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Lostfalco's Extensive Nootropic Experiments [Curated]

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#2401 clstrfck

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Posted 28 May 2015 - 10:29 AM

Hi there! Haven't been here for a while, so I'am not sure if this has already been discussed. My problem with LLLT is that after about 10 days of doing the TULIP regimen I get very depressed. Or to be more specific, I'am in a state of total sadness. I usually do LLLT every other day for about 30 sec/spot on forehead. If I do the whole brain/head and the combined time is above 5 minutes I get these terrible feeling of sadness. It fades after like 2 days when I stop LLLT.

 

Interesting thing is, I started "LifeExtensions Mitochondrial Energy Optimizer" yesterday (without LLLT) and about 20 minutes after ingesting the capsules I get the same kind of feeling, though not that intense. So I wonder if there could be any connection with mitochondrial biogenesis and this heightened state of emotions.

 

The ingredients from the LEF formula are:

 

Serving Size 4 capsules:

 

Vitamin B6 100 mg

Calcium carbonate 230 mg

Sodium 25 mg

Carnosine 1000 mg

Acetyl-L-Carnitine arginate dihydrochloride 675 mg

Benfotiamine 150 mg

R-Lipoic Acid 150 mg

BioPQQ 10 mg

Luteolin 8 mg

 

It bothers me a lot since I enjoy the benefits from LLLT until that emotional rollercoaster kicks in. I tried many different combinations, with and without supplements. Maybe I will start a new trial and work my way up very slowly. If someone had a similar experience I would love to hear your opinion. I still try to understand some of the more advanced stuff and a big thank you goes to lostfalco for his great recommendations. I still enjoy reading "The Machinery of Life"!



#2402 lostfalco

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Posted 31 May 2015 - 03:13 AM

PDE4i + PDE5i = object memory enhancement

 

According to this study it looks possible to take lower doses of each and still get the desired effects. This is big news because it means that we might be able to avoid the projectile vomiting associated with rolipram! It also means that some of the weaker PDE4 inhibiting herbs could still be effective if combined with a little Viagra. Speaking of which...

 

I am still a really big fan of PDE5i for memory consolidation. I have noticed positive effects from both Tadalafil (been testing for months) and Sildenafil (been testing for a few weeks). My Vardenafil just arrived and I'm going to give that a go tomorrow. Tbh, I can see myself keeping at least one of these in my stack for a long time. Just scroll back through the last 3 or 4 pages of this thread to check out numerous studies on the learning and memory potential for PDE5i. =)

 

 

http://www.ncbi.nlm....pubmed/25896769

 

Neuropharmacology. 2015 Apr 17;95:361-366. doi: 10.1016/j.neuropharm.2015.04.008. [Epub ahead of print]

Object memory enhancement by combining sub-efficacious doses of specific phosphodiesterase inhibitors.

Abstract

The second messengers cGMP and cAMP have a vital role in synaptic plasticity and memory processes. As such, phosphodiesterases inhibitors (PDE-Is), which prevent the breakdown of these cyclic nucleotides, represent a potential treatment strategy in memory decline. Recently it has been demonstrated that cGMP and cAMP signaling act in sequence during memory consolidation, with early cGMP signaling requiring subsequent cAMP signaling. Here, we sought to confirm this relationship, and to evaluate its therapeutic implications. Combining sub-efficacious doses of the cGMP-specific PDE type 5 inhibitor vardenafil (0.1 mg/kg) and cAMP-specific PDE type 4 inhibitor rolipram (0.01 mg/kg) during the early and late memoryconsolidation phase, respectively, led to improved memory performance in a 24 h interval object recognition task. Similarly, such a sub-efficacious combination treatment enhanced the transition of early-phase long-term potentiation (LTP) to late-phase LTP in hippocampal slices. In addition, both object memory and LTP were improved after administration of two sub-efficacious doses of the dual substrate PDE type 2 inhibitor BAY60 7550 (0.3 mg/kg) at the early and late consolidation phase, respectively. Taken together, combinations of sub-efficacious doses of cAMP- and cGMP-specific PDE-Is have an additive effect on long-term synaptic plasticity and memory formation and might prove a superior alternative to single PDE-I treatment.

Copyright © 2015 Elsevier Ltd. All rights reserved.

 


Edited by lostfalco, 31 May 2015 - 04:03 AM.


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#2403 lostfalco

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Posted 31 May 2015 - 03:59 AM

Possible experimental suggestions from this rodent study:

1. Take PDE5 right after learning.

2. Take PDE4 3 hours after learning. 

 

http://www.ncbi.nlm....pubmed/17207788

 

Eur J Pharmacol. 2007 Mar 8;558(1-3):107-12. Epub 2006 Dec 1.

Time-dependent involvement of cAMP and cGMP in consolidation of object memory: studies using selective phosphodiesterase type 2, 4 and 5 inhibitors.
Abstract

The present study investigated the time-dependent memory enhancing properties of three selective phosphodiesterase inhibitors (PDE-I) vardenafil(PDE5-I), rolipram (PDE4-I) and BAY 60-7550 (PDE2-I) in the object recognition task. In particular, the time-dependent involvement of cAMP and cGMP in memory consolidation was assessed by altering the time points of drug administration. Vardenafil (1 mg/kg, p.o.), rolipram (0.03 mg/kg, i.p.), and BAY 60-7550 (3 mg/kg, p.o.) were tested in rats with a 24 h delay between the learning and the test trial. The PDE-Is were administered at different time points, i.e. directly after, 1 h, 3 h and 6 h after the first trial. Using a 24 h interval, vardenafil only showed an effect on object memory when injected directly after trial 1, rolipram only showed an improvement when injected 3 h after trial 1 and BAY 60-7550 improved memory when injected either directly after or 3 h after trial 1. No treatment effects were found when the compounds were administered 1 h or 6 h after the first trial. Our results extend our previous data that different types of PDE-Is affect different stages of memory consolidation. Moreover, the present study provides further support that selective PDE-Is can influence memory consolidation in a time-dependent manner, assumingly by elevating central cAMP and cGMP levels.

