Can Machines Read Yet?

Sort of, and not very well.

Reading- such a pleasure, but never time enough to read all that one would like, especially in technical fields. Scholars, even scientists, still write out their findings in prose- which is the richest form of communication, but only if someone else has the time and interest to read it. The medical literature is, at the flagship NCBI Pubmed resource, at about 30 million articles in abstract and lightly annotated form. Its partner, PMC, has 5.5 million articles in full text. This represents a vast trove of data which no one can read through, yet which tantalizes with its potential to generate novel insights, connections, and comprehensive and useful models, were we only able to harvest it in some computable form.

That is one of the motivations for natural language processing, or NLP, one of many subfields of artificial intelligence. What we learn with minimal effort as young children, machines have so far been unable to truly master, despite decades of effort and vast computational power. Recent advances in "deep learning" have made great progress in pattern parsing, and learning from large sets of known texts, resulting in the ability to translate one language to another. But does Google Translate understand what it is saying? Not at all. Understanding has taken strides in constricted areas, such as phone menu interactions, and Siri-like services. As long as the structure is simple, and has key words that tip off meaning, machines have started to get the hang of verbal communication.

But dealing with extremely complex texts is another matter entirely. NLP projects directed against the medical literature have been going on for decades, with relatively little to show, since the complexity of the corpus far outstrips the heuristics used to analyze it. These papers are, indeed, often very difficult for humans to read. They are frequently written by non-English speakers, or just bad writers. And the ideas being communicated are also complex, not just the language. The machines need to have a conceptual apparatus ready to accommodate, or better yet, learn within such a space. Recall how perception likewise needs an ever-expanding database / model of reality. Language processing is obviously a subfield of such perception. These issues raises a core question of AI- is general intelligence needed to fully achieve NLP?

I think the answer is yes- the ability to read human text with full understanding assumes a knowledge of human metaphors, general world conditions, and specific facts and relations from all areas of life which amounts to general intelligence. The whole point of NLP, as portrayed above, is not to spew audio books from written texts, (which is already accomplished, in a quite advanced way), but to understand what it is reading fully enough to elaborate conceptual models of the meaning of what those texts are about. And to do so in a way that can be communicated back to us humans in some form, perhaps diagrams, maps, and formulas, if not language.

The intensive study of NLP processing over the Pubmed corpus reached a fever pitch in the late 2000's, but has been quiescent for the last few years, generally for this reason. The techniques that were being used- language models, grammar, semantics, stemming, vocabulary databases, etc. had fully exploited the current technology, but still hit a roadblock. Precision could be pushed to ~ %80 levels for specific tasks, like picking out the interactions of known molecules, or linking diseases with genes mentioned in the texts. But general understanding was and remains well out of reach of these rather mechanical techniques. This is not to suggest any kind of vitalism in cognition, but only that we have another technical plateau to reach, characterized by the unification of learning, rich ontologies (world models), and language processing.

The new neural network methods (tensorflow, etc.) promise to provide the latter part of the equation, sensitive language parsing. But from what I can see, the kind of model we have of the world, with infinite learnability, depth, spontaneous classification capability, and related-ness, remains foreign to these methods, despite the several decades of work lavished on databases in all their fascinating iterations. That seems to be where more work is needed, to get to machine-based language understanding.

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Whom do You Trust?

We have placed our lives in the hands of Silicon Valley companies. Do they earn and keep that trust?

It used to be that banks made a big show of trustworthiness and stability. They would build classical edifices of stone to signify their solidity, and use names like "trust", "fidelity", "savings", "citadel", etc. This dates back to the 1800's, when there was no regulation, and banks could collapse from one day to the next, taking all their depositor's money with them. We got a brief taste of that in the recent banking / credit crises- the savings and loan debacle, and the 2008 subprime catastrophe. But generally, banks these days are rather boring from a depositor perspective, more concerned about appearing friendly and neighborly than awesomely immovable. Deposit insurance and other regulations have removed virtually all the risk of retail banking, and computers have simplified and automated its accounting mechanics. On the other hand, bigger investors (and borrowers) would have been wise to pay more attention to the trustworthiness of such institutions and their products through the subprime, securitization, and housing bubble periods, when so many were sold a bill of goods.

