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The Huskies used in sled racing are remarkable animals.
The annual Iditarod race has teams of dogs competing to
cover 1600km in 9 days. This is equivalent to 4
marathons/day for 9 days straight at world-record pace
while dragging a human, camping gear and a selection of
snacks through the snow.
They're able to do this because
they have an astonishing capacity to metabolize fuel into
movement, recordings of dogs with VO2max above 280 ml
O2/kg/minute exist while even chemically enhanced
humans struggle to reach 80.
Now, VO2max is a slightly silly measurement, but I've
managed to work out* that they're making about 1100W of
useful propulsive force. Herein lies the origin of the logic
used by tedious human running enthusiasts. After doing
some jogging, they're 73% likely** to tell you about how
humans are the finest runners... persistence hunting, etc.
Obviously, humans can't out-sprint dogs, as experienced by
many a fleeing criminal and humans, have failed to win the
Iditarod*** so far. The truth is that mammals are around
25% efficient and fur-coated huskies overheat quickly
unless the ambient temperature is low, while fur-less
sweaty humans do OK.
But can we use this, 1100W running output at 25%
efficiency means each dog is generating 4.4kW or almost
3x more than a puny American space heater. Can we use
this for domestic heating? Of course! a large hamster-style
exercise wheel would work but would be noisy, expensive
and the dog wouldn't be able to dutifully follow you around
heating specific rooms. So, careful deployment of the
mitochondrial uncoupler 2,4, dinitrophenol will get you the
heat output without all the running.
By simply checking the weather forecast and consulting the
handy wall-chart, varying doses of dnp can be added to the
morning food to achieve the desired temperature. For
large and poorly insulated houses, additional dogs are
recommended. Canny pet food manufacturers will latch on
to the opportunity and likely provide wall charts & DNP for
free with the cases and cases of additional dog food.
*by reading around the subject of exercise "science". I feel
somewhat dirty now.
** the remaining 27% is the ongoing mystery of this knee
pain, the surgeon said to give it 6 weeks but after 2 I felt
OK, but now it hurts again, I can't work it out.
*** the Iditabike record, humans riding bikes over the same
course, is about twice as long.
DNP
https://acronyms.th...edictionary.com/DNP
damn near perfect (and others) [DenholmRicshaw, Dec 31 2019]
Wikipedia: Scleroderma § Pathophysiology
https://en.wikipedi...rma#Pathophysiology
Mentioned and quoted in my anno [notexactly, Jan 03 2020]
Mitochondria Bioenergetics & Disease
https://www.youtube...watch?v=1aCHrHwm_AI
[bs0u0155, Jan 03 2020]
Void coefficient
https://en.wikipedi...ki/Void_coefficient
[Voice, Jan 05 2020]
Inferno: My Week On DNP (T-nation)
https://web.archive...erno-my-week-on-dnp
There's a reason even bodybuilders avoid "mitochondrial uncouplers" [sninctown, Jan 08 2020]
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Annotation:
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This should be fine. The only snag is that overzealous
administration of DNP can cause rather dramatic heart
problems - a recent discovery on my part. |
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We had always assumed, based on observation, that you are completely heartless. Is this in fact incorrect ? |
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Partly. I'm down part of an atrium. |
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//down part of an atrium// |
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Christ, well, I'm fairly sure I advised caution, somewhat
uncharictaristically. Aside from any causation, dnp does
reduce infarct sizes by up to 40% in various models, so in
different circumstances, it could have been better/worse... |
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Oh not, don't call him that - you're just feeding his Messiah complex. He'll be trying the walking-on-water thing again, and it's just so embarrassing (but very, very funny - we move the stepping stones, you know). |
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Well, to be fair, I had titrated up to the edge of
hyperthermia
over a very long time. In retrospect, I suppose it makes
sense that
cardiac muscle would suffer more from inadequate oxygen
than from excess heat (that, at least, is my current theory).
