Saturday, December 27, 2014

A Spear-chucking Bacterium

Vibrio Cholerae impales its victims with a metal-tipped, poisoned, rifled, spear.

Life is tough all over, but particularly bad for microbes. Without a glimmer of consciousness, and with hardly any tools at hand, (or hands), they still struggle, suffer, and die in astronomical numbers. One of the more fascinating and classic areas of discovery in the field is the beauty and complexity of the T4 phage, which is a virus that infects bacteria like E. coli. It has a lunar-lander like structure that docks to its victim and injects the DNA (from a highly pressurized head chamber) which then kills it while producing hundreds of new viruses.

But it is only in recent years that a connection has been drawn between this phage injection mechanism and what bacteria do to each other. What has been sedately called the type VI bacterial secretion system, used by Vibrio cholerae and Pseudomonas aeruginosa, among many other species of bacteria, turns out to actually be a violent spearing mechanism they use to kill competing bacteria and also mammalian host cells during an infection.

Model of the spearing system, on right, compared with the T4 viral system on left. The spear is in purple, while the contractile sheath is in green, and the base is yellow. In later experiments (in movie, etc.) the sheath is tagged with a fluorescent protein (GFP), allowing it to be easily visualized in the light microscope.

This was recently described in an NIH talk by John Mekalanos, and also in various publications from his group. One representative film clip is linked below.

Still from movie of the Vibrio spear in action, link here.

One of the more remarkable aspects of this mechanism is its scale. Sausage-shaped bacteria typically are closest to each other at the side, so the apparatus begins assembling at the side of the Vibrio cell. This injector assembles clear across the interior of the cell, forming a thin thread almost 500nm long which has, in addition to the base plate that nucleates the process, an inside spear and an outside sheath.

Electron micrograph of a poised spear assembly in a Vibrio cell. Note the extraordinary length, of about 500 nm. The scale bar is 100nm. T6SS is type six secretion system, IM is inner membrane, and OM is outer membrane. Note the detail of the basal body at the top spanning both membranes.

The outside sheath is spring-loaded, and when triggered (how that happens is unknown) winds down in a matter of milliseconds to half its original length, thrusting out the spear, while also turning it like a drill. In his talk, Mekalanos showed that the spear is tipped by a pointed protein his lab had recently discovered, that contains a zinc-coordinated domain that gives it particular stability. Behind the tip, the spear also is festooned with a variety of toxins, because simply spearing a nearby cell is not enough to kill it. Vibrio injects both eukaryotic-directed toxins such as one that cross-links actin and thus paralyzes the cell and another that modifies the cAMP signalling system causing massive ion and water efflux, as well as several bacterial-directed toxins to clean out the competition, such as inhibitors of cell wall (peptidoglycan) synthesis.

Sample killing, where Vibrio (red) were mixed with Pseudomomas (green) cells. The spearing system sheath is labeled in red and green respectively. In each horizontal set of time lapse images, a spear from a Pseudomonas cell (green) impales a neighboring Vibrio cell and either causes it to swell locally or to lyse entirely, losing its optical contrast (arrows).

An interesting wrinkle in the story is that each bacterium that has this kind of system also has a complement of immunity proteins that neutralize the various toxins that it creates. The bacteria are not terribly bright, and live in close proximity, so they frequently spear each other. One wouldn't want that kind of thing to be fatal. But Vibrio doesn't need immunity from the eukaryotic-specific toxins, which do not affect bacteria, including itself.

Once the spear is thrown, another protein comes along to quickly disassemble the spent apparatus, and another one re-assembles from a new base plate somewhere else inside the bacterium. Quite a bit more is waiting to be learned here, like the triggering mechanisms, and the details of assembly, but not only is this knowledge helpful in addressing a significant pathogen, (though one we hope to not meet in the developed world), but it is an example of the breathtaking complexity, and even beauty, in biology, even in the midst of the most desperate dramas.


Notes in passing:
  • NBA may exit feudal world, go socialist.
  • Bird speech and human speech.. not so different, perhaps.
  • Am I giving philosophy a bad rap, for being a home for insurgent theists?
  • Free market short-term-ism and self-immolation, cont.
  • $721 million in mid-term political funding came from fossil fuels. Thanks!
  • Not just an increase in the minimum wage, but in overtime coverage as well.
  • Religion as psychotherapy, cont. Some people need answers really, really badly.
  • Bill Mitchell on Japan: "Let it be noted that the Japanese government 10-year bond yield hit 0.33 per cent overnight. That tells you that all the scaremongering that has been going on over the last twenty years about hyperinflation, the Japanese government running out of money, the bond markets dumping the yen, and the rest of it were self-serving lies designed to advance a particular ideological position at the expense of the broader social well-being."