In this new computerized world, our faith turns out to be more at risk elsewhere, among the custodians not so much of our money, but of our selves in all exposed dimensions - messages, emails, pictures, documents, conversations, backups - our data. Our financial data is still of highest concern, but now that communications have migrated to myriad "platforms", we have so much more to worry about. What used to be securely private is now much less so. Electronic communication used to be confined to ATT, which came under significant regulation. Now it is a wild west of whoever can convince us to try a new service sure to enhance our lives or reputations, and all for free. Google led the way with incredible search capabilities, followed by Amazon, Myspace, Facebook, Paypal, Twitter, iTunes, Instagram, Roku, Pinterest, Linkedin, Netflix, Reddit, and countless other purveyors and services. Every one requires an account, with lock and key, every one collects our data, and most monetize it for ads, spam, and who knows what else.

Do they merit our faith? This becomes an increasingly urgent question as more of our lives migrate to digital form, and the companies we deal with gain increasing power by virtue of their custody over those forms. Are they responsible fiduciaries? Facebook and Google offer an instructive contrast. Google lives mostly by search, and while using ads, has carefully kept the search space clean enough to facilitate use. Its YouTube subsidiary is perhaps its most social media-y, pushing suggestions drawn from the user's viewing history. Since stochastically, this will ramify outwards into new areas, it can facilitate those looking for more extreme content to head in that direction. But different companies clearly carry different ecosystems and ideas of where to draw the line.

Facebook has been notorious for its obscure, ever-shifting intefaces, its constant foisting of new content and tools, and its devil-take-the-hindmost attitude to user data and privacy. Everything is open, except its own operations. All data is ripe for pushing to advertisers, and whatever it takes to get more clicks goes. Where Google remains dominant and comfortable in its search sphere and ancillary businesses, Facebook had made a scientific project of developing the most addictive tools to get people uncomfortable in their social networks, forced to like and be liked in an endless and downward hedonic treadmill. As an introvert, I am largely unaffected, but others seem to be hopelessly ensnared in the depressing exercise of social comparison.

Then there is the fake news. The new platforms act as publishers with vast powers of propagation, to viral degress unheard of in past ages of humdrum paper publishing. But at the same time they eschew the responsibility of publishers to vet media they purvey and provide a gatekeeping function that has been a critical, if unacknowledged heart of the rights of the free press. We have yet to get used to this world where power and reach are unconnected with curated cogency and minimal economic marketability.

Reputation is coming to the fore, as it once did for banks. Apple is making a great deal of its security and login operations, that they as a philosophy and business do not sell user data, being in the hardware business instead. Facebook has taken a big reputational hit through its bad behavior, particularly its release of data to the Republican-affiliated trolls in England, but also for its many other practices and attitudes. Governance is another issue. Facebook is extremely unusual in its monarchical shareholder model, where the founder has all the voting power, and the public none. How was this allowed as a "public" company?

Regulation is needed, on many levels. That has been the time-tested way to address market failures in the face of new technologies and market practices. Reputation alone is a poor way to police companies that have grown too big for many, if not most people, to do without. Antitrust, corporate governance, user data protection and use restrictions, transparency of data custody, and responsible free speech curation are all areas that need work. We should have a government that is willing to do that work, instead of one that lurches from one tweet to the next.

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• On lies.
• The cold war is back, and trilateral.
• Some arguments against a job guarantee, which actually sound more like arguments for it.
• Winter is coming. (Press "max")

Backward and Forward... Steps to Perception

Perception takes a database, learning, and attention.

We all know by now that perception is more than simply being a camera, getting visual input from the world. Cameras see everything, but they recognize nothing, conceptualize nothing. Perception implies categorization of that input into an ontology that makes hierarchical sense of the world, full of inter-relationships that establish context and meaning. In short, a database is needed- one that is dynamically adaptive to allow learning to slice its model of reality into ever finer and more accurate categories.

