Bloodlines and Bastards: the Genetics of Hybrid Vigor

Why do outcrossed hybrids show "hybrid vigor", sometimes outperforming either parent?

In good archetypal practice, the prince from one kingdom marries the princess from another, bringing two distinct families together to "invigorate the bloodline", and achieve what geneticists call hybrid vigor, or heterosis. On the other hand, royal families sometimes inbreed, either on purpose, as in ancient Egypt, or by accident, as among the fusty houses of Europe. Such inbreeding leads to genetic decline, as recessive traits become exposed. Better to have Princess Diana running through the china shop than be saddled with hemophilia! Or better yet, have the king litter the land with bastards who, in another archetype, are more robust and vigorous than the proper, and sickly, royals.

In the first approximation, the underlying explanation for these outcomes is deleterious recessive alleles, which are common and arise through mutation. The effect of any individual one may be small, especially in the heterozygotic state, thus they accumulate over time in a normal population, and survive in direct proportion to how deleterious they are. If genetically similar people have children, the likelihood is higher that such alleles that are normally hidden by a complementary wild-type allele will come together and show their defect. If A is the wild-type allele, and a is the recessive, defective allele, then the cross Aa X Aa ==yields==> AA, Aa, and aa, of which the latter offspring is defective or dead, assuming that the a allele is important enough to affect survival. That is the simple story of inbreeding depression, and understandable enough. But why are some hybrids even better off than either parent? Corn is notorious for benefiting from hybridization. The genetics of that are a bit more complicated.

Inbreeding or outbreeding?

A great paper from 1934 laid the groundwork of this field. Sewall Wright stated that this effect was going to be explained not by genetics, but by the biochemistry of the individual loci. The hybrid effect is going to be the net sum over many thousands of genes whose variants, whether good or bad, work out their effects in the development and maintenance of the resulting organism. Some researchers have invoked "overdominance", for instance, where a hybrid at a particular locus is better adapted than either parent. The most famous example is sickle cell anemia, where the hybrid or heterzygote is somewhat protected from malaria. But overdominance is not going to be the general explanation, since such finely tuned allele relationships are rare, and because this tuning is naturally specific to a given population and environment. The likelihood of cross-breeding to an outside genome, adapted to other conditions, benefiting this kind of locus is going to be slim.

No, the more general explanation recognizes that the overwhelming majority of recessive and otherwise deleterious alleles are mechanistically missing function- either partially or wholly. And that they are selectively deficient as well, representing not an advantage to heterozygote, but a slight disadvantage, due to reduced amounts of whatever it is they encode and do. For most enzymes and other functions, half the normal amount is far, far better than none (especially when regarded as enzymes, which are often produced in excess). So, assuming that either population has drifted into a condition where they are homozygous for some minor function, mating with an outside group instantly remediates all those fully defective loci, bringing in 50% molecular function and likely much more than 50% selective function. It also works in both directions- making up deficiencies from both partners of the cross.

But such homozygous recessive/defective loci will be rare, if they have significant functions. More common will be a large pool of heterozygotic recessive alleles. The hybrid cross, between partners that are complementary wild-type at such loci, guarantees some function (at least 50%) at each of those loci, and provides a 50% chance of 100% function. Both are significantly higher rates than for an inbreeding cross, where the chances at each locus of this type are 50% (for 50% function) and 25% (for 100% function), respectively. Summed over numerous loci with complementary character, or just a few key ones, this can have dramatic effects on the resulting offspring. This is the fundamental origin of "heterosis", another name for hybrid vigor. The figure below from one of the reading papers shows this effect constituted in the test tube with enzymes.

An experiment hybridizing enzymes in test tubes.  A set of four enzymes from glycolysis was set in various "parental" solutions at some arbitrary concentration value (blues and yellows). Then such parents were "mated" into "hybrid" solutions (one per row here) and assayed for enzymatic flux. The midline denotes the flux of the hybridized (mixed) enzymes, while the blue and yellow balls represent the respective parental values. One can easily see that across the collection, the hybrid value on average exceeds the mean parental value, and never falls below that of the worst parent. And the hybrid value often surpasses even the best parental value, exhibiting strong heterosis. The explanation offered for this is that each parent may have had a different limiting step/enzyme that was complemented by that supplied by its "mate".

How distant can such crosses be? There is a limit, clearly, since with greater distance, genetic incompatibilities begin to arise, (incipient speciation), which begin to strongly impair fitness, usually affecting fertility first, before other traits. So hybrid vigor arrives at a sweet spot of ... distant enough to have a significant number of distinctive recessive and wild-type alleles, but not so distant that the genomes are no longer compatible at those loci which are evolving most rapidly, which tend to be those involved in immunological functions and those involved in reproduction, which are scenes of notorious arms races of pathogenic and sexual selection, respectively.

Hybrid vigor is complemented by a much more insidious process, the concentration and disposal, via the lottery of sex, of bad alleles into unfortunate offspring that either die before birth (miscarriages) or suffer from their deficiencies through life. While outcrossing hides such recessive alleles, the next cross (F2, in the parlance) brings them back, all mixed and matched with each other, some of which are likely to be dead. That is why farmers using seeds from their hybrid corn crop are bound to be disappointed with a motley field of scarecrows. Inbreeding likewise brings out recessive loci, and the more advanced the inbreeding program, the more "pure-bred" a strain is, the more every locus is homozygous, for good or for ill.

Hybrid vigor is thus an evanescent affair, delaying the inevitable reckoning of bad alleles with their grim reaper- natural selection. Some populations (Mennonites, Ashkanazi Jews) are more inbred, and stricken with more dramatic genetic defects that appear for that reason at higher frequency, but all deficiencies are time bombs that, even if they are well-hidden by their recessiveness and rarity, can eventually meet up to form homozygotes and bode ill for their host.

Human heterozygosity decreases with distance from Southern Africa, as predicted by the Out-Of -Africa hypothesis. As populations move, they leave some of their genetic patrimony/matrimony of variation behind (called a bottleneck effect).

Conversely, the rate of predicted deleterious alleles goes up with distance from Southern Africa. This is thought to arise from the relaxation of selection which is the definition of rapid range edge expansion. Genetic bottlenecks with small populations can also fix deleterious mutations, (i.e. bring them to 100% of the population), overwhelming selective effects, and bequeathing them to succeeding populations, no matter how large.

Reading:

• Sewall Wright, 1934 - describing hybrid vigor in enzymatic terms.
• Julie Fievet et al. 2018 - performing the experiments to validate Wright's theory.
• Brenna Henn, et al, 2016 - human genetics vs geography and prehistoric migration.
• Francois Vasseur et al. 2019 - more studies of heterosis in plants, focusing on nonlinear phenotypic effects.

