Saturday, December 26, 2015

A Gentle Touch at Metaphase

Dynamic modeling of the metaphase chromosomes as microtubules push them about.

One of the more magical phenomena of biology is the orchestrated congregation and division of chromosomes at the midline of a eukaryotic cell at mitosis, or cell division. One has to keep reminding oneself that there is no central brain organizing the process- it is driven by a network of molecules regulating each other and conjuring collective organization and action out of blind chemistry.

What are the mechanics involved? The main force comes from the microtubules originating at the spindle poles, which connect in somewhat noisy fashion to the chromosomes, especially to the kinetochores that are located at the middle of each chromosome at its centromere. About 10 to 30 microtubule plus ends are stuck into each kinetochore, when everything is working properly. Microtubules are fascinating structures in themselves- they can exert force in either direction, either (+) growing by polymerizing more of their subunits, or (-) by shrinking and losing subunits. This is quite apart from the various cargo carriers that use the motor kinesin to travel along stable microtubules to ferry materials around cells.

Electron microscopy of microtubule ends (bottom), and as stuck into
a kinetochore (at right). When splayed out, the end is de-polymerizing
and retreating. When straight, the end is advancing by polymerization.

The strongest forces come from the microtubules docked successfully to kinetochores. Having all the kinetochores docked is a key prerequisite for proceeding with cell division, to insure that each daughter cell gets a full set of chromosome copies. But there is another, weaker force, which comes from microtubules touching other areas of the chromosomes, away from the kinetochores. These attachments (called the polar ejection force, or PEF) are much simpler, and only push in one direction, away from the spindle and towards the midline of the cell. They connect to chromokinesins distributed all over the chromosome arms. A recent paper modeled what is known about these forces, and concluded that it is the PEF that gives the key nudge to line all the chromosomes up properly at the midline, while the kinetochore-attached forces swing rather wildly back and forth, causing the chromosomes to oscillate as they gradually find their equilibrium position.

A still from a video that shows the typical oscillation
of chromosomes being tugged back and forth by
their attached microtubules. The chromosomes are
the dark globules beneath the labelled molecules (red
is the microtubules, green is the kinetochores and
spindle poles).

A third force or factor is the attachment strength between the two copied chromosomes, the two partnered kinetochores. This is trivial, however, as it acts like a rather stiff spring which can not be broken until the signal is given for the cell actually divide and the paired chromosomes part to opposite sides.

The researchers use video recordings of labelled human HeLa cells to document the back-and-forthings of the mitotic chromosomes, and using a basic model of the forces involved develop a more detailed model of the dynamics they are seeing. The upshot is that while the strong kinetochore forces are switching back and forth, (and forms another story about how the kinetochore-microtubule connections are made and regulated), insuring capture of each kinetochore, the PEF, which is about 1/3 as strong, consistently pushes each chromosome towards the center, thus biassing the net force to line everyone up at the midline. These two processes are collaborative, since alignment in a single row / plate at the center also helps to insure that all the kinetochores are captured, on both sides. There is an additional consideration, which is that each kinetochore needs to associate with only one spindle, not with both. This is probably helped by the stochastic push-pull process, where microtubules, which are relatively stiff themselves, rapidly attach and detach from the kinetochore, which has a rigid, single orientation.

Schema and results from the cited paper. On left are the forces at work,
including a spring force between the paired kinetochores (green). The other
graphs show the deduced forces for individual kinetochore excursions,
with the PEF and inter-kinetochore spring force (right) much weaker than
the main kinetochore microtubules, which show much more dramatic
directional switching.

Once each kinetochore has successfully docked with microtubules from the opposite spindle pole, how are their motions coordinated? The researchers find that switches in direction are led 4/5 of the time by the side that is shorter and pulling towards its pole. The stiff connection between the two chromosomes then quickly transmits this switch in motion to induce the partner kinetochore+microtubules to follow suit, after which the pair is once again heading together in the opposite, direction. The bias in the tendency to switch directions also helps keep the chromosomes centrally postioned. But why does this bias happen? That remains unanswered, and likely is also due to the gentle, but persistent, PEF.

All this is a prelude, once the spindle checkpoint is passed and the paired chromosomes fire their release rockets, to when the kinetochore-associated microtubules pull hard and in unison toward the poles. This transition orchestrated by other molecular signals which have been well-studied, particularly the anaphase promoting complex. Life is a process, and a network, which knows no end and few boundaries.

  • Our war on fish.
  • Mars is not a backup planet.
  • Yes, we can, and must, do a carbon tax.
  • Brains have male and female traits, but no one is pure here.
  • Islam has a branding problem, and a self-fulfilling isolation problem.
  • Or perhaps we have the branding problem.
  • Sandra Bland aftermath: everything is OK!
  • What is lithium used for?
  • Judging the Federal Reserve. Good, but it could have been so much better.
  • Bill Mitchell on the core problems of the EU:
"The French drove the process of integration and became increasingly influenced by the Monetarist thinking, which pushed them closer to the German emphasis on monetary control and fiscal thrift. What the French didn’t appreciate was that this emphasis could not deliver effective outcomes to its own economy much less the broader European Member States, given the fact that German manufacturing and its trade capacity was superior in every way."

Saturday, December 19, 2015

We Just Found the Outrage

The GOP reaches a new low in incivility and untruthfulness.

The recent Republican debate struck a new low for our body politic. Not much remarked, but striking to anyone suffering through it, was a new tone of empty vitriol directed especially at President Obama. The Republicans have been consumed with hate since he was elected, but I have never seen decorum drop to quite such a low level.

"America has been betrayed. We've been betrayed by the leadership that Barack Obama and Hilary Clinton have provided to this country over the last number of years." - Governor Chris Christie.
"This is why -- this is what I said at the beginning that this administration, Barack Obama and Hillary Clinton through their foreign policy, have betrayed the American people, because the weakness they've displayed has led to Putin's incursions in the Middle East and in eastern Europe, and has led -- has led to significant problems in the Middle East as well, and the death and murder of lots of folks." - Governor Chris Christie
"As far as other people like in the migration, where they're going, tens of thousands of people having cell phones with ISIS flags on them? I don't think so, Wolf. They're not coming to this country. And if I'm president and if Obama has brought some to this country, they are leaving. They're going. They're gone." - Donald Trump
"One of the things I would immediately do, in addition to defeating them here at home, is bring back the warrior class -- Petraeus, McChrystal, Mattis, Keane, Flynn. Every single one of these generals I know. Every one was retired early because they told President Obama things that he didn't want to hear." - Carly Fiorina
"This president and this is what the focus ought to be, it's not the differences between us, it's Barack Obama does not believe America's leadership in the world is a force for good. He does not believe that our strength is a place where security can take place." - Former Governor Jeb Bush
"And let us remember one other thing. Hillary Clinton and Barack Obama are responsible for the growth of ISIS because they precipitously withdrew from Iraq in 2011 against the advice of every single general and for political expediency. It's not these people up here. It's Hillary Clinton." - Carly Fiorina
"Well, Wolf, I'll tell you what reckless is. What reckless is is calling Assad a reformer. What reckless is allowing Russia to come into Crimea and Ukraine. What reckless is is inviting Russia into Syria to team with Iran. That is reckless. And the reckless people are the folks in the White House right now. Barack Obama and Hillary Clinton are the reckless people." - Governor Chris Christie
"Barack Obama has said he doesn't believe in American leadership or America winning -- he is wrong." - Senator Ted Cruz
  • The word "kill" came up 26 times in the debate
"I would certainly be open to closing areas where we are at war with somebody. I sure as hell don't want to let people that want to kill us and kill our nation use our Internet. Yes, sir, I am." - Donald Trump
  • Then there was the bizarre over-inflation of ISIS as a threat.
"Regarding national security, we need to restore the defense cuts of Barack Obama to rebuild our military, to destroy ISIS before it destroys us." - Former Governor Jeb Bush

The "reckless" charge is particularly ironic in light of Barack Obama's predecessor, who sort of defines the term, including the "killing of lots of folks" part. At any rate, extreme competition among a very crowded field of mediocre candidates has lowered the level of rhetoric, to what I would regard as unconscionable levels. How do they expect to be treated in office, and how do they expect the office to maintain its value if they as public officials make of it such a pig-sty?

