Greetings, lostfalco. Have you established pre-experiment values for tests such as digit span (forward and backward) and visual response time, as baseline metrics to be compared to measurements as you proceed? What will your before/after metrics be? Any particular blood tests?
Lostfalco's Extensive Nootropic Experiments [Curated]
#3931
Posted 13 December 2022 - 02:07 AM
#3932
Posted 14 December 2022 - 06:45 PM
I've been checking in and reading along LostFalco! Hope the iq increase works. U should look into 40 years of zen too
Thanks Q! I appreciate it. I'll look into it. I'm definitely hoping to enhance the efficiency and connectivity of my control networks over my default node network. This has been correlated with the benefits of experienced meditators. (See study below)
"Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self-monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation."
To be honest, I've already noticed massive increases in this ability (subjectively) from my Circadian enhancements and Bright Light Therapy in particular.
It's been the missing cognitive piece I've been looking for my whole life. My brain is a perfectly balanced/contained nuclear fusion reaction right now.
It's hard for me to imagine it getting much better. I hardly even recognize the person I've become.
I'm gonna toggle one more synaptogenesis switch though! lol
Speaking of Bright Light Therapy, have you looked into it for bipolar depression?
"BLT has shown reliable effectiveness and safety in treating patients with bipolar depression and should be considered a clinically relevant approach in accelerating patients' therapeutic response and reducing the impact of long-lasting therapy." (see study below)
I've also added a $39.99 device to my recommendations so that it should be affordable for a lot more people. See here: https://www.lostfalco.com/devices/
Also, sleep is super important in bipolar disorder and wearing blue blocking glasses starting 3 hours before bed has been shown to increase melatonin in humans. (see study below)
"Short wavelength-blocking glasses (Ultraspec 2000, https://www.uvex.com/en) were dispensed for the subjects to wear in the evenings for 2 weeks. The transmission spectrum of the glasses was confirmed, showing that the lenses absorb approximately 99% of light shorter than 540 nm, and transmit approximately 90% longer than 540 nm."
"...the Uvex lenses block 99% of blue light, and the goal of this experiment was to decrease short wavelength stimulation to the highest degree possible."
"Therefore, all subjects wore the glasses for at least 3 h, although some wore them longer based on their habitual bedtime."
"Night-time melatonin at baseline was 16.1 ± 7.5 pg mL−1 (Figure 4). After the two-week experimental period, night-time melatonin statistically significantly increased 58% to 25.5 ± 10.7 pg mL−1 (effect size r = −0.44, t19 = −3.95, P = 0.0005)."
"The increase in night-time melatonin and increased sleep duration afforded from the Uvex glasses was robust..."
I've added Uvex blue light blocking glasses to my recommendations here: https://www.lostfalco.com/devices/
They are only $12.50.
Anyway, I will create an entire bipolar protocol sometime in 2023.
It's 100% on my to do list.
It seems to be quite a circadian disorder and the most effective treatments bear this out (see study below on Lithium and clock genes).
"These data suggest that trait‐like differences in cellular rhythms negatively influence lithium treatment in BD patients, and that one of the mechanisms by which lithium may exert its therapeutic effects is by shifting period."
I hope you're doing ok and I hope you find things that help you!
And, of course, remember that I'm not a doctor so take my advice with the proper skepticism and always trust your doctor over me. =)
Feel free to show your doctor these studies though and get his/her feedback.
Meditation, Control Networks, Default Mode Network
https://www.ncbi.nlm...les/PMC3250176/
Meditation experience is associated with differences in default mode network activity and connectivity
Abstract
Many philosophical and contemplative traditions teach that “living in the moment” increases happiness. However, the default mode of humans appears to be that of mind-wandering, which correlates with unhappiness, and with activation in a network of brain areas associated with self-referential processing. We investigated brain activity in experienced meditators and matched meditation-naive controls as they performed several different meditations (Concentration, Loving-Kindness, Choiceless Awareness). We found that the main nodes of the default-mode network (medial prefrontal and posterior cingulate cortices) were relatively deactivated in experienced meditators across all meditation types. Furthermore, functional connectivity analysis revealed stronger coupling in experienced meditators between the posterior cingulate, dorsal anterior cingulate, and dorsolateral prefrontal cortices (regions previously implicated in self-monitoring and cognitive control), both at baseline and during meditation. Our findings demonstrate differences in the default-mode network that are consistent with decreased mind-wandering. As such, these provide a unique understanding of possible neural mechanisms of meditation.
Bright Light Therapy
https://www.scienced...165032722012009
Effectiveness of light therapy as adjunctive treatment in bipolar depression: A pilot study
Abstract
Background: About 1 and 4 % of people suffering from depression is affected by bipolar disorder. Few patients respond to the first-line antidepressants, and a 4-week latency pharmacological treatment period has been observed. This pilot study aimed to evaluate the effectiveness and safety of bright light therapy (BLT) in accelerating and increasing therapeutic response in patients with bipolar depression.
Methods: A pilot study was conducted. Patients with bipolar depression, already treated with antidepressants, were included. The treatment group was composed of patients treated with antidepressants combined with BLT (30 min/4 days a week at 10,000 lx for eight weeks). The control group included patients treated with antidepressants with exposure to red light (30 min/4 days a week at a red light for eight weeks). MADRS, HAMD-17, CGI-S, FSS, and QoLS were collected at the baseline and after 4 and 8 weeks of treatments.
Results: Forty-one patients (18 males and 23 females; mean age 49.1 ± 15 years) were included in the study. After four weeks, MADRS and HAMD-17 scores in treatment groups were significantly lower than those reported in the control group (p < 0.001). After eight weeks, all scales except FSS reported significantly lower values in patients treated with BLT (p < 0.0001).
Limitations: Small sample size and significant heterogeneity in the antidepressant treatments.
Conclusion: BLT has shown reliable effectiveness and safety in treating patients with bipolar depression and should be considered a clinically relevant approach in accelerating patients' therapeutic response and reducing the impact of long-lasting therapy.
Blue Light Blocking Glasses
https://www.ncbi.nlm...les/PMC7229994/
Attenuation of short wavelengths alters sleep and the ipRGC pupil response
Abstract
Exposure to increasing amounts of artificial light during the night may contribute to the high prevalence of reported sleep dysfunction. Release of the sleep hormone melatonin is mediated by the intrinsically photosensitive retinal ganglion cells (ipRGCs). This study sought to investigate whether melatonin level and sleep quality can be modulated by decreasing night-time input to the ipRGCs.