What's especially annoying is that you get out of breath
when
your skeletal muscles want more oxygen, but not when
cardiac muscle does. Live and learn, just about. On the
plus side, the best time to have a cardiac adventure is when
you're young and fit enough to enjoy it. |
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Interested to know how/why DNP reduces infarct size. |
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It doesn't, exactly; the infarct remains the same size, but the heart expands enormously, so relatively speaking the infarct is smaller. |
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As to the original idea, huskies - while having many laudable qualities - are not ideal in many homes, due to their large size. They do not, for example, make good lap dogs. The fact that they persist in trying to be lap dogs ("When I was a puppy I sat on my Pink Blob ... just because I am now a 55 Kg block of muscle and bone, capable of casually crushing a human thorax by gravity alone is no impediment to me jumping up and wanting fuss") is problematic. |
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There are smaller breeds that, even without DNP enhancement, can act as very efficient heat sources. |
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Henceforth I shall rely exclusively on your medical wisdom,
[8th]; assuming of course that every other human, bab[b]oon
and kohlrabi is dead. |
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Here's me thinking that DNP means Damn Near Perfect - see
link |
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Denholm - Naturally Pleasant. |
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Hmm. According a paper, DNP reduces cerebral infarct
damage (and presumably also cardiac infarct damage) by
stopping mitochondria going bananas at the time of infarct.
Interesting. |
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This would be where the term Three Dog Night comes from. |
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//Interested to know how/why DNP reduces infarct
size.// //stopping mitochondria going bananas at the
time of infarct. Interesting.// |
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The protective effect of low level uncouplers on
ischemia/reperfusion injuries is as old as the hills, it
seems to get re-discovered/published every now and
then. Theres support from natural equivalents like
uncoupling proteins (UCP1/2/3, I'm still not fully
convinced it's their full-time job) and a selection of
Voltage-gated mitochondrial channels,
mitoKatp/mitoKca2+ which when opened seem
protective. There's evidence from the mtDNA subtypes
too, people with mtDNA that codes for leaky
mitochondria seem to do better. |
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Getting a bit hand wavy, ischemia blocks O2 AND
substrate, ATP starts to fall and the system tries to
compensate by opening all the taps. You get a fully
reduced respiratory chain with no outlet, glucose is
rapidly used as a temporary fix, but it's the fuel for the
redox buffer system (Glucose>NADPH>GSH). NADPH falls
in an attempt to hold up mito membrane potential,
further depleting the redox buffer. O2 arrives back, the
fully reduced respiratory chain reduces a load of O2 to
the
ROS superoxide and you get downstream damage that
extends beyond the confines of the original injury.
Uncoupler effectiveness AND superoxide production rises
in a very non-linear (4th power?) manner with membrane
potential. A little leak can prevent a lot of superoxide. |
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//you get out of breath when your skeletal muscles want
more oxygen, but not when cardiac muscle does// |
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Is that true? The signaling is all CO2/O2, adrenergic
stimulation through adrenaline/ephedrine etc, will
increase heart rate and you'll get slightly out of breath
without moving. There would be a problem if the
plumbing didn't link the CO2/O2 to the sensors properly. |
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// Is that true?// I think I think that I meant: when you
are "normally" exhausted, you get lots of extra CO2 from all
your skeletal muscles, which you perceive as being out of
breath. But if you're tanked up on DNP, maybe your heart
struggles to get enough O2 (or to get rid of enough CO2)
even
though your blood is reasonably well oxygenated and low in
CO2. Maybe. We're talking pretty high doses (600mg/day). |
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//A little leak can prevent a lot of superoxide.// That's
also interesting. In fact, you are full of interesting things!
