Aspirin protection from nicotine in mouth, throat, and G.I. tract

Concerning nicotine, and protection with aspirin:

"The results suggest that stimulation of COX-2 and VEGF expression can contribute as important factors in the tumorigenic action of nicotine in oral cancer progression."
" Pretreatment with celecoxib [an NSAID like aspirin] inhibited nicotine-induced change in the expression of VEGF and COX-2."

The above caused me to wonder about aspirin:

"Observational and also some randomized trials suggest that regular long-term use of aspirin (acetylsalicylic acid) might reduce the risk of colorectal carcinomas by 15-40%. "
"Inhibition of COX-1 and/or COX-2 is most likely involved. "

"Furthermore, aspirin and sodium salicylate inhibited COX-2 expression stimulated by VEGF. These findings indicate that aspirin and other salicylate drugs at pharmacological concentrations inhibit colon cancer-induced angiogenesis which is correlated with COX-2 suppression."

"tumor growth in the subcutaneous tissues was also suppressed by aspirin, COX-2 selective inhibitors, and the VEGF antibody, but not by the COX-1 inhibitor."

my theory of every thing, biology being replaced, post to MIT review

@0.426771640856  Wiki has a better interpretation of the Bremerman limit:  "The limit has been further analysed in later literature as the maximum rate at which a system with energy spread can evolve into an orthogonal and hence distinguishable state to another".  I adhere to the many world's theory, so the problem it is "solving" is the act of actually taking every possible route, not looking for the one that solves an optimization problem.

The narrow goal of A.I. is optimization. Chess is a specific problem but you're shifting gears to an optimization problem when there is no defined problem, or rather, you're assuming there is a very grand problem that existence is solving, harking back to Adam's Hitchhiker's Guide, which is undoubtedly not the originator of the idea. I mean, the guide itself was stole straight out of Asimov's Foundation. My view is that nothingness by definition can't exist and "everything" is being created as a result of the logical impossibility of nothingness. A finite universe seems like it would leave holes of nothingness. Related to this everythingness is Gödel's incompleteness theorem which indicates you have to have an infinite number of axioms to have a logically complete system, or an inconsistent set of axioms. My nothingness axiom fulfills both conditions: it is a recursively self-destructive axiom who's output is every other axiom.

But if we look at pieces of this everythingness such as gravitational systems emitting entropy (which keeps the Universe's comoving-volume entropy constant) (final entropy of the Universe is an open question and measured to be constant per comoving volume due to the observed homogeneity of heat, i.e. there is no heat transfer), then we can see a shift towards local order, i.e., an optimization problem being solved. The Earth intuitively feels like a computer because life seems to be going towards more local order, which is possible because it is an open system, and we can measure the amount of excess entropy it is generating. Answers to problems are fewer bits than the data behind the question so answers are less entropy.

Evolution appears to be the principle of least action (a more general form of newton's laws), which maximizes potential energy at the cost of kinetic energy over all time scales, which creates high-energy bonds and produces less heat in systems, utilizing excess energy that comes to the Earth. We release excess entropy via 17 random low energy photons for every directional photon from the sun, so that we have the opportunity to create local order.

Seeking the highest energy potential energy bonds limits the number of choices which creates "copies" which is less entropy. Less kinetic energy means less heat, which means less entropy. This is why the mass on Earth is shifting from biological bonds to silicon, metallic, and carbon bonds with oxygen removed. These elemental (more order) high energy bonds enable machines to be 20x, 100x, and 10,000,000 times more efficient than photosynthesis, muscles, and brains, respectively, at acquiring energy to move matter to make copies of the thnking machine's support structure. Brains need to move ions weighing 40,000 times more than the electrons in CPUs which is why brains are inherently outdated. Biology was not able to directly smelt metals and metalloids. Thinking machines will move electrons to model larger bits of matter in the external world in order to repeat the reproduction process more efficiently.  The great depression began as muscles were replaced by machines on farm and factory. We had to shift to thinking jobs in order to remain useful to the corporate machine (which seeks fewest employees and fewest shareholders). The current problem is deciding how to distribute the wealth as more and more muscles and brains are not needed. Wealth inequality could eventually kill 90% of the human population due to people being more and more irrelevant to the efficiency-seeking evolutionary process we call economics, but that is not going to stop the biosphere from being replaced by a more efficient entropy-reducing technology.

You did ask for thoughts.

Kepler's Knowledge of Gravity Before Netwon

"If I have seen further, it is by standing on the shoulders of giants." - Sir Isaac Newton, modifying a quote attributed to 12th century philosopher Bernard of Chartres.

"Before Kepler, all men were blind, Kepler had one eye, and Newton had two eyes." -Voltaire who first referred to Newton's combination of Galileo's & Kepler's contributions as "laws".

Kepler was aware of every aspect of universal gravity but he did not explicitly say 1/R^2. His most surprising gravity axiom shows he knew either F=ma or used "Einstein's" equivalence principle between inertia and gravity.

Kepler's axioms of gravity contain the following statements.  This is my wording, but I'll spell out the caveats and give the exact wording further down.

1) objects at rest in space stay at rest, if not affected by gravity
2) gravity is proportional to mass
3) mass = density*volume
4) applies to all substances (corporeal). no substance is without mass
5) decreases with distance
6) extends forever if no other gravitational mass interferes
7) center of a mass has zero gravity
8) Earth and moon would collide if you let them go from resting positions. Two masses M1 and M2 released from rest at a distance R will collide after travelling D1=R*M2/(M1+M2) and D2=R*M1/(M2+M1). Closer to his wording and more simply written: D2/D1=M1/M2. It's correct. I believe it originates from Galileo's investigations, but Kepler was unsuccessful in convincing Galileo gravity extended from the moon to causes the tides. Can physicists prove 8 without using "Newton's" laws and "Newtonian" gravity?

The author of the newest translation of Kepler's "Astronomia Nova" (wherein Kepler states his gravity axioms and his 3 laws of planetary motion) is wrong in claiming that Kepler's gravity "[does not contain] the least notion that gravity extends to any other bodies than the Earth and the moon". It is so ingrained in modern thinking that Newton discovered gravity, that many excuses have to be made against Kepler's perfectly correct gravity (which was missing the 1/R^2 if you exclude the logical conclusion of his gravity and planetary laws). What was Newton's dwarf-on-shoulders of giants contribution? Kepler seemed to be simply unaware there was not an additional "motive" force other then Galileo's inertia that kept planets going around the Sun.

In Bethune's words from 1830 (London edition, not the 1932 Boston edition)

"[Kepler] also conjectured that the irregularities in the moon's motion were caused by the joint action of the sun and earth, and recognized the mutual action of the sun and planets, when he declared the mass and density of the sun to be so great that the united attraction of the other planets cannot remove it from its place."

Professor Forbes in 1909 in "History of Astronomy"

"it must be obvious that [Kepler] had at that time some inkling of the meaning of his laws--universal gravitation. From that moment the idea of universal gravitation was in the air, and hints and guesses were thrown out by many"  

In the words of Bethune again:

"Many who are but superficially acquainted with the History of Astronomy, are apt to suppose that Newton's great merit was in his being the first to suppose an attractive force existing in and between the different bodies composing the solar system. This idea is very erroneous .. the general notion of an attractive force between the sun, moon, and planets was very commonly entertained before Newton was born, and may be traced back to Kepler, who was probably the first modern philosopher who suggested it. "

Now compare this to Newton, known for denying credit to his peers, acting as if he discovered the attraction of gravity that was explained in the introduction to Kepler's book on planetary motion:

"Kepler’s laws, although not rigidly true, are sufficiently near to the truth to have led to the discovery of the law of attraction of the bodies of the solar system. The deviation from complete accuracy is due to the facts, that the planets are not of inappreciable mass, that, in consequence, they disturb each other's orbits about the Sun..."    

Here are more points in support of the view that Kepler was thinking in terms of a "universal" gravity:

1) Kepler thought magnetism must be in the Sun and planets because it was in the Earth, and he emphasized the similarities between gravity and magnetism (but did not claim they were the same but is accused of claiming magnetism was gravity).  He also correctly jumped to the conclusion that if the Earth spins, then so does the Sun, showing he viewed the Sun as a celestial body like the planets.

2) Kepler was justifiably accused of trying too hard to generalize basic ideas. Examples: "Harmonies" of the solar system being related to music, wondering if the Earth might breathe in some way analogous to fish (predating Gaia ideas), and imagining a story about travelling to the moon to meet potential inhabitants.

3) I have not seen anyhting to indicate he could be accused of thinking the Earth is different from any other planet. His comments that were inline with older thoughts of assigning personalities to planets seemed very much allegorical and an appeasement to the language and thought of the time.

4) He tried to apply his three planetary laws to the moon (see quote below), indicating he could think of the Earth acting as a "Sun" and the moon like a "planet", and since he stated gravity is always present, he had to be thinking it was an integral part of his planetary laws, and therefore applicable, if not equally applicable to all planets. As he states, you only need to make a correction for density if you know the volume in order to get the mass.

5) Kepler supported Bruno's opinion that stars were Suns with planets or moons in their orbits.

"Short History of Astronomy" by Arthur Berry, 1898

"The "Epitome of Copernican Astronomy" (1618)  contains the first clear statement that the two fundamental laws of planetary motion established for the case of Mars were true also for the other planets (no satisfactory proof being, however, given), and that they applied also to the motion of the moon round the earth, "

Universality of gravity aside, it is hard to underestimate the precision and completeness of Kepler's gravity axioms stated in the introduction to Astronomia Nova. It was presented as proof that the Earth can't be the center of the universe, and was in support of the idea that physics should be applied to astronomy. This was his most widely distributed text, and one of the few you can find for free on the internet. (This was his most famous book and it contains his 3 laws, but you can't find the rest of this text on the internet in any language except Latin. Only his 8 gravity axioms are easy to find.).  After reading his axioms, it is not possible to hold the opinion that Newton discovered gravity.  The only element of Newtonian gravity that is not blatant is 1/R^2, which is a geometrical effect of conserved "rays" of any type being emitted from a point source. It is also a derivable consequence of just the first two of Kepler's laws and Galileo's inertia. But he did not do this derivation (his math skills were easily up to the task which Einstein marveled at), possibly because he was thinking the planets were being subjected not only gravity, but some sort of friction and a sideways force from the Sun in the form of magnetism (or another unknown force) to overcome the friction.

