girls killed in a Christmas morning house fire has sued the city, his ex-wife's contractor boyfriend and several others who did work on the home, saying they all had roles into making it into a "firetrap."
Matthew Badger's lawsuit, filed Wednesday in Superior Court, alleges that contractor Michael Borcina failed to install a smoke detection system while doing renovations on the $1.7 million Victorian house in Stamford. Borcina escaped the blaze along with the girls' mother.
The lawsuit alleges that Borcina was to oversee installation of a hard-wired smoke detection system after beginning renovations at the three-story waterfront home but failed to complete the project as scheduled in April 2011 and left the ground floor without heating.
"The girls died before they could escape the home, which had become a firetrap as a result of months of substandard construction leading up to the fire," according to the lawsuit, which was first reported by the Stamford Advocate.
The lawsuit also says city officials knew or should have known that Borcina served as the home's general contractor but didn't have a state home improvement contractor's license.
Borcina's criminal attorney, Eugene Riccio, said Thursday that another attorney was being hired to handle the civil case. Stamford's director of legal affairs, Joseph Capalbo, declined to comment.
The home's architect, electrician and general contractor listed on the building permit were included as defendants.
Last month, Stamford State's Attorney David Cohen said he found no criminal negligence in investigating the fire, which has been blamed on a bag of fireplace ashes that had been discarded in a mudroom.
The fire killed 7-year-old twins Grace and Sarah Badger, 9-year-old Lily Badger, and their maternal grandparents, Lomer and Pauline Johnson.
The grandparents' estates have notified the city of their intent to sue.
The girls' mother, Madonna Badger, told NBC's "Today" show the bag of ashes didn't seem dangerous because Borcina ran his hands over them before putting them on top of a plastic bin.

subset: commoncrawl


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SCCC/ATS "Kids College" Looking For Instructors
KSCB News - May 7, 2012 4:20 pm
Do you love working with children? Join Seward County Community College/Area Technical School this summer as an instructor for Kids College.
Kids College is accepting proposals from potential instructors for summer 2012. Do you have a talent that you can share with children who are first through sixth grade? You don�??t need to be a certified teacher, but you should love what you do and have a gift for sharing your skills with others. Consider teaching courses in technology, art, culture, business, music, history, science, sports and more. You are limited only by your imagination. The success of Kids College has always depended on the imagination and enthusiasm of the teachers. It is up to you to develop class ideas that you think will be both educational and enjoyable for your students.
Kids College consists of two sessions, which are July 16-19 and July 23-26. Each session is Monday through Thursday with classes from 8 a.m. to 10 a.m. and 10:15 a.m. to 12:15 p.m. You can commit to one or two classes for one or two weekly sessions. This is a paid position; however, we cannot provide compensation for travel, lodging, or meals. Payment varies according to the number of students in a class.
If you are interested in teaching at Kids College, contact the SCCC/ATS Office of Business & Industry, 620-417-1171


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Texas McCombs ·
Directory ·
Profiles ·
Linda Gerber
Current McCombs School of Business Faculty or staff?
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Senior Lecturer
Senior Lecturer, Department of Marketing Administration.
Dr. Linda Gerber received her B.B.A. and Ph.D. in Marketing from the University of Texas at Austin. She has served on the marketing faculty at University of Missouri and American University in Washington, D.C. From 1985 through 1989 she was director of the graduate business programs for Boston University's Overseas Programs, based in Germany. She joined the faculty at the University of Texas at Austin in 1990, where, in addition to her teaching responsibilities, she served as Director of Academic Programs for the Center for International Business Education and Research (CIBER) from 1990 through 1999. In her work with CIBER she created and managed programs designed to enhance the global perspective of business education. During this time she was active in developing language programs for business students, supervised all international exchange and scholarship programs in the College of Business, and initiated curricular programs related to international business. In addition, she has served as a review panelist for several U.S. Department of Education grant programs and as an external evaluator for international business education programs at various U.S. colleges and universities. Her international teaching experiences include temporary positions at ESC - Paris, ESADE in Barcelona, the Helsinki School of Economics, and the Steinbeis Institute in Stuttgart and Berlin.
Dr. Gerber is currently the director of the International Business major program in the McCombs School of Business and teaches a course on International Trade and Investment. In addition, she conducts an international business simulation game for students in the McCombs Business Foundations Summer Institute.
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2014 NFL Draft: Johnny Manziel leaves Texas A&M for NFL
Call him Johnny Pro Football.
As expected, Texas A&M quarterback Johnny Manziel, the 2012 Heisman Trophy winner, is forgoing his junior and senior seasons with the Aggies to declare for the 2014 NFL draft. Manziel made the decision official on Wednesday after reports of him signing with an agent and LeBron James' marketing firm on Tuesday. Manziel filed his declaration papers in the morning, according to NFL.com's Gil Brandt.
To be clear, Manziel has officially submitted declaration papers to #NFL for inclusing in 2014 draft, part of record 80 underclassmen.
— Gil Brandt (@Gil_Brandt) January 8, 2014
"After long discussions with my family, friends, teammates, and coaches, I have decided to make myself available for the 2014 NFL Draft," Manziel said. "The decision was not an easy one, but we all felt this was the right time to make the next step toward a professional career. My experiences here and the support of this school, Coach (Kevin) Sumlin, Chancellor (John) Sharp, my teammates, my classmates and Aggie football fans everywhere will be something that I carry with me for the rest of my life. I'll always be an Aggie."
Manziel is bound to be the most scrutnized and most intriguing prospect in the strong QB class. Although he has stiff competition high in the first round, including fellow underclassmen Teddy Bridgewater (Louisville) and Blake Bortles (Central Florida), Manziel is expected be a top-10 overall pick.
MORE: Manziel images | New 2014 NFL Mock Draft | List of early entries
It's more likely Manziel becomes a top-5 overall pick. Although there are questions of Manziel, listed at a generous 6-1, 210, being undersized and lacking ideal technique, he has a wow factor that can't be denied. His dazzling athleticism allows him to make big plays with his arm and his feet, tailored to the NFL trend of an explosive dual threat. Russell Wilson, with improvisational skils Manziel also possesses, has turned into an elite talent for the Seattle Seahawks. There's strong evidence Manziel, the Heisman Trophy winner in the 2012 season, can be just as thrilling.
He is the best quarterback to ever wear an Aggies' uniform, setting school records in passing yards, passing touchdowns and total offense in 2013 when he amassed 4,873 total yards. He's not a wild gun-slinger, either, as his school-record 69.9 completion percentage attests.
The Jacksonville Jaguars (No. 2), Cleveland Browns (No. 4) and Minnesota Vikings (No. 8) seem like the best possible destinations. The Houston Texans could use a QB at No. 1, but even with Manziel's Texas background, Bridgewater is a better overall prospect.