 



#2404 lostfalco

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Posted 31 May 2015 - 01:43 PM

Our old friend Dr. Gonzalez-Lima is back with a new study!

 

1064nm LLLT enhanced prefrontal cortex executive function in young, healthy volunteers with increased cytochrome oxidase activity as the primary proposed mechanism. Badass!

 

Full pdf here. http://homepage.psy....ogy_InPress.pdf

 

http://www.ncbi.nlm....pubmed/26017772

 

J Neuropsychol. 2015 May 28. doi: 10.1111/jnp.12074. [Epub ahead of print]

Improving executive function using transcranial infrared laser stimulation.

Blanco NJ1,2Maddox WT1,2,3,4Gonzalez-Lima F1,3,5.
Abstract

Transcranial infrared laser stimulation is a new non-invasive form of low-level light therapy that may have a wide range of neuropsychological applications. It entails using low-power and high-energy-density infrared light from lasers to increase metabolic energy. Preclinical work showed that this intervention can increase cortical metabolic energy, thereby improving frontal cortex-based memory function in rats. Barrett and Gonzalez-Lima (2013, Neuroscience, 230, 13) discovered that transcranial laser stimulation can enhance sustained attention and short-term memory in humans. We extend this line of work to executive function. Specifically, we ask whether transcranial laser stimulation enhances performance in the Wisconsin Card Sorting Task that is considered the gold standard of executive function and is compromised in normal ageing and a number of neuropsychological disorders. We used a laser of a specific wavelength (1,064 nm) that photostimulates cytochrome oxidase - the enzyme catalysing oxygen consumption for metabolic energy production. Increased cytochrome oxidase activity is considered the primary mechanism of action of this intervention. Participants who received laser treatment made fewer errors and showed improved set-shifting ability relative to placebo controls. These results suggest that transcranial laser stimulation improves executive function and may have exciting potential for treating or preventing deficits resulting from neuropsychological disorders or normal ageing.

 


Edited by lostfalco, 31 May 2015 - 01:53 PM.

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#2405 magta39

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Posted 31 May 2015 - 11:56 PM

Lostfalco are you still using tadalafil drops from superiorpeptides?  Do consider it a quality and safe product?



#2406 lostfalco

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Posted 01 June 2015 - 04:05 AM

Lostfalco are you still using tadalafil drops from superiorpeptides?  Do consider it a quality and safe product?

Hey, magta...yeah, that's what I've been using. I've had no problems with them at all but there is some guesswork involved. I haven't done a chemical analysis on their products or anything but they seem pretty effective to me. Of course, feel free to use a more trusted source if you have one. =)


Edited by lostfalco, 01 June 2015 - 02:29 PM.

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#2407 clstrfck

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Posted 03 June 2015 - 04:57 AM

Probably an interesting article. Can't access it though.

 

Mitochondriotropics: A review of their mode of action, and their applications for drug and DNA delivery to mammalian mitochondria

 

Abstract

Since compounds targeting mitochondria exhibit diverse accumulation mechanisms and chemical features, various questions arise. Do such “mitochondriotropics” have a characteristic chemistry? What are mitochondrial uptake mechanisms? Do mitochondriotropics necessarily accumulate in mitochondria or merely have access? Is the concept “mitochondriotropic” of any practical value? To seek answers, a non-biased sample of > 100 mitochondriotropics was generated from the review literature. This dataset was examined using: physicochemical classification; quantitative structure-activity relations (QSAR) models; and a Fick–Nernst–Planck physicochemical model. The ability of the latter two approaches to predict mitochondriotropic behaviour was assessed, and comparisons made between methods, and with current assumptions. All approaches provided instructive pictures of the nature of mitochondriotropics. Thus although lipophilic cations are regarded as the commonest structural type, only a third were such. Much the same proportion were acids, potentially or actually anions. Many mitochondriotropics were electrically neutral compounds. All categorizations involved overall molecular properties, not the presence of “mitochondriotropic tags” — again contrary to literature concepts. Selective mitochondrial accumulation involved electric potential, ion-trapping, and complex formation with cardiolipin; non-specific accumulation involved membrane partitioning. Non-specific access required only low lipophilicity. Mitochondrial targeting did not preclude additional accumulation sites, e.g. lysosomes. The concept “mitochondriotropic” remains useful, although may imply access, not accumulation. QSAR and Fick–Nernst–Planck approaches are complementary — neither is universally applicable. Using both approaches enabled the mitochondriotropic behavior of > 80% of the dataset to be predicted, and the physicochemistry of mitochondriotropics to be specified in some detail. This can facilitate guided syntheses and selection of optimal mitochondriotropic structures.

 

Link: http://www.sciencedi...16836590700291X


Edited by naturesmind, 03 June 2015 - 04:58 AM.


#2408 lostfalco

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Posted 03 June 2015 - 04:12 PM

What's up, my friends? So, I finally got started on a methylene blue experiment today but before I get distracted by that I wanted to share with you guys one of the best supplements I've ever tried. 

 

For the past two and a half weeks I've been testing out Prototype Nutrition's Ur Spray (no affiliation). It's ursolic acid and I've been using one to three sprays on my forehead every 2 hours or so. I just spray it on and then rub it in. My guess is that its primary mechanism is anti-inflammation as it seems to clear up any brain fog within minutes. There are many other possible mechanisms as you'll see in the studies below so I'm definitely open to other possibilities. 

