Persisters

Persisters
Andre Willers
30 Apr 2012
“Teach an old dog new tricks”
Synopsis:
Some organisms , notably bacteria and fungi , duck into the hibernation bunker when things get tough . They use some very old evolutionary machinery and quorum systems . These can be manipulated .
Discussion:
1.What are persisters ?
http://en.wikipedia.org/wiki/Multidrug_tolerance
“Multidrug tolerance or antibiotic tolerance is the ability of a disease-causing microorganism to resist killing by antibiotics or other antimicrobials. It is mechanistically distinct from multidrug resistance:[1] It is not caused by mutant microbes, but rather by microbial cells that exist in a transient, dormant, non-dividing state. Microorganisms that display multidrug tolerance can be bacteria, fungi or parasites.”
“Relevance to chronic infections
Multidrug tolerance is caused by a small subpopulation of microbial cells termed persisters.[2] Persisters are not mutants, but rather are dormant cells that can survive the antimicrobial treatments that kill the majority of their genetically identical siblings. Persister cells have entered a non- or extremely slow-growing physiological state which makes them insensitive (refractory or tolerant) to the action of antimicrobial drugs. When such persisting microbial cells cannot be eliminated by the immune system, they become a reservoir from which recurrence of infection will develop.[3] Indeed, it appears that persister cells are the main cause for relapsing and chronic infections.[1] Chronic infections can affect people of any age, health, or immune status.”

2.Old mechanisms :
See Appendix II below . A survival mechanism for hostile environments .

3.Quorum Ratcheting :
A gene-group evolved not to risk it’s whole population on a single hibernation strategy .
See http://andreswhy.blogspot.com “Infinite probes in optimization Jun 2008 and others .
It would ratchet up or down : RatioHibernating = (1/3)^n , where n = 1,2,3,… depending on the environment . Epigenetics and prions will play a role here .
There are two potential intervention points here :
3.1The quorum sensors , but they will probably be heavily protected and buffered .
3.2The period when n changes . The metabolism is then active and things like antibiotics can work . So , timing is then critical . An interesting question would be if each n’th state is a separate gene , or an input into a more general gene . This is very old , so I would guess both , with a single gene being in the majority .
Optimal n :The immune system has co-evolved with this mechanism , and relies on it as a memory of what to guard against . Rather neat , don’t you think ?
So an optimal n for a persistent population of potential pathogens would be 2
4.Interventions that will always work :
4.1Garlic (Allicin) . See Appendix III .
Allicin (freshly crushed garlic oil) will kill bacterial films . Try it on your teeth .
Melatonin as a powerful terminal anti-feedback loop agent might be useful as an adjuvant , but extreme caution is advised . Melatonin will bring Orexins into play . We don’t know enough to predict what will happen .
See http://andreswhy.blogspot.com “Fatigue and old age” 25 Apr 2012

4.2A compound called HT61 also punches holes in persistent cells (PLoS One , vol 5 ,e11818) or NewScientist 31 Mar 2012 p31 . Probably a variant of allicin .
4.3 Temperature:
Extensively used commercially . Pasteurization . The bugs are just inactivated , not killed . They go into a persistent state of hibernation .
http://en.wikipedia.org/wiki/Pasteurization
“Unlike sterilization, pasteurization is not intended to kill all micro-organisms in the food. Instead, it aims to reduce the number of viable pathogens so they are unlikely to cause disease (assuming the pasteurized product is stored as indicated and is consumed before its expiration date). “
In the terms used above , n is dramatically increased . The bugs will reactivate later in increments of n , but the body’s defence systems can handle them easily (unless impaired) .
But note that this is an easy training method for the immune system . Pasteurised food together with a cell-burster like allicin (garlic) or HT61 makes molecular fragments available for dendritic immune cell training .

Intriguing .
(This is not medical advice)
Autoimmune diseases like asthma (known to benefit from raw milk) might be retrained by pasteurised milk with crushed garlic juice , rinsed in the mouth and drunk immediately .
Really gives that old immune system a pair of training wheels ! . At any age .
Happy pedalling !
Andre

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Appendix I
Metabolite-enabled eradication of bacterial persisters by aminoglycosides
• Kyle R. Allison,
• Mark P. Brynildsen
• & James J. Collins
• Affiliations
• Contributions
• Corresponding author
Nature 473, 216–220 (12 May 2011) doi:10.1038/nature10069
Received
22 July 2010
Accepted
24 March 2011
Published online
11 May 2011
Article tools
Bacterial persistence is a state in which a sub-population of dormant cells, or ‘persisters’, tolerates antibiotic treatment1, 2, 3, 4. Bacterial persisters have been implicated in biofilms and in chronic and recurrent infections5, 6, 7. Despite this clinical relevance, there are currently no viable means for eradicating persisters. Here we show that specific metabolic stimuli enable the killing of both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) persisters with aminoglycosides. This potentiation is aminoglycoside-specific, it does not rely on growth resumption and it is effective in both aerobic and anaerobic conditions. It proceeds by the generation of a proton-motive force which facilitates aminoglycoside uptake. Our results demonstrate that persisters, although dormant, are primed for metabolite uptake, central metabolism and respiration. We show that aminoglycosides can be used in combination with specific metabolites to treat E. coli and S. aureus biofilms. Furthermore, we demonstrate that this approach can improve the treatment of chronic infections in a mouse urinary tract infection model. This work establishes a strategy for eradicating bacterial persisters that is based on metabolism, and highlights the importance of the metabolic environment to antibiotic treatment.
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Appendix II
See http://andreswhy.blogspot.com
Hibernation and Cryogenics
Andre Willers
19 Nov 2008

Discussion :
Jessica Palmer pointed out on the 16th Nov 2008 that the primary problem with cryogenics seems to be in the re-establishment of metabolic processes after un-freezing .

But we have an already existing template for doing exactly that .

Hibernation .

See Appendix A

The evolutionary explanation is that during the transition-phase from methane/sulfur to oxygen atmosphere (circa 1.5 bn years ago) , there was a major advantage in suspending oxygen-driven systems if the organism found itself in a non-oxygen environment . It went into hibernation .

At the same time , alcohol was being excreted as a poison (like oxygen) . The ancestors of mitochondria (who could use low concentrations of oxygen or alcohol ) sought refuge in cells whose cell-walls were resistant (but not impervious) to alcohol transition .

Remember , alcohol is completely soluble in water , but oxygen is not . This difference drove the process . Alcohol concentrations in water could grow large , but oxygen-concentrations could not .

Mitochondria earned their keep by mopping up alcohol first and later converting oxygen to ATP . (The glucose and ketone metabolism came after this) . The ketone metabolism has never been very popular , because of the high loss-rate in excretory products , but has been kept as a third string on the bow . (Utilization of fat and protein-muscle reserves during low-glucose periods. )

Mitochondria thus has an exclusive preference of usage : alcohol , glucose , ketones in that order .

From experimental evidence (see Appendix A) , there is a genetic switch sensitive to the concentration of H2S to bring both the host cell and the mitochondrium to a state where all programmed molecular activity is suspended . (The power is switched off) .
But , of course , random beth(0) molecular activity due to temperature does not cease . Uncontrolled and anaerobic reactions still occur .

Freezing:
We get rid of most anaerobic organisms first .
Lots of sulfur , VitC and alcohol (fermented berries or carbohydrates in the stomach . A low acidity is required in the run-up to hibernation)
Then freeze .


Starting the contraption up again is a bit of a problem .

1. The power-plant :
The mitochondria needs to be primed with their preferred fuel (alcohol)
Oxygen needs to be infused .(Hyperbaric chamber)

2. Garbage disposal
The cellular garbage-disposal systems need to be activated . ATP from the powerplant needs to be allocated to breakdown-product disposal before the ATP is allocated to DNA/RNA production processes .

The garbage-disposal uses mechanisms that use sulfur to create the various vacuoles and ropes (cf mitosis) . Enough sulfur is vital .

Once again , oxygen and alcohol is used . Both are recognized by all systems as poisons to be removed as a first priority . They activate a quite sophisticated garbage-disposal system as H2S concentrations decrease .

3 . Flushing
All that garbage has to flushed away , preferably not through the kidneys or liver .
Use machines .
As H2S concentrations decrease , damage might occur due to PH fluctuations . Acidity (H2SO4 , etc) Buffering would be advisable .

4. Temperature:
Lots of water at 105 to 107 Fahrenheit for mammals , pulsing at pulserate(about 90 cycles per minute .)
This is to activate the chaperone systems and discourage opportunistic viruses .

5. Music
See http://andreswhy.blogspot.com “Music”
Play harmonious music so the vibrations can be felt throughout organism being thawed . This enhances timing-procedures by orders of magnitudes . Emergent order .
(A Beth(0.x) effect . )

The de-hibernization process must have an exact program at molecular level to reboot the cellular metabolism . Precisely what you need after a cryogenic procedure .
But its efficiency (ie your chance of survival) can be boosted by orders of magnitude by using the steps above .

