Saturday, April 22, 2017

How Speech Gets Computed, Maybe

Speech is just sounds, so why does it not sound like noise?

Even wonder how we learn a language? How we make the transition from hearing how a totally foreign language sounds- like gibberish- to fluent understanding of the ideas flowing in, without even noticing their sound characteristics, or at best, appreciating them as poetry or song- a curious mixture of meaning and sound-play? Something happens in our brains, but what? A recent paper discusses the computational activities that are going on under the hood.

Speech arrives as a continuous stream of various sounds, which we can split up into discrete units (phonemes), which we then have to reconstruct as meaning-units, and detect their long-range interactions with other units such as the word, sentence, and paragraph. That is, their grammar and higher-level meanings. Obviously, in light of the difficulty of getting machines to do this well, it is a challenging task. And while we have lots of neurons to throw at the problem, each one is very slow- a mere 20 milliseconds at best, compared to about well under a nanosecond for current computers, about 100 million times faster. It is not a very promising situation.

An elementary neural network, used by the authors. Higher levels operate more slowly, capturing broader meanings.

The authors focus on how pieces of the problem are separated, recombined, and solved, in the context of a stream of stimulus facing a neural network like the brain. They realize that analogical thinking, where we routinely schematize concepts and remember them in relational ways that link between sub-concepts, super-concepts, similar concepts, coordinated experiences, etc. may form a deep precursor from non-language thought that enabled the rapid evolution of language decoding and perception.

One aspect of their solution is that the information of the incoming stream is used, but not rapidly discarded as one would in some computational approaches. Recognizing a phrase within the stream of speech is a big accomplishment, but the next word may alter its interpretation fundamentally, and require access to its component parts for that reinterpretation. So bits of the meaning hierarchy (words, phrases) are identified as they come in, but must also be kept, piece-wise, in memory for further Bayesian consideration and reconstruction. This is easy enough to say, but how would it be implemented?

From the paper, it is hard to tell, actually. The details are hidden in the program they use and in prior work. They use a neural network of several layers, originally devised to detect relational logic from unstructured inputs. The idea was to use rapid classifications and hierarchies from incoming data (specific propositional statements or facts) to set up analogies, which enable drawing very general relations among concepts/ideas. They argue that this is a good model for how our brains work. The kicker is that the same network is quite effective in understanding speech, relating (binding) nearby (in time) meaning units together even while it also holds them distinct and generates higher-level logic from them. It even shows oscillations that match quite closely those seen in the active auditory cortex, which is known to entrain its oscillations to speech patterns. High activity at the 2 and 4 Hz bands seem to relate to the pace of speech.

"The basic idea is to encode the elements that are bound in lower layers of a hierarchy directly from the sequential input and then use slower dynamics to accumulate evidence for relations at higher levels of the hierarchy. This necessarily entails a memory of the ordinal relationships that, computationally, requires higher-level representations to integrate or bind lower-level representations over time—with more protracted activity. This temporal binding mandates an asynchrony of representation between hierarchical levels of representation in order to maintain distinct, separable representations despite binding."

This result and the surrounding work, cloudy though they are, also forms an evolutionary argument, that speech recognition, being computationally very similar to other forms of analogical / relational / hierarchical thinking, may have arisen rather easily from pre-existing capabilities. Neural networks are all the rage now, with Google among others drawing on them for phenomenal advances in speech and image recognition. So there seems to be a convergence from the technology and research sides to say that this principle of computation, so different from the silicon-based sequential and procedural processing paradigm, holds tremendous promise for understanding our brains as well as exceeding them.

Sunday, April 16, 2017

Are You a Turtle?

The many types of personality types. Review of "The Five Elements", by Dondi Dahlin.

It may be trite to say that people are different. Yet it bears repeating, as we routinely lose sight of that simple fact in our private echo chambers of righteous self-regard. We routinely assume that everyone is on some level the same as we are, and then are left befuddled and shocked when an election turns that idea on its head. In our personal lives, we routinely assume that others see what we see, and care about what we care about, and get angry when they blithely ignore that sock on the floor, or the monthly budget. Thus it is perennially important to raise consciousness about the depth and durability of human differences, so that we can live together more harmoniously, with greater understanding.

Personality and temperament have been an ongoing theme on this site, so it was a pleasure to find a new book on the subject that is as compelling as anything I have read. There are many systems that try to schematize the protean landscape of human personality, from the ancient (the four humors) to the pseudo-scientific (Jung's) and more systematic (Myers-Briggs), and the more frankly scientific (the five factor model). Dahlin is a California New-Age scion whose family has long used the Chinese five-element system to understand themselves and others.

Who are you? Who am I?

There are virtues to using such a simple system. On the surface, it captures extreme personality types, which can then be combined to come up with a more nuanced model of a particular person's style. To recount them very briefly, the Water type is introverted, slow, inner-directed, and creative. The Wood type is type-A, always doing, with a task list in hand, and impatient with ritual. The Fire type is the happy-go-lucky, life-of-the-party type, intensely interested and charming one minute, then off to something new the next. The Earth type is the home and family-oriented type, the human doormat, always serving others. And the Metal type is cool, idealistic, minimal. They subscribe to Dwell magazine.

There is a great deal more to say, of course, and Dahlin says it very well, with warmth, verve, and fascinating anecdotes. Each type has its spiritual approaches, its physical and relationship needs, its manifestations in childhood. Dahlin even supplies special exercises for each type, drawn from her experience as a dancer. This book, more than the others of this genre that I have read, prompted me to think about other people in my life through its lens, which brings out particuliarities and deeper themes that tend to get lost in the hubbub of normal relations.

Are these personality types genetic? Dahlin's mother writes in the forward about the experience of being pregnant with children of different elements. Their personalities were markedly different well before birth. Dahlin herself notes, however, that personalities can change with time, during childhood and after trauma, which suggests that they are canalized styles of expression, solutions to the problems of life, which are not entirely determined. Indeed, the genetics of twins indicates that stable personality traits are determined only about half genetically, and half by other influences, whether environmental or stochastic.

Dahlin notes that most couples are of different types- opposites really do attract, and often complement each other as well. This suggests two things- that the insofar as personality type is genetic, the stable population distribution of different types is a matter of balanced selection. This should not come as a surprise, as many other species show personalities and stable population distributions of different types, down to ants and their castes, as an extreme form. The second implication is that appreciation of different types (using whatever system you like) is highly important at all levels- to our personal lives as well as our public and work lives, to promote understanding and lift a veil of mystery from our often unthinking view of the "other".