It's been said (maybe shown) that low-dose DNP slows
ageing in mice, even though the dose isn't enough to lead to
weight loss. If some part of ageing is down to superoxide
(in either healthy cells, or in senescent cells), that might
make sense. |
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// reduces a load of O2 tothe ROS superoxide // |
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What about the lactic acid pathway ? That's prominent in oxygen-deficient metabolism. |
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// [stuff about ischemia and reactive oxygen species] // |
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Do you think uncouplers might be effective against scleroderma, then? |
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// Its proposed pathogenesis is the following: It begins with an inciting event at the
level of the vasculature, probably the endothelium. The inciting event is yet to be
elucidated but may be a viral agent, oxidative stress or autoimmune. Endothelial cell
damage and apoptosis ensue[…]. […] The damaged endothelium then serves as a
point of origin for blood clot formation and further contributes to ischaemia-
reperfusion injury and the generation of reactive oxygen species. // |
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Wikipedia also says that scleroderma can be a cause of Raynaud's, but I thought I'd
read also that Raynaud's can trigger scleroderma attacks in the extremities by
causing ischemia due to how it cuts off circulation there, but maybe that was just
my (inaccurate?) inference last time I read about this stuff. |
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// But if you're tanked up on DNP, maybe your heart struggles to get enough O2 (or
to get rid of enough CO2) even though your blood is reasonably well oxygenated and
low in CO2. Maybe. // |
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//Why would that occur?// Because, on DNP, you heart uses
more O2 (and makes more CO2) - in effect, it (and all your
muscles and other energy-using bits) is wasting a lot of
energy. |
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//maybe your heart struggles to get enough O2// |
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You're forcing the mitos to work harder, but the heart
isn't moving any more than usual, I wonder what
proportion of cardiac perfusion is semi-
peristaltic / contraction derrived? Beating in organisms
predates hearts. |
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//We're talking pretty high doses (600mg/day).// |
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er... about 50-80uM whole body, and it accumulates.
That's nuts, Bodybuilders, at least on forums, don't go
that high and they're not the most risk averse folk. |
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//low-dose DNP slows ageing in mice, even though the
dose isn't enough to lead to weight loss. If some part of
ageing is down to superoxide (in either healthy cells, or in
senescent cells), that might make sense// |
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I don't know how carefully energy expendature is looked
at, it might be compensated by downregulated leak
pathways. It might push marginal mitochondria /cells
over
the edge to degradation. I'm not sure if mtDNA quality has
been checked. Bottom line is, mitochondrial membrane
potential isn't well studied. Even people in the know,
parrot figures of 180mV in their introductions, which is
true when the mitos are ripped from their cells and with
succinate rammed backwards through it's transporter. In
cells, I reckon cells dial the mitochondria up and down on
demand to mitigate risk. |
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//What about the lactic acid pathway ?// |
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I covered that in "glucose is rapidly used as a temporary
fix," |
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But, the heart isn't set up to run on glucose, it's
ketone / fatty acid adapted. Glucose (and
glycogen / creatine shuttle) helps cover bioenergetic
dynamic range in tissues like skeletal muscle which go
from 0.002W to 100W in a moment. The heart has low
dynamic range, in a young athlete, maybe 50bpm to
200bpm. It's also responding downstream of a lot of
systemic buffering. I reckon glucose is mostly covering
the redox buffering. |
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//That's prominent in oxygen-deficient metabolism.// |
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We don't have any of that, the lactate is just shuttled to
liver mitochondria as part of the Cori cycle and greater
glutamine/alanine shuttles. I have some fanciful theories
about enzyme- generated H2O2 supplementing complex
IV, but it's all still O2 in the end. |
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//Do you think uncouplers might be effective against
scleroderma, then?// |
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You're dealing with the immune system. That's a complex
variable, bunch of scary cells. There's been a tiny bit of
work with MS models and DNP, but nothing major and no
obvious mechanism. There's an immune component to a
lot of the big poorly understood diseases, and likely a
mitochondrial component within that, they are, after all
undercover bacteria hoping to evade the immune system. |
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I've linked a vid that is, I think, generally interesting with
regard to mitochondria - metabolsim - medicine. |
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//That's nuts, Bodybuilders, at least on forums, don't go
that high and they're not the most risk averse folk.// In
retrospect, yes, it was a little rash. In mitigation, your
honour, I titrated the dose up over many weeks, keeping an
eye on temperature. At one point I was running a couple of
degrees too hot, and dialled it back a bit (or, to be precise,
spread the dose out more evenly across the day). The
whole heart-damage possibility never really occurred to me. |
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I also think that you develop a tolerance to the stuff.