Subjects (ages 17–42, n = 21) wore short wavelength-blocking glasses prior to bedtime for 2 weeks. The ipRGC-mediated post illumination pupil response was measured before and after the experimental period. Stimulation was presented with a ganzfeld stimulator, including one-second and five-seconds of long and short wavelength light, and the pupil was imaged with an infrared camera. Pupil diameter was measured before, during and for 60 s following stimulation, and the six-second and 30 s post illumination pupil response and area under the curve following light offset were determined. Subjects wore an actigraph device for objective measurements of activity, light exposure, and sleep. Saliva samples were collected to assess melatonin content. The Pittsburgh Sleep Quality Index (PSQI) was administered to assess subjective sleep quality.
Subjects wore the blue-blocking glasses 3:57 ± 1:03 h each night. After the experimental period, the pupil showed a slower redilation phase, resulting in a significantly increased 30 s post illumination pupil response to one-second short wavelength light, and decreased area under the curve for one and five-second short wavelength light, when measured at the same time of day as baseline. Night time melatonin increased from 16.1 ± 7.5 pg mL−1 to 25.5 ± 10.7 pg mL−1 (P < 0.01). Objectively measured sleep duration increased 24 min, from 408.7 ± 44.9 to 431.5 ± 42.9 min (P < 0.001). Mean PSQI score improved from 5.6 ± 2.9 to 3.0 ± 2.2.
The use of short wavelength-blocking glasses at night increased subjectively measured sleep quality and objectively measured melatonin levels and sleep duration, presumably as a result of decreased night-time stimulation of ipRGCs. Alterations in the ipRGC-driven pupil response suggest a shift in circadian phase. Results suggest that minimising short wavelength light following sunset may help in regulating sleep patterns.
Lithium
https://www.ncbi.nlm...les/PMC9149148/
Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi‐disciplinary literature review and agenda for future research from the ISBD task force on chronobiology
Abstract
Symptoms of bipolar disorder (BD) include changes in mood, activity, energy, sleep, and appetite. Since many of these processes are regulated by circadian function, circadian rhythm disturbance has been examined as a biological feature underlying BD. The International Society for Bipolar Disorders Chronobiology Task Force (CTF) was commissioned to review evidence for neurobiological and behavioral mechanisms pertinent to BD.
Drawing upon expertise in animal models, biomarkers, physiology, and behavior, CTF analyzed the relevant cross‐disciplinary literature to precisely frame the discussion around circadian rhythm disruption in BD, highlight key findings, and for the first time integrate findings across levels of analysis to develop an internally consistent, coherent theoretical framework.
Evidence from multiple sources implicates the circadian system in mood regulation, with corresponding associations with BD diagnoses and mood‐related traits reported across genetic, cellular, physiological, and behavioral domains. However, circadian disruption does not appear to be specific to BD and is present across a variety of high‐risk, prodromal, and syndromic psychiatric disorders. Substantial variability and ambiguity among the definitions, concepts and assumptions underlying the research have limited replication and the emergence of consensus findings.
Future research in circadian rhythms and its role in BD is warranted. Well‐powered studies that carefully define associations between BD‐related and chronobiologically‐related constructs, and integrate across levels of analysis will be most illuminating.
Edited by lostfalco, 14 December 2022 - 08:59 PM.
#3933
Posted 15 December 2022 - 01:32 AM
Greetings, lostfalco. Have you established pre-experiment values for tests such as digit span (forward and backward) and visual response time, as baseline metrics to be compared to measurements as you proceed? What will your before/after metrics be? Any particular blood tests?
Greetings, Advocatus Diaboli.
These are great questions. I'm really thinking hard about them right now. Here's why...
Over the past few years my view on 'intelligence' has changed significantly. I used to think in terms of metrics like working memory, reasoning, processing speed, etc. (see chart from Haier's 'The Neuroscience of Intelligence' below)
Haier.JPG 48.82KB 0 downloads
My reading of John Sweller and his cognitive load theory completely upended this for me.
In Sweller's view, the storehouse of long term memory is the key area to focus on, not working memory.
In fact, working memory is intentionally limited by evolution to prevent us from making anything other minor changes to our long term memory.
Why would evolution do this?
Answer: the human brain has been slowly built by 4 billion years of evolution (from single celled organisms on up to us; humans only appearing in the past 300,000 years by current anthropological estimates) and that massive storehouse that is our subconscious is a treasure to be protected in the same way that DNA is protected inside the nucleus of a cell and is copied to RNA before translation in order to protect the valuable information DNA contains.
Thus, we have a working memory of 4 plus or minus 1 items and can only input a few items into it at a time. (hence, 'cognitive load' in Sweller's view)
This functions as an intentional evolutionary bottleneck that prevents us from making large changes to long term memory...because we'd probably screw it up! lol
On the other hand, we can build mental models in our long term memory and send those entire structures at one time into one or more of the slots of our working memory (the subconscious sending information into our conscious mind).
These structures can be virtually unlimited in size.
This enormous asymmetry has lead me to believe that true intelligence is the ability to send larger and more complex mental structures into working memory from our long term memory which we can then compare in our conscious mind with the input coming in from the outside world.
I think about it this way.
I've been alive for 44 years and from birth my brain has received almost completely uninterrupted streams of data from my eyes, from my ears, from interoceptors inside my body, from exteroceptors on my skin, tongue, stomach, etc.
Using this unfathomably large data set it has built intricate, immaculate structures using the 86 billion neurons, 86 billion glial cells, and 1,000 trillion synapses that is my brain.
Getting as much of this subconscious machinery as possible to simultaneously send data to my conscious mind is what I think the essence of intelligence is.
Once I do this, the only thing remaining to do is to check this subconsciously generated cognitive structure against reality using my conscious mind.
This is why I call my memory technique Spaced Generation Learning.
It is primarily about the act of 'generating' cognitive structures which enter working memory,
My goal with MDMA + Bright Light Therapy is to enhance synaptogenesis with MDMA and stimulate all those new synapses with light which will thereby open up new pathways from my long term memory (subconscious) to my working memory (my consciousness).