  • Fairness, inequality and just deserts.
  • We are still in a zero world, and need more fiscal support.
  • United uses a complex market to get passengers into its seats, but when it wants them out, it calls the police.
  • Where is the GOP going with Social Security? Not towards security.
  • Tax cuts serve the rich, unsurprisingly.
  • The disaster of privatization.
  • The disaster of deregulation. Who can call this populist?
  • We are going Byzantine.
  • Remember when Trump promised everyone even better health care?
  • An economist on carbon taxes.

Saturday, April 8, 2017

American Exceptionalism Rests on the Middle Class

What happens to our country when the middle class disappears? Review of Ganesh Sitaraman's "The Middle Class Constitution".

We are in a crisis right now in the US. Our government has been taken over by plutocrats who are busily reversing every progressive and public-spirited policy they can get their hands on. The worst nightmare of the nation's founders, revolving around demagogues, rule by extreme wealth, deepening political corruption, and mass immiseration, is coming to pass. Thomas Piketty's work on the nature and growth of economic inequality was the first major intellectual shot against this development, from an econometric perspective. Sitaraman's new book is the second, putting our economic inequality and its political consequences into historical and legal perspective, as a far greater matter than mere economics- rather, as a constitutional crisis.

The US has been since its founding exceptional on the world stage, not for our apple pie or iPhones, but for our democratic social system. Now the world is filled with democracies, so our position as one of the more mediocre ones in terms of governance, public services, health status, and overall happiness is perhaps not such a surprise. But at the beginning, we were truly revolutionary, and Lincoln was not far off when he posed the Civil War as a test whether government by the people would survive globally. (Switzerland, however, probably would have pressed on with its own experiments).

Why did this experiment happen here? According to Sitaraman, and to Toqueville, and to many of the founders themselves and other observers, it happened because the economic condition of Americans was substantially one of equality. Immigration put most people on a similar footing, which is to say, poor. The availability of land to all who wanted to work it provided a base of subsistence to these immigrants, and a foundation of modest wealth. The ideology of the early colonies and Republic was one of severe allergy to class distinctions, titles, and the like. There were some wealthy people, but nothing like the disparities that we would see later, either in the guilded age, or today.

Our constitution reflects these origins, and depends on continued rough equality with a predominant middle class. Sitaraman makes it clear that historically, constitutions have always reflected the economic conditions they sought to rule. Where feudalism and serfdom was the rule, so was autocracy. And oligarchy or autocracy have been the rule through the vast majority of human history, with democracy only possible at the lowest levels of rural and small-town society, where equality was likewise occasionally possible. Golden-age Greece, our democratic ideal, was more like an oligarchy of the free men of the city. Karl Marx had a point when he maintained that ownership of the means of production controls the nature of the class system, and thence the political system. Even Aristotle recognized, that while a true middle class polity was impossible in the power-economics setting of the ancient world, it would be the ideal polity, composed of that class of people who are neither so greedy and power-mad that they would factionalize and corrupt the system, nor so poor that their only wish would be to revolt and overthrow it.

Our rough equality continued through the frontier era, when anyone could pull up stakes and get land out west. Conditions were increasingly difficult the farther west one went, until the coastal paradise of California and Oregon gave one last great frontier of fertile land. This availability of land amounted to a job guarantee for its day, allowing any willing person to work and make money regardless of the willingness of an employer to hire. Farming certainly had its own terrible risks, between the weather, pests, and fluctuating markets. But no able person had to be destitute.

Now, we are neither an agricultural society, nor have any frontiers left. We exist in a new form of feudalism where employers have no governance responsibility to their employees. Employees are purely at will, and may be fired at any time for any reason. It is ironic that we so fetishize political freedom and legal equality, while practicing, in our corporate culture, the most retrograde feudalism. For all the regulations that modestly ameliorate this condition, most workers are in a dramatically assymetric and powerless position. It wouldn't be so bad if the economic system were not also unstable, experiencing crises of demand and investment that force millions of workers into destitution. Additionally, the closing of the frontier and other restrictions have made land, housing, and rents increasingly subject to scarcity costs far above their construction costs. This makes destitution a far more probable and chilling prospect.

Sitaraman cites disturbing research into our political system that makes the case that we are already living in an oligarchy/plutocracy. The fact is that each of our politicians is for sale, the media system is run by corporations, and much of the governmental regulatory apparatus that was supposed to protect us from the predatory special interests have instead been captured by them. This latest research shows that the actions of our political system accord essentially none of the time with the preferences of the lower 90% of the population, and all of the time with the preferences of the rich and super-rich. Our so-called leaders, thanks to various forms of legal corruption, are steeped in the social melieu of the rich, its super-PACs, and its propaganda organs, from cable channels, to think tanks, to lobbyists. The rest of us hardly stand a chance. Even at state and local levels, the rich have been funding dramatic new advances in corruption and propaganda, which have turned our nation into a sea of red.

This is how wealth translates to power, and the US may have entered a terminal loop where the plutocracy is so entrenched and so shameless about leveraging that power into yet more power, that there is nothing further to do, short of revolution. The breathtaking nepotism, incompetence, greed, and immorality of our current administration merely puts an exclamation point on a decades-long process that has not only reshaped the political system into a frank plutocracy, but reshaped the economic system as well into one that freezes out the middle class, by dramatically lowering taxes on the rich and reducing public facilities and services, among many other policies.

Middle classes do not happen by accident. The natural course of events, given the Malthusian pressures documented so dryly by Thomas Piketty and many others, is towards competitive differentiation, with winners gathering more power and wealth, which, once it reaches a high level, grows by natural accretion and compounding (where it is not more actively leveraged) far beyond anyone's needs, and losers finding it ever more difficult to find a way into a brutally rigged system. Classically, this was expressed by ownership of land, to which the answer has been land reform, which is to say, expropriation. Sitaraman provides a fascinating aside on the sequel to the Civil War.
"The most eloquent advocate for confiscation and redistribution was Thaddeus Stevens. The clubfooted Pennsylvania congressman proposed confiscating the estates of the top 10% of wealthy rebel planters, which at the time amounted to those with more than $10,000 or more than two hundred acres of land. With that land, which he pointed out would leave 90 percent of southerners untouched, every freedman could be given forty acres. The remainder wold be sold at auction and used to fund veteran pensions, compensate the injured, and retire the war debt. Steven's reasoning acknowledge that this ction would be revolutionary, but he also deemed it necessary for preserving republican government. "The whole fabric of Southern society must be changed," he declared in a speech to constituents in 1865: 
"Without this, this government can never be, as it has never been, a true republic. Heretofore, it had more the features of aristocracy than of democracy. The Southern States have been despotisms, not governments of the people. It is impossible that any practical equality of rights can exist where a few thousand men monopolize the whole landed property. ... If the South is ever to be made a safe republic, let her lands be clutivated by the toil of the owners, or the free labor of intelligent citizens. This must be done even though it drive her nobility into exile. If they go, all the better."