How does the brain do that? The work of Karl Friston has been revolutionary in this field, though probably not well-enough appreciated and admittedly hard for me and others not practiced in mathematical statistics to understand. A landmark paper is "A theory of cortical responses", from 2005. This argues that the method of "Empirical Bayes" is the key to unlock the nature of our mental learning and processing. Bayesian statistics seems like mere common sense. The basic proposition is that the likelihood of some thing is related to our naive model (hypothesis) of its likelihood arrived at prior to any evidence or experience, combined with evidence expressed in a way that can weight or alter that model. Iterate as needed, and the model should improve with time. What makes this a statistical procedure, rather than simple common sense? If one can express the hypothesis mathematically, and the evidence likewise, in a way that relates to the hypothesis, then the evaluation and the updating from evidence can be done in a mechanical way.

Friston postulates that the brain is such a machine, which studiously models the world, engaging in what statisticians call "expectation maximization", which is to say, progressive improvements in the in detail and accuracy of its model, driven by inputs from sensory and other information. An interesting point is that sensory input functions really as feedback to the model, rather than the model functioning as an evaluator of the inputs. We live in the model, not in our senses. The overall mechanism works assiduously to reduce surprise, which is a measure of how inputs differ from the model. Surprise drives both attention and learning.

Another interesting point is the relationship between inference and learning. The model exists to perform inference- that is the bottom-up process of judging the reality and likely causes of some event based on the internal model, activated by the input-drive attention. We see a ball fall down, and are not surprised because our model is richly outfitted with calculations of gravitation, weight, etc. We infer that it has weight, and no learning is required. But suppose it is a balloon that floats up instead of falling- a novel experience? The cognitive dissonance represents surprise, which prompts higher-level processing and downward, top-down alterations to the model to allow for lighter-than-air weights. Our inferences about the causes may be incorrect. We may resort to superstition rather than physics for the higher-level inference or explanation. But in any case, the possibility of rising balls would be added to our model of reality, making us less surprised in the future.

The brain as a surprise-minimizing machine. Heading into old age, we are surprised by nothing, whether by great accumulated experience or by a closure against new experiences, and thus reach a stable / dead state. 

This brings up the physiology of what is going on in the brain, featuring specialization, integration, and recurrent networks with distinct mechanisms of bottom-up and top-down connection. Each sensory mode has its specialized processing system, with sub-modules, etc. But these only work by working together, both in parallel, cross-checking forms of integration, and by feeding into higher levels that integrate their mini-models (say for visual motion, or color assignment) into more general, global models.

"The cortical infrastructure supporting a single function may involve many specialized areas whose union is mediated by functional integration. Functional specialization and integration are not exclusive; they are complementary. Functional specialization is only meaningful in the context of functional integration and vice versa."

But the real magic happens thanks to the backward connections. Friston highlights a variety of distinctions between the forward and backward (recurrent) connections:

Forward connections serve inference, which is the primary job of the brain most of the time. They are regimented, sparsely connected, topographically organized, (like in the regular striations of the visual system). They are naturally fast, since speed counts most in making inferences. On the molecular level, forward connections use fast voltage-gated receptors, AMPA and GABA.

Backward connections, in contrast, serve learning and top-down modulation/attention. They are slow, since learning does not have to obey the rapid processing of forward signals. They tend to occupy and extend to complimentary layers of the cortex vs the forward connecting cells. They use NMDA receptors, which are roughly 1/10 as fast in response as the receptors use in forward synapses. They are diffuse and highly elaborated in their projections. And they extend widely, not as regimented as the forward connections. This allows lots of different later effects (i.e. error detection) to modulate the inference mechanism. And surprisingly, they far outnumber the forward connections:

"Furthermore, backward connections are more abundant. For example, the ratio of forward efferent connections to backward afferents in the lateral geniculate is about 1 : 10. Another distinction is that backward connections traverse a number of hierarchical levels whereas forward connections are more restricted."