Do you see how this sets most views of intelligence on their head?
My goal could be called 'back-to-front' as opposed to 'front-to-back'...if we consider long term memory to be coming from the back our brain and working memory to be housed in the front of the brain just for the sake of our thought experiment, of course. This isn't meant to be taken too physiologically literally.
So, I ask myself what could my metric could be?
My best answer right now is future problem solving.
Will I be able to generate creative, lateral thinking solutions to biological problems (my main focus) going forward?
Tbh, the metric seems like it's going to have to be mostly subjective on my part and the the observable metric for you guys is going to be my output over the next year.
I just don't see things like forward and backward digit span as being that valuable right now in my current view of intelligence.
My view might change and I'm really thinking hard about it right now.
Regardless, I do feel like the value I can provide for everyone watching and reading is going to be the safety (or not) of combining MDMA with Bright Light Therapy.
If I become an incoherent rambling mess then that will be a cautionary n=1 for everyone watching. lol
Hopefully that doesn't happen and I think that probability is pretty low.
I've taken MDMA before and I've used Bright Light Therapy a million times and I've already tested a low dose version of them together.
But, ya never know.
Anyway, that's a long, rambling answer for you but it's the best I've got right now.
I'll let you know if I change my mind.
Good questions though.
#3934
Posted 15 December 2022 - 01:38 AM
Hey everyone! My Abstract Wednesday post is going to have to wait until tomorrow.
Q did it and Advocatus Diaboli brought up some good thoughts that occupied my mind and I wanted to give them proper answers.
I have been updating my Diet post on my site it's a work in progress but check it out for now for some new information: https://www.lostfalc...t-deficiencies/
My Abstract Wednesday post is freaking long as hell anyway so it'll be best to wait until tomorrow so I can edit it a little.
Have a great night!
Chat with you tomorrow.
LF Out.
#3935
Posted 15 December 2022 - 03:00 AM
Thanks for the response, lostfalco.
You write in post #3933:
"Tbh, the metric seems like it's going to have to be mostly subjective on my part and the the observable metric for you guys is going to be my output over the next year."
I hope you'll try to squeeze in at least one objective measure, so that the hoi polloi will be ineluctably impressed with the result.
“When you can measure what you are speaking about,
and express it in numbers, you know something about it”
– Lord Kelvin
#3936
Posted 15 December 2022 - 10:04 PM
Thanks for the response, lostfalco.
You write in post #3933:
"Tbh, the metric seems like it's going to have to be mostly subjective on my part and the the observable metric for you guys is going to be my output over the next year."
I hope you'll try to squeeze in at least one objective measure, so that the hoi polloi will be ineluctably impressed with the result.
“When you can measure what you are speaking about,
and express it in numbers, you know something about it”
– Lord Kelvin
No problem Advocatus Diaboli.
I'm thinking it through for sure.
#3937
Posted 15 December 2022 - 10:11 PM
So, I broke my rule and actually started writing a full post for Abstract Wednesday (instead of just keeping it simple and posting interesting studies) and it's gotten too big to post yet.
I'll get it finished this weekend and make it my weekend post instead.
It centers around the main theme that we've been focusing on recently and expands it somewhat...that theme being neuromodulators in the retina and how they affect the response of intrinsically photosensitive retinal ganglion cells to light.
If we can enhance this response, then we can enhance the signal sent to the suprachiasmatic nucleus and therefore sync up ALL of our body's processes to the most refined degree possible.
The main neuromodulators in the retina that we'll be looking at are dopamine, adenosine, acetylcholine, and melatonin.
The real focus, of course, is how those neuromodulators affect our retina's response to light and thus our brain's response to light.
We enhance the brain, first and foremost, through the eyes.
This is our most fundamental discovery that sets the whole nootropics world on its head.
We've genuinely found the master switch...and it's light (of course it f*ckin is...life is built around light causing atomic/molecular movement...should've seen this earlier, but oh well...we've got it now and it is POWERFUL as f*ck!)
Such exciting times.
Here's a study to tide you guys over.
Talk to you guys soon!
LF Out.
https://www.ncbi.nlm...les/PMC6441387/
Circadian regulation in the retina: From molecules to network
Abstract
The mammalian retina is the most unique tissue among those that display robust circadian/diurnal oscillations. The retina is not only a light sensing tissue that relays light information to the brain, it has its own circadian "system" independent from any influence from other circadian oscillators. While all retinal cells and retinal pigment epithelium (RPE) possess circadian oscillators, these oscillators integrate by means of neural synapses, electrical coupling (gap junctions), and released neurochemicals (such as dopamine, melatonin, adenosine, and ATP), so the whole retina functions as an integrated circadian system. Dysregulation of retinal clocks not only causes retinal or ocular diseases, it also impacts the circadian rhythm of the whole body, as the light information transmitted from the retina entrains the brain clock that governs the body circadian rhythms. In this review, how circadian oscillations in various retinal cells are integrated, and how retinal diseases affect daily rhythms.
Edited by lostfalco, 16 December 2022 - 08:13 PM.
#3938
Posted 19 December 2022 - 01:05 AM
Hello my friends!
Just a quick update tonight...my weekend post has reached the length of a short novella so it's not quite ready yet. lol
I'll get it up soon for you guys though.
Everything is still a go for December 26th.
I'll keep you guys updated throughout the week this week.
Talk to you soon!
#3939
Posted 19 December 2022 - 11:53 AM
So, I feel bad that I didn't give you guys anything valuable yesterday so let me give you something of simple yet immense value today.
If you are not familiar with the work of Drew Berry, then you are in for a treat.
Along with Bertrand Russell (logic), Einstein (physics/mental modeling), Turing (computation), Kahneman/Tversky (biases/heuristics/base rates/statistical thinking), etc. Berry is one of my intellectual heroes.
When you see the videos below you'll understand why.
I have benefitted immeasurably from his work over the years.
Actually being able to picture what is going on at the cellular level has incalculable value for us as self-experimenters.
We HAVE to understand Brownian motion and the idea that a human can be modeled as what I like to call a 'heated water sphere'.
Before you get too weirded out, remember that ALL models are wrong in some way.
The point, of course, is not that the model is wrong it's that the model is USEFUL (typically conceptually useful).