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Signal transduction
Signal transduction occurs when an extracellular signaling[1] molecule activates a specific receptor located on the cell surface or inside the cell. In turn, this receptor triggers a biochemical chain of events inside the cell, creating a response.[2] Depending on the cell, the response alters the cell's metabolism, shape, gene expression, or ability to divide.[3] The signal can be amplified at any step. Thus, one signaling molecule can cause many responses.[4]
- 1 History
- 2 Environmental stimuli
- 3 Receptors
- 4 Cellular responses
- 5 Major pathways
- 6 See also
- 7 References
- 8 External links
In 1970, Martin Rodbell examined the effects of glucagon on a rat's liver cell membrane receptor. He noted that guanosine triphosphate disassociated glucagon from this receptor and stimulated the G-protein, which strongly influenced the cell's metabolism. Thus, he deduced that the G-protein is a transducer that accepts glucagon molecules and affects the cell.[5] For this, he shared the 1994 Nobel Prize in Physiology or Medicine with Alfred G. Gilman.
The earliest MEDLINE entry for "signal transduction" dates from 1972.[6] Some early articles used the terms signal transmission and sensory transduction.[7][8] In 2007, a total of 48,377 scientific papers—including 11,211 review papers—were published on the subject. The term first appeared in a paper's title in 1979.[9][10] Widespread use of the term has been traced to a 1980 review article by Rodbell:[5][11] Research papers focusing on signal transduction first appeared in large numbers in the late 1980s and early 1990s.[12]
Signal transduction involves the binding of extracellular signalling molecules and ligands to cell-surface receptors that trigger events inside the cell. The combination of messenger with receptor causes a change in the conformation of the receptor, known as receptor activation. This activation is always the initial step (the cause) leading to the cell's ultimate responses (effect) to the messenger. Despite the myriad of these ultimate responses, they are all directly due to changes in particular cell proteins. Intracellular signaling cascades can be started through cell-substratum interactions; examples are the integrin that binds ligands in the extracellular matrix and steroids.[13] Most steroid hormones have receptors within the cytoplasm and act by stimulating the binding of their receptors to the promoter region of steroid-responsive genes.[14] Examples of signaling molecules include the hormone melatonin,[15] the neurotransmitter acetylcholine[16] and the cytokine interferon γ.[17]
The classifications of signalling molecules do not take into account the molecular nature of each class member; neurotransmitters range in size from small molecules such as dopamine[18] to neuropeptides such as endorphins.[19] Some molecules may fit into more than one class; for example, epinephrine is a neurotransmitter when secreted by the central nervous system and a hormone when secreted by the adrenal medulla.
Environmental stimuli
With Sensing of environments at the cellular level relies on signal transduction; many disease processes, such as diabetes and heart disease arise from defects in these pathways, highlighting the importance of this process in biology and medicine.
Various environmental stimuli exist that initiate signal transmission processes in multicellular organisms; examples include slime molds secrete cyclic adenosine monophosphate upon starvation, stimulating individual cells in the immediate environment to aggregate,[22] and yeast cells use mating factors to determine the mating types of other cells and to participate in sexual reproduction.[23]
Receptors can be roughly divided into two major classes: intracellular receptors and extracellular receptors.
Extracellular receptors are integral transmembrane proteins and make up most receptors. They span the plasma membrane of the cell, with one part of the receptor on the outside of the cell and the other on the inside. Signal transduction occurs as a result of a ligand binding to the outside; the molecule does not pass through the membrane. This binding stimulates a series of events inside the cell; different types of receptors stimulate different responses and receptors typically respond to only the binding of a specific ligand. Upon binding, the ligand induces a change in the conformation of the inside part of the receptor.[24] These result in either the activation of an enzyme in the receptor or the exposure of a binding site for other intracellular signaling proteins within the cell, eventually propagating the signal through the cytoplasm.
In eukaryotic cells, most intracellular proteins activated by a ligand/receptor interaction possess an enzymatic activity; examples include tyrosine kinase and phosphatases. Some of them create second messengers such as cyclic AMP and IP3, the latter controlling the release of intracellular calcium stores into the cytoplasm. Other activated proteins interact with adaptor proteins that facilitate signalling protein interactions and coordination of signalling complexes necessary to respond to a particular stimulus. Enzymes and adaptor proteins are both responsive to various second messenger molecules.
Many adaptor proteins and enzymes activated as part of signal transduction possess specialized protein domains that bind to specific secondary messenger molecules. For example, calcium ions bind to the EF hand domains of calmodulin, allowing it to bind and activate calmodulin-dependent kinase. PIP3 and other phosphoinositides do the same thing to the Pleckstrin homology domains of proteins such as the kinase protein AKT.
G protein-coupled
G protein-coupled receptors (GPCRs) are a family of integral transmembrane proteins that possess seven transmembrane domains and are linked to a heterotrimeric G protein. Many receptors are in this family, including adrenergic receptors and chemokine receptors.
Signal transduction by a GPCR begins with an inactive G protein coupled to the receptor; it exists as a heterotrimer consisting of Gα, Gβ, and Gγ.[25] Once the GPCR recognizes a ligand, the conformation of the receptor changes to activate the G protein, causing Gα to bind a molecule of GTP and dissociate from the other two G-protein subunits. The dissociation exposes sites on the subunits that can interact with other molecules.[26] The activated G protein subunits detach from the receptor and initiate signaling from many downstream effector proteins such as phospholipases and ion channels, the latter permitting the release of second messenger molecules.[27] The total strength of signal amplification by a GPCR is determined by the lifetimes of the ligand-receptor complex and receptor-effector protein complex and the deactivation time of the activated receptor and effectors through intrinsic enzymatic activity.
A study was conducted where a point mutation was inserted into the gene encoding the chemokine receptor CXCR2; mutated cells underwent a malignant transformation due to the expression of CXCR2 in an active conformation despite the absence of chemokine-binding. This meant that chemokine receptors can contribute to cancer development.[28]
Tyrosine and histidine kinase
Receptor tyrosine kinases (RTKs) are transmembrane proteins with an intracellular kinase domain and an extracellular domain that binds ligands; examples include growth factor receptors such as the insulin receptor.[29] To perform signal transduction, RTKs need to form dimers in the plasma membrane;[30] the dimer is stabilized by ligands binding to the receptor. The interaction between the cytoplasmic domains stimulates the autophosphorylation of tyrosines within the domains of the RTKs, causing conformational changes. Subsequent to this, the receptors' kinase domains are activated, initiating phosphorylation signaling cascades of downstream cytoplasmic molecules that facilitate various cellular processes such as cell differentiation and metabolism.[29]
As is the case with GPCRs, proteins that bind GTP play a major role in signal transduction from the activated RTK into the cell. In this case, the G proteins are members of the Ras, Rho, and Raf families, referred to collectively as small G proteins. They act as molecular switches usually tethered to membranes by isoprenyl groups linked to their carboxyl ends. Upon activation, they assign proteins to specific membrane subdomains where they participate in signaling. Activated RTKs in turn activate small G proteins that activate guanine nucleotide exchange factors such as SOS1. Once activated, these exchange factors can activate more small G proteins, thus amplifying the receptor's initial signal. The mutation of certain RTK genes, as with that of GPCRs, can result in the expression of receptors that exist in a constitutively activate state; such mutated genes may act as oncogenes.[31]
Histidine-specific protein kinases are structurally distinct from other protein kinases and are found in prokaryotes, fungi, and plants as part of a two-component signal transduction mechanism: a phosphate group from ATP is first added to a histidine residue within the kinase, then transferred to an aspartate residue on a receiver domain on a different protein or the kinase itself, thus activating the aspartate residue.[32]
Integrins are produced by a wide variety of cells; they play a role in cell attachment to other cells and the extracellular matrix and in the transduction of signals from extracellular matrix components such as fibronectin and collagen. Ligand binding to the extracellular domain of integrins changes the protein's conformation, clustering it at the cell membrane to initiate signal transduction. Integrins lack kinase activity; hence, integrin-mediated signal transduction is achieved through a variety of intracellular protein kinases and adaptor molecules, the main coordinator being integrin-linked kinase.[33] As shown in the picture to the right, cooperative integrin-RTK signalling determines the timing of cellular survival, apoptosis, proliferation, and differentiation.
Important differences exist between integrin-signalling in circulating blood cells and non-circulating cells such as epithelial cells; integrins of circulating cells are normally inactive. For example, cell membrane integrins on circulating leukocytes are maintained in an inactive state to avoid epithelial cell attachment; they are activated only in response to stimuli such as those received at the site of an inflammatory response. In a similar manner, integrins at the cell membrane of circulating platelets are normally kept inactive to avoid thrombosis. Epithelial cells (which are non-circulating) normally have active integrins at their cell membrane, helping maintain their stable adhesion to underlying stromal cells that provide signals to maintain normal functioning.[34]
Toll gate
When activated, toll-like receptors (TLRs) take adapter molecules within the cytoplasm of cells in order to propagate a signal. Four adaptor molecules are known to be involved in signaling, which are Myd88, TIRAP, TRIF, and TRAM.[35][36][37] These adapters activate other intracellular molecules such as IRAK1, IRAK4, TBK1, and IKKi that amplify the signal, eventually leading to the induction or suppression of genes that cause certain responses. Thousands of genes are activated by TLR signaling, implying that this method constitutes an important gateway for gene modulation.
Ligand-gated ion channel
A ligand-gated ion channel, upon binding with a ligand, changes conformation to open a channel in the cell membrane through which ions relaying signals can pass. An example of this mechanism is found in the receiving cell of a neural synapse. The influx of ions that occurs in response to the opening of these channels induces action potentials, such as those that travel along nerves, by depolarizing the membrane of post-synaptic cells, resulting in the opening of voltage-gated ion channels.
An example of an ion allowed into the cell during a ligand-gated ion channel opening is Ca2+; it acts as a second messenger initiating signal transduction cascades and altering the physiology of the responding cell. This results in amplification of the synapse response between synaptic cells by remodelling the dendritic spines involved in the synapse.
Intracellular receptors, such as nuclear receptors and cytoplasmic receptors, are soluble proteins localized within their respective areas. The typical ligands for nuclear receptors are lipophilic hormones like the steroid hormones testosterone and progesterone and derivatives of vitamins A and D. To initiate signal transduction, the ligand must pass through the plasma membrane by passive diffusion. On binding with the receptor, the ligands pass through the nuclear membrane into the nucleus, enabling gene transcription and protein production.
Activated nuclear receptors attach to the DNA at receptor-specific hormone-responsive element (HRE) sequences, located in the promoter region of the genes activated by the hormone-receptor complex. Due to their enabling gene transcription, they are alternatively called inductors of gene expression. All hormones that act by regulation of gene expression have two consequences in their mechanism of action; their effects are produced after a characteristically long period of time and their effects persist for another long period of time, even after their concentration has been reduced to zero, due to a relatively slow turnover of most enzymes and proteins that would either deactivate or terminate ligand binding onto the receptor.
Signal transduction via these receptors involves little proteins, but the details of gene regulation by this method are not well-understood. Nucleic receptors have DNA-binding domains containing zinc fingers and a ligand-binding domain; the zinc fingers stabilize DNA binding by holding its phosphate backbone. DNA sequences that match the receptor are usually hexameric repeats of any kind; the sequences are similar but their orientation and distance differentiate them. The ligand-binding domain is additionally responsible for dimerization of nucleic receptors prior to binding and providing structures for transactivation used for communication with the translational apparatus.
Steroid receptors are a subclass of nuclear receptors located primarily within the cytosol; in the absence of steroids, they cling together in an aporeceptor complex containing chaperone or heatshock proteins (HSPs). The HSPs are necessary to activate the receptor by assisting the protein to fold in a way such that the signal sequence enabling its passage into the nucleus is accessible. Steroid receptors, on the other hand, may be repressive on gene expression when their transactivation domain is hidden; activity can be enhanced by phosphorylation of serine residues at their N-terminal as a result of another signal transduction pathway, a process called crosstalk.
Retinoic acid receptors are another subset of nuclear receptors. They can be activated by an endocrine-synthesized ligand that entered the cell by diffusion, a ligand synthesised from a precursor like retinol brought to the cell through the bloodstream or a completely intracellularly synthesised ligand like prostaglandin. These receptors are located in the nucleus and are not accompanied by HSPs; they repress their gene by binding to their specific DNA sequence when no ligand binds to them, and vice versa.
Certain intracellular receptors of the immune system are cytoplasmic receptors; recently identified NOD-like receptors (NLRs) reside in the cytoplasm of some eukaryotic cells and interact with ligands using a leucine-rich repeat (LRR) motif similar to TLRs. Some of these molecules like NOD2 interact with RIP2 kinase that activates NF-κB signaling, whereas others like NALP3 interact with inflammatory caspases and initiate processing of particular cytokines like interleukin-1β.[38][39]
Second messengers
First messengers are the intercellular chemical messengers (hormones, neurotransmitters, and paracrine/autocrine agents) that reach the cell from the extracellular fluid and bind to their specific receptors. Second messengers are the substances that enter the cytoplasm and act within the cell to trigger a response. In essence, second messengers serve as chemical relays from the plasma membrane to the cytoplasm, thus carrying out intracellular signal transduction.
The release of calcium ions from the calreticulin when inactive.
Calcium is used in many processes including muscle contraction, neurotransmitter release from nerve endings, and cell migration. The three main pathways that lead to its activation are GPCR pathways, RTK pathways, and gated ion channels; it regulates proteins either directly or by binding to an enzyme.
Lipophilic second messenger molecules are derived from lipids residing in cellular membranes; enzymes stimulated by activated receptors activate the lipids by modifying them. Examples include diacylglycerol and ceramide, the former required for the activation of protein kinase C.
Nitric oxide
Nitric oxide (NO) acts as a second messenger because it is a free radical that can diffuse through the plasma membrane and affect nearby cells. It is synthesised from arginine and oxygen by the NO synthase and works through activation of soluble guanylyl cyclase, which when activated produces another second messenger, cGMP. NO can also act through covalent modification of proteins or their metal co-factors; some have a redox mechanism and are reversible. It is toxic in high concentrations and causes damage during stroke, but is the cause of many other functions like relaxation of blood vessels, apoptosis, and penile erections.
Redox signaling
In addition to nitric oxide, other electronically activated species are also signal-transducing agents in a process called semiconductive biological macromolecules.[40]
Cellular responses
Gene activations[41] and metabolism alterations[42] are examples of cellular responses to extracellular stimulation that require signal transduction. Gene activation leads to further cellular effects, since the products of responding genes include instigators of activation; transcription factors produced as a result of a signal transduction cascade can activate even more genes. Hence, an initial stimulus can trigger the expression of a large number of genes, leading to physiological events like the increased uptake of glucose from the blood stream[42] and the migration of neutrophils to sites of infection. The set of genes and their activation order to certain stimuli is referred to as a genetic program.[43]
Mammalian cells require stimulation for cell division and survival; in the absence of growth factor, apoptosis ensues. Such requirements for extracellular stimulation are necessary for controlling cell behavior in unicellular and multicellular organisms; signal transduction pathways are perceived to be so central to biological processes that a large number of diseases are attributed to their disregulation. Three basic signals determine cellular growth:
Stimulatory (growth factors)
Transcription dependent response
For example steroids act directly as transcription factor (gives slow response, as transcription factor must bind DNA, which needs to be transcribed. Produced mRNA needs to be translated, and the produced protein/peptide can undergo Posttranslational_modification (PMT))
Transcription independent response
For example epidermal growth factor (EGF) binds the epidermal growth factor receptor (EGFR), which causes dimerization and autophosphorylation of the EGFR, which in turn activates the intracellular signaling pathway .[44]
- Transcription dependent response
- Inhibitory (cell-cell contact)
- Permissive (cell-matrix interactions)
The combination of these signals are integrated in an altered cytoplasmic machinery which leads to altered cell behaviour.
Major pathways
Following are some major signaling pathways, demonstrating how ligands binding to their receptors can affect second messengers and eventually result in altered cellular responses.
- MAPK/ERK pathway: A pathway that couples intracellular responses to the binding of growth factors to cell surface receptors. This pathway is very complex and includes many protein components.[45] In many cell types, activation of this pathway promotes cell division, and many forms of cancer are associated with aberrations in it.[46]
- cAMP-dependent pathway: In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase) (see picture), and, thus, further effects depend mainly on cAMP-dependent protein kinase, which vary based on the type of cell.
- IP3/DAG pathway: PLC cleaves the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) yielding diacyl glycerol (DAG) and inositol 1,4,5-triphosphate (IP3). DAG remains bound to the membrane, and IP3 is released as a soluble structure into the cytosol. IP3 then diffuses through the cytosol to bind to IP3 receptors, particular calcium channels in the endoplasmic reticulum (ER). These channels are specific to calcium and allow the passage of only calcium to move through. This causes the cytosolic concentration of Calcium to increase, causing a cascade of intracellular changes and activity.[47] In addition, calcium and DAG together works to activate PKC, which goes on to phosphorylate other molecules, leading to altered cellular activity. End-effects include taste, manic depression, tumor promotion, etc.[47]
See also
- DNA damage checkpoints
- Functional selectivity
- GTPases
- Hormones as signals
- Protein phosphatase
- Redox signaling
- Transduction
- Two-component regulatory system
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- ^ Burger M, Burger, JA et al. (1999). "Point mutation causing constitutive signaling of CXCR2 leads to transforming activity similar to Kaposi's sarcoma herpesvirus-G protein-coupled receptor". J. Immunol. 163 (4): 2017–2022.
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External links
- Netpath - A curated resource of signal transduction pathways in humans
- Signal Transduction - The Virtual Library of Biochemistry and Cell Biology
- TRANSPATH(R) - A database about signal transduction pathways
- s STKE - Signal Transduction Knowledge EnvironmentScience', from the journal Science, published by AAAS.
- Signal Transduction at the US National Library of Medicine Medical Subject Headings (MeSH)
- UCSD-Nature Signaling Gateway, from Nature Publishing Group
- LitInspector - Signal transduction pathway mining in PubMed abstracts
- Huaxian Chen, et al. A Cell Based Immunocytochemical Assay For Monitoring Kinase Signaling Pathways And Drug Efficacy (PDF) Analytical Biochemistry 338 (2005) 136-142
- www.Redoxsignaling.com
- Signaling PAthway Database - Kyushu University
- Cell cycle - Homo sapiens (human) - KEGG PATHWAY [1]
- Pathway Interaction Database - NCI
- Literature-curated human signaling network, the largest human signaling network database
- Articles to be merged from April 2013
- All articles to be merged
- All articles with unsourced statements
- Articles with unsourced statements from March 2010
- Articles with links needing disambiguation from September 2013
- Pages containing cite templates with deprecated parameters
- Commons category with local link same as on Wikidata
- Cell biology
- Cell signaling
- Neurochemistry
- Signal transduction