Where does the backward signal come from, in principle? In the brain, error = surprise. Surprise expresses a violation of the expectation of the internal model, and is accommodated by a variety of responses. An emotional response may occur, such as motivation to investigate the problem more deeply. More simply, surprise would induce backward correction in the model that predicted wrongly, whether that is a high-level model of our social trust network, or something at a low level like reaching for a knob and missing it. Infants spend a great deal of time reaching, slowly optimizing their models of their own capabilities and the context of the surrounding world.

"Recognition is simply the process of solving an inverse problem by jointly minimizing prediction error at all levels of the cortical hierarchy. The main point of this article is that evoked cortical responses can be understood as transient expressions of prediction error, which index some recognition process. This perspective accommodates many physiological and behavioural phenomena, for example, extra classical RF [receptive field] effects and repetition suppression in unit recordings, the MMN [mismatch negativity] and P300 in ERPs [event-related potentials], priming and global precedence effects in psychophysics. Critically, many of these emerge from the same basic principles governing inference with hierarchical generative models."

This paper came up due to a citation from current work investigating this model specifically with non-invasive EEG methods. It is clear that the model cited and outlined above is very influential, if not the leading model now of general cognition and brain organization. It also has clear applications to AI, as we develop more sophisticated neural network programs that can categorize and learn, or more adventurously, develop neuromorphic chips that model neurons in a physical rather then abstract basis and show impressive computational and efficiency characteristics.

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Postmodernism: License to Lie

A continuation of the Enlightenment project turned around to burn it all down, and our political system went along for the ride.

The discontents of modernism are legion. It is soul-less, rational, scientistic, dehumanizing. And the architecture is even worse, exemplified by the glass box skyscraper. Modernism was the stage after the self-satisfied Victorian age, our last unconscious period when Westerners felt confident in our myths, our cultural superiority, and our untroubled right to all the fruits of the Earth. Modernism came in the wake of Nietzsche and World War 1, which left all those certainties in tatters, followed by an even more destructive World War 2. But from America rose a new unbounded ethos of progress through cooperation and science, leading to the UN, the EU, the conquering of air and space, and the comfortable dispensation of the fossil-fueled late Cold War West.

The long-term theme has been increasing consciousness, from the Enlightenment onwards, adopting ever more realistic views of the physical and social world. Art was first to experience this startling realism. Then politics, with the slow destruction of the myth of monarchical and aristocratic superiority. And finally religion, from the work of Nietzsche and Darwin, among many others. Throughout, science has been steadily dis-enchanting the world, removing Earth from the cosmic center, mystical vitalism from the chemistry of life, and God from among our forefathers and mothers. With modernism, we had reached a new level of consciousness. We could look at ourselves as one among many world cultures, accepting "other" forms of religion, art, and world view as good, perhaps even co-equal, with those of the West. Frills and decoration were out, myth was relentlessly exposed, and we sought to plumb the psychological depths as well, exposing our complexes and deep motivations.

Then in 1970's France, the postmodernist school took it up another notch, trying to show that all our remaining certainties were also questionable, and could be deconstructed. Whatever narratives we live by, even the most attenuated reliance on general progress through the evident workings of civic, capitalist, and scientific institutions, were unmasked as just another forum for power politics, patriarchy, and elite control of the society's metanarrative. Build all the skyscrapers and Hubble telescopes you want, it all boils down to Game of Thrones in the end. All narratives were destabilized, and not only was nothing sacred, nothing had meaning at all, since interpretation is an ever-flexible tool that gives authority to the reader/viewer, with little left over for the author (or for "reality"). Anything can be read in innumerable layers, to mean ... practically anything. The narratives we can not help but to live by are all ripe for deconstruction, but then how does reality relate to our (limited) cognition of it? That gets us right back to the foundations of philosophy in the Platonic cave.