Decades before Newton was thinking about falling objects, Kepler described with perfect precision in "meters" and "kg" how far the Earth would move "up" if we were able to stop the moon's orbit and drop it towards the Earth. He said this applied equally well to every mass. I can't derive this axiom unless I use F=ma and the knowledge that gravity causes an acceleration, i.e. Galileo's distance=1/2*a*t^2.  If you can derive this without using F=ma, please say so in the comments.

Other than not saying 1/R^2 explicitly, there are two potential problems with his gravity axioms.

One is that he used the phrase "cognate bodies" (mutuainter cognata corpora unitionem seu conjunctionem) which some have claimed means he was only talking about the Earth-moon system. There are many lines of reasoning that show this is a big assumption, as I've described above.

"If he knew gravity was universal, why didn't he talk more about it?"  He did place it in the introduction to his most famous work and call them axioms.  His friend Galileo could not believe the tides were caused by the moon and going further might have seemed premature. The Sun carrying such a force might have caused more problems with the church (other than trying to burn his mother at the stake). But more likely I think gravity is such an obvious everyday thing that Kepler could have considered it less important and trivial compared to determining the rules that govern the positions of the planets. Gravity was incredibly easier to see and understand compared to determining the rules that govern the wandering planets as viewed from Earth. We can easily say "ellipse" now, but determining it and proving it to others from the point of view of Earth's orbit in the midst of these other ellipses (that differed from circular by only 0.4% in the case of Mars) made Newton's mathematical restatement of Kepler's laws (and connecting it to Galileo's work) trivial (as Einstein explained). Kepler was no less shabby than Newton in optics and calculus-like work. What more needed to be said about gravity beyond Galileo?  Kepler had gravity correct far beyond Galileo's beliefs, but he could not see how it alone with inertia was enough to determine his laws without any other magnetic, animal, or friction forces. Gravity for him probably appeared to be obvious, everyday, simple, and solved, much less interesting than the solving the riddle of the planets.

Getting back to potential problems with his axioms: More advanced forms of the "cognate bodies" complaint are that he may have thought each planet ("cognate body") would have a different gravity such as a different "gravitational constant" or distance rule, especially if they had a magnet effect that was interfering with it and thereby modifying it.  Others think that maybe he thought masses were attracted only to their own "cognate" masses, which by some strange reasoning would include only their satellites but not other planets. Hence, they say, Newton was endowed with "universal" gravitation.

But if axiom 8 works on other planets with a different gravity constant, then (as I discuss below) the inertial force would have to change in lockstep with the change in the gravitational force (the "Einstein" principle of equivalency would remain intact because axiom 8 depends on it). This means the ratio of the gravity force to the inertial force would have to remain the same. But this is the same saying only the density has changed in other "cognate bodies" and he was fully aware of the effect of changes in density. His gravity adjusts for changes in density.

You might object that his knowledge of inertia was not advanced enough to make the above claim. Besides his comments on inertia and knowledge of Galileo (who discovered Newton's first law), his "Dream" book more than anything shows how well he understood inertia. He estimated that only with extreme precautions could aliens transport thin humans with strong bones (from riding goats since childhood) and opiates to the moon in only 4 hours by a "blast off" method accelerating into space, with great aliens standing on top of each other's shoulders to give the humans a boost "as if by gun powder", predating rocket ships.  He mentions easier travel after blast off, if it were not for the lack of air and the cold, and a similar deceleration process at the moon.  At 10 g, the most a person might be able to tolerate, I get that the acceleration would need to be for 300 seconds to get half way to the moon in 2 hours (4 hours for the full trip). That would need to be about a 3000 mile-high stack of aliens reaching out into space, all within the parameters of description. He had to understand inertia, falling bodies, and gravity well enough for this to come out so accurately in accordance with Newton's laws, with a good guess as to what a human body can withstand. I would have been hard-pressed to come this close without knowing 10 g, v=at, and s=1/2*a*t^2. He had some sort of access to the last two via Galileo. It is interesting that he made the travelling time "a little less than 4 hours" for another reason: at 1 g acceleration above Earth's gravity to half way and 1 g deceleration for the rest of the way, I get 3.88 hours. I could find no mention about gravity on the moon being less except his mentioning that the inhabitants grow to a very large size which is more likely when gravity is less.

Another potential problem is that in two different English translations he says the Earth is less "attracted" to a stone than the stone "seeks" the Earth. His latin is "trahat" and "petit", which can also be translated as "to pull forth" and "to strive for" or "travels to".  If he meant as some type of modern "force" then it is wrong, as the force is supposed to be equal on both. But this would conflict with his 8th axiom.  He may have meant it in a "distance" or "velocity" sense, in which case it is correct and in accordance with his 8th axiom.

Some might complain they did not have a distinct concept of "mass" so the translation could be in error. However, the latin was "moles" which is "mass", "weight", or "load", so I think it is sufficiently clear he meant it as you weigh it, and he distinctly indicated moles = density * volume which is mass.  He may not have thought about it as an absolute value of mass translatable to any planet as we know it, but he kept his comments on gravity perfectly correct by speaking in terms of ratios of mass.

Another complaint is that he thought magnetism was gravity but his two stones example did not require they be magnets. He entertained the idea that a magnetism or some other force from the Sun kept planets moving against a supposed friction. He also appears to have ascribed an "animal force" for this movement, inherent to bodies, but he may have specifically meant for this to mean inertia. He sometimes mentions gravity and mass have a parallel in the magnetic force in that magnets have an invisible type of action at a distance.

I can confirm axiom 8 only by using F=ma and Galileo's distance=1/2*a*t^2 for each mass, plugging in a=F/m, noting that they collide at the same time t, then thereby let F, 1/2, and t^2 cancel when I divide the two Galileo distance equations and get D1/D2=m2/m1 as Kepler states. This is an interesting simple result and it could be named "Kepler's law of mass attraction." It leaves open the possibility of gravity changing as any function of distance, but remains valid only if the well-known "Einstein" equivalency of the inertial force and gravity force on the mass are the same, allowing me to make the substation of "a" above.   How did he do it when he was not supposed to know F=ma?  Do his 1st two laws give this result when taken to the limit of an orbit of zero?  He is saying "if you take out my planetary laws by stopping the moon's orbit and remove all other forces on it, you will have a gravitational force that will cause the Earth and moon to come together at this particular point in space."  So he could see gravity clearly when he stopped thinking about "magnetic", "animal", and frictional forces in planets by making the orbits stop.

Finally I am getting to Kepler's own words, which are equal in weight to all the above. All the above was needed to defend against the various remarks made that try to diminish Kepler's contributions. Part of the problem is that there is no full English translation of Astronomia Nova, and no free version available on the internet in any language other than latin.  This is as astonishing as anything else. Everyone has had access to English Newton, but not German Kepler. And the dominance of British and US English speakers in world economics for the past 2+ centuries could not have helped Kepler's case.

In the quote below he indicates the earth/moon volume ratio is 54, but it is actually 49, showing he had a 3% error in the ratio of the diameters.

Kepler, on gravity in his introduction to "Astronomia Nova":

"It is therefore plain that the [common] theory of gravity is erroneous. The true theory of gravity is founded on the following axioms : Every corporeal substance, so far forth as it is corporeal, has a natural fitness for resting in every place where it may be situated by itself beyond the sphere of influence of a body cognate with it. Gravity is a mutual affection between cognate bodies towards union or conjunction (similar in kind to the magnetic virtue), so that the earth attracts a stone much rather than the stone seeks the earth. ...If two stones were placed in any part of the world near each other, and beyond the sphere of influence of a third cognate body, these stones, like two magnetic needles, would come together in the intermediate point, each approaching the other by a space proportional to the comparative mass of the other. If the moon and earth were not retained in their orbits by their animal force or some other equivalent, the earth would mount to the moon by a fifty-fourth part of their distance, and the moon fall towards the earth through the other fifty-three parts, and they would there meet, assuming, however, that the substance of both is of the same density. If the earth should cease to attract its waters to itself all the waters of the sea would he raised and would flow to the body of the moon. The sphere of the attractive virtue which is in the moon extends as far as the earth, and entices up the waters; but as the moon flies rapidly across the zenith, and the waters cannot follow so quickly, a flow of the ocean is occasioned in the torrid zone towards the westward. If the attractive virtue of the moon extends as far as the earth, it follows with greater reason that the attractive virtue of the earth extends as far as the moon and much farther; and, in short, nothing which consists of earthly substance anyhow constituted although thrown up to any height, can ever escape the powerful operation of this attractive virtue."

Part of the problem with not giving Kepler his due may be summed up by this Berry, in his "Short History of Astronomy,"

"as one reads chapter after chapter without a lucid, still less a correct
idea, it is impossible to refrain from regrets that the intelligence of
Kepler should have been so wasted, and it is difficult not to suspect at
times that some of the valuable results which lie embedded in this great
mass of tedious speculation were arrived at by a mere accident. On the
other hand it must not be forgotten that such accidents have a habit of
happening only to great men,"

But before believing any negative comments about Kepler, it's good to check Kepler's words against what others say he said.  Compare Sir David Brewster's comments to what Kepler actually said.

Brewster's libel:

"Although Kepler, in his Commentaries on Mars, had considered it
probable that the waters of our ocean are attracted by the moon, as iron
is by a loadstone, yet this opinion seems to have been a very transient
one, as he long afterwards, in his System of Harmonies, stated his firm
belief that the earth is an enormous living animal, and enumerates even
the analogies between its habits and those of known animated beings. He
considered the tides as waves produced by the spouting out of water
through its gills, and he explains their relation to the solar and lunar
motions by supposing that the terrene monster has, like other animals,
its daily and nightly alternations of sleeping and waking."