• Trump before the raving gun nuts ... next week one shoots up a synagogue. Does this resemble a well-regulated militia or mind?
• A pervasive lack of character.
• First, the elite lost control of religion, then art. What is next? The economy?
• Where do good jobs come from? From policy, not accidents.
• Losing Afghanistan.. now, we just don't want to know.
• Bill Mitchell on May Day, veils and myths.

Are We Too Powerful?

What is wrong with our foreign policy? Is it that our military is too big? Review of "The Power Problem", by Christopher Preble.

What is power? A simple and evocative word, but a complicated concept that we Americans seem naive about. We have the most nuclear bombs of anyone on the planet. But would we ever use them? Obviously not. So they do not really increase our power in many, most, and possibly any practical ways. The only setting where nuclear bombs are useful is the precise opposite of the one we occupy- a case like North Korea, which with only a handful deliverable bombs, and the madness to use one, can effectively deter us from ever attempting to overthrow their system. It represents power in only the most existential extremity, and none at all in the usual hurly burly of diplomacy, conflict, terrorism, and small wars.

Similar considerations apply to other levels of military power. We can precision-bomb anyone, anywhere, but does that make us powerful? Not if power really means getting other people to do what you want. Over the last couple of decades, terrorists have shown that they have the power to make us to what they want- start wars, drop bombs all over the place, aggravate a lot of friends, create ungoverned spaces, and make air travel miserable for millions. But have we had the power to make them do what we want? Precious little, other than the extremely blunt method of killing them piecemeal in a game of whackamole which is reaching a dispiriting state of functional surrender in Afghanistan, and stalemate elsewhere.

For people will do what they want, and military methods are never a good or efficient way to make them do otherwise. Rome ran a very militaristic and terroristic system, which is the way things have to be if others are going to bent to one's will by military means. This is the problem of international relations, and particularly our problem having taken on the role of the world's policeman, and gotten embroiled in numerous conflicts ranging from bitterly disappointing (Vietnam, Syria, Afghanistan) to catastrophic (Iraq).

Preble is writing out of the Cato Institute, (and in the realist tradition I have reviewed recently), and adopts a nuanced libertarian stance- that we should not do so much, should allow others to do more, that standing down a little bit would benefit everyone, especially ourselves. The record of the last few decades speaks for itself- that we have made several very bad blunders, mostly by rushing to the "military option" with too little thought. Preble puts a lot of focus on the military- how expensive it is, how intrusive into the rest of society, how wasteful, and how its very size and capability encourage policy makers to use it, like the proverbial hammer. He is an exponent of the Powell doctrine, which sought to hedge our enthusiasm by asking some critical questions, principally whether a particular military action really addresses a national security interest of the United States. Preble is of the opinion that our true interests are quite narrow- simply defense of the continental territory, and that everything else about our world-wide hegemony is not a core interest and could be de-emphasized, if not jettisoned.

Exhibit A is our Middle East policy. The word "inane" comes up in Preble's discussion, and it is hard to disagree. Despite our alarm over the Arab oil embargos of the 1970s, oil has generally found a way to market whatever we do. When we have tried to block exports from countries such as Iraq and Iran, their oil has found markets anyhow, if in reduced amounts, for the simple reason that they have little else to live from. Not even the richest petrostates can refrain from exports for very long. So our decades of support for some of the most retrograde governments imaginable, including garrisons in Saudi Arabia (now shuttered), Kuwait, Qatar, Bahrain, and elsewhere in the Gulf, to "keep the shipping lanes open" and "maintain the flow of oil" have been mostly a waste of time and resources- a deep strategic error. Our only policy should be to deny broad control over the oil centers to strategic enemies such as Russia, or now China. But ISIS? How are they so different from the Saudis? Each sells oil as enthusiastically as it can.

This points to the real problem of US power, which is not so much the seductions of military Rambo activities, but the plain stupidity that they enable and amplify. We have a foreign policy run by amateurs, by definition. The president is rarely elected for foreign policy credentials, and then builds a team (see Hillary Clinton) hardly any more knowledgeable or judicious. Our ambassadorial ranks are filled with political donors and flaks. The congress has given up any hope of retrieving its war powers.  And our professionals, in the State Department and wider intelligence community, have numerous problems as well. How can we make this system work better?

I don't think that trimming our ambitions and letting the world go to the dogs, which is to say, to whichever other powers such as China and Russia have the ambition to take our place, is the only solution. We have good intentions (at least outside of the current administration) and have been generally justfied in our post-World War 2 Pax Americana, despite numerous costly blunders. We have also been served by those good intentions, which generate acquiescence, if not enthusiasm, on the part of our many allies and friends towards our dominant role, which in turn brings us benefits in economic and strategic terms. Not enough to offset the cost, perhaps, but having a stable world is difficult to value, really. Having and keeping many friends is the surest way to proceed to a peaceful world, which is our ultimate goal. In this sense, our competition with China should be on the basis of who can be friendlier and more supportive of an orderly state of affairs among the many other countries of the world.

The question is how to continue our relatively benevolent services without winding up in grievous error because we want to "fix" some problems a bit too enthusiastically. Preble raises the question of alliances, pointing out their inherent danger. If we promise mutual protection with a vast number of frontier countries, from South Korea to Ukraine, we should not be surprised to be drawn into conflicts not of our choosing, which may be unwise. Allied countries naturally feel a bit more free to provoke their neighbors given such protection, and we only need to think of World War 1 to understand the danger of such interlocking, tripwire alliances. So one approach is to make our relations with other countries more contingent, dependent on continuing good relations rather than legalistic (which is ultimately fictitious anyhow) in character. We should have friendship treaties with many, but alliances with few. But that is a minor point, since most of our rushes into action have been justified in other ways.

The deeper problem is not in having a military that is too strong, or alliances that are too promiscuous, but in having a policy-making apparatus that lacks intelligence. For all our NSA, CIA, and other capabilities, we blundered into Iraq for reasons that involved personal psychology (Bush, Cheney), intelligence failures (CIA), failures of integrity (Rumsfeld, the military, CIA), failures of institutional balance (State vs military and CIA), and further failures of intelligence- in lacking knowledge not only of the state of Saddam's power structure and capabilities, but of the culture we would be faced with were we to succeed in removing him. It was portrayed as the liberation of Paris all over again, plus lots of oil. The absurdity of this vision comes down to the insularity of everyone in power and the weakness of countervailing institutions (i.e. the State Department) that might have had a better grasp of the matter.