This approach clearly follows the modernist and psychoanalytic line of excavating ever deeper into our sources of motivation, meaning, and narrative. Indeed, other disciplines, like anthropology, psychology, and even economics (in its study of institutions) have long preceeded the postmodernists. But one has to ask two big questions. First, is there some limit of analysis beyond which, even if the analysis is valid, human functioning is so destabilized that, for all the intellectual benefits, we end up inert, stripped of larger motivating narratives and reduced to mere units of immediate consumption, mediated by our TV sets and phones? Second, have they gone too far? Is the postmodernist analysis actually valid in all its implications? An excellent article in Areo chews over some of these problems.

Being scientifically and psychoanalytically inclined, I would have to answer no to the first question, and yes to the second. While unproductive over-analysis can lead some people to inertia, any correct analysis in psychological, cultural, or other terms can not help but illuminate the human condition. This is in general a big plus, and not one to be discarded because it is uncomfortable or destabilizing to our customary life and traditions. We dealt with Darwininan evolution, (well, most of us did), and can still reach for the stars. Sources of narrative and motivation are vast and perpetually self-created. Losing the old gods and myths is not a serious problem if we have new and significant tasks to replace them with. For example, nothing could be more dire than global climate heating- it is the central problem of our time, and tackling it would give us collective, indeed eschatological, meaning. What makes this moment particularly painful and fake is not that we lack an animating myth or center, but that we are dithering with regard to the true and monumental tasks at hand, blocked by a corrupt system and various defects of human nature.

The second question more pointed, for if the postmodernist analysis is not generally true, then we hardly have to worry about the first question at all. This is a very tricky area, since much of the postmodernist critique is valid enough. We live by many myths and narratives. But its earthshaking claims to destabilize everything and all other forms of truth are clearly false. Many fields, not just science, have a living commitment to truth that is demonstrably valid, even if the quest is elusive, even quixotic. Take the news media. While the tendency to endless punditry is lamentable, there is a core of factual reporting that is the product of a great deal of worthy dedication and forms a public good. Whatever the biases that go into selecting the targets of reporting, their products, when true, are immune to the postmodern critique. The school board really did fire its superintendent, or put a bond on the next election ballot. The fact that we have a president who fears "perjury traps", labels all truthful reporting about him "fake news", and allies with propaganda outlets like FOX and RT should not put anyone in any doubt that truth, nevertheless, exists.

Why some religious people have cottoned to the postmodern approach is somewhat mysterious and curious, for while postmodernism has mightily attempted to destablize reigning cultural orthodoxies, particularly those of science, it is hardly more kind to clericalism or religion in principle. At best, it may allow that these are at least honest about their (false) mythos/narrative basis, unlike the devious subterfuges by which science channels its bourgeois interests into claims to the really, really true narrative, which thus have posed the more interesting challenge in the postmodern literature. But make no mistake, if religion were the reigning cultural power, the deconstructionists would make mincemeat of it.

What makes Deepak Chopra so laughable?

But postmodernism has nevertheless filtered down from the academy to popular culture, destabilizing verities and authorities. Did they seek to have Republican policians declare that "we make our own reality"? Did they foresee the internet and its ironic capacity, not to make us all Orwellian drones with the same beliefs, but to let us stew voluntarily in propaganda-laced echo chambers, losing touch with reality all the same? At issue is the nature and status of factual authority, which we are so shockingly confronted with in this political moment. Coordinated assaults on our capacity for reason, from the wingnut right and its unhinged media, the new masters of the internet, the Russians, and the lying sleazebag who found his moment amongst the chaos, have posed this problem in the starkest terms. What is truth? Are there facts? What is an authoritative narrative of leadership, of care for the future and the nation? Should public policy be responsive to facts, or to money and nepotism? What is the point of morality in a fully corrupt world? Why is gaslighting a new and trending word?