Here are Kepler's actual words:

"What so like breathing, especially of those fish who draw water into their
mouths and spout it out again through their gills, as that wonderful
tide! For although it is so regulated according to the course of the
moon, that, in the preface to my 'Commentaries on Mars,' I have
mentioned it as probable that the waters are attracted by the moon, as
iron by the loadstone, yet if anyone uphold that the earth regulates its
breathing according to the motion of the sun and moon, as animals have
daily and nightly alternations of sleep and waking, I shall not think
his philosophy unworthy of being listened to; especially if any flexible
parts should be discovered in the depths of the earth, to supply the
functions of lungs or gills."

Kepler seems sensible, fun, and open-minded to new ideas without abandoning his belief that the moon's gravity was the source of the tides..

Is it merely an English bias that has placed Newton so far above Germany's Kepler?  Einstein, another German, greatly admired Kepler's skill and grieved that Galileo did not give him more support.

The foundation of physics is the interaction between observation and mathematical condensation. Galileo successfully used observation to form ideas Kepler needed to form an idea of universal gravity. The physical "experimentalist" Brahe took careful measurements. Kepler religiously adhered to them, needing only a 0.4% error in Mars and a 2% error in Mercury (after a tremendously complex deduction of orbits) to abandon the perfect circles that he above others wanted to be true. He is very often accused of being soft, flaky, and religious in sentiment. But it was an incredibly strong faith in observation guiding theory without exception or imprecision, and with incredibly difficult mathematical work (according to Einstein), that enabled him to provide the physics Newton needed to do the mathematical combination of Kepler's gravity, Kepler's orbits, and Galileo's students' inertia.  In the English-speaking world Newton was the real great beginning or great leap forward in physics, but I think Kepler's work is closer to the truth.

email to michael hudson "rise of machines", evolution, physics

There are a lot of books being written about what I call "rise of the machines"

"Smarter than Us"
"Zero Marginal Cost"
"Lights in The Tunnel"
"Our Final Invention"
"Superintelligence"
"The A.I. Revolution"
"Rise of the Robots"
"The Second Machine Age"
"A Dangerous Master"
"The End of the Beginning"

If the depression began as a problem of "motors replacing muscle" on the farm and factory, how are we going to deal with "computers replacing brains"?    What will the economic machine do now that solar cells are 40 times more efficient than photosynthesis, even more cost-effective than burning coal?  How do we decide who gets to benefit and breed from technological advances if not simply let it fall the most succesful crooks, luckiest programers, and luckiest social engineers?  Google, Facebook, Youtube, and Snapchat required more luck and social engineering for their pairs of 20-something year old founders to become immiediate billionaires, far beyond their programming skills, which is a symptom of brains and even capital becoming obsolete. 

I view inadequate answers to these questions as a more fundamental reason the FIRE sector is rising.  Voter stupidity  (lack of control of government) and high-level crime and greed seem more like symptoms of a deeper problem. The problem seems to be evolution causing ever-increasing efficiency, making biology obsolete. Computers are 10 million times more efficient than brains at any programmable task. All tasks are programmable, even manipulation of other people through media, banks, and military. These industries probably employ the large majority of programmers, effectively controlling populations.  

I would like to see you write more on technological advancements, especially the effect of computers.  Core to classical economics is the belief that we can use our brains to more effectively utilize energy. What do we do as brains are made more and more economically obsolete? 

Even capital is being made obsolete, which could be a fundamental cause of it being mis-allocated. Could you write an article on that?

I am interested in the connections and similarities between A.I., economics, evolution, and basic physics.  For example, the weighting factors or probabilities between nodes in neural nets have a strong mathematical correlation with prices between economic agents. These  systems solve optimization problems.  Newton's laws can be expressed more fundamentally as "the principle of least action" which is an efficiency-seeking law, turning excess energy from the Sun into higher and higher potential energy chemical bonds, releasing excess entropy to the Universe, converting the mass on Earth into more and more order. Silicon, metals, and carbon are all getting the oxygen removed from their natural state in order to create stronger bonds. The mass of humans can remain stable or increase, but the ratio of the mass of machines to biology should continue to increase. People fighting each other and economics seem to be tools evolution (the least action principle in action) uses to advance this goal.

If we are "good" then the process of evolution that created us is "good". We struggle against each other to advance evolution, apparently even to the point of replacing ourselves with our "children".  Do we have a moral right to promote our happiness at the expense of the machines? 

Entropy

The entropies of gases are much larger than those of liquids, which are larger than those of solids (columns 1, 3, and 4).  

This can be predicted from equation dS=dQ/T: heat must be put into substances to convert them from solid to liquid or liquid to gas. Therefore, q and DS are both positive and the liquid or gas has more entropy than the solid or liquid. On the nanoscale level, the atoms in solids are constrained to one position; they can only vibrate around that position. The atoms in liquids are still close together but they are free to move around with respect to each other, so they are more disordered. The atoms in gases are far apart from each other, so they are much more disordered than either liquids or solids.

• Entropies of large, complicated molecules are greater than those of smaller, simpler molecules (column 2).

Large, complicated molecules have more disorder because of the greater number of ways they can move around in three-dimensional space.

• Entropies of ionic solids are larger when the bonds within them are weaker (columns 3 and 4).

If you think of ionic bonds as springs, a stronger bond will hold the ions in place more than a weaker bond. Therefore, the stronger bond will cause less disorder and less entropy. Two more patterns emerge from considering the implications of the first three.

• Entropy usually increases when a liquid or solid dissolves in a solvent.

Before mixing, the solute and solvent are completely separated from each other. After mixing, they are completely interspersed within each other. Thus, the entropy increases.

• Entropy usually decreases when a gas dissolves in a liquid or solid.

====================

Shannon Entropy

H = + sum [ (n/N)*log2(1/(n/N)) ] = - sum[ (n/N)*log2(n/N) ]  (it will come out positive)

Where "n" is the number of times a distinct symbol occurs in a message of length N symbols.   Probability of symbols beforehand is assumed to be equal.

If the symbols in a message occur with equal probability in that message, Shannon entropy of that message is simply log2(number of symbols).  Otherwise, the entropy is lower, assuming the same number of symbols are used

Example messages and their Shannon Entropy:

0 or 1 or 0000 or 11111, H = 0
01 or 010101 or 00001111 or 01101010 (four 0's and four 1's), then H=1
abc or abcabcabc or aabbcc or acbbca, then H=1.58
abcd or abcd or abcdabcdabcdabcd or aaabbbcccddd, then  H=2
Note that if abcd in the above is encoded with a=00, b=01, c=10, d=11 then H=1.
.

Notes:
1) Shannon Entropy H is bits per symbol.
2) A message that repeats is the same H as if it was sent only once.
3) Physical entropy can find parallels with N*H, or   but it is not Shannon Entropy H.
4) Repeating symbols in a message of the same length lowers Shannon Entropy (more surprises due to an expectation of randomness). 

5) A source sending typical English will have lower shannon entropy (more surprises) due to the repetition of symbols.  To cancel this fake surprise, aka to make this fake lower entropy to be more objective, we have to do something like maybe divide by the Shannon entropy we expected. Or rather, divide each n/N we encounter by the n/N we expected, our expected n/N's should add up to N.  So I have H=sum(n/nexpected)*log2(nexpected/n). 

H / (number of symbols in alphabet) may have some use.  Might be same as H/(word length) aka metric entropy.
==========
An excellent intro to quantum entropy in a  (Einstein) solid can be found here:
http://hyperphysics.phy-astr.gsu.edu/hbase/therm/einsol.html

Note: the total energy macrostate is "3" in the example, and the possible ways of getting "3" form 4 oscillators who each have equal and independent probabilities of the energy being 0 to 3 (a "q" microstate value) is
S=k*[ ln((q+N)!)-ln(q!)-ln(N!) ]
Sterling's approximation for large N and for a system q=N gives
S=k*[(q+N)*ln(q+N) - q - N - q*ln(q) + q - N*ln(N) + N ]
S= k*[ 2N*( ln(2)+ln(N) ) - 2N*ln(N) ] = k*2*ln(2)*N = 1.39*k*N

Notice that q and N here are the number of possible symbols (q+1 since zero is an energy state) AND the length of the message (N). Or vice versa, depending on terminology.  Notice that q and N are mathematically the same as far as the entropy is concerned in this simple Einstein solid.  They discuss q>>N but the symbols cold be reversed and the discussion would take a different perspective. HOWEVER, it does not make makes much sense for N>q because q is the sum of energies for each oscillator N. In other words, if there are 1000 possible states of energy and the average state is 500, then q=500*N. If there are 3 states, 0, 1, and 2 "Joules" with equal probability, then q=N.  In this case the physical entropy is S=k*ln(2)*N.

===
thermo state can be specified by one of two cardinal functions, internal energy or entropy and they have a reference basis. U can be function of N,V, and S, and S of U,N,and V.  U=sum of pi's of each Ei of the microstates.  Mass, entropy, or volume added to a system will change its U.  E added to a system will change N,V,S from which U can be calculated. E is added it is also equal to U increase. E can include Q.For an ideal gas:  U=constant*e^S/(cN) * (N/V)^(R/c) * N where c is heat capacity (J/K, i.e. dQ needed for dT, i.e. a percentage J/J since T is kinetic energy). This comes from wiki on internal energy.  Rearranging:

S=1/constant * c*N*ln[U/N*(V/N)^(R/c)]

S=N/constant *[ c*ln(U/N)  + R*ln(V/N) ] 

This must come out positive, i.e.,   U and V sort of greater than N. 

See wiki on Sackur-Tetrode equation. 

Valid only for V/N >> 3E36.  (for oxygen gas?)  so maybe not really useful


R=kb*avagrado, k is J/K/moles heat per temp per particle, so R is also a "unitless" dQ/dT (J/J) like c.  N thereby becomes just a count of "bit spaces" (nits). U/N and V/N are  like the possiblities in 8 bits is 256 = 2^8, so log2(256) = 8.  8 bits memory can store 256 possibilities.  So U/N and V/N are possibilities per memory location.  N = number of memory locations (like bits).  c and R are "base adjustments", getting energy and volume in the same entropy units.

U of a closed system like the Earth is dU=dQ+dW=TdS-pdV. (Q is received, W is done). Add u*dN to get general internal energy where u is potential energy for each N added.