So while Preble is dubious about expanding the State Department, "its aim is to relate to foreign nations, not to run them", that is exactly where we need to go to gain a more intelligent foreign policy. But in a very specific way. We need more knowledge of local cultures that is useful to us. Right now, the customary tour is for a two or three years. This is enough time to get a feel for local conditions and make lots of high-level contacts. But it is no way to gather deep knowledge of the wellsprings of local sentiment, and the wheels that make everything work in that culture. It is that knowledge that we were missing in Iraq, and in Vietnam, and in the Balkans, and many of our other misadventures. We should keep the short tour officers- they are less likely to be captured by the local culture, and keep their service-to-America discipline. But we should add a cadre of officers that are a sort of cross between Peace Corps and Foreign Service, who specialize in learning about one other place for the long haul, and are not under threat or obligation to move elsewhere, unless they wish to do so. A sort of Lawrence of Arabia model, who might make themselves useful by writing books about the local culture, reports for the local embassy, etc. They would necessarily be more loosely tied to the US government bureaucracy, and their knowledge would come with some caveats. We probably cultivate a variety of locals currently who provide such key knowledge, but it seems that it does not always make a sufficient impression to affect our policy, due to failures in translation.

Knowledge is power. Some white privilege and great cinematography doesn't hurt either.

The next question is how to slow the rush to war, and weigh expertise more heavily in our foreign policy councils, such that all this deep knowledge and intelligence from the field gets used to actually make decisions, rather than brushed aside by an incurious or incautious executive. The current structures of departments and the interdepartmental process through the NSC, are effective in shaping rational policy. But again, there are a lot of amateurs at this table. Every one at the top level is a political appointee, other than the President herself. While the Secretary of State should be speaking for the arm of the government that is deeply knowledgeable in foreign affairs, and for its expert employees, that is hardly a given. The NSC needs at least one representative from the professional ranks of the State Department, and also needs at least one representative from Congress, to exercise its oversight and constitutionally balancing role. In compensation, the council could probably do without the drug policy advisor, Energy Secretary, and White House Chief of Staff. This would make our core foreign policy-making institution more professional, accountable, and responsive to knowledge from the field. It needs also to take its long-term policy role more seriously, and spend less energy on micromanagement.

Turning back to our over-militarized stance in the world, using force less requires not so much that our military be made smaller. We have prowling through all the oceans shockingly powerful submarines to which no one pays much attention or wishes to use. No, the problem is one of strategic conception- that we fail to realize how limited the effective role of military action is, compared with the vast scope for friendly and constructive engagement with other nations.

Military power is simply the power to kill people, not to make them do or think what you want. As we learn in the old Westerns, coercion is the least effective, least humane, and least durable way to run a society. The model of global policing (if that is what we are doing) needs to be one of community policing, not of SWAT teams dropped from Apache helicopters. In Afghanistan and Iraq, we routinely killed the wrong people because we did not know true local conditions and got our "intelligence" from bad sources. That is what you get with the SWAT team model. Our own civil war can serve as another touchstone here. What if some other country had barged in and told us what was right, and had started an occupation? That would not have gone over well. The opportunities for insurgency and simmering ongoing warfare would have been quite a bit higher, though there was plenty of that in the postwar South as it was. The point is that our blithe talk about "the military option" routinely fails the most elementary test of foresight- to put ourselves in the other party's shoes.

• Our total debacle in Syria. But warning.. propaganda is likely here.
• Smart is sexy.
• Factory farming- not a pretty sight. 
• Some charter schools are frauds.
• Who could be less qualified than Herman Cain to serve on the Fed?
• Yes, it looks very bad.
• Brain injury is common, and dangerous.
• In Australia, a war on cats.

New Phases in the Nucleus

Special molecular interactions generate new phases of matter in various globs within the nucleus... but why?

One of the great events, near or at the orgin of life, was the advent of membranes- stable, flexible, but also rather tough structures build from amphipathic molecules, with water-loving head groups at one end and water-repellent, oil-like chains elsewhere. They sandwich together spontaneously to make the membrane (bilayer) sheet, which constitutes a separate phase from both the outside and inside of the cell. Getting across it is impossible for many molecules, which is highly protective, but has also necessitated a large zoo of transporters, channels and other mechanisms for transactions cells need to make with the outside.

Typical membrane, with a hydrophobic, oily interior that keeps it structurally coherent and impermeable to most aqueous substances. Note that it is, on a molecular scale, quite thick- bigger than most proteins.

It has gradually become apparent that the nucleus (whose envelope is a double membrane and which was borne of another great event in life- the origin of eukaryotes) harbors quite a variety of other phases of macromolecules, constituting zones, globs, speckles, assemblies- organelle-like structures that make study of the nucleus rather interesting. The story begins with the nuclear pore, which is where any moderate to large size molecule, up to partially constructed ribosomes, has to go to enter or leave the nucleus. Such cargo typically has a short segment in its protein chain that serves as a "signal", either for nuclear export or import. These signals bind to specialized transporter proteins which themselves have an unusual decoration of hydrophobic protein segments (HEAT repeats). The nuclear pore is lined with proteins carrying another decoration, forming an unstructured hydrophobic and homophilic mesh or gel of FG-repeats (named for their composition of phenylalanine and glycine) inside the pore. The transporter HEAT repeats can bind weakly,  but specifically, to these FG-repeats, or perhaps better, melt into them, and thus pass easily through the pore. It is a very clever scheme for controlling transport tightly with a mechanism that costs virtually no energy, since the transport is passive, going down the various molecules's concentration gradients.

Diagram of one nuclear pore complex. showing especially the mesh of FG-repeat protein tails that compose its interior and fringes. These interact with compatible transporter molecules to let large proteins and complexes through by selective diffusion.

But that is not all. The nucleus has long been known to have a large zone, the nucleolus, where ribosomal RNA genes are transcribed and where much of the assembly of ribosomes takes place. It is a dense mass of DNA, RNA, and proteins specialized to these tasks, a veritable factory for making this most abundant and complex component of cells.

An electron micrograph of one ribosomal gene in the act of being transcribed. Each rRNA transcript is a separate "branch" on this Christmas tree, showing the conveyor belt/factory nature of the process. Image at top, tracing at the bottom. The field is about 2.5 micrometers. This is only one of many ribosomal generation processes taking place within the nucleolus.

More recently, several other structures have been discovered in the nucleus, including speckles of RNA splicing components, Cajal bodies, PML bodies, paraspeckles, and others. And researchers have now realized that some transcriptional activation machinery forms similar blobs, called "super-enhancers". These have particularly high gene expression activity and seem to comprise a critical mass of regulatory RNAs, DNA-binding transcription factors, and a mess of mediators, histone modifiers, and other regulatory proteins in a sort of molten glob that segregates from the rest of the already-dense nuclear milieu. These are regarded as distinct liquid phases. Since DNA and RNA can bend, particularly between long-range enhancer regions and the promoter and coding regions of genes, it is possible to pack a lot of activity into a small, furiously active glob. And the high cooperativity that is implicit in the formation of such a glob is modeled, by a recent paper, to cause a sharp rise in transcriptional activation as well.