This is not even to delve into Mr. Trump's ugly past rhetoric. In this debate, he continued to expound on his "strength", as shown by his willingness to kill relatives of terrorists, and to prohibit Muslims from immigrating to the US. From a left perspective, the GOP is a motley circus, but that doesn't excuse us from paying some attention and noting that we all share in the national discussion and need to draw some lines of basic decency if our politics is not to descend to the level of farce, and worse.

  • Some are uncomfortable with this language.
  • A few more lies.
  • Is ISIS going to kill us all?
  • Which side are the Saudis on, really? What a change from the 60's, when a Muslim military alliance was forged against Israel. And how did that work out?
  • And they don't just imprison political protesters, they behead them.
  • A look back at the Arab spring. Note especially (and in connection with the new Saudi "coalition") how the social and economic dominance of the military in Muslim countries like Egypt, Syria, and Pakistan has no relationship to its effectiveness. It is empty, political, patriarchal machismo writ large.
"If Islamic fundamentalist forces managed to become dominant among the organized forces in those uprisings, with no exception, it is surely due, on the one hand, to the practical and/or political weakness of the Left, but, on the other hand, it is also and above all a product of decades of rule by the despotic regimes. No one should miss that. The Syrian regime was not a shield against Islamic fundamentalism, nor were Mubarak or Ben Ali, and nor are Assad and Sisi today." 
Islam as a religion and ideology, of course, seems to go unnoticed. Time and again in this discussion, it come up in passing as the most powerful regional ideology, by far. What does modern liberalism have to offer in its place?
"Add to this the very active involvement of the regional counterrevolutionary stronghold represented by the Gulf oil monarchies, which did their best to strengthen the Islamic fundamentalist component of the Syrian opposition at the expense of anything else. Because, a real democratic uprising is the major threat to them like it is for Assad. In a sense, they concurred with the Assad regime in promoting the Islamic fundamentalist component of the opposition at the detriment of the secular democratic."

Saturday, December 12, 2015

Odysseus Among the Stars

Star Trek as an Odyssey retold.

Star Trek is one of the great narratives of our time, burrowing into the cultural unconscious with its optimism, classic storylines, inexhaustable fund of aliens, and dash of humor. What other story is equally classic, with a hero who commands his ship through a long series of adventures, who meets aliens of many descriptions, and gets out of one bizarre scrape after another? Why Odysseus, of course!

Realizing this clarified to me the staying power and deep resonance of this new myth. Odysseus wasn't big on preaching the benefits of a peaceful Federation, (though that may have been an implicit lesson to its original listeners, binding together a Greek world constantly at war), but on the other hand, he had heard of most of the monsters and gods he meets, getting more of a head start than Kirk has. Like Odysseus, Kirk is a winner, happy to seduce a woman if that will save his ship, using deception and every wile to get what he wants. Or to go in with guns blazing if that is needed. While Odysseus had a home to go back to, Star Trek dispenses with that bit of plot, concentrating on the voyage exclusively, the far more engaging part of the story.

One big difference is the role of Spock. Odysseus has no significantly characterized companions from what I recall, none whom one would call a number two. While a soldier and coming back from war, the military organization of his ships is hardly mentioned and seems rather lax. Odysseus keeps his own counsel and gets little help from his sailors, who die right and left in various misadventures. Nor are aliens brought along on his voyage. Time after time, he flees as fast as he can from each monster in turn.

A medical officer with a shamanic touch, like McCoy, might not have been unknown to the Greek world, but Spock is another matter. He exemplifies the classical philosophical position of Stoicism, but this hardly had much place in the original tale, outside of mundane forbearance of disasters which rain down constantly. Odysseus doesn't involve himself in much philosophical discussion, or introspection, which becomes such an important part of Greek culture only later. The Odyssey is a tale of action, not thought. Spock introduces both an element of diversity and philosophical perspective, (especially an occasional check on senseless violence), which is sorely needed in what is also, among its other themes, a pean to what was at the time a growing US federation of democratic and peaceful planets, er nations.

Modern, contemporary, retro, or classic?

  • We are on the ISIS side, in Yemen, along with Saudi Arabia.. why? Why take sides in the Sunni-Shia showdown?
  • Narratives and theories of anorexia.
  • New US jobs are heavily low-wage.
  • Hope, belief, and con games large and small.
  • Why are bitter, fundamentalist losers messing everything up?
  • Bill Mitchell on basic income.
  • Is quietist Dawa fundamentalism better than militant Wahabi and Salafi fundamentalism?
  • Trump is blowing up the code. FOX/GOP can not wash its hands of what it has wrought.

Sunday, December 6, 2015

Raising Consciousness

New methods to detect and characterize consciousness in the brain. AKA, going beyond Granger causality to understand brain dynamics.

Neuroscience and the study of consciousness has to date peeked at the living human brain via MRI, and analyzed it by correlation, trying to join slight activity signatures to various mental tasks and subjective experiences. There has been a great deal of speculation about what the neural correlates of consciousness are, complete with fanciful mathematical theories (phi, critique of phi, gamma waves, etc.) But none has been convincing, though there has been a general coalescence around some ideas- that consciousness involves fleeting coalitions among many brain areas coordinated to some degree by anatomical connection and rhythmic oscillation in the gamma band.

Getting beyond that, to a more detailed theory of consciousness, will take not only better techniques of looking at the brain, with higher time and space resolution, but also better analytical methods & theories to make sense of the vast amount of activity we see and data we already gather.

As David Eagleman illustrated in his excellent PBS show on the brain, there is a storm of activity taking place all the time, associated, as usual, with the words "billions" and "trillions". Somehow, it gets the job done, but figuring all this out from the outside requires another order of analysis. A recent paper describes new mathematical methods that appear very promising, for determining causality within a complex network like the brain.
"A dilemma is that overly realistic and detailed simulations often require a number of unknown parameters and can obscure physiological principles. It is, therefore, not straightforward to instantiate an appropriate reductive model that capture dynamical complexity and diversity across multiple brain areas. "

The problem, for a complex dynamic system, is that correlation methods alone are extremely crude. Imagine probing a computer's internal circuits with a correlation meter, and expecting to figure out its logic and mechanisms- it would be impossible. The system is non-linear, which means that a signal here can lead to negative signals there, or to vastly amplified signals, or altered patterns of waves, etc., so that simple correlations among points of activity have very limited analytical power. Then there is feedback and other network behavior that can obscure the directionality of causation.

The next step of analysis has been Granger causality, which is an extension of correlation analysis to a time series. Compare two time series of events, and if changes in one series routinely predict changes in the other, (i.e. correlate with a time lag), that supports a hypothesis of causality from one series to the other. But this method relies on the two variables being independent, and also struggles with non-linear effects, as other correlation methods do.