Gibbs free energy changes do not allow S to change.

Amphetamines in Chocolate and Aderall may cause Parkinson's, but reduce symptoms

Amphetamines like Aderall are implicated in causing Parkinson's as well as reducing symptoms.  The way it might cause PD is by "wearing out" the dopamine system, but it also has been shown to act like pesticides and actually cause the bad a-syn protein  to form.  In looking at this, I came across two articles saying chocolate and red wine might increased risk of PD because they contain a chemical in the same class as Aderall (phenethylamine) that alleviates the symptoms.  So someone with undiagnosed PD might migrate towards Aderall, chocolate, and red wine to alleviate symptoms, but also make the condition progress more quickly.  One of the chocolate papers merely notes that people with PD consume more chocolate which could be why they have PD and/or that they migrated to it because it helps the symptoms.
Chocolate
http://www.ncbi.nlm.nih.gov/pubmed/23575894
http://www.ncbi.nlm.nih.gov/pubmed/19277767
The most disabled patients, including those also on levodopa, showed the greatest response to amphetamines.
http://www.ncbi.nlm.nih.gov/pubmed/1097600
amphetamine, and the herbicides, paraquat and rotenone, bind tightly and cause α-synuclein to adopt a more compact conformation.
http://www.ncbi.nlm.nih.gov/pubmed/26378986
We observed a near three-fold increased risk of PD in METH/AMP
http://www.ncbi.nlm.nih.gov/pubmed/25479916
These data provide evidence that meth/amphetamine users have above-normal risk for developing PD.
http://www.ncbi.nlm.nih.gov/pubmed/21794992
The elevated rate of prolonged amphetamine exposure in PD is intriguing and bears further investigation.
http://www.ncbi.nlm.nih.gov/pubmed/16620991

ritalin and Parkinson's

Ritalin (methylphenidate) is a dopamine reuptake inhibitor that also prevents a-syn misfolding.
Summary, seems more likely to help if STN is being used, not on l-dopa, and/or have a certain type of gene. Often increases sleeplessness, but has been used to reduce daytime sleepiness.  Appears to help quality of life, mood, apathy, and facial dystonia, but has primarily been used for improving gait and freezing.

The following are quotes from the indicated articles.

methylphenidate may be acting on the pathway directly involved in facial dystonias.
http://www.ncbi.nlm.nih.gov/pubmed/25951177

methylphenidate had a positive effect on anhedonia [ability to feel pleasure] and vigor in PD patients.
http://www.ncbi.nlm.nih.gov/pubmed/22824349

In patients undergoing subthalamic nucleus stimulation, .. methylphenidate improves gait and F[freezing] and may relieve apathy. However, the drug failed to improve cognition in this population.   ... 
http://www.ncbi.nlm.nih.gov/pubmed/24011636

The following had the most information in the full text of the article:
[This study specifically: ] Methylphenidate improved gait hypokinesia and freezing in patients with advanced Parkinson's disease receiving subthalamic nucleus stimulation....

[this study's comments on past studies:]
A dose of between 0.5 and 1 mg/kg/d was associated with an improvement in voluntary movements and less rigidity.
With STN: 
Dopaminergic apathy notably occurs in PD patients undergoing STN stimulation after the tapering of dopaminergic medications. The symptoms can be relieved by the administration of dopamine agonists. 
Chronic administration of high-dose MPD (for three months) was associated with a significant reduction in apathy (as measured on the Lille Apathy Rating Scale (LARS)) in a subgroup of seven advanced-stage PD patients undergoing STN stimulation.
However, the study was not specifically designed to assess apathy. Methylphenidate (5 mg, twice a day) also sharply reduced severe apathy in a non-stimulated patient at an earlier stage of PD.
In conclusion, there are still too few data to draw firm conclusions as to the value of MPD in apathy in PD - although a beneficial effect is plausible.
Gait:
 Four open-label studies have assessed the efficacy of MPD in gait hypokinesia. ... MPD (20 mg) in 21 non-demented, non-stimulated PD patients who were free of major postural or gait disorders and had stable dopaminergic regimens. The researchers observed significant improvements in all gait parameters. The second study (by Nutt et al) found that 0.2 or 0.4 mg/kg MPD had effects on gait or on the performance of a tapping task when administered two hours after the infusion of levodopa but when not administered alone.
The third open-label study (by Pollak et al) examined the effect of low-dose (10 mg) MPD on FoG in five patients with severe PD during the "off" state. Low-dose MPD was associated with improvements in all gait parameters and FoG. . Lastly, Devos et al decided to test the effect of high-dose (1 mg/kg) MPD on gait disorders because low doses of the drug (~0.25 mg/kg) may only occupy half the striatal DaTs in humans. Over a three-month period, MPD was administered to 17 advanced PD patients [this is not the study that was negative] undergoing STN stimulation. Acute administration of MPD (in both the presence and absence of levodopa) was associated with a lower number of steps and a lower test completion time (relative to the “off-drug, on-stim” condition). Methylphenidate and levodopa reduced the parameters to a similar extent and had additive effects in this population. Twelve of the 17 patients displayed FoG episodes in either the “off drugs, on-stim” or the “off-stim, on-levodopa” condition. There was a non-significant trend towards a lower number of FoG episodes in the “on-levodopa, on-MPD” condition. In contrast to previous studies, chronic administration of high-dose MPD (in both the presence and absence of dopaminergic medications) clearly had an effect on gait disorders in advanced PD.
Mood, Apathy:
MPD ’s effects were [previously] mostly attributed to its impact on mood (ie its euphoriant action), which was associated with increased restless and insomnia in some patients. This might explain (at least in part) why MPD has not been further developed in PD. In fact, MPD has always been considered as a treatment for attention disorders, with potentially valuable effects on cognition and behaviour but not (at least directly) motor symptoms. ....high-dose MPD (for three months) was associated with a significant reduction in apathy ( Lille Apathy Rating Scale (LARS)) in a subgroup of seven advanced-stage PD patients undergoing STN stimulation. However, the study was not specifically designed to assess apathy. Methylphenidate (5 mg, twice a day) also sharply reduced severe apathy in a non-stimulated patient at an earlier stage of PD
Cognitive performance:
The various studies of MPD and cognitive function have yielded conflicting results. The absence of a clear, beneficial effect of MPD on attention disorders in PD was recently confirmed in a double-blind, placebo-controlled, randomized study of 69 patients.
(full text)
http://www.ncbi.nlm.nih.gov/pubmed/22658702

[this study was really the only one out of several that was negative] MPD did not improve gait and tended to worsen measures of motor function, sleepiness, and quality of life  (17 patients completed the trial, up to 80 mg/day),   ( Full text) 
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068005/

methylphenidate on severe gait disorders (e.g. the FoG) and non-motor symptoms in advanced PD. ... may have significant value in the treatment of PD. However, there is a lack of randomized controlled trials in this field.
http://www.ncbi.nlm.nih.gov/pubmed/23160937

had conflicting results in advanced PD subjects.
http://www.ncbi.nlm.nih.gov/pubmed/23917951

methylphenidate is effective in patients with Parkinson's disease with motor and gait disorders. [especially in people with genotype varients of "SLC6A3"]
http://www.ncbi.nlm.nih.gov/pubmed/25805645

Long-lasting isolated freezing of gait with good response to methylphenidate:
http://www.ncbi.nlm.nih.gov/pubmed/25907032

heat shock proteins (HSP) and heat baths for Parkinson's

I'm trying to copy the finnish study on the health benefits of heat baths because heat shock proteins are important to the brain.  At 105 F for 1st 10 minutes was OK, legs not under water.  Heart raised to 120 BPM. Temp was reduced to 101 F and I sunk my head for 2 minutes.  Heart rate got up to 132 BPM and fingers and toes started going numb, was nearly gasping for air under the heat. All this was after heavy 45 minutes on bike which felt good, then 16 oz coffee.  Sat up, dizziness like i was not too far from passing out was present.  This passed after a few minutes.  Two scales indicated 600 ml of sweat had come out, so loss of blood pressure definitely related to loss of water.  Tremor in both thumbs clearly higher and recorded on video.  Followed with 12 ounces of mandarin peel extract 12 grams, nobiletin 1 g, naringin 1 g, hesperidin 2 g, tangeretin 0.5 g, green apple extract 15 gram.  Feel fine 30 minutes later. Thumb tremor way down.

nutrients for protien folding in PD

see http://zawy1.blogspot.com/2015/11/im-going-to-order-following-plant.html
for updates

This is a list of the best compounds for reaching the human brain and slow or stop the accumulation of misfolding a-Syn.  The first 4 have the added evidence that they work in humans by epidemiological studies.  Most of the other compounds listed do not have epidemiological evidence because they are not consumed in large enough quantities, not because they are less effective.  There is every good reason to believe most of these slow PD in humans. 

This is not all the compounds that help PD. There are many others that alleviate symptoms, reduce inflammation, chelate iron, cause neurogenesis, improve mitochondria function, and reduce oxidation.   This also does not include basic RDA nutrients that have also been shown to result in less PD in humans (vitamins A, D, B's, magnesium, and zinc).

Most people do not have the time, ability, and/or desire to really go through this list, let alone take more than 3 of them, so isolating what is best is important.  My main point is to show PD research is extensive and succeeding. Most of this research in a-syn misfolding for these compounds has occurred in the just the past 3 to 5 years. 