The book ends with a relatively standard plea, in the Bernie Sanders/Elizabeth Warren frame of argument, for higher consciousness of these facts and trends, in order to frame a new phase of social activism. Sitaraman has great respect for the Progressive era of the late 19th century, which brought us the progressive income tax, anti-trust, and the regulatory state, among other innovations. Thinkers and movements of this time took a fundamental look at our system and recognized that one more agency would not be enough- we needed constitutional amendments and deep reform. Today, with the Supreme Court wielding the First Amendment like bludgeon against the very citizens it was designed to protect, drowning them in corporate doublespeak, and with our politico-economic power system declining into bannana republic levels of dysfunction and disparity, it is time again to crank up the volume of protest, and direct it to fundamental and radical aims, such as taking money out of politics, remaking corporate governance on a more democratic model, and restoring a tax and public financing policies that sustainably strengthen the middle class.

  • A clown is in charge of our economic policy.
  • Pay should not be a big secret.
  • Another lie ... and another.
  • We need a new privacy regime.
  • China is the last country to want any change in North Korea.
  • They really are better than everyone else.
  • Corrupt enrichment.
  • Health care is one of the bigger drivers of inequality.
  • Economic graph of the week. Corporations are saving more, growing fatter, while everyone else grows thinner.

Saturday, April 1, 2017

Con Men Bring Us Hope

Herbalife, Christianity, Scientology, and the Trump Network. Only I can connect the dots!

The New Yorker carried a remarkable article recently, ostensibly about Herbalife. That is the network or multilevel marketing company that makes its money luring would-be entrepreneurs to new careers selling a powdered food-related product, and charging them for every step towards their doom. The story was structured around a short that hedge fund star Bill Ackman attempted against Herbalife, thinking that a good dose of negative publicity could cause the pyramid scheme to collapse.

But the short ended in tears, as the stock recovered robustly and still trades at relatively high levels, with a respectable P/E of 19. It turned out that investors all knew the company was a scam. They didn't need to be pursuaded with flashy slides and conference calls. But getting the message to Herbalife's actual customers / marks was another matter, far beyond Ackman's PR capacity. The beauty of network marketing is that every person in the operation is motivated to spread the gospel. It is a theo-capitalist virus, made for growth on the back of desperate people's dreams.

Where were the regulators in all this? Well you may ask. The current Republican regime doesn't think much of any kind of regulation, representing, as they do, the predators of the system. The story brings up the extremely interesting tale of Donald Trump's own foray into network marketing, a window into his character like no other. This was an even more tenuous proposition, claiming to convey Trump's valuable business insights to its entrepreneur members, thereby allowing them to become rich in the wake of the 2008 recession. The scheme naturally ended up in court, then sold off to some other paragon of capitalism. What interest would such a person have in the victims of his form of capitalism? What credence should his voters have in his promises to help the little people?

Trump's character on display- always looking for a sucker.

Anyhow, the FTC did finally look into Herbalife, and issued a fine as well as directives to clean up its business. The fine was apparently sent to Herbalife distributors (who are also customers) who have been using it to buy more Herbalife products. The re-organization forced Herbalife to reclassify thousands of its distributors as customers so that it would have some customers actually buying products, instead of a multilevel network of distributors all selling down-line to suckers who thought they were also running a business. But naturally Herbalife found a way around this as well, spinning the whole thing as an FTC endorsement of their business model, and happy to putatively do the re-organization. Shares went up and all is well.
Herbalife is robust to whistleblowers, truth-tellers, the FTC, short sellers, and bad publicity in general.

The lesson from all this is that con men are virtually ineradicable, especially when we have toothless regulators. People are naturally, and necessarily, optimistic. America runs on optimism, yet optimism breeds the deceit and lies that are so easily passed off by psychopaths like Mr. Trump and the many other bottom-feeders of our competitive, capitalist system. Without regulation, a Gresham dynamic takes hold, honest business people can't make a dollar, and the entire system descends into a mire of curruption. Just look at the business climate in a country like Russia or Afghanistan.

But what if there are no regulators, because the con is not (ostensibly) business-related? What if a religion is being sold, with the most absurd visions of heavenly bliss (if you believe) and personal empowerment? Scientology started out as a sort of new-age psychotherapy. But when it met with derision from the from professional psychological community, and official sanction and bankruptcy for offering medicine (and selling E-meters) without a license, it was re-organized as a religion. Presto- not only could it continue as a quack medical cult, but it became tax-exempt as well! Now its members can believe in their hidden thetan abilities, purified "clear" states of consciousness, and extraterrestrial origins without skeptical questions from official bodies.

Religious cons are unimaginably more ornate and bold than business cons. Just think of the Jesus story. Who could have come up with such a thing? But given enough time, and enough idle dreaming and theological imagination, and, well, anything is possible. Now the entire world is saved, except for the non-believers who are all going to hell. We are so crushed by reality, so filled with hope that life should be better, and can be better if we only dream hard enough, that those who have crossed the line between reality and imagination have only to assert their confidence, for someone to believe them.

So the con men, mystics, and preachers, whether cynical, self-deluded, or psychopathic, make a matched set with the credulous, lost, and desperate. And aren't we all desperate, at some level? Desperate that this life, filled as it is with trials and pain, should be so difficult and end so definitively? What can the truth say about that? It is a perennial question, whether we put ourselves into the hands of yet another purveyor of hope, or practice moderation in this, as in so many other things.

Saturday, March 25, 2017

Centrioles Have Mothers Too

Penetrating the mysteries of one of our most attractive organelles.

The centriole is one of the more glamorous, yet enigmatic, structures of the eukaryotic cell. Yes, it has beautiful ultrastructure. Yes, it serves as the fabulous astral center of the spindle poles that organize mitosis. And yes, it has been studied for well over a century. But does all that mean it is well understood? Absolutely not.

