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.-- bs0u0155, Dec 31 2019 DNP https://acronyms.th...edictionary.com/DNPdamn near perfect (and others) [DenholmRicshaw, Dec 31 2019] Wikipedia: Scleroderma § Pathophysiology https://en.wikipedi...rma#PathophysiologyMentioned 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-dnpThere's a reason even bodybuilders avoid "mitochondrial uncouplers" [sninctown, Jan 08 2020] 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.-- MaxwellBuchanan, Dec 31 2019 We had always assumed, based on observation, that you are completely heartless. Is this in fact incorrect ?-- 8th of 7, Dec 31 2019 Partly. I'm down part of an atrium.-- MaxwellBuchanan, Dec 31 2019 //down part of an atrium//
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...-- bs0u0155, Dec 31 2019 // Christ //
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).-- 8th of 7, Dec 31 2019 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.
Interested to know how/why DNP reduces infarct size.-- MaxwellBuchanan, Dec 31 2019 It doesn't, exactly; the infarct remains the same size, but the heart expands enormously, so relatively speaking the infarct is smaller.
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.
There are smaller breeds that, even without DNP enhancement, can act as very efficient heat sources.-- 8th of 7, Dec 31 2019 Henceforth I shall rely exclusively on your medical wisdom, [8th]; assuming of course that every other human, bab[b]oon and kohlrabi is dead.-- MaxwellBuchanan, Dec 31 2019 Here's me thinking that DNP means Damn Near Perfect - see link-- DenholmRicshaw, Dec 31 2019 Denholm - Naturally Pleasant.-- MaxwellBuchanan, Dec 31 2019 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.-- MaxwellBuchanan, Jan 01 2020 This would be where the term Three Dog Night comes from.-- 2 fries shy of a happy meal, Jan 01 2020 //Interested to know how/why DNP reduces infarct size.// //stopping mitochondria going bananas at the time of infarct. Interesting.//
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.
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.
//you get out of breath when your skeletal muscles want more oxygen, but not when cardiac muscle does//
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.-- bs0u0155, Jan 02 2020 // 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).
//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.-- MaxwellBuchanan, Jan 02 2020 // reduces a load of O2 tothe ROS superoxide //
What about the lactic acid pathway ? That's prominent in oxygen-deficient metabolism.-- 8th of 7, Jan 02 2020 // [stuff about ischemia and reactive oxygen species] //
Do you think uncouplers might be effective against scleroderma, then?
Wikipedia [link] says:
// 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. //
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.
// 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. //
Why would that occur?-- notexactly, Jan 03 2020 //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.-- MaxwellBuchanan, Jan 03 2020 //maybe your heart struggles to get enough O2//
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.
//We're talking pretty high doses (600mg/day).//
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.
//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//
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.
//What about the lactic acid pathway ?//
I covered that in "glucose is rapidly used as a temporary fix,"
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.
//That's prominent in oxygen-deficient metabolism.//
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.
//Do you think uncouplers might be effective against scleroderma, then?//
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.
I've linked a vid that is, I think, generally interesting with regard to mitochondria - metabolsim - medicine.-- bs0u0155, Jan 03 2020 //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.
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.
//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.
I'm seriously beginning to wonder if biology might be more complicated than I'd given it credit for.-- MaxwellBuchanan, Jan 03 2020 //a tolerance to the stuff.//
I'd guess compensation via thyroid function?
//It sounds like a design flaw;//
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.
//biology might be more complicated than I'd given it credit for//
We don't know how complicated it is. But we have climate nailed, so any day now.-- bs0u0155, Jan 03 2020 // I'm seriously beginning to wonder if biology might be more complicated than I'd given it credit for. //
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... "
// It sounds like a design flaw; a bit like a nuclear reactor/generator whose coolant is circulated by the electricity it generates itself. //
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...?
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.
Once that one stops, you can open the lid and remove the cooked sprouts.-- 8th of 7, Jan 03 2020 //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.//
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.-- Loris, Jan 03 2020 <Placeholder for weary homily regarding the inexplicable stupidity of humans/>
Well, class, would anyone like to answer [Lors]'s question ?
Anyone ... ?-- 8th of 7, Jan 03 2020 Come on man, spit it out.-- Loris, Jan 03 2020 //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.
//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.
BTW, enjoyed the linked mitochondria video, apart from the bit where he goes a bit fuzzy and talks about qi.
//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.