 

Please read up on it before you try it as there are some potential fertility issues associated with it. http://examine.com/s...s/Ursolic Acid/

 

If anyone decides to test it out, let me know. I'm curious to hear if it works for anyone else or if it's just me. Ya know...ymmv and all that. =)

 

Here's the product I've been using. http://prototypenutr...m/ur-spray.html

 

 

http://www.ncbi.nlm....pubmed/17692828

 
Biochem Pharmacol. 2007 Oct 1;74(7):1078-90. Epub 2007 Jul 10.
Ursolic acid ameliorates cognition deficits and attenuates oxidative damage in the brain of senescent mice induced by D-galactose.
Abstract

Ursolic acid (UA), a pentracyclic triterpene, is reported to have an antioxidant activity. Here we assessed the protective effect of UA against the d-galactose (D-gal)-induced neurotoxicity. We found that UA markedly reversed the D-gal induced learning and memory impairment by behavioral tests. The following antioxidant defense enzymes were measured: superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR). The content of the lipid peroxidation product malondialdehyde (MDA) was also analyzed. Our results indicated that the neuroprotective effect of UA against D-gal induced neurotoxicity might be caused, at least in part, by the increase in the activity of antioxidant enzymes with a reduction in lipid peroxidation. And UA also inhibited the activation of caspase-3 induced by D-gal. Furthermore, we found that UA significantly increased the level of growth-associated protein GAP43 in the brain of D-gal-treated mice. These results suggest that the pharmacological action of UA may offer a novel therapeutic strategy for the treatment of age-related conditions.

 

 

http://www.ncbi.nlm....pubmed/20133359

 

Cereb Cortex. 2010 Nov;20(11):2540-8. doi: 10.1093/cercor/bhq002. Epub 2010 Feb 4.

Ursolic acid attenuates D-galactose-induced inflammatory response in mouse prefrontal cortex through inhibiting AGEs/RAGE/NF-κB pathway activation.
Abstract

Evidence shows that administration of D-galactose (D-gal) induces reactive oxygen species (ROS) production and inflammatory response resulting in neurodegenerative changes. Ursolic acid (UA), a triterpenoid compound, has been reported to possess antioxidant and anti-inflammatory properties. Our previous studies have demonstrated that UA could protect mouse brain against D-gal-induced oxidative damage. In the present study, we examined the protective effect of UA against D-gal-induced inflammatory response in the prefrontal cortex and explored the potential mechanism of its action. Our results showed that UA administration significantly improved behavioral performance of D-gal-treated mice in step-through test and Morris water maze task. One of the potential mechanisms of this action was decreased advanced glycation end products (AGEs), ROS, and protein carbonyl levels in the prefrontal cortex of D-gal-treated mice. Furthermore, the results also showed that UA significantly reduced the number of activated microglia cells and astrocytes, decreased the expression of CD11b and glial fibrillary acidic protein, downregulated the expression of iNOS and COX-2, and decreased interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in the prefrontal cortex of D-gal-treated mice. Moreover, UA significantly decreased AGEs induced the expression of receptor for advanced glycation end products and inhibited NF-κB p65 nuclear translocation in the prefrontal cortex of D-gal-treated mice. The aforementioned effects of UA could attenuate brain inflammatory response.

 

http://www.ncbi.nlm....pubmed/24000005

 

Brain. 2013 Oct;136(Pt 10):3038-50. doi: 10.1093/brain/awt224. Epub 2013 Sep 2.

Ursocholanic acid rescues mitochondrial function in common forms of familial Parkinson's disease.

Abstract

Previous drug screens aiming to identify disease-modifying compounds for Parkinson's disease have typically been based on toxin-induced in vitro and in vivo models of this neurodegenerative condition. All these compounds have failed to have a reliable disease-modifying effect in subsequent clinical trials. We have now established a novel approach, namely to screen an entire compound library directly in patient tissue to identify compounds with a rescue effect on mitochondrial dysfunction as a crucial pathogenic mechanism in Parkinson's disease. The chosen Microsource Compound library contains 2000 compounds, including 1040 licensed drugs and 580 naturally occurring compounds. All 2000 compounds were tested in a step-wise approach for their rescue effect on mitochondrial dysfunction in parkin (PARK2) mutant fibroblasts. Of 2000 compounds, 60 improved the mitochondrial membrane potential by at least two standard deviations. Subsequently, these 60 compounds were assessed for their toxicity and drug-like dose-response. The remaining 49 compounds were tested in a secondary screen for their rescue effect on intracellular ATP levels. Of 49 compounds, 29 normalized ATP levels and displayed drug-like dose response curves. The mitochondrial rescue effect was confirmed for 15 of these 29 compounds in parkin-mutant fibroblasts from additional patients not included in the initial screen. Of 15 compounds, two were chosen for subsequent functional studies, namely ursocholanic acid and the related compound dehydro(11,12)ursolic acid lactone. Both compounds markedly increased the activity of all four complexes of the mitochondrial respiratory chain. The naturally occurring compound ursolic acid and the licensed drug ursodeoxycholic acid are chemically closely related to ursocholanic acid and dehydro(11,12)ursolic acid lactone. All four substances rescue mitochondrial function to a similar extent in parkin-mutant fibroblasts, suggesting a class effect. The mitochondrial rescue effect depends on activation of the glucocorticoid receptor with increased phosphorylation of Akt and was confirmed for both ursocholanic acid and ursodeoxycholic acid in a Parkin-deficient neuronal model system. Of note, both ursocholanic acid and ursodeoxycholic acid also rescued mitochondrial function in LRRK2(G2019S) mutant fibroblasts. Our study demonstrates the feasibility of undertaking drug screens in Parkinson's disease patients' tissue and has identified a group of chemically-related compounds with marked mitochondrial rescue effect. Drug repositioning is considered to be a time- and cost-saving strategy to assess drugs already licensed for a different condition for their neuroprotective effect. We therefore propose both ursolic acid as a naturally occurring compound, and ursodeoxycholic acid as an already licensed drug as promising compounds for future neuroprotective trials in Parkinson's disease.