The new method, called convergent cross-correlation mapping (CCM) or cross-embedding, arrives from a recent ecology paper that asked what causes the unusual cycles of anchovies and sardines, each of which go through boom and bust cycles which seem anti-correlated with each other. Do they compete with each other's food sources? Is there a predator cycle that determines their abundance? The authors conclude that each population is driven by sea surface temperature, independently of the other. The causality went precisely from temperature to each species' abundance, not from either species to the other. The new method uses correlation, but through some higher-level math that better accommodates non-linear systems with feedback characteristics.

This paper showed a nice example of the method, analyzing the predator-prey relationship of the classic protists, Didinium and Paramecium. The dynamic cyclicity is very clear (in A), but what causes what? The Granger method could call it either way, depending on how you set the lag time. The cross-embedding method (rho, on the Y-axis of B) finds a higher amount of information provided by the Paramecium graph against the Didinium graph, suggesting that the predator exerts stronger top-down control of Paramecium than the reverse. In other words, the subject variable (Paramecium in this case) is more dependent on, and thus directly informative about, the driving variable (Didinium) than the reverse. A feature of this method is that it provides stronger results (suggesting true causality) the longer the time series, whence the "convergent" in its name.

A Didinium eating a Paramecium.
Population dynamic between the predator Didinium and its prey, Paramecium. 

Getting back to humans, (or thereabouts), another recent paper used this method to look at neural correlates of consciousness in macaque monkeys. They used electrodes applied directly to the exposed brain surface, getting much higher signal and resolution than when they only applied to the scalp. The monkeys were either anesthetized or conscious and behaving in various ways to test visual and other forms of perception / consciousness. The question was whether, over large distances in the whole brain, correlates of consciousness can be detected. (They also have prior work, using Granger methods.)

Electrode map and anatomical codes, top. At bottom, an example of one electrode pair and its analysis shows directionality of signaling, from #118 (red, visual cortex) to #41, (green, motor and somatosensory cortex).

The answer is that they can get significant signals from awake and behaving brains that are not only different from anestheized brains, but also reflective of an expected hierarchy of directionality and complexity, for instance that the visual system is causal towards signals in the frontal cortex during visual perception, and that the frontal areas overall have significantly higher complexity than the primary sensory processing areas at the rear of the brain.

Complexity and directionality measures among major brain areas in macaque brains under different conditions, using cross-embedding analysis. Consciousness is easily detectable, among other significant characteristics.
"Based on this method, we simultaneously characterized the large-scale cortical interaction and the dynamical complexities embedded in individual area activities. It revealed that the awake brain has a hierarchical structure of the dynamical complexity, where the frontoparietal areas had more complex dynamics than visual areas. Intriguingly, this hierarchy was linked to the directed cross-area interaction from visual to frontoparietal areas. To our best knowledge, this is the first study reporting clear cortical hierarchy in terms of dynamical complexity, as well as its relationship to the global cortical interaction. Moreover, we found that this hierarchy was universal across different behavioral/sensory conditions and disappeared after the loss-of-consciousness induced by either of two different anesthetization methods. These results indicate that this hierarchical structure is correlated with the level of consciousness rather than its specific contents reflecting perception or action."

This work is not unique in finding distinctions between conscious and unconscious states, but the improved data analysis is a significant step forward in teasing out reliable correlates of consciousness as observed from (sort-of) outside. Of course it is still a long, long way from telling what the content of that conscious state is, let alone sharing it in any rich way. And, being based on naked brain EEG, it is not clinically useful either.

  • Who is subsidizing the coal industry? You are.
  • One party is at fault.
  • And is also wrong. I mean really, really wrong.
  • And is also corrupt.
  • Update from the god & gun nuts. Update two.
  • Other things that are wrong...
  • What is your anti-capitalist stance?
  • Using dispersants on oil spills does no good.
  • This week in the WSJ: corruption at the Afghan anti-corruption committee.

Saturday, November 28, 2015

The Women of Deseret

What about feminism? A collision with the modern world. 

Continuing from last week, a particularly interesting topic in the field of Mormonism is the role of women. The church calls itself a "restored" Christianity, which is a fundamentalist position, in that it claims to attempt to reproduce the conditions of the early church, and proselytizes on that basis. This includes naming apostles, extending priesthood to all men, and thorough-going patriarchy. It even meant, during its formative period in the mid to late 1800's, polygamy, based on a bit of cherry-picking from the Old Testament.

Polygamy was also based on a revelation from god to Joseph Smith. One that his (sole) wife at the time, Emma, knew what to do with. She physically burned that revelation, by some accounts. She also agitated against this new doctrine, turning the female relief society into such a dangerous organ that the church leaders shut it down for a couple of decades, after which it was reconstituted and has behaved in properly submissive fashion ever since.

An intriguing aspect of polygamy is the patent lies and dissimulation practised in its defense. The Mormon authors of "The Mormon Expereince" insist that a large part of the rationale (as was the case for Muhammed and Islam) was to provide for otherwise unattached women, the destitute, and to correct for an excess of women due to warfare, etc. But the West in the US always had an excess of men (though see here). More tellingly, polygamy was not a matter of charity, but a reward to the highest officers of the church for their obvious spiritual blessings, to be converted into power and children. The fourth president of the church had six wives and forty-three children. The book also relates that if economically possible, a husband would build separate houses for each of his wives.

This hardly reflects how harmonious the institution was on behalf of women, or how charitable it was towards the destitute. No, it portrays a system of power-mad men, perhaps not wearing huge beards, but otherwise rewarding themselves in a way that suggests that they were somewhat impatient about becoming gods only in the afterlife.

Brigham Young, with what resembles a rather Islamist beard.

It is a problem we also see with the veil on Islamic women. How do we judge and react to oppression when its victims are acquiescent or even explicit supporters of the system and part of a culture which, whatever its flaws, is valued by its members? Can a system of oppression be so insidious as to be invisible? This comes up in the black lives matter movement, not that blacks in the US are acquiescent or supporters of racism, (though studies show that they are also unconsciously color-ist and racist by way of indoctrination), but that non-blacks require continual consciousness raising to a condition that is so ingrained in the social fabric and unconscious that great harms are inadvertantly, and continually done, while rationalizations accrue without end whenever a question or difficulty arises.

There is no objective judgement about social affairs, unfortunately. One group may be treated differently on an objective basis, yet that treatment be justified by any number of value judgements and attitudes whose quality is not objective at all. To take the devil's advocate position for a moment, it is clear that women and men are different, mentally as well physically. Thus it is no surprise that women may typically want different things out of life than men, and might naturally prefer a social system with roles which are different and respectively suited to each gender, both in talent and desire.

To go even deeper, all social organization involves oppression. Every relationship involves expectations and some desire to get something from the other person or change the other person. No one is innocent of manipulation, least of all the infant in its crib. We are social beings, instinctively ready to make commitments of service and sacrifice, working for family, company, nation in return for uncertain, and surely incommensurate, benefits. And ultimately we benefit from the social structures we are enmeshed in, in countless ways. But that is hardly freedom. No one is free.

So the question of civil rights, of equality, and freedom, are ones of degree, not of black and white. The problem of feminism (the problem that has no name!) is one of enumerating the various qualities of people of both genders and asking which ones are relevant to our various (modern) social roles, instead of throwing a lace-trimmed blanket over the whole thing by saying that men are better than women and should run the society from top to bottom, perhaps because they are more violent and warlike.