Model of condensed super-enhancers, (C, bottom), compared with run-of-the-mill enhancers, (C, top).  Their transcriptional activity (red) is, due to their greater size and stability, likely to be higher and far more consistent than that of even strong enhancers.

Why? One reason is that physical stability helps to keep the machine going, in contrast to usual interactions in the nucleus and elsewhere that are more sporadic, and fall apart as soon as they come together. Transcriptional activation, to take one example, relies on the coalescing (collusion, if you will!) of dozens of different proteins and complexes, all of which have to be available for other interactions as well, if dynamic gene regulation is to take place all over the genome. Most of these interactions are thus weak, so there is a critical mass (and perhaps composition) that distinguishes enduring, high-activity enhancer complexes, which can then be termed super-enhancer globs, from the normal form of enhancer that comes together on a far more temporary, ad-hoc basis. It is yet one more way, based on, but emergent from, the detailed composition of an enhancer, to turn up the gain on the target process that they regulate- transcription.

Different phases of matter thus have very significant roles in the cell, especially in the nucleus, allowing the establishment of mini-organelles / factories for operations that can be more efficient via the time-honored route of separation and specialization. They add to the sense of a sort of convergent evolution, since we already knew that there are conveyor belts, (DNA and RNA templates), just-in-time material and metabolic logistics, transport networks (actin, microtubules), and extraordinarily complex management methods in play.

• The pathological tau proteins in Alzheimer's bind to the nuclear pore proteins and gum up the works.
• One reason why our tax filing system is insane.
• Even evangelicals are getting fed up.
• Krugman is has it sort of backwards- Medicare for all may be politically difficult, but other countries show it can be done. Accomplishing much via a Green New Deal, on the other hand, is, while critically important, also very difficult.
• We have a savings glut.
• Craven catering to the Taliban, cont.
• Religiosity and brain damage?
• Impeachment richly warranted, but unlikely due to craven corruption.
• Veblen and the rot of inequality.
• Another view of MMT.

Breaking Secrets

A small way to increase labor power.

Why is inflation so persistently low? Even when the government is on a spending and tax-forgiveness binge, and interest rates have been rock-bottom for a decade? I have been spending some time with a left-inflected economics textbook from the 80's by Samuel Bowles et al., which gives a view of our situation that contrasts significantly from the mainstream free-market, neoliberal economics we have been fed for the last few decades. Perhaps its basic point is that capitalism only works when labor is exploited, yielding a surplus product. No profits = no capitalism. Thus the overarching aim of capitalists is to extract excess value from labor, over what is being paid out.

This extraction process has many dimensions, but a few of the salient ones deal with a odd role of markets in capitalism. Most people working in the capitalist system are not working in markets. They are employees, whose work is not bid on an hourly basis, who do not personally sell what they personally make, in a market. They exist in a command economy, quite divorced from this fantasm called "the free market". If they do not get along with their boss, they are fired. They are evaluated, not by market outcomes, but by subjective opinions of others around them, and are subject to a complex bureaucracy of control by the firm they are employed by. While the firm has market interactions with the outside, on the inside it is hardly different from a communist enterprise, indeed a good deal more heartless. Much of what corporations and the capitalist class lobbies for is not freer markets (heaven forbid!), but more ways to control workers, whether that is by right-to-work, weakening unions, keeping disputes out of open court, colluding with each other to not poach workers, staging "team-building" activities, stealing worker pay, reducing safety net programs, etc. So, contrary to the right-wing ideology of freedom, one of the main tasks of capitalists and their political servants is to reduce the freedom of workers.

The principal sword dangling over the employee is unemployment. That is the ultimate sanction, and is essential to the functioning of the whole system. Unlike other markets for goods, the labor market never clears, or settles on the stable demand/supply point. As the book comments, employers do not need to have a line of unemployed machines standing outside the gates to encourage the machines inside the factory to work harder. But they do need unemployement, both to support the command economy inside the firm, and also to keep the wages paid below the actual value given by labor. This connects additionally to one of the reasons for the business cycle- to raise unemployment and thereby "discipline" worker demands, in addition to moderating input prices and clearing out inefficient firms. It turns out that the full business cycle, including recessions, is as central to capitalism as capital itself. We can not have only good times, if corporations are going to clear profits by exploiting workers.

Which ultimately brings us back to inflation. We had a "great" recession in 2008, which led to very high unemployment and durably reduced output. Workers were very well disciplined, to the point that large numbers left the work force entirely. One consequence of all this discipline and lowered expectation has been that employers could get away with not raising pay. The trend of economic growth/benefits going entirely to the capitalists and rich, and none to workers, has continued at an accelerated pace through the period. A side effect of all this low pay is low inflation. This is in dramatic contrast to the late 1960's and 1970's, when worker power was high, unionization was high, and demands for pay were high. Workers expected not just cost of living raises, but seniority and productivity raises as well. Incidentally, the public sector, which is highly unionized and in a special position with political power over its employers, is a relic of that outdated world, resulting in bloated pay and pensions, which are now unheard of in the trenches of the real economy.

Workers have not gained from productivity increases for forty years.

So things are, from a long-term perspective, unbalanced. And what did voters in their wisdom do about it in 2016? They elected a hypercapitalist, who conned them into thinking that he wanted to do something for workers. Ha! Obviously, the progressive agenda is far more pertinent to workers, seeking to reduce instead of increase capitalist power. Progressives seek to increase worker power in a myriad of ways- regulation, a higher minimum wage, better safety net, more public services, higher wealth and income taxes. The strongest proposals so far aim at the lowest end of the scale- setting a living minimum wage, and also establishing the principle of jobs for all- a job guarantee that would set an even more robust floor for the job market and seriously impair the fear that unemployment inspires. Will capitalism survive? I think so- the Scandinavian countries have far more civilized regimes of public goods and worker protection, and seem to do OK.

But what about the bulk of workers in the middle rungs of the economy? Some additional thinking needs to be done to bolster their prospects in the fight with capitalists. While unions are highly beneficial for their members, their benefits are intrinsically balkanized and can be highly damaging to their industries- think of the car industry. A better way is to institutionalize broadly some of the benefits that unions have pioneered, such as the weekend, regulatory worker protections, and rights of political and economic organization.

One idea that I think would be very useful would be to break the secrecy on salary. One of the principal benefits of union membership is the transparency that it provides to workers- knowlege of what everyone is being paid, as a step to negotiating contracts. One of the greatest powers that corporations have, to steal pay and discriminate against classes of employees, is to keep pay secret, as though it were some kind of sacred trust. But many workplaces have transparent pay structures, such as union shops, boardrooms, and professional sports teams, and the sky has not fallen. What average workers need is government mandated transparency on pay in every workplace, so that everyone can see how they and others are being treated. Few measures would as effectively show injustice, generate fairer treatment, and give workers a more realistic picture of their prospects at a current or a future employer.