 

http://www.ncbi.nlm....pubmed/21835916

 

J Biol Chem. 2011 Oct 7;286(40):34914-22. doi: 10.1074/jbc.M111.232116. Epub 2011 Aug 11.

A high content drug screen identifies ursolic acid as an inhibitor of amyloid beta protein interactions with its receptor CD36.
Abstract

A pathological hallmark of Alzheimer disease (AD) is deposition of amyloid β (Aβ) in the brain. Aβ binds to microglia via a receptor complex that includes CD36 leading to production of proinflammatory cytokines and neurotoxic reactive oxygen species and subsequent neurodegeneration. Interruption of Aβ binding to CD36 is a potential therapeutic strategy for AD. To identify pharmacologic inhibitors of Aβ binding to CD36, we developed a 384-well plate assay for binding of fluorescently labeled Aβ to Chinese hamster ovary cells stably expressing human CD36 (CHO-CD36) and screened an Food and Drug Administration-approved compound library. The assay was optimized based on the cells' tolerance to dimethyl sulfoxide, Aβ concentration, time required for Aβ binding, reproducibility, and signal-to-background ratio. Using this assay, we identified four compounds as potential inhibitors of Aβ binding to CD36. These compounds were ursolic acid, ellipticine, zoxazolamine, and homomoschatoline. Of these compounds, only ursolic acid, a naturally occurring pentacyclic triterpenoid, successfully inhibited binding of Aβ to CHO-CD36 cells in a dose-dependent manner. The ursolic acid effect reached a plateau at ~20 μm, with a maximal inhibition of 64%. Ursolic acid also blocked binding of Aβ to microglial cells and subsequent ROS production. Our data indicate that cell-based high-content screening of small molecule libraries for their ability to block binding of Aβ to its receptors is a useful tool to identify novel inhibitors of receptors involved in AD pathogenesis. Our data also suggest that ursolic acid is a potential therapeutic agent for AD via its ability to block Aβ-CD36 interactions.

 

 

http://www.ncbi.nlm....pubmed/11355692

 

Mol Cells. 2001 Apr 30;11(2):137-43.

Inhibitory effect of ursolic acid purified from Origanum majorana L on the acetylcholinesterase.

Abstract

We screened 139 herbal spices in search of the acetylcholinesterase (AChE) inhibitor from natural resources. AChE inhibitors, which enhance cholinergic transmission by reducing the enzymatic degradation of acetylcholine, are the only source of compound currently approved for the treatment of Alzheimer's Disease (AD). Among these herbs, edible plants and spices, the ethanol extract from Origanum majorana L. showed the highest inhibitory effect on AChE in vitro. By sequential fractionation of Origanum majorana L. the active component was finally identified as ursolic acid (3 beta-Hydroxyurs-12-en-28-oic acid). The ursolic acid of Origanum majorana L. inhibited AChE activity in a dose-dependent and competitive/non-competitive type. The Ki value (representing the affinity of the enzyme and inhibitor) of Origanum majorana L. ursolic acid was 6 pM, and that of tacrine was 0.4 nM. The concentration required for 50% enzyme inhibition of the active component (IC50 value) was 7.5 nM, and that of tacrine was 1 nM. This study demonstrated that the ursolic acid of Origanum majorana L. appeared to be a potent AChE inhibitor in Alzheimer's Disease.

 


Edited by lostfalco, 03 June 2015 - 04:16 PM.

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#2409 Lucas N

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Posted 03 June 2015 - 04:59 PM

Amazing Falco. Can't wait for try it.

 

How many sprays (serves) the bottle have? 53 bucks for 240ml. It worth the price for you?



#2410 APBT

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Posted 03 June 2015 - 08:19 PM

Probably an interesting article. Can't access it though.

 

Mitochondriotropics: A review of their mode of action, and their applications for drug and DNA delivery to mammalian mitochondria

 

Abstract

Since compounds targeting mitochondria exhibit diverse accumulation mechanisms and chemical features, various questions arise. Do such “mitochondriotropics” have a characteristic chemistry? What are mitochondrial uptake mechanisms? Do mitochondriotropics necessarily accumulate in mitochondria or merely have access? Is the concept “mitochondriotropic” of any practical value? To seek answers, a non-biased sample of > 100 mitochondriotropics was generated from the review literature. This dataset was examined using: physicochemical classification; quantitative structure-activity relations (QSAR) models; and a Fick–Nernst–Planck physicochemical model. The ability of the latter two approaches to predict mitochondriotropic behaviour was assessed, and comparisons made between methods, and with current assumptions. All approaches provided instructive pictures of the nature of mitochondriotropics. Thus although lipophilic cations are regarded as the commonest structural type, only a third were such. Much the same proportion were acids, potentially or actually anions. Many mitochondriotropics were electrically neutral compounds. All categorizations involved overall molecular properties, not the presence of “mitochondriotropic tags” — again contrary to literature concepts. Selective mitochondrial accumulation involved electric potential, ion-trapping, and complex formation with cardiolipin; non-specific accumulation involved membrane partitioning. Non-specific access required only low lipophilicity. Mitochondrial targeting did not preclude additional accumulation sites, e.g. lysosomes. The concept “mitochondriotropic” remains useful, although may imply access, not accumulation. QSAR and Fick–Nernst–Planck approaches are complementary — neither is universally applicable. Using both approaches enabled the mitochondriotropic behavior of > 80% of the dataset to be predicted, and the physicochemistry of mitochondriotropics to be specified in some detail. This can facilitate guided syntheses and selection of optimal mitochondriotropic structures.

 

Link: http://www.sciencedi...16836590700291X

 

FULL TEXT:


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#2411 lostfalco

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Posted 03 June 2015 - 10:55 PM

Amazing Falco. Can't wait for try it.

 

How many sprays (serves) the bottle have? 53 bucks for 240ml. It worth the price for you?