And even more importantly, it is a project of recognizing and accepting diversity among people, so that even if women and men mostly abide by their stereotypical interests and roles, exceptions are not judged as abnormal, destabilizing, even evil. To take another example, Mormons are no great friends of introverts:
"If our composite family contains members who are temperamentally introverts or 'loners', people preferring quieter life-styles, the church programs may seem uncomfortable- or they may be looked upon as opportunities to emerge from a shell and may help to develop a more balanced personality."

The "life-style" of homosexuality is likewise a source of horror, of course.

In the context of feminism, sure, relatively few women are lesbians, or are interested in joining the infantry, or running for president. But some are, and why not let them? What point do the normative, rather than descriptive, gender roles that conservative, patriarchial institutions like the Mormon church enforce to various degrees, and push with vast amounts of propaganda, serve?

I think there are two main answers. One is the raw power of the patriarchy. As the reader may recall, it took a decade and a half after the civil rights movement for the Mormon church to ask God about the fitness of blacks for the ministry. Here is president Spencer Kimbal writing to the church:
"... we have pleaded long and earnestly on behalf of these, our faithful brethren, spending many hours in the Upper Room of the Temple supplicating the Lord for divine guidance. He has heard our prayers, and by revelation has confirmed that the long-promised day has come when every faithful, worthy man in the Church may receive the holy priesthood, with power to exercise its divine authority, and enjoy with his loved ones every blessing that flows therefrom, including the blessings of the temple."

Note the word "man". Whether they are beseeching god on behalf of women, we have no idea. Personally, I doubt it. The transparent secular motivation of this revelation, as transparent as the federally induced revelation banning polygamy almost a century before, could hardly be more obvious. The patriarchial system likewise, with its old testament tradition, is a institution of power, with clear secular motivations. Why else deny the obvious: that women have as much access to god as men, whatever that might mean?

The second attraction of strict roles is plain orderliness and security. If the family and church is automatically organized by way of gender roles, then that is one less source of conflict and negotiation, or so it might seem to the naive. More psychologically, some standard of "normal" is a powerful organizing principle for us individually and socially. Teenagers want nothing but to be normal, and dread the opposite. People contemplating marriage are more secure in knowing that their partners are thoroughly indoctrinated into their role's "normal" template, minimizing surprise and heartbreak. Mormon institutions up and down the ladder, such as the Women's Relief Society, hum along based heavily on the slotting of all their round pegs into nice, round holes.

One could also bring up from the archetypal depths the common image of the father figure as decider and leader, and the mother figure as nurturer and consoler. Are such images innate, or are they programmed by the patriarchy itself? And even if innate, where else do we so give in to our instincts to pattern all of society on such an archaic basis? The fact of the matter is that women are natural executives, deciding on life and death as effectively, if less violently, as men.

Maturing as individuals out of wild uncultured children involves no end of repression and self-control, to form acceptable adults ready for taking on responsible, interconnected roles in society. What is one more bit of repression, for women to accede to the patriarchial system, in all its social, political, and other dimensions?

Of course, it is simple unfairness, a reflection of ancient feudal and tribal orders where the strong rode herd over the weak. We do not accede to such systems any more in politics and professional life. (With apologies to the GOP, Donald Trump, and our whole campaign finance system.) Why should we do so elsewhere? If the Mormon church really thought so highly of the family and motherhood, it would have opened the priesthood and high offices to women long ago.

The Mormons supposedly believe in the constitution, voting for political (if not ecclesiastical) office, and ironically were leaders in women's suffrage, back in the 1800's. But that constitution is based on the enlightenment principle of equality among all people, and the need for secular, practical, and compelling reasons to deviate from that fundamental assumption. Sure, the constitution in its original incarnation debilitated women, not to mention blacks, but that has since been repaired, again by voting processes, not revelation. The Mormon church, for all its protestations of protecting the family and the sacred roles of each gender, is in this respect an anachronism. Just as much as protecting the family from the homosexual "lifestyle" is an anachronism.

Is it in this respect a "restored" church of Jesus Christ, thus a purposeful anachronism? Obviously, I am no expert. But just because patriarchy was the norm in antiquity, and all the apostles as well as prophets were men does not mean that Jesus (if and however he existed) was not open to the feminine in a spiritual and apostolic sense. There is first of all the adulation and semi-divinity of Mary. Then there is the quasi-apostle-ship of Mary Magdalene. She seems to have had more importance and faith than the rest of the apostles. Indeed, Christianity started off as a religion very accepting of women in powerful positions. In all its cherry-picking, the Mormon church seems to have, in its attachment to hierarchical patriarchy, restored the structure of Catholicism rather than the broad dispensation of Jesus.

  • A little feminist outrage.
  • What happens when social order breaks down.
  • Nihilism may be a problem, but not ISIS's problem.
  • Why friends with Saudi Arabia, and not with ISIS?
  • Is Iran really the enemy? Or would it be a better friend than the Sunnis?
  • Sam Harris on Islam.
  • Want to hear more JFK assassination theories?
  • Someone is wrong on the internet. Not to say that a recession in the near future is impossible, but raising interest rates would bring it on faster, rather than helping solve it once it arrived. We have to get over expecting monetary authorities to be the only adults in the room.
  • Lawrence Lessig on equality.
  • Requiem for Douglass North.
  • Appreciation for John Locke, and modernity.
  • Is renewable energy reaching liftoff?
  • On the mechanics of the Fed and its rate liftoff.
  • Paul Mason on basic income and the end of work.

Saturday, November 21, 2015

The People of Deseret

Mormonism: From a prophet talking through his hat to a quasi-state with lessons for us all. Review of "The Mormon experience" by Leonard J. Arrington and Davis Bitton.

What happens when god speaks to an otherwise unremarkable man, telling him to found a new religion? In the case of Islam, that prophet conjured a mishmash of Christianity and Judaism into a new doctrine that took its world by storm. The stronger subtext, however, was Arab tribalism. It is that tribalism that finds such rich expression in the martial and ceaselessly vitriolic aspects of the Quran, and in the problems we face internationally today.

Meanwhile, in upstate New York, another prophet received his revelation, and after authoring an even more bizarre scripture, (though likewise a pastiche of Old and New testament materials, in part), trod a similiar path of nascent church building, continuing prophecy, practical leadership, occasional skirmishes with enemies, mass migration, and even polygamy. As an aside, the book I am working from was written by Mormons, indeed by an official church historian, so while detailed and highly interesting, is hardly an unbiased account. A chapter on the role of women is particularly tortured in its apologetics.

The parallels are deeply interesting, yet the differences are stark. Mormonism flirted with armed resistance, but very sparingly, and has been a stable and exceedingly peaceful part of the national scene for the last century. Its proselytizing is determinedly, boringly, peaceful. Both religions emphasize charity within their community and separation from gentiles, (termed infidels in the Quran), yet Mormonism has always had a much stronger internal governance structure, even though it has never (to my knowledge) had pretensions of running a fully autonomous state or of providing a comprehensive legal code, as Islam has. Indeed, Mormons regard the US constitution as divinely inspired. Mormonism has been dedicated first and foremost to self-reliance, practical development and social togetherness, for its cultural subtext was American frontier can-do-ism, rather than Arab tribalism.

One might think the differences to be subtle, after watching lots of Westerns. Clans, clan wars, and plenty of six-shooters seem to characterize the epoch. But in reality, Americans were probably more obsessed with orderly self-government and institution building. The annals of early California are full of systems of law passed for transient mining camps, and an eagerness for setting up local and state governments. From the first charters that authorized colonization by the English and Dutch in North America and the long legal traditions and enlightenment that the colonists had left behind, to the newness of the land and the colonist's ideals of freedom in a promised land, Americans were experts in self-government. Indeed the Western is not typically a celebration of lawlessness, but  quite the contrary- is a cautionary tale of its baleful consequences. Every Bonanza show ends with the forces of law and order triumphant.