//tubes with coloured water in them// That's for amateurs. Real professionals can work without the colour.-- MaxwellBuchanan, Jan 03 2020 // 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; //
No, you've missed the crux of the problem. As usual. Do you do it deliberately ?
<Click>
<Brings up powerpoint diagram of NaK-cooled sub powerplant/>
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).
<Throws 3mW laser pointer at [MB]/>
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.
You may begin now.
// Real professionals can work without the colour. //
Well there you are, that's something for you to aspire to in 2021, isn't it ?-- 8th of 7, Jan 03 2020 Some bright person did mention that //of course the core continues to push out heat for a while even after you shut it down//.
However, thanks for the laser pointer, I will add it to my collection.-- MaxwellBuchanan, Jan 03 2020 // Some bright person did mention //
Yes, that was [Loris].
<Overlay reading "NEGATIVE VOID COEFFICIENT" appears at bottom of diagram/>-- 8th of 7, Jan 03 2020 Yes, obviously, we'd all assumed that from the beginning from the way you were standing. There are treatments for constipation, you know.-- MaxwellBuchanan, Jan 03 2020 Yes, a well known one is working with a reactor with a positive void coefficient.-- 8th of 7, Jan 03 2020 // 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. //
Then how is it that "your blood is reasonably well oxygenated and low in CO2"?-- notexactly, Jan 05 2020 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.
In other words, DNP might cause a local (rather than body- wide) shortfall of oxygen.-- MaxwellBuchanan, Jan 05 2020 Well even if no one else does I appreciate your self-sacrificing n=1 study on the effects of DNP on the human body.-- Voice, Jan 05 2020 Thanks. On the plus side, I have now had just about every medical examination, imaging and test available to mankind.-- MaxwellBuchanan, Jan 06 2020 We have a special offer on invasive probing this week, if you're interested ...-- 8th of 7, Jan 06 2020 //examination, imaging and test available//
Did you pass through a US airport recently? High temperature on the thermal cameras leads to a swab test extremely positive for nitrated hydrocarbons...-- bs0u0155, Jan 06 2020 Hmmmm ...
"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.
No need to carry a firebomb if you are a firebomb ... add a few carefully selected medications to boost the effects ...
<Chuckling/>
<Targets bioscanners on [xen] to determine body fat/moisture ratio/>-- 8th of 7, Jan 06 2020 //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.
//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.-- MaxwellBuchanan, Jan 06 2020 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.
Dehydration and a high fat-to-muscle ratio seem to be precursors, plus a sedentary lifestyle.
Ingestion of ethanol in a concentrated form might help.-- 8th of 7, Jan 06 2020 You'll struggle to get your blood alcohol much above 1.5%. I suppose it might partition slightly into fat, but even then...
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.-- MaxwellBuchanan, Jan 06 2020 Is there a video ?
We would almost pay to watch that ...-- 8th of 7, Jan 06 2020 Alas this was back in the days before video. Moreover, it is not something I plan on repeating.-- MaxwellBuchanan, Jan 06 2020 // the same subjective effect as 100mg/day //
How would you describe that subjective effect, [MB]? Also, what [Voice] said. About n=1.-- pertinax, Jan 07 2020 Subjective effect as in being hot and sweaty, which is the most noticeable effect of DNP.-- MaxwellBuchanan, Jan 07 2020 Ah, so that's what you're telling the young ladies now, is it ?-- 8th of 7, Jan 07 2020 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?-- pertinax, Jan 07 2020 “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)-- 8th of 7, Jan 07 2020 //what was the expected / intended result// the intended result was pain-free weight loss. To be fair, that bit of it worked really well.-- MaxwellBuchanan, Jan 07 2020 //intended result was pain-free weight loss.//
The heating bill and invention of ski-shorts were pleasent side effects.-- bs0u0155, Jan 07 2020 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.
*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.-- 8th of 7, Jan 07 2020 Well, frankly [8th] it serves you right for drilling that hole in the partition.-- MaxwellBuchanan, Jan 07 2020 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.
And in a way, we were correct. Not that that helps with stopping the flashbacks and the panic attacks ...-- 8th of 7, Jan 07 2020 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.-- sninctown, Jan 07 2020 // 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 //
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.
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.
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 ...-- 8th of 7, Jan 07 2020 //or at least remain damp? I don't know.//
Maybe a mesh suit for huskies with blocks of dry ice?-- bs0u0155, Jan 07 2020 random, halfbakery