Would we get more inflation? Perhaps. But there are many ways to skin that cat, with credit, monetary and fiscal policy, rather than worker suppression. It is time for a little capitalist suppression- to right an economy, and a society, far out of kilter.

• How best to raise taxes?
• Stiglitz on the thorough-going corruption of the Trump administration.
• Lying without shame.. will it win the next election too?

That's Cool: Adolescent Brain Development

Brain power and integration increases with development, particularly in the salience network and in the wakeful, attentive beta waves.

We see it happen, but it is still amazing- the mental powers that come on line during child development. Neurobiologists are starting to look inside and see what is happening mechanistically- in anatomical connectivity, activity networks, and brain wave patterns. Some recent papers used fMRI and magnetoencephalography to look at activity correlations and wave patterns over adolescent development. While the methods and analyses remain rather abstruse and tentative, it is clear that such tendencies as impulsivity and cognitive control can be associated with observations about stronger brain wave activity at higher frequencies, lower activity at lower frequencies, and inter-network integration.

An interesting theme in the field is the recognition that not only is the brain organized physically in various crinkles, folds, nodules, etc., and by functional areas like the motor and sensory cortexes or Broca's area, involved in speech production, but that it is also organized in connectivity "networks" that can cross anatomical boundaries, yet show coherence, being coordinately activated inside much more densely than outside the network. An example is the default mode network (DMN, or task-negative network), which happens when adults are just resting, not attending to anything in particular, but also not asleep. This is an example of the brain being "on" despite little conscious mental work being done. It may be our unconscious at work or play, much like it is during sleep on a much longer leash. As one might imagine for this kind of daydreaming activity, it is strongly self-focused, full of memories, feelings, social observations, and future plans. Anatomically, the DMN extends over much of the brain, from the frontal lobes to the temporal and parietal lobes, touching on regions associated with the functions mentioned, like the hippocampus involved in memory, temperoparietal areas involved in sociality/ theories of mind, etc. There are roughly twenty such networks currently recognized, which activate during different mental fuctions, and they provide some answers to the question of how different brain areas are harnessed together for key functions typical of mental activity.

Two networks relevant to this current work are the salience network (SN) and the cingulo-opericular network (CN or CO). The latter is active during chronic attention- our state of being awake and engaged for hours at a time, termed tonic alertness. (This contrasts with phasic alertness, which is much shorter-term / sporadic and reactive).  It is one of several task-positive networks that function in attention and focus. The salience network spans cortical (anterior insula an dorsal anterior cingulate) and subcortical areas (amygdala and central striatum) binding together locations that play roles in salience- assigning value to new events, reacting to unusual events. It can then entrain other brain networks to take control over attention, behavior, thoughts, etc.

fMRI studies of the activity correlations between brain networks. The cingulo-opercular and salience network connections (gray) take a large jump in connectivity to other regions in early adolescence. At the same time, fronto-parietal network connections (yellow), characteristic of frontal control and inhibition of other networks, take a dive, before attaining higher levels going into adulthood.

Here we get to brain waves, or oscillations. Superimposed on the constant activity of the brain are several frequencies of electrical activity, from the super-slow delta waves (~ 1Hz) of sleep to the super-fast gamma waves (~50 Hz) which may or may not correlate with attention and perception. The slower waves seem to correlate with development, growth, and maintenance, while the faster waves correlate with functions such as attention and behavior. Delta waves are thought to function during the deepest sleep in resetting memories and other brain functions, and decline sharply with age, being pervasive in infants, and disappearing by old age. Faster waves such as theta (5-9 Hz), alpha (8-12), and beta (14-26 Hz) correlate with behavior and attention, and are generally thought to help bind brain activities together, rather than transmitting information as radio waves might. Attention is a clear example, where large brain regions are bound by coordinated waves, depending on what is being attended to. Thus the "spotlight of attention" is characterized both by the activation of selected relevant brain areas, and also by their binding via phase-locked neural oscillations. These are naturally highly variable and jumbled as time goes on, reflecting the saccadic nature of our mental lives.

One of the papers above focused on theta and beta waves, finding that adolescents showed a systematic move from lower to higher frequencies. While fMRI scans of non-oscillatory network activity showed greater integration with age, studies of oscillations showed that the main story was *de-coupling mainly at the lower frequencies. What this all seems to add up to is a reduction of impulsivity, via reduced wave/phase coupling between especially between the salience and other networks, at the same time as control over other networks is more integrated and improved, via increased connectivity. So control by choice goes up, while involuntary reactivity goes down. It is suggested that myelination of axons, as part of brain development along with pruning extra cells and connections, makes long-range connections faster, enabling greater power in these higher frequency binding/coordination bands.

Brain wave phase coordination between all areas of the brain, measured by frequency and age. Low frequencies associated with basal arousal, motor activity, and daydreaming are notably less correlated in adults, while beta-range frequencies about 25 Hz, associated with focused attention, are slightly more correlated. 

Is this all a little hand-wavy at this point? Yes indeed- that is the nature of a field just getting to grips with perhaps the most complicated topic of all. But the general themes of oscillations as signs/forms of coordination and binding, and active sub-networks as integrating units of brain/mental activity on top of the anatomical and regional units are interesting developments that will grow in significance as more details are filled in.

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Addiction, Exorcism, and the American Dream

Review of Beautiful Boy.

Why is drug addiction such a widespread and dangerous scourge? A lot has been made of the despair of the working class especially in declining rural areas- a crisis of meaning and survival at the short end of the capitalist system. But there is higher anxiety everywhere in our unequal, precarious, and atomized system. Even in wealthy Marin, where the story of this movie originates, parents are in what seems like fight to the death to get their offspring into colleges to fulfil an overwhelming set of competitive expectations. No wonder young adults, even when well-to-do, already feel themselves in a rat race which it would be pleasant to check out of, momentarily. Then add in the viciousness of modern drugs like crystal meth and fentanyl, and you have a lethal witches' brew.

Still from the movie. Timothee Chalamet playing Nic Sheff, and Steve Carrel playing David Sheff.

We used to regard Russia as a demographic basket case, with declining population riven with alcoholism in the wake of the Soviet collapse. Now we are facing a similar downward dynamic- a social rot punctuated by self-destruction through drugs and suicide. The ultimate source seems to be broad insecurity, which was precisely the point of the economic and cultural reforms of the recent Republican epoch, starting with Ronald Reagan. The benefits of competition and division were trumpeted, and the rich were feted as job creators and entrepreneurs, and given absurd benefits like a tax rate on investment profits half as high as the rate on labor income. Companies developed an ideology of serving profits to the exclusion of all other goals, which meant the destruction of stable life schedules, stable jobs, and stable communities. The Reagan era gave rise to wide-spread homelessness, the ultimate warning to labor to keep its head down. And a broad reduction of safety nets of all sorts, from corporate pensions to onerous rules for welfare, which was divided into a puzzle of ungenerous programs.