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GLENDORA, Calif. --
At the annual celebration, St. James presented the Leadership Award to NHRA President Tom Compton. This award recognizes individuals or corporations that have undertaken extraordinary measures and show outstanding initiative in promoting diversity with the racing industry.
"The credit goes to our founder and my mentor Wally Parks, who created this organization 62 years ago. He did it to find places for people to enjoy this great sport and his hobby," Compton said. "We have racers at every level across the country and it has always been that way. It is the most accessible major form of motorsports in the world and we are very proud of that and this award means a lot to the NHRA."
Enders received the Outstanding Achievement Award after her history-making season by becoming the first woman to win in the Pro Stock class at the race at Route 66 Raceway in Chicago. She scored two No. 1 qualifying spots and won four races to finish fourth in the 2012 points standings.
Enders became the third female to win this award and joins Ashley Force Hood who received it in 2010 and 2011 recipient, Danica Patrick.
"This is a huge honor to receive the Outstanding Achievement Award by Lyn St James," Enders said. "I have been a part of Lyn's program from day one. She does so much for women in all forms of motorsports and it means the world to me for her to recognize what we accomplished this year. To have my name on a list with women like Ashley Force Hood and others who have received this award is pretty awesome."
"NHRA has a tremendous history of participation and success for women in racing, and I'm extremely proud of Erica, who is also a graduate of our driver development academy. Women now have victories in every national class of NHRA," St. James said.
"Unfortunately, she's not able to be here due to the fact that she's getting married this weekend, but I suspect she has her sights set on a championship in the future. NHRA has a commitment to cultural, technical, and geographical diversity and has generated championships for drivers, such as this year when Antron Brown was the first African-American to win a Top Fuel championship, and dates back to Shirley Muldowney, the first driver ever to win three national championships in Top Fuel. We applaud their leadership."
The team owned by Victor Cagnazzi who Enders raced for during her historic season, were honored with an Opportunity Award during the evening. This award recognizes teams, individuals or sponsors that create significant opportunities for women drivers to excel within the industry.
The Women in the Winner's Circle Awards is the foundation's major fundraiser, celebrating the success of women in racing, helping them build strong ties with each other and with the motorsports community, and honoring those who have provided leadership and opportunities for women in racing.


