Superlubricity nano-structured self-assembling coating repairs surface wear, decreases emissions and increases HP and gas mileage.
Globally about 15 percent of manmade carbon dioxide comes from vehicles. In more developed countries, cars, trucks, airplanes, ships and other vehicles account for a third of emissions related to climate change. Emissions standards are fueling the lubricant additives market with innovation.
Up to 33% of fuel energy in vehicles is used to overcome friction. Tribology is the science of interacting surfaces in relative motion inclusive of friction, wear and lubrication. This is where TriboTEX, a nanotechnology startup is changing the game of friction modification and wear resilience with a lubricant additive that forms a nano-structured coating on metal alloys.
This nano-structured coating increases operating efficiency and component longevity. It is comprised of synthetic magnesium silicon hydroxide nanoparticles that self-assemble as an ultralow friction layer, 1/10 of the original friction resistance. The coating is self-repairing during operation, environmentally inert and extracts carbon from the oil. The carbon diamond-like nano-particle lowers the friction budget of the motor, improving fuel economy and emissions in parallel while increasing the power and longevity of the motor.
TriboTEX has a Kickstarter campaign that has just surpassed $100,000 in funding. The early bird round has just closed that offered the product at one half the cost of its retail. The final round offers the lubricant system self-forming coating at 75 percent and is ending shortly. The founder Dr. Pavlo Rudenko, Ph.D. is a graduate of Singularity University GSP11 program.
How could global economic inequality survive the onslaught of synthetic organisms, micromanufacturing devices, additive manufacturing machines, nano-factories? (http://www.beliefnet.com/columnists/lordre/2016/04/obsessed-with-equality-my-techno-utopia.html#S5Ogqvv8PL36KMDo.99)
Narrated by Harry J. Bentham, author of Catalyst: A Techno-Liberation Thesis (2013), using the introduction from that book as a taster of the audio version of the book in production. (http://www.clubof.info/2016/04/liberation-technologies-to-come.html)
Ray Kurzweil’s well-received book, The Singularity is Near, is perhaps the best known book related to transhumanism and presents a view of inevitable technological evolution that closely resembles the claim in the later (2010) book What Technology Wants by Wired co-founder Kevin Kelly.
Kurzweil describes six epochs in the history of information. Each significant form of information is superseded by another in a series of stepping stones, exposing a universal will at work within technology towards extropy (this is seen by Kevin Kelly as intelligence and complexity attaining their maximum state possible). The first epoch is physics and chemistry, and is succeeded by biology, brains, technology, the merger of technology and human intelligence and finally the epoch in which the universe “wakes up”. The final epoch achieves what could be called godhood for the universe’s surviving intelligences (p. 15).
Artificial intelligence, which Kurzweil predicts to compete with and soon after overtake the human brain, will mean reverse-engineering the human brain as a direct offshoot of developing higher resolution when scanning the brain (much as genome synthesis was the offshoot of being able to sequence a complete genome) (p. 25–29, 111–198). This is a source of particular excitement to many, because of Kurzweil and Google’s genuine efforts to make it a reality.
An interest in abundance and a read of J. Craig Venter’s Life at the Speed of Light will make Chapter 5 of Kurzweil’s book of particular interest, as it discusses genetics and its relationship to the singularity. Genetics, nanotechnology and robotics are seen as overlapping revolutions that are set to characterize the first half of the Twenty-First Century (p.205). Kurzweil addresses the full understanding of genetics, e.g. knowing exactly how to program and hack our DNA as in J. Craig Venter’s synthetic biology revolution (p. 205–212).
Kurzweil predicts “radical life-extension” on top of the elimination of disease and expansion of human potential through the genetics advancements of teams like J. Craig Venter’s. J. Craig Venter covered life extension and human enhancement in his 2013 book, but also drew special attention to the ongoing engineering of beneficial microbes for purposes of making renewable resources and cleaning the environment. Another prospect for abundance noted by Kurzweil is the idea of cloning meat and other protein sources in a factory (this being an offshoot of medical cloning advances). Far from simply offering life extension to the privileged few, Kurzweil notes that such a development may have the potential to solve world hunger.
To cover the nanotechnology revolution, Kurzweil visits nanotechnology father K. Eric Drexler’s assessments of the pros and cons in this field. In some ways, Kurzweil could be faulted for expecting too much from nanotechnology, since his treatment of the subject contrasts sharply with Drexler’s characterization of it as simply being “atomically precise manufacturing” (APM) and primarily having industrial ramifications. In Radical Abundance, Drexler specifically discourages the view echoed by Kurzweil of “nanobots” swimming in our body in the near future and delivering miracle cures, seeing such expectations as the product of sci-fi stories and media hype.