I digress because, coming out of this tradition, Mormons are compulsive organizers. From the first with Joseph Smith at the helm, they selected or elected apostles and other governing bodies. The succession after Smith's death brought an even more talanted organizer to the helm, Brigham Young, who managed the hegira from their freshly constructed city of Nauvoo, Illinois to what the Mormons called for some time the State of Deseret, now Utah.

The beehive symbolizes Mormonism and Utah.

The original territorial government featured Brigham Young as governor, and other church leaders in all other offices. This seemed completely natural at the time, and few even paid much attention to the formality of elections. When the Federal government attempted to appoint its own officers to oversee the territory, the Mormons simply ran all their affairs unaltered, using a shadow system where church officers held all the power and the obedience of the people. It took far sterner measures from the US government, including moves threatening to destroy the church entirely, before the Mormons acceeded to federal supremacy, normal political forms, and particularly the illegality of polygamy, which finally happened concurrent with the grant of statehood in 1896.

The beehive is a fitting symbol, expecially of the early Mormon experience, which in the early Utah period was one of extreme hardship leavened only by thorough social organization and communal support. Communal larders were set up from the tithes which were all paid in kind, and in turn fed the poor and placated the local Indians. Communal effort was essential to manage the scarce water, for agriculture was only possible by irrigation. When the Union Pacific railroad building project came through, Brigham Young arranged for Mormons to do the work in the territory, to prevent the immigration of undesirable elements. Then he used a large part of the proceeds to build his own railroad within the state. And in a thousand other ways, from the territorial militia to the building of the Salt Lake City temple, orderly government and communal activity was and remains fundamental to Mormonism. (How ironic, however, that beehives have a queen as their president, who has mated with multiple husbands.)

To some, this degree of togetherness can seem rather creepy, and there is a dark side of extreme patriarchy and conformity. Plural marriage, for instance, was not just an odd and occasional peculiarity, but a reward and sign of church leadership, reserved for top officials. It was Old-Testament patriarchy, and natural selection, in action, Mormon style. But there are also positive lessons for our national economic questions, which largely turn today (in the right-left spectrum) on how together we feel, and how high we wish to set the dial of brutal competitiveness and laissez faire, versus a more compassionate egalitarianism. Mormons are typically Republicans due to their social conservatism. Yet their social organization was at the outset virtually communistic, with high social mobility with the possibility of high office (for men), and thoroughly organized social support. This organization was highly effective, not only socially, but economically, taming an extremely forbidding wilderness and creating a strong state out of nothing. Mormons teach us yet again that it takes management and cooperation to run a successful society, not just competition.

Does it also take religion? Mormonism is explicitly Christian, which, hard as it is for an atheist to say, has contributed, on balance, a peace and compassion-oriented ethic or at least counter-weight to other social forces, over the last millennia. (As has Buddhism in its sphere, even more effectively.) Does strong social bonding require something beyond the Lockean contract, of a more spiritual nature? Does the civic religion of baseball, George Washington, and the Bill of Rights suffice to keep everyone in the US working on the common projects of e pluribus unum, or is a more comprehensive narrative required, of humans as embryonic gods, America as the promised land, and our lives in eternity built upon our diligence, faithfulness, and loving kindness in this life?

It is a difficult question when faced with the obvious social efficacy of bizarrely false and seemingly impractical doctrines- not to imagine that such doctrines are true, but to consider whether we as humans can be communally motivated, idealistic, and purpose-driven without them. We differ, some people being allergic to religious drama, and others being unfulfilled without it. Yet societies can not operate without some degree of fervor and common narrative, to clothe the brute competition that forms the base of natural and social existence, and emphasize more idealistic and cooperative ends. What we have on the national scene in the US is a fraying of this narrative, as the wealthy have pulled away, into their gated compounds and isolated social world, even while they control the political system and put anything resembling the public good on the back burner. The sclerosis and atomization are palpable. The Mormon church carried their narrative and communal principle to extremes, sorely testing the constitutional principle of separation of church and state, but also showing the effectiveness of communalism.

Turning back to the comparison with Islam, great communal projects, especially of a charitable nature, are hardly unknown in Islam, particularly during its golden age. But something about the traumatic collision with the West seems to have sapped the ability of the Islam to function as an effective governing philosophy or ideology. The impulse towards fundamentalism is sadly, and ironically, the opposite from what is needed, and is not just the province of a small extreme minority, but represents the leading direction in the world of Islam, from its twin leading sects / countries, Saudi Arabia and Iran. It took centuries for Judaism to adapt to the position of a minority religion during its diaspora, giving up its dreams of temporal (and Temple) power. Perhaps something similiar, (though hopefully less protracted, degrading, and traumatic), possibly coming from Muslim diaspora in Europe, the US or Indonesia, will be needed to burn off the bitter elements and steer Islam in a new direction.

  • Yes, ISIS is Islamic. Ultra-Islamic.
  • American misadventures in the Muslim world. Why so many bad choices and terrible allies?
  • More on comparative religions.
  • More somewhat aimless, yet apposite, discussion of "whence Islam".
  • Is ISIS fighting a strictly Sunni-Shia civil war, or something a little more ideological and theological? And just how broad is its support?
  • Taliban status report.
  • Our State Department defends crime and immorality.
  • Outstanding TED talk on the minds of animals.
  • David Eagleman's wonderful brain.
  • Honestly, if we are short of our inflation target, the solution is very simple.
  • Is Uber evil, or not so bad?
  • Wall Street votes Republican ... why does anyone else?
  • Some notes on Adam Smith.
  • Splitting hairs on printing money.
  • Indeed, dropping the gold standard and fiscal stimulus saved Japan from the depression.
  • While European policy has not done so.
  • Sanders Snippet of the Week:
"We have a system, which during the 1990s allowed Wall Street to spend $5 billion in lobbying and campaign contributions to get deregulated. Then, ten years later, after the greed, recklessness, and illegal behavior of Wall Street led to their collapse, it is a system which provided trillions in government aid to bail them out. Wall Street used their wealth and power to get Congress to do their bidding for deregulation and then, when their greed caused their collapse, they used their wealth and power to get Congress to bail them out."

Saturday, November 14, 2015

Babes in the Woods

Review of the film Restrepo, about US soldiers lost in Afghanistan.

Restrepo is perhaps the foremost cultural document of US involvement in Afghanistan, an documentary of platoon assigned to one of the hottest zones in the war. As film-making, it is very good, mixing post-action interviews and perspective with close footage embedded at the front. Restrepo is the name of an outpost in the Korengal valley of Kunar province some ways west of the Pakistani border, which this platoon founded and held against constant attack by the local population, Taliban, et al. The outpost and valley were later given up to the Taliban after further years of futility. (The film's sequel, named Korengal, is a sentimental pastiche of outtakes from the first effort.)

The men are exemplars of our armed forces; extremely young, immature, good-natured, and given enormous fire-power. They are shattered when a fellow soldier is killed, but kill their enemies with light-hearted glee. Their leader comes across as exemplary as well; disciplined, profane, and effective. Yet something seems sorely missing- knowledge about the social and political setting they have helicoptered into.

