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# Reverse osmosis effect in narrow tubes concentrates urine in the kidney Contrary to normal ("forward") osmosis, reverse osmosis moves water against the osmolarity gradient, from the salt water side to the fresh water side. It allows the production of fresh water from salt water, and is the most widely used desalination method worldwide. Reverse osmosis is normally pressure-based, but, a different type of reverse osmosis takes place in narrow tubes (micrometer scale) that also moves water in the direction opposite to normal osmosis, and therefore allows the production of fresh water. Such an effect is the basis of how the kidney concentrates urine, and it takes place in the thin segment of the nephron (it is why the nephron has evolved a narrow segment. ) In the kidney, the narrow tube effect is amplified by pressure, and the kidney adjusts how much it wants to concentrate the filtrate by adjusting the glomerular filtration pressure. To do this, it has evolved the tubuloglomerular feedback system in the juxtaglomerular apparatus. The role of tubuloglomerular feedback is simply to regulate the strength of the reverse osmosis effect in the thin segment, and it acts both locally via renin and systemically via angiotensin to achieve sufficient filtration pressure. This allows the body to prevent dehydration. The kidney thus concentrates urine by pressure, although the pressure itself is not the basis of the effect, it only amplifies the effect that is inherent to narrow tubes. # The role of adsorbed water in the mechanism of osmosis It was discovered in 2009 that the driving force for osmosis is the thin layer of adsorbed water that forms at hydrophilic surfaces. This adsorbed phase of water has the unusual (and unpredicted) property of being charge polarized, it releases protons into the surrounding water that gets positively charged, and itself gains a negative charge from the surplus of hydroxide ions it is left with. The force behind this charge polarization effect is analogous to the force in semiconductor junctions: diffusion, from thermal energy. Water in the adsorbed phase (that is a semi-solid phase that is halfway between liquid and solid phase) auto-ionizes just like liquid water, but contrary to water in the liquid phase the hydroxide ions are locked into the semi-solid mass that is anchored to the hydrophilic surface. The more mobile hydrogen ion will diffuse outwards to a larger extent than the hydroxide ion, causing the charge separation effect. Osmosis happens when there is an asymmetry between the thickness of the adsorbate on either side of a membrane. The asymmetry will cause protons to "even out their concentration" around the combined negative mass of the adsorbates on either side, so that the charge distribution is balanced out. The relative surplus and deficit of protons that results, will cause hydroxide ions on the exosmotic side (where water is moving from) to break down into dioxide, water and electrons, and the electrons will transfer over to the endosmotic side where there is a surplus of protons, and combine with the protons and dioxide to form dihydrogen monoxide, water. Water itself does not physically "move", it is broken down and built up on either side of the membrane. Only electrons and protons move during osmosis. The effect is analogous to what takes place in an acid-base battery. Salt impairs the formation of the adsorbed phase in the same way it impairs the solid phase by freezing point depression (a colligative property), and an increase in osmolarity on one side will decrease the amount of adsorbate at the membrane on that side, causing the effect of proton equilibration and the subsequent breakdown of hydroxide ions on the hypoosmotic side of the membrane. Pressure, acts in an opposite way to increase the thickness of the adsorbate, and therefore generates an osmotic transfer of water in the reverse direction to osmolarity-based osmosis, away from the pressure. In narrow tubes, the proximity of the adsorbate around the circumference of the tube and across the diameter causes an increase in the net positive charge of the lumen of the tube, and this effect will be yet another factor in how the protons even out their concentration (charge wise) across both sides of the membrane of the tube. This provides a method for reverse osmosis that can operate at very low pressures, such as that within the filtration system of the kidney. Since pressure increases the amount of adsorbate, it also increases the repulsion effect in the lumen of narrow tubes, and this allows the kidney to regulate the strength of the urine concentration mechanism by regulating the filtration pressure. # The loop of Henle recirculates dioxide, the cathode in osmosis The glomerular filtration tubular reabsorption pattern is physiologically complicated, and the peculiar and intricate loop design of the nephron has motivated a physiological model that explained why such as loop had been selected for, evolutionarily. This motivated the theory that the kidney operated by forward osmosis (osmolarity-based) and generated an osmolarity gradient using a counter-current multiplication mechanism, and that the loop of Henle had evolved to facilitate this process. The true reason for the loop of Henle is much more directly tied