On the subject of artificial intelligence, there can be no doubt that Kurzweil is ahead of all of us because of his personal background. In his estimate, artificial intelligence reverse-engineered from the human brain will immediately “exceed human intelligence” for a number of reasons even if we only design it to be on par with our intelligence. For example, computers are able to “pool their resources in ways that humans cannot” (p. 259–298). In addition, Kurzweil forecasts:
The advent of strong AI is the most important transformation this century will see. Indeed, it is comparable in importance to the advent of biology itself. It will mean the creation of biology that has finally mastered its own intelligence and discovered means to overcome its limitations. (p. 296)
From our viewpoint in 2014, some of Kurzweil’s predictions could be criticized for being too optimistic. For example, “computers arriving at the beginning of the next decade will become essentially invisible, woven into our clothing, embedded in our furniture and environment”, as well as providing unlimited Wi-Fi everywhere (p. 312). While no doubt some places and instruments exist that might fit this description, they are certainly not in widespread use at this time, nor is there any particular need among society for this to become widespread (except perhaps the Wi-Fi).
Another likely over-optimistic prediction is the view that “full-immersion virtual reality” will be ready for our use by the late 2020s and it will be “indistinguishable from reality” (p. 341). In Kurzweil’s prediction, by 2029 nanobots in our bodies will be able to hack our nervous systems and trick us into believing a false reality every bit as convincing as the life we knew. We are in 2014. There is no full-immersion virtual reality system based on nanotechnology set to be on the market in 2020. A few dedicated gamers have the Oculus Rift (of which there will no doubt be a constant stream of successors ever reducing weight, trying to look “sexier”, and expanding the resolution and frame-rate over at least one decade), while there is no sign whatsoever of the nanotechnology-based neural interface technology predicted by Kurzweil. If nanotech-based full-immersion virtual reality is going to be possible in the 2020s at all, there ought to at least be some rudimentary prototype already in development, but (unless it is a secret military project) time is running out for the prediction to come true.
Part of the book addresses the exciting possibilities of advanced, futuristic warfare. The idea of soldiers who operate robotic platforms, aided by swarms of drones and focused on disrupting the enemy ability to communicate is truly compelling – all the more so because of the unique inside view that Kurzweil had of DARPA. Kurzweil sees a form of warfare in which commanders engage one another in virtual and physical battlefields from opposite sides of the globe, experiencing conflicts in which cyber-attack and communication disruption are every bit as crippling to armies as physical destruction (p. 330–335). Then again, this trend (like the idea of building missile-defense shields) may ultimately lead to complacency and false assumptions that our security is “complete”, while that foreign suppliers like Russia and China are also modernizing and have many systems that are thought to be on par with the US. A lot of US military success may be down to picking on vulnerable countries, rather than perfecting a safe and clean form of warfare (most of Saddam’s deadliest weapons were destroyed or used up in the First Gulf War, which alone could account for the US having so few casualties in the 2003 war.)
Although saying that the singularity will eliminate the distinction between work and play by making information so easily accessible in our lives, Kurzweil predicts that information will gain more value, making intellectual property more important to protect (p. 339–340). This sentiment is hard to agree with at a time when piracy and (illegally) streaming video without paying is already increasingly a fact of everyone’s life. If all thought and play is going to qualify as a creative act as a result of our eventual integration with machines, it only becomes ever harder to believe that such creative acts are going to need monetary incentives.
The book discusses at length how to balance the risks and benefits of emerging technologies. Of particular resilience is Kurzweil’s view that relinquishing or restraining developments can itself expose us to existential risks (e.g. asteroids). I myself would take this argument further. Failing to create abundance when one has the ability to do so is negligent, and even more morally questionable than triggering a nanotech or biotech disaster that must be overcome in the course of helping people.
Kurzweil goes through what seems like an exhaustive list of criticisms, arming singularitarians with an effective defense of their position. Of interest to me, as a result of penning a response to it myself, was how Kurzweil rebuts the “Criticism from the Rich-Poor Divide” by arguing that poverty is overwhelmingly being reduced and benefits of digital technology for the poor are undeniable. Indeed, among the world’s poor, there is no doubt that digital technology is good and that it empowers people. Anyone who argues this revolution is bad for the poor are just plainly ignoring the opinions of the actual poor people they claim to be defending. There has been no credible connection between digital technology and the supply of disproportionate benefits to wealthy elites. If anything, digital technology has made the world more equal and can even be regarded as part of a global liberation struggle.
Unfortunately, there is a major argument absent from the book. Kurzweil’s book precedes the revelations of mass surveillance by NSA whistleblower Edward Snowden. As a result, it fails to answer the most important criticism of an imminent singularity I can think of. I would have to call this the “Argument from Civil and Political Rights”. It takes into account the fact that greedy and cruel nation-states (the US being the most dangerous) tend to seek the monopoly of power in the current world order, including technological power. By bridging the gap between ourselves and computers before we create a more benevolent political and social order with less hegemony and less cruelty, we will simply be turning every fiber of our existence over to state agencies and giving up our liberty.