Much of the film is taken up with firefights, each side taking potshots at the other. The Taliban set occasional ambushes, but the US soldiers seem only to act as fire bait. They never seem to control the terrain. They set up key forts and mini-forts, and patrol on occasion. But the wider landscape is not theirs to control. Physically, the country is mountainous and thus favorable to guerrilla warfare rather than a mechanized army. And for all our space-based intel, it appears that knowing where the enemy is continues to be extremely challenging.

But the social landscape is even worse, completely incomprehensible to youngsters from the US. Sure, they have GPS, maps and doubtless all the intel our government can provide. But not knowing the local language is an enormous block. The soldiers are tongue-tied trying to relate to villagers through interpreters, hardly getting to first base, as it were, in the campaign for hearts and minds while they are busily tramping through the villager's homes and shooting up the countryside. Their lip service about projects and benefits for the villagers in return for cooperation could just as well have been spoken in Klingon.

Each village is manned by a skeleton crew of boys and ancient codgers. The women are sequestered, and all able-bodied men are off shooting at the Americans. Language barrier or not, the degree of possible cooperation could hardly be more clear. The film-makers don't investigate the local terrain either. They are fully embedded in that sense, not stepping beyond the wire of US control. Could they have clarified the degree to which, and reasons why, the local populace acceed to the terror of the devil they know over the foreign devil they had seen once before, in Soviet uniforms? Doubtful, I am sure, but the question virtually answers itself.

If the US were a traditional conquerer, this wouldn't make much difference. The Afghan men would be killed, the women sold off into slavery, and, as Rome did before us, we would call it peace. But we have renounced such wholesale terror and aim to behave by a higher moral code, as well as hoping to gain friends by practicing temperate and targeted warfare.

Were we even a traditional 20th century conquerer, we would have sent in far more more soldiers. The platoon of Restrepo is hopelessly out-gunned, despite their technical resources. If they had been welcomed as friends, a light footprint might have been sufficient. But at it was, near the border to Pakistan where the Taliban was comfortably ensconced as valued allies of the Pakistani government pursuing its bigoted war against all neighbors, in a rural region were the people are even more attached to their guns and religion (and control of their women) than they are in West Virginia, well, the welcome was not friendly at all. It was like being set down as a lonely platoon on the Ho Chi Minh trail and told to stop the traffic. In that case, as we now know, all the bombing in the world wasn't enough.

Our occupation of Europe after World War 2 succeeded largely because of cultural knowledge and affinity. We knew how to be friendly to a population utterly burned out by war, and even in Japan, we made friends in the wake of the nuclear bomb, due to Japan's strong Westernizing project that had been in motion for the preceeding near-century. In the Middle East, we seem to have very little cultural affinity. Islam is at the core of this, I think, as it combines a bigoted attitude towards infidels (and many forms of social and technical progress) with a lack of governing discipline that leads to endless free-lancing, militia formation, and romantic heroism. Why is government by a polygamous royal family in Saudi Arabia acceptable in the modern world, and accepted as the center and heart of the Islamic world? Yes, it resembles the feudal or even tribal orders of the past. But what kind of justification is that? When is the revolution in political theory and social justice going to happen in the Islamic world?

In Afghanistan, we started well ahead, as the population was not, on the whole, pro-Taliban. But social power is not always democratic, and in Afghanistan, it is a traditional and brutal competition between armed gangs, run by natural predators. Some youngsters from the US might have understood this, but not those in this man's army. Gang warfare is particlarly a matter of social knowledge, knowing were invisible lines are drawn, who is big, who is small, how far to push each person, and what each tag and sign signify. The soldiers of Restrepo are almost completely blind in this respect, which in combination with their other shortcomings made them rather unsuccessful.

But this was just a part of the larger policy. Where are we generally in Afghanistan? The country is slowly losing ground to the Taliban. The government is disorganized and corrupt. Without the US to prop it up and feed the maw of corruption, it is not really clear whether the central government is a going proposition. Which is somewhat odd for a culture so obsessed with morality and honor. Unfortunately honor is a very ambiguous sort of virtue, given to competitiveness and winning over all other considerations, causing suicide bombers to wear burkhas and the like. One may even take it as a cautionary tale for our own slow path towards hyper-competition and feudalism in the West.

After almost fifteen years of occupation / assistance, most Afghan's first allegiance still seems to be tribal rather than national. The cultural elite treat the national government as a part-time affair, good while someone else is paying the bills, but not essential to their power centers, which remain local, in the form of tribal structure, militias, local extortion rings, smuggling, and other pursuits that one might call organized crime. The police operate similarly, by bribery and abuse of citizens. We allied ourselves with the existing powers to get things done locally, while at the same time attempting to change the game nationally by setting up a veneer of democracy and modern bureaucracy in association with ostensibly friendly Afghans. It has been a confusing mess, as much to our own soldiers as to the Afghans whose hearts and minds we intended to change.

  • Now that the Taliban has it so good, it can have fights among rival gangs.
  • Evidently we have to get out of the Middle East because they really are nuts after all, and deserve their caliphate.
  • Why the US needs to police the world, and needs more than kids to do it. Some good, some not so good arguments.
  • On the other hand...
  • A Mormon insurgent politely asks for change.
  • What is going on in Asia and Japan, from a left perspective?
  • More about the robots and unemployment, using the horse analogy.
  • Decoding Republican love of small government.
  • Neural oscillations track both speech and music.
  • Image of the week- life expectancy across the US. The Red South needs better health care and lifestyle ... why are they so dead-set against it? Another aspect of feudalism.

Saturday, November 7, 2015

Where Did My Soul Go?

Exploring the neurocircuitry of loss-of-consciousness seizures.

While the question of a physical basis of consciousness is batted around by armchair philosophers, it is no light or abstract matter for people whose consciousness doesn't work as it should. From coma to narcolepsy, epilepsy and schizophrenia, there are many ways that consciousness can be disturbed for organic reasons (not even to mention pharmacologic and recreational interventions). One type of epilepsy, absence seizure, is a particularly interesting example, characterized by brief (10 seconds) loss of consciousness with no other symptom, typically. The subject just stares into space, or lets the current action such as speaking slow to a crawl. Memory of this time is absent, and the subject is not conscious. Then everything picks up again as though nothing had happened. It sort of resembles a reboot of a machine or computer.

Epilepsy, of which there are dozens of kinds, generally is a syndrome of electrical/chemical over-activity and over-synchrony somewhere in the brain. Our normal state is a chaotic noise from which a surface EEG captures occasional regularities. Consciousness seems to be the occasional and restricted synchrony of coalitions of neurons reaching the various areas which give it content, whether visual, abstract, tactile, etc. Probably also not just any neurons, but coalitions anchored in the cortical and thalamic areas that are most closely associated with loss of consciousness when they are injured. Beyond this, it is not yet possible to say just what consciousness is in physical, anatomical terms.

Yet there is a good deal known about the electrochemical circuits of epilepsy, which is one route to learning more about consciousness in general. Many patients have been helped by careful investigation of where their seizures begin, and intervening by either removing some portion of that brain tissue, or implanting electrodes that give corrective shocks continuously. In the case of absence seizures, which may be a particularly incisive and minimal disruption of consciousness, the driver seems to be a circuit between the cortex and thalamus.

The thalamus sits atop the midbrain and brainstem, and is the gateway to the cortex, relaying sensory information from outside and motor signals back downwards. In the sensory direction, this is an inter-active process. The cortex sends many connections back, at least in part to direct the spotlight of attention to selected inputs. The thalamus also plays central roles in sleep/wakefulness, as it is the source of the slow wave patterns of deep sleep, and damage to it can cause coma.