The postmodernists insisted, as does our current president, that every category and supposed fact is a mask for power. They saw hobgoblins of social construction and violent dominance in the most innocent scientific facts and institutions. Such an attitude might be provocative and occasionally fruitful, but it has been taken way too far, rendering fields most affected (in the humanities) stripped of coherence, let alone authority. Leaving us with a modern art bereft of ideals other than shock, and the most banal literature and identity-based histories. It is also a sort of zero-sum-ism, needlessly oppositional and Manichaean. In their haste to unmask and tear down all idols and intellectual achievements that unify humanity, they have generated a sort of war against all meaning which is deeply anti-human- not just deconstructive, but destructive.

Yes, our narratives are in perpetual conflict. Different religions, political viewpoints, and cultures have distinct narratives and each seeks to win the hearts and minds in order to rule human soceity. The Reformation offers abundant examples of this, as does our current political scene. But at the same time, reality itself forms another, and very influential, locus in this conflict. For all the other narratives claim to be accurate views of reality, whether claiming that god is real, Catholicism is the true church, or that Republicans have a more accurate and effective view of economics and human nature. Each stakes its claims on discernment of how reality works, including the moral and other aspects of what people really want out of their social system. Do they want a king to look up to, or a representative government that may be more moderate and effective?

So narratives are not just thrashing our their conflicts on an entirely archetypal / mythical / power basis, as the postmodernists seem to assume. Rather, they are negotiating views of reality, including moral and social realities, which can be interrogated in large degree by reason generally and science specifically. Creationism and climate change denialism are just the most flagrant examples of narratives that seek social dominance on the backs of religious delusion and/or simple greed. And for all the equivocation of the postmodernists, they can be definitively dismissed given the knowledge we have outside of these or other narrative claims. The growth of mature consciousness means expanding our abilities to judge the reality-claims of narratives in a dispassionate way, considering both physical but also the psycho-social realities we share, and progressively leaving our psychological baggage behind.

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What Happened to the Monarchs?

Monarch butterflies are in crisis.

Flying over the Midwest, it is easy to see the impact of humans. The land is neatly tiled into monoculture farms, with hardly a wild spot in sight. Unseen is the chemical crusade that has happened over the same time period, making insects and weeds sparse on this land as well. All this has contributed to a phenomenally productive agriculture, making our food with almost factory-like consistency using a variety of high-tech machinery, chemicals, and plenty of CO2 emissions. But each of these assaults on nature has also multiplied the plight of (among many others) the Monarch butterfly, which eats weeds, is an insect, and migrates over astonishing distances in a multigenerational trek to communal wintering sites. While Eastern populations of Monarchs are in decline and in peril, the condition of the separate Western population, which circulates up the Sierra and back down the Pacific coast, is dire, headed towards extinction.

"... the Midwest lost more than 860 million milkweeds between 1999 and 2014, mostly in agricultural fields" -Entomology Today

Monarch butterflies have a curious method of migration. While birds live several years, and thus may commute several times over their lifespan, (for instance from Northern breeding grounds to Carribean or South American wintering sites), Monarch butterflies live only roughly a month. But they also migrate over long distances, either from Mexico up through the Eastern US and Midwest, or from Coastal California across Central California, to the Sierras, then North to Oregon and Washington, then back down in fall. Like birds, the Monarchs use these routes to move through optimal habitats as the Northern Hemisphere goes through its seasons. But the migration must encoded in their genes, not learned from experience or from others, since it takes several generations to make the trek, somewhat like the colonization space ships of science fiction, which would go through many generations to get to, say, Alpha Centauri.

Now a rare sight.

It also means that Monarchs rely on suitable environments (which is to say, the milkweed) every step of the way. And our technologies of weed, insect and physical habitat extermination are making enormous swathes of their routes uninhabitable, not to say lethal. The Western population is down from millions in the 1980's to 30,000 today. This is not sustainable, and likely to drop to zero unless big changes happen to render the landscape less lethal. Thankfully, there are many milkweed species, many of which can grow widely in the region, if allowed to.