Suppose PRISM or some program like it exists, and my mind can be read by it. In that case, my uploaded existence would be no different from a Gitmo detainee. In fact, just interfacing with such a system for a moment would be equivalent to being sent to Gitmo, if the US government and its agencies exist. It does not matter how benevolent the operators even are. The fact that I am vulnerable to the operators means I am being subjected to a constant and ongoing violation of my civil rights. I could be subjected to any form of cruelty or oppression, and the perpetrator would never be stopped or held accountable.
It gets worse. With reality and virtual reality becoming indistinguishable (as predicted in this book), a new sort of sadist may even emerge that does not know the difference between the two or does not care. History has shown that such sadists are most likely to be the ones who have had more experience with and thus have obtained more power over the system. It is this political or social concern that should be deterring people from uploading themselves right now. If we were uploaded, what followed could never evolve beyond being a constant reflection of the flawed social order at the time when the upload occurred. Do we want to immortalize an abusive and cruel superpower, corporate lobbyists, secret police, or a prison? Are these things actually worth saving for all eternity and disseminating across the universe when we reach the singularity?
Despite the questions I have tried to raise in this review, I am still convinced by the broad idea of the singularity, and Kurzweil articulates it well. The idea, as promoted by Max More and quoted by Kurzweil (p. 373) that our view of our role in the universe should be like Nietzche’s “rope over an abyss” trying to reach for a greater existence, with technology playing a key role, helps encourage us to take noble risks. However, I believe the noble risks are not risks taken out of desperation to extend our lives and escape death, or risks taken to make ourselves look nice or something else petty. Noble risks are taken to ensure our future or the future of humanity, often at the expense of the present.
I would discourage people from trying to hasten the singularity because of a personal fear of their own death, as this would probably lead to irrational behavior (as occurs with the traditions that promote transcending death by supernatural means). Complications from society and unforeseen abuses, especially by our deeply paranoid and controlling states that are far too primitive to react responsibly to the singularity, are likely to slow everything down.
In this essay I argue that technologies and techniques used and developed in the fields of Synthetic Ion Channels and Ion Channel Reconstitution, which have emerged from the fields of supramolecular chemistry and bio-organic chemistry throughout the past 4 decades, can be applied towards the purpose of gradual cellular (and particularly neuronal) replacement to create a new interdisciplinary field that applies such techniques and technologies towards the goal of the indefinite functional restoration of cellular mechanisms and systems, as opposed to their current proposed use of aiding in the elucidation of cellular mechanisms and their underlying principles, and as biosensors.
In earlier essays (see here and here) I identified approaches to the synthesis of non-biological functional equivalents of neuronal components (i.e. ion-channels ion-pumps and membrane sections) and their sectional integration with the existing biological neuron — a sort of “physical” emulation if you will. It has only recently come to my attention that there is an existing field emerging from supramolecular and bio-organic chemistry centered around the design, synthesis, and incorporation/integration of both synthetic/artificial ion channels and artificial bilipid membranes (i.e. lipid bilayer). The potential uses for such channels commonly listed in the literature have nothing to do with life-extension however, and the field is to my knowledge yet to envision the use of replacing our existing neuronal components as they degrade (or before they are able to), rather seeing such uses as aiding in the elucidation of cellular operations and mechanisms and as biosensors. I argue here that the very technologies and techniques that constitute the field (Synthetic Ion-Channels & Ion-Channel/Membrane Reconstitution) can be used towards the purpose of the indefinite-longevity and life-extension through the iterative replacement of cellular constituents (particularly the components comprising our neurons – ion-channels, ion-pumps, sections of bi-lipid membrane, etc.) so as to negate the molecular degradation they would have otherwise eventually undergone.
While I envisioned an electro-mechanical-systems approach in my earlier essays, the field of Synthetic Ion-Channels from the start in the early 70’s applied a molecular approach to the problem of designing molecular systems that produce certain functions according to their chemical composition or structure. Note that this approach corresponds to (or can be categorized under) the passive-physicalist sub-approach of the physicalist-functionalist approach (the broad approach overlying all varieties of physically-embodied, “prosthetic” neuronal functional replication) identified in an earlier essay.
The field of synthetic ion channels is also referred to as ion-channel reconstitution, which designates “the solubilization of the membrane, the isolation of the channel protein from the other membrane constituents and the reintroduction of that protein into some form of artificial membrane system that facilitates the measurement of channel function,” and more broadly denotes “the [general] study of ion channel function and can be used to describe the incorporation of intact membrane vesicles, including the protein of interest, into artificial membrane systems that allow the properties of the channel to be investigated” [1]. The field has been active since the 1970s, with experimental successes in the incorporation of functioning synthetic ion channels into biological bilipid membranes and artificial membranes dissimilar in molecular composition and structure to biological analogues underlying supramolecular interactions, ion selectivity and permeability throughout the 1980’s, 1990’s and 2000’s. The relevant literature suggests that their proposed use has thus far been limited to the elucidation of ion-channel function and operation, the investigation of their functional and biophysical properties, and in lesser degree for the purpose of “in-vitro sensing devices to detect the presence of physiologically-active substances including antiseptics, antibiotics, neurotransmitters, and others” through the “… transduction of bioelectrical and biochemical events into measurable electrical signals” [2].