Electron micrographs of centrioles. The inset is a cross-section of one centriole barrel, showing the 9 X 3 microtubule structure as well as the inner cartwheel that seems to be its construction scaffold. The main image shows a side-ways cross-section of a mother-daughter pair of centrioles, (forming a centrosome), showing their length and relationship. Also shown is the nimbus of microtubules coming out of what is called the peri-centriolar material, or PCM. How those relate functionally to the core structure is still not known.

Centrioles are one of the many radical innovations of eukaryotic cells, forming the core(s) of centrosomes, which organize mitosis, and of cilia, which are the novel eukaryotic solution to cellular locomotion. They are are a barrel-shaped quasi-crystalline arrangement of microtubule proteins, grown on a central wheel of template proteins, called the cartwheel. For cilia, these microtubules clearly serve as the foundation stones of microtubule rods that grow out into the long appendage. But things get far more murky at the mitotic spindle core, where a profusion of microtubules emerge from an amorphous zone around the centrioles, but are not templated directly by them. The nature and history of this structure remains quite mysterious, especially as it turns out that some eukaryotic cells can get by without centrioles at all.

Centrosomes are in red, at what are also called the microtubule organizing centers, organizing the green microtubules that  in turn organize the separation of DNA (blue) during mitosis. 

In addition to these starring, if not obligatory, roles, centrioles have another charismatic property, which is that they reproduce in a clearly parental fashion. Every cell cycle is accompanied by the division of the centriole pair into single centriole mothers, which then give birth to new centriole daughters from their sides. While most of the molecular actors in this centriole mini-drama are known, as are some of their roles, a great deal remains to be found out about how the whole process is put together.

Detailed scheme of centriole (green) and centrosome (the whole green + yellow mess) duplication during the cell cycle. The structures are reasonably well known, the molecules and their roles less so. Note the roles of Plk4, Sas6 and colleagues in generation of the nascent cartwheel scaffold at G1/S. Plk4 itself will be disposed of later on, towards M phase.  

A recent paper described some more about how the first steps of this replication process take place. The cooperation of the centrioles with the larger cell cycle is naturally very deep. Some labs have found that the key kinases (which attach regulatory phosphates to other proteins) that regulate the cell cycle operate out of the centrosome- the structure containing the centriole pair. And the centrioles in turn are subject to key kinase steps that license when they can replicate. Key molecules of this process have the name Sas, after a genetic screen for spindle assembly defective mutants, each of which was given a Sas# name. Sas4, Sas5, and Sas6, for instance, are proteins that make up most of the central cartwheel scaffold upon which the centrosomal microtubules are built, along with another protein, Cep135. But the story starts much earlier. Sas6 is brought to the key location on the mother centriole's side by a kinase, Zyg1, which in turn is brought there by Spd2. How did Spd2 get there, and what does it do? Could it be turtles all the way down?

No, the authors identify Sas7 as the protein that binds to Spd2 and gets centriole pregnancy underway. Sas7, finally, is at the centriole all the time, and is activated not by recruitment, but by the cell cycle. One key finding was that all the other known initiating mutations (of Zyg1 and Spd2) depend on Sas7 for their action and localization, but not the reverse. They also find that the centrioles of mutant cells are significantly diminished, missing quite a bit of the outside structure. This suggests that Sas7 is a structural component at just the right position, around the outsides of the mother centriole, to participate in the construction of daughter centrioles.

Complete deletion of Sas7 renders the organism dead. But a partially inactivating mutation (temperature sensitive) allows its function to be observed. Here, the wild-type cells show flamboyant microtubule (green) organization during mitosis. The mutant at the restrictive temperature shows a mess, where centriole duplication has failed and the DNA (orange) is dispersed around one pole instead of being nicely pulled between two poles.

Mutant Sas7 also causes structural problems for centrioles. The outsides of the lower centrioles are severely depleted of material, whatever it is.

But that leaves one last question- what licenses / initiates the beginning of centriole duplcation, given this need for Sas7 and Spd2 interaction and given the need for tight coupling with the cell cycle, and why does it happen at only one position on the side of the mother, rather than all over? This article does not touch on those issues, and one has to revert to other reviews to gain some insight. Zyg1 is known in other species as Plk4, and seems to be the critical link to the cell cycle. Whether its activation is driven in particular ways is not yet known, but its destruction is known to be driven by the SCF complex that funnels many critical cell cycle proteins into the proteasomal trash bin at the the transition between G2 and M phase (with partner betaTrCP). However, how the localization is restricted to one position on the mother is not known at all. The only relevant fact is that supplying an excess of Plk4 can prompt initiation of multiple daughters. Thus one reviewer is reduced to speculating about a concentration-sensitive positive feedback mechanism that forces all the activity to localize in one place.

So, even after all these years, of both macroscopic and molecular study, this beauty still holds quite a bit of mystery. Will resolving it make us happier?

Sunday, March 19, 2017

Why ATP?

Inside cells, the major energy carrier is ATP. Why, and what might have come before?

Two weeks ago, we learned about the intricate mechanism by which organisms transduce energy from a proton gradient into ATP, using a rotating, motor-like enzyme: the ATP synthase. Proton gradients are one important way for organisms to store and distribute their energy, just as we do macroscopically with fossil fuels, and the body does with glucose, distributed through the blood. Inside cells, ATP is the primary short-term form of energy distribution, with longer term stores taking the form of various carbohydrates, lipids, and, in general, all the components of the cell, which can be phagocytosed in times of need (or even entire cells, which can commit suicide and be consumed by others when needed).

But what is so great about ATP? It comes up constantly as the extra ingredient that makes difficult reactions go forward. Drug efflux pumps use ATP. Actin uses ATP to create physical force during its filament assembly and projection, as does myosin, which is the motor that pulls on actin to create muscle action. Likewise, dynein, which moves things along microtubules- another form of locomotion used in cell division and nerve cell organization, among much else. Translation uses a net of four ATP per amino acid incorporated, in the form of one ATP=>AMP (worth two ATP=>ADP), and two GTP, which are close cousins of ATP. ATP fuels our chemical purification factories, such as the kidneys, whose various chemical pumps all depend on a master gradient driven by the ATP-using sodium / potassium antiporter. Countless regulatory pathways use ATP to attach a phosphate to a protein, thus changing its activity, often dramatically. Whenever our enzymes are doing something that is energetically impossible on its own, it is a good bet that ATP is supplying the extra oomph. And life naturally depends on many such impossible steps.