to the mechanism of osmosis: it recirculates the dioxide that is required for the cathode reaction in osmosis, so that the reverse osmosis process in the thin segment can reabsorb more water than would otherwise be possible with a single-pass of the dioxide. The recirculation of dioxide is complicated and it explains the complicated patterns of reabsorbtion in the kidney. Dioxide is relased into the nephron in the thin segment (thin descending limb) when water is reabsorbed by reverse osmosis (and transported out of the kidney via the ascending vasa recta. ) This dioxide has to be returned into the medulla and the blood stream, or it will be extreted in the urine. To reabsorb the dioxide, the kidney uses osmosis all over again, and moves water back into the ascending thin limb of the loop of Henle. This seemingly counterproductive arrangement, where there is no net osmotic transfer of water, has evolved to faciliate the non-osmotic reabsorbtion of water from the collecting duct system. The reverse osmosis in the thin descending limb dehydrates the medulla, and favours the diffusion of water from the collecting duct tree and concentrates the urine before it leaves through the papilla. The water reabsorbed from the collecting duct, is in a 1:1 relationship with the water that is osmotically transferred into the thin ascending limb. The water that loops around from the collecting duct to the ascending thin limb and back again, faciliates the recirculation of dioxide via the vasa recta (that moves in the direction opposite to the loop of Henle. ) # Tubuloglomerular feedback is subordinated vasopressin, and operates reflexively to decisions by the hypothalamus Tubuloglomerular feedback responds to vasopressin, and vasopressin is ultimately the control mechanism for urine concentration, thereby subordinating the kidney under the hypophysis and the brain. The role of vasopressin is to increase the resistance in the collecting duct tree, by contracting fibroblast-like cells in the kidney medulla, and also to increase water permeability of the collecting duct epithelium by aquaporin channels. The tubuloglomerular autoregulatory system responds to an increase in water reabsorbtion from the collecting duct, by sensing a decrease in filtrate osmolarity at the macula densa region of the thick ascending limb, and upregulates the reverse osmosis mechanism in the thin descending limb of the loop of Henle by increasing the glomerular filtration pressure through renin and angiotensin. Or, rather, it senses only osmolarity increase (concentrating urine more than what is required by vasopressins effect), and release of renin is the default and it gets downregulated whenever macula densa senses that the urine is concentrated more than it should be.
# Reverse osmosis effect in narrow tubes concentrates urine in the kidney Contrary to normal osmosis, reverse osmosis moves water against the osmolarity gradient, from the salt water side to the fresh water side. It allows the production of fresh water from salt water, and is the most widely used desalination method worldwide. Reverse osmosis is normally pressure-based, but, a different type of reverse osmosis takes place in narrow tubes (micrometer scale) that also moves water in the direction opposite to normal osmosis, and therefore allows the production of fresh water. Such an effect is the basis of how the kidney concentrates urine, and it takes place in the thin segment of the nephron (it is why the nephron has evolved a narrow segment. ) In the kidney, the narrow tube effect is amplified by pressure, and the kidney adjusts how much it wants to concentrate the filtrate by adjusting the glomerular filtration pressure. To do this, it has evolved the tuberoglomerular feedback system in the juxtaglomerular apparatus. The role of tuberoglomerular feedback is simply to regulate the strength of the reverse osmosis effect in the thin segment, and it acts both locally via renin and systemically via angiotensin to achieve sufficient filtration pressure. This allows the body to prevent dehydration. The kidney thus concentrates urine by pressure, although the pressure itself is not the basis of the effect, it only amplifies the effect that is inherent to narrow tubes. # The role of adsorbed water in the mechanism of osmosis It was discovered in 2009 that the driving force for osmosis is the thin layer of adsorbed water that forms at hydrophilic surfaces. This adsorbed phase of water has the unusual (and unpredicted) property of being charge polarized, it releases protons into the surrounding water that gets positively charged, and itself gains a negative charge from the surplus of hydroxide ions it is left with. The force behind this charge polarization effect is analogous to the force in semiconductor junctions: diffusion, from thermal energy. Water in the adsorbed phase (that is a semi-solid phase that is halfway between liquid and solid phase) auto-ionizes just like liquid water, but contrary to water in the liquid phase the hydroxide ions are locked into the semi-solid mass that is anchored to the hydrophilic surface. The more mobile hydrogen ion will diffuse outwards to a larger extent than the hydroxide ion, causing the charge separation effect. Osmosis happens when there is an asymmetry between the thickness of the adsorbate on either side of a