We can use simplified models to give us insights that we might not see were we overwhelmed by too much data.
Take, for example, a map of the united states.
That map is wrong is SO many ways!
There are mountains in the United States.
Where are they?
Where are all the freaking rivers?
The United States is WAY bigger than that.
Anyway, you get the idea.
The map is wrong...but it's supposed to be!
However, it gives you insights into the relative sizes, shapes, and positions of the states in relation to each other and to the United States taken as a whole.
It's useful in that it allows COMPARISONS (one of THE most fundamental ideas of human thought that I will return to time and time again in the coming months) that we would not have been able to see otherwise. (Metal Ball Studios has some cool relative size comparison vids...see vid below on the Solar System for an example)
Also, see the video linked below for how ABSURDLY slow the speed of light is at cosmic scales.
And that's as fast as things get in our universe!
Human mental scales and comparisons can be VERY misleading when extrapolated out of their evolutionarily forged environments (human speeds, temperatures, sizes (both microscopic AND cosmic), etc.).
But, we have to work with the mental machinery we've got and this relates to the very simple idea that 'the map is not the territory."
Wikipedia actually states this idea quite well so I've quoted the first section in full at the end of this post. https://en.wikipedia...ritory_relation
Ok, back to biology.
As I mentioned, we can VERY simplistically model a human as a sphere of heated water using our height as the diameter and 1/2 our height as the radius (we could actually further model ourselves as an oscillating sphere of heated water since our temperature (taken orally) oscillates in a circadian fashion between 97.3 degrees Fahrenheit (early morning) and 99.1 degrees Fahrenheit (afternoon/evening) centering around 98.2 degrees Fahrenheit. "No man ever steps into the same river twice, for it's not the same river and he's not the same man." -Heraclitus (attributed)).
Why is this important?
Because heated water means that the molecules of water are in motion AND the fact that the water is enclosed in a sphere means that the randomness of the motion occurs within constraints (ie. randomness is reduced within the enclosure of the sphere).
There is 'randomness within constraints'.
This internal water molecule motion can move substances along following Brownian motion.
Here's what it looks like.
First, visualize these events occurring WITHOUT the constraints of the sphere.
The particles would just fly off in all different directions (randomness).
Now, visualize that same molecular motion occurring inside our sphere (this is called contrastive explanation OR contrastive visualization (I made that second one up, but you get the idea...visualize without the constraint, then visualize with the constraint AND then COMPARE those two visualizations to see what is different AND what is Not-Different...this is a MAJOR way conceptual insights are formed!).
The tiny molecules represent water and the larger molecule could represent something like dopamine, let's say. (dopamine is a neuromodulator that diffuses throughout the cell via volume transmission and attaches to metabotropic g-protein coupled receptors (as CONTRASTED with ionotropic receptors)...it does this in the retina and is a MAJOR player in our ability to enhance ourselves. I'll explain this more in future posts.)
Now, place two substances inside our heated water sphere and this motion can then be used to bring those substances together so that chemical reactions can occur and new structures can be built or new signaling cascades can be initiated.
This is also why I think that hot springs on the surface of the Earth are VERY plausible sources of abiogenesis (more so than hydrothermal vents, at least; see study below) and why heat produced by a prokaryote during endosymbiosis plausibly stabilized the internal temperature inside the archaea that absorbed it and allowed the combination to branch out into other environments and build multicellular organisms with less competition for resources (see study below).
If new structures can be built then randomness inside the heated water sphere can be reduced further (because the structures will further limit motion).
Iteratively repeat this process over time and you can see how order can arise from randomness over time (we define time as events happening within the universe (a clock tick at a point in space (defined using three dimensional coordinates), a train arrival at a point in space, etc.) following Einstein (this is only ONE way to define time). See On the Electrodynamics of Moving Bodies: https://users.physic...ing/specrel.pdf
If this is starting to sound A LOT like the electron transport chain and the proton motive force then you've got it!
This brings us back to Drew Berry and his 'animations of un-seeable biology."
Check out these works of art and make sure you are picturing the vibrations and movements depicted here (Berry does a fantastic job visualizing these for us).
We are spheres of constant motion and we can harness and coordinate this motion using light, food, exercise, and circadian timing rules!
Our human physical events (clock gene expression) are synced to external environment physical events (Earth Rotation causing photon interaction with us for example).
Like pendulums that sync when brought into proximity (see video below), we must sync our Brain Clock, Body Clock, and Biome clock with the 'Light, NOT-Light' cycle caused by the Earth's Rotation relative to the Sun.
Hmm...I guess that's four clocks.
The video below has 5 syncing pendulums. Close enough! lol
I told you guys TIME was fundamental. (*shrug)
Enjoy!
https://en.wikipedia...ritory_relation
"The map–territory relation is the relationship between an object and a representation of that object, as in the relation between a geographical territory and a map of it. Polish-American scientist and philosopher Alfred Korzybski remarked that "the map is not the territory" and that "the word is not the thing", encapsulating his view that an abstraction derived from something, or a reaction to it, is not the thing itself. Korzybski held that many people do confuse maps with territories, that is, confuse conceptual models of reality with reality itself. These ideas are crucial to general semantics, a system Korzybski originated.
The relationship has also been expressed in other terms, such as "the model is not the data", "all models are wrong", and Alan Watts' "The menu is not the meal." The concept is thus quite relevant throughout ontology and applied ontology regardless of any connection to general semantics per se (or absence thereof). Its avatars are thus encountered in semantics, statistics, logistics, business administration, semiotics, and many other applications.
A frequent coda to "all models are wrong" is that "all models are wrong (but some are useful)," which emphasizes the proper framing of recognizing map–territory differences—that is, how and why they are important, what to do about them, and how to live with them properly. The point is not that all maps are useless; rather, the point is simply to maintain critical thinking about the discrepancies: whether or not they are either negligible or significant in each context, how to reduce them (thus iterating a map, or any other model, to become a better version of itself), and so on."