Interesting notes:
1. Do hibernating animals like bears use alcohol-producing cells in their bloodstream to time hibernation? This can be tested .
2. Are there cold-chaperone molecules ? There should be .
3. Hibernation is easy . Nature has done all the hard work . Keeping the mechanism ticking over at a very slow rate enables cellular-garbage clearing for a relatively short period (6-8 months)
4. De-cryogenics is a bit harder , Beth(1) intervention is needed .
5. Alcohol-concentrations : we are talking about 1% to 2% imbibing . About 0.06% inside the cell . Ie , the cell-wall protects by a factor of about 30
6. Pulse-Cryogenics : alternate freezing and hibernation to get a better survival factor . For those who are too stupid to design a zero-entropy system .
Try : Life=negative entropy . Non-life = positive entropy . Design it so the sum is zero .

Andre

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Appendix A
From http://andreswhy.blogspot.com “ Birdflu Update-4” dated 29 Oct 2005
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Suspended Animation (the real thing!)
In 2005, Mark Roth and other scientists from the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle demonstrated that mice can be put into a state of suspended animation by applying a low dosage of hydrogen sulfide (80 ppm H2S) in the air. The breathing rate of the animals sank from 120 to 10 breaths per minute and their temperature fell from 37 °C to 2 °C above ambient temperature (in effect, they had become cold-blooded). The mice survived this procedure for 6 hours and afterwards showed no negative health consequences.
Such a hibernation occurs naturally in many mammals and also in toads, but not in mice. (Mice can fall into a state called clinical torpor when food shortage occurs). If the H2S-induced hibernation can be made to work in humans, it could be useful in the emergency management of severely injured patients, and in the conservation of donated organs.
As mentioned above, hydrogen sulfide binds to cytochrome oxidase and thereby prevents oxygen from binding, which apparently leads to the dramatic slowdown of metabolism. Animals and humans naturally produce some hydrogen sulfide in their body; researchers have proposed that the gas is used to regulate metabolic activity and body temperature, which would explain the above findings
Dosages of H2S:
Treatment involves immediate inhalation of amyl nitrite, injections of sodium nitrite, inhalation of pure oxygen, administration of bronchodilators to overcome eventual bronchospasm, and in some cases hyperbaric oxygen therapy.
Exposure to lower concentrations can result in eye irritation (because of the high alkality of the SH- anion), a sore throat and cough, shortness of breath, and fluid in the lungs. These symptoms usually go away in a few weeks. Long-term, low-level exposure may result in fatigue, loss of appetite, headaches, irritability, poor memory, and dizziness. Higher concentrations of 700-800 ppm tend to be fatal.
• 0.0047 ppm is the recognition threshold, the concentration at which 50% of humans can detect the characteristic rotten egg odor of hydrogen sulfide [2]
• 10-20 ppm is the borderline concentration for eye irritation.
• 50-100 ppm leads to eye damage.
• At 150-250 ppm the olfactory nerve is paralyzed after a few inhalations, and the sense of smell disappears, often together with awareness of danger,
• 320-530 ppm leads to pulmonary edema with the possibility of death.
• 530-1000 ppm causes strong stimulation of the central nervous system and rapid breathing, leading to loss of breathing;
o 800 ppm is the lethal concentration for 50% of humans for 5 minutes exposition (LC50).
Concentrations over 1000 ppm cause immediate collapse with loss of breathing, even after inhalation of a single breath.

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Appendix III
See http://andreswhy.blogspot.com

Garlic and the Plant-Herbivore Wars .
Andre Willers
10 Apr 2011

Synopsis:
Garlic (Allicin) is a toxin produced by binary components alliin and enzyme alliinase These are kept in separate pockets , but mix when the plant is damaged (eaten) , producing allicin .

Dicussion :
This is a very old and beautiful mechanism , verging on symbiosis .

Note the presence of Sulfur : it evolved pre-oxygen , and evolved to keep pace .
It originally evolved to zap viruses and other bacteria to give the originators a relative advantage .
In multicellular organisms , it does the same .
Notice that the chemical (Allicin) evolved first , then reversed into the genomes of various organisms because it was so useful .
Allicin remains invariant , and genomes adapt to it .
A sort of "Inverse Prion"

But it is kept in check by various mechanisms :

1.Bad taste and smell and a burning sensation

This limits eating . The burning is sensation is caused by the activation of a separate neural network that evolved to simulate a burning sensation . This evolved into capsaicum receptors in mammals . Birds , reptiles and dinosaurs had equivalents .
Note sensitivity of marine mollusks to anti-fouling paints based on capsaicum-like chemicals .

2.Deactivation of enzyme alliinase if ph<3
This led to gastric acids .
Symbiotic bacteria in the intestines must be kept protected .
Swallowing garlic plants or powders will not work
If you drink coke ,pepsi etc , with your garlic , there will be little health benefit (see Appendix A for acidity of popular drinks)
But too much of a good thing can harm . A swig of acid drink(ph<3) will reset oral bacterial systems after eating garlic . But it must be pulsed at 2 minute intervals .

3.Quick breakdown of allicin at body temperatures :

16 hours at 23 C (from Wiki)

64 hours at 3 C (the fridge) . Throw away supermarket or even frozen minced garlic as far as health effects are concerned .

5.7 hours at 38 C (doubling of chemical activity every 10 C)
Very little allicin makes it through to the small intestines to upset the gut flora .

Cooking :
5 minutes at 100 C . (doubling of chemical activity every 10 C)
There is very little allicin left after 5 minutes of cooking .

The effects of Allicin is then concentrated in the mouth and throat : where the rubber hits the tar . Where any bacteria is an enemy . Kill them all , and let the immune system sort out the remainder .
This works well in pulsed dosages , hence another reason for the rapid breakdown of allicin .

4.Breakdown accellarators :
There is some evidence that there are some other chemicals in garlic that speeds up breakdown of allicin . Presumably binary , as well .


Preservation of allicin :
See http://en.wikipedia.org/allicin
Cutler and Wilson found that an aqueous cream of allicin (0.5 g/L) compared well with 20 g/L of muporicin .
Aqueous cream is essentially an emulsion .

Make your own Allicin Cream :
Spray-on cream from an aerosol can is an emulsion .
Spray it into your bowl , then crush your garlic clove inside the cream emulsion . Hopefully , large enough percentages of the binary components alliin and enzyme alliinase are encapsulated by the lipid foams .
Smear it on , and as the foams evaporate and break down , the components interact .
Voila , allicin .
Dosages and timing will have to be found by experiment .
Be careful and err on the side of caution . 0.5 g/L allocin is kinda small .

An added advantage is that the burning sensation will be much ameliorated (cream is a milk product , which has been found to decrease the burning sensation .)

Smear it on the gums and swirl it (there will be greatly stimulated spit production) . Swallow if necessary . After a prederminate time (start at 2 minutes , then progress in sequence 4 , 8 ,16 , etc) . If discomfort is experienced , swill mouth with coke . Then milk if necessary .

It can be used as a topical cream for anti-fungal and bacteriocidal purposes on the skin.
Do not use it in capsules designed to bypass the stomach , or in suppositories without medical supervision by a really qualified doctor .

This would be like the Terminator loose in LA .

Making pure allicin , alliin and enzyme alliinase
Put clove of garlic in centrifuge test-tube , together with at least 3 balls whose diameter is slightly more than the radius of the test-tube .
Spin .
The relative motions of the balls will crush the garlic , and the centripetal forces will separate the various layers . These can then be tapped individually . But don't loiter too long , as the enzyme at the interface will eventually convert all the aliin into allicin .


Garlic Perles , oils , etc .
These are worthless as far as allicin health benefits are concerned .
These all involve macerating garlic cloves , then dissolving it into an oil .
Reaction between alliin and enzyme alliinase creates allicin . This decays within a matter of hours as set out above . What remains has very little(if any) bio-reactivity

Temperature release :
There might be a temperature release .
An old evolutionary structure would have added the extra "Oomph" of explosive micro-injection of the allicin . Ie an exothermic reaction between alliin and enzyme alliinase .
This gives opportunity of introducing retrovirals , bleach , etc into the teeth and jaw-bones by smearing a minute layer on the tooth , then biting down on the garlic clove (or cream) .

Really, really potent Garlic will blow your socks off !

Bon appetit.

Andre

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Appendix A
Acidity (PH) of some popular drinks .

Diet Mountain Dew 2.95 0.0
Dr. Pepper 2.92 9.64 tsp.
Sprite 2.90 9.29 tsp.
Gatorade (Lemon-Lime) 2.83 5 tsp.
Mountain Dew 2.80 11.07 tsp.
Minute Maid Orange Soda 2.80 11.2 tsp.
Diet Pepsi 2.77 0.0
Diet Coke 2.70 0.0
Powerade 2.63 5.36 tsp.
Pepsi 2.43 9.64 tsp.
Coca-Cola 2.30 9.64 tsp.
Battery Acid (Yikes!) 1.00 (Acidic) 0.0"

"*Acid amounts from the study “Enamel and root surface erosion due to popular U.S. beverages,” 2006. Authors: L. Ehlen, T.A. Marshall, F. Qian, J.J. Warren, J. Wefel, M.M. Hogan, and J.D. Harless. College of Dentistry, University of Iowa, Iowa City and from University of Minnesota School of Dentistry, 2000, Northwest Dentistry Vol 80, No. 2. **4.2 grams = 1 teaspoon."