Hey Lucas, each serving is 50 sprays...so it should last a couple of months at least. 

 

"Dosing for all PN sprays are designed to be 50 sprays per dose. There are 7.2 grams of actives in the sprays, thus you are looking at approximately 249 mgs of active per 50 sprays. You can apply all at once or split between two applications."

 

Btw, I forgot to mention that it's Arginine Ursolic Acetate which is acetate and arginine bonded to ursolic acid. So, there are possible epigenetic effects and vasodilation in addition to the numerous effects of ursolic acid. This is just speculation though. Anyway, I look forward to hearing your experience. I hope it's good! =)



#2412 lostfalco

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Posted 03 June 2015 - 11:39 PM

 

 

Link: http://www.sciencedi...16836590700291X

FULL TEXT:

 

Thanks, APBT!



#2413 lostfalco

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Posted 03 June 2015 - 11:47 PM

Hi there! Haven't been here for a while, so I'am not sure if this has already been discussed. My problem with LLLT is that after about 10 days of doing the TULIP regimen I get very depressed. 

 

 I still enjoy reading "The Machinery of Life"!

Hey naturesmind, if LLLT is making you depressed then I would suggest dosing less often. Try once every 2 or 3 days or even once a week. In the Gonzalez-Lima study they found that effects of one LLLT dose can positively affect emotions for weeks. Check out the study here for more info. http://pdfsr.com/pdf.../i-ve-seen-the 

 

I love "The Machinery of Life" too. It's such a simple, beautiful book. I'm really glad it's benefited you!



#2414 BigPapaChakra

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Posted 05 June 2015 - 03:46 AM

http://www.eurekasel.../128159/article

 

Beyond Mitochondria, What Would be the Energy Source of the Cell?


header-btm.png
Author(s): Arturo S. Herrera, Maria del C.A. Esparza, Ghulam Md. Ashraf, Andrey A. Zamyatnin and Gjumrakch Aliev 
Pages 32-41 (10)
Abstract:
Currently, cell biology is based on glucose as the main source of energy. Cellular bioenergetic pathways have become unnecessarily complex in their eagerness to explain that how the cell is able to generate and use energy from the oxidation of glucose, where mitochondria play an important role through oxidative phosphorylation. During a descriptive study about the three leading causes of blindness in the world, the ability of melanin to transform light energy into chemical energy through the dissociation of water molecule was unraveled. Initially, during 2 or 3 years; we tried to link together our findings with the widely accepted metabolic pathways already described in metabolic pathway databases, which have been developed to collect and organize the current knowledge on metabolism scattered across a multitude of scientific articles. However, firstly, the literature on metabolism is extensive but rarely conclusive evidence is available, and secondly, one would expect these databases to contain largely the same information, but the contrary is true. For the apparently well studied metabolic process Krebs cycle, which was described as early as 1937 and is found in nearly every biology and chemistry curriculum, there is a considerable disagreement between at least five databases. Of the nearly 7000 reactions contained jointly by these five databases, only 199 are described in the same way in all the five databases. Thus to try to integrate chemical energy from melanin with the supposedly well-known bioenergetic pathways is easier said than done; and the lack of consensus about metabolic network constitutes an insurmountable barrier. After years of unsuccessful results, we finally realized that the chemical energy released through the dissociation of water molecule by melanin represents over 90% of cell energy requirements. These findings reveal a new aspect of cell biology, as glucose and ATP have biological functions related mainly to biomass and not so much with energy. Our finding about the unexpected intrinsic property of melanin to transform photon energy into chemical energy through the dissociation of water molecule, a role performed supposedly only by chlorophyll in plants, seriously questions the sacrosanct role of glucose and thereby mitochondria as the primary source of energy and power for the cells.

- See more at: 


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#2415 lostfalco

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Posted 07 June 2015 - 01:33 AM

http://www.ncbi.nlm....pubmed/25966949

 

J Cereb Blood Flow Metab. 2015 May 13. doi: 10.1038/jcbfm.2015.87. [Epub ahead of print]

Low-level light in combination with metabolic modulators for effective therapy of injured brain.

Abstract

Vascular damage occurs frequently at the injured brain causing hypoxia and is associated with poor outcomes in the clinics. We found high levels of glycolysis, reduced adenosine triphosphate generation, and increased formation of reactive oxygen species and apoptosis in neurons under hypoxia. Strikingly, these adverse events were reversed significantly by noninvasive exposure of injured brain to low-level light (LLL). Low-level light illumination sustained the mitochondrial membrane potential, constrained cytochrome c leakage in hypoxic cells, and protected them from apoptosis, underscoring a unique property of LLL. The effect of LLL was further bolstered by combination with metabolic substrates such as pyruvate or lactate both in vivo and in vitro. The combinational treatment retained memory and learning activities of injured mice to a normal level, whereas other treatment displayed partial or severe deficiency in these cognitive functions. In accordance with well-protected learning and memory function, the hippocampal region primarily responsible for learning and memory was completely protected by combination treatment, in marked contrast to the severe loss of hippocampal tissue because of secondary damage in control mice. These data clearly suggest that energy metabolic modulators can additively or synergistically enhance the therapeutic effect of LLL in energy-producing insufficient tissue-like injured brain.Journal of Cerebral Blood Flow & Metabolism advance online publication, 13 May 2015; doi:10.1038/jcbfm.2015.87.

 


Edited by lostfalco, 14 June 2015 - 02:00 PM.


#2416 BigPapaChakra

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Posted 11 June 2015 - 05:41 AM

Does anybody know if this source is okay for H2 sticks? http://www.livingwat...om/science.htmlI believe it is actually a site dedicated to/created by Dr. Hidemitsu Hayashi himself, and thus potentially different than the H2 sticks on amazon? If so, it would be great, the sticks are $79.95 and purportedly lasts for 6 months. This is another source of the same thing: http://www.hydrogeninmywaterbottle.com/html/purchase.php

 

There is then this source for an H2 infusing machine: http://www.alkaway.com.au/they carry a machine that reduces fluoride and all that but also infuses H2 into water for like $500 or $600, and also have Mg metal tablets as supplements.