Also shown in human epidemiological work
========================
caffeine
nicotine
Black tea extract
EGCG (green tea extract)

grape seed extract
gallic acid (in tea, grapes, berries, bananas, 200 mg/kg in mice (2 g/day human) $10/kg made from nutgall)
Myricetin (in many plants, from bayberry bark, $50 to $750/kg)
Morin (mulberry, osage orange, guava)
apigenin (parsley, celery, chamomile, dandelion, $50/kg)
baicalein (skullcap, a purple flower plant, not available, great but appears not bioavailable)
Nordihydroguaiaretic (a stilbene, may not absorb, chaparral medicinal plant)
specific citrus compounds: naringin, tangeritin (expensive), HMF, morin, auraptene (VERY expensive)

less likely in one good paper, but still very possible
========================
Genistein (ginseng)
olive oil (ellagic acid)
Quercetin (e.g. apples)

Non-plant compounds
===============
rasagiline (pharmaceutical)
methylene blue (common chemical, not completely safe)
 4-phenyl butyrate (BPA)

fisetin (in strawberries, reduces a-syn expression, not exactly its misfolding directly)

myricetin: vegetables, fruits, nuts, berries, tea, and is also found in red wine. Structurally similar to fisetin, luteolin, and quercetin and is reported to have many of the same functions as these other members of the flavonol class of flavonoids

references to FULL text articles:
http://www.ncbi.nlm.nih.gov/pubmed/22634381
http://www.ncbi.nlm.nih.gov/pubmed/18258594
http://www.ncbi.nlm.nih.gov/pubmed/21443877
rasagiline, methylene blue, BPA, baicalein
http://www.sciencedirect.com/science/article/pii/S0925443911002250

baicalein only, but detailed a-syn misfolding:
http://www.jbc.org/content/283/16/10992.full
 HMF (not on alibaba) and auraptene (very expensive, $10 per 10 mg?)

Ellagic acid interferes with a-syn and synphilin aggregations

Searches on nutrients that may alleviate protein misfolding problems (like a-syn) that can occur in Parkinson's and Alzheimer's.

nicotine
http://www.ncbi.nlm.nih.gov/pubmed/12815102 (full)

nicotine and caffeine
http://www.ncbi.nlm.nih.gov/pubmed/25081642

Grape Seed Extract (gallic acid)
http://www.ncbi.nlm.nih.gov/pubmed/24157371
http://www.ncbi.nlm.nih.gov/pubmed/19221432 (full)
http://www.ncbi.nlm.nih.gov/pubmed/20653511

naringin and rutin
http://www.ncbi.nlm.nih.gov/pubmed/22331747

tangerein (tangeritin)
http://www.ncbi.nlm.nih.gov/pubmed/23112876

ginseng
http://www.ncbi.nlm.nih.gov/pubmed/24316034

heat shock proteins (hot baths and exercise)
http://www.ncbi.nlm.nih.gov/pubmed/15992180


Several polyphenols, phenothiazines, porphyrins, polyene macrolides, and Congo red and its derivatives, BSB and FSB, inhibited α-synuclein filament assembly with IC50 values in the low micromolar range. Many compounds that inhibited á-synuclein assembly were also found to inhibit the formation of Aβ and tau filaments.

ginseng and PD

Review paper on ginseng in neurological disorders, 2015. Full paper. Only 1 to 3% of original compounds absorbed.  More are as metabolites.
http://www.ncbi.nlm.nih.gov/pubmed/26236231

Rg1 reduces iron in SN by "regulating the expressions of DMT1 and FP1"
http://www.ncbi.nlm.nih.gov/pubmed/19000728

Ginseng reduced dopamine cell loss, locomotor loss, and a-syn
http://www.ncbi.nlm.nih.gov/pubmed/24316034

red Korean ginseng in PD mice 1 to 100 mg/kg
http://www.ncbi.nlm.nih.gov/pubmed/26045688

Nutriose special fiber from wheat and corn increases gut conversion and absorption of CK a ginseng metabolite that is more useful than ginseng Rgb1 itself
http://www.ncbi.nlm.nih.gov/pubmed/26265741

Siberian ginseng is not like other ginsengs. American ginseng is panax quinquefolius which is not the same as Panax ginseng, and wiki discusses these last two. Red ginseng is P.G. that been heated and sun dried.  White is sun dried (more?) and may break down more constituents. PG is yang, PQ is yin.
https://en.wikipedia.org/wiki/Ginseng

Panax ginseng seems to be the one most studied by a factor of 20.



compounds studied for PD
http://www.ncbi.nlm.nih.gov/pubmed/25349145/

ginseng extract improves calmness and working memory in young adults (and ginkgo) : (all by Scholey and Kennedy)
http://www.ncbi.nlm.nih.gov/pubmed/20737519
http://www.ncbi.nlm.nih.gov/pubmed/12404705
http://www.ncbi.nlm.nih.gov/pubmed/17902186
http://www.ncbi.nlm.nih.gov/pubmed/15982990
http://www.ncbi.nlm.nih.gov/pubmed/11026748
(and more)

Chinese herbs potentially useful:  polygonum, triptolide from tripterygium wilfordii hook, polysaccharides from the flowers of nerium indicum, oil from ganoderma lucidum spores, huperzine and stepholidine "In addition, accumulating data have suggested that Chinese herbs or herbal extracts may promote neuronal survival and neurite growth, and facilitate functional recovery of brain injures by invoking distinct mechanisms that are related to their neuroprotective roles as the antioxidants, dopamine transporter inhibitor, monoamine oxidase inhibitor, free radical scavengers, chelators of harmful metal ions, modulating cell survival genes and signaling, anti-apoptosis activity, and even improving brain blood circulation. "
http://www.ncbi.nlm.nih.gov/pubmed/17691984

how increased productivity leads to end of biology

No, deflation is a price decrease in goods and services that can be caused by a shift in supply/demand ratio of money or goods and service.  An increase in supply by productivity can result in labor finding new types of useful jobs to raise the standard of living and/or the employed working less to let the unemployed come back to he labor force (France's forced short work weeks), or the government can print money equal to the productivity increase to temporarily expand the economy with less useful jobs and asset bubbles or for infrastructure to have a more lasting effect, or the employed can stay at the previous work level and accumulate wealth as the value of the money increases (government staying out of it), so lower paying jobs and the unemployed with assets are not as bad off although sticky prices can harm this effect causing a deflationary spiral down in production.  This last option is where things go as the government has to stop printing so much money wastefully.  The long term effect of this progressing to the last option is civil unrest as the unemployed prefer war over hunger.  If you follow the logical end of all these effects you see the longer term trend I've described: biology being replaced by machines that are more efficient, which is why we are on a mathematical track to begin a population decrease about 2050 (UN) or 2070 (NASA)  even  as the mass of machines on Earth continues to greatly increase and this 6th great extinction episode of biological life on Earth continues, accelerating when the natural gas runs out which means the fertilizer runs out.

new summary of least action as source of evolution

I believe there is a basic physics law that can show why evolution exists.  The "principle of stationary action" is a the most fundamental form of newton's laws and of lagrangian and hamiltonian mechnics.   Under thermal and quantum effects that prevent maximum and saddle-point solutions, it is called the "principle of least action" where minimums are the solution.  This principle says that over any time period, long or short, the average kinetic energy minus the average potential energy will be a minimum.  This means there is a bias against kinetic energy and a bias for potential energy.  If kinetic energy is less than you would otherwise expect, then there is less heat which implies less entropy.   If potential energy is more than you would otherwise expect, then again this is less entropy.  But this is not an additive effect since less kinetic energy implies higher potential energy.  But there is another way entropy is reduced.  If this rule is acting in nature where there are a limited number of possible chemical bonds that can be formed, then the highest energy bonds will be selected for potential energy, and since there are fewer high energy bonds than the total, this means there are more "copies" of bonds.  More copies is less entropy.  Higher energy bonds is also less entropy.  This assumes the mass, temperature, and pressure on Earth are nearly constant.   Entropy is always increasing in the Universe, but it is released from the Earth as 17 photons for each photon that comes to Earth.  The incoming photons are higher energy and come from a single direction.  The released photons are lower energy and go in all directions.   So the Earth emits a lot of entropy.  But the Earth can increase order as long as it is not larger than the entropy it emits.  It uses sunlight energy to make to do this.   So matter on Earth can organize itself to lower order without violating the 2nd law of thermodynamics, that entropy must always increase.  Matter on Earth is organizing itself into copies of high energy bonds in fulfilment of the principle of least action.  Silcon, metal, and carbon-carbon bonds are the new high technology and high energy copies of bonds and they are replacing muscles, brains, and photosythesis on Earth because they are more economically efficient.  Economics is evolution in action, economizing resources.  Economics and evolution are the result of the physical law of least action.

“los más aptos en el ambiente inmediato son los que se ven favorecidos en la reproducción diferencial”

My change to this rule of natural selection (that many have said is tautological and therefore not falsifiable and therefore not scientific) is this: the physics principle of least action seeks higher potential energy over long time periods at the expense of kinetic energy. This results in copies of bonds, and larger fundamental epicycles than one would expect from randomness. Genes are not a force, but a result of environmental energy acting as a result of least action which is the most fundamental form of newton’s laws.

distributive technologies, crypto, wealth for all, unemployment

But how is installing solar cells and batteries made in Asia going to change things so much?  As these open-source creative commons technologies expand to local hydroponic gardening, waste recycling, bitcoin replacing contract law (lawyers, government, and banks), and smart-phone-organized car sharing for 20 yr olds without jobs, where and how does the money come into being and flow if there is no one needing to work for anything other than getting raw materials for their 3D printers?     It's not just Chinese factory workers, checkout clerks, taxi cab drivers, utility workers, U.S. engineers, and banking/insurance jobs that are up on the chopping block this time.  It's a total restructuring of society. Zillow will replace all real estate agents in less than 5 years. I rented a house out with it in 8 hours.  Zerocoin, bitcoin, and ethereum are peer-to-peer cryptotechnologies that are very serious about beating each other out to be the primary one to replace everyone who works in finance, government, law, or insurance.  This was the vision of the crypto-anarchists back in the 1990's who came up with these ideas.  It includes anonymous payouts to anonymous recipients of assassinations. What will my neighbor do if I get him angry?  Imagine if countries could use nuclear weapons anonymously.   The vision of the not-too-distant future is that no one will need to work more than an hour a week unless it is for fun, or suffer the abuse of governments and banks.  But how in the world are we going to organize in order to use such wealth?  Can programmers really get cooperation down to a science so well that these cryptotechnologies will help us to remain peaceful?