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Legislation – Knowledge Direct
Rules of Intestacy
This article explains how your estate will be distributed under the laws of England and Wales. It also touches briefly on how this differs from the laws of Scotland and Northern Ireland.
The rules of intestacy are the rules governing the distribution of a person's assets where no will has been made and they are regarded as UK domiciled.
Unless an individual wishes for someone else to decide what happens to their assets when they die, it is important towrite a will. A will is an important legal document which allows the individual to detail how their assets (estate) are distributed following their death. It also names the persons they would like to be responsible for administering the distribution of their estate in accordance with the will, referred to as executors or legal personal representatives (LPRs).
It is important to write a new will to reflect any changes in circumstances or those of intended beneficiaries. Executors must act in accordance with the last valid will of an individual.
If an individual dies without leaving a valid will, the Court must decide who should administer their estate regardless of whether these would have been the people the deceased would have wanted to handle their estate.
An estate must be distributed in accordance with the rules of intestacy.
In England and Wales under the Law Reform (Succession) Act 1995, a wife, husband or civil partner* does not take a share on intestacy unless he or she survives the deceased for 28 days. If the wife, husband or civil partner does not survive this period, distribution will take place as if there was no surviving wife, husband or civil partner. This change applies to deaths on or after 1 January 1996.
Personal property is, for example: car, furniture, pictures, clothing, jewellery. Children inherit on reaching age 18 or marrying below that age.Half-brothers and -sisters only inherit if there are no full brothers and sisters. Stepbrothers and stepsisters do not qualify under intestacy rules.
An adopted child is treated as the legitimate child of the adopter(s). A child legitimated takes an interest as if born legitimate.An illegitimate child takes any interest provided there is satisfactory proof of parentage.
All relatives are described as blood relationships; therefore the wife of an uncle, bearing the courtesy title aunt, does not qualify under intestacy rules.
The property of a man or woman who is divorced does not go to the ex-spouse under the intestacy rules.
The property of a man or woman who completed dissolution of a registered civil partnership does not go to the ex-civil partner under intestacy rules.
In Scotland, the Succession (Scotland) Act 1964 enforces some additional statutory and legal rights. Scottish Law requires a beneficiary to be alive at the date of the deceased's death to validly receive a claim.When a person domiciled in Scotland dies intestate, the Scottish rules for the distribution of the estate of a deceased person take effect, subject to certain rights against the estate which are due
to a surviving husband, wife or civil partner and the children of the deceased. These rights must be satisfied before the remainder of the estate can be distributed.
Where the term moveable estate is used this refers to any items that can be physically moved from one location to another. Net moveable estate means all moveable property after deduction for any debts of the deceased's have been settled.
There are two types of rights to consider, 'Statutory Prior Rights' and 'Legal Rights'.
Statutory Prior Rights
The Statutory Prior Rights of a surviving husband, wife or civil partner* are:
*as defined in the Civil Partnership Act 2004
Legal Rights
These are as follows:
Jus relictae
Jus relicti
The Statutory Prior Rights take precedence over Legal Rights and after both these rights have been satisfied, the estate of the person who died without making a will (intestate) in Scotland is distributed in a similar fashion to Englandand Wales.
In Northern Ireland the Northern Ireland Administration of Estates Act (Northern Ireland) 1955 governs the distribution of a deceased's assets. The Succession (Northern Ireland) Order 1996 amended the 1955 Act to include a 28-day survivor succession clause in order to make a valid claim on an estate as in England and Wales.
In Northern Ireland if the deceased has no children and there are no surviving parents, brothers, sisters or nephews and nieces, then the surviving husband, wife or civil partner inherits the residual estate absolutely.Thereafter the general principles of distribution of a deceased's estate shown in the England and Wales chart above would be followed. However the Northern Ireland rules do differ slightly from those in England and Wales.
Updated: April 2020
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Calling all kids who like to stir things up in the kitchen....
Building off the success of the inaugural Healthy Lunchtime Challenge & Kids' State Dinner in 2012, Michelle Obama is teaming up with Epicurious, the US Department of Education, and the Department of Agriculture to host a nationwide recipe challenge to promote healthy eating among America's youth.
"Last year's Kids State dinner was one of my favorite events we've ever done for 'Let's Move!' because it perfectly captured how young people, parents, community leaders and businesses can come together for innovative, healthy solutions," said Ms. Obama. "Last year's young chefs impressed and inspired me with their creativity, and I can't wait to welcome a whole new group to the White House this summer and taste their creations."
The second Kids' State Dinner invites parents or guardians and their children, ages 8-12, to create and submit an original lunch recipe that is healthy, affordable, and tasty. In support of Ms. Obama's "Let's Move!," program designed to tackle childhood obesity, each recipe must adhere to the guidance that supports USDA's MyPlate (at ChooseMyPlate.gov). Entries must represent each of the food groups, either in one dish or as parts of a lunch meal, including fruits, vegetables, whole grains, lean proteins and low-fat dairy foods, with fruits and veggies making up roughly half the plate or recipe.
All US states and territories are invited to participate. Fifty-six children and their parent/guardian will be flown to the nation's capital where they will have the opportunity to attend a Kids' "State Dinner" at the White House this July or August, hosted by Ms. Obama. A selection of the winning healthy recipes will be featured.
Recipes can be submitted April 3 through May 12, online at recipechallenge.epicurious.com, or via mail at "The Healthy Lunchtime Challenge c/o Epicurious.com," 1166 Avenue of the Americas, 15th Floor, New York, NY 10036.
Winners will be notified at the end of June.
For more information and contest rules visit recipechallenge.epicurious.com.