Abiogenesis in Hot Springs
https://www.liebertp...9/ast.2019.2045
The Hot Spring Hypothesis for an Origin of Life
Abstract
We present a testable hypothesis related to an origin of life on land in which fluctuating volcanic hot spring pools play a central role. The hypothesis is based on experimental evidence that lipid-encapsulated polymers can be synthesized by cycles of hydration and dehydration to form protocells. Drawing on metaphors from the bootstrapping of a simple computer operating system, we show how protocells cycling through wet, dry, and moist phases will subject polymers to combinatorial selection and draw structural and catalytic functions out of initially random sequences, including structural stabilization, pore formation, and primitive metabolic activity. We propose that protocells aggregating into a hydrogel in the intermediate moist phase of wet-dry cycles represent a primitive progenote system. Progenote populations can undergo selection and distribution, construct niches in new environments, and enable a sharing network effect that can collectively evolve them into the first microbial communities. Laboratory and field experiments testing the first steps of the scenario are summarized. The scenario is then placed in a geological setting on the early Earth to suggest a plausible pathway from life's origin in chemically optimal freshwater hot spring pools to the emergence of microbial communities tolerant to more extreme conditions in dilute lakes and salty conditions in marine environments. A continuity is observed for biogenesis beginning with simple protocell aggregates, through the transitional form of the progenote, to robust microbial mats that leave the fossil imprints of stromatolites so representative in the rock record. A roadmap to future testing of the hypothesis is presented. We compare the oceanic vent with land-based pool scenarios for an origin of life and explore their implications for subsequent evolution to multicellular life such as plants. We conclude by utilizing the hypothesis to posit where life might also have emerged in habitats such as Mars or Saturn's icy moon Enceladus.
Heat and Eukaryogenesis
https://www.ncbi.nlm...les/PMC5682861/
Some Liked It Hot: A Hypothesis Regarding Establishment of the Proto-Mitochondrial Endosymbiont During Eukaryogenesis
Abstract
Eukaryotic cells are characterized by a considerable increase in subcellular compartmentalization when compared to prokaryotes. Most evidence suggests that the earliest eukaryotes consisted of mitochondria derived from an α-proteobacterial ancestor enclosed within an archaeal host cell. However, what benefits the archaeal host and the proto-mitochondrial endosymbiont might have obtained at the beginning of this endosymbiotic relationship remains unclear. In this work, I argue that heat generated by the proto-mitochondrion initially permitted an archaeon living at high temperatures to colonize a cooler environment, thereby removing apparent limitations on cellular complexity. Furthermore, heat generation by the endosymbiont would have provided phenotypic flexibility not available through fixed alleles selected for fitness at specific temperatures. Finally, a role for heat production by the proto-mitochondrion bridges a conceptual gap between initial endosymbiont entry to the archaeal host and a later role for mitochondrial ATP production in permitting increased cellular complexity.
Edited by lostfalco, 19 December 2022 - 03:14 PM.
#3940
Posted 19 December 2022 - 11:59 AM
Longecity wouldn't let me link these in my last post so I'm putting them here. =)
Edited by lostfalco, 19 December 2022 - 12:17 PM.
#3941
Posted 19 December 2022 - 12:18 PM
The Speed of Light at Cosmic Scale
#3942
Posted 21 December 2022 - 11:39 AM
Hello my friends!
For my Wednesday post I decided to respond to a redditor who just started a nocturnal job. I've copied it below for your reading enjoyment.
My work schedule is lightening up right now because of the holidays so I'll be posting throughout the week leading up to my Moonshot Cycle session one starting on December 26th.
Stay tuned!
https://www.reddit.c...nergy/?sort=new
A nocturnal lifestyle is going to be very challenging for a diurnal human. It's going to take a while to shift your circadian rhythm to match your new work schedule but it can be done!
The number one key is that you need your schedule to be the same EVERY day. And by every day, I mean ALL seven days of the week. You need to go to bed at the same time and wake up at the same every single 24 hour period. If you are shifting back and and forth from a nocturnal weekday schedule to a more diurnal weekend schedule you will ALWAYS be tired. There is no biological way around this. Our bodies have clock genes (first and foremost in the suprachiasmatic nucleus of the hypothalamus but also in just about every cell of our entire body) that sync with the daily rhythm of light and dark caused by Earth's Rotation. These clock genes control the sequential expression of all genes throughout your body on an approximately 24 hour cycle. (see Satchin Panda's "The Circadian Code" for a great introductory summary of the VAST scientific literature on this subject)
The good news for you is that with the invention of electric lighting we can now control the light in our environment and with light blocking glasses and blackout curtains we can limit the light in our environment. So, for the sake of clarity, I will assume that you are waking up at 8pm and going to sleep at 12pm. You must get 7 to 9 hours of sleep to maintain optimal health/function (see Dr. Matt Walker’s excellent book “Why We Sleep” for the scientific justification for this claim). Thus, you must sleep from 12pm to 8pm every day.
In order to fall asleep at 12pm you are going to want to start raising your melatonin levels by wearing blue light blocking glasses starting around 9am or 10am. Blocking blue light has been shown to enhance melatonin secretion and enhance sleep in humans. Just go to Amazon and search for Uvex Blue Blocking. They are only $13.
https://www.ncbi.nlm...les/PMC7229994/
"Short wavelength-blocking glasses (Ultraspec 2000, https://www.uvex.com/en) were dispensed for the subjects to wear in the evenings for 2 weeks. The transmission spectrum of the glasses was confirmed, showing that the lenses absorb approximately 99% of light shorter than 540 nm, and transmit approximately 90% longer than 540 nm."
"...the Uvex lenses block 99% of blue light, and the goal of this experiment was to decrease short wavelength stimulation to the highest degree possible."
"Therefore, all subjects wore the glasses for at least 3 h, although some wore them longer based on their habitual bedtime."
"Night-time melatonin at baseline was 16.1 ± 7.5 pg mL−1 (Figure 4). After the two-week experimental period, night-time melatonin statistically significantly increased 58% to 25.5 ± 10.7 pg mL−1 (effect size r = −0.44, t19 = −3.95, P = 0.0005)."
"The increase in night-time melatonin and increased sleep duration afforded from the Uvex glasses was robust..."
Additionally, core body temperature is a major signal to your body that it is time to sleep. Lowering the ambient temperature will cause your core to send blood to your extremities to warm them and thus cool your core. The sweet spot for sleep enhancement is around 65 to 67 degrees fahrenheit so you will want to turn your AC down to 65ish degrees at around 10am.