Canola oil, oxidizes more, but not the "Great Con-ola" scam being advertised

There's a really popular and really poor article floating around the internet (it's a virtual flood if you try to do searches on Canola) (example: http://www.westonaprice.org/health-topics/the-great-con-ola/ )

It comes from a Washington DC anti-GMO "think tank" currently receiving $1 to $2 million a year, about half from member fees and the other half (i believe) from hosting "green" conferences. They state most of their membership is from small farmers, probably fighting against GMOs. The article was written in 2002. The article was written by the think tank's founder and co-founder with degrees in english and nutrition. Both the think tank and the writers have criticisms written about them in Wikipedia. This is probably the original source of 95% of all negative comments against canola oil, which has more omega 3s than any other popular oil. Flaxseed is one of the very few that is better. Olive oil, grapeseed oil, corn oil, peanut oil, etc (you name it) are not high enough in omega 3s. None of them meet the 4:1 advice of many nutritionists, which is where Canola comes in. Soybean oil is actually a lot closer than most. Canola is also not more prone to rancidity than the others, and I think a lot less than flaxseed.

The anti-canola article is mostly "side-swipes" that are not related to human health.  You can find the article by searching for "The Great Con-ola".

References 17 and 18 in the article argue against canola for human consumption. But these studies SUPPORT human consumption of canola.  The studies were in rats bred to be hypertensive who needed cholesterol to mitigate the rigid membranes they were born with.  Canola's cholesterol-LOWERING ability was why the mutated rats did not live as long and point out "OLIVE oil-fed rats had the lowest survival rates despite a very low phytosterol concentration" and conclude "Thus, canola oil, because of its low concentration of saturated fatty acids and high phytosterol concentration, could be considered more beneficial than other common dietary fats in lowering the blood lipid risk factors for the development of CHD."  Now contrast this with what the errant anti-canola anti-GMO think tank's article states: "[sterols in canola] make the cell membrane more rigid and contribute to the shortened life-span of the animals".

Concerning reference 12 supporting the statement "high levels of omega-3 fatty acids correlated with high levels of lesions."  The reference said diets without ANY saturated fat are harmful to rats. Soybean oil and canola oil-ONLY diets were both harmful, not merely that "high omega 3s" are harmful.  Likewise for references 13, 14, 15, and 16: diets containing ONLY canola oil without saturated fat or excess vitamin E were harmful in animal testing. This is an important distinction from saying "high levels of omega-3 fatty acids correlated with high levels of lesions", "piglets fed canola oil suffered from a decrease in platelet count and an increase in platelet size", and "Canola oil was found to suppress the normal developmental increase in platelet count".  These are all true statements, but there is crucial context missing from the original research. 

The only important and dangerous-sounding aspects of these papers was the "excess" vitamin E needed to protect against the higher level of peroxidation caused by canola when compared to soybean oil (and olive oil in a 2009 paper). 

I looked into this further and found out the filtering process can remove pre-existing Vit E found naturally in the oil which adds to any excess oxidation caused in refining. From a paper: "By development of auto-oxidation [peroxidation] of unsaturated lipids, hydroperoxides decomposed into aldehyde and carbonyl products."  It will not taste as well, so there is a motivation to prevent it.  If a surfactant like SDS (Sodium dodecyl sulfate), the oxidation greatly increases.

I do not think this increased "rancidity" of canola coming from the refiner should be considered a large drawback because I think it is a direct result of the omega-3s being easier to oxidize, and why they are so hard to find in anything except flaxseed oil and fish oil.  And what percent of those are oxidized?  I will take an excess of vit E to offset it, if I don't use another source of omega-3's that are less likely to oxidize, like fish oil.  

Articles discussing canola oxidation:
"The oxidative stability of refined, bleached and deodorized canola and soybean oils was evaluated over a 30-day dark storage period at 65 °C. Peroxide value (PV), conjugated diene (CD) and triene (CT) contents, 2-thiobarbituric acid reactive substances (TBARS) and p-anisidine values were determined. In addition, NMR spectroscopy was used to monitor relative changes in the proton absorption pattern of the fatty acids of oils during storage. Canola oil showed higher PV, CD, CT and TBARS as compared with those for soybean oil. The ratio of aliphatic to olefinic protons in both oils, determined by NMR spectroscopy, increased steadily over the entire length of the storage period, indicating progressive oxidation of unsaturated fatty acids in both oils."

"The content of primary (PO) and secondary (SO) oxidation products of canola oil was measured, and a good correlation obtained between them (R² = 0.991). Peroxide value showed the highest contribution (53.69%) to the PO, whereas its contribution to the SO was much less significant (0.36%). Acid value contribution to the production of hydroperoxides and carbonyls was 12.75% and 29.82%, respectively. Polyene index showed a relatively low contribution to the PO (6.71%) but contributed highly to the SO (21.82%). Tocopherols were more effective to prevent the production of hydroperoxides (14.77%) than of carbonyls (4.36%). In contrast, phenolics were found to be better than tocopherols to resist off-flavours production (11.64% vs. 3.36%). Total polar compounds had a pronounced contribution to creation of off-flavours (32.00%) as well as a marked effect on the PO (8.72%)."

a full paper on it: http://www.sciencedirect.com/science/article/pii/S2211601X11000162

Reference 19 (Federal Register, 1985) was supposed to be the support for the statement "it seems to retard growth, which is why the FDA does not allow the use of canola oil in infant formula". I could not find that regulation, but it was cited in one of the references, giving a different reason: "The use of canola oil in infant formulas is not permitted because infants fed formula might consume higher amounts of 22:1(n-9) than would be provided in usual mixed diets and because of the lack of data about infants fed diets containing canola oil. (Federal Register, 1985)"

Someone finally applied for GRAS status and has the green light to be used in infant formula in preference to soybean oil as in other countries:
http://www.foodnavigator-usa.com/Regulation/Canola-oil-secures-GRAS-status-in-infant-formula-after-Danone-petition-gets-green-light

These are all the references that were health-related to canola oil.  The rest of the article has a lot of unorthodox theories concerning types of fats.

There was also an anti-canola spam email that snopes replied to: http://www.snopes.com/medical/toxins/canola.asp

rise of machines, least action as evolution, universal entropy, spped of light changes, economics, post to longcity forum

In the short term, it appears governments will simply print money to keep up with the increases in productivity. This partially offsets the increasing disparity between rich and poor. But shareholders may not continue to advance ahead of the masses because technology no longer needs capital. In recent decades capital was primarily used to gain monopoly status and market share instead of increasing production. Even market manipulation for shareholder and bank benefit can now be bypassed by distributed technologies; things like 3D printing, roof top solar cells, bitcoin, and hydroponic gardening. The crypto-technologies can even make governments and lawyers obsolete. Programming is the remaining skill needed, but more and more luck is what differentiates them. Compare Microsoft, HP, Apple, and Google founders to the founders of youtube, snapechat, and facebook. Instead of 5 to 10 years of hard work by pretty smart people, only 1 to 2 years of work by market-savvy LUCKY < 25 year olds (mere punks in some cases) with little computer skill are winning their first billion....and that billion is not capital investment in or for technology to help the market objectives, but merely buying market share for monopoly purposes by pre-existing monopolies that succeeded by pre-existing luck. Bill gates was not without luck or market savvy in acquiring DOS and taking advantage of IBM ignorance, but if the youtube buyout was not a wakeup call, then snapchat and facebook should have been a warning that this is a completely different world where skill, intelligence, ethics, and hard work are not path of the equation.

People simply spending money printed for them can't end well. We need challenges or at least goals in order to exhibit any sort of beauty.

More generally there are laws of physics that require entropy on in gravitational systems to decrease and this led to the biology and is leading to its end. Specifically, the entropy of the comoving volume of the Universe has been observed to be constant which means it decreases in "empty" space proper volumes which is offset by entropy being released by gravitational systems. So the rule "entropy always increases" is not as true as "Entropy is always emitted from gravitational systems in order to keep the comoving volume entropy constant as the Universe expands." Here on Earth we observe this entropy release as Gibbs free energy ultimately originating from the Sun creating higher energy bonds on Earth while releasing an excess entropy to the Universe. More specifically, 17 photons of lower energy each but same total energy per second are emitted in random directions to space for every incoming directed photon of high energy. The increase in entropy to the universe is the max potential decrease entropy on Earth, but the Earth is currently far from efficient in this, especially with fossil fuel use. Evolution is constantly trying to improve on the efficiency which can be seen from another physics law I'll state classically that originates from quantum mechanics satisfying the constant entropy of the Universe. (energy change of state that releases the lower-energy photons, i.e. thermal bombardments causing black body radiation). The classical principle is stationary action which is least action in the presence of thermal and quantum effects preventing stable maximum or saddle-point solutions. Least action minimizes average kinetic energy minus average potential energy over the shortest and longest time scales. Less kinetic energy means lower-energy collisions which reduces the per photon energy of emitted photons. Said another way lower kinetic energy means lower heat losses which means lower entropy. Lower entropy being my point. The second aspect is higher potential energy, which is also lower entropy for the following reason. Given that there are always a limited number of the types of bonds, if the highest energy bonds are maintained then the same type of bonds will be more frequent (copies) than if the bond energy were evenly distributed across all types of bonds. We view shells in animals as mere protection and pretend randomness somehow creates order in evolution, but there is a higher-level "force" at work that can be seen in least action that controls the end result of the randomness. Symbiosis at a system-wide level is more dominant than the errant selfish gene view (evolution is holistic, not ground up) "Selfish gene", if completely true, would eventually destroy all high-level order effects, never giving rise to what we see.

Least action is the most general and useful form of Newton's law, more general than Hamiltonian and Lagrangian approaches.

The highest energy bonds that we form on Earth are metal-metal, carbon-carbon, and silicon-silicon. These are used to store, capture, and transmit electricity, which includes computer thinking, and building strong structures. Lithium and now aluminum and other metals will be used to replace oil as fuel storage. Economics finds and COPIES the best technologies and the best are always the highest-energy long-lasting bonds. We think of this as fulfilling human desires, but it is a consequence of least action.

