#sam-e

[lorib643]

Methylation

Methylation risk variant results MTHFR, CBS, COMT, MTR and MTRR I had a DNA test done through ancestry. I sent the results to Life DNA and got some information. They had an offer on methylation genes so I had that analyzed. Out of 10 genes, 7 had risk variants. The variants are not unusual. Some of them lead to an increase in homocysteine which when increased can be a heart attack risk.  I …

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[nightingaletrash]

I’m back on my Mass Effect bs and specifically my theory that the Benefactor of the Andromeda Initiative is a rogue AI.

Little to nothing is known about the Benefactor save for a few details:

They hide behind a shifting guise of multiple species and gender, while using a female voice

They were able to provide the Initiative with apparently unlimited resources to supplement Garson’s fortune

They knew the Reapers were coming which is their supposed motivation for funding the Initiative

Only a handful of individuals were aware of the Benefactor’s involvement; Jien Garson, Alec Ryder, and (presumably) the first six successors for the position of Initiative Director. All of whom are now dead. Alec was killed in the accident on Habitat 7, Garson was murdered to silence her, and the successors were reported as casualties of the Scourge. But considering Garson was also presumed a casualty of the Scourge, it’s much more likely that they were also murdered to ensure no one in Andromeda knew about the Benefactor’s existence, which left Tann (the eighth-in-line, and someone with no knowledge of the Benefactor) to take up the role of Director.

Now onto why I think the Benefactor is a Rogue AI.

In the novel Mass Effect: Andromeda - Initiation, a kernel of SAM’s AI data is stolen and Cora Harper is sent to retrieve it or see it destroyed before it has the chance to be disseminated throughout the Milky Way. In the end the data is destroyed, but it’s revealed that one of the thieves may have been able make a copy of the data which they could then sell regardless.

Towards the end of the novel, Jien Garson appears in hologram form to Cora Harper where she reveals that there are other groups that want to get their hands on the AI tech and have it be available in the Milky Way. AI is the core of the Andromeda Initiative after all. And Garson states that the one behind it all, the one pulling all the strings and manipulating events surrounding the Initiative, ‘wants it more than any of us, and is willing to do anything to see it come to life.’

Organic-AI integration first appeared in Mass Effect 2′s Project Overlord DLC, which also served as the driving motivation behind Katherine Nigh, or Knight, in the Firefighters sidequest. It’s also an overarching theme in Initiation, which multiple examples of Organic-AI integration ranging from beneficial (Cora and SAM-E) to horrifying (Medea and the Augments). So we can guess that universal acceptance of this integration is key to the Benefactor’s ultimate goal; fleeing the Reapers wouldn’t exactly be unique or interesting, and if all they wanted was to escape the Reapers, why try to leak SAM’s AI data in the Milky Way? Initiation takes place after the Battle of the Citadel and around the time that the Collectors were abducting colonies, so its not like that those events happened before the Benefactor’s ‘suspicions’ about the Reapers were confirmed. They knew the Reapers were coming, and still tried to leak SAM’s data.

As Garson said, the Benefactor is willing to do anything to ensure the dispersal of SAM’s technology and see it fully realised with no restrictions. And probably not for altruistic purposes. More likely the Benefactor has recognised that AI like the Geth would never be accepted by organics (whether this is true or not depends on Shepard’s choices in ME2 and ME3), and that AI needed to try a different tact to have any real and unrestrained presence in the galaxy. So they’re pushing for the Organic-AI integration seen in Andromeda, but they likely have more sinister designs than the co-existence we’ve seen so far between SAM and Ryder.

Their plans are probably more aligned with Medea’s actions, though not in the exact same way. While Medea wanted to kill the personnel of Quiet Eddy and altered lab-grown, cybernetically-enhanced humans into weapons to do so, the Benefactor is likely looking to use organics as physical hosts for AI, enabling them to interact with the world directly.

Additionally, a rogue AI could hack all number of accounts for funds and resources and sufficiently cover their tracks, which accounts for their ‘unlimited’ resources.