ATP, the molecule. The orange groups are called phosphoanhydride groups, or phosphate groups for short.  Each of those groups carries a negative charge.

The last bond in ATP, which is broken (via hydrolysis with water) to make ADP + phosphate, provides about 30 kJ/mol. In comparison, a hydrogen bond, such as those that hold DNA strands together, are about 8 kJ/mol, and a normal carbon-carbon bond has about 360 kJ/mol. It takes a lot of energy to build up organic molecules, which is why such extraordinary measures like photosynthesis were developed during evolution, (taking about 3,100 kJ/mol worth of ATP and NADPH to produce one sugar molecule). But most other processes that just need a chemical nudge are well within the range of that ADP-P phosphate bond. Breaking the second-to-last instead of the last bond, to release diphosphate and AMP, yields about 41 kJ/mol, for a little extra energy when needed.

Sometimes the phosphate bond is referred to as "high-energy", but that doesn't mean it is a strong bond. One of the strongest bonds is the triple bond between the two atoms of atmospheric nitrogen, which takes 945 kJ/mol to break. Quite the opposite- instead of requiring lots of energy to break, the phosphate bond gives up those 30 kJ/mol energy when hydrolyzed (that is to say, the reaction is exothermic). Those negative charges really want to get away from each other! That makes it an energy store instead of an energy sink. But due to the its high negative charge, it is not easily attacked by water, which means it is kinetically stable and does not spontaneously degrade- again, an important property for an energy store. It takes an small enzymatic nudge to do the job- something our proteins are very good at.

 Indeed, the weakness of the phosphate bond is its strong point, as it makes an excellent "leaving group". That means that it reacts enthusiastically, taking away two electrons when a nucleophilic attack is directed against its neighbor. Hydrolysis by water is the most common mode of attack, or by a target compound or protein that ends up with the phosphate group attached. The phosphate's negative charge is also beneficial, so that chemical intermediates to which it is attached are instantly given a charge, which confines them within the membrane. This can be a significant issue for the many small molecules of metabolic reaction chains.

Table from Westheimer, discussing the utility of phosphate for organic chemistry. Human chemists do not have enzymes at their disposal, so have to use much more caustic and active leaving groups than the chemists of molecular biology can.

But there is a problem from an evolutionary perspective, which is that phosphorous is hard to come by in geological terms. This is a debatable point, but many researchers contend that mineral phosphates are all highly insoluble, and have been since the Earth was formed. Phosphorous could thus be likened to gold- a precious and rare element that changes hands frequently as a medium of exchange, but whose actual abundance is exceedingly low. For example, our bodies are thought to break and reform over 400 pounds of ATP per day, but have only 0.1 pound on hand at any moment.

Whatever the geological case, one research group was inspired to look for possible pre-phosphorous chemistries in the early history of life. They propose that ATP and its phosphate-carrying colleagues may have been a later development in early biotic chemistry, though it was well-entrenched by the time of the last common ancestor of all life, abbreviated LUCA. They took a somewhat round-about route in their analysis, trolling through all the known reactions among existing organisms (KEGG) to find those which do not rely on phosphate. Then they tried to assemble from those as much of a basic metabolism as possible. What they came up with (a phosphate-free metabolism) is interesting.

This metabolism is highly dependent on thioesters, which place sulfur in the place of oxygen in bonds with carbon. The thioester bond is worth, in free energy of hydrolysis terms, about as much as the phosphate bond, but it is not as good a leaving group as phosphate, and does not reliably confer charge on its targets. This chemistry is still used in many biological reactions, however, by way of coenzyme A. With this chemistry, and with numerous metal-containing enzymes, they can access about 315 reactions and 260 metabolites of the roughly 700 metabolites of core metabolism- an impressive achievement, really. The set of reactions they come up with are biased towards those of core metabolism, those using iron and other metal cofactors, and those known to have been key to early life, and to those accessible to shorter genes and proteins with a minimal complement of amino acids.

Naturally, to pull in reactions from all sorts of odd and currently-existing bacteria to stand in for the  possibilities of early evolution is hazardous, but it does indicate that phosphate-free biology is conceivable, if inefficient and incomplete. But it is the geological debate about phosphorous / phosphate availability that needs to be resolved first before this issue becomes pertinant and interesting at all.

  • Some bureaucratic problems at NIH.
  • Notes from the ground in Afghanistan.
  • Republicans do not know what they are doing. And probably don't care.
  • Class warfare, against the class he campaigned for.
  • Is empirical economics a mirage, or a grail?
  • Who explains our stagnation better?
  • The Putin connection just gets swampier.
  • Starving government may make the rich temporarily richer, but everyone else much poorer.
  • Catholics led the way in weakening insurance.

Saturday, March 11, 2017

The Treacherous Invisibility of Sociality

We are dealing with phantasms, which makes drawing a line among them difficult.

It is easy to take potshots at science for its blinkered focus on the measurable and the concrete. How many people have pulled out the famous Shakespeare line about the many more things, poor Horatio, than are dreamt of in your philosophy? How many times does the newest research in social sciences tell us what anyone with common sense already knows? However, on the other side, the quest by softer sciences, like economics and ecology, to man up and drown themselves in math in order to satisfy their envy of the "hard" sciences. There are clearly conflicting emotions on the matter, which occasionally boil over into Trumpism and general anti-elitism.

But understanding by way of careful observation, useful simplification / reduction / schematization is what all scholarship and learning is about. One can't get around learning about something in detail if one wants to master it, either operationally or intellectually. The scientific method was revolutionary development, not only for science per se, but for philosophy and specifically for psychology. It expresses a skepticism of knowledge gained by theoretical, authoritarian, and armchair means, untethered from whatever the object purports to be, whether physics or biblical texts or history. Just as we suspect statements made by our current president when based on nothing, likewise we should suspect other claims lacking evidence of a rigorous, empirical kind.

But there is a deep problem, which is that our most important issues and forms of knowledge are social, not measurable and concrete. While science struggles to grasp social patterns and knowledge from its particular perspective- and not yet terribly successfully- those patterns are at the same time experienced richly in everyday life by everyone and portrayed with great variety and complexity in the arts. It is the core of drama- who knows what, who likes whom, and can I see through layers of deceit.  All of this is invisible in the conventional sense. It may be encoded somewhere in our brains, but the proper level of analysis is clearly not that of the neuron. As scientists, we are left with questionnaires, polls, and, generally, utter blindness when it comes to this most important apparatus of our lives.