 

All, if reliable, cheaper options than the Lourde's machine for those who can't currently afford to drop over $1000 on it. 



#2417 lostfalco

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Posted 11 June 2015 - 02:17 PM

Does anybody know if this source is okay for H2 sticks? http://www.livingwat...om/science.htmlI believe it is actually a site dedicated to/created by Dr. Hidemitsu Hayashi himself, and thus potentially different than the H2 sticks on amazon? If so, it would be great, the sticks are $79.95 and purportedly lasts for 6 months. This is another source of the same thing: http://www.hydrogeninmywaterbottle.com/html/purchase.php

 

There is then this source for an H2 infusing machine: http://www.alkaway.com.au/they carry a machine that reduces fluoride and all that but also infuses H2 into water for like $500 or $600, and also have Mg metal tablets as supplements.

 

All, if reliable, cheaper options than the Lourde's machine for those who can't currently afford to drop over $1000 on it. 

Hey Papa, I tried that source for hydrogen sticks and didn't have a great result. Just my experience though. I haven't tried that H2 machine or the supplements. I wish the Lourde's machine wasn't so freaking expensive!



#2418 BigPapaChakra

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Posted 11 June 2015 - 03:55 PM

Thanks for the heads up, Falco. 

 

This is Alkaway's H2 machine: http://www.alkaway.c...op/ultrastream/on the page there is this document that shows that it purportedly does infuse a lot of H2: http://www.alkaway.com.au/wp-content/uploads/2013/12/UltraStream-and-SD501-chemical-analysis.-23Oct2013.pdf  (authored by Tyler LeBaron) 

 

So, for $600 (plus fluoride filtration and all that) it seems pretty nice; but I've heard that some people have "negative reactions" from filters that utilize KDF technology. I don't know if that is true or not, but someone on a facebook group told me so, and it worried me since I'm so sensitive to things. 

 

I may email the company and ask about return policies, if they've heard of negative reactions, etc. and see what they say, as I really want to try H2 water.  



#2419 lostfalco

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Posted 14 June 2015 - 12:55 AM

http://www.ncbi.nlm....les/PMC4143009/

 

Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12228-33. doi: 10.1073/pnas.1322912111. Epub 2014 Jul 28.

Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons.

Abstract

L-lactate is a product of aerobic glycolysis that can be used by neurons as an energy substrate. Here we report that in neurons L-lactate stimulates the expression of synaptic plasticity-related genes such as Arc, c-Fos, and Zif268 through a mechanism involving NMDA receptor activity and its downstream signaling cascade Erk1/2. L-lactate potentiates NMDA receptor-mediated currents and the ensuing increase in intracellular calcium. In parallel to this, L-lactate increases intracellular levels of NADH, thereby modulating the redox state of neurons. NADH mimics all of the effects of L-lactate on NMDA signaling, pointing to NADH increase as a primary mediator of L-lactate effects. The induction of plasticity genes is observed both in mouse primary neurons in culture and in vivo in the mouse sensory-motor cortex. These results provide insights for the understanding of the molecular mechanisms underlying the critical role of astrocyte-derived L-lactate in long-term memory and long-term potentiation in vivo. This set of data reveals a previously unidentified action of L-lactate as a signaling molecule for neuronal plasticity.

 

 

http://www.ncbi.nlm....pubmed/25128877

 

Neurobiol Learn Mem. 2014 Dec;116:46-58. doi: 10.1016/j.nlm.2014.08.004. Epub 2014 Aug 14.

Acute exercise improves motor memory: exploring potential biomarkers.

Abstract

We have recently shown that a single bout of acute cardiovascular exercise improves motor skill learning through an optimization of long-term motor memory. Here we expand this previous finding, to explore potential exercise-related biomarkers and their association with measures of motor memoryand skill acquisition. Thirty-two healthy young male subjects were randomly allocated into either an exercise or control group. Following either an intense bout of cycling or rest subjects practiced a visuomotor tracking task. Motor skill acquisition was assessed during practice and retention 1 h, 24 h and 7 days after practice. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), epinephrine, norepinephrine, dopamine and lactate were analyzed at baseline, immediately after exercise or rest and during motor practice. The exercise group showed significantly better skill retention 24h and 7 days after acquisition. The concentration of all blood compounds increased significantly immediately after exercise and remained significantly elevated for 15 min following exercise except for BDNF and VEGF. Higher concentrations of norepinephrine and lactate immediately after exercise were associated with better acquisition. Higher concentrations of BDNF correlated with better retention 1 h and 7 days after practice. Similarly, higher concentrations of norepinephrine were associated with better retention 7 days after practice whereas lactate correlated with better retention 1h as well as 24 h and 7 days after practice. Thus, improvements in motor skill acquisition and retention induced by acute cardiovascular exercise are associated with increased concentrations of biomarkers involved in memory and learning processes. More mechanistic studies are required to elucidate the specific role of each biomarker in the formation of motor memory.

 


 

 


Edited by lostfalco, 14 June 2015 - 12:59 AM.


#2420 Christian Hunter

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Posted 17 June 2015 - 09:20 AM

I agree w Chung_Pao, and would point to testosterone as the single most efficacious cognitive enhancing, mood lifting, and overall quality-of-life boosting tool in my personal (rather extensive) arsenal.

And to your question stablemind, I've been on test for roughly 10 years now and almost exclusively on a topical version (either Androgel, or a cream from a compounding pharmacy).

Recently I gave test cypionate a try and have really, really disliked the results! Specifically, I gained about 8lbs of water weight in ~10 days (on 165lbs baseline), the once weekly injections cause uncomfortable levels in my system (either too high or too low), and oh, they're injections with a inch and a half long intramuscular needle! NOT FUN!