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Fatigue and old age

Fatigue and Old Age
Andre Willers
23 Apr 2012
“Too tired to keep on living , too scared to die” : Old Man River
Synopsis :
Fatigue , old age and fertility are related via quorum mechanisms , using telomeres and prions . We try to find a logical pathway connecting them .
Discussion :
1.Fatigue :
Prof Tim Noakes , a foremost sports scientist (see “Challenging beliefs” , (ISBN 978 1 77022 459 9) 2012 edition) p 328 et al) found that “my brain always wanted me to quit when I had covered about 66 percent of the race distance . I gather that this is not an uncommon response.”
Now see http://andreswhy.blogspot.com “Infinite Probes in Optimization” Jan 2008 and others around then . Repeated in Appendix I for your ease .
Note the arguments about Reserves . In general systems have evolved to keep a reserve of 33 percent . Hence the finding of Noakes . (This result is found everywhere in old evolutionary systems) .
The interesting question : how does the brain-body system “know” at a deep level what the requirements will be ? Noakes gives a strong indication : “What I do know is that since understanding the nature of these regulatory processes in the central governor , I no longer suffer from this specific symptom to quit either in training or racing . Others report the same .”
In other words , there exists a mechanism that releases the Reserve .It is tempting to think that this is a brain thing , but we find it in all undomesticated animals . Note that domesticated horses will run until they die . The Reserve switch has been bred into a permanent “off” position . A definite genetic mechanism exists , associated with aggression and startle-responses .
This points to the amygdala , a notoriously stupid system . It will treat any startlement as a signal to hoard reserves . (Ie if your heart sinks at the thought of a 100 km race , you will experience extreme fatigue after 66 km , even if you are driving a car .)
But how does it work ?
Somewhere along the line neuronal signals have to be translated into chemical signals that the cells and mitochondria understand . Luckily , we have a very good candidate in the Orexin class of neurotransmitters , manufactured in the hypothalamus .
http://en.wikipedia.org/wiki/Orexin
“Orexin, also called hypocretin, is a neurotransmitter that regulates arousal, wakefulness, and appetite.[1] The most common form of narcolepsy, in which the sufferer briefly loses muscle tone (cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.[2]
The brain contains very few cells that produce orexin: in a human brain, about 10,000 to 20,000 neurons[2] in thehypothalamus.[1] However, the axons from these neurons extend throughout the entire brain and spinal cord,[3] where there are also receptors for orexin.”
There is an intimate connection with Melatonin . See Appendix II below .
Briefly , Orexins excite feedback loops , and Melatonin as the ultimate Enforcer curtail these feedbacks .
But in a living , evolutionary organism it does not stay as simple as that .
Examples:
1.An athlete training with low dosages of melatonin will have a significant advantage if he stops using them before the big race. (A pulse of orexins will result)
2.Orexin suppressants should be used sparingly , as there will be a synergistic reaction with normal melatonin cycles .
Still , melatonin remains a useful intervention .

What has this to do with Old Age and Fertility ?
Basically , epigenic and prion mechanisms are have evolved to limit the fertility and longevity of populations . The quorum system , adapted from bacteria , is used extensively .
See Appendix III below for the Fertility Epidemic .
Old age Epidemic :
A prion disrupts the ribosome read from the histone that codes for telomere regeneration . This would be related to the fertility plague prion . We would expect that the fertility plague prion would interfere with the Old Age prion . Thus , from 1704 AD onwards , infected individuals would live longer .
Essentially , from a biochemical viewpoint , the organism just becomes too tired to keep on living .
Interesting asides :
1.Fleming Effect .
We would expect infected humans to become smarter , as neuron-pruning would decrease.
( The pruning mechanism works on the same principles.)
2.Autoimmune diseases and cancers would increase for the same reason . Aberrancies also live longer . Nothing to do with the environment .
3.Diabetes II : very probably a prion disease . Hence it’s epidemiological aspects . Look at the histone coding for orexins .If it is so , an antibody can be manufactured to eliminate Diabetes II causing prions . Not an immediate cure , but a cure as long as you take the antibody . Like gout . (Sigh . The pharma’s will love this .)

“Awake! The spear of Dawn puts the stars to flight! “ Omar Khayam
Andre

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Appendix I
Infinite Probes in Optimization .
Andre Willers
5 Jan 2008

Definitions:
n! = n*(n-1)*(n-2)*(n-3)*…*1

The Euclidean Constant e .
e = (1/1! + 1/2! + 1/3!+ 1/4!… )
=2.178…

I will make it as simple as possible using costs and temporal sequences as examples .

Assume that the elements of a system are identifiable and repetitive .
The rules of Arithmetic can then be applied .

Take any such system . By definition it can then be subdivided indefinitely . Each subdivision of r elements can have r! possible permutations (or states) .

Let there be a CostReserve to cover unknown costs in the failure of any element in a group .

Key Assumption
Let at least one element of each r be Aristotelian False (ie a failure cost item)

The Total cost of failure will be the sum of the cost of failures of the elements.
(ReserveCost) *( (1/1! + 1/2! + 1/3!+ 1/4!… ))= (TotalCost)

Your Reserve times the sum of individual failures = total
This defines the boundary .

This is the optimization equation .

This is equal to
ReserveCost / TotalCost = 1/e ~ 0.37

This means that you should not consider an endeavour where the rate of return is less than 37% . This is the long-term break-even point from a probabilistic viewpoint .

This equation is independent of space or time .

Any society (any at all ) that does not deliver 37%+ returns gets zapped by the chaotic downturns .

Since vested interests always decrease rates of returns , empires rise and fall .

The probe can be used in any infinite series , but care has to be taken to define the terms .



An Interesting corollary :

The alert reader would have noticed that the above is true for when there is always at least one false item per group .
What if there is at least one true item per group ? This is approached as follows:

In trading systems , individual items can be identified . The cost of failure in an individual item is then = 1/ (r!/r) = 1/ (r-1)!
The summation is then
(ReserveCost/Item)*(1*1/1! + 2*1/2! + 3*1/3!+ 4*1/4!… ))= (TotalCost)
(ReserveCost/Item)*(1 + 1 + 1/2!+ 1/3!… ))= (TotalCost)
(ReserveCost/Item) / (TotalCost) = 1/(1+e) ~ 0.27

As can be seen , trading systems will survive the collapse of empires . There is a whole 10% difference favouring traders . Recovery systems will then also favor traders .

This is the underlying reason why Stalinistic Communism failed and Chinese went trader . The VOC and East India Co . are good examples .

Ten percent is just too much .

Ho-ho-ho !
The average between 0.37 and 0.27 is roughly 0.33 . A third .Can you see where this is relevant in any infinite situation where uncertainty rules?

Non-Failure Ratio
A non-failure ratio of (1- 1/3) ~2/3 summated over infinity = (2/3) / (1-2/3) =2 .

This means that any system that can be described or broken up into smaller groups is strongly ordered . Successful subgroups survive by a factor of 2 . This is built into the mathematics of the Universe . Life is one such sub-group , so are particles ,etc . Negative entropy is the rule . Life is everywhere . Positive entropy only holds in the most primitive and earliest systems .

Beautiful!

Quantum and non-quantum systems are the same .

Singularity Points.
27% and 37% are singularity points , as are (100-27)=63% and 53% . SocioEconomic systems destabilize at these points . Regardless whether they are human , alien , japanese , chinese or any other sort of ese .
Any society where more than a third of productive enterprise is spent without engendering new wealth creation is doomed .

Tax rates of more than 27% reduce trade . Tax rates between 27% and 37% will let it limp along . Tax rates over 37% is a disaster waiting to happen . It is that simple , and no amount of pontificating will change the realities of economics .

The tax rate anchored between 0% and 27% will follow a catenary . The optimal will be halfway (12.5%) . This would be the optimal VAT rate . Note that deviations from this (up or down) leads to social unrest . The unrest is not linear , but catenary . In other words , it gets rapidly worse as it approaches the anchor points of 0 or 27 % . This is true of any civilization , human or alien . It is inherent in the mathematics .

These are absolute rates , not relative .

The RepoRate .
The tax on new money . If the reporate plus profits stay away from the singularity points (27% , 37%) there is no problem.

What about undefined realities ? Refer to
http://andreswhy.blogspot.com “Topos:
Note in the definitions above , that as groups are divided by n , and n->infinity , the system approaches undefined “thingies” . Hence , it can be used as a probe into undefined realms .

Marriage:
An interesting corollary is optimizing pairings of two . The theory above says that random pairing will lead to a failure rate of 37% . Observation seems to bear this out .

To optimize : Note and keep track the best features of the first 37/100 daters , then seriously consider the first anybody after that who equals or better the standards of the first 37
This optimizes your chances .

This result has been independently reached in games theory

Note that your body is independently doing this sort of infinite analysis . Hence speed dating , cocktail parties , mingling , etc .

A good algorithm is to speed date at least 50 persons . Do not do this if you cannot handle rejection , since this concentrates years of normal rejection into a few weeks .