Whether this is by faster clearance or by adaptations in the
mitochondrial gubbins I have no idea. |
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//I wonder what proportion of cardiac perfusion is semi-
peristaltic / contraction derrived?// It sounds like a design
flaw; a bit like a nuclear reactor/generator whose coolant is
circulated by the electricity it generates itself. |
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I'm seriously beginning to wonder if biology might be more
complicated than I'd given it credit for. |
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//a tolerance to the stuff.// |
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I'd guess compensation via thyroid function? |
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//It sounds like a design flaw;// |
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Design opportunity! The faster it pumps, the faster it
pumps, directly proportional. Just modulate the tubing
size in development. In the grand scheme of things, a
heart that isn't pumping needs no supply anyhow. |
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//biology might be more complicated than I'd given it
credit for// |
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We don't know how complicated it is. But we have
climate nailed, so any day now. |
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// I'm seriously beginning to wonder if biology might be more complicated than I'd given it credit for. // |
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Naah, it's just a whole bunch of tubes with coloured water in them, and that's pretty thick coming from someone whose family are notorious for never offering credit unless it's the means for leveraging a hostile takeover further down the line... "No, we're quite happy with 49% of the equity, for now... " |
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// It sounds like a design flaw; a bit like a nuclear reactor/generator whose coolant is circulated by the electricity it generates itself. // |
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Is that more or less of a design flaw than having the pumps driven by an external (grid) electrical supply, or by backup generators that can be flooded out...? |
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Pumps driven by independent backup steam turbine circuits, and passive circulation, are the remedy. It's largely mechanical - as long as the core is hot, thus needing cooling, there will be power for the pumps. Once it cool enough, the circuits shut down in sucession until it's only residual decay heat keeping the smallest one ticking over. |
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Once that one stops, you can open the lid and remove the cooked sprouts. |
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//Pumps driven by independent backup steam turbine circuits, and
passive circulation, are the remedy. It's largely mechanical - as long
as the core is hot, thus needing cooling, there will be power for the
pumps. Once it cool enough, the circuits shut down in sucession
until it's only residual decay heat keeping the smallest one ticking
over.// |
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I must admit I wonder why nuclear reactors can't have a fall-back
that uses the excess heat itself to shutdown safely.
I mean - there must be a good reason, otherwise they'd all do it. |
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<Placeholder for weary homily regarding the inexplicable stupidity of humans/> |
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Well, class, would anyone like to answer [Lors]'s question ? |
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Come on man, spit it out. |
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//I wonder what proportion of cardiac perfusion is semi-
peristaltic / contraction derrived?// If there were any
intelligence behind the design of the heart, you woudn't
have an aorta with a coronary blood supply hanging off it.
Instead, blood would run from the left
ventricle straight through coronary arteries, of which
there'd be a healthy redundancy. |
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//compensation via thyroid function// Possible, I guess;
but 600mg/day ended up having the same subjective effect
as 100mg/day used to, so that's a heck of a compensation. |
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BTW, enjoyed the linked mitochondria video, apart from
the bit where he goes a bit fuzzy and talks about qi. |
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//would anyone like to answer [Lors]'s [sic] question ?