membrane. The asymmetry will cause protons to "even out their concentration" around the combined negative mass of the adsorbates on either side, so that the charge distribution is balanced out. The relative surplus and deficit of protons that results, will cause hydroxide ions on the exosmotic side (where water is moving from) to break down into dioxide, water and electrons, and the electrons will transfer over to the endosmotic side where there is a surplus of protons, and combine with the protons and dioxide to form dihydrogen monoxide, water. Water itself does not physically "move", it is broken down and built up on either side of the membrane. Only electrons and protons move during osmosis. The effect is analogous to what takes place in an acid-base battery. Salt impairs the formation of the adsorbed phase in the same way it impairs the solid phase (a colligative property), and an increase in osmolarity on one side will decrease the adsorbate at the membrane on that side, causing the effect of proton equilibration and the subsequent breakdown of hydroxide ions on the hypoosmotic side of the membrane. Pressure, acts in an opposite way to increase the thickness of the adsorbate, and therefore generates an osmotic transfer of water in the reverse direction to osmolarity-based osmosis. In narrow tubes, the proximity of the adsorbate around the circumference of the tube causes an increase in the net positive charge of the lumen of the tube, and this effect will be yet another factor in how the protons even out their concentration (charge wise) across both sides of the membrane of the tube. This provides a method for reverse osmosis that can operate at very low pressures, such as that within the filtration system of the kidney.
# Liquids that can auto-ionize show a p-n junction effect when adsorbed to surfaces ABSTRACT: When the adsorbed phase of a liquid auto-ionizes by transfer of a hydrogen ion, the conjugate anion is locked into the adsorbed phase, while the hydrogen ion is free to move by diffusion. The diffusion current  of the protons is opposed by a drift current  within the electric field that forms as the adsorbate loses protons to the liquid and gets negatively charged. The equilibrium between these currents is a separation of charges into a negatively charged adsorbate with a positively charged layer of liquid on top of it. This effect is analogous to the charge polarization seen at the p-n junction  in semiconductors like a diode or transistor.
# Liquids that can auto-ionize show a p-n junction effect when adsorbed to surfaces Consider individual molecules in a liquid such as methanol or water. At surfaces these molecules can bind to, each molecule that anchors to the surface can serve as an anchor for further molecules, and so forth. With this effect, multiple layers of immobile molecules can form at the surface. The molecules will also bond sideways within each layer, and should orient themselves in whatever way fits best. The organization that forms should be an intermediary between the solid phase of the substance, and the liquid phase. If the liquid can auto-ionize by transfer of a hydrogen ion, the hydrogen ion will be free to move while the conjugate anion is locked into the adsorbed phase. As the hydrogen ions diffuse outwards, an electric field strength will increase between the then negatively charged adsorbed phase, and the surrounding protonated liquid. The equilibrium is a separation of charges into a positively charged layer of liquid phase on top of the negatively charged adsorbed phase. Because the charges are physically separated, the probability of recombination of the ions is reduced, and the result is an increase in the number of ionized molecules.
# The auto-ionization of absorbed water at hydrophilic surfaces Consider individual water molecules, that are hydrogen bonded to a hydrophilic surface (i.e., a surface that can hydrogen bond to water molecules. ) These molecules will physically anchor to the surfaces, and can also hydrogen bond to other water molecules, providing an anchor to them as well. With this effect, multiple layers of immobile water can form at the hydrophilic surface. The water will also hydrogen bond sideways within each layer, and should orient themselves in whatever way fits best. The organization that forms should be an intermediary between the solid phase of water - ice - and the liquid phase, and probably more towards the solid phase. Since this intermediary is partially liquid, hydrogen bonds in it will continuously break and reform. Every time a hydrogen bond is broken, there is a probability of transferring a hydrogen ion from one water molecule to the other. These hydrogen ions will be mobile relative to the adsorbed water that is immobile, and can gradually diffuse away, while the hydroxide ions remain locked into the adsorbed phase. As the hydrogen ions diffuse outwards, an electric field strength will increase between the then negatively charged adsorbed water, and the surrounding hydronium ions. The equilibrium is a separation of charges into a positively charged layer of liquid water on top of the negatively charged adsorbed phase. Because the charges are physically separated, the probability of recombination of the ions to water is reduced, and the result is an increase in the number of ionized water molecules.