But sometimes the cortico-thalamic connections get too strong, and evolve into a positive feedback loop of ~ 3Hz waves that characterize the absence seizure. In susceptible persons, (it is a syndrome of children, typically), brief hyperventilation can cause it routinely. This suggests a possible connection with the sleep circuitry, related to the yawning, dizziness, and other effects of hyperventilation.

EEG waves during an absence seizure, which lasts from a few to 20 seconds.

Obviously, the brain circuitry has been difficult to figure out. Not only is the brain in general, and the human brain in particular, hard to experiment on, but the thalamus is especially central and hard to get to. The authors of a recent paper resort to computational modelling, based on the experimental work of others (and their own prior work). The idea is to get as much of the detailed knowledge into a model as possible, and then ask whether the seizures can be reproduced, and if so, what can be done about them.

The answer is that .. yes they can. The model below describes what is known generally about the network involved. It brings in another key anatomical site, the basal ganglia, which sit right next to the thalamus and conduct signals from the cortex to it, substantially increasing the complexity of the network.
Circuitry diagram of brain elements and connections involved in absence seizures, as used in the current paper's model. Glutamate connections are excitatory, while GABA connections are inhibitory.

One theme is that not all connections in the brain are excitatory, as though neuronal connections were simple wires. The red (glutamate neuro-transmitter) arrows represent activating connections, while the blue (GABA) arrows represent inhibitory connections. Just like in organizational management or artificial circuitry, the careful balancing of positive and negative feedback results in optimal control. Here, after constructing a ~40 parameter model containing everything known about the circuitry, the authors find that an unusual and recently-found inhibitory circuit that points from the basal ganglia (GPe, globus pallidus externa) directly back to the cortex might be critical for damping absence seizures.

Dialing up the inhibitory circuit voltage (-Vcp2) from the globus pallidus externa to the cortex, to a modest degree, reliably shuts down the firing rate (Øe) that is characteristic of absence seizures.

A further example of their data, (below), plotting (A, B) the voltage (Vse) from the thalamus (SRN, specific relay nuclei) to the cortex, versus the delay of action (tau in milliseconds) of the inhibitory circuit between the thalamus internal nuclei, TRN (thalamic reticular nucleus) and SRN. Extending the delay, or increasing the excitatory feedback voltage, moves the graph up and right, towards higher-firing states, as show in the lower individual graphs. The absence-seizure type of firing is in graph D, corresponding to the light blue area of graph A.

The absence seizure oscillation (SWD) happens in a sort of sweet spot of voltage applied between the thalamus (SRN) to the cortex. The vertical axis (tau) describes the lag characteristic of the inhibitory circuit between the TRN and SRN areas within the thalamus, which is also influential over the absence seizure oscillation.

While this kind of modelling is no substitute for empirical investigation, it is tremendously useful to advance scientific theorizing and speculation about the systems at hand. Systems about which our knowledge is increasingly complicated to the point that we may not be able to understand them without the help of computerized models that can keep track of a myriad of details and dynamics. In this case, the hypothesis might be, that if treatment is really necessary, an electrode placed into the basal ganglia / globus pallidus externae, to stimulate its inhibitory action with modest constant voltage, may be one way to go about it.

Saturday, October 31, 2015

Happiness is a Warm Gun

Rights, schmites. Gun fetishism is a psychological and social disorder.

It would be helpful in our gun debates if those opposing gun controls were named more accurately, not as "defenders of gun rights", or "staunch supporters of second amendment rights", and the like, but as gun fetishists. Reading their works makes it clear how intense their feelings are, and how unmoored from rational public policy, historical context, or constitutional history. Let alone from basic respect for human psychology. They are captivated by an heroic narrative of phallic power conferred by the gun, validating their social position, and enabling their defense, perhaps in a dramatic (not to say climactic) public showdown spraying bullets at dark miscreants, or as a last-ditch defense of the home bunker at the end times.

Unfortunately, while most people are responsible enough to carry that rather intense psychological valance without accident, and without cracking up, the idea that everyone is, and that we would be better off with free-flowing guns for the whole population, is empirically false, and thus a dangerous fantasy. Ironically, one gun blog that I read keeps harping on the idiocy of police gun usage. They use bad muzzle discipline. They barge in on the wrong houses. They shoot the wrong people. They try to hide behind procedure and the blue line. No kidding. But how is this an argument that we can trust the average gun-owning Joe to have better, more disciplined behavior? This line of argument also betrays the anti-state insurrectionism at the core of the gun fetishist's concerns. Which is quite ironic and in direct contradiction to the second amendment's historical roots which support a democratic, local, state, which is of course, what the well-regulated militia serves, and what does the regulation.

Rights are not natural, god-given, or inherent. They are political conventions; gifts we give each other to make society work smoothly and afford maximal happiness. The Bill of Rights had to be written down precisely because the rights it enumerated were not natural or inevitable. They were developed over the preceeding centuries in the English and Colonial traditions as ideals and social accommodations. The first amendment is exemplary, embodying the enlightenment lesson that established religions were good neither for the state nor for religion, and tended to foster civil war and corruption.

The second amendment is likewise an historical fossil, though far less relevant to us today than the first amendment. It specifically predicates the right to have guns on the need for a well-ordered militia. Today, we have well-ordered militias, but they are not based on citizen enrollment, let alone on the conscription of personal arms, but on an entirely different principle of professional enlistment and civilian / republican oversight and command. The broader right to keep arms was certainly cherished in the Colonies, as it still is in rural areas of the US that have a light police footprint and plenty of animals to shoot. But the second amendment doesn't address that convention. It is predicated on the specific historical situation the colonists found themselves in, where Britain tried to disarm a populace that was violently hostile to its imposed, foreign, rule. A populace that was happy with its existing local institutions of government.

The idea that guns in the hands of the populace are essential to fending off tyranny should have died with the civil war. No matter how many guns the South had in private hands, they were no match for a full military confrontation. Whatever one's view of the war's conclusion, whether the imposition of tyranny or a righteous victory, private guns made no difference. In the Wild West of the ensuing epoch, the prevalence of guns was not generally a boon to public peace and civil society, and many frontier towns made gun control one of their first orders of business. It would be truly ironic if in deference to people with significant mental health issues, we forgot this common sense legacy and went back to an open or concealed-carry gun free-for-all in the US.

For the focus of the NRA and the gun fetishists in general is frankly pathological. At the drop of a hat, they resort to phenomenal hyperbole, (Over my dead body! From my cold, dead hands!). They shriek about totalitariansm and god's commandment to defend their families from evil. They abominate the "gun grabbers" who would castrate them. So they stockpile guns in a never-enough compensation for whatever else ails them. Power is hard to come by, and it is inexorably ebbing away from the white male god-fearing class. No wonder that the Obama presidency has seen such vitriol and extremism coming from this political class, to its own detriment, really.

What to do about it? The first step would be to call this spade what it is. Not some reasonable, British-empire-resisting group with balanced public policy arguments. Not upholders of ancient and inalienable rights. But people with a screw loose: fetishists for a phallocentric symbol of a political order which is not going to come any closer when Hillary Clinton becomes president.

Speaking practically, is there a place for guns at all? Sure- in hunting, (as personally appalling as that is as some kind of "sport", and however poisonous in its use of lead), in self-protection in rural areas, and in simple collecting and possession. Guns should not be prohibited. But they should be allowed under very stringent conditions, in view of their extreme psychological valence and demonstrated harmfulness. Handguns, for instance, have no use outside of killing people, which makes the fact that there are over 100 million of them in the US somewhat alarming. Owners should be fully registered, and should have to take yearly refresher courses in safety and handling, have a safe to keep them in, legal liability for their control, and a continuously clean criminal and mental health record. There should be no open carry other than for uniformed officers, (or hunting in rural areas), and concealed carry only for specific needs approved and documented on the registration.