Hard to read?

What hides, and what exposes, the social matrix? Language is the premier medium, of course, going far beyond the pheromones, grunts, dancing, and grooming of other animals. Blushing, facial expression, and eye direction, are a few more biological examples of other ways we externalize our social feelings. Yet there is great value in hiding feelings as well, whether out of politeness or deceit. Indirection, subtlety, puns, jokes, allegories, metaphors, a single look. The cues, even when present, are devilishly hard to read, which prompts theories about how sociality drove gains in human intelligence. So even on the social level, let alone the scientific level, it is hard to know what is going on beneath the surface, where sociality truly resides.

An inference of sociality, constructed in typical mid-20th century fashion.

The result of all this is that we are very enthusiastic inferrers and theorists. Conspiracy theories, truthers, birthers are some of the more extreme manifestations, but we all have to do a lot of reading between the lines just to survive as social beings. What is a soap opera but the carefully and gleefully managed reveal of social facts that are not, in timely fashion, apparent to the participants? Some people are more skilled at all this reading and inferring than others are. Extroverts enthusiastically wade into this murky unknown, while introverts regard it as hostile territory, and tend temperamentally to populate the scientific ranks, struggling to find certainty in an uncertain and largely invisible world.

What becomes treacherous about all this is the over-enthusiastic inference of things that are not there. On the social plane this can be over-sensitivity to slights and oversights. But it can also be religion- the natural inference of sociality to inanimate phenomena. Animism seems the most natural human condition, anthropomorphizing everything around us from insects to mountains, and putting ourselves into subtle social relations with it all. The rise of patriarchy seems to have prompted a massive shift from animistic patheism to father-centric monotheism. The theological object is no more real, however, for being consolidated and blown up out of all proportion. It is still an over-enthusiastic inference of sociality / personhood put on the void. Smarter theists have given up trying to explain particular aspects of reality via crackpot theology, such as electricity or evolution. Yet "everything" is still somehow fostered, created, or underpinned by this phantasm, much as prostate health is "supported" by the latest herbal supplement or hemeopathic nostrum.

What's the harm? On the social plane, over-inference leads to a lot of drama, but is quite finely tuned and bounded by actual, empirical, interactions (though our politically partisan echo chambers breake this model). It is how we evolved to deal with each other. On the philosophical plane, it has been disastrous, giving us centuries of bad ideas, intolerant theologies, and mis-directed energies. Think of all the monks and nuns praying away in their cloisters to non-existent deities for undeserving patrons. And today we are still living in a world at war over religious differences, all based on imaginary inferences created out of the template of our social assumptions and desires.

Saturday, March 4, 2017

Round and Round We Go, Making ATP

The mechanism of the proton energy pump that lies deep within, and gives us ATP.

One of the more elegant and dynamic structures in biology is that of the ATP synthase, which lies at the heart of the mitochondrion's conversion of its proton / electromotive gradient into ATP. This large enzyme is not static, but functions like a carousel, whirling around as it lets in groups of H+ ions. Naturally, it has been heavily studied to learn the secrets of why such motion is necessary, and how it works, in detail.

Basic view of ATP synthetase components. The lower complex (a,b,c, epsilon,) is  often called Fo, and is embedded in the membrane bilayer, which otherwise keeps H+ protons out. Top is the internal side (of the bacterium or mitochondrion) and bottom is the outside, where H+ has been pumped by the processes of oxidative phosphorylation. The c subunits comprise the spinning rotor, causing the gamma subunit, which reaches up into the F1 (alpha, beta), to crank the non-spinning F1 proteins through a series of shape changes that prompt them to synthesize ATP.

The primary product of mitochondiral respiration, which burns our food in a controlled way using oxygen, is a transmembrane proton gradient, which is a mechanism that mitochondria inherited from their free-living bacterial ancestors. While it may seem odd that pumping protons out of the cell into the vast outside is a way to efficiently store energy, it was the original battery technology, a charged state that can later be used by many other processes, like transporters that couple the energy-releasing import of H+ with the energy-using import of K+, (a symporter), or with the energy-using export of Na+ (and antiporter). Yes, life is all about chemistry!

ATP quickly became an important chemical currency for life, but only small amounts can be made directly from breaking up food molecules like glucose by glycolysis. Much more can be made by carefully tuning the respiratory chain to export protons (or import electrons) during the stepwise transformations of glucose to smaller molecules, and then later using that electrical / proton gradient for other needs such as making ATP.

Thus the ATP synthetase was born, but it was not born in a vacuum. Rather it seems to have been derived from prior structures that used protons to drive flagellar rotation. The tails of bacteria do not wave side to side, but rather rotate, which, given their particular semi-rigid structure, can drive bacteria forward. At the flagellar base is a rotating motor which lets in H+ ions as its energy source. This structure was evidently married with what seems to have originally been a DNA helicase- a donut-shaped ATP-using enzyme that travels along DNA, prying open the double-helix. Such enzymes are necessary during DNA replication and meiosis, of which at least replication was an ancient process. The ATP-using character of this helicase was reversed to be ATP-generating in its new setting, which is biochemically easier than it seems. Indeed, the whole ATP synthetase can still today run in reverse to use up ATP when needed.

More detailed representation of the ATP synthetase. The plasma membrane is in yellow, inside the cell (or mitochondrion) is above, and outside is below. The outside has a higher concentration of tiny water triads, which represent H3O+, or H2O plus a proton. They dock to the blue transmembrane portion (Fo) of the enzyme, as shown in green and red at the key interface. The protons are handed off to coordinate with portions of the protein in highly regulated fasion. Above, ADP comes into the synthetase part of the enzyme (F1), gets a phosphate group added (yellow and red) to become ATP. 

Two videos of this process are linked above. #2 is accompanied by a great submersible soundtrack, and shows greater detail for the ATP synthesis mechanism. And a video from the paper discussed has even higher detail, showing particularly the extensive structural reshaping that goes on within the F1 subunits that are making ATP. That mechanism could be the subject of another post.

The mechanical details are that H+ is let in only at the interface of the rotating (blue) and stationary (red) parts of the Fo membrane portion of the enzyme. It is allowed in to bind only at one site per segment (green dots), which then rotate around and eventually come back to another part of the stationary part where the H+ is finally let out via a different channel, into the cell. This specific directionality of binding and release is a sort of ratchet which lets the chemical energy in the H+ gradient drive rotational motion.