But this is just a small example of the harm humans are doing to the natural world. We are a plague, and have initiated a new age in biology- the Anthropocene, complete with our own mass extinction event. While the process is well underway here in California, it is only beginning in regions like the Amazon and Africa, whose human populations are growing steadily and whose natural environments are being decimated and whose wildlife is declining, including being directly killed and eaten. Climate heating will kill off far more species, until we end up in a world of mega-cities separated by monoculture croplands and nature reserves that will be faint shadows of a vanished, and richer, world.

• A study in lying, corruption, debasement, and character.
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• But is the Fed overly skittish now?
• Should we be giving foreign aid to the Targaryens?
• How about we fly less, and let the Monarchs fly more?

Cancel the National Debt

Elizabeth Warren or Bernie Sanders should stand up and say that they will eliminate the national debt.

National debt clocks seem to go in and out of style with the political fortunes of Republicans. When they are in power, the bond vigilantes are at bay, clocks get put away, and tax cuts and wars blow up the deficit with hardly a finger-wag. But when tables turn, watch out! The debt becomes a national emergency, and think of the children, who will have to pay it all back!

After a few cycles of this nonsense, many have realized the mythical nature of the whole construct, first and foremost the school of MMT economics. Conventional conceptions of the debt are significantly out of date. For one thing, no one is going to have to pay this debt back. It is continually rolled over, and if we attempted to pay it back out of a fiscal surpluses, it would be disastrous, contracting the economy for lack of net spending from the government, which is the source of money for net economic expansion. (Ignoring the banking sector for the moment.)

Back when our money was not made and managed by the government, but rather based on some commodity like gold or silver, the Federal government was as constrained as anyone else- to match spending with income. It had two choices to pull money out of the larger economy for its own needs- taxation or borrowing. Taxes tend to be broad-based and quite unpopular. Borrowing, via bonds, (which were, in a way, the original fiat money), on the other hand, targets quite specifically those who have money to spare - the rich - so is politically efficient. But borrowing also indebts the state to the ongoing interest payments, which may temporarily come from further borrowing, but must ultimately come from taxation (or increased inflation, if the government can influence the monetary system and wishes to abuse its credit). Thus we had war bonds during the Civil War and the World Wars of the last century.

A bond, issued 1936

Now we are in a slightly different world, that of fiat money, where the federal government runs the monetary system completely and explicitly, with the power of printing money, but also the duty of controlling inflation. There is no more scarcity of gold, or scarcity of money, for that matter. It is an elastic system, under conscious control. Now the government creates money via its spending, and that money is meant to supply the expansion of the whole system- our economic growth, our hunger for imports and the matching hunger of foreigners for dollars, our savings needs, etc. Yet we still have a statutory requirement to match net spending (over taxation) with bond issuance- thus the growing national debt. (again, ignoring the banking sector for the moment). That statutory requirement is a relic of the old system and should be scrapped.

Not only that, but we should also end the re-issuance of debt, gradually exchanging it, as it comes due, for regular dollars instead. That way, we could save the hundreds of billions of dollars ($389 billion in 2019) we give to rich people and foreign countries in interest payments on their bond holdings. $30 billion alone goes to China, to reward them for the currency manipulation they engaged in back in the 2000's to take our manufacturing jobs. That is quite a deal! In this way, we could retire the national debt, not by paying it down through higher taxes, but simply by converting it to dollars, which we can create with a keystroke, just as we created the bonds in the first place.

The idea that our practice of bond issuance prevents inflation, by draining dollars from the economy, is problematic in terms of scale. Bonds are hardly a frozen form of money. For individual holders, our debt functions as the equivalent of money. They are savers, and holding dollars or bonds makes relatively little difference- they are not going to go on spending binges over the loss of 3% interest. On the other hand, on the macro-economic scale, the swap of dollars for debt would change the complexion of savings, since this rentier class will still seek income. They will seek to invest this money productively, and if safe government bonds are not available, they will tend to invest in the real economy, such as loans, real estate, companies, etc. This may drive some inflation, so we would have to be on our guard. But it would also drive real investment, which would be a good thing, and would drive down interest rates, also a good thing, especially in view of the troublesomely high rate of interest over time recorded by Thomas Piketty. The implementation would be controllable- if inflation appeared as a result, the program could be slowed down or reversed at any time. Perhaps we should start with a mere trillion dollars exchanged per year.