How ironic, then, that Donald Trump offered to fix all this for workers, restoring the greatness and jobs of America. Who suspected that he came from a Republican tradition whose first order of business, when given power, has been to hand money to the rich? Who suspected that his policy ideas came more from the tabloid headlines of the 80's and 90's (not to say his fascist forebears in the 30's) than from the issues the working class face today? Who suspected that the greatest epoch in American history, after World War 2, was actually our period of highest taxation, culminating in, not coincidentally, the Apollo space program, which was hardly a capitalist venture?

Reagan, George W. Bush, and Trump each cloaked themselves as shamans for an anxious society, ready to exorcise the demons of economic malaise and insecurity, as well as those of Vietnam. While Democrats offered laundry lists of melioration, Republicans could do no such thing, their object being to strengthen hierarchy and help the better-off. They have instead lighted on a more tribally / religiously tinged approach, offering a broad ideology of conservatism (however radical the implementation, and departure from the existing system) and order, which would by some mystery of compassionate conservatism redound to the benefit of all after generous payouts to the few.

On the military front, they authored a series of military misadventures that climaxed with the criminal debacle in Iraq. On the economic front, they pushed hard-line capitalism as the cure-all to bring economic growth, starving the state with deregulation, outsourcing, and bitter budget / deficit battles as a purgatorial nostrum that would rejuvenate an ailing system. Curiously, however, the treatment never worked for the middle class and poor, keeping them economically static and ever more insecure, while the rich and super-rich pocketed all the proceeds.

Economic vitality needs some dynamism and destruction. But people and communities need stability and a basic level of egalitarianism to feel human and have basic freedoms. The founders foresaw that rising wealth and inequality might make of America the same class-ridden culture they had fled in Europe. Their hopes were tied not just to the new republican structure they were building, but also, in economic terms, to the frontier- the jobs-for-all program of its day- which would continue to offer all Americans (and immigrants from all over the world) the option of a decent and hard-working living, preventing excessive inequality.

Now the frontier is gone, the population continues to rise, and the only solution from the "conservative" right is to squeeze the middle class and poor relentlessly in a spiral of anxiety that drives everyone to work and live under ever less humane conditions. We need a better balance that builds more unifying social structures and public goods, reels back the excesses of extreme capitalism, and gives people breathing space and freedom to dream of being more than cogs in a machine.

RB: Short Name For a Complicated Protein

A key cancer protein operates in a huge network of regulatory protein interactions.

RB stands for retinoblastoma, one of the first diseases tied to a causal oncogene, now also called RB. For lack of time, this will be a very short post about a very lengthy story- how complicated one protein can be. The RB protein doesn't really do much on its own. It isn't an enzyme, or bind DNA, or do other dramatic things. But it binds to a lot of other proteins- 322 have been documented to date. And one protein that it binds to and represses, the transcription factor (family) E2F, is a key activator of cell division, promoting transcription of many other genes including cyclins and cyclin-dependent kinases that run the cell cycle. So RB is typically a key actor that keeps cells quiescent in G1 phase, the normal non-dividing state most of our cells are in. And this is how mutations in RB promote cancer, by removing this brake.

A recent paper expanded this story by investigating some of the regulation of the RB protein, which has at least 15 sites where it gets a phosphate group added (phosphorylated) by regulatory proteins called kinases. The most prominent regulatory kinases are the cell cycle dependent kinases, or CDK. Naturally when a cell does really want to divide, these function to turn RB off, via certain of these phosphorylations. The authors erased each of these phosphorylation sites, and then restored one at a time, asking what binds to them and their effect is. The upshot is that each site turned out to show a distinct pattern of downstream effects, indicating that different proteins bind more or less well to each phosphorylated form. These proteins include transcriptional regulators of a wide variety of kinds, and affect differentially the expression of key genes like BRCA1, 2, and MSH2, and processes ranging from DNA repair to oxidative phosphorylation to protein secretion.

Diagram of the sites of phosphorylation of RB by other proteins. The amino acid sequence goes from left to right, and functional regions of RB that bind to other proteins are colored.

"Collectively, this mass spectrometric analysis identified 438 proteins with a statistically significant enrichment in complexes with at least one of the 16 forms of RB examined. The 22 proteins significantly enriched with all forms of RB included multiple E2F and DP [E2F partner] proteins."

Evolution has had several billion years to tinker with these systems. So while the solution sometimes has been elegance incarnate, (like the DNA molecule), other times it is a messy network of sprawling and mystifying scope. It is one reason why biologists will remain tied to their benches for decades to come.

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Patterns of American Extremism

John Calhoun and the coming of the Civil War. Review of "Heirs of the Founders", by H. W. Brands.

Our politics are straining under back-breaking burdens. We are still saddled with several undemocratic compromises of the founders, are corrupted by money and corporate interests, and profess a democracy which in even its best incarnations is, historically, a brief reprieve betwixt tyrannies and oligarchies of various forms, inevitably brought down by the greed, fears, and passions of its subjects. We are experiencing division to a degree not seen since the civil war, and corruption, even treason at the highest levels of government. Where is all this going?

A recent multi-biography focused on the leading politicians of the early to mid-1800's: Daniel Webster, from Massachusetts, Henry Clay, from Kentucky, and John Calhoun, from South Carolina. Yoking them together this way is common in the teaching of this era, but it does something of a disservice to their strikingly divergent contexts and paths. Webster was a natural supporter of Northern interests, including Union, tariffs, but not abolition. He eventually agreed with the compromise of 1850 that enforced the fugative slave policy of the South, since that policy was written explicitly into the constitution. Clay was the most ambitious of the set, leading the Senate through decades of policy and legislative compromise. His lodestar was also Union, made increasingly difficult by the relative economic decline of the South, the entrenchment of slavery, and the fatal compromises that had already been made in the original constitution.

Mysterious, Romanesque bust of John Calhoun, senator and vice president from South Carolina.