I really hope Bioware picks this storyline up again in the next Mass Effect game, as it’s supposed to be uniting both OT and Andromeda storylines, and gives us the chance to see how the Benefactor’s plans in the Milky Way have developed, as well as giving us insight into what their plans for Andromeda are.

[darkishtimes]

The Internet Explorers | 1.01

— The Internet Explorers —

“Its not all about finding the memes out there, its about coming to terms with the memes that are ourselves.”

X

[justryderthings]

JRT: wondering how much of sam-e is in sam.

[omegastation]

I saw your posts on Ellen and SAM and thought I would communicate my theory. Which is that SAM is actually Ellen. That Alec had captured her essence somehow, digitised it, algorithimed it and uploaded it into SAM. Therefore Cora could not become pathfinder unless Ellen remained hidden. The teasing memory triggers would allow the twins to learn about this slowly so as not to burn out their brain. And they would kinda get their mother back.

Sorry I’m late in answering this! I read some parts of Initiation again to answer. Under a cut for spoilers.

In Initiation, Alec refers to SAM as "he/him."Cora believes he designed SAM-E with a better-than-average personality matrix. Later she believes SAM-E has "Ryder's sarcasm."SAM-E himself explains that he is built to adapt and become suited to *her personality*, that it's basically how he changes and evolves.

Now, from the chapter from Alec's pov, he wakes up in his lab:"More often than not he slept in his lab, though he’d been making an effort to stop doing that. Ellen didn’t like it."

And he thinks:"It hurt, not having her around to watch his back."

From his pov, he thinks of SAM as "SAM." (I mean, obviously, if it was Ellen, they wouldn't write it but like... I gotta point it out). When SAM asked if it would be terrible to have another version of him around, Alec answers:

“But even an AI developed from your codebase isn’t you, SAM. The problem is that you-AI-kind, if we want to call you that-are just too complex for predictive models or simulations to nail down. I took a chance on you because I think I’m right-I think a symbiotic fusion of organic and artificial intelligence is the key to successful coexistence. But what works under controlled conditions could go completely pear-shaped if every Tom, Dick, and hairy alien starts tinkering with your code.”

I believe, and I hope I’m not mistaken, that his SAM is now developing as he is because of his exposure to Alec and his personality. He has a codebase, is designed to do tasks, but in the end, he has his own personality and evolution.

At some point Alec and SAM talk about dangerous AIs, I feel like this scene helps understand their relationship:

“Then perhaps I could train a successor that will remain here, and teach it to guard against poorly trained others.”Alec frowned and shut off the shower, toweling off. “This is new,” he said. “You’ve never shown any interest in reproduction before.”“No sapient being wishes to be alone,” SAM replied.“You aren’t. Every Pathfinder team lead has a SAM installation.”“Not like me.”That was true. The other SAMs were… limited, at least in comparison with Ryder’s personal SAM. The Initiative had insisted on it, and he’d agreed, in order to have a chance to finish the end-stage development. And he’d kept his word. The SAM units he produced for the Initiative’s use were precisely what they’d asked for: adaptive, intelligent software that ran on the platform of an organic being’s body, enhancing and augmenting it at will.His SAM, however, was for his use, and he was going to develop that one however he damn well pleased-to the limits of the SAM’s capabilities. What the Initiative didn’t know wouldn’t hurt them.“Let’s just see if we can’t get you perfected before we start talking about transference,” Alec said. “First things first.”

Alec thinks SAM has to be perfected. And he is possessive of his SAM. Another moment from the scene: Alec tells SAM: "What if something happens to me, and you transfer to the next Pathfinder-” Harper, he’d been hoping, although… “-and that person is an asshole?”"We know from this Alec believes - in that moment - that Cora would have to be his successor.