To get a picture of the overall scale, the US has about $100 trillion of overall wealth, of which about 20% is Federal bonds. But about a third of those bonds are held in the government, such as the Social Security accounting fiction of a "trust fund". And as noted above, the Fed owns about 10% of the debt in addition. So the remaining amount is, in the larger scheme of things, not enormous, and while monetizing it will alter investment practices, is unlikely to be catastrophic.

In conventional economic terms, this proposal would dramatically alter the money supply and bond markets, moving the LM curve (in the IS/LM model) right-wards, increasing output, decreasing interest rates, and causing inflation. The Fed spends much of its time managing the Federal bond market, selling and buying bonds in its efforts to control short term interest rates. After the 2008 crisis, the Fed accumulated $2-3 trillion, about a tenth of all bonds outstanding. It was accused of monetizing the debt by buying so much, lowering interest rates and pumping dollars into the system instead. But inflation stayed very low. We are in a somewhat more normal regime now, but over the last decade, the Fed has never attained its inflation target, so in those terms, one can say that, instead of trying to raise interest rates by selling bonds, as they have been doing over the last year, they should just continue monetizing the debt, until it is all gone, then send those bonds to the shredder.

Are there other ways to manage interest rates and inflation? This is where MMT has some problems, and fails to (to my knowledge) truly grapple with control of the monetary system. Suppose the pool of Federal bonds were 1/10 the size it is now or less, which would be much more manageable in fiscal terms. The Fed might own most of them at any one time, but might not have, in its view, the firepower, or the depth of a market to trade in, to affect interest rates across the board. It might need to trade in corporate bonds instead, which might not be the worst thing. Perhaps it should be using other tools, however, as its ultimate aim is to regulate lending and inflation, towards which control of interest rates is only a (blunt) mechanism. It is lending by banks that creates money in the private system, leading to speculative bubbles, inflation, and contractions and depressions. This money is much more labile (in the form of loans/credit that are subject to being paid back or called in, among other risks) than that coming from government spending. Thus the need for close regulation.

In China, for instance, the state owns the big banks, and can direct their lending explicity. No need to mess with the putatively free interest rate market. Similarly, the Fed regulates the banks, and could, for example, raise underwriting standards or capital requirements in boom times, lowering them in slack times. Another approach, of course, is using the government's fiscal policy. By spending more or less, or altering taxation, (such as changing the withholding rates), the Federal government can easily (if such spending alterations are easy) affect the inflation rate, which is after all the point of the interest rate control policy. In this way, interest rates can generally be kept low, bond issuance be ended, and the value of the money be kept stable. Ironically, despite MMT getting the rap of advocating fiscal profligacy, the real consequence of MMT is that the government would have to be even more disciplined and conscious in its monetary policies, (yet also more democratic), than the current system of leaving all the hard choices to a technocratic Fed, while spending more or less blindly, in policy terms (until a crisis hits, and even then, still shooting in the dark).

Getting back the debt reduction plan, would such a program contribute to the global savings glut? Yes, by discontinuing what is clearly the premier safe investment world-wide. But that is just too bad- we will benefit far more by cleaning up our books and saving ourselves the interest being paid out than we lose. At one stroke, we would free our political discourse from this charade of fiscal probity, free our government of the payment of hundreds of billions in interest- an enormous and seemingly endless stream of subsidies to the rich, and increase domestic investment.

• A contrary view on MMT.
• On the history of debt instruments.
• Baltimore- another kind of student loan.
• Impeachment, yes.
• An online ad tax?
• The academic life.. manuscript hostage negotiations.
• Remember when Republicans complained about executive overreach?

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.