Thirdly, you will want to limit ambient light before and during sleep. So, get some blackout curtains from Amazon. I use the Eclipse Fresno Modern Blackout but feel free to get whatever curtain you want.
Upon waking at 8pm you will want to signal to your body that it is daytime using light within an hour or 2 of waking. This will signal your suprachiasmatic nucleus to shift your whole body into an active waking state. Get bright light bulbs for your house or you can use a bright light therapy box. The Verilux HappyLight has been used in the scientific studies and is only $40. I would strongly encourage using this either upon waking or within an hour or two of waking. Test different times out and see what works best for you.
Bright light in the morning will increase your core body temperature, sync your brain and body’s clocks, and give you energy to start your workday.
You’ll also want to keep the lights pretty bright throughout your workday to keep energy levels up. Daylight ambient light in the shade is approx 20,000 lux on a sunny day. You can use your light therapy box throughout the day (10,000 lux) or bright lights in your work environment. Up to you how you arrange it. Midday bright light therapy (30min at 10,000 lux bright white light) has been shown to increase subjective wakefulness and energy levels in humans.
In addition to light and temperature another major synchronizer of our body’s daily rhythms is food intake. You will want to eat your three meals per day at the same times every day with an 8 to 12 hour eating window (see Satchin Panda’s work again for the data here).
Thus, if you are waking up at 8pm with a 10 hour feeding window then you will want to eat breakfast at 9pm, lunch at 1:30am, and dinner at 6:30am while making sure you finish by 7am.
It is vitally important that you do this in order to sync your peripheral body clocks with your central brain clock.
Eat as much as you want for your meals but make sure that you do not eat between meals or after your last meal. Your body needs to repair itself since digestion causes damage to lining of the stomach and not-eating allows this repair process to occur.
You’ll also want to eat fiber with each meal since your microbiome also syncs up with your brain and body clocks. I recommend 10g of dextrin (it’s only $13 and is virtually tasteless) at the beginning of each meal but feel free to get fiber however you choose. Adult male humans need 30 to 38g of fiber per day and almost no one gets this much. It makes a huge difference for health and energy levels and will sync your biome clock to your body clock to your brain clock.
Ok, that’s enough for now. There is SO much more but that should give you a nice start. Take your caffeine one hour before you use the light therapy box to enhance the effects of both. Do this in the morning (your morning) and at your midday.
The retinohyptohalamic tract has adenosine receptors and if you block them with caffeine that will enhance glutamate release onto the suprachiasamtic nucleus. The suprachiasmatic nucleus is the master regulator the entire body so if you enhance its activities you will give yourself the best chance of regulating everything your body does. Health and energy is about balance! Perfect regulation can give you perfect balance.
I hope you find something that works for you!
Edited by lostfalco, 21 December 2022 - 12:08 PM.
#3943
Posted 21 December 2022 - 03:16 PM
Here's a new study that elucidates my current view of intelligence.
As always, it could be wrong but in my opinion it is the best that current science has to offer.
"Central to modern neuroscientific theories of human intelligence is the notion that general intelligence depends on a primary brain region or network, engaging spatially localized (rather than global) neural representations. Recent findings in network neuroscience, however, challenge this assumption, providing evidence that general intelligence may depend on system-wide network mechanisms, suggesting that local representations are necessary but not sufficient to account for the neural architecture of human intelligence."
"The results of our study demonstrate that general intelligence can be predicted by local functional connectivity profiles but is most robustly explained by global profiles of whole-brain connectivity."
I genuinely believe that genius is the ability to send more intricate and expansive mental structures from the subconscious brain to the conscious brain.
I got this idea from reading John Sweller's cognitive load theory but I also got it from this guy: "Imagination is more important than knowledge. Knowledge is limited. Imagination encircles the world." -Albert Einstein
What is imagination?
It is the ability to create new worlds in your conscious mind.
These new worlds are made of constituent parts and thus the ability to recombine these fundamental constituents in novel and expansive ways and send them to your conscious brain is the most likely definition of intelligence in my view.
These ideas are behind my decision to dose MDMA for massively enhanced synaptogenesis (at 3 equidistant points over 6 weeks) while simultaneously using bright light therapy during the sessions and then every day for the 6 week duration of my Moonshot Cycle in order to enhance not just connectivity but whole brain efficiency.
As the study states below, "Our findings further suggest that the improved efficacy of global theories is not reducible to a greater strength or number of connections, but instead results from considering both strong and weak connections that provide the basis for intelligence."
We'll see what happens on starting on December 26th! lol
https://pubmed.ncbi....h.gov/36537816/
Investigating cognitive neuroscience theories of human intelligence: A connectome-based predictive modeling approach
Abstract
Central to modern neuroscientific theories of human intelligence is the notion that general intelligence depends on a primary brain region or network, engaging spatially localized (rather than global) neural representations. Recent findings in network neuroscience, however, challenge this assumption, providing evidence that general intelligence may depend on system-wide network mechanisms, suggesting that local representations are necessary but not sufficient to account for the neural architecture of human intelligence. Despite the importance of this key theoretical distinction, prior research has not systematically investigated the role of local versus global neural representations in predicting general intelligence. We conducted a large-scale connectome-based predictive modeling study (N = 297), administering resting-state fMRI and a comprehensive cognitive battery to evaluate the efficacy of modern neuroscientific theories of human intelligence, including spatially localized theories (Lateral Prefrontal Cortex Theory, Parieto-Frontal Integration Theory, and Multiple Demand Theory) and recent global accounts (Process Overlap Theory and Network Neuroscience Theory). The results of our study demonstrate that general intelligence can be predicted by local functional connectivity profiles but is most robustly explained by global profiles of whole-brain connectivity. Our findings further suggest that the improved efficacy of global theories is not reducible to a greater strength or number of connections, but instead results from considering both strong and weak connections that provide the basis for intelligence (as predicted by the Network Neuroscience Theory). Our results highlight the importance of considering local neural representations in the context of a global information-processing architecture, suggesting future directions for theory-driven research on system-wide network mechanisms underlying general intelligence.
Edited by lostfalco, 21 December 2022 - 04:07 PM.
#3944
Posted 24 December 2022 - 07:24 PM
Happy Holidays my friends!
I'm writing a ton of content for you guys these days but I'm WAY too ambitious. lol
It's getting so involved that I have a million things to confirm or reject and follow up on before I release it publicly.