#2421 Godof Smallthings

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Posted 17 June 2015 - 09:56 AM

How much testosterone per day?

 

What happened before you found your sweet spot - because I assume you must have experimented somewhat to find your optimum dose?



#2422 montana2012

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Posted 17 June 2015 - 02:15 PM

Has anyone else experienced mild cognitive decline following a long PQQ cycle? I take it every now and then these days, but ever since that few month Doctor's Best "cycle" I did @ 10mg EOD, I just feel very subtly retarded, or more like, my brain isn't utilizing energy the way it used to. I just don't go feel like going into explanations, very short-spoken. Mitochondria isn't as efficient.The immediate effect is amazing, however. 

Has anyone else experienced anything similar? There could be something else at play.


Edited by montana2012, 17 June 2015 - 02:18 PM.


#2423 Kalliste

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Posted 17 June 2015 - 03:14 PM

Since this thread is almost a separate forum I'd like to add that there is some concern regarding MitoQ and neural stem cells. It might apply to other stuff targeting mitochondria or it might not.



#2424 Jochen

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Posted 17 June 2015 - 04:18 PM

Since this thread is almost a separate forum I'd like to add that there is some concern regarding MitoQ and neural stem cells. It might apply to other stuff targeting mitochondria or it might not.

 

What is the concern and what are the references? Thanks for pointing it out in advance!



#2425 BigPapaChakra

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Posted 17 June 2015 - 06:39 PM

This is awesome. Likely out of most individuals' budget, but it seems to currently be the modality closest to direct brain photobiomodulation:

 

http://www.vielight....ranasal-light/ 

 

Transcranial+intranasal high powered 810nm pulsed at 10hz; one of the LED bases directly targets the Default Mode Network. For anyone who has followed the TAG-Sync/neurofeedback threads, you'll likely be aware of the DMN and how important it is in overall emotional regulation, sense of self, etc. This method of PBM would essentially be targeting the DMN and the hypothalamus/midbrain, while irradiating the blood, all at the same time.

 

Only $1500  ;)


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#2426 BigPapaChakra

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Posted 17 June 2015 - 06:55 PM

Copying some of the most important information from the inventors notes: 

 

http://www.vielight....ntor-notes.pdf 

 

"Since light penetrates significantly more deeply into the brain from an intranasal position (in the nose) than from transcranial (on the head) locations,6 it is logical that a light source located in the intranasal position is crucial if one is looking for a comprehensive PBM treatment of the brain. On its own merit, researchers have already found that Intranasal Light Therapy has positive outcomes with neurologic conditions in humans, such as insomnia,23 mild cognitive impairment,24 Alzheimer’s disease,25 Parkinson’s disease,26 27 28 29 schizophrenia,30 migraine and headaches,31 32 and stroke (cerebral infarction)33 34 35 36. For more details, please see http://www.medicligh...Stimulation.pdf.

 

(..)

 

Therefore, outcomes can be improved significantly if intranasal PBM is combined with transcranial LEDs. This leads to the next question: “How can we incorporate transcranial LEDs with the intranasal LED to create an efficient and effective device?” This leads me to consider targeting only selected areas of the brain, which are the hubs of the key networks, primarily the Default Mode Network (DMN) and secondarily, the Salience Network (SN) : Treat these busy and extensively connected hubs and the whole-brain would receive treatment.

 

For a long time, I thought it would be difficult to achieve an effective and portable device with a transcranial system, so I focused on the intranasal light therapy devices that I co-invented earlier (with patents issued and pending). Although the intranasal devices aim at some of the most important nuclei located in the ventral (under) side of the brain, they are incomplete because the dorsal (or upper) areas have been ignored. With new understanding of the DMN, there is now an opportunity to create a portable and affordable transcranial system by targeting these locations.

 

Dr. Juanita Anders (who is also one of our science advisors) and her research collaborators investigated the wavelength dependence of light scatter and absorbance in intraparenchymal brain tissue using 660, 808, and 940nm wavelengths. Their research indicated that the 808nm wavelength light demonstrated superior CNS tissue penetration.8 This is also reflected in an earlier study which showed that wavelengths of around 810 nm penetrated deepest into the tissues of the spinal cord

 

The efficacy differences between pulsed and continuous wave light are not entirely clear but the evidence are tilted in favor of pulsed wave.66 Generally, ultra-short pulses can penetrate deeper when pulses are intermittent but set at a higher power. Pulsing, as opposed to continuous exposure, prevent the undesirable thermal effect (building up of heat) when a relatively high power is used. In turn, high powered pulsed light would result in more cellular energy (ATP), as demonstrated in a study on rabbits.67 Another mechanism of action involves the pulsed photons promoting chromophores to excited states in the upper tissue layer. This opens the way for more photons to enter into the tissue during the next pulse. In contrast to continuous wave, superior results were obtained when lasers at 808 nm were pulsed at 100 Hz and 1000 Hz.68

 

In addition, pulsed mode comes with a “duty-cycle”, which is the on-off relative interval. I have chosen 50% duty-cycle for our NIR devices because it resembles closely to the even square waves of brain oscillation. My hypothesis is that this facilitates entraining the brain into the alpha wave (between 8 to 10 Hz). Although there are no clinical data, the alpha state is suggested to have antidepressant quality as well as a booster of the immune system. In summary, the main reason for adopting 10 Hz pulsed mode remains the significantly low stress scores when traumatized animal brains were exposed to 810 nm light energy pulsing at 10 Hz.69

 

Besides the need to reach hard-to-access locations in the brain, there is a need for more light to penetrate deeper into brain tissue into areas like the posterior cingulate cortex (important for Alzheimer’s and a key hub in the DMN), the precuneus (a hub of the DMN) and to the substantia nigra (important for Parkinson’s) and the brainstem. With our more powerful Transcranial diode using 810 nm LED diode we are able to extract a consistent 41 mW of power at this time while the closest that I have seen is about 30 mW. This means that the Neuro delivers about twice the power of the 810 Infrared intranasal model. This calculated higher power delivers deeper penetration into the without causing tissue damage.83 Our field test in this area appears to confirm this. Feedback received from the field indicates that it has been particularly helpful with brain fogginess, impaired cognition and chronic facial pain. As these are anecdotal experiences, the next stage is to carry out controlled studies for validation. In this respect, we have started a pilot study on Alzheimer’s disease and dementia at the time of writing. In summary, we are aiming to achieve, quicker and more consistent neurologic outcomes with the Neuro by directing therapeutic light energy with more energy and deeper penetrating ability to the hubs of the DMN.