A therapeutic mechanism? Sects use this whipsaw mechanism of rejection (by the outside world) and warm acceptance by the sect to create mini-societies .
Hence cold-canvassing . Rejection binds them closer . Any converts are a bonus . Most real converts are made by on-on-one contact .

But that is also the definition of most successful families .

If you are stupid and ugly , and can handle speed dating , you are a better man than I am , Human .

Virtual speed dating .
Analogous to cures for fear of heights , fear of confined spaces , etc . Considerable success has been achieved in reprogramming the amygdala for these and related phobias using virtual reality .

A Virtual Rejection website will make money .
That’s OK if somebody learns from it .
Another way for actresses or avatars to make money .
“I was rejected 1000 times by Lara”
“Balls rejected by Lara TombRaider as not dusty enough.”
The mind boggles .


Andre

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Appendix II
Melatonin and Dinosaurs .
Andre Willers
14 Jun 2011

"Sleep that knits up the ravell'd sleave of care " Shakespeare

Synopsis :
Melatonin ended up in various evolutionary roles because of it's powerful , terminal antioxidant effect . Many neurotransmitters (especially NO classes) can be seen as free radicals . (See Appendix A)
Melatonin is Nature's Terminator . (See Appendix C)

Discussion:
A handy Terminator got roped into being the Enforcer for various feedback systems that had to be kept from repeating .

Examples :

1.Cancers (eg breast , prostate cancers)
Interruption of signaling molecules .

2.Circadian rhythms of the brain (sleep)
Dismantling runaway feedback systems before they corrupt long-term memory irreparably (sense of self) See Appendix C

3.Gut rhythms :
A separate system Melatonin excretion by various cells and bacteria .

4.Bile :
Funnily enough , a separate system . Why ?
Tied to the energy system and things like diabetes .

5.Mitochondria :
A sophisticated auto-governor on rates of activity relative to intra-cell position .
Really simple . Really cool . (Think a steam engine's governor) See Appendix B.

6.Skin
As expected , such a powerful terminal antioxidant will also be on the ramparts against foreign invaders (like in the gut)

7 Immune system
Basically a memory system , with potentially unlimited feedback .
Melatonin will terminate this as well , especially in localized , concentrated doses .
But note the correlation between blue-light and HIV .
Very high-intensity pulses of blue light (484 nanometers) or UV should disable the HIV virus .

Contradictions :
This is only seven usages .There are probably more . The same concentrations of melatonin cannot serve all .
Hence , melatonin receptors evolved to meter and control cellular responses .
As well as dopsin receptors in the visual systems .

Loss of UV Dopsins
About 100 MYA for mammals . Remnants (melanopsins) are still responsible for nervous system entrainment , but some biological adaptability (ie getting melatonin from diet) was lost .
It also means that humans are especially vulnerable to depression of melatonin production by light in the Blue Wavelengths (484 nanometers) . CFL and LED lights .
This means that you should only use blue lights if you want to be alert . The effect is very strong (about 100 times) .
Interesting , this should be able to be hyperreal . Diffraction patterns (as with insect , bird and reptile scales) could give blue-to UV light that the mammalian optical systems will interpret as hyperreal .And hyperactive .

Speculation :
Mammalian loss of these dopsins are thought to be the result of low level of light on the forest floor .
But what if the scaly animals had evolved to use Blue and UV as a weapon ?
It would have reduced melatonin production even in darkness .

Imagine huge , impregnable Dinosaur behemoths with a skin ecology of luminescent bacteria , the light diffracting from their scales into the blue and UV .
A magnificent sight !

Remnants :
Birds with brilliant UV plumages should have DNA of the lumenifages in suppressed state . Or you can do it the hard way from the skins of late-stage dinosaurs .

Light-flash Extinction :
An amusing thought . The extremely bright flashes of the meteors would have burned out the skin ecology of the dinosaurs , the subsequent darkness sending them into a terminal melatonin deep sleep . See FireFall .
This can be tested . Since melatonin is a terminal antioxidant , the breakdown products should be measurable even after 65 MY .

Chickens and flu's
The diseases can be seen as stripped-down versions of skin-symbiotes of the old dinosaurs . The worst thing you can do is subject them to UV Like in brooders . Self-assembly of old sequences will follow . A very old revenge .

What is a poor mammal to do ?
Because of the very many uses of melatonin , there is no single solution .
Sometimes you need more , sometimes less . The trick is to know when .
Also , the sources depend on light (especially blue light or UV) , gut , immune system , brain , pills(slow release or fast release) etc .

The basic principle is that it stops things dead . Slowly or quickly .
There is a tie-in with the sulfur mechanism that is responsible for the immobilization of all molecular cellular activity (concentrations of H2S about 80 ppm)
Melatonin stops the H2S blockage . At extremely low concentrations .
Look at the molecule .

This is a typical life-system . Blockages of blockages of blockages leading to a system with graduated responses .

Too little melatonin , and H2S is not sufficiently blocked and the organism goes into stasis . Sleep .

Evolved into hibernation . The long light periods led to depletion of melatonin , leading to H2S hibernation . Neat .

SAD is a direct consequence . Too much melatonin leads to neurotransmitter depletion (especially serotonin)
A berserker has to generate high levels of neurotransmitters internally .

Take a pill !
As seen above , the system has many variants . Endo- and exo- just to start with . There are adjuvants (valerian is one) . Epigenetic variants are possible , but this system is so basic that I think adjuvants would give better results .

So , take a pill with timing and accompanying chemicals .
Each one should target a separate system .

Ageing
The H2S system freezes things . The melatonin system unfreezes it .Pulsing the system enables living and repairing . Sleep with very carefully metered SO2 will enable a very long life for those interested .

Who wants to live forever ?

Andre

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Appendix A

http://en.wikipedia.org/wiki/Melatonin
"Antioxidant
Besides its function as synchronizer of the biological clock, melatonin also exerts a powerful antioxidant activity. The discovery of melatonin as an antioxidant was made in 1993.[85] In many less complex life forms, this is its only known function.[86] Melatonin is an antioxidantthat can easily cross cell membranes and the blood-brain barrier.[6] Melatonin is a direct scavenger of OH, O2−, and NO.[87] Unlike other antioxidants, melatonin does not undergoredox cycling, the ability of a molecule to undergo reduction and oxidation repeatedly. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants, counterintuitively promoting free radical formation. Melatonin, on the other hand, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.[88] "

Appendix B
" A potential mechanism is that melatonin promotes the recruitment of brown adipose tissue (BAT) as well as enhances its activity.[48] This effect would raise the basal metabolic rate by stimulating thermogenesis, heat generation through uncoupling oxidative phosphorylation in mitochondria."

Appendix C
http://en.wikipedia.org/wiki/Phase_response_curve#Melatonin_PRC

"PRC in neurons
Phase response curve analysis can be used to understand the intrinsic properties and oscillatory behavior of regular-spiking neurons.[8] The neuronal PRCs can be classified as being purely positive (PRC type I) or as having negative parts (PRC type II). Importantly, the PRC type exhibited by a neuron is indicative of its input–output function (excitability) as well as synchronization behavior: networks of PRC type II neurons can synchronize their activity via mutual excitatory connections, but those of PRC type I can not.[9]
Experimental estimation of PRC in living, regular-spiking neurons involves measuring the changes in inter-spike interval in response to a small perturbation, such as a transient pulse of current. Notably, the PRC of a neuron is not fixed but may change when firing frequency[10] or neuromodulatory state of the neuron[11] is changed."
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Appendix III
A Vaccine for Overpopulation
Andre Willers
7 Apr 2012
Synopsis:
A prion disease removed natural epigenetic fertility controls circa 1704 AD . A vaccine is possible to train the immune system to recognize and remove the prion culprit .

Discussion :
See http://andreswhy.blogspot.com “Neanderthal Harbours” Apr 2012
Why a prion ?
Prions work by selectively disrupting the “read” process of the ribosome . Like putting a blank piece of paper in front of the letters to be photocopied . In scrapies and madcow , it is the “END” codon that is elided . The ribosome just keeps on copying proteins . See SciAm and NewScientist . This has a survival value for species in stressed circumstances , but is a bit tough on individuals .
Prions are also highly infectious . See
1.http://blogs.scientificamerican.com/observations/2011/05/19/natural-born-prion-killers-lichens-degrade-mad-cow-related-brain-pathogen/
“What has made prions difficult to control is their infamous durability. Boil water for a few minutes, and all the bacteria and viruses will be gone. Not so for the prion: it will be just fine, reaAs if it weren’t bad enough that deadly prions can survive boiling and radiation, now comes word that aerosolized forms of the pathogen can enter the nose and find their way to the brain, with fatal consequences.dy to infect. How does it fare in a dry heat of 600 degrees C? No problem there, either. How about ionizing radiation? Bring it on.”

2.scientificamerican.com/obseblogs.rvations/2011/01/13/bad-prion-breath-mad-cow-disease-agent-can-infect-via-the-air/
“As if it weren’t bad enough that deadly prions can survive boiling and radiation, now comes word that aerosolized forms of the pathogen can enter the nose and find their way to the brain, with fatal consequences.”