# The auto-ionization in microscopic ice layer at hydrophilic surfaces ABSTRACT: Water at hydrophilic surfaces forms an up to 0.5 mm thick layer of ice, anchored to the surface by hydrogen bonds. The auto-ionization of this ice behaves differently from liquid water, because of an inequality between the ionic constituents. There is a higher degree of ionization than in liquid water, and the ionic constituents are also physically compartmentalized from one another. This physical compartmentalization results from an inequality in how mobile the ions are. The hydrogen ions are free to move, but the hydroxide ions are locked with hydrogen bonds inside the molecular lattice of the solid phase. The hydrogen ions ability to diffuse allows them to escape outwards into the surrounding water, and the negative charge that builds up in the ice keeps the ejected hydrogen ions close to it. The result is that the ions and their charges are physically polarized into a negatively charged ice layer, and a positively charged layer of water on top of it. This physical compartmentalization prevents reassociation of the ions into water, and contributes to the high degree of ionization seen in the ice. The different constraints for reassociation also provide a force to grow the ice. Each new one-atom thick molecular sheet is nucleated on top of the ice from the positively charged surrounding water. Like with the auto-ionization of liquid water, the ionization increases with temperature, including heating by infrared radiation. The negative charge of the ice is stabilized by hydrostatic pressure, and the ice increases in thickness as pressure increases.
# Is exclusion zone water simply "ionized ice ? ABSTRACT: Water at hydrophilic surface forms a phase that excludes particles. This phase has been proven to release hydrogen ions into the surrounding water, leaving a negatively charged, hydroxide-rich, solid phase where particles are excluded, and positively charged, hydronium-rich, liquid water around it. This charge polarization might be comparable to the p-n junction in a diode. At the p-n junction, electrons transfer from the negatively doped  (n-type) silicon into the positively doped  (p-type) silicon, as a result of diffusion into the electrically conductive p-type  silicon. The electric field that forms pulls the electrons back towards the n-type silicon, in a drift current . The equilibrium between the diffusion current  and drift current  is a charge polarized double layer at the p-n junction. # Introduction In 1947, Bell Laboratories demonstrated the first working transistor. The physical basis of the transistor is the charge polarized double layer that forms at the p-n junction. Thanks to this charge polarization effect, transistors can be turned on and off by a tiny electrical voltage. The laws of physics that support the charge polarization at the p-n junction, formed the basis of the computer revolution, and the modern world. What if similar physical principles also explain the charge polarization effect seen when water contacts hydrophilic surfaces? Normal ice will exclude particles. Hydrophilic surfaces allow water to hydrogen bond to the surface, and can support the formation of a single molecular layer of ice. This initial layer, anchored to the hydrophilic surface, in turn allows water in the liquid phase to hydrogen bond to it, and supports another one-atom thick layer of ice. This effect is why hydrophilic materials support ice formation. The exclusion zone phenomena occurs at temperatures far above the melting point of ice. At these temperatures, hydrogen ions in the ice will have high kinetic energy, and diffuse out into the surrounding liquid water (that is conductive to the diffusion of hydrogen ions. ) Like in a transistor, an electric field will form, and it pulls the hydrogen ions back towards the ice. The equilibrium is a charge polarized double-layer. This ionization prevents the ice from growing larger than a few hundred micrometers, because of the strong negative charge in the ice. # Prior work The charge polarization effect in the interfacial water  phase has been discovered and documented by Gerald Pollack and colleagues, and many effects of it have been discovered such as that it is the cause of osmosis. The charge polarization has been theorized to result from a compression of the normal solid phase of ice, each molecular sheet is free to move relative to the others, like a liquid made up of individual one-atom thick layers of ice. Hydrogen ions are ejected because of the compression. The phase is stable because each atomic sheet is shifted slightly, so that oxygen atoms face hydrogen atoms. This liquid-solid  phase of water, that Gerald Pollack named the fourth phase of water , could very well be what exclusion zone water looks like at the molecular level. The compression is one explanation of why hydrogen ions are ejected from the phase. But, diffusion and drift of hydrogen ions is also a possible explanation. # Ice as a p-type material  relative to liquid water Ice, at temperatures above the freezing point where hydrogen ions will tend to diffuse out of the ice, can be defined as a p-type material  relative to the bulk water (that is n-type ). The reason is that the hydroxide ions within the ice are locked in place much more strongly than the hydrogen ions. When a hydrogen ion is able to escape by diffusion, the hydroxide ion remains locked in place. This can be contrasted to the auto-ionization of water where the OH- and H3O+ will sort of dance along with each other through the water, and the drift current  will dance along the diffusion current . The ice therefore can only release hydrogen ions (or holes  if using the same terminology as with semiconductors), while electrons can be thought of as moving from the bulk water into the ice (again borrowing the terminology used in semiconductors, where only one charge carrier moves but the other is conceptualized as moving in the opposite direction. ) Thus, the ice is p-type  relative to the bulk water, the bulk water releases  electrons, and the ice releases holes . This model for the charge polarized double layer in interfacial water  is thus truly analogous to a p-n junction, a junction between a positive-type and negative-type material where exchange of charge carriers occurs. # The p-n junction or the fourth phase of water? Many effects that have been discovered to be caused by the interfacial water  phase, such as osmosis, rely on the charge polarization effect. As such, they could also be explained by a p-n junction  mechanism for the charge polarization.