// I don't see problem with using over-temperature to drive
a shutdown. Presumably it's done indirectly at the moment,
with core temperature feeding back to motorized control
rods; you could add a heat-dependent control-rod pusher
easily enough to couple things more tightly. And yes of
course the core continues to push out heat for a while even
after you shut it down, but having a fail-safer shutdown
mechanism wouldn't hurt. |
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//tubes with coloured water in them// That's for
amateurs. Real professionals can work without the colour. |
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// I don't see problem with using over-temperature to drive a shutdown. Presumably it's done indirectly at the moment, with core temperature feeding back to motorized control rods; // |
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No, you've missed the crux of the problem. As usual. Do you do it deliberately ? |
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<Brings up powerpoint diagram of NaK-cooled sub powerplant/> |
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The issue is cooling the core after the scram. Triggering the scram and whacking in the rods is the easy part. As [Loris] has recognized, the issue is sustaining coolant circulation from decay heat (short-lived nuclides) and the low level of residual fissions from delayed neutrons (all done and dusted in a few seconds, actually). |
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<Throws 3mW laser pointer at [MB]/> |
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Now, perhaps you would be good enough to use that solid-state coherent light source to indicate on the diagram the path of the primary coolant circuit; alternatively, we will be delighted to demonstrate the effects of this 1kW laser on your personal bodily particles. |
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// Real professionals can work without the colour. // |
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Well there you are, that's something for you to aspire to in 2021, isn't it ? |
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Some bright person did mention that //of course the core
continues to push out heat for a while even after you shut it
down//. |
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However, thanks for the laser pointer, I will add it to my
collection. |
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// Some bright person did mention // |
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<Overlay reading "NEGATIVE VOID COEFFICIENT" appears at bottom of diagram/> |
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Yes, obviously, we'd all assumed that from the beginning from
the way you were standing. There are treatments for
constipation, you know. |
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Yes, a well known one is working with a reactor with a positive void coefficient. |
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// Because, on DNP, you heart uses more O2 (and makes
more CO2) - in effect, it (and all your muscles and other
energy-using bits) is wasting a lot of energy. // |
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Then how is it that "your blood is reasonably well
oxygenated and low in CO2"? |
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Because, if you're just sitting around, your overall oxygen
demand might still be low. What I mean is, since the heart is
always working, and since DNP increases its oxygen demand,
it might not be able to pull in enough O2 from its blood
supply, even though that blood is well oxygenated. |
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In other words, DNP might cause a local (rather than body-
wide) shortfall of oxygen. |
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Well even if no one else does I appreciate your self-sacrificing n=1 study on the effects of DNP on the human body. |
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Thanks. On the plus side, I have now had just about every
medical examination, imaging and test available to mankind. |
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We have a special offer on invasive probing this week, if you're interested ... |
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//examination, imaging and test available// |
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Did you pass through a US airport recently? High
temperature on the thermal cameras leads to a swab test
extremely positive for nitrated hydrocarbons... |
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"Spontaneous human combustion" being adequately explained by the "wick effect", this suggests that some humans with particular physiological characteristics are little more than self-propelled incendiary devices, requiring only the correct environmental conditions and a suitable low energy ignition source. |
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No need to carry a firebomb if you are a firebomb ... add a few carefully selected medications to boost the effects ... |
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<Targets bioscanners on [xen] to determine body fat/moisture ratio/> |
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//Did you pass through a US airport recently?// I don't
think I've been through whilst on DNP. I have been through
a day or two after pausing it, and wondered if it would
register on the explosives swab, but I don't think they
swabbed my belongings (or me) on those occasions. Also,
DNP is a fairly widely-used chemical in several industries, so
I hope they'd not be throwing all users in gaol on suspicion
of tourist attacks. |
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//a few carefully selected medications// [bs] is probably
your man there. But I'd very much doubt if any biochemical
process could get you much above 60°C - all your
biochemistry would denature before you got to that point. |
