it's not a Beta-amyloid thing

Kenneth Collins k.p.collins at worldnet.att.net
Sat Jun 29 20:51:43 EST 2002


thank you for your reply. i'll see what i can do with its stuff.

John H. wrote in message ...
>The research community is well aware that it is not a beta amyloid thing,

the tenacious few.

>and in things biological whether or not one can talk about any specific
>starting point for any specific condition is becoming increasingly
>problematic.

in my view, the 'starting point' is the one-way flow of energy from order to
disorder that is what's described by 2nd Thermo [WDB2T]. this stuff maps an
energy-gradient that's everywhere extant within physical reality. following
this 'map', by climbing local energy gradients, 'translates' to 'moving
toward' food sources, increasingly. when the gradient diminishes, an
organism 'knows' that it should try moving in another direction.

this is exactly what occurs in bacterial chemotaxis.

anyway, because WDB2T is everywhere extant, and because everything within
physical reality is rigorously-coupled to it, evolutionary dynamics,
themselves 'move toward' it, the result being that biological systems are
structured, in their entirety, with WDB2T as a 'starting point'.

knowledge of this permits one to tweak any experimental design until it
coincides with WDB2T.

>Beta amyloid is essential, in itself not a problem, only when
>it take on particular structures leading to the phosphorylation of Tau
>(which is a caspase effector) does neurodegeneration really get a swing on.

i confess, i know not whether or not what you say, immediately-above, is
True.

in the perspective in which i work, such specific details 'do not matter'
[NQI [not quite it] they matter, but, given any particular experimental
design, one 'pins' this or that with respect to WDB2T, doing the same with
all parms, one by one, and one gradually 'moves toward' understanding of the
integrated dynamics inherent. [i've rewritten both Physics and Chemistry in
the analogous way.] if you 'wonder' why, i wanted to contribute, couldn't
afford to do it in the 'traditional' way [grad school, etc.], so i
'looked-elsewhere' for some way in which i could contribute. my work
converged upon the WDB2T approach, yielding some useful results - a
contribution.]

>Interestingly, at least according to one review I read recently these
>plagues begin in the extracellular spaces but I believe beta is produced in
>the ER.

surely a WDB2T-relevant site :-)

>
>Antioxidants have some benefit in Alz but are not the answer, the effect is
>limited and by the time symptoms appear the low level inflammatory response
>is well underway, a self propagating process perhaps via il1 prodn by
>microglia and il1 itselt stimulates beta a prodn, though there are
obviously
>precursors to this activation that lead to the pathology occurring.

i'd begin by doing the differential-scan stuff that i've written about.

in my view, the whole thing is a break-down in the rigorous coupling of
molecular dynamics with the neural activation that, 'normally' rigorously
couples nervous system and external environment, and which makes
'memory'-encoding rigorously-addressible.

in my view, the break-down within such rigorous coupling occurs because the
failure of one [or more] TD E/I-minimization mechanism[s], the result being
that the rigorous-coupling is rendered increasingly week, which is an
anti-WDB2T circumstance that should be detectable in the form of augmented
topologically-distributed 'randomness' within neural activation [observable
as augmented high-frequency 'components' [TD E/I(up)] within
differential-scans]. initially, the differential-scan methodology has to
make use of a trial-and-error approach, ranging widely, both in
neuroanatomical target, and range within target, accumulating 'clues' or
'signs' of the sought-after high-frequency stuff, gradually converging upon
the big picture of the underpinning 'abnormal' neural activation dynamics.

when this convergence occurs, then, and only then, does one turn to
molecular assay, seeking to discover what's broken-down to yield the
augmented 'randomness' that's been delineated.

note that the whole technique, including the molecular 'phase' and its
Chemistry [Physics], is, itself, constructed rigorously around WDB2T.

>
>"Making predictions on the molecular stuff" is a crock. Nothing in my,
>theirs, or your current understanding permits such exuberant
extrapolations.
>We still don't even understand calcium waves for brains' sake and I think
>the presumption that one can create a set of principles that will determine
>all neural states and conditions betrays an under appreciation of just how
>indeterminate biological processes are and more importantly just how bloody
>ignorant we are.

given a detailed description of any experimental design, and using the WDB2T
approach, prediction is straight-forward. the method is so solid that one
can run enhancements to the experimental design in one's head [of course,
iff the original experiment is replicable, and it's best to go forward in
small steps. this or that enhancement will have its own direction with
respect to the WDB2T 'map', so one has to work to isolate such directional
stuff as much as possible.].

it works be-cause WDB2T extends everywhere within physical reality.

this approach can be robustly-automated.

>
>Make this prediction:
>
>A person under chronic personal stress working on a high cognitive load for
>many months, foregoing sleep,

result: TD E/I(up), having wide-spread ramification which must be
sorted-out, and cross-correlated via differential-scanning.

i'd start by developing a brainstem differential-scanning technique

>maintaining dietary restriction but not sufficient supplementation,

same, but i'd also target the hypothalamus early-on.

>relying on coffee too much

same.

>and refuses to sleep until exhausted,

same

>has failing source and primary memory and is demonstrating
>increased attentional difficulties

i'd trace the TD E/I(up), using the differential-scanning technique[s], as
in my earlier discussion, with respect to the Alzheimer's problem, above.

> combined with increasing social isolation

here, i'd just reiterate NDT already-reified stuff.

>who spends one's days playing computer games rather than attending to the
>approx 250 pdfs to be read(hopeless, he'll never make it) and an urgent MSS
>re-submission.

"boredom"; AoK, Ap5, 7 8.

>How will such behaviour impact on Nfkb-cox 2- pge2
>/transcription -synthesis in the hippocampus with respect to LTP, EAA, and
>the differential expression of iNos and nNos, assuming that nNos is
>requisite for LTP induction and maintenance while iNos has potentially
>deleterious consequences on cell viability. And just to make it
interesting,
>see if you can invoke an explanation for the dopaminergic failure in the
pfc
>and why this has attentional implications.

it's all fall-out, as above, in cross-correlating molecular assays with the
'map' of WDB2T converged upon during the differential-scanning 'phase'.

Prediction: it'll all 'map' WDB2T, rigorously.

>
>Will the subject get the reading done and the MSS rewritten or will the
>editors tell him to piss off and what will be the state of his pfcs and
>hippocampus at the end of it all?

probably not, because he's, obviously, on the verge of being unable to feed
or shelter himself, and, within the the prescious energy-flow that remains
his, it's, obviously, of higher-priority to do the stuff that remains
needing to be done :-)

>
>
>John H.
>[...]

on my, analogous, part, i had to make the correlated decision long ago,
Hoping folks were getting-it, and, otherwise, doing what's necessary to
Guard Free Will.

if i were financially solvent, i'd set aside some of each day's energy-flow
to doing a "rewrite", but i cannot afford even to print what i write as it
is, let alone purchase updated texts, and photocopy all the articles that'd
have to be included in an Honest rewrite of AoK. i can't even afford to take
all my previous years' work out of the boxes into which i had to put it,
upon this or that forced move, some of the boxes going back 30 years,
unopened, handled only during the arm-stretching stuff inherent in moving
them, being able only to not fail my Obligation, as Scientist, to maintain
the documentation that they constitute.

so, i do what i can, as Opportunity shows itself.

thank you for a Generous instance of such Opportunity.

you cannot imagine what your Gift means to my Being.

Cheers, John, ken [k. p. collins]





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