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#editing technique
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I recently finished a short story I want to edit, but this is what always gets me: it feels too big. There's things I want to add, but they're so vague and nebulous. There's things I want the story to do, but I don't know how. There's things I want it to be, and I have no idea where to start. There's just too much. I've been writing for more than 20 years and it's always like this with editing.
I wish I could say editing gets easier every time you do it, but... uh, that is not my experience. My best advice for editing is to use the Chunk It method:
First, focus on the Big Picture items. Does the plot make sense? Can you specifically identify which parts you want to add more to? Can you nail down why? Is the point of your story clear? Maybe there's an emotion or a relationship you need to clarify, but it's hard to see unless you specifically look for it.
Next, Step It Out. Identify the Beginning, Middle, and End of your story. What are the important plot points in between? Where's the first and second turn? For a short story, you may not have many steps, but being able to identify them may help you stop getting lost in the woods.
Third, get down to the nitty gritty but only if you've figured out why needs fixing first. What can you do to fix these problems? Go back to the plotting board, switch some ideas out to see if they work better. Explain your plot to a third party - even a rubber ducky would help.
Word choice and sentence structure should always be last - you don't want to waste an hour on a paragraph you will delete down the road. Believe me, a glaring typo or bad wording may haunt you until you have to change it, but don't get bogged down in grammar fixes until you're satisfied with everything else.
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jcmarchi · 2 months
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Scientists develop a rapid gene-editing screen to find effects of cancer mutations
New Post has been published on https://thedigitalinsider.com/scientists-develop-a-rapid-gene-editing-screen-to-find-effects-of-cancer-mutations/
Scientists develop a rapid gene-editing screen to find effects of cancer mutations
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Tumors can carry mutations in hundreds of different genes, and each of those genes may be mutated in different ways — some mutations simply replace one DNA nucleotide with another, while others insert or delete larger sections of DNA.
Until now, there has been no way to quickly and easily screen each of those mutations in their natural setting to see what role they may play in the development, progression, and treatment response of a tumor. Using a variant of CRISPR genome-editing known as prime editing, MIT researchers have now come up with a way to screen those mutations much more easily.
The researchers demonstrated their technique by screening cells with more than 1,000 different mutations of the tumor suppressor gene p53, all of which have been seen in cancer patients. This method, which is easier and faster than any existing approach, and edits the genome rather than introducing an artificial version of the mutant gene, revealed that some p53 mutations are more harmful than previously thought.
This technique could also be applied to many other cancer genes, the researchers say, and could eventually be used for precision medicine, to determine how an individual patient’s tumor will respond to a particular treatment.
“In one experiment, you can generate thousands of genotypes that are seen in cancer patients, and immediately test whether one or more of those genotypes are sensitive or resistant to any type of therapy that you’re interested in using,” says Francisco Sanchez-Rivera, an MIT assistant professor of biology, a member of the Koch Institute for Integrative Cancer Research, and the senior author of the study.
MIT graduate student Samuel Gould is the lead author of the paper, which appears today in Nature Biotechnology.
Editing cells
The new technique builds on research that Sanchez-Rivera began 10 years ago as an MIT graduate student. At that time, working with Tyler Jacks, the David H. Koch Professor of Biology, and then-postdoc Thales Papagiannakopoulos, Sanchez-Rivera developed a way to use CRISPR genome-editing to introduce into mice genetic mutations linked to lung cancer.
In that study, the researchers showed that they could delete genes that are often lost in lung tumor cells, and the resulting tumors were similar to naturally arising tumors with those mutations. However, this technique did not allow for the creation of point mutations (substitutions of one nucleotide for another) or insertions.
“While some cancer patients have deletions in certain genes, the vast majority of mutations that cancer patients have in their tumors also include point mutations or small insertions,” Sanchez-Rivera says.
Since then, David Liu, a professor in the Harvard University Department of Chemistry and Chemical Biology and a core institute member of the Broad Institute, has developed new CRISPR-based genome editing technologies that can generate additional types of mutations more easily. With base editing, developed in 2016, researchers can engineer point mutations, but not all possible point mutations. In 2019, Liu, who is also an author of the Nature Biotechnology study, developed a technique called prime editing, which enables any kind of point mutation to be introduced, as well as insertions and deletions.
“Prime editing in theory solves one of the major challenges with earlier forms of CRISPR-based editing, which is that it allows you to engineer virtually any type of mutation,” Sanchez-Rivera says.