This energy is then coupled to the second element, the top (F1) complex, where the six red/pink ATP synthase subunits surround the blue shaft which comes up from the rotating Fo component. While those subunits are held stably by the orange stator element at the outside, the blue shaft is like a washing machine rotor that wrenches around, distorting each of the ATP synthase subunits in turn in ways that induce them to carry out the reaction of adding a phosphate group to ADP to form ATP.

A recent paper describes new structural and mutational studies on this enzyme complex, to look for some further mechanistic details. It used primarily cryo-electron micoscopy, which is sufficient to resolve shapes of helices in proteins, though not detailed atomic locations. Yet one can combine this with mutations, prior X-ray structural studies, selective inhibitors, and other modeling to make some interesting inferences. The key one which these authors make is that there is a critical arginine (R) amino acid in the (a) subunit, or the static red part of Fo above (orange in the diagram below), which seems to be the key to H+ conveyance. This amino acid tends to be positively charged, so it would readily bind with an aspartic acids coming along as part of the (c) subunits, popping off their bound hydrogens. It is also genetically essential, as mutations are lethal.

The proposal is that this arginine is specially exposed to the internal side of the membrane, via a channel, (curved arrow leading upward to the cytoplasm in the diagram below), and also positioned such that it can latch onto aspartic acids the blue (c) subunits after rotation. These aspartic acids (D) are carrying the protons that came in via the complementary channel from below (outside) before they started their trip around the carousel. All that time, the membrane has protected those protons from displacement by other chemicals, such as water, other proteins and amino acids, etc.

Image of the proton-conducting interface within the Fo subunit of the ATP synthase. The static (a) subunit is portrayed in orange at rear, while the passing set of c subunits (there are ten of them) are going by in front as a pink band, though dimmed for clarity. The c subunits are progressing from right to left, with hydrogens coordinated on the key aspartate (D) residue #61 on each (c) subunit of the rotating set. As they pass, they are captured by the arginine (R) residue on the static A subunit and released in the only direction possible, up the chute into the cell. Immediately thereafter, the c subunit band passes to another channel where protons can load up again from the external solution.

Those protons are portrayed above by the band containing "c D61", indicating an aspartic acid (D) on a (c) subunit's 61st coded position, whose proton could be displaced by the arginine on the other (a) subunit as it is going by. The gray band of (c) subunits is travelling towards the left, so the idea is that aspartic acid-coordinated protons coming in from the right hit the blue arginine first, where the aspartate and arginine, with their different and complementary charges, bind directly and immediately, releasing the coordinated H+ which then shoots right up the channel to the cytoplasm. At the very next position, protons come in from the outside (periplasm) to bind to the just-vacated D61 spot on the (c) subunit. It is an elegant and very spare, atomic and electrochemical ratchet.

  • Are things settling down at the White House? No. No.
  • Freedom for me, but not for thee.
  • Lying is a conservative tradition.
  • And Sanders won't have it. He is still leading the way.
  • What is the answer to the fiduciary rule? Index funds.
  • The portrait.
  • A losing war against tribalism and corruption.
  • Religion and war- the deep connection.
  • We have lost a decade of normal economic growth.
  • Born in the USA.
  • A trade policy that works.
  • Corporations are exiting the public sphere. Why not regulate private companies as well?

Saturday, February 25, 2017

Welcome to the New Class System

Yes, there is a class system in America, and it organizes our politics.

Communists have spent 150 years trying to convince us that economic status determines class in modern societies. But most people wouldn't have it- neither the diagnosis, nor the prescription of a dictatorship of the proletariat. We are far more complicated than this reduction to the most basic dimension of existence. We have other identities and values that confer status. Who is classier- Barack Obama, or Donald Trump, who is worth many times more?

This seems to inform our recent election, explaining the attraction Trump held on such a large section of the electorate. A section that has felt scorned by the meritocratic elite that has sprung up over the last couple of generations. The bicoastal, college-educated, Whole Foods shoppers who have taken over the Democratic party, the levers of government, and the media. They are the politically correct libtards who have climbed up the class ladder via its new mechanism of ivy league education, rather than old money or blue blood.

People of the heartland have dutifully sent their children off to college, only to see them indoctrinated into the liberal cosmopolitan ethos and turn their backs as they headed off to the coasts. And what has happened? Working class people have been oppressed by the economic system run by this new elite, which is itself under the thumb of the modern corporation, when it is not a unionized cog of a sclerotic public sector.

The resentment, while fueled by economics, is experienced far more viscerally as cultural, as condescension towards "fly-over" country, the South, Texas, religion, State's rights, and any place not "progressive". Obama's gaffe about people clinging to guns and religion was far more damaging than any policy statement. Was it condescending? Yes. Was it true? Of course. Well, the clingers saw their revenge in Donald Trump, a man clearly of their own class, despite his totally different background (New York!). His very classlessness was a marker of a certain class, and his rude comments about the non-whites, his mafioso bling, his religion as thin as a KKK sheet, were all signs of the right class, one that would take power in a new Jacksonian revolution.

Andrew Jackson- true populist, not fake populist.

But a funny thing happened on the way to this supposed populist revolution. It turns out that the Republican coalition, which Trump exemplifies so well, is made up of two classes, not just one. The resentful social clingers are just one part of it. The populous part, but hardly the most powerful. The other part is money. Pure, unadulterated greed. The 1%, and the 0.001% particularly, are the true soul of the conservative movement and Republican party, buying its elections and ordering up its policies. The new administration now has a plutocrat in every henhouse, whose clear goals are to destroy the walls that the government, in its liberal incarnation, has put up against their greed and predation.

These, finally, are the people who exemplify the communist maxim about class being determined by the ownership of the means of production. Despite having all they could wish for, they are defined by their desire to have more. Trump himself lives for the competitive zeal of destroying others, via deals, insults, and bullying. He is also dynastically inclined, grooming his offspring to inherit the empire. Being insecure in their wealth, they also feed endless propaganda about how great they are, how appropriate it is to put the most "successful" people in charge of all affairs, how success in business, or inheritance, betokens public virtue rather than its opposite.

So the test of the new regime, telling us whom it really serves, is coming when they let their money speak, via the budget and tax policies. Will inheritance taxes be eliminated? Who gets the most from the tax cuts? Why destroy the consumer financial protection agency? We know the answers already, and it does not accord in the least with a populist program. Trump has been meeting assiduously with CEOs to ask them what policies they would like, how workers should be treated, and taxes reduced. What can possibly be populist about the outcome? How thoroughly can they entrench a new system, where democracy is fully neutered, in favor of plutocracy?