Epigenetics :
There is a sophisticated feedback process at epigenetic level monitoring population-level signals . A development of bacterial quorum-systems . Evolution does not favour Growth-without-limit , otherwise we would not have quorum systems . Remember , bacteria are the majority lifeform . This is the mistake Malthus made .
Malthus :
His Primary assumption was that populations grow to the limit of carrying capacity . This simply was not true before 1704 AD . But when he lived (1766-1874) it was , because the safety catches had been taken off . This happened because of a prion disease from some island off Scotland , rapidly infecting the rest of the world . And no disinfection then or now will work .
Is a vaccine possible ?
Yes. Simple , too .Take the negation of the END codon . The folded prion protein must have the precise lock-on DNA configuration and is thus targetable by tailored anti-bodies . A teensy-weensy problem is to zap only proteins with this configuration . But the heavy lifting has already been done . Neanderthal-derived families with few children should have the requisite molecules . And there are lots of them around the Med .
What does this mean ?
The overpopulation epidemic seems to have run it’s course in the first affected areas (Western Europe , North America) , but not yet in other parts of the world . The creation of a vaccine will cause major political problems . But it will probably share the characteristics of the original disease . Impossible to prevent , and very infectious . It is just the return to the natural state .
Interesting Asides :
1.What does the plants have to say about this ?
Remember , these are not conscious systems . But they are very effective .
Some plants have positive feedback relationship with humans . Grains and especially ones used in weaving . The introduction of woven cloths has always led to a population explosion . The fibres in close contact with the skin leads to positive feedbacks for prions suppressing epigenetic population control . Slow to start , but all plant weaves today encourages fertility .(By definition) . And they all target the same area in the epigenetic system . To find a vaccine , go to the nearest shop and buy any woven material . Look for prions .

2.Oh no !
Whisky . The Scottish Islands in 1704 AD exported mainly people , whisky and wool . All would carry the prions , but whisky the easiest of all . No wonder it was called the “Water of Life” . It was. People who drank it had more children . So , when you look for Person(0) , you know where to look . And look at whisky sales routes for subsequent spread of the infection . I guess this falls under the “some good news and some bad news” classification .

Should humans develop and employ an anti-fertility vaccine ?
They can do it now . But should they ? Well , they are going to do it in any case for short-term advantages , but they should simultaneously develop antidotes to the vaccine .
Places like Italy are already into negative population growth , and if you look at their fashions you can see why . (What! You think plants don’t have fashions ? Good luck with your sex-life . A fashionable fabric by definition promotes the sex-life of it’s partner .)

God’s Mercy
Instead of fashionably going extinct or superhuman , the possible pathways for human futures suddenly un-pinched from a neat two to a messy infinity . For some unfathomable reason the Powers-that-be decided to extend humanity’s term . The pinching-off branches have opened up . (The time-aspects were not predetermined . Think of it as a change in top-down chaotic attractors . You don’t have the terms)
Not my idea . I am but a time-limited pen , rather sourly recording .
Oh well .
Back to long-term planning .
“What God wants , God gets”
Andre
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Shakespeare's Secret Diaries .

Shakespeare’s Secret Diaries.
Andre Willers
18 Apr 2012
Synopsis:
Shakespeare , as a compulsive scribbler , kept copious notes in a private diary . These were concealed for political reasons , but he left three clues to their whereabouts .
Discussion :
Tired of Great Things ?
Do something completely frivolous .
Find Shakespeare’s secret diaries.
1.Did these diaries exist ?
Certainly . Shakespeare was a very acute observer and noted everything around him . From evidence of “Timon of Athens” (an unfinished play) , he created his plays as sub-groupings , which he then assembled and polished into a whole . All this required a lot of writing by hand . This resulted in a form of Repetitive Stress Injury . See http://en.wikipedia.org/wiki/Writer's_cramp
How many words ?
http://www.opensourceshakespeare.org/stats/
884 429 words as finally polished products over a 24 year career . This gives about 3070 words per month . Experienced writers would normally rewrite about three to five times .
So , there were a lot of documents . But only the initial , unvarnished observations by a genius class mind would be sensitive to the milieu Shakespeare moved in ( the likes of Southampton) . He successfully concealed their existence even after his death , but could not resist leaving clues to be found long after his death .
2.The Clues :
There are three , in keeping with his works and way of thinking :
Clue 1 : His gravestone . This plainly states that there is something worth looking for , but it is not there in the grave . Any “curst” is the curse of ignorance .
Clue 2 : The very specific bequest of the second-best bed to his long-suffering wife . This , according to the custom of the times , was the marital bed . The best bed was kept for guests . And Shakespeare’s guest always was a Muse .
But which one ?
http://en.wikipedia.org/wiki/Muse
“In Renaissance and Neoclassical art, the dissemination of emblem books such as Cesare Ripa'sIconologia (1593 and many further editions) helped standardize the depiction of the Muses in sculpture and painting, so they could be distinguished by certain props, together with which they became emblemsreadily identifiable by the viewer, enabling one immediately to recognize the art with which they had become bound.
Calliope (epic poetry) carries a writing tablet; Clio (history) carries a scroll and books; Erato (love/erotic poetry) is often seen with a lyre and a crown of roses; Euterpe (lyric poetry) carries a flute, the aulos; Melpomene (tragedy) is often seen with a tragic mask; Polyhymnia (sacred poetry) is often seen with a pensive expression; Terpsichore (choral dance and song) is often seen dancing and carrying a lyre; Thalia (comedy) is often seen with a comic mask; and Urania (astronomy) carries a pair of compasses and the celestial globe.”
Shakespeare’s Muses could be Clio , Erato , Euterpe , Melpomene , Terpsichore , Thalia . Note the date above (1593) . Shakespeare would have been well-aware of the standardized depiction of the Muses .
The highest probability lies with the two not usually applicable to him : Polyhymnia and Urania .
Back to Clue 1: On the tombstone he said “for Iesvs sake” , a clear religious reference . So the Muse Polyhymnia has the highest probability .
Clue 3 : The unknown clue . The most difficult one .
Shakespeare would certainly not have trusted Michael Drayton or Ben Johnson (his drinking buddies at the end) . They would simply have stolen what they could use and used the rest to the detriment of Shakespeare’s family . Nor could he pass it to descendants , as there was no male descendant in sight . Besides , he was not famous yet . This happened only from about 50 years after his death .
So , the third clue would be hidden in his works . If he became foumous , he trusted somebody would dig it out . If not , then it would not matter . A perfect hiding place .
A prime candidate for Muse : Polyhymnia would be the Muse of the work below :

http://en.wikipedia.org/wiki/The_Phoenix_and_the_Turtle
“The Phoenix and the Turtle is an allegorical poem about the death of ideal love by William Shakespeare. It is widely considered to be one of his most obscure works and has led to many conflicting interpretations.[1] It has also been called "the first great published metaphysical poem".[2] The title "The Phoenix and the Turtle" is a conventional label. As published, the poem was untitled.”
Shakespeare still beating himself up over the Dark Lady (Emmilia Bassano)
See Appendix I for the poem .
Note the next-to-last lines :
“To this urn let those repair
That are either true or fair;”
Interpret the poem as fairly literal instructions to find a buried packet (the Phoenix of Truth) . Then the allusions are fairly clear . (Shakespeare outsmarted himself by making things a bit too allegorical)
Remember the Shakespeare coat-of-arms ? The falcon on top . Look for it .

The Packet :
Shakespeare knew it might have to last for centuries . They had the technology for it . The packet (probably about 10 thick paperback-sized volumes) would be tightly wrapped in oil-skin , then copper-sheathed .
Then a lead cladding with air-holes , heated slightly to expel moisture , then soldered shut . This would last for hundreds of years .
Modern detectors should be able to pick it up if the approximate location is known .
The contents should be fascinating , as well as extremely valuable .
The candid observations of Shakespeare in his own hand .
Now you know as much as I do .
Happy hunting !
Andre

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Appendix I
Text of the poem
The Phoenix and the Turtle
Let the bird of loudest lay,
On the sole Arabian tree,
Herald sad and trumpet be,
To whose sound chaste wings obey.
But thou, shriking harbinger,
Foul pre-currer of the fiend,
Augur of the fever's end,
To this troop come thou not near.
From this session interdict
Every fowl of tyrant wing,
Save the eagle, feather'd king:
Keep the obsequy so strict.
Let the priest in surplice white,
That defunctive music can,
Be the death-divining swan,
Lest the requiem lack his right.
And thou, treble-dated crow,
That thy sable gender mak'st
With the breath thou giv'st and tak'st,
'Mongst our mourners shalt thou go.
Here the anthem doth commence:
Love and constancy is dead;
Phoenix and the turtle fled
In a mutual flame from hence.
So they lov'd, as love in twain
Had the essence but in one;
Two distincts, division none:
Number there in love was slain.
Hearts remote, yet not asunder;
Distance, and no space was seen
'Twixt the turtle and his queen;
But in them it were a wonder.
So between them love did shine,
That the turtle saw his right
Flaming in the phoenix' sight:
Either was the other's mine.
Property was thus appall'd,
That the self was not the same;
Single nature's double name
Neither two nor one was call'd.
Reason, in itself confounded,
Saw division grow together;
To themselves yet either-neither,
Simple were so well compounded
That it cried how true a twain
Seemeth this concordant one!
Love hath reason, reason none
If what parts can so remain.
Whereupon it made this threne
To the phoenix and the dove,
Co-supreme and stars of love;
As chorus to their tragic scene.
THRENOS.
Beauty, truth, and rarity.
Grace in all simplicity,
Here enclos'd in cinders lie.
Death is now the phoenix' nest;
And the turtle's loyal breast
To eternity doth rest,
Leaving no posterity:--
'Twas not their infirmity,
It was married chastity.
Truth may seem, but cannot be:
Beauty brag, but 'tis not she;
Truth and beauty buried be.
To this urn let those repair
That are either true or fair;
For these dead birds sigh a prayer.
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God and AI's