Lungs have evolved to make sure blood pressure stays up, with angiotensin II. Fits with my idea that gas exchange is osmotic, and, osmosis is H+ moving, H3O2- breaking down, e- moving, and H2O forming with external O2. Hypoxic pulmonary vasoconstriction (HPV) reflex might also fit with osmotic gas exchange.
Osmosis consumes and produces water An acid-base battery will consume and produce water, while providing an electrical current (Weng, 2019). The chemical basis of this is the asymmetric distribution of hydrogen in the two compartments of an acid-base cell. The alkaline compartment has a shortage of H, it favours H2O collapsing into O2 while releasing 4 electrons, and the acidic compartment has an excess of H, and favours the production of water as long as electrons are provided from the alkaline compartment. An acid-base battery produces its proton gradient by adding a base, such as potassium hydroxide, to one compartment, and an acid, such as hydrochloric acid, to the other. Since the proton gradient is what powers the acid-base battery, and not the mechanism used to generate it, it is reasonable to predict that other ways of generating a proton gradient should result in a similar acid-base battery, one that also consumes and produces water while releasing an electrical current. It has recently been discovered that osmosis is driven by the generation of a proton gradient across the osmotic membrane (Zhao, 2009). Knowing that a proton gradient is what powers an acid-base battery, it can be predicted that a similar behaviour should occur from the proton gradient in osmosis. Water ought to be consumed in one compartment, and produced in the other, accompanied by an electric current. That osmosis is powered by a proton gradient has gone undiscovered since the machinery  that generates this gradient, a thin layer of an electrically polarized solid phase of water, generated from the water pushing against the sides of the container, is not visible without a microscope. This compressed ice  is favoured at surfaces because it is denser than water, because it has excluded the protons that link the molecular ice sheets together in ice. This compressed ice  is inherently a proton pump  because it will eject its protons away from the surface it forms against, leaving a net negative charge at the surface. This negative surface charge will force protons to transfer to the other side of the surface, if the surface is permeable to protons. It therefore provides a means to generate a proton gradient that does not rely on the addition of acid and base, and should be expected to move water in the same way an acid-base battery does.
Consider two water filled containers separated by a membrane only permeable to protons and electrons. One compartment has a pump attached to it, that can increase hydrostatic pressure in it. The other has a one-way valve, that can relieve pressure, and is filled to the rim with water so that there is minimal air inside. Applying pressure with the pump will increase the gel phase at the membrane in the pump compartment. Since the vent compartment has lower pressure, it will have a thinner adsorbed water phase layer. The gel phase excludes protons, and asymmetry in the gel layers on either side of the membrane is a motor for pumping protons across the membrane. Loss of protons from the pump compartment, causes H2O to break down into O2, releasing electrons. The electrons also transfer across the membrane, and combine with the protons to form hydrogen gas. This hydrogen gas increases the pressure in the vent compartment, and is ventilated via the one-way valve. This experiment evaporates water by applying pressure, and this can be verified or falsified by weighing the combined water mass before and after the experiment. A tiny air pocket can be left before the valve, to make it easier to see that water is not being ventilated (the O2 in this air pocket will quickly be used up in the beginning of the experiment to form a minimal amount of water, after which only H2 will be produced. )
Consider two containers separated by a membrane only permeable to protons and electrons. It makes sense that a membrane would restrict permeable to the smallest units that people usually deal with, everything else such as atoms or molecules being much bigger. The hydrostatic pressure at the membrane is higher in the compartment to the left with a taller water column. The pressure increases the adsorbed gel phase at the membrane, since this phase of water has a higher density (the reverse of pressures effect on freezing point for ice. ) This causes asymmetry of the gel phase on both sides of the membrane, propelling protons over it to even out their distribution. Electrons will follow along to balance the charge, forcing water to break down in the compartment to the left. Since there is oxygen available to the compartment to the right, water will form there. Water appears to move across the membrane.