Thus my proposal of gradually integrating artificial ion-channels and/or artificial membrane sections for the purpse of indefinite longevity (that is, their use in replacing existing biological neurons towards the aim of gradual substrate replacement, or indeed even in the alternative use of constructing artificial neurons to, rather than replace existing biological neurons, become integrated with existing biological neural networks towards the aim of intelligence amplification and augmentation while assuming functional and experiential continuity with our existing biological nervous system) appears to be novel, while the notion of artificial ion-channels and neuronal membrane systems ion general had already been conceived (and successfully created/experimentally-verified, though presumably not integrated in-vivo).
The field of Functionally-Restorative Medicine (and the orphan sub-field of whole-brain-gradual-substrate-replacement, or “physically-embodied” brain-emulation if you like) can take advantage of the decades of experimental progress in this field, incorporating both the technological and methodological infrastructures used in and underlying the field of Ion-Channel Reconstitution and Synthetic/Artificial Ion Channels & Membrane-Systems (and the technologies and methodologies underlying their corresponding experimental-verification and incorporation techniques) for the purpose of indefinite functional restoration via the gradual and iterative replacement of neuronal components (including sections of bilipid membrane, ion channels and ion pumps) by MEMS (micro-electrocal-mechanical-systems) or more likely NEMS (nano-electro-mechanical systems).
The technological and methodological infrastructure underlying this field can be utilized for both the creation of artificial neurons and for the artificial synthesis of normative biological neurons. Much work in the field required artificially synthesizing cellular components (e.g. bilipid membranes) with structural and functional properties as similar to normative biological cells as possible, so that the alternative designs (i.e. dissimilar to the normal structural and functional modalities of biological cells or cellular components) and how they affect and elucidate cellular properties, could be effectively tested. The iterative replacement of either single neurons, or the sectional replacement of neurons with synthesized cellular components (including sections of the bi-lipid membrane, voltage-dependent ion-channels, ligand-dependent ion channels, ion pumps, etc.) is made possible by the large body of work already done in the field. Consequently the technological, methodological and experimental infrastructures developed for the fields of Synthetic
Ion-Channels and Ion-Channel/Artificial-Membrane-Reconstitution can be utilized for the purpose of a.) iterative replacement and cellular upkeep via biological analogues (or not differing significantly in structure or functional & operational modality to their normal biological counterparts) and/or b.) iterative replacement with non-biological analogues of alternate structural and/or functional modalities.
Rather than sensing when a given component degrades and then replacing it with an artificially-synthesized biological or non-biological analogue, it appears to be much more efficient to determine the projected time it takes for a given component to degrade or otherwise lose functionality, and simply automate the iterative replacement in this fashion, without providing in-vivo systems for detecting molecular or structural degradation. This would allow us to achieve both experimental and pragmatic success in such cellular-prosthesis sooner, because it doesn’t rely on the complex technological and methodological infrastructure underlying in-vivo sensing, especially on the scale of single neuron components like ion-channels, and without causing operational or functional distortion to the components being sensed.
A survey of progress in the field [3] lists several broad design motifs. I will first list the deign motifs falling within the scope of the survey, and the examples it provides. Selections from both papers are meant to show the depth and breadth of the field, rather than to elucidate the specific chemical or kinetic operations under the purview of each design-variety.
For a much more comprehensive, interactive bibliography of papers falling within the field of Synthetic Ion-Channels or constituting the historical foundations of the field, see Jon Chui’s online biography here, which charts the developments in this field up until 2011.
First Survey
Unimolecular ion channels:
Examples include a.) synthetic ion channels with oligocrown ionophores, [5] b.) using a-helical peptide scaffolds and rigid push–pull p-octiphenyl scaffolds for the recognition of polarized membranes, [6] and c.) modified varieties of the b-helical scaffold of gramicidin A [7]
Barrel-stave supramolecules:
Examples of this general class falling include avoltage-gated synthetic ion channels formed by macrocyclic bolaamphiphiles and rigidrod p-octiphenyl polyols [8].
Macrocyclic, branched and linear non-peptide bolaamphiphiles as staves:
Examples of this sub-class include synthetic ion channels formed by a.) macrocyclic, branched and linear bolaamphiphiles and dimeric steroids, [9] and by b.) non-peptide macrocycles, acyclic analogs and peptide macrocycles [respectively] containing abiotic amino acids [10].
Dimeric steroid staves:
Examples of this sub-class include channels using polydroxylated norcholentriol dimer [11].
pOligophenyls as staves in rigid rod b barrels:
Examples of this sub-class include “cylindrical self-assembly of rigid-rod b-barrel pores preorganized by the nonplanarity of p-octiphenyl staves in octapeptide-p-octiphenyl monomers” [12].