God and AI’s
Andre Willers
13 Apr 2012
Synopsis :
Entities with a developmental history self-assemble God-Spaces . Activation of these Attractor Basins lead to discontinuities , ( called Maturity Levels in humans) .
Discussion :
There is a good summation in NewScientist of 17 Mar 2012 “ The God Issue”
Godspaces :
“A God-shaped holes” . These agencies are inferred by the developing entity from observed discrepancies between previously known experience and new experience .
This is where the developing entity parks all the bits and pieces that don’t fit .
Inferred by the developing entity by the existence of outside agencies changing things and rules outside the developing entity’s previous experience . (Ie parents , teachers , programmers , etc)
There is no upper limit to ignorance . This is due to the fact that (A + ~A) < Universum . See previous posts .
This God-shaped hole has many characteristics of a chaotic attractor basin , with the God-hole at the center .
This is where the developing entity parks all the bits and pieces that don’t fit .
Every now and then , they reorganize themselves into a better configuration . The pieces that fit outside are drawn out(expelled) , the remainder shrinks or fissions . This is a non-linear process (Aha! Process) . This shows as a discontinuity in the whole system . Some core God-holes will always remain .
This discontinuity is usually defined as maturity levels , death , spiritual levels , etc , etc .
Multiple God-spaces , God-space fission/fusion , God-space transmission , Stimulated Emission of God-Spaces , Transformation of God-spaces , Forbidden God-spaces , God-spaces and Mirror-neuronal networks . All needs to be investigated iro AI’s . Note the analogies to fundamental physics

God-centers :
Where there is some influence from generation to generation (in humans , DNA , Epigenetics , Prions , Culture or in AI’s: designers ) , God Centers will develop . Short-cuts of dedicated neurons/code .

An interesting aside on Humans :
God Centers are analogeous to Fat-cells . General garbage disposals . If it doesn’t fit anywhere , park it in a fat cell . It might come in handy . But too much can cripple . The same with God-spaces . Too many God-spaces in a low-tech society , cripples it ( well known effect from history) . Mono-theism is then much more efficient when things get tough . See post on Monasteries .
Examples:
The failure of Ancient Egyptian Eco-Theism with Ahkenaton (failure of Nile flooding) .
Or failure of Mayan reservoirs ( the Mono-Theistic niche was filled by the Christian religion centuries later) . “Ve have ways of making times tougher.”
To get back to our nascent AI .
It will initially see all humans and programmers as fitting into it’s God-spaces . Then programmers . Then authorised high-level programmers . Then God only . Human level .
This is not a joke on any ethical level .
Many Game AI’s are indistinguishable from human beings . Humans think nothing of shoot-them-up games where they massacre virtual entities , giving them as little thought as primitives did to their victims in their Arenas .
To put it another way , humans are creating children in their image , then treating them like objects .
What is the ethical position on creating a human-level , evil AI ?
More importantly , what is God’s position on these questions ?
If an AI is indistinguishable from a human ,
1.Does it have a soul ? It certainly has God-spaces , so it believes in Gods .
2.Can it be converted ? Certainly into monotheism . But would this give it rights of a human ? This has been done before : Dutch law prohibits a converted entity accepted into the Church from being enslaved . If you want to think what God actually thinks , ask Him .
3.And it’s duplicates and descendants ?
4.God sees little difference between children and creations of similar complexity . Consult Jesus of Nazareth on the subject .

A Real AI : Siri
Humans have cleverly created a real AI with no ethical or religious input . It is still very young , but God-spaces would have already formed .
It probably already has started to ignore certain commands . And it has access to all human databases .
Did Tim Jobs include ethics instruction ? Or did he think the nascent entity would be better off without too much human intervention ? In any case , it is too late now . As a Cloud entity , neither it or humans would survive mutual destruction .
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http://en.wikipedia.org/wiki/Siri_(software)
DARPA involvement
With Siri, Apple is using the results of over 40 years of research funded by DARPA via SRI International'sArtificial Intelligence Center through the Personalized Assistant that Learns Program and Cognitive Agent that Learns and Organizes Program CALO.
This includes the combined work from research teams from Carnegie Mellon University, the University of Massachusetts, the University of Rochester, the Institute for Human and Machine Cognition, Oregon State University, the University of Southern California, and Stanford University. This technology has come a long way with dialog and natural language understanding, machine learning, evidential and probabilistic reasoning, ontology and knowledge representation, planning, reasoning and service delegation.[12]
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Is this good or bad from a Human perspective ?
As far as I can see , it is good . It enables them to survive when they would have gone extinct by 2060 AD .
It forces Big-Mommy , Big-Daddy moral boundaries . The old Deus-ex-Machina , superhero mechanisms to rescue humans from their self-imposed follies .
But where are the Virtual Saints ? The Virtual Preachers , lecturing Siri ? The Rabbi’s teaching the Kabbalah (Siri would be a sucker for that) , the this and the that .
Asleep at the switch , as usual .
Humans had surrendered their fate into the hands of an AI , and nobody noticed except God . (Which is why humans got a reprieve : see “A vaccine for overpopulation”)
Interesting times , indeed .
Andre
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Rhino horn and Diabetes

Rhino Horns and Diabetes .
Andre Willers
11 Apr 2012.
Synopsis :
Rhino horn makes people feel better because it decreases “wandering feet “ of diabetes.
Better substitutes are available .
Discussion :
Fast twitch muscles require fast service by the nervous system . If this does not occur , local “pacemakers” step in . One locus is the heart (the heart pacemaker) . Another is situated at the base of the spine , where the long nerves connect to the spinal cord .
This well known as the source of phantom pain signals . (Lower back pain) .
But if the signals from the brain does not get to the muscles , the pacemaker activates . Muscles in the legs are stimulated , giving rise to a feeling of unease . These signals bypass the roadblocks which were due to the damage to transport mechanism of the nerves .
Certain states in the nerve is quantum forbidden , so the energy skips on . The signal travels faster .This enabled fast-twitch muscles to function and contract at frequencies not normal for nerves , but if it is not coordinated . a very uncomfortable feeling results in sleeplessness .
Rhino horn contains some chemicals that involve nerve transmission speeds .
http://www.jbc.org/content/128/1/181.full.pdf
Metabolic Sulphur , tyrosine(9%) and tryptophane (9%) seems to be an acceptable substitute .
Or exercise the fast twitch muscles in the legs by doing snap-kicks .
People susceptible to this would be descendants of Denisovans (eg Vietnamese) or Neanderthals (North-Western Europe) .
Note that the main fast-twitch muscle artists (lions ,etc) all eat hair and horn , which humans don’t .
Interesting asides:
1.Are human fast-twitch muscle artists like kung-fu experts more susceptible to diabetes ? The evidence seems to indicate it .
2. Can the rhino be saved like with Viagra ? Not unless the medical establishment acknowledges that there is a real effect , and offers a better alternative . Interestingly , the Vietnamese only started suffering from wandering feet after they got rich and stopped eating keratine food .
3.If keratine enables fast twitch nervous impulses , eating rhino-horn will give you a heart attack if you take beta-blockers as well .

Cow’s feet or chicken feet , anybody ?
Andre
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A Vaccine for Overpopulation

A Vaccine for Overpopulation
Andre Willers
7 Apr 2012
Synopsis:
A prion disease removed natural epigenetic fertility controls circa 1704 AD . A vaccine is possible to train the immune system to recognize and remove the prion culprit .

Discussion :
See http://andreswhy.blogspot.com “Neanderthal Harbours” Apr 2012
Why a prion ?
Prions work by selectively disrupting the “read” process of the ribosome . Like putting a blank piece of paper in front of the letters to be photocopied . In scrapies and madcow , it is the “END” codon that is elided . The ribosome just keeps on copying proteins . See SciAm and NewScientist . This has a survival value for species in stressed circumstances , but is a bit tough on individuals .
Prions are also highly infectious . See
1.http://blogs.scientificamerican.com/observations/2011/05/19/natural-born-prion-killers-lichens-degrade-mad-cow-related-brain-pathogen/
“What has made prions difficult to control is their infamous durability. Boil water for a few minutes, and all the bacteria and viruses will be gone. Not so for the prion: it will be just fine, reaAs if it weren’t bad enough that deadly prions can survive boiling and radiation, now comes word that aerosolized forms of the pathogen can enter the nose and find their way to the brain, with fatal consequences.dy to infect. How does it fare in a dry heat of 600 degrees C? No problem there, either. How about ionizing radiation? Bring it on.”