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When "The Simpsons" debuted on Dec. 17, 1989, "The Cosby Show," then in the last of its amazing five-season run as the nation's No. 1 show, ruled the airwaves. From the start, the animated and dysfunctional Simpson clan presented a very different take on American family life than the flesh-and-blood, high-achieving Huxtables. But the more enduring and defining legacy of Matt Groening's creations came in turning a funhouse mirror on the popular culture of the past quarter century, part "Saturday Night Live"-style, but more like classic MAD magazine.
See for yourself starting Thursday, when Fox's FXX channel launches a round-the-clock, DVR-busting marathon of all 552 "Simpsons" episodes, broadcast in order, along with the 2007 theatrical movie inspired by the show. That's a dozen days of "Simpsons" – or the length of an average visit to Moe's by Barney Gumble.
If that sounds like too much of a good thing – or of a dubious thing, like Duff beer, Krusty burgers and doughnuts (mmm… doughnuts!) – well, overindulgence is just "The Simpsons" way. The marathon, a prelude to the upcoming Simpsons World digital platform, offers an opportunity to shout woo-hoo! for a comedy classic – as well as trace the evolution of a show that starts its 26th season next month as the longest-running scripted primetime TV program in U.S. history.
U.S. & World
Revisiting "Simpsons" episodes lets us relive great moments and discover others we might have missed the first time around – all while unlocking a satire time capsule and providing a chance to think about a show that, on the surface, eschews deep thought. Here are some things to look for as FXX celebrates TV's most durable nuclear family:
•Drawing a Crowd: The renderings of Homer, Marge, Bart, Lisa and Maggie have morphed over the years from scraggly lined, rough, vertical faces to their current iconic images. Some of the voices are different, too – Homer's gruff tones, in particular, have softened. The same goes for Seymour Skinner's voice, which has journeyed from stentorian to beaten-down exasperation.
•Springfield Tourism: Guest appearances, which have grown in frequency over the last 25 years, mark perhaps TV's greatest cumulative primetime collection of talent since "The Ed Sullivan Show": Three Beatles, Michael Jackson, Mick Jagger, Liz Taylor, Magic Johnson, Justin Timberlake, Anne Hathaway and Stephen Hawking have lent their voices (and, in many cases, faces) to the show, to name a scant few.
•Treehouse of Delights: The annual Halloween-themed "Treehouse of Horrors" episodes have provided some of the best "Simpsons" moments – ever, as Comic Book Guy would say. Cases in point: parodies of "The Island of Dr. Moreau" (starring Dr. Hibbert), "It's the Great Pumpkin, Charlie Brown" (with Milhouse perfectly cast as Linus) and "The Twilight Zone" (in which Homer skips through dimensions to the real world – maybe the best Simpson sequence of them all).
•Sentimental Journeys: Forget about the Fox show's trademark sardonic streak – "The Simpsons" can spur a tear faster than Mr. Burns can release the hounds. The tone was set in the first episode, a Christmas special that brought Santa's Little Helper to 742 Evergreen Terrace. The death of Lisa's saxophone hero Bleeding Gums Murphy, the fortuneteller episode in which an adult Lisa (nearly) gets married to a snob and the backstory of Homer's desertion by his 1960s radical mom (Glenn Close) all show surprising heart and rank among the series' most memorable installments.
•Having Cows: As much as "The Simpson" mocks sitcoms, it echoes the form – most prominently in catchphrases, some of whose popularity have dissipated with time: "Ay, caramba!" "Don't have a cow, man." "Eat my shorts!" "I'm Bart Simpson – who the hell are you?" But "D'oh!" and "Woo-hoo!" have become seemingly permanent additions to the language.
•A Homer Run: The catchphrase continuum starts with Bart, the show's original breakout character, and extends to Homer, who, for all the citizens of Springfield and celebrity visitors, is the closest thing to being the star of "The Simpsons." He'll never replace Bill Cosby as America's Dad, but he's the best father Bart, Lisa and Maggie will ever have.
Check out FXX's clever preview for the marathon below as viewers prepare to take an extended summer vacation to Springfield:
Jere Hester is founding director of the award-winning, multi-media NYCity News Service at the City University of New York Graduate School of Journalism. He is also the author of "Raising a Beatle Baby: How John, Paul, George and Ringo Helped us Come Together as a Family." Follow him on Twitter.