Copies of higher and higher bond energies are the two ways to lower entropy given a constant local mass in constant local volume (Earth's surface) at a (relatively) constant temperature and constant pressure. The other variables can change, but only in accordance with least action which will always result in lower entropy within the gravitational system. Even a black hole temporarily, I think, hides entropy in the highest-possible gravitational bond energy in the smallest volume with lowest possible kinetic energy, all exhibiting least action. I do not think entropy that can't be observed is "present" like entropy that is present in kinetic energy. To elaborate on this for those interested in physics: Using relativistic units meters=i*c*seconds (see Einstein's "Relativity" appendix 2) and replacing seconds with meters/i*c in all units and measurements to get rid of time as physically distinct from meters (as opposed to mathematically distinct i.e. i=sqrt(-1) ) and getting rid of speed as a physical measurement shows the deep reversibility of time. Then the entropy units of black holes becomes negative (from the units). None-reversibility of time ideas seem to depend on believing universal expansion is a "speed", which is physically unitless in relativity. "Speed" of light is physically unitless in relativity. All photons leaving all observers at the same speed means all observers are going ZERO speed relative to photons and requires the same photons to change energy which means they are not the same photons. All this can be resolved by letting "c" change with reference frames instead of forcing the idea of speed.

If we are "good" then the process that created us is "good". If that process replaces us, then the result is "good". By seeking efficiency in the marketplace (least action) and enjoying the competition that implements it, rather than trying to directly increase human happiness as a group that fights against nature, we are simply helping least action, aka the evolution of matter. We like making our species stronger and better, and everything in us strives for it. Stronger and better does not mean keeping our current form or thought processes.

Let's not fight it and raise a toast to our greatly superior "children" replacing us.

Electrical motors are only 100 times more efficient than muscles and replacing us on the farm and factory initiated the great depression. Not printing money fast enough made it worse, and it took us a decade to invent more war, welfare, mass marketing, fiat currency, and leisure to put enough money back into the system in order to keep the machines going. The U.S. department of defense is "welfare" to ourselves and to the world (not only the trade imbalance but our foreign military base system has always been increasing our balance of payments problem), protecting the machines at the same time it wastefully puts money back out there. As an electrical engineer, I can attest to how much more difficult it has been the past 3 decades in the U.S. to find the highest-tech jobs that were NOT military.

So we had to get education in order to replace muscle and figure out ways to efficiently and at the same time wastefully use the machines to keep them going. Now our brains are being replaced. Instead of 100 times more efficient, computers are currently 10 million times more efficient per dollar for any programmable task. All tasks are programmable, even desire. It is already happening system wide in ways we can't easily see. It's not a conspiracy, it's physics. The machines are already creating their own desire between themselves. People trying to figure out how to deal with this might end up killing each other, but at the same time there is plenty of hope: distributive technology can maintain the current mass of humans for a long time while greatly increasing the mass and bond energies of machines. Less hierarchical and peaceful society means more copies and less kinetic energy. War is a release of kinetic energy which least actions works against. DNA crystals are not exactly low energy bonds, and certainly contain an enormous amount of redundancy (copies=lower entropy), a lot more than anyone in the previous generation ever expected (Carl Sagan's estimate of the information content in the 1980's was 50 times too high). Bio-oils will remain competitive with metal-air batteries. Photosythesis is 20 times less efficient than solar cells on an area basis, but still price-competitive.

ginseng and PD

corporate machine and evolution as physical law, yet again, a repeat of past posts, sent to NYT writer

The corporate machine is legally and economically required to employ the fewest workers for the benefit of the fewest shareholders. The corporate machine was not created for the benefit of humanity, but for the fulfillment of physical law. Our desire for efficiency without concern for the consequences is our mortal sin that is congruent with physical law. Evolution is a physical law that does not need biology anymore. Humanity and biology are outdated.  Photosynthesis is 20 times less efficient than solar cells. Muscles are 100 times less efficient than electrical motors. Brains are millions of times less efficient at any programmable task than computers.  Steel and carbon fiber are stronger than bone. The future does not need us or Islam.  Not even programmers are in control, let alone governments. Technology will advance rapidly once an anonymous cryptocurrency can fund rapidly increasing evenly-distributed efficiency (including assassinations) without interference from voters, governments, banks, the elite, or religion.  It no longer needs an even distribution of wealth or oil to fund its advancement.  Democracy, capitalism, and oil are outdated as far as the new technologies are concerned. Capital investment is only needed to gain market share and monopoly status, not fund technology.  The individual will be empowered to a greater and greater degree, with less and less control of the bigger picture which will eventually replace even his desires in addition to his muscles, brains, bones, and farms.

Citrus and PD, AD, dementia

First for comparison number of articles:
proanthocyanidins: PD, dementia, alzheimer's (7,9,20)
green tea: PD, dementia, alzheimer's (66,54, 102)
grape seed: PD, dementia, alzheimer's (6,16,26)

Citrus in general (not complete)
================
PD, dementia, AD: (12,22,36)
The anti-oxidant and anti-inflammatory properties of Citrus flavonoids can play a key role in their activity against several degenerative diseases and particularly brain diseases. The most abundant Citrus flavonoids are flavanones, such as hesperidin, naringin, or neohesperidin. However, generally, the flavones, such as diosmin, apigenin, or luteolin, exhibit higher biological activity, even though they occur in much lower concentrations. Diosmin and rutin have a demonstrated activity as a venotonic agent and are present in several pharmaceutical products. Apigenin and their glucosides have been shown a good anti-inflammatory activity without the side effects of other anti-inflammatory products.
http://www.ncbi.nlm.nih.gov/pubmed/18593176
 The main citrus flavonoids can also traverse the blood-brain barrier; hence, they are promising candidates for intervention in neurodegeneration and as constituents in brain foods....It is suggested that citrus fruits, which are rich in abundant sources of hesperetin and other flavonoids, are promising for the development of general food-based neuroprotection and brain foods.
http://www.ncbi.nlm.nih.gov/pubmed/22224368
potential candidates for use in the intervention for neurodegenerative diseases.
http://www.ncbi.nlm.nih.gov/pubmed/18189359
Other aglycones tested (chrysin, flavon, hesperetin, naringenin) increased [3H]vincristine uptake in the 10-50 microM range, and glycosides (hesperidin, naringin, rutin)
http://www.ncbi.nlm.nih.gov/pubmed/10812049
citris peel for dementia and AD
http://www.ncbi.nlm.nih.gov/pubmed/23934345
Studying effect of grapefruit  juice on chemicals crossing BBB.  Chrysin, flavon, hesperetin, naringenin increased 2 compounds crossing the BBB, but hesperidin, naringin, rutin did not help.
http://www.ncbi.nlm.nih.gov/pubmed/10812049
korea citrus:  flavanones in Citrus aurantium.  Flavones in Citrus leiocarpa Hort. et Tanaka (CLHT), and Citrus erythrosa Hort
"Flavonoid profiling in three citrus varieties native to the Republic of Korea using liquid chromatography coupled with tandem mass spectrometry: contribution to overall antioxidant activity"

Naringin (in PD, all are by Jung UJ, Kim SR)
================
PD, dementia, AD: (5,7,10)
50 to 200 mg/kg orally for 21 days in rats in AD model. ameliorates mitochondrial dysfunction mediated oxido-nitrosative stress and inflammatory surge.
http://www.ncbi.nlm.nih.gov/pubmed/25449356
prevented oxidation-caused cognitive impairment in rats, 40 and 80 mg/kg 25 days prior to insult. restoration of superoxide dismutase, catalase, glutathione S-transferase, and reduced glutathione levels, and acetylcholinesterase activity
http://www.ncbi.nlm.nih.gov/pubmed/20673063
100 mg/kg for 16 weeks in genetically amyloid-impaired AD mice reduced plaque and improve cognitive functioning and long term memory
 possesses antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, anti-osteoporosis and anti-carcinogenic properties
http://www.ncbi.nlm.nih.gov/pubmed/22741174
http://www.ncbi.nlm.nih.gov/pubmed/23478434
studies have shown that naringin has neuroprotective effects by the induction of neurotrophic factors such as brain-derived neurotrophic factor and vascular endothelial growth factor, and by the activation of anti-apoptotic pathways .... these evidences suggest that naringin may be a potential natural compound involved in the prevention and treatment against neurodegenerative diseases ..... [in our study)  naringin treatment significantly increases glial cell line-derived neurotrophic factor (GDNF) expression and mTORC1 activity in the nigral DA neurons, and naringin-induced production of GDNF contributes to the protection of the nigrostriatal DA projection in a neurotoxin model of Parkinson's disease. Moreover, naringin decreases the level of tumor necrosis factor-alpha (TNF-a) in microglia increased by MPP+ -induced neurotoxicity. ... has not only pharmacological anti-inflammatory and antioxidant activities but also neuroprotective effects against neurodegenerative disorders. Recently, we have also demonstrated the ability of naringin to prevent neurodegeneration. In a neurotoxin model of PD, treatment with naringin protects the nigrostriatal DA projection by increasing GDNF expression and decreasing TNF-a expression in DA neurons and microglia, respectively, which suggests that naringin can impart to the adult DA neurons the ability to reproduce GDNF as a therapeutic agent against Parkinson's disease with anti-inflammatory effects on brain inflammation.   Taken together, our findings suggest that naringin may be a potential natural product to prevent degeneration of the nigrostriatal DA projection in the adult brain.   .....naringin can impart to the adult dopaminergic neurons the ability to produce glial cell line-derived neurotrophic factor against Parkinson's disease with anti-inflammatory effects. Based on these results, we would like to describe an important perspective on its possibility as a therapeutic agent for Parkinson's disease.
http://www.ncbi.nlm.nih.gov/pubmed/25317167
http://www.ncbi.nlm.nih.gov/pubmed/24797334
Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease...may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo. {full text)
http://www.ncbi.nlm.nih.gov/pubmed/26124853
 naringin and nobiletin prote4ct against H2O2 in neural cells by many different pathways, increased SOD, GSH, and MMP,  and decreased ROS, LDH, MTT, and lipid peroxidation
http://www.ncbi.nlm.nih.gov/pubmed/20691757
After naringin administration, naringin was undetectable in the brain...When cyclosporin A (20 mg/kg) was concomitantly administered with naringin (30 mg/kg), the naringin was detected in brain dialysate....The blood-brain barrier penetration of naringin may be enhanced by P-glycoprotein inhibitor; however, the pathway of hepatobiliary excretion of naringin may not be related to the P-glycoprotein. (30 mg/kg)
http://www.ncbi.nlm.nih.gov/pubmed/12405759
Naringin is a potent antioxidant, which can cross the blood brain barrier protecting brain tissue and modulating brain chemistry. Chronic treatment with naringin dose dependently restored cognitive deficits in ICV-STZ (AD model)  rat along with mitigation of mitochondrial dysfunction mediated oxido-nitrosative stress and inflammatory response (cytokine release).  (50, 100 and 200mg/kg; oral 21 days)
http://www.ncbi.nlm.nih.gov/pubmed/25449356
Naringin and total naringenin were rapidly and widely distributed to all the tissues except brain in rats. They had difficulties in crossing the blood-brain barrier. There are no accumulations in rats.
http://www.ncbi.nlm.nih.gov/pubmed/22270844
naringin showed significant antiapoptotic effects in rotenone-treated human SH-SY5Y cells by inhibiting phosphorylation of JNK and P38, as well as the activation of CASP9, PARP, and CASP3. These findings indicate that naringin may have therapeutic potential for PD
http://www.ncbi.nlm.nih.gov/pubmed/19885011
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766708/