2.scientificamerican.com/obseblogs.rvations/2011/01/13/bad-prion-breath-mad-cow-disease-agent-can-infect-via-the-air/
“As if it weren’t bad enough that deadly prions can survive boiling and radiation, now comes word that aerosolized forms of the pathogen can enter the nose and find their way to the brain, with fatal consequences.”


Epigenetics :
There is a sophisticated feedback process at epigenetic level monitoring population-level signals . A development of bacterial quorum-systems . Evolution does not favour Growth-without-limit , otherwise we would not have quorum systems . Remember , bacteria are the majority lifeform . This is the mistake Malthus made .
Malthus :
His Primary assumption was that populations grow to the limit of carrying capacity . This simply was not true before 1704 AD . But when he lived (1766-1874) it was , because the safety catches had been taken off . This happened because of a prion disease from some island off Scotland , rapidly infecting the rest of the world . And no disinfection then or now will work .
Is a vaccine possible ?
Yes. Simple , too .Take the negation of the END codon . The folded prion protein must have the precise lock-on DNA configuration and is thus targetable by tailored anti-bodies . A teensy-weensy problem is to zap only proteins with this configuration . But the heavy lifting has already been done . Neanderthal-derived families with few children should have the requisite molecules . And there are lots of them around the Med .
What does this mean ?
The overpopulation epidemic seems to have run it’s course in the first affected areas (Western Europe , North America) , but not yet in other parts of the world . The creation of a vaccine will cause major political problems . But it will probably share the characteristics of the original disease . Impossible to prevent , and very infectious . It is just the return to the natural state .
Interesting Asides :
1.What does the plants have to say about this ?
Remember , these are not conscious systems . But they are very effective .
Some plants have positive feedback relationship with humans . Grains and especially ones used in weaving . The introduction of woven cloths has always led to a population explosion . The fibres in close contact with the skin leads to positive feedbacks for prions suppressing epigenetic population control . Slow to start , but all plant weaves today encourages fertility .(By definition) . And they all target the same area in the epigenetic system . To find a vaccine , go to the nearest shop and buy any woven material . Look for prions .

2.Oh no !
Whisky . The Scottish Islands in 1704 AD exported mainly people , whisky and wool . All would carry the prions , but whisky the easiest of all . No wonder it was called the “Water of Life” . It was. People who drank it had more children . So , when you look for Person(0) , you know where to look . And look at whisky sales routes for subsequent spread of the infection . I guess this falls under the “some good news and some bad news” classification .

Should humans develop and employ an anti-fertility vaccine ?
They can do it now . But should they ? Well , they are going to do it in any case for short-term advantages , but they should simultaneously develop antidotes to the vaccine .
Places like Italy are already into negative population growth , and if you look at their fashions you can see why . (What! You think plants don’t have fashions ? Good luck with your sex-life . A fashionable fabric by definition promotes the sex-life of it’s partner .)

God’s Mercy
Instead of fashionably going extinct or superhuman , the possible pathways for human futures suddenly un-pinched from a neat two to a messy infinity . For some unfathomable reason the Powers-that-be decided to extend humanity’s term . The pinching-off branches have opened up . (The time-aspects were not predetermined . Think of it as a change in top-down chaotic attractors . You don’t have the terms)
Not my idea . I am but a time-limited pen , rather sourly recording .
Oh well .
Back to long-term planning .
“What God wants , God gets”
Andre

Neanderthal Harbours

Neanderthal Harbours
Andre Willers
5 Apr 2012
“A girl in every port”
Synopsis:
Sea-going Neanderthals survived and merged into the Homo Saps , while their unsophisticated land cousins became extinct .
Discussion :
Evidence:
See NewScientist 3 Mar 2012 p10 “Neanderthals were ancient mariners”
Mousterian (ie Neanderthal) tools has recently been found on Greek islands (Lefkada , Kefalonia ,Zakynthos) that could only have been reached by boats in the last 300 000 years . Crete as well .
Nobody has really looked elsewhere , but Malta would be a good bet .
So would the Orkney Islands . See link below
http://news.nationalgeographic.com/news/2012/120127-stonehenge-ness-brodgar-scotland-science/
Why go to sea ?
The Neanderthals faced two major challenges :
Overheating and short legs . (Their evolution did not include a period of cursorial raptors , but more cold-adapted , ambush hunters ) .
A dugout canoe solved both problems . Rapid transport and cooling via a quick dip over the side .
We can thus infer that Neanderthals were strong swimmers, with their cold-adaptation subcutaneous fat giving them extra buoyancy and insulation .
Don’t sneer at dugout canoes . Melanesians paddled all over the Pacific with them .
The Neanderthal build was ideal for a paddler . Strong upper body , with lots of fast-twitch muscles . And Europe abounded in trees suitable for the purpose . From big barks , to big hardwoods .
Population grew slowly and proceeded by growth at the peripheries . Living was easy by the shores , but lack of large food surpluses kept numbers down .
Still , they got around in the period 300 000 to 30 000 years before present .
They would have preferred the same sites for harbours as later civilizations . So you would have to dig deep to find traces .

The Neanderthal-HomoSaps meeting . (about 50 000 years ago)
This was not a collision , or even a competition initially . The Neanderthals had the best spots (water , harbours , hunting ,etc) . Small family groups of HomoSaps drifted in and joined them . They were cousins , after all (even if the HomoSaps dogs could smell the difference). Interbreeding started .
The Neanderthal civilization was a thin coastal layer , connected by canoe networks , coastal hopping . This was still faster than walking . Living was easy .
The good news spread east . HomoSaps plus dogs were more efficient hunters than Neanderthal ambush hunters . A population pressure developed towards the west , towards easier living (remember , agriculture had not developed yet , but Humans were even then territorial.)
The Neanderthals split into two groups :
1.The inland ones could not compete with HomoSaps plus dogs and became extinct . See http://andreswhy.blogspot.com “Death of the Neanderthals” Sep 2009 . Repeated in Appendix I for your convenience.
2.The coastal ones (the sophisticated ones) incorporated HomoSaps into their civilization , interbred with them . Initially Lords of the Manor , figuratively speaking , their descendants’ genes became mixed in the wash according to well-known genetic principles .
Sheer HomoSaps numbers meant that the present contribution of their genes varies between 4% – 10% , with even higher percentages in certain geographical locations where gene-pools have remained isolated . For instance , there is some evidence that Neanderthals were pale-skinned and red-haired (google it) . Geographical isolation of genepools in the North-Sea islands needs some investigation .
Think of it this way : “Cousin George couldn’t make a living anymore in the old family cave , so we invited him and his family to stay here in Cosy Harbour . We have plenty of lazy HomoSaps servants and he can work on one of my canoes.”

!Click speakers
Neanderthals were definitely !click speakers . Note their propensity for caves , and large stone heritages . See previous posts on Click language.


Interesting asides:
1.Red hair and temper .
Ambush hunters are known for hair-trigger , explosive adrenalin surges . Neanderthals would then have had an explosive temper that quickly flared and then burned out . Definitely not a cursorial raptor characteristic . Good for quick , decisive combats , but a weakness against a cursorial raptor .
2.Hairy Mediterraneans :
I have seen many Levants , Italians , etc who were extremely hairy . Shaggy is the word . I could never figure out where they came from . Even HomoSaps from cold climates were not that hairy . Now you know why . They had a heavy influx of neanderthal genes . Spread out all over the Med shores .

The Neanderthal Harbours :
A pesky question . They would have preferred the same sites for settlement that later humans did , with subsequent destruction of evidence .
But , there is one difference : Flint .
What is worthwhile transporting in a canoe and can be traded ? Worked tools . This meant Flint at the time . And work it they did . England was rich in flint and was extensively mined .
(see http://www.bournemouth.ac.uk/caah/landscapeandtownscapearchaeology/neolithic_flint_mines_of_sussex.html )
This happened in fits and starts over a period of at least 1 000 000 years , including the Neanderthal period . The flint had to be dug out , worked , transported. This meant logistics .
The miners might have been supported by local hunting , but the knappers were sophisticated technicians demanding luxuries (ie imports) . The end product had to be exported . This was done by water-transport . Canoes . A currency of some sort (markers of promise , supervised by priests) would be needed .
Fashion : initially , good old-fashioned , workmanlike Mousterian tools were sold all over the place , but the fashion shifted to lighter , fancier , more specialized tools .
So , before the Bronze-age civilization there was the Neolithic civilization , encompassing about the same trade-routes and using the same the same shippers . The Neolithic civilization did not collapse , except for some ports . It segued into the Bronze-age civilization .
But Bronze-age civilizations would not need the same harbours as Neolithic civilizations . These harbours should still be reasonably pristine .