John Calhoun was different altogether. While the others tacked repeatedly to maintain the Union and its institutions, Calhoun lit out towards a bitter and uncompromising pro-Southern, pro-slavery position. He was the one who repeatedly threatened secession before the Congress. He was the one who turned intellectual and moral summersaults to defend slavery as consonant with the constitution, the founders, and human decency and progress. This was a time, of course, when Native Americans did not even get this level of discussion- they were packed off to Oklahoma with hardly a bleeding heart on their side. Racism was endemic, and the point of America was not harmony, but the manifest destiny of the Europeans who were remaking the continent. Still, the blatant FOX-news quality of Calhoun's arguments is unmistakable. Here he compares the state of African Americans in Massachusetts to those in the South:

"By the very latest authentic accounts, there was one our of every twenty-one of the black population in jails of houses of correction, and one out of every thirteen was either deaf and dumb, blind, idiot, insane, or in prison. ... The condition of the African race throughout all the states where the ancient relation between the two races has been retained enjoys a degree of health and comfort which may well compare with that of the laboring population of any coiuntry in Christendome; and it may be added that in no other condition or in any other age or country, has the negro race ever attained so high an elevation in morals, intelligence, or civilization."

All this led to a clear break:

"I have, Senators, believed from the first that the agitation of the subject of slavery would, if not prevented by some timely and effective measure, end in disunion. Entertaining this opinion, I have, on all proper occasions, endeavored to call the attention of each of the two great parties which divide the country to adopt some measure to prevent so great a disaster, but without success. The agitation has been permitted to proceed, with almost no attempt to resist it, until it has reached a period where it can no longer be denied or disguised that the Union is in danger. You have thus forced upon you the greatest and the gravest question that can ever come under your consideration: How can the Union be preserved?"

Calhoun brooked no embarrassment or qualm about slavery. As an institution, it was good, not bad; growing, not dying. While Clay and the founders generally hoped that it would wither away, though economic evolution and plain moral decency, Calhoun stood for its unrepentant expansion. The constitution was also behind him. The constitution gave Southern states the representation of 3/5 of its slaves, but none of their voting. The constitution said nothing about any powers the Union might have to restrict slavery in new states. The constution explicitly forbade the harboring of runaway slaves. The country had lost sight of its duties to the South, and were the abolitionists not muzzled from speaking their inconvenient moral truths, the South would have no more of it.

It is a story of a whole section of America gone off its moral rocker, in service of plain greed and conservatism. A religion has also evolved in the South that seems to blend the authoritarianism and social conservatism of Catholicism with independent elite governance and a scrim of protestant theology. When the South did secede, the Union government let loose a torrent of progressive legislation. One senses strongly that we could and would do the same today but for the anchor of a Southern political culture still petrified by true equality, dedicated to feudal economic relations, and to defend itself, still spouting the mantra of state's rights. The map of Red states tells the story.

Political divisions over the last sixty years, by presidential election.

But it is the media and media leaders that serve to normalize immoral positions. Climate change is only an example, but perhaps the clearest and most dire of our time. Failure to act is simply criminal- an act of sabatoge against the future of every citizen and the entire biosphere. A fair portion of our culture, driven by right wing media and its nexus of money and fear, drives an utterly immoral political culture of denial, mean-ness, and blind conservatism. Trump has nowhere near the intellect or facility of John Calhoun, but the brazen support of palpably destructive policies, the headlong divisiveness, the antipodean moral compass have a certain resemblance.

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Deranged Transcription

.. in autism, schizophrenia, and bipolar syndromes.

It is clear that human evolution over the last few millenia has been particularly rapid for mental/cognitive traits. This seems to have created the hazard of unintended consequences in the form of mental illness, when this high-strung and finely tuned system goes haywire. There has been a steady stream of genome variants discovered to be associated with prominent mental illnesses like schizophrenia, autism, and bipolar disorder. These variants are inherited (not sporadic, like the mutations responsible for most cancers) and tend to be either rare or have very slight effects, for obvious reasons.

"The majority of disease-associated genetic variation lies in noncoding regions enriched for noncoding RNAs (ncRNAs) and cis-regulatory elements that regulate gene expression and splicing of their cognate coding gene targets."

One feature that stands out among the genetic variants that have been found to date are that they are rarely in coding regions, thus do not affect the sequence of the protein encoded by the affected gene. Instead, they affect regulation- the delicate mechanisms by which genes are turned on and off in particular places and times. It is now common knowledge that humans have hardly more genes than fish or potatoes. It is gene regulation that makes us what we are, and recent decades have revealed whole new mechanisms and participants in this regulation, such as long non-coding RNAs.

A recent paper conducted a fishing expedition to find how gene regulation varies among people with mental illness, in a quest to find causal changes and molecular patterns characteristic of these syndromes. They had access to thousands of brain samples, and put them through a modern analysis of transcripts, including from 16,541 protein-coding genes and 9,233 genes expressing short or long regulatory RNAs. One theme that came up is that they found many differences among gene splice forms. Most eukaryotic genes are spliced after they are transcribed, being composed on the genome of a series of separate coding exons. This splicing (removing the intervening intronic RNA and joining the coding exons) is highly regulated and for many genes, fundamentally influential on what protein they ultimately produce. Some genes have dozens of different splice forms, many with significantly different roles. For example, a key functional domain like an inhibitor or a DNA-binding region may be left out of one form, converting its encoded protein into one that performs functions precisely opposite to those of the full-length form.

Screen shot from the NIH gene resource, showing the human gene titin, which encodes the largest known protein, which structurally spans the muscle sarcomere. Each green segment is an exon, totalling 363. Each horizontal line is a distinct splice form, varying in which exons are included. Skeletal and cardiac muscle express different splice forms of this protein, and sequence variations in this gene are responsible for some syndromes such as dilated cardiomyopathy.

After putting their brain tissue samples through purification and sequencing of all the RNAs, and alignment with known sequences, the authors came up with a set of differences of gene expression between affected and control subjects. They claim that a quarter of all the genes they looked at were noticeably affected by one of the three disorders they looked at- autism, schizophrenia, and bipolar disorder. Naturally, this finding may be a consequence of wide-spread structural and functional changes in affected brains that may be well downstream from any causative factor. There was relatively little overlap between the three. Schizophrenia showed the most differentially expressed genes/splice forms by far (several-fold more than the others), and shared about half of those seen differentially expressed in bipolar disorder, and one-fifth of those in autism. One might speculate that on the whole, schizophrenia is a more severe disorder which would lead to more dramatic differences in gene expression in an absolute sense.

"Notably, 48 DS [differentially spliced] genes (10%; FDR = 8.8 × 10−4) encode RNA binding proteins or splicing factors, with at least six splicing factors also showing DTE [differential overall transcript expression] in ASD [autism spectrum disorders] (MATR3), SCZ [schizophrenia] (QKI, RBM3, SRRM2, U2AF1), or both (SRSF11)."