When they began working on this project, Sanchez-Rivera and Gould calculated that if performed successfully, prime editing could be used to generate more than 99 percent of all small mutations seen in cancer patients.
However, to achieve that, they needed to find a way to optimize the editing efficiency of the CRISPR-based system. The prime editing guide RNAs (pegRNAs) used to direct CRISPR enzymes to cut the genome in certain spots have varying levels of efficiency, which leads to “noise” in the data from pegRNAs that simply aren’t generating the correct target mutation. The MIT team devised a way to reduce that noise by using synthetic target sites to help them calculate how efficiently each guide RNA that they tested was working.
“We can design multiple prime-editing guide RNAs with different design properties, and then we get an empirical measurement of how efficient each of those pegRNAs is. It tells us what percentage of the time each pegRNA is actually introducing the correct edit,” Gould says.
Analyzing mutations
The researchers demonstrated their technique using p53, a gene that is mutated in more than half of all cancer patients. From a dataset that includes sequencing information from more than 40,000 patients, the researchers identified more than 1,000 different mutations that can occur in p53.
“We wanted to focus on p53 because it’s the most commonly mutated gene in human cancers, but only the most frequent variants in p53 have really been deeply studied. There are many variants in p53 that remain understudied,” Gould says.
Using their new method, the researchers introduced p53 mutations in human lung adenocarcinoma cells, then measured the survival rates of these cells, allowing them to determine each mutation’s effect on cell fitness.
Among their findings, they showed that some p53 mutations promoted cell growth more than had been previously thought. These mutations, which prevent the p53 protein from forming a tetramer — an assembly of four p53 proteins — had been studied before, using a technique that involves inserting artificial copies of a mutated p53 gene into a cell.
Those studies found that these mutations did not confer any survival advantage to cancer cells. However, when the MIT team introduced those same mutations using the new prime editing technique, they found that the mutation prevented the tetramer from forming, allowing the cells to survive. Based on the studies done using overexpression of artificial p53 DNA, those mutations would have been classified as benign, while the new work shows that under more natural circumstances, they are not.
“This is a case where you could only observe these variant-induced phenotypes if you’re engineering the variants in their natural context and not with these more artificial systems,” Gould says. “This is just one example, but it speaks to a broader principle that we’re going to be able to access novel biology using these new genome-editing technologies.”
Because it is difficult to reactivate tumor suppressor genes, there are few drugs that target p53, but the researchers now plan to investigate mutations found in other cancer-linked genes, in hopes of discovering potential cancer therapies that could target those mutations. They also hope that the technique could one day enable personalized approaches to treating tumors.
“With the advent of sequencing technologies in the clinic, we’ll be able to use this genetic information to tailor therapies for patients suffering from tumors that have a defined genetic makeup,” Sanchez-Rivera says. “This approach based on prime editing has the potential to change everything.”
The research was funded, in part, by the National Institute of General Medical Sciences, an MIT School of Science Fellowship in Cancer Research, a Howard Hughes Medical Institute Hanna Gray Fellowship, the V Foundation for Cancer Research, a National Cancer Institute Cancer Center Support Grant, the Ludwig Center at MIT, a Koch Institute Frontier Award, the MIT Research Support Committee, and the Koch Institute Support (core) Grant from the National Cancer Institute.
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dimeadozencows · 4 months
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I have endured what no one on earth has ever done before
I put my lips to the hands of the man who killed my son
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saltpepperbeard · 3 months
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Yeah, it's a piece of twine. For @blakbonnet 🎉💖. Happy Birthday to my dearest, sweetest clown! Babe, if I could gift you the renewal announcement, I would. Really quite whack that they haven't yet, because you assuredly deserve that on your special day. You deserve the world, really. Thank you for making the fandom space that much more special, and thank you for always enabling me <3 SJDKSSD. Idc what anyone says; we're in it for the long run, babe. We'll CLOWN FOREVERMORE. Love you so much, and hope you have a wonderful day <333
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speakofcompersion · 2 months
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Happy anniversary, Circle ♡
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makerscockandballs · 2 years
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that’s how it went right
[Image ID: Three-panel comic about Dragon Age 2. The first panel shows Anders and Hawke, who is depicted as a brown man with long black hair tied into a ponytail and wearing a red cape. Anders is angrily gesturing with his hands and finishing up a speech with "...Andraste's words that magic should not rule over man. It is not ruling to simply wish for the same rights as any man!". In the second panel, Hawke lays a hand on his shoulder with a sympathetic look and says "So true bestie." to which Anders looks dumbfounded. In the third panel, only Anders is depicted in all grey and a blush on his face as he stares at the floor in disbelief. Behind him, google searches are depicted that each say: "where to but engagement rings in kirkwall", "spells to make your ass fatter", "average fereldan dick size", "how to find out if your crush likes men", "fereldan courting rituals", "marriage certificates for fugitives" and "deepthroat tutorial". ./ End ID]
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muldxr · 6 months
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ghoul boys high five!
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dyingbuck · 2 months
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one sad old man
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skeletonrodeoqueen · 19 days
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Well jack, don't make me flash these baby blues ⚡️
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couthbbg · 5 months
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you don't have to be sorry, no. x . x . x . x . x . x . x . x . x
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cowardlykrow · 1 month
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I just needed to say: I LOVE YOUR ART SM
It's great and I am obsessed--!
THANK YOU SO MUCH OTL
My gut tells me you would appreciate this scribble 💚
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brb-on-a-quest · 4 months
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I had a thought last night, and even though the only canon bat source I've had is WFA, and I've only *just* started getting into fanfic, so characterizations may not be accurate/have been done before, but IDK. I need this to exist out there.
Timothy Drake-Wayne writes fics sometimes.
It started off with the necessity of creating so many fake IDs. One thing led to another and Tim was coming up with backstories for all the Johns, Marys, and Joes that he invented while doing his Gotham digital surveillance. After all, he was trying to make these people's fake IDs look as real as possible, which meant more than just a name on a couple of sheets of paper.
It means creating a fake digital footprint. For each one.
So, on the rare occasions when things are calmer, and he's not immediately needed, he sits on his computer and types out head cannons for each of the OCs he has created. He spends a lot of time doing research on different cultures, neurodivergencies, physical abilities, and backgrounds to try and 1) paint accurate pictures and 2) learn. He hides the world building tidbits in a secret folder that he's taken so many measures to hide from Oracle (she already knows, but she doesn't actively look after finally figuring out what the folder of names, complete with physical descriptions, life stories, and preferences is out of respect for Timothy). (Also, all this writing knowledge actually comes in handy for crime-solving things, but he doesn't fully realize it at the time).
Tim even went as far as to make social media accounts for some of his favorites and posts bits and pieces of the head cannons to make them, again, seem like real people. Just in case. As a precaution. You never know.
Jason finds out somehow, in a freak accident and collision of siblings that so often happens. Tim is sweating bullets, trying to steel himself for the endless teasing. He is fully prepared to delete every single file that's in that folder and deny that it ever exists for all eternity.
Except Jason doesn't. Jason's too much of a literary nerd (granted, he prefers more classic literature than social media fics, but this is another thing he can connect with his little brother on- he's *excited*) to tease Tim about the writing. He kind of persuades Tim to take more time for his hobby because Tim has some markings of talent in his very specific creative niche. Tim may have also convinced Jason to try it exactly once, to create a fake Twitter profile for Mr. Darcy and create shitposts from his point of view. He has a great time with it once, and then he moves on (but sometimes he creates other accounts for other characters that Tim doesn't know about).
They make a pact between the two of them not to tell the others; they'd ask too many questions and make it less fun.
But every once in a while, Tim would walk into Jason's place to crash for a bit, steal all of his Red Bull, update Jason on his writing projects, and get writing advice.
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saltpepperbeard · 4 months
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Stede + Looking Spicy 🔥🔥🔥 For @bizarrelittlemew 🎉💖. Happy Belated Birthday, dearest Ida! So sorry for the holdup. One could say there were some uh, eXTENUATING CIRCUMSTANCES. But regardless of everything going on, I still hope you had the most marvelous day, and I'm sending you so much love, so many hugs, and all the Rhys Shots you could possibly ask for. Stiddies? Leggies? Hair? You got it, babe. I'm there. I'm always in awe of you and your talent, and I hope to have the honor of creating alongside you for many, many more months to come. Cheers and love to you always <3
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trustiskingandqueen · 3 months
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I'm a summer dream, I'm a real light beam - I'm worthy of all the goodness and the love that the world's gonna give to me I'ma give it back ten times, people, are you ready? If you think you're alone hold on, I'm coming - x
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oh-gh0st · 6 months
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awwww they're on a date !
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sophsun1 · 1 year
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