Sensible gun control would not get rid of all guns. Yet it is obviously effective in countries (i.e. every developed country other than the US) where it is public policy. While it is perhaps impolite to cast psychological aspersions on our gun nuts, they have brought it on themselves with the antics of the NRA and the broader gun-show, gun-crazy video game, gun-crazy Hollywood movie culture we have to deal with. Such raw, potent, fondle-able power is undeniably attractive, but it also corrupts. Guns keep corrupting impressionable (typically male) minds in very damaging ways, and we really can do better against this menace.

  • A little history of English gun laws, militias, etc.
  • WSJ: Guns are already so bad and so prevalent, that we can't do anything about them. Win!
  • Religious people think it is a spiritual issue.
  • True gun nuts hate the GOP.
  • Just how expensive is free speech? Too expensive for you, that's for sure.
  • Better banking for the poor.
  • Yes to carbon pricing / taxing.
  • The military can't do it alone in foreign policy, needless to say. One-year attention spans lead to endless conflict.
  • A visit to the creation museum.
  • Bill Gates: "Since World War II, U.S.-government R&D has defined the state of the art in almost every area."
  • State subsidies go to big companies.
  • Markets reward lying ... how could we have known?
  • Progress in statistics.
  • But no progress in economics. WSJ Nobel laureates still dare not speak the words "low aggregate demand", but prefer to blame the Fed for low interest rates, and low interest rates for low corporate borrowing and investment. As though borrowers would borrow more at higher rates.

Saturday, October 24, 2015

With a Little Help From My Chaperones

Ribosomes need hundreds of helper proteins during construction.

One of the premier machines of molecular biology is the ribosome. It weighs in at about 3 million daltons, or hydrogen atom-equivalents, and has a huge catalytic core of RNA surrounded by 79 proteins. Due to its ancient origin, mixed composition, and large size, it is also very complicated to produce, yet needs to be made in prodigious amounts. Its manufacture begins in its own organelle, the nucleosome, which is a small compartment within the nucleus where the many copies of genomic DNA that encode ribosomal RNAs get transcribed. Countless events happen thereafter, chemically modifying the RNA, adding proteins, chemically modifying them with various phosphate, acetyl, and methyl groups, and transporting the nascent ribosomal halves out of the nucleus to the cytoplasm. One irony is that the proteins added to the ribosome are all synthesized (by pre-existing ribosomes, naturally) in the cytoplasm and thus have to be transported into the nucleus individually before being re-exported as part of the assembled ribosome halves.

While most proteins and RNAs fold themselves and assemble naturally, based solely on their sequences / composition, the bigger they are and the bigger the complexes they participate in, the more help they tend to need from special proteins called chaperones. The ribosomal RNA uses 76 helper snoRNAs to get itself folded and modified correctly. For assisting the folding of proteins, there are two classes of helpers, general chaperones which help proteins fold by exposing them alternately to hydrophobic and hydrophilic surfaces, and specific chaperones that bind to one or a few target proteins, typically right as they come off the ribosome production line, to prevent them from aggregating with the wrong crowd, and to transport them to the right place for assembly. Assistance for ribosomal RNA folding may have been the original function of some ribosomal proteins which are now essential for function and permanent parts of the mature structure. But now the ribosomal proteins themselves need chaperones, to the tune of about 200, for proper assembly.

A recent paper discussed an example of a specific ribosomal chaperone, Acl4, which ferries the ribosomal protein Rpl4 to its mark. Rpl4 is an average-sized protein, about 50,000 daltons, but its structure is remarkably splayed-out, rather than compact. When assembled, part of its structure reaches into the exit tunnel of the ribosome, where newly synthesized protein chains come out, and seems to help them stay in the straight and narrow, especially hydrophobic segments that would be tempted to stick to themselves or other proteins, clogging the tunnel.
Structure of Rpl4. The blue part sticks into the protein chain exit tunnel, and is evolutionarily conserved, while the red part reads over the surface of the ribosome, touching several other ribosomal proteins, with unknown function.

Position of Rpl4 (red) on the ribosomal large subunit. PTC labels the peptide transferase center, or synthetic core of the ribosome, and the emerging amino acids chained into a protein are black circles. The hydrophobic knee of the nascent protein tunnel is where the key segment of Rpl4 (4) has a role, along with some other ribosomal proteins (17, 39).

But this ability to manage hydrophobic protein segments implies that Rpl4 is itself, in that region, hydrophobic, and thus prone to aggegation. This is in addition to the rest of the structure, which reaches across several other proteins on the ribosomal surface, in snake-like fashion. While researchers know that this latter structure is essential, they do not know yet what it does. This intriguing protein clearly needs help in assembly. The researchers hypothesized such a chaperone helper, and went out to find it using a tagged version of RPL4 with which they could easily co-purify whatever stuck to it, including several of its ribosomal protein colleagues. But there was one more protein, called Acl4. Unfortunately, the researchers didn't come up with this name themselves, but were scooped by others who published similar data only a few months before. So it goes.

Using a series of engineered deletions of the Rpl4 protein, the researchers show that Acl4 binds over the key hydrophobic area of Rpl4, as one would expect. They additionally show that Acl4 binds to Rpl4 even before it is fully synthesized, also as one would expect for a specialized protein chaperone. In yeast cells, neither protein is actually essential. Strains with either or both genes deleted still live, though grow very slowly. They would never survive in the wild.

Knowing the nuts and bolts of how our biological molecules operate, particularly the extraordinary lengths evolution has gone to fix and fine-tune systems that must have been functional enough in their much simpler, early incarnations, fosters an appreciation of the messiness of the molecular world. Sometimes huge size and complexity is a product of endless jury-rigging, not of exquisite design.

Drama of ribosomal synthesis, for a few actors. Rpl4 (green) is synthesized in the cytoplasm, and captured by Acl4 (purple). Then both transport to the nucleus, where they dock to the assembling ribosome, which is then in due time transported back out to its final destination. Acl4 cycles back by itself for another load. A minor pathway also exists in the absence of enough Acl4, where a generic nuclear transport conductor, importin, can bring Rpl4 into the nucleus, since Rpl4 contains the necessary targeting signals in its sequence.

  • Investment is better than saving.
  • "...  if the corruption persisted, the Taliban would win, no matter how many American troops joined the fight."
  • Mice stutter too.
  • Are we really that bad? And if so, is the answer to self-destruct? "If Western governments desired to reduce the number of people trying to find safety in Europe, and the suffering that results from such attempts, they would refrain from invading other countries, from impoverishing their peoples, from providing arms to repressive regimes that collaborate with the West, from requiring neoliberal policies that create inequality and poverty, and from destroying the world by their consumption of fossil fuels."
  • Krugman on Japan's timidity trap ... it needs 4% inflation, with all available tools.
  • Gun nuts packing purple prose: "I have seen many homeschoolers on the trail with parents, reading literature and learning real American history, when men were free, rather than the fabricated crap and lies they learn in public schools that passes for history, taught by the collectivist lemmings."
  • Nuns in a pickle.
  • Annals of feudalism: Hey, let's make worker's comp optional!
  • And then off-load the cost to the taxpayer.
  • Up from poverty, around the world.
  • Up from draught.. by ending traditional water rights.