Synthetic Polymers:
Examples of this sub-class include synthetic ion channels and pores comprised of a.) polyalanine, b.) polyisocyanates, c.) polyacrylates, [13] formed by i.) ionophoric, ii.) ‘smart’ and iii.) cationic polymers [14]; d.) surface-attached poly(vinyl-n-alkylpyridinium) [15]; e.) cationic oligo-polymers [16] and f.) poly(m-phenylene ethylenes) [17].
Helical b-peptides (used as staves in barrel-stave method):
Examples of this class include: a.) cationic b-peptides with antibiotic activity, presumably acting as amphiphilic helices that form micellar pores in anionic bilayer membranes [18].
Monomeric steroids:
Examples of this sub-class falling include synthetic carriers, channels and pores formed by monomeric steroids [19], synthetic cationic steroid antibiotics [that] may act by forming micellar pores in anionic membranes [20], neutral steroids as anion carriers [21] and supramolecular ion channels [22].
Complex minimalist systems:
Examples of this sub-class falling within the scope of this survey include ‘minimalist’ amphiphiles as synthetic ion channels and pores [23], membrane-active ‘smart’ double-chain amphiphiles, expected to form ‘micellar pores’ or self-assemble into ion channels in response to acid or light [24], and double-chain amphiphiles that may form ‘micellar pores’ at the boundary between photopolymerized and host bilayer domains and representative peptide conjugates that may self assemble into supramolecular pores or exhibit antibiotic activity [25].
Non-peptide macrocycles as hoops:
Examples of this sub-class falling within the scope of this survey include synthetic ion channels formed by non-peptide macrocycles acyclic analogs [26] and peptide macrocycles containing abiotic amino acids [27].
Peptide macrocycles as hoops and staves:
Examples of this sub-class include a.) synthetic ion channels formed by self-assembly of macrocyclic peptides into genuine barrel-hoop motifs that mimic the b-helix of gramicidin A with cyclic b-sheets. The macrocycles are designed to bind on top of channels and cationic antibiotics (and several analogs) are proposed to form micellar pores in anionic membranes [28]; b.) synthetic carriers, antibiotics (and analogs) and pores (and analogs) formed by macrocyclic peptides with non-natural subunits. [Certain] macrocycles may act as b-sheets, possibly as staves of b-barrel-like pores [29]; c.) bioengineered pores as sensors. Covalent capturing and fragmentations [have been] observed on the single-molecule level within engineered a-hemolysin pore containing an internal reactive thiol [30].
Summary
Thus even without knowledge of supramolecular or organic chemistry, one can see that a variety of alternate approaches to the creation of synthetic ion channels, and several sub-approaches within each larger ‘design motif’ or broad-approach, not only exist but have been experimentally verified, varietized and refined.
Second Survey
The following selections [31] illustrate the chemical, structural and functional varieties of synthetic ions categorized according to whether they are cation-conducting or anion-conducting, respectively. These examples are used to further emphasize the extent of the field, and the number of alternative approaches to synthetic ion-channel design, implementation, integration and experimental-verification already existent. Permission to use all the following selections and figures were obtained from the author of the source.
There are 6 classical design-motifs for synthetic ion-channels, categorized by structure, that are identified within the paper:
“The first non-peptidic artificial ion channel was reported by Kobuke et al. in 1992” [33].
“The channel contained “an amphiphilic ion pair consisting of oligoether-carboxylates and mono- (or di-) octadecylammoniumcations. The carboxylates formed the channel core and the cations formed the hydrophobic outer wall, which was embedded in the bilipid membrane with a channel length of about 24 to 30 Å. The resultant ion channel, formed from molecular self-assembly, is cation selective and voltage-dependent” [34].
“Later, Kokube et al. synthesized another channel comprising of resorcinol based cyclic tetramer as the building block. The resorcin-[4]-arenemonomer consisted of four long alkyl chains which aggregated to forma dimeric supramolecular structure resembling that of Gramicidin A” [35]. “Gokel et al. had studied [a set of] simple yet fully functional ion channels known as “hydraphiles” [39].
“An example (channel 3) is shown in Figure 1.6, consisting of diaza-18-crown-6 crown ether groups and alkyl chain as side arms and spacers. Channel 3 is capable of transporting protons across the bilayer membrane” [40].
“A covalently bonded macrotetracycle4 (Figure 1.8) had shown to be about three times more active than Gokel’s ‘hydraphile’ channel, and its amide-containing analogue also showed enhanced activity” [44].