Interestingly, the authors also tested (in animals) whether drugs used to treat these major disorders could generate the differences seen above. The answer was no- differential expression was somewhat affected by lithium, but not significantly by the others tested. Secondly, the authors wheeled in a separate method, sifting through genomic variations to find other genes with variations known to be causally associated with these diseases, and guess whether these variations (aka mutations) might affect transcriptional expression. The results did not overlap very well. For bipolar disorder, none of the 17 genes identified by this latter method overlapped with the differentially expressed genes identified by the first method.

Part of the general scheme of the experiment, and schematic results. Isoforms of some genes show differences in disease vs control tissues, and patterns from many such genes and differences can be assembled to diagnose particular cells or processes that are being notably affected. But note in the middle panel that the quantitative difference in the alternative splicing pattern between disease and control for this particular example is minuscule- in the 1 to 4% range. It may be statistically significant, but could be minor in effect. The last panel illustrates fold-change ranges for non-coding long RNAs among the different syndromes and known patterns of cell-type expression, in a schematic sense. Genes known to be expressed in microglia showed particularly significant changes.

So what did they get? Mainly a lot of little fish, and quite a few that had already been suggested to be important for brain function by other methods. One prominent theme was the involvement of immune-related genes. Genes characteristic of astrocyte and microglia cell expression, and of interferon responses, among other signatures, were significantly up-regulated. This agrees with other work indicating that inflammatory mechanisms are used to prune synapses and cells generally in the brain, and this process is over-active in schizophrenia. An example gene is complement C4A, which encodes part of a key immune system that identifies and clears foreign material with the help of phagocytes. It used to be thought that the central nervous system was immune-privileged, i.e. not surveiled by it or affected by it. But that turns out to be very far from the truth, and this gene's overexpression is genetically identified as a causal factor for schizophrenia.

Another big fish they caught was a gene called RBFOX1. Certain spliced forms were significantly less abundant in the affected tissues, supporting a long line of work identifying variations in this gene as candidate causal factors for autism, and its function as an RNA binding protein that regulates the alternative splicing of other genes as well as their later transcript stability and lifetime. Reduced function of this protein is known to increase neuronal excitability and increase seizures. It seems thus to be a key node in neuronal development and functional regulation, through its control of the expression of other genes.

Did these authors find anything new? That is naturally hard to say at this point, since such conclusions would require quite a bit of followup work to analyze the function of novel genes that were found. The expedition showed that it was technically capable of hauling in not only a lot of fish, but many known already to be significant in these syndromes, either causally or as markers and downstream effects. Choosing which to track down to their actual biology is a difficult question- one that must come next. It is a catch that may provide sustenance for many students and post-docs to come.

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• California's housing crisis is rooted in NIMBY permiting, not economics.
• Treason and felony? Not so bad after all.

Music Notation Needs a Redo

Music notation can be better.

Music notation is one of those conventions that solidified long before it was critically analyzed, and well before the advent of even remotely modern usage. The fact that sharps and flats involve special symbols, either in the key signature or as "accidentals", is a sure sign of a hack that has ossified into a standard- one that is painful to learn and use. But the most painful aspect of modern music notation is that the same note appears in contrasting places in different octaves- on different staffs, and in different locations on a single staff. For example, for normal piano music, where both treble and bass staffs are provided, and the note "C" sometimes hits a line, but elsewhere sits between lines. The position alternates going up the staves because the (C) major scale on which the notation is based has an odd number of notes- seven per octave.

Early music notation, dating from roughly 1000 CE. We don't need no sharps or flats!

These characteristics make note reading, not to mention sight reading, very difficult to learn, a big turnoff to the young students who may otherwise be quite enthusiastic about making music. Ranging from the central hand position is made substantially more difficult by the precisely opposite locations that the farther-ranging notes have in this notation system. All this becomes second nature eventually for advanced and professional musicians, but it is clearly a long and arduous process, needlessly difficult. Indeed, many famous musicians never learned to read music, maybe in part because of its notational difficulty.

One solution is to make smaller staffs, only one per octave, with a one-tone gap between each. This would make each octave look identical, and successive octaves could be stacked as needed. Modern printing could surely make such a system as compact as the current 5-line staff, which carries two octaves, if one counts one supplementary line below and two above.

A chromatic notation with each of the twelve tones on its own level, and an even number of notes occupying a full staff, ready to repeat in a regular way to other octaves.

Another solution is to lay out the whole chromatic scale, which has a separate position for each note in the customary Western 12-tone scales including sharps and flats, as separate notes. The number of notes per octave becomes even (twelve), providing consistency in note position. And the need for sharp and flat notation is reduced if not obviated. A downside is that the representation of chords would change dramatically, relative to the typical triads or sevenths that look so regular on a conventional staff.

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• Bill Mitchell on modern economics as a pro-capitalist cabal.
• Surveillance capitalism.
• If you use VPN, you have trust your provider completely.

At the Climate's Mercy

Volcanic eruptions have interrupted our fragile existence.

A recent research article made the news, telling of the worst year to be alive: 536 AD. This was surely the darkest moment of a dark age, and scientists have tracked its source to volcano(s) in Iceland. It darkened skies around the world, led to a ~4ºF drop in temperature, and crop failures throughout Europe and the near east, and crop delays in China. There seem to have been repeated eruptions over the ensuing years, though perhaps volcanos elsewhere contributed. The result was the coldest decade in at least 2,000 years, and a plague in 541-3 that wiped out at least 1/3 of the Byzantine population, among others. It took decades for Europe to recover, notably shown by ice cores with high lead pollution about 640 AD, showing that silver mining in France had recovered, presumably being pursued for minting coins.

Turner's "Chichester Canal", of 1828, thought to reflect some of the atmospheric effects of the  1816 global volcanic pall.

There have been several similar, though less extreme, events, like the "year without a summer" in 1816, due to the eruption of Tambora in Indonesia. This vocano is estimated to have ejected 40 cubic miles of material, but only lowered temperatures in Europe by about 3ºF, yet caused substantial famine, snowfalls in June, frost in August. A much smaller eruption, of Krakatoa in 1883 also caused dramatic sunsets and world-wide cooling, but had far less devastating effects, being smaller, and because it happened in August, and did not affect the following summer as severely.

Are our agricultural systems robust enough to withstand such an event today? I doubt it. We have optimized and stretched in every direction, supporting vast urban populations, without a thought given to adverse events of global scope. The only significant failsafe is that most agricultural production goes to supporting livestock, which under duress could be used directly for human consumption.

Conversely, we are engineering a permanent climate disruption of equal proportion but in a warming direction, by our emissions of CO2. Will temperatures go up by 3ºF? 4ºF? 5ºF? We are already at 2ºF, (vs temperatures at 1900), with much more baked in from our past emissions, and from their relentless continuance and growth. Will we survive if agriculture has to move to Canada and Siberia? If Florida and New York are under water? Sure, but at what cost to ourselves and more importantly, to the natural world?

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