So, once again, the clingers, true to their social concept of class, are being sold down the river by their comrades in the GOP, whose interests lie precisely in keeping them downtrodden, while throwing an occasional bit of social red meat in their direction, plus plenty of propaganda via the house organs.

In the end, we have three classes in the US, pulling in quite different directions. The downtrodden middle and lower classes, the cosmopolitan liberal middle, and the plutocratic top end. As Hillary Clinton found out, democracy alone isn't enough in the face of an antiquated constitution, shameless opponents, and buckets of money. How the Republican coalition continues to hold in the face of its stark contradictions has long been, and remains, a mystery, especially from the vantage point of California, where that contradiction has doomed it to obscurity. But clearly the social class consciousness of the Republican base is far stronger elsewhere, and can be traded on with what seems like impunity.

  • Colleges as class incubators.
  • Oh, those out-of-touch technocrats.
  • Feelings of white victimhood ... of all things.
  • Piracy on Australia: when free markets don't work. "If you decrease your output by half but as a consequence increase your price by a factor of ten, you’re better off decreasing your output."
  • Other precedents for Trump.
  • Making America great, with BS.
  • And lies.
  • Swamp draining? More like swamp-a-lago.
  • Someone must and will lead on climate change.
  • Stiglitz on Trump.
  • Black on Arrow: Crime still pays, and economics is not rational.
  • Win for inequality- let's repeal fuel efficiency standards!
  • Whence Macedonia?
  • China rising.
  • Everyone deserves a union.
  • Wealth distribution is a policy issue, not a technology issue.

Saturday, February 18, 2017

Memories ... In the Corners of My Mind

Where Do Memories Go? Where Do They Stay? How do we get them back?

There has been some debate about where memories end up in our brains, whether in the hippocampus exclusively or distributed through much of the neocortex. The spectacular case of HM, who could not form new memories after his entire hippocampus was removed, (plus some other nearby structures), indicated that older memories were still accessible from elsewhere, while all new memories are formed and reside at least temporarily in the hippocampus. However some types of memories do not appear to get re-distributed from the hippocampus. HM was missing quite a bit of explicit (also called declarative) memory from prior to his surgery, for instance, including everything in the prior year, and decreasing amounts going backwards for eleven more years. Other types of memory, such a short-term, working, implicit, motor, and procedural memories remained functional, however, for new formation as well as retrieval.

It is known that sleep plays an important role in the "consolidation" and redistribution of explicit memories within the hippocampus and from there to the cortex. During sleep, significant memories are replayed, which strengthens their encoding and allows their replication to more stable storage in the cortex. Ironically, sleep prevents forgetting. The redistribution process can take months to years, accounting for the deficits experienced by HM. On the other hand, sleep impairs, while new novel experiences enhance, the consolidation of some memories within the hippocampus, probably by enhancing the salience of the entire sequence of experiences. Current work indicates that memories get to the cortex quite quickly, with a "parallel process" between both areas strengthening them over time.

A recent study looked at this memory consolidation process, and asked what happens to conflicting memories- which might prompt over-writing of an initial memory with a later, corrected one. Yes, this was another study done with rats and mazes, testing their ability to retain memories of locations over various time periods, and over intervening activities, such as sleep, after the target location was changed. The rats learned the locations of both targets quite quickly, and returned to those locations preferentially in future trials, a week later, no matter where the actual target was.

If the rats where allowed to sleep between the switched training sessions, they lost the first memory more than if they had been deprived of sleep and exposed to further novel events between training sessions. This led to a conclusion that the hippocampal encoding (but not the cortical) is enhanced by activity and novelty, rather than sleep. The next step in the experiment was to alter the memory type by allowing the rats to explore the training area extensively for a few days prior to the training. This allowed them to gain a fuller context for the experiences to come, context that is believed to be stored not only in the hippocampus, but also in the cortex, being part of the consolidated and distributed memory system. After this protocol, rats allowed to sleep significantly out-remembered the sleep deprived rats when tested, and performed particularly well if the experimenters threw in a cruel trial a day after training, where no target was present in the maze at all.
An example of one test of a rat trained the week before. The training runs were, first target top left, followed by sleep, and second, target at bottom right, followed by distraction and sleep deprivation. The rat clearly remembered the second training much better. This was true even if the training regimens were reversed, and the one followed by sleep occurred second.

Lastly, the researchers studied molecular markers in their subject's brains, to see where cell and synapse growth was taking place in response to all these exciting events. For all conditions, the brains showed a great deal of neural activity and synaptic consolidation, i.e. expression of genes like cFos and Zif-268, right after training. However five hours later, things were a little different. Expression in the hippocampus was significantly down among animals who had gotten some sleep, but up if they were sleep deprived.

Conversely, marker expression in the cortex was the reverse- up in rats who had slept, down in those continually kept awake with more play and other novelties. This was particularly interesting since sleep alone drove a significant decline in cortical expression of these genes in control animals. That such brief training events can have effects on such gross brain areas through subsequent sleep, for hours and days, may argue more for the traumatic nature of the training, (done in water mazes, where the rats are desperately searching for a hidden platform), than normal learning in, say, a school environment.

Nevertheless, this kind of work shows what is going on in the field of memory research, as we try to figure out why, where, and how memories are distributed in the brain, which ones are kept, which ones erased, how they are schematized and compressed, and how they are retrieved again and altered during that retrieval. In this case, the researchers make the claim that their procedures have dissected a difference between cortical memory formation, which is enhanced by sleep and inhibited by intervening learning and activity, versus hippocampal memory formation, which experiences the reverse.

They did not have much to say in the end about conflicting memory formation, since the rats seemed to deal with this aspect just fine, (though less well after sleep). They remembered both maze solutions, even if one had been superceded by another for a few training runs. But the relational nature of cortical memory, which seems to grasp memories better if they are situated in a known matrix of prior experience, is interesting. And the speed of this cortical memory consolidation is also interesting- a matter of days, not the weeks or months that has been the model in the wake of HM.

  • Plutocrats in charge of the Treasury, after a crisis they caused.
  • Another institution could be permanently damaged.
  • Treason is only if the other party does it.
  • China is the story of our time.
  • Review of Too Big to Fail.
  • We do not need to settle for depression economics.
  • Remember the EPA!
  • Sanity is getting the upper hand, and the nuts won't have it.
  • What the Islamic & Persian world did for math.