Saturday, December 20, 2014

Governance in Venice

Good governance gave Venice a thousand years of prosperity and renown.

The idea that the US is the oldest democracy in the world is far from the truth. Even if you qualify it as  "existing" or "continuously existing", the Swiss have one far older, (making allowances for a brief Napoleonic regime), as do the Icelanders. But more important is that forms of government are very plastic. What we call a democracy in the US is a far cry from actual self-rule, given the vastly greater influence of the moneyed classes and the advertising arts over who gets elected, than anyone in the demos. Oligarchy would be more like it. Republic it may be, but democracy it is not.

But oligarchies aren't all bad. Just think of the Catholic church, which has functioned continuously (give or take a few anti-popes) for about a thousand years, and with less historical certainty for another thousand back to the time of the first bishops of Rome. Its organizational stability has been impressive, even as it has gone through vast changes in theology, morals, and power.

Venice in its heyday was a somewhat similar republic / oligarchy, and an extremely well-ruled one. A wonderful history of Venice tells a story that I had never learned in school, of the long and proud reign of Venice over a commercial empire that grew across the Eastern Mediterranean and beyond. From its extremely humble origins in the 568 in a malarial lagoon, Venice developed a communal government as well as an adavanced (and state-run) ship manufacturing system which, combined with skillful seamanship, diplomacy, a dedication to business, and occasional military prowess, earned her a durable mercantile empire. This was centered on the India trade, which ran through several routes, such as the silk road, the Byzantine ports, and the Arab caravans. Venice was the home of the Polo family, which famously followed these routes to the ends of the earth.

Symbol of Venice, the winged lion of St. Mark.

In 1204, its power was such that, as a particularly horrific and misguided part of the fourth Crusade, Venice led her allies to attack and sack Constantinople, a theretofore unimaginable feat, given the reputation of its walls and military. This was, for the Eastern Empire, a disaster it never recovered from, after which it limped along till its final defeat under the scimitars of the Turks in 1453. Venice, too, was eventually boxed in by the Ottomans, who in their own prime ran a highly capable fleet and threatened Venice in the Adriatic and even its own lagoon, while relieving it of its Greek and other far-flung possessions.

What finally sent Venice into decline (well before being crushed by Napoleon and then assimilated into the modern state of Italy) was the Northern European revolution in navigation and trade, as the Portugese and then Dutch overtook the India trade directly by way of the horn of Africa. Thereafter, Venice became poorer, and more embroiled on its landward side with the complexities of Italian feudal feuds, including with various Popes.

Through it all, Venice had a remarkable system of government. "Byzantine" doesn't do it justice, as there were ten layers of elections to go through among various bodies before the supreme leader, the Doge (a variant of "Duke"), was elected. Each Doge was constitutionally restricted in his scope of independent action, and also given a specific document of restrictions, usually the fruit of past excesses or corruptions that the community had learned from. The civil service was very efficient, and many times over her history, when Venice found herself in a tight spot, she put out the call for various special taxes, donations, and forced loans, which were typically met with great generosity. Each Doge set an example by distributing vast amounts of his own wealth when elected, and many followed that up with other gifts to the city during their rule and in their bequests. The degree of civic committment at all levels is striking, especially in this day when some parties cry about the most infinitesimal increment of taxation.

At the base of the state was the Grand Council, whose membership of about 1500 was originally elected among the population at large, but by 1296 became hereditary to the Venetian nobility, i.e. the rich. Thereafter, new families were allowed in very sporadically, when the state was under stress, and for large payments, but generally, membership was tightly closed and formed the core of the oligarchy, and the voting base insofar as it was a republic. Various more select bodies such as the ministers to the Doge, the Senate, (sixty members), Zonta (sixty more members), and Venice's own Inquisition / Star chamber / NSC- the Council of Ten- were chosen from this Great Council.

One might note that the early Roman republican system was hardly less complex, and also led to hundreds of years of good, if, again relatively oligarchical, government. Universal sufferage was extremely uncommon in large bodies before modern times, partly for technical and ideological reasons, but also because universal education was equally uncommon. But given an oligarchy, the complexity of these great examples such as Venice seem to reflect relatively little cost, and provide an extensive filter of checks and balances that so frequently succeeded in putting the best people in charge.

The effect of this good governance was to provide durable prosperity and promote human values, even in the midst of terrible times, such as several severe bouts of the plague. Its commitment to great art and architecture was legendary. And while Venice was not an intellectual leader in the Renaissance, its enthusiastic and free printing establishments were the largest in Italy and played a central role in transmitting knowledge from the Byzantine archives to the scholars of Europe. In time of our own when political ideologues dream of drowing their own governments in bathtubs, and refuse to govern countries they themselves have conquered, it is important to remember what a blessing (and a lesson) good government is.