Another scene that I think is important, because it shows how Alec perceives SAM and his role:

Later, as Alec finished shaving and started to dress, SAM said, “Lieutenant Harper wanted to know how SAM-E felt about integrating more closely with her.”That was… Damn it. He kept his voice neutral, though he knew it was futile. “And how did SAM-E feel?”“He liked being asked, but vocal stress and fluctuations in your heart rate suggest that you are displeased she did.”“I just don’t want you to get used to that, SAM. You have a job to do-an important, mission-critical job. Sometimes getting that job done is going to mean obeying orders without question, whether you understand or agree with them or not.”Even as he said this, Alec felt like a complete hypocrite.After all, hadn’t he once been terrible at following orders, especially without question? This is karma, he thought irritably. Every hard time I ever gave my old COs is coming back to bite me now. Regardless, the same principle applied. Those COs had been wrong to demand lockstep behavior from a man who could innovate rings around them, and it was probably wrong of Alec to forever expect an AI to obey without question.“I would, of course, prioritize preservation of my organic partner’s life in critical situations,” SAM noted, sounding thoughtful. “But as you said, that would be only sometimes.”“That would be whenever I tell you to,” Alec said firmly. “However, as you begin to understand me better, the goal is that you will learn what’s important to me, and to organics in general. But until then-”“I see,” SAM said. “You are of course correct, Alec. I’ll modify my response matrix to reflect this.”Alec suppressed the urge to let out a sigh, though SAM would probably detect the aborted impulse anyway. He really needed to have a talk with Lieutenant Harper about giving her AI ideas.

Btw, when Cora learns about SAM-E being an AI, she starts talking about the possibility of AIs wiping out billions. And Alec's answer is: "All tools are dangerous, used incorrectly."My personal opinion on this is that he views SAM as a means to an end. 

Next, we have two interesting parts of a later scene, in order:

“SAM,” he said. He sat in front of one of the terminals in his lab, rubbing his eyes.“The course of action you’re considering is ill-advised, Pathfinder,” SAM replied.Alec almost laughed, though he wasn’t entirely surprised. “And how do you know what I’m considering?”

and

“He fell, SAM.”“My apologies. He fell, and you assisted his landing with military-grade hand-to-hand techniques.” A meaningful pause. “As I recall, Assistant Director Hachian tendered his resignation as soon as he regained consciousness, citing ‘that bastard Ryder’ as one of several job dissatisfaction factors.”Alec made a face. He was really going to have to figure out which of SAM’s humor heuristics was responsible for the AI developing that deadpan vocal inflection. And he stopped himself from continuing to tap his hand.

-> I think familiarity means SAM is starting to guess and understand Alec the way someone very close to him (constantly attached, really) would. BUT truthfully Alec doesn't know what he's doing - he has to "figure out" SAM's personality.

Now when SAM Node is about to be destroyed, SAM tells Alec in his private comm: “Thank you for creating me, Alec. I wish you luck in the mission to Andromeda.”Alec is legit going to kill himself trying to save him. He tells Cora: “We need SAM, damn it. They never understood his potential.”Of course, he means *he* needs SAM.

But that's when he realizes that his own SAM can only be used by someone who shares his genetic makeup:

He supposed that was true. And he wished he could tell her the whole truth: that he’d actually meant for Harper and her AI to get attached to each other. That he’d hoped their integration would prove SAM’s adaptability… and transferability. If things had worked as they should have, then SAM would have been the one to integrate into SAM-E when Ryder died, not the other way around. Harper would then have been the new Pathfinder.But the degradation curve had been too steep, and too inevitable. SAM-E hadn’t been adapting properly to Harper, and the maladaption rate had been increasing. His stuttering and constant errors had actually been warning signs of an impending systemic breakdown. If Ryder hadn’t had to reintegrate him with SAM because of the emergency, he would’ve had to do it eventually anyway, lest SAM-E inadvertently harm Harper on a biological level.But that was real hurt in Harper’s expression, and Alec couldn’t bring himself to compound her grief by telling her that SAM-E had been doomed from the beginning.At least SAM-E hadn’t died for nothing. Now Alec knew that no one would be able to inherit Alec Ryder’s personal SAM—the most advanced of them all, and the one he hoped would unlock humanity’s ultimate potential—except someone who shared his genetic makeup. Harper could not become the new Pathfinder, but forewarned was forearmed. Now Alec just needed to decide which of his two children would end up burdened with the future of their entire species.

At the end of the book, SAM's memories are now linked with SAM-E's:

“So I hear.” Harper glanced around at the ceiling, then nodded as she spied a camera array in one corner. “Do you remember what I promised SAM-E, then? After one of the times he saved my life?”“Yes, those memories are part of me, Lieutenant.” And—Alec blinked. Did SAM actually sound… shy? Embarrassed, maybe.“Good.” Harper faced one of the undamaged processor-walls, picked a middling-level node, and stood on her tiptoes to kiss its paneling. “There.”“Uh,” Alec said, flummoxed. “Am I going to have to get a chaperone for you and my AI, Harper?”

I don't think he would react like this if at this point he thinks of SAM as Ellen.

With Initiation over, we know there are months before the Initiative starts launching.

Two possibilities:-Ellen herself worked with Alec before, in unseen scenes by us, to integrate herself into SAM. If she did it, the plan would be to “download” her into SAM and making her SAM after SAM is perfected and Alec resolves the Pathfinder transfer. But we know from the book that he didn’t exactly plan for his kids to have that role so I’m not sure the theory/headcanon could hold. And if Ellen “becomes” SAM, SAM (his own essence) will be gone. So Ellen would pretend to be SAM.

-I think Alec can potentially use Ellen's essence and upload it but... accidentally. I don’t believe he’s entirely in control of SAM. He could create parameters that would make SAM very close to Ellen but Ellen would still be Ellen and SAM would be SAM with Ellen's personality. Only Alec knows that even if he did all that, 1. it wouldn't be his wife (not really), 2. SAM as Ellen would eventually adapt and change and become their own person. So in a way, he might lose Ellen twice. Another possibility is using her consciousness in a virtual environment situation but I don't think he would do it. My main reasoning for that is that Ellen wouldn't like it, she didn't wish for that and Alec, despite his flaws, loved her enough not to do something that cruel to her.

Okay I'm done lol

What do you think? I’m not exactly saying it’s impossible. I think canon tells us, so far, that the theory doesn’t entirely work BUT Alec was known to have secrets and things could have dramatically changed after Initiation. In the end we aren’t in his head so it’s hard to tell :) 

[fade-touched-eezo]

Okay, but what if that little piece of artwork in Cora’s area on the Tempest wasn’t by the current SAM, but by SAM-E?

[mirasmixtape]

http://open.spotify.com/user/miratunek/playlist/7zOrMzFtOWWk0O4a2zoSAR

ocean - Yaeger

Nuggets - Mura Masa ft. Bonzai

VIP Wet Dreams - Tella Viv

Ashanti - Unge ferrari

Keep My Head Up - LNKAY

Not Down 4 Whatever - IMAN

Don’t You Worry - Marlene

Dela På Hälften (RMH Remix) - Parham ft Adam Tensta, Eboi, Nebay Meles

Spela Över - Parham

0400 - Julia Adams

Litt for mye - Lovless ft. Philip Emilio

Champagne - Adoo, Baba Moe, Sam-E

Mirror - Hyuna

Rough Soul - Goldlink ft April George

NA B YA - Peejay ft Zion.T

Bad4U - Loveless ft Awa

Alene - Arif

Vi Burde Ha Vært På Film - No. 4

Blood Under My Belt - The Drums

Gamble - TOKiMONSTA

Ring Ring Ring - Somdef ft. Verbal Jint, Paloalto, DPR LIVE & CAR, THE GARDEN

Where - Laybacksound

MAKE YOU SAY - Rachel Foxx

Beautiful Little Fools - Jorja Smith

Nostalgia - JON VINYL

Froot - Marina and the Diamonds

Make You Love Me - Jarreau Vandal ft Zac Abel

Det Hvide Snit - Aksglæde

[didanawisgi]

Epigenetics and pharmacology

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439868/#b12

Progress in pharmacology

Historically, there has always been pharmacology; however it wasn't always termed as such. From prehistoric use of plants as medicines, such as aspirin-like compounds from the bark of willow trees or other salicylate-rich plants in ancient Egyptian and Greek times, man has used drugs to control our physiology. Pain management is a good example of how Pharmacology has developed over time – from medicinal products with unknown ingredients that helped, through to chemically-synthesised purified compounds with known structure and activity – pharmacological science has developed our understanding and creation of therapeutically-useful compounds.

The epigenetic era

With recent improvements in understanding of the actual function of the entire genome, pharmacology has to modify itself further to think of tackling diseases not in the conventional ‘drug-receptor’ sense, but in a more ‘global-response’ sense. Drugs may not be designed to be as exact to a particular ligand or specific to a particular gene or protein subtype, they may indeed have to be able to be more broad-acting over a range of epigenetic large-scale events. These larger-scale epigenetic regulatory mechanisms may span more than one gene or family of proteins, they may in fact regulate large groups of genes (Figure 1). Importantly, the advantage to this approach is that often, the epigenetic variations can be the underlying cause of a particular disease, and simply targeting one protein of the multiple pathways involved may be futile. Diseases such as cancer often have many different mutation variations that are difficult to detect, predict and effectively treat, leading too often to relapse. Epigenetics of cancers may be the key to more effective treatments.

Nutrition and the epigenome

There are several theories why a healthy balanced diet rich in fresh fruit and vegetables is good for your health. What may be undervalued as a mechanism by which our diet is able to stave off diseases of old age (cancer, cardiovascular diseases, dementia, etc.) is the role of epigenetics. Epigenetic modifications are heritable with simultaneous dynamics, plasticity and reversibility, and as such they are prone to changes upon external stimuli including diet. One of the strongest links between diet and the epigenome exists in one carbon metabolism where nutrients including methionine and folate are needed for synthesis of a methyl donor, S-adenosylmethionine (SAM) (Stefanska et al., 2012). Any imbalances in the intake of these nutrients will impact the rate of methylation reactions in the human body and consequently DNA methylation patterns and histone methylation marks followed by alterations in chromatin and gene expression. Recent studies of the genome-wide DNA methylation profiles in different cancers reveal that hypermethylation and silencing of genes is only one side of the story. An almost equal number of gene promoters is activated following loss of DNA methylation marks (demethylation) (Stefanska et al., 2011). These genes are putative drivers of carcinogenesis and metastasis. Using SAM as a tool to methylate and silence this group of genes appears to be a tailored way to impair metastasis (Shukeir et al., 2015). The function of SAM in increasing DNA methylation has been also used in treatment of Alzheimer's disease with promising results in animal models (Scarpa et al., 2006). Pharmacological intervention with SAM restores the epigenetic control of the β-secretase gene by hypermethylation and silencing followed by a decrease in formation of amyloid plaques.

The last decade of research has provided us with numerous pieces of evidence supporting the role of many other diverse groups of dietary compounds, particularly polyphenolics, in modifying the epigenetic marks. A few representatives of polyphenols, such as resveratrol, genistein, and curcumin, have been demonstrated to regulate gene expression through affecting several epigenetic components, from DNA methylation through histone modifications to microRNAs (Stefanska et al., 2012). Apart from catechol compounds that reduce intracellular SAM pools available for DNA and histone methylation, polyphenols lack a direct link with the epigenetic machineries and the mechanisms underlying their epigenetic action are yet to be determined. The importance of epigenetic mechanisms in shifting the disease phenotype towards the healthy phenotype will be crucial to the adaptation of these compounds in pharmacological therapeutic approaches. With technological advances and next generation sequencing, the future will allow us to switch from studying candidate genes and single pathways to exploring a comprehensive genome-wide view of epigenetic effects of diets and isolated compounds and elaborating on underlying mechanisms of their epigenetic actions.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439868/pdf/bph0172-2701.pdf