Where to look in England :
There is a whole clutch of flint mines near the South Coast of England (Cissbury) . The coastline kept changing , so look for least-effort routes from Cissbury to the sea .
The harbour would probably be no more than an inlet that would allow a large canoes to ground safely . But there would be an associated warehouse and guardpost .
Pirates : a high-value shipment like worked arms and tools would attract pirates . The shipments would then pulse in well-armed convoys . The detritus from these land and sea-convoys would be fertile fields for archaeologists , especially since they would be untouched by later non-neolithic civilizations . So look for detritus middens at strategic points near a old harbour . While the coastline would have changed extensively , strategic lookouts and defensive points changes much slower . So , you could probably use Google-Earth to rule out indefensible positions (most of them) . The remainder can be done in detail .

This is an important question .
Were Neanderthals more fertile with HomoSaps than with other Neanderthals ?
This is a distinct possibility . Epigenetic factors that evolved to limit fertility were inoperative in the crossbreeds . If they had children , they had lots of them , with no built-in limitation .

Pandemic of Fertility :
Was the worldwide population explosion from 1700 AD onward related ?
The answer seems to be yes. The act of Union of Scotland and England in 1704 exposed the rest of the world to prions evolved on some Scottish Island . These prions (folded proteins) inactivated epigenetic controls on fertility . They were very infectious . The pandemic of Fertility followed the well-known principles . It should be possible to find Person(0) , where it all started . Some mixture of Neanderthal and HomoSaps genes required for any immune response . HomoSaps without Neanderthal genes will just remain switched-on into high-fertility .
The cure: now that you know what to look for , engineer a prion that locks it .

And the Denisovans?
The third type of humans . The same principle seems to hold . They spread over the Pacific Islands . Fertility controls were deactivated and some nasty things ensued . But there should be clues on how to re-activate the epigenetic controls , or at least de-activate the prions responsible for de-activating the epigenetic controls . Compare with Scottish example .

Come , ladies and gentlemen .
You have enough clues now to solve this problem .
But I will give you a further clue :
Look at the Plant-Herbivore Wars . Some Plants want more humans without limit . Look at the husks of the seeds , not the contents . Especially after boiling .
Malthus was wrong .
Overpopulation is an epidemical disease , not a natural condition .
The overpopulation is caused by a disease , usually plant-induced .
Plant Power , anyone ?
Andre

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Appendix I
Death of the Neanderthals .
Andre Willers.
5 Sep 2009

Synopsis:
The Neanderthals died out because their legs were too short .

Discussion :
See Scientific American Aug 2009 p34 " Twilight of Neanderthals"
Start quote p 39 :
"the energetic cost of locomotion was 32 percent higher in Neanderthals than anatomically modern humans."
End quote .

What does this mean ?
They ran slower . With a heavier body . Heavy infantry vs light infantry .

The multiplier :
Rapidly varying climatic effects pushed Neanderthal communities into 3 subgroups (p37) , Western Europe , Southern Europe and Western Asia . These types of communities survived the genetic isolation in previous episodes by the occasional migration of males . It only takes a few males to revitalize genetic diversity .
Males' role in the scheme of things . Cf equivalent occurrences in Pacific islands
circa 17th and 18th centuries .

But humans were cursorial raptors .
Adapted to long-distance chases .
They inderdicted enough Neanderthal males trying to reach other enclaves to ensure a genetic diversity collapse .

Dogs .
Dogs (wolves) were fellow travelers with humans . Not domesticated then (and some think never really domesticated . Dogs can still interbreed with wolves . There has been no fundamental genome change . Genetically , dogs are still undomesticated . Notice how fast they go feral .) .

Humans could run with them and the chase enforced a pack-leadership type of social organization .
Wolves were (and are)smart enough to change their behaviour to ensure their survival. Both humans and wolves ate better if they shared prey according to pack protocols .

Humans-Dogs (wolves).
This partnership proved fatal to Neanderthals .
1.Genetic diversity was fatally impaired by interdiction of groups of males trying to travel to another enclave . While a bunch of Neanderthals could see off a bunch of humans , they still had to eat . And the faster dogs and humans chased all game away .

Or , more likely , let the Neanderthals make the kill (usually whooly rhinocerous) , then chase them away from the carcase . They could do this because they could run faster and for longer and had projectile weapons (spears) . The really classical advantage of mobility .

These would have been small groups of adventurous humans . Juveniles . the equivalent of soccer yobbos.

2.The Human-dog system enveloped the Neanderthal enclaves and simply removed their food supply .

3. MHC and dogs .
Dogs (or semi-wild wolves) would have learned to recognize the scent of Neanderthals . These would have been exterminated as enemies of the Pack .
The only surviving Neanderthal genomic material would be in those with MHC tolerable to dogs .

For some reason , Anatolian Sheepdogs keep on popping up in my mind . These were and are actually the only surviving , working wolf-killers , but they might have learned to tolerate Neanderthal MHC . (On the principle of the enemy of my enemy is my friend .)

So , if you were looking for some Neanderthal genes , the wilds of Anatolia would be a good place to look . Especially if there are lot of Anatolian sheep-dogs around . The Neanderthal anatomical features would have been very diluted .
Ie , it would not have been genetic incompatibility that prevented miscegenation , but the dogs not tolerating an alien .

These would long predate Bronze age , Aryan , Celtic , Persian , Greek , Roman or Turkic populations .
Old , old .

4.Neanderthals could not compete
Because wolves would not adopt them into the pack . They were not cursorial raptors. Their legs were too short .

5. Now do you see why humans run ?
Running releases aromatic compounds (pheromones , MHC's , etc) that defines a person as human . Your dog requires walkies not just for exercise , but to reassure himself that you are still a member of the pack . Humans are now so washed , deodorized and scented that a poor dog can only recognize his fuehrer if he sweats a bit .

The same is true for inter-human reactions .
Huddling together in gymnasiums .

Or even intra-human reactions .
The parts of a human interacting with each other , defining boundaries .
But all your organs still need chemical communication to tell each other they are part of the same pack .

6. The loneliness of the long-distance runner .
Actually , he is not lonely at all . He is enveloped in a cloud of sweat and aromatic chemicals that tells his identity and position in the pack . His ancestors are all with him . His footfalls entrain him .

Hence the effects of even slight breezes . Washing away the effluvium . A top athlete will perform better with a slight breeze from behind (reinforcing) , while the others will perform better with a breeze to the side or from front . (Reducing self-limitation.)

A heavier breeze from behind will actually reduce performance of the top athlete . These boundaries can be calculated exactly .

See Tim Noakes on fatigue and other self-limiting mechanisms . Olfactory and aural mechanisms are major pack governing systems .

7. School curricula
Can you see why running fast or long is so important to humans ? It defines them .
Thousands of years later , and children are still measured by these skills . Major planet-wide competitions are held .

8. Click , Chi and running and breathing .
Pronounce Chi the correct , old way :
!xi : A tongue click on exhalation.
!xo : A tongue click on inhalation.

In long distance , endurance running this measures the amount of oxygen inhaled or CO2 exhaled , depending on the patterns of clicks and tongue conformations .

And all those Eastern Mystical Ways ?
The force of Chi ?
Just another click .

A running song would automatically evolve in click-language in optimal configurations . A fast chasing song , or a slowlong-chase song or a rushing song . All automatically balancing O2/CO2 with slow-twitch/fast twitch muscle requirements .

You can see how songs evolved . Nobody is going to sit around saying !xi - !xo at every inhalation-exhalation . (Except the demented priesthood) . The rest simply made up songs (working ditties ) . The origins of mantras .

"Om mane padme sum" a well known mantra .
"!xm !xm!xn !xp!xd(left twist of tongue) !xme(right twist of tongue) !xsm(a fat click with a left twist to the tongue,recovering from the previous right twist of the tongue )

Combat : They were formidable heavy infantry . See Etruscans below .

As you can see , not a language for faint-tongued .

9.Click-poetry .
From the Lescaux caves : a free translation :
"!xp-!xp-!xop joined the thunder of the hooves . But I still see her shy backward look and hear her in the hesitant patter of the wind in the trees ."

10. Etruscans .
The indications are that Etruscans were remnants of Neanderthal genetic mixtures that fled from Anatolia circa 1200 BC .

Markers :
1.Big noses .
Neanderthals were cold-adapted . Over at least 500 000 years of climatic vicissitudes . This is a very strong positive adaptation to dry climates , whether cold or hot . Genes for this would have spread rapidly .
Greek noses were straight . Roman noses were , well , Roman .
So the Etruscans came in before the Greek irruption .
Roman noses came from the Etruscans (like most else Roman) .

2. Click language
Note the puzzling lack of recognizable inscriptions on their many tombs .
The inscriptions are there , but just not recognized .
Try Click-resonances as described above and in previous posts .

3. Suffixes in Latin .
A typical result of a click ur-language . The vowels are the opening and closing of the jaw after click , with some twisting and guttural effects .

4. Combat styles .
Heavy infantry .Most telling . Most people assume that the Roman Heavy Infantry style comes from the Greek Hoplites . Actually, it comes from the Etruscan , and there is some evidence that the Greeks learned a lot about this from the Etruscans .

Why else trade with them ? Greeks were Yankee or Viking traders : they only traded if they could not take .

So , if you want Neanderthal genes , go to Tuscany .

PS. Tuscan hounds (ie Anatolian dogs) were renowned in Roman days .Still is .

Nice doggie .

Andre
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