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Jc913 necesitaba un nuevo diseño de otro y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 33 diseños de 11 diseñadores freelance.
Cities are big places and tastes are all over the map. While there's no shortage of local opinions online, it's still too difficult to find advice that relates to your (or your friends') own unique taste.
As a result you either end up having to wade through pages of user reviews, rely on just one editor's opinion, or go to the same places again and again.
Metropolist solves this problem with more personalized local advice. As you keep track of the places you like (and dislike) Metropolist begins showing you all sorts of customized information helping you make better decisions about how to spend your hard-earned free time and cash.
Metaphorically speaking, we're Pandora for cities.
Metropolist's target audience are active urbanites age 21-35 looking to make decisions with more personalized, relevant advice. They probably use sites like Yelp or New York Magazine (as a regional example) but often find themselves wading through the information and reviews trying to form their own opinion. They think of themselves as individuals with discerning palettes and enjoy spending time exploring their cities.
I currently have a logo and site graphics that are generally in-line with how I envision the site's branding (attached). However, I am not a designer by trade and these images need "sprucing up" and made more professional (for example, right now my images render sort of blurry but I don't know how to fix that). I am attaching a comparable image for this purpose but feel free to also be creative with other ideas.
Therefore, this contest is to update the logo images (logo_large.png, logo_small.png, tagline.png) in a more professional style using the comparison image (tumblr_icon.png) as a starting point. By "more professional" I mean high resolution, less blurryness, etc. Again I am not a designer by trade. Please keep the logo images the exact same dimensions and generally the same color palette.
Please note I have other site images that I would like the winner of the contest to update in a similar manner but I obviously have more flexibility for original design and a much larger budget, but let's discuss after the contest.