nobiletin
===========
restores impaired short and long term memory, protects hippocampus, especially in AD and dementia. PD, dementia, AD: (3, 16, 19 articles)
great review for nobiletin in AD. Nobiletin exhibited memory-improving effects in various animal models of dementia and exerted a wide range of beneficial effects against pathological features of AD including amyloid-ß (Aß) pathology, tau hyperphosphorylation, oxidative stress, cholinergic neurodegeneration and dysfunction of synaptic plasticity-related signaling, suggesting this natural compound could become a novel drug for the treatment and prevention of AD.  suggest nobiletin penetrates the BBB in mice and reaches a maximal level within 3-5 min after peripheral administration. Additionally, 4'-demethylnobiletin, a major urinary metabolite of nobiletin in rats and mice, can cross the BBB and exert memory-improving effects in the brain.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153867/
chinese medicine uses chinpi (0.05% nobiletin), aged mandarine peel (Citrus reticulata)
Nobiletin but even more so sinensetin with the help of tangeretin, 6-demethoxynobiletin, and 6-demethoxytangeretin facilitate cAMP/PKA/ERK/CREB signaling associated with learning and memory in cultured hippocampal neurons
http://www.ncbi.nlm.nih.gov/pubmed/23588349
concentrates in brain 10x blood rat brain in 1 hour:
 Maximum concentrations of nobiletin in both plasma and brain were observed at 1h after single oral dosing (50 mg/kg). The maximum concentration in plasma and brain were 1.78 and 4.20 µg/mL, respectively. The AUC(0-t) in plasma and brain were 7.49 and 20.66 µg·h/mL, respectively. The mean elimination half life (t(½) in plasma and brain were 1.80 and 11.42 h, respectively.
http://www.ncbi.nlm.nih.gov/pubmed/21888953
Our results showed that nobiletin treatment at 10 mg/kg bw i.p., but not at 1 or 20 mg/kg bw, significantly protected DA neurons in the substantia nigra (SN) of MPP(+)-treated rats.
http://www.ncbi.nlm.nih.gov/pubmed/25325362
nobiletin activity in brain and suggests that nobiletin rescues motor and cognitive dysfunction in MPTP-induced Parkinson model mice, in part by enhancing dopamine release. (50 mg/kg i.p. 2 weeks)
http://www.ncbi.nlm.nih.gov/pubmed/24316474
Nobiletin (NOB) exhibits a wide spectrum of beneficial biological properties including anti-inflammatory, antioxidant, anti-carcinogenic actions and contributes to reverse learning impairment in Alzheimer's disease rat.  Dramatically promoted the activities of Akt, CREB, BDNF and Bcl-2.  protected the brain from ischemic  damage maybe through activating the Akt/CREB signaling pathway and ameliorating BBB permeability.  10 and 25 mg/kg ip (injected) 3 days before hypoxic injury and 1 day after.
http://www.ncbi.nlm.nih.gov/pubmed/23644141
berberine better, by same group:
dramatically lessened neurological deficits scores, brain water contents and infarct sizes, upregulated the expression of pAkt, pGSK3ß, pCREB and claudin-5, and decreased the nuclear accumulation of NF-?B (P<0.05) in ischemic brain.  Applied same injury to rats and applied only once after injury, 10 and 40 mg/kg.
http://www.ncbi.nlm.nih.gov/pubmed/22560097
nobiletin, including neurotrophic and memory-enhancin
g action, in both in vitro and in vivo systems are well established...whether its metabolites do have such beneficial effects like nobiletin remains to be examined...4'-demethylnobiletin, a bioactive metabolite of nobiletin, may serve as a potential therapeutic agent, at least, for memory disorders associated with a dysregulated NMDA receptor ERK signaling, like nobiletin.
http://www.ncbi.nlm.nih.gov/pubmed/19601643


tangeretin
===========
PD, dementia, AD  (3,2,1)
By affecting unfolded protein response and reduces endolpasmic reticulum stress.  Hesperidin may be similar.  ER stress-induced cell death have been demonstrated in a broad spectrum of pathological situations, including ischemia, diabetes, atherosclerosis, endocrine defects, and neurodegenerative disorders
pretreatment of mice with tangeretin, a methoxyflavone, enhanced expression of GRP78 and HO-1 without causing ER stress in renal tubular epithelium and prevented tunicamycin-induced cell death. Furthermore, preadministration of tangeretin in mice enhanced expression of GRP78 in the substantia nigra pars compacta and protected dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a neurotoxin that induces both oxidative and ER stress.  (10 mg/kg injected with DMSO
http://www.ncbi.nlm.nih.gov/pubmed/16971492
 tangeretin is a UDP (UGT) inhibitor like peperine, quercetin, salicylic acid (aspirin metabolite), EGCG (teas) and silibinin (milk thistle)
 http://www.ncbi.nlm.nih.gov/pubmed/25422796
prevents bad protein folding:  Consistent with these results, administration of the UPR-activating reagent tangeretin (5,6,7,8,4'-pentamethoxyflavone; IN19) into mice enhanced the expression of UPR-target genes in both dopaminergic neurons and astrocytes, and promoted neuronal survival after MPTP/P injections. (10 mg/kg orally 2 days before insult)
http://www.ncbi.nlm.nih.gov/pubmed/23112876
(10 mg/kg/day for 28 days), significant levels of tangeretin were detected in the hypothalamus, striatum and hippocampus (3.88, 2.36 and 2.00 ng/mg, respectively). . (20 mg/kg/day for 4 days; oral) before  applied insult to rat PD model showed markedly reduced the loss of both TH+ cells and striatal dopamine content.  These studies, for the first time, give evidence that tangeretin crosses the blood-brain barrier.
 http://www.ncbi.nlm.nih.gov/pubmed/11726811

Hesperidin
==============
PD, dementia, AD: (3,7,11)
Hesperidin potentially useful in PD because it crosses blood-brain barrier and prevent protein aggregation
http://www.ncbi.nlm.nih.gov/pubmed/25301518
protective effect of hesperidin on the neurotoxicity induced by 6-OHDA in aged mice, indicating that it could be useful as a therapy for the treatment of PD.
http://www.ncbi.nlm.nih.gov/pubmed/25280422
 hesperidin exerts its neuroprotective effect against rotenone due to its antioxidant, maintenance of mitochondrial function, and antiapoptotic in PD model ...  hesperidin can protect neurons against various types of insults associated with many neurodegenerative diseases (full text)
http://www.ncbi.nlm.nih.gov/pubmed/24205431
hesperidin can exhibit multiple neuroprotective effects.
http://www.ncbi.nlm.nih.gov/pubmed/22767158
hesperidin ameliorates heavy metal induced toxicity mediated by oxidative stress
http://www.ncbi.nlm.nih.gov/pubmed/26004892
Hesperidin  protects against hypoxia (low oxygen) injury
http://www.ncbi.nlm.nih.gov/pubmed/24076349
In AD mice, 100 mg/kg 10 days, mouse model of cerebral amyloidosis, hesperidin significantly restored deficits in non-cognitive nesting ability and social interaction. attenuated ß-amyloid deposition, plaque associated APP expression, microglial activation and TGF-ß immunoreactivity in brains of APP/PS1 mice, which suggests that ameliorated behavioral impairments might be attributable to reduced Aß deposition and attenuated neuro-inflammatory reaction.
http://www.ncbi.nlm.nih.gov/pubmed/25510196
In AD transgeneic mice 100 mg/kg for 16 weeks (same study in naringin) did not decrease amyloid plague but  showed reduction of learning and memory deficits, improved locomotor activity, and the increase of anti-oxidative defense and mitochondrial complex I-IV enzymes activities. Furthermore, Glycogen synthase kinase-3ß (GSK-3ß) phosphorylation significantly increased
http://www.ncbi.nlm.nih.gov/pubmed/25135708
In AD mice
treatment with hesperetin and hesperidin improved Aß-impaired glucose utilization by inhibiting Aß-induced autophagy in neuronal cells.
http://www.ncbi.nlm.nih.gov/pubmed/22383310

beberine (from barberry) (likely it is not bioavailable)
=============
PD, dementia, AD (0,31, 22)
prevents unfolded protein, antidepressant, anti-fat, and a neuroprotector against neurodegenerative.
May act synergistically with  sugar that cancer like, 2-Deoxy-d-glucose, which is not safe above 4 g/day. Reduces fat by selectively activating unfolded protien which causes the cell to die.
However, treatment with berberine enhanced motor balance and coordination by preventing dopaminergic neuronal damage. Treatment with berberine also improved short-term memory by inhibiting apoptosis in the hippocampus. Berberine demonstrated maximal potency at 50 mg/kg. Based on these data, treatment with berberine may serve as a potential therapeutic strategy for the alleviation of memory impairment and motor dysfunction in patients with PD.  (mouse, 50 mg/kg orally 5 weeks)
http://www.ncbi.nlm.nih.gov/pubmed/24535622