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No, not to actually trigger the reaction or raise body temperature above normal; something to increase the victim's predisposition to ignite under the right conditions. |
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Dehydration and a high fat-to-muscle ratio seem to be precursors, plus a sedentary lifestyle. |
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Ingestion of ethanol in a concentrated form might help. |
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You'll struggle to get your blood alcohol much above 1.5%. I
suppose it might partition slightly into fat, but even then... |
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The closest I've come to actually achieving personal
combustion was when I decided to try fire-breathing. I was
wise enough to choose isopropanol as my fuel of choice, but
not wise enough to know that pure IPA (not the beer) causes
immediate and painful dehydration of the oral mucosa,
leading to a sort of reflexive blow-gasp manoeuvre. Given
that I was facing the source of ignition (in anticipation of a
spectacular and controlled flame-thrower effect rather than
an agonised uncontrolled blow-gasp), the whole thing went
very, very much awry. |
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We would almost pay to watch that ... |
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Alas this was back in the days before video. Moreover, it is
not something I plan on repeating. |
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// the same subjective effect as 100mg/day // |
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How would you describe that subjective effect, [MB]? Also,
what [Voice] said. About n=1. |
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Subjective effect as in being hot and sweaty, which is the
most noticeable effect of DNP. |
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Ah, so that's what you're telling the young ladies now, is it ? |
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And dare I ask what was the expected / intended result of the
experiment? Or was it more of an "I wonder what happens if I
press *this* button" sort of experiment? |
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“Some humans would do anything to see if it was possible to do it. If you put a large switch in some cave somewhere, with a sign on it saying 'End-of-the-World Switch. PLEASE DO NOT TOUCH', the paint wouldn't have time to dry ..." (Pterry Pratchett) |
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//what was the expected / intended result// the intended
result was pain-free weight loss. To be fair, that bit of it
worked really well. |
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//intended result was pain-free weight loss.// |
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The heating bill and invention of ski-shorts were pleasent
side effects. |
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Having had the misfortune to view [MB] in his figure-hugging* Lycra® garb from short range, we are obliged to inform you that you are completely and totally wrong about the second part of that. |
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*Think of a ten-days-dead Humboldt squid stuffed into a pair of well-used nylon tights. Concentrate on that image. When you've stopped retching, think of all the ways it could be worse. |
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Well, frankly [8th] it serves you right for drilling that hole in
the partition. |
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We were curious; we couldn't work out what the strange noises were. It sounded like, well, very like someone trying inexpertly to stuff a deceased squid into a pair of used nylon stockings. |
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And in a way, we were correct. Not that that helps with stopping the flashbacks and the panic attacks ... |
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Some Iditarod tell-all books claim that sled dogs run best when it's
cold out...anecdotally, zero Fahrenheit is optimal for sled dog
performance. I suspect the sled dogs would not be very happy
running full speed at room temperature. Maybe if there was a way for
the dog to sweat like a human, or at least remain damp? I don't know.
Another anecdote is that rowers can row (erg) faster if blown with a
fan for better cooling. I suspect human Arctic travelers typically don't
push the limits in this area since that results in sweat, which would
then freeze. Come to think of it, that might be why wolves don't
sweat...so their fur doesn't get wet and then freeze in the snow. |
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// if there was a way for the dog to sweat like a human ... why wolves don't sweat...so their fur doesn't get wet and then freeze in the snow // |
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Canines don't have epidermal sweat glands, except in their pads and nose; temperature control is through the mucous membranes, by panting. Heat is dissipated by evaporation. |
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Because of their coat, sweating wouldn't be an efficient form of heat dissipation as the hair deliberately traps a layer of dead air next to the skin. |
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Getting wet, even in freezing weather, doesn't seem to be particularly bothersome to medium and large dogs. They leap in and out of icy water with every indication of enjoyment. There is clearly an evolutionary adaptation- in the case of Spaniels, it seems to take the form of a minaturized 5MW thermal nuclear reactor ... |
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//or at least remain damp? I don't know.// |
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Maybe a mesh suit for huskies with blocks of dry ice? |
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