I'll post it soon once it's ready. I promise.
Moonshot Cycle is still a go starting on Monday.
I'm planning on dosing at 9am CST on Monday, Dec 26th.
I'll take 100mg MDMA (sublingual) at 9am and then a half dose (50mg sublingual) between 1 and 2 hours after the first dose...depending on how I'm doing. (I've taken MDMA before...this ain't my first rodeo. lol)
I'll have a friend here monitoring me the whole time so I'll take my cues from him.
I'm going to take it sublingually so absorption should be very fast and the half life should (theoretically) be shorter than the usual approximate 6 hours.
Psilocybin has about half of the usual half life when taken intravenously so I would guess MDMA would be similar when taken sublingually...but there's no way to know for sure.
We'll find out. lol
Anyway, if the half life is closer to 3 hours, that would put me dosing at 9am, dosing again at 10am (earlier than the usual 1.5 to 2 hours in the studies), and finishing around 3 hours later at 1pm.
I've thought a lot about posting and I'll post once when I dose (just to let you guys know I've started), once in the middle (around 11am), and once at the end (1pm).
That way, I can study throughout (if I'm able), go for a walk, breathe, meditate, listen to music, make sure I get my bright light dose in, etc.
For my bright light, I'm going to do it in the morning as usual for 30 min and then I'm going to do another 30 minutes at the peak onset which should occur at about the 1 hour mark (or a little before) when I re-dose.
So, that's...
100mg MDMA sublingual at 9am CST
50mg MDMA sublingual at 10am CST (if I'm ok)
30 min, 10,000 lux, Bright Light from 12 inches away starting at 10am.
I'm going to take my caffeine as usual in the morning upon waking at 5am which is 200mg sublingual powder and breakfast at 6am as usual.
I'll take 20mg of testosterone in the morning at 6am as subcutaneous Testosterone enanthate (this is double the normal 10mg of test that a young, healthy male produces per day).
I'll take 200mcg of Sermorelin at bedtime which is 10pm for me.
I'll stay on the Test and Sermorelin for the whole 6 week Moonshot Cycle and then 6 weeks after that...so 12 weeks.
I'm going to skip lunch on my dose day since I'll be high as f*ck and then get right back into my circadian rhythm and eat dinner at 530pm.
I'll keep everything else the same (all my circadian enhancements) going forward for the next three weeks until my second Moonshot Session and then continuing on for the foreseeable future.
So, that's the plan right now.
The goal, of course, is massive synaptogenesis caused by MDMA followed by enhanced full brain connectivity and efficiency caused by Bright Light Therapy, good diet, exercise, plenty of water, etc.
The real effects of MDMA are not seen during the session itself...it's after when the true magic begins (I really couldn't give a sh*t about getting high at this point in my life).
It massively upregulates BDNF expression and subsequent synaptic growth in the days (and sometimes) weeks after dosing.
That's why ALL the Circadian enhancements and dietary elements matter so much!
You've got to give your body the best structural materials to build with so it can build the best synaptic structures.
All of my future posts will explain this in molecular detail, but there are some hints here:
http://www.lostfalco...t-deficiencies/
and here...
https://www.lostfalc...lcos-day-frame/
and here...
https://www.lostfalc...cements-so-far/
I have an encyclopedia of things to show you guys in the coming weeks and months.
We're on fire already and we're just getting warmed up.
Have a great rest of your day!
I'll be in touch tomorrow.
LF Out
Edited by lostfalco, 24 December 2022 - 07:37 PM.
#3946
Posted 25 December 2022 - 10:30 PM
Edited by Q did it!, 25 December 2022 - 10:38 PM.
#3947
Posted 25 December 2022 - 10:32 PM
Maybe we "Lost" him
#3948
Posted 26 December 2022 - 02:14 AM
I've taken MDMA from the same source before. Started with a low dose (5mg) then 25mg and gradually escalated over time. I also tested 25mg from this batch a few weeks ago with no issues so I'm not super concerned. Do I have 100% assurance of purity...nope. But this is the best I can do for now.
As far as Narcan goes...no. I'm not too concerned with it being tainted with opioids so I don't see the need since naloxone only works for opioid overdose.
I'm also not even taking a huge dose of MDMA to begin with. Truth is, I'm easing into it as I've kept the polypharmacy minimal.
I think my risk is reasonable and I have a sober friend here with me in case something goes unexpectedly.
You never know for sure, but I think I've covered my bases as best I can.
#3949
Posted 26 December 2022 - 02:18 AM
Tomorrow will be intriguing for sure!!
Thanks Q!
I think I'm mostly concerned about saying something absurdly stupid when I post in the middle at 11am. lol
Hopefully you guys won't judge me too harshly if I'm raving on and on about kaleidoscope robot unicorns. ha
We'll see what happens.
Edited by lostfalco, 26 December 2022 - 02:56 AM.
#3950
Posted 26 December 2022 - 02:22 AM
Maybe we "Lost" him
haha I was lost a long time ago Lsdium.
"FoundFalco" doesn't quite have the same ring to it. lol
I think I prefer being a little 'lost'.
Keeps life interesting.
See you tomorrow with dilated pupils and incoherent blatherings!
#3951
Posted 26 December 2022 - 02:53 AM
Alright my friends, Moonshot Eve is upon us.
I spent the whole day today preparing everything and attempting to reduce the entire edifice of human biology to the oscillation of a proton as it spontaneously dissociates from H2O and then returns (so, H2O to (H+ AND OH-) to H2O and on and on).
I think it actually works.
If you think about where the protons come from in the matrix of mitochondria, they actually come from water.
Mito.JPG 17.94KB 0 downloads
Hydrogen dissociates from H2O due to the random motion of the heated water inside the matrix and then is grabbed by the electron transport chain complexes and pumped across into the intermembrane space.
This leaves OH- in the matrix and H+ in the intermembrane space which creates the charge differential across the membrane which draws the proton back across through ATP-synthase. (click on pic to make it bigger)
Capture.JPG 38.54KB 0 downloads
But where does that proton go once it enters back into the matrix?
It could get pumped back across the membrane or attach to H2O to create H3O...OR...it could be said to join back up with OH- and create H2O again.
In a sense, water simply loses a proton and then regains it over and over again.