“Inorganic derivative using crown ethers have also been synthesized. Hall et. al synthesized an ion channel consisting of a ferrocene and 4 diaza-18-crown-6 linked by 2 dodecyl chains (Figure 1.9). The ion channel was redox-active as oxidation of the ferrocene caused the compound to switch to an inactive form” [45]
B STAVES:
“These are more difficult to synthesize [in comparison to unimolecular varieties] because the channel formation usually involves self-assembly via non-covalent interactions” [47].“A cyclic peptide composed of even number of alternating D- and L-amino acids (Figure 1.10) was suggested to form barrel-hoop structure through backbone-backbone hydrogen bonds by De Santis” [49].
“A tubular nanotube synthesized by Ghadiri et al. consisting of cyclic D and L peptide subunits form a flat, ring-shaped conformation that stack through an extensive anti-parallel β-sheet-like hydrogen bonding interaction (Figure 1.11)” [51].
“Experimental results have shown that the channel can transport sodium and potassium ions. The channel can also be constructed by the use of direct covalent bonding between the sheets so as to increase the thermodynamic and kinetic stability” [52].
“By attaching peptides to the octiphenyl scaffold, a β-barrel can be formed via self-assembly through the formation of β-sheet structures between the peptide chains (Figure 1.13)” [53].
“The same scaffold was used by Matile etal. to mimic the structure of macrolide antibiotic amphotericin B. The channel synthesized was shown to transport cations across the membrane” [54].
“Attaching the electron-poor naphthalenediimide (NDIs) to the same octiphenyl scaffold led to the hoop-stave mismatch during self-assembly that results in a twisted and closed channel conformation (Figure 1.14). Adding the compleentary dialkoxynaphthalene (DAN) donor led to the cooperative interactions between NDI and DAN that favors the formation of barrel-stave ion channel.” [57].
MICELLAR
“These aggregate channels are formed by amphotericin involving both sterols and antibiotics arranged in two half-channel sections within the membrane” [58].
“An active form of the compound is the bolaamphiphiles (two-headed amphiphiles). (Figure 1.15) shows an example that forms an active channel structure through dimerization or trimerization within the bilayer membrane. Electrochemical studies had shown that the monomer is inactive and the active form involves dimer or larger aggregates” [60].
ANION CONDUCTING CHANNELS:
“A highly active, anion selective, monomeric cyclodextrin-based ion channel was designed by Madhavan et al (Figure 1.16). Oligoether chains were attached to the primary face of the β-cyclodextrin head group via amide bonds. The hydrophobic oligoether chains were chosen because they are long enough to span the entire lipid bilayer. The channel was able to select “anions over cations” and “discriminate among halide anions in the order I-> Br-> Cl- (following Hofmeister series)” [61].
“The anion selectivity occurred via the ring of ammonium cations being positioned just beside the cyclodextrin head group, which helped to facilitate anion selectivity. Iodide ions were transported the fastest because the activation barrier to enter the hydrophobic channel core is lower for I- compared to either Br- or Cl-“ [62]. “A more specific artificial anion selective ion channel was the chloride selective ion channel synthesized by Gokel. The building block involved a heptapeptide with Proline incorporated (Figure 1.17)” [63].
Cellular Prosthesis: Inklings of a New Interdisciplinary Approach
The paper cites “nanoreactors for catalysis and chemical or biological sensors” and “interdisciplinary uses as nano –filtration membrane, drug or gene delivery vehicles/transporters as well as channel-based antibiotics that may kill bacterial cells preferentially over mammalian cells” as some of the main applications of synthetic ion-channels [65], other than their normative use in elucidating cellular function and operation.
However, I argue that a whole interdisciplinary field and heretofore-unrecognized new approach or sub-field of Functionally-Restorative Medicine is possible through taking the technologies and techniques involved in in constructing, integrating, and experimentally-verifying either a.) non-biological analogues of ion-channels & ion-pumps (thus trans-membrane membrane proteins in general, also sometimes referred to as transport proteins or integral membrane proteins) and membranes (which include normative bilipid membranes, non-lipid membranes and chemically-augmented bilipid membranes), and b.) the artificial synthesis of biological analogues of ion-channels, ion-pumps and membranes, which are structurally and chemically equivalent to naturally-occurring biological components but which are synthesized artificially – and applying such technologies and techniques toward the purpose the gradual replacement of our existing biological neurons constituting our nervous systems – or at least those neuron-populations that comprise the neo- and prefrontal-cortex, and through iterative procedures of gradual replacement thereby achieving indefinite-longevity. There is still work to be done in determining the comparative advantages and disadvantages of various structural and functional (i.e. design) motifs, and in the logistics of implanting the iterative replacement or reconstitution of ion-channels, ion-pumps and sections of neuronal membrane in-vivo.
The conceptual schemes outlined in Concepts for Functional Replication of Biological Neurons [66], Gradual Neuron Replacement for the Preservation of Subjective-Continuity [67] and Wireless Synapses, Artificial Plasticity, and Neuromodulation [68] would constitute variations on the basic approach underlying this proposed, embryonic interdisciplinary field. Certain approaches within the fields of nanomedicine itself, particularly those approaches that constitute the functional emulation of existing cell-types, such as but not limited to Robert Freitas’s conceptual designs for the functional emulation of the red blood cell (a.k.a. erythrocytes, haematids) [69], i.e. the Resperocyte, itself should be seen as falling under the purview of this new approach, although not all approaches to Nanomedicine (diagnostics, drug-delivery and neuroelectronic interfacing) constitute the physical (i.e. electromechanical, kinetic and/or molecular physically-embodied) and functional emulation of biological cells.