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Friday, November 2, 2012
OOTD: Orange Hooded Anorak + Polka Dot Scarf + Suede Boots
22 comments:
Hi Mimi,ReplyDelete
Cute! That orange just pops. Enjoy your B-day weekend. I may go and see Flight. Love me some Denzel too :-)
Great look Mimi! You're a scorpio like me. My birthday was Halloween. Enjoy date night and your birthday!ReplyDelete
Scorpios Rock!! Woot!Woot! Today's my birthday and the start of my weekend also! Happy Early Birthday and have a great one!!ReplyDelete
Cute as a button as usual! Orange is a really good color on you!ReplyDelete
i love this look, especially your jacket! ON has had some amazing things this year :)ReplyDelete
C's Evolution of Style
Haapy B-day. Love the orange jacket. I just picked up an Anorak from ON last weekend also, in army green. I got to wear it once before Sandy brought in the coat weather. lololol. Have a great b-day weekend.ReplyDelete
- AnonymousNovember 2, 2012 at 12:57 PM
So 'grown woman' freekaky freaky Fresh! Lol !!!ReplyDelete
I wuv you!!!
- AnonymousNovember 2, 2012 at 1:03 PM
Great look, as usual :-) You are being so nice, posting every day, no fail... thanks for that! Hope you have a marvelous Birthday weekend with your lovely family!! Bendiciones para todos!!!ReplyDelete
- NatalieNovember 2, 2012 at 1:34 PM
Everyday Chic...Love it!ReplyDelete
Looking- AMAZING as usual! Happy Birthday!!!ReplyDelete
Happy Birthday! Scorpio to Scorpio. Enjoy Gorgeous, you deserve it!!!ReplyDelete
- AnonymousNovember 2, 2012 at 5:37 PM
Love the scarfReplyDelete
Oh I wish I could wear orange as well as you do. What a great outfit. have a wonderful birthday. Yes, I will probably watch Flight.ReplyDelete
- AnonymousNovember 4, 2012 at 12:15 PM
luv, luv,luv your style!!!! I check your page everyday for inspiration, I am plus size 16/18 and i look to you for great ideas. Your not plus size but how can anyone not find inspiration in you....ReplyDelete
please keep it coming fall is my favorite time of year, so i will be on here everyday checking!!!
Can't wait to go get my anorak from ON!!!
Love this jacket!!! Happy Birthday!!!ReplyDelete


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Because some properties are obsolete in Oracle Forms, you cannot directly convert Forms 6i FMTs and MMTs to Oracle Forms FMBs and MMBs using Forms Developer.
To convert a Forms 6i FMT or MMT to an Oracle Forms 11g FMB or MMB, do the following:
Use the Forms 6i Builder or Compiler to convert the Forms 6i FMT or MMT to a Forms 6i FMB or MMB.
Then, use Forms Developer to convert the Forms 6i FMB or MMB to an Oracle Forms FMB or MMB. Open the Forms 6i source files in the Oracle Forms Builder, save them, then recompile them; or use the Oracle Forms Compiler.