I'm pretty sure this video shows concrete evidence for a completely new model of osmosis, https://youtu.be/zzVa_tX1OiI?t=175.. In his experiment, the ammeter is connected in series between the voltage supply and the load. The amperage (shown on the ammeter) is decreasing when he plugs the compartment that receives current, by Ohm's law, I = V/R, resistance must have increased. What explanation is there for that the resistance increases? I suggest that O2 is acting as a cathode to complete the circuit. The electrons are combining with O2 and with the protons continuously fed from the other compartment (where the opposite reaction 4 OH- --> O2 + 2 H2O + 4 e- breaks down water to keep electrostatic neutrality, those electrons leave the load and continue to the power source. ) Plugging the tube removes O2. The idea is that water does not move during osmosis, only protons and electrons move. https://doi.org/10.5281/zenodo.4290233.
I developed an idea over the past year, since January, that I think might have some potential. It predicts osmosis is misunderstood. https://doi.org/10.5281/zenodo.4290233 I'm pretty sure concrete evidence is seen in this video, https://www.youtube.com/watch?v=zzVa_tX1OiI. The current dies when he plugs the oxygen supply. The metal conductor does not pass through the membrane, so I assume the loss of current coming back is from loss of oxygen evolution reaction 4 OH- --> O2 + 2 H2O + 4 e-, providing the electrons, as a result of loss of H+ being consumed by production of water in first compartment (it is loss of H+ that causes surplus of OH- and the breakdown of water into dioxygen gas. )
Osmosis produces water from external oxygen The adsorbed water-phase that forms at contact zones separates water into its ionic constituents, the hydroxide forms a crystalline structure closest to the membrane, (H3O2-)n, and the protons form a layer of H3O+ on top of it. The ordering of water at contact zones is a colligative property, and is promoted in the water compartment and impaired in the salt compartment. It is the asymmetry in the adsorbed water phase on either side of a membrane that causes a transfer of protons to the hyperosmotic compartment during osmosis. The protons reorder around the combined charge of the hydroxide layer on both sides of the membrane, that acts like a motor. (Zhao, 2009; Pollack, 2013) The loss of protons from the water compartment forces water to decompose into dioxide, there is not enough hydrogen to sustain the water. This reaction releases one electron per water, and the electrons will move towards a region of lower negative charge, the salt compartment. This electrical potential was measured by Jaques Loeb in 1921, and corroborated by Gerald Pollack in 2009. When external oxygen is supplied to the salt compartment, it will combine with the protons and electrons that were transferred from the water compartment, and produce water. Water itself does not move across the membrane. It only appears to move. That external oxygen is required for osmosis is a hypothesis that can be easily tested experimentally by performing a standard osmosis experiment without external oxygen in the salt compartment. The author has not done so. References Zhao, Q., Ovchinnikova, K., Chai, B., Yoo, H., Magula, J., & Pollack, G. H. (2009). Role of Proton Gradients in the Mechanism of Osmosis. The Journal of Physical Chemistry B, 113(31), 10708 10714. https://doi.org/10.1021/jp9021568 Pollack, G., 2013. The Fourth Phase Of Water. Seattle: Ebner and Sons. Loeb, J. (1921). THE ORIGIN OF THE POTENTIAL DIFFERENCES RESPONSIBLE FOR ANOMALOUS OSMOSIS. Journal of General Physiology, 4(2), 213 226. https://doi.org/10.1085/jgp.4.2.213