The field of functionally-restorative medicine in general (and of nanomedicine in particular) and the field of supramolecular and organic chemistry converge here, where these technological, methodological, and experimental infrastructures developed in field of Synthetic Ion-Channels and Ion Channel Reconstitution can be employed to develop a new interdisciplinary approach that applies the logic of prosthesis to the cellular and cellular-component (i.e. sub-cellular) scale; same tools, new use. These techniques could be used to iteratively replace the components of our neurons as they degrade, or to replace them with more robust systems that are less susceptible to molecular degradation. Instead of repairing the cellular DNA, RNA and protein transcription and synthesis machinery, we bypass it completely by configuring and integrating the neuronal components (ion-channels, ion-pumps and sections of bilipid membrane) directly.
Thus I suggest that theoreticians of nanomedicine look to the large quantity of literature already developed in the emerging fields of synthetic ion-channels and membrane-reconstitution, towards the objective of adapting and applying existing technologies and methodologies to the new purpose of iterative maintenance, upkeep and/or replacement of cellular (and particularly neuronal) constituents with either non-biological analogues or artificially-synthesized-but-chemically/structurally-equivalent biological analogues.
This new sub-field of Synthetic Biology needs a name to differentiate it from the other approaches to Functionally-Restorative Medicine. I suggest the designation ‘cellular prosthesis’.
References:
[1] Williams (1994)., An introduction to the methods available for ion channel reconstitution. in D.C Ogden Microelectrode techniques, The Plymouth workshop edition, CambridgeCompany of Biologists.
[2] Tomich, J., Montal, M. (1996). U.S Patent No. 5,16,890. Washington, DC: U.S. Patent and Trademark Office.
[3] Matile, S., Som, A., & Sorde, N. (2004). Recent synthetic ion channels and pores. Tetrahedron, 60(31), 6405-6435. ISSN 0040-4020, 10.1016/j.tet.2004.05.052. Access: http://www.sciencedirect.com/science/article/pii/S0040402004007690:
[4] XIAO, F., (2009). Synthesis and structural investigations of pyridine-based aromatic foldamers.
[5] Ibid., p. 6411.
[6] Ibid., p. 6416.
[7] Ibid., p. 6413.
[8] Ibid., p. 6412.
[9] Ibid., p. 6414.
[10] Ibid., p. 6425.
[11] Ibid., p. 6427.
[12] Ibid., p. 6416.
[13] Ibid., p. 6419.
[14] Ibid., p. 6419.
[15] Ibid., p. 6419.
[16] Ibid., p. 6419.
[17] Ibid., p. 6419.
[18] Ibid., p. 6421.
[19] Ibid., p. 6422.
[20] Ibid., p. 6422.
[21] Ibid., p. 6422.
[22] Ibid., p. 6422.
[23] Ibid., p. 6423.
[24] Ibid., p. 6423.
[25] Ibid., p. 6423.
[26] Ibid., p. 6426.
[27] Ibid., p. 6426.
[28] Ibid., p. 6427.
[29] Ibid., p. 6327.
[30] Ibid., p. 6427.
[31] XIAO, F. (2009). Synthesis and structural investigations of pyridine-based aromatic foldamers.