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No thread on this?
Maybe you all haven't heard?
Roland has a boutique version of the D-50.
Do want?
(I do)
Moderators: MetroSonus, Plink Floyd
Plink Floyd wrote:@ 2:35 is one of my fave D-Fitty demonstrations:
ClavAnother wrote:Plink Floyd wrote:@ 2:35 is one of my fave D-Fitty demonstrations:
That's basically why I keep saying the d50 might have the best synth action if all time. (Sound wise that was crap though)
ElectricPuppy wrote:True. At the time, that was THE sound. I personally don't care to ever hear it again, though.
I lusted after a D-50 when they came out, but I recall it being something like $2500. In late-80's dollars.
Users browsing this forum: No registered users and 7 guests


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All in all, from what I've learned from active attorney's in my area, is that where you went to school is far less important than if you're good at what you do.
Non ABA schools are a very good option considering you can practice law almost anywhere so long as you pass the bar in California and practice for a few years before applying to take the bar in another state.
The ABA is nice but is very over rated. I think people are going to see a shift as the cost v. benefit of attending an ABA school is not what it once was when you compare dollars and cents.
Let me repeat- - only attend a non ABA accredited law school after you have exhausted all efforts and been rejected by the above established schools which are working towards accreditation.
One of the most important questions to ask is "What do I want to do after law school?" If you can answer that, it will help you figure out if a CBA school is a good option.
Honestly, I'd never even heard of most of the schools you mentioned (except Cooley) before reading this post....


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Not only is that the title of Tomi's latest book, it's also the title of a course at Oxford University on December 3-4 led by Tomi, Alan and myself.
Hope you'll know someone who ought to be there! Book Your Place
The following is from the University of Oxford's Continuing Education site.
About the CourseMobile is emerging as the 7th mass media channel, whilst legacy mass media witnesses a decline. This course presents a journey through some of the most advanced content and media services deployed on mobile phones, in the most advanced mobile telecoms countries such as Japan, South Korea, Hong Kong and Finland.
Intending to build on the content of Tomi T. Ahonen's sixth book 'Mobile as 7th of the Mass Media', the course provides a unique opportunity to explore the taxonomy of the seven mass media, with an emphasis on what lessons can be learned when newer media are introduced.
The course will begin by examining the overall industry and the consumers of mobile content, before moving on to explain how to build compelling content to mobile, and exploding the myths of the limitations of supposedly too small keypads and tiny screens. The most promising early media content types: music, gaming, TV, internet, advertising and social networking will also be discussed.
All delegates will receive a free copy of Tomi T. Ahonen's book Mobile as 7th of the Mass Media.
Tomi T. Ahonen speaks to CNN - watch the video here
Who is it for?Anyone in the current legacy media space who wants to understand new media, thus digital media executives in television, print, radio, cinema, recordings industries and advertising; all in the internet businesses who are interested in the future of the web; and those within mobile who work with media and convergence. No prior knowledge of mobile telecoms or media is necessary.
Course Presenters
- Tomi T. Ahonen MBA, Independent 3G Strategy Consultant and Author
- Alan Moore, Author and CEO of SMLXL
- David Cushman, Director of Social Media, Brando Digital
Course Content
- The environment of mobile
- Mobile industry ecosystem
- Digital convergence and mobile, 5 industries
- Customer of Mobile - Gen C
- The 7 Media
- Legacy mass media Print, Recordings, Cinema, Radio, TV
- Internet as first interactive media
- Communities of Purpose and Long tail
- Mobile as 7th of the Mass Media
- Inherently threatening
- interactive
- Seven Unique benefits of Mobile
- Clash of the Media
- Print, Recordings, Cinema vs Mobile
- Radio vs Mobile
- TV vs Mobile
- Internet vs Mobile
- Mobile Services and Applications
- Evolution of handset - 8 C's
- The Six M's service creation theory
- Widgets
- Community and Mobile
- Group forming theory
- Mobile social networks
- Marketing and Advertising
- Social Advertising Intelligence
- and mobile advertising
- Making it magical
- beyond the obvious with some case examples
- Shazam, AQA, Blyk, Tohato, Flirtomatic, Cameraphone Dictionary
- Summaries, conclusions, Q and A
VenueDepartment for Continuing Education, Rewley House, Oxford
First day registration from 8.30am when course materials will be distributed.
Refreshments from 8.30am on the first day plus two 30 minute breaks during the day and a one-hour lunch break.
The course will begin at 9.00am and end at approximately 5.00pm on each day.


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Officials are discouraging travel in southeastern Missouri until crews clear the roads from what was expected to be heavy snowfall with blizzard conditions.
The National Weather Service placed 13 counties from the Bootheel to north of Cape Girardeau under a blizzard warning from Tuesday night to midday today. Total accumulations were expected to range from three inches in the Bootheel to 12 inches farther north.
The Missouri Department of Transportation issued a travel advisory late Tuesday afternoon urging motorists to stay off the roads. State maintenance engineer Beth Wright said whiteout conditions would make driving dangerous and complicate road-clearing efforts.
MoDOT recommends checking its online Traveler Information Map for current road conditions. The agency also says its free Traveler Information app for tablets and mobile devices has recently been upgraded.
Traveler Information Map: http://maps.modot.mo.gov/timi/


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Super Street Fighter 4 Arcade '2012 Edition' changes detailed
Capcom has outlined the buffs, nerfs, and tweaks coming to the Super Street Fighter IV Arcade Edition 2012 patch.
Capcom has outlined the changes coming to Super Street Fighter IV from the promised 2012 Edition patch. As expected, some tournament favorites like Akuma and Yun, have been tweaked to make them less devastating, though overall Capcom says it is "focusing on buffing up weaker characters, rather than nerfing existing ones."
The Capcom Europe blog gathers up translations on the Capcom Unity blog. Most of the classic characters like Ryu, Ken, Sagat, and Chun-Li are getting only minor changes to make them more user-friendly, while others like Blanka and Zangief are receiving general balance changes. Some characters like T. Hawk are just receiving changes to make up for the rest of the roster's alterations.
Most characters received minor buffs, but Gouken, Adan, and Hakan seem to be getting the lion's share of improvements. Akuma is receiving some light nerfing, particularly in move loops, and C. Viper and Seth are both receiving a bit of a downgrade as well. Yun, usually cited as the most overpowered character, is probably getting the most nerfs. Capcom says this is to make him less of a "scrubby character" and to focus his talents on "players with strong technical skills."
The announcements didn't outline specific release plans for the balancing patch, but it's planned for location testing in Japanese arcades soon.
Steve Watts posted a new article, Super Street Fighter 4 Arcade '2012 Edition' changes detailed.
Capcom has outlined the buffs, nerfs, and tweaks coming to the Super Street Fighter IV Arcade Edition 2012 patch.
It is good to see the new release of good games any way. Those classic arcade games are great and every one should try it.