 

Based on the theory of Biphasic Dose Response, which basically says that low energy dose heals but high energy dose damages,84 people who are very sensitive to electromagnetic energy or people with brain infections may experience a headache while using the Neuro. Based on this, I generally recommend that the Neuro be used for 20 minutes per treatment but not more than once every two or three days. The milder 810 Infrared intranasal device can be used daily to complement the Neuro. Another point to consider is how do we maximise the benefits from the use of the Neuro or the 810 Infrared? Since the DMN is activated when we are not performing any task, and usually when our eyes are closed, we want to apply the Neuro or the 810 Infrared intranasal device s with our eyes closed.85 While using the Neuro, the circulatory and immune system can be treated simultaneously using the Vielight 633 Red or the 655 Prime intranasal devices."


Edited by BigPapaChakra, 17 June 2015 - 06:56 PM.

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#2427 Luxflux

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Posted 17 June 2015 - 08:28 PM

Has anyone else experienced mild cognitive decline following a long PQQ cycle? I take it every now and then these days, but ever since that few month Doctor's Best "cycle" I did @ 10mg EOD, I just feel very subtly retarded, or more like, my brain isn't utilizing energy the way it used to. I just don't go feel like going into explanations, very short-spoken. Mitochondria isn't as efficient.The immediate effect is amazing, however. 

Has anyone else experienced anything similar? There could be something else at play.

 

PQQ interferes with glutathione production. I say this because I am one of those people who responds tremendously to NAC supplementation, and I had a similar reaction to PQQ. Try taking some NAC and see if it helps.



#2428 Jochen

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Posted 18 June 2015 - 03:48 AM

This is awesome. Likely out of most individuals' budget, but it seems to currently be the modality closest to direct brain photobiomodulation:

 

http://www.vielight....ranasal-light/ 

 

Transcranial+intranasal high powered 810nm pulsed at 10hz; one of the LED bases directly targets the Default Mode Network. For anyone who has followed the TAG-Sync/neurofeedback threads, you'll likely be aware of the DMN and how important it is in overall emotional regulation, sense of self, etc. This method of PBM would essentially be targeting the DMN and the hypothalamus/midbrain, while irradiating the blood, all at the same time.

 

Only $1500  ;)

 

Thanks for that. Shame they want to capitalise on the LLLT so much. I have their intranasal and I actually like it, but I would not really consider this 'neuro' device. I would rather save up a bit more (read as a lot more) for the bioflex device by Dr Kahn : http://drkahnblog.bioflexlaser.com/. The nice thing about bioflex is that you can use different wavelengths for different purposes. Main focus on the latter is healing though.

 

The nice thing about this neuro is that it looks quite convenient to have on your head. Maybe they should go for a full blown helmet like the crazy hair dude :-) http://www.overmachogrande.com/



#2429 BieraK

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Posted 18 June 2015 - 04:59 AM

Another study from Dr Gonzalez-lima :)

http://www.ncbi.nlm....les/PMC4428125/
 

Protection against neurodegeneration with low-dose methylene blue and near-infrared light
F. Gonzalez-Lima* and Allison Auchter

Neurons are metabolically protected against degeneration using low-level methylene blue and near-infrared light interventions. Both of these novel interventions act by a cellular mechanism involving enhancement of the electron transport chain in mitochondria, which promotes energy metabolism and neuronal survival (Gonzalez-Lima et al., 2014). Methylene blue preferentially enters neuronal mitochondria after systemic administration, and at low-doses forms an electron cycling redox complex that donates electrons to the mitochondrial electron transport chain. Low-level near-infrared light applied transcranially delivers photons to cortical neurons that are accepted by cytochrome oxidase, which causes increased cell respiration and cerebral blood flow. Breakthrough in vivo studies with these interventions suggest that targeting mitochondrial respiration may be beneficial for protection against different types of neurodegenerative disorders.

The purpose of this paper is to provide an update on the cellular mechanisms mediating the neuroprotective effects of low doses of methylene blue and near-infrared light, and to argue that the neurotherapeutic benefits of these two different interventions share the same cellular mechanism of action based on stimulation of mitochondrial respiration. Presented first is the explanation of the biochemical redox action of low-dose methylene as an electron cycler on the mitochondrial electron transport. Presented second is the explanation of the biophysical action of near-infrared light as a photon donor to cytochrome oxidase that also serves to stimulate mitochondrial electron transport. We finish with a comparison of these two interventions and how they share a common cellular mechanism with similar properties such as energy transfer, low-dose hormetic dose-responses, and enhanced capacity for oxidative metabolic energy production, which serve to protect nervous tissue from degeneration.

 



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#2430 Kalliste

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Posted 18 June 2015 - 05:28 AM

 

Since this thread is almost a separate forum I'd like to add that there is some concern regarding MitoQ and neural stem cells. It might apply to other stuff targeting mitochondria or it might not.

 

What is the concern and what are the references? Thanks for pointing it out in advance!

 

 

Greg from MitoQ has followed up on the issue in the MitoQ thread.

http://www.longecity...e-8#entry732872


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