[69] Freitas Jr., R., (1998). “Exploratory Design in Medical Nanotechnology: A Mechanical Artificial Red Cell”. Artificial Cells, Blood Substitutes, and Immobil. Biotech. (26): 411–430. Access: http://www.ncbi.nlm.nih.gov/pubmed/9663339
Asteroid hazard in the context of technological development
It is easy to notice that the direct risks of collisions with asteroids decreases with technological development. First, they (or, exactly, our estimation of risks) decrease due to more accurate measurement of them — that is, at the expense of more accurate detection of dangerous asteroids and measurements of their orbits we could finally find that the real chance of impact is 0 in the next 100 year. (If, however, will be confirmed the assumption that we live during the episode of comet bombardment, the assessment of risk would increase 100 times to the background.) Second, it decreases due to an increase in our ability to reject asteroids. On the other hand, the impact of falling asteroids become larger with time — not only because the population density increases, but also because the growing connectedness of the world system, resulting in that damage in one place can spread across the globe. In other words, although the probability of collisions is reducing, the indirect risks associated with the asteroid danger is increasing. The main indirect risks are: A) The destruction of hazardous industries in the place of the fall — for example, nuclear power plant. The entire mass of the station in such a case would evaporated and the release of radiation would be higher than in Chernobyl. In addition, there may be additional nuclear reactions because of sudden compression of the station when it is struck by asteroid. Yet the chances of a direct hit of an asteroid in the nuclear plants are small, but they grow with the growing number of stations. B) There is a risk that even a small group of meteors, moving a specific angle in a certain place in the earth’s surface could lead to lunch of the system for the Prevention of rocket attacks and lead to an accidental nuclear war. Similar consequences could have a small air explosion of an asteroid (a few meters in size). The first option is more likely for developed superpowers system of warning (but which has flaws or unsecured areas in their ABM system, as in the Russian Federation), while the second — for the regional nuclear powers (like India and Pakistan, North Korea, etc.) which are not able to track missiles by radars, but could react to a single explosion. C) The technology to drive asteroids in the future will create a hypothetical possibility to direct asteroids not only from Earth, but also on it. And even if there will be accidental impact of the asteroid, there will be talks about that it was sent on purpose. Yet hardly anyone will be sent to Earth asteroids, because such action can easily be detected, the accuracy is low and it need to be prepared for decades before event. D) Deviations of hazardous asteroids will require the creation of space weapons, which could be nuclear, laser or kinetic. Such weapons could be used against the Earth or the spacecrafts of an opponent. Although the risk of applying it against the ground is small, it still creates more potential damage than the falling asteroids. E) The destruction of the asteroid with nuclear explosion would lead to an increase in its affecting power at the expense of its fragments – to the greater number of blasts over a larger area, as well as the radioactive contamination of debris. Modern technological means give possibility to move only relatively small asteroids, which are not global threat. The real danger is black comets in size of several kilometers which are moving on elongated elliptical orbits at high speeds. However, in the future, space can be quickly and cheaply explored through self-replicating robots based on nanoteh. This will help to create huge radio telescopes in space to detect dangerous bodies in the solar system. In addition, it is enough to plant one self-replicating microrobot on the asteroid, to multiply it and then it could break the asteroid on parts or build engines that will change its orbit. Nanotehnology will help us to create self-sustaining human settlements on the Moon and other celestial bodies. This suggests that the problem of asteroid hazard will in a few decades be outdated. Thus, the problem of preventing collisions of the Earth with asteroids in the coming decades can only be a diversion of resources from the global risks: First, because we are still not able to change orbits of those objects which actually can lead to the complete extinction of humanity. Secondly, by the time (or shortly thereafter), when the nuclear missile system for destruction of asteroids will be created, it will be obsolete, because nanotech can quickly and cheaply harness the solar system by the middle of 21 century, and may, before . And third, because such system at time when Earth is divided into warring states will be weapon in the event of war. And fourthly, because the probability of extinction of humanity as a result of the fall of an asteroid in a narrow period of time when the system of deviation of the asteroids will be deployed, but powerful, nanotechnology is not yet established, is very small. This time period may be equal to 20 years, say from 2030 — until 2050, and the chances of falling bodies of 10 km size during this time, even if we assume that we live in a period comet bombardment, when the intensity is 100 times higher — is at 1 to 15 000 (based on an average frequency of the fall of bodies every 30 million years). Moreover, given the dynamics, we can reject the indeed dangerous objects only at the end of this period, and perhaps even later, as larger the asteroid, the more extensive and long-term project for its deviation is required. Although 1 to 15 000 is still unacceptable high risk, it is commensurate with the risk of the use of space weapons against the Earth. In the fifth, anti-asteroid protection diverts attention from other global issues, the limited human attention and financial resources. This is due to the fact that the asteroid danger is very easy for understanding — it is easy to imagine, it is easy to calculate the probabilities and it is clear to the public. And there is no doubt of its reality, and there are clear ways for protection. (e.g. the probability of volcanic disaster comparable to the asteroid impact by various estimates, is from 5 to 20 times higher at the same level of energy – but we have no idea how it can be prevented.) So it differs from other risks that are difficult to imagine, that are impossible quantify, but which may mean the probability of complete extinction of tens of percent. These are the risks of AI, biotech, nanotech and nuclear weapons. In the sixth, when talking about relatively small bodies like Apophis, it may be cheaper to evacuate the area of the fall than to deviate the asteroid. A likely the area of the impact will be ocean. But I did not call to abandon antiasterod protection, because we first need to find out whether we live in the comet bombardment period. In this case, the probability of falling 1 km body in the next 100 years is equal to 6 %. (Based on data on the hypothetical fall in the last 10 000 years, like a comet Klovis http://en.wikipedia.org/wiki/Younger_Dryas_impact_event , traces of which can be 500 000 in the craters of similar entities called Carolina Bays http://en.wikipedia.org/wiki/Carolina_bays crater, and around New Zealand in 1443 http://en.wikipedia.org/wiki/Mahuika_crater and others 2 impacts in last 5 000 years , see works of http://en.wikipedia.org/wiki/Holocene_Impact_Working_Group ). We must first give power to the monitoring of dark comets and analysis of fresh craters.
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