That could actually be the MOST fundamental energetic source of life.
If you picture this proton oscillating on and off from water and you put something in between then you could actually do work.
There would still be electromagnetic forces in between the H+ and the OH- pulling them back together.
Have the proton go through one opening in a barrier and then pass back through another opening as it attracts back to OH- and you've got a proton motive force without electrons!
You don't actually need them to get life generating bioenergetics started.
Hmm...really interesting.
I'm going to have to think about this more.
I already wrote a bunch about it but I need to clean it up for publication.
That's how I spent my Christmas Day! lol
Oh, and I had some great family time too.
I hope you guys all had a wonderful day today!
I'll see you guys back here at 9am CST for dose one of Moonshot Session One.
Heading towards the new year with a bang.
The good kind of bang I hope! ha
Talk to you guys in the morning.
LF Out
Edited by lostfalco, 26 December 2022 - 02:59 AM.
#3952
Posted 26 December 2022 - 03:22 AM
re: post 3951
The good kind of "bang" is "bhang".
#3953
Posted 26 December 2022 - 02:57 PM
re: post 3951
The good kind of "bang" is "bhang".
Seth, is that you?
#3954
Posted 26 December 2022 - 02:59 PM
Hello my friends!
It's 9:00 am CST so it is time for Moonshot Session One.
I've already done 30min of bright light therapy, exercised, eaten, taken 20mg of testosterone this morning, 200mcg sermorelin last night, etc...
Everything is ready to go.
The two main goals are this:
1. Massive Synaptogenesis (100mg sublingual MDMA taken at 9am CST and 50mg sublingual MDMA taken at 10am CST (if I'm doing ok))
2. Enhanced full brain connectivity and efficiency (30min Bright Light Therapy at 10am and every day for the duration of the 6 week cycle)
I think you guys are all up to speed on what the plan is.
Remember, the real effects are not going to be during the dosing (although it'll be interesting to see how that goes. lol) but in the coming days as my brain builds new synaptic connections.
Thus, my activities over the next few days and weeks will be just as important as the activities during the dosing time.
What that said, 3....2....1.....dose!
I'll check back in with you guys at 11am CST...I hope! lol
Disclaimer: I recommend that literally NO ONE else try this. I'm crazy. =)
#3955
Posted 26 December 2022 - 04:58 PM
Blood pressure good.
Doing great.
Lost in wordless imagery.
Time VERY slow.
Eyes long to be closed to trace my endless recesses.
Spanning connective tracing out.
Words do not matter.
Feynman and Einstein right. Always right,
Not the words...the thing. Not the math...the things.
All is nested temporality.
Self event frequency compared to self event frequency.
So high. Still mildly lucid.
Can let go, or reign in.
Not powerless...still surprising amount of control if need be.
Can bring it back under my control or get lost down endless path.
Still surprising choice amidst chaos.
Will check back at 1pm.
Lost in thought.
Sublingual VERY different than oral.
Mix of blurred clarity amidst extreme time dilation.
Why do I share myself? lol
Enjoy the show.
It's real.
#3956
Posted 26 December 2022 - 07:12 PM
Still good.
Still VERY high.
Enjoying the exploration.
Well check back in a 3pm, CST.
Edited by lostfalco, 26 December 2022 - 07:13 PM.
#3957
Posted 26 December 2022 - 08:52 PM
Still doing great.
Powerful mental effects compared to body effects with sublingual dosing.
Very long lasting....still feeling effects strongly.
Will check back in 5pm CST when more lucid
#3958
Posted 26 December 2022 - 08:57 PM
I don't suffer from depression just Mania if I don't get sleep. The reason latuda works is due to its ability to depress my nervous system and let me sleep. Even Ambian (if I spelt that right) does not work on me.
My primary wants to switch me over to naltrexone over time and low dose. I don't know a lot about this one. But latuda has caused weight gain and negative impact on physical pleasure. And I and numb to pain for the most part. Just numb.
So I need to take more a action on this. Taking all my morning supplements most are what Dave recommends alone with phenylpiracetam and aniracetam plus perceptions. Ran out of calamari omga3 oil. something that definitely impacts my mental state if take through the day in half grams say 5g total a day.
Doing better then ever. But sense starting working nights years ago, i i still am not at that state if high performance. I would read 500 700 pages a day. Along with class work and personal projects. I want to get to that point I would be at now if I hadn't made that epigenetic overflow of change from the initial episode.
#3959
Posted 26 December 2022 - 10:54 PM
Still doing great.
Stiil feeling very noticeable mental effects so long after dosing.
Quite the marathon but I'm doing just fine.
Calling it a day for today.
Need rest.
Will check back in tomorrow morning,
Love you guys! (of course I do, I'm on an empathogen. lol)
Goodnight
Edited by lostfalco, 26 December 2022 - 10:55 PM.
#3960
Posted 27 December 2022 - 12:03 AM
@lostfalco, coming out of the woodwork as someone who frankly had forgotten I was subscribed to the thread years ago... to say you are a gem and I appreciate your coming back to share both your latest developments and most recently this fascinating experiment.
I belong in the camp that believes in the power and utility of substances like MDMA and think it commendable and brave of you to include it in your designs. I have full faith that you will come out the other end having gained valuable insights
Also tagged with one or more of these keywords: nootropic
Science & Health →
Brain Health →
Nootropic Stacks →
how would you describe Cerebrolysin to a person unfamiliar to nootropics?Started by davidwood557 , 01 Oct 2024 nootropic |
|
|
||
Round Table Discussion →
Business →
Retailer/Product Discussion →
J 147 Powder to Treat Alzheimer’s DiseaseStarted by Peptide.ltd , 18 Apr 2024 j 147 powder, j 147 supplement and 1 more... |
|
|
||
Science & Health →
Brain Health →
Montelukast?Started by mp_double , 25 Jan 2024 nootropic, anti-inflammatory and 1 more... |
|
|
||
Science & Health →
Brain Health →
Nootropic Stacks →
What are the most effective NOOTROPICS based on science?Started by Forever21 , 30 Oct 2021 nootropic |
|
|
||
Science & Health →
Brain Health →
Dihexa?Started by brendan1 , 05 Sep 2021 nootropic |
|
|
14 user(s) are reading this topic
0 members, 14 guests, 0 anonymous users