"The more one studies the domestic history of Venice, the more inescapable does the conclusion become: by whatever political standards she is judged, she compares favorably with any nation in Christendom- except, arguably, in the days of her final dotage. Nowhere did men live more happily, nowhere did they enjoy more freedom from fear. The Venetians were fortunate indeed. Disenfranchised they might be; they were never downtrodden. Although, being human, they might occasionally complain of their government, not once in all their history did they ever rise up against it; such few attempts as there were at rebellion were inspired by discontented nobles, never by the populace." 
"Alone of all the states of Catholic Europe, it had never burnt a heretic."

  • We need a war on cars.
  • "Christians more supportive of torture than non-religious Americans."
  • Still some problems in the intersection of race and genetics.
  • Investing vs disinvesting, in our environment, in ourselves.
  • Just how hosed is the middle class in the US? Part 1.
  • Does Obama gain anything by caving to cave dwellers?
  • Bill Black #2: Appeals court says insider trading is OK.
  • Sony lets the terrorists win.
  • Death and youth.
The American dream comes true.

Saturday, December 13, 2014

With Shifafa on the Side

Poetry in America is OK.

The state of formal poetry is rather grim these days. Poet laureates are named, nationally and at other levels, and are then mostly ignored. Books of poetry are indigestable, and progressive forms are militantly unreadable. The New Yorker and other magazines gamely continue to publish poems, but to me, it seems a vain pursuit. It is a sad tale of a vibrant form in the humanities being academi-sized, perhaps like philosophy and economics, to irrelevance. But perhaps there is more going on.

Some fields do extremely well in academia, particularly the hard sciences. But the softer the field, the less it can be transmitted by formal methods, and perhaps the more it is killed rather than nurtured by the conformity, the drive to explicit formulations, the competitiveness, the prosody of the logos.

Poetry, however, is doing fine outside of formal institutions. It lives as always most happily with its musical muse. And that great American art form, jazz, is one of its finer incarnations, with word play aplenty. An example is "The Frim Fram Sauce", a standard from the Nat King Cole era.

I don't want french fried potatoes,
Red ripe tomatoes,
I'm never satisfied.
I want the frim fram sauce with the ausen fay
With shafafa on the side. 
I don't want pork chops and bacon,
That won't awaken
My appetite inside.
I want the frim fram sauce with the ausen fay
With chafafa on the side. 
A fella really got to eat
And a fella should eat right.
Five will get you ten
I'm gonna feed myself right tonight. 
I don't want fish cakes and rye bread,
You heard what I said.
Waiter, please serve mine fried
I want the frim fram sauce with the ausen fay
With shafafa on the side. 
A fella really got to eat
And a fella should eat right.
Five will get you ten
I'm gonna feed myself right tonight. 
I don't want fish cakes and rye bread,
You heard what I said.
Waiter, please serve mine fried
I want the frim fram sauce with the ausen fay
With shafafa on the side. 
(now if you don't have it, just bring me a check for the water!)
- Redd Evans

Some singers (Diana Krall, I'm looking at you!) leave out the concluding line, i.e. the punchline, leaving the audience mystified. And then she has the audacity to intimate that it is all sexual inuendo! Anyhow, the song is a great example of poetry that looks pretty dry on the page coming alive with music, since as sung, it is smart, melifluous wordplay.

Perhaps poetry is not meant to be dry, to be subject to "readings", with apologies to Shakespeare. Country artists are another class of homegrown poets who know how to make a line sing.

No, we're not the jet set
We're the old Chevrolet set
Our steak and martinis
Is draft beer with wieners. 
-George Jones

  • Ten commandments, modernized version.
  • "However, Pakistan has a history of releasing jihadists who seek to destroy the Pakistani state if the government feels it will further its goals of destabilizing Afghanistan or India."
  • Obamacare is doing just fine.
  • Minimum wage increases are paid by customers, not through unemployment.

Saturday, December 6, 2014

Measures of Consciousness

Can EEG be used to tell whether someone is conscious, and to what degree?

The remarkable discovery that some people with no outward sign of consciousness are still, within, quite conscious indeed, has been both sobering and a spur to better ways to detect consciousness directly. The orginal studies used fMRI, which is extremely laborious and expensive. Far cheaper would be to be able to tell a patient's state from an EEG, i.e. reading their brain waves from electrodes on the scalp. A recent study attempted to do that, using a high density array of 96 electrodes.

Patients with disorders of consciousness come in many kinds. From the EEG perspective, one is tempted to say that all happy brains are alike; every unhappy brain is unhappy in its own way. But the very unhappy ones are put in two classes these days, those in a vegetative state, and those in a minimally conscious state, which is significantly better, particularly with the ability to follow action with the eyes, or some similar ability to react to the surroundings, at least sporadically.

The researchers used high density EEG recordings, ten minutes long, from 26 normal people, 13 in a vegetative state, and 19 in a minimally conscious state. This status was evaluated according to a standard checklist of tests, called CRS-R. The hunt was to develop some kind of algorithm out of the large amount of EEG data that would reliably classify their patients, using the CRS-R tool as a standard of comparison. One would assume that if these researchers are successful, they could go on to run blinded trials to validate their  EEG analysis for clinical use, but it didn't sound like they got that far.

Brain wave power vs frequency, for human controls, those with minimal consciousness (MCS), and those in a vegetative state (VS).

There are dramatic differences, though, between the subjects. A summary of their brain wave power vs frequency (above) shows that the alpha band has a strong peak in normal people, which is utterly missing in those who are impaired. Conversely, patients with disorders of consciousness (DoC) had much higher delta band power. As discussed in a recent post, alpha waves are a sign of consciousness, but not really of active thought, rather they characterize an alert, relaxed state, especially in the visual cortex, ready to process data, but not actively processing. Theta and delta bands are more common in sleep and coma. One might surmise that they have something to do with healing and regeneration, which fits with this current data. The graphs also show raised gamma wave power in those with impaired consciousness, which the authors interpret as an incidental phenomenon due to involuntary muscle movement that causes electromyographic noise, i.e. electrical activity from muscles, not from brain waves.

But is there a quantifiable test to be made out of this? While there are significant differences in the wave pattern, it is merely statistically detectable, not an absolute, every-time kind of distinction.

Connectivity metrics among EEG electrodes, clustered into color-sets. Note long-range and strong connectivity in delta band of VS patients, theta band of MCS patients, and alpha band of controls. 

The researchers also provide more detailed maps of connecting / correlating activity among their electrodes, which makes interesting viewing. Note here again that the most active and longest-range connections are in the alpha waves in the control group, the theta waves in the MCS group, and the delta waves in the VS group. They point out that not only strength, but also the distance of interaction is a significant metric. The VS group shows mostly localized connections in the alpha waves, for instance.

Comparison of EEG node connectivity computed for three patients in a vegetative state,  after being asked to imagine themselves playing tennis. Patient P3 is clearly following along. Colors come from an arbitrary clustering algorithm that groups more-connected nodes.

They even go on to reproduce the "locked-in" patient test, asking patients to imagine playing tennis. As shown, two of the three patients show quite disorganized patterns in the alpha waves, while the third had dramatically long-distance and strong wave action. The third patient was classed as being in a vegetative state, but scored highly on all the EEG metrics that this group used, and thus appears to be a case that is more accurately diagnosed by newer methods of EEG or fMRI than by the standard CRS-R diagnostic checklist. Indeed, this patient appears to be a locked-in candidate, but the researchers note that in other brain wave frequencies, this patient looked more impaired, and say little more about her or him.
"In particular, though these prominent differences between the brain networks of P1 and P3 could perhaps be attributed to aetiology, it could not explain away the differences between P2 and P3, as both had suffered traumatic brain injury. It is also interesting to note that though P3's alpha network properties were clearly very prominent outliers as compared to P1 and P2, delta and alpha power in P3 were much less exceptional. Hence characterising network signatures of spectral connectivity could considerably improve our understanding of residual brain function in behaviourally uncommunicative patients who nevertheless demonstrate covert awareness."

The researchers go on to analyze their data in various ways, but while very interesting, none looks like a slam-dunk for telling the classes of patients apart in definitive fashion, quite yet. Such methods are sure to arrive at some point, however, as better tools are developed, and now that we know how much can be hidden behind the facade of immobility after traumatic brain injury.

  • Finance is pretty much all bad.
  • The Ferguson prosecutor played defense attorney, not prosecutor. And the grand jury played regular court jury, not grand jury. Police deserve some leeway in this respect, but then there should be an alternate form of review, like a civilian oversight board that would fire a policeman and could ban them from future police work after a culpable or unnecessary killing.
  • An industry of fear and hate.
  • Oh, those nasty atheists!
  • A small hate problem at the fringes.
  • The American dream is now dead. And would be dead-er if people knew what is going on.
  • You will never guess who is the mastermind behind the global warming hoax.
  • Antarctica is melting.
  • Cruise ships? You don't want to go there.
  • Krugman- just who is stupid?
  • TNR in throes of death.
  • Destruction of the state as normal policy.
  • History of capitalism, another iteration of feudalism, colonialism, etc.

Saturday, November 29, 2014

Comparing Pontificating Paradigms

When vastly different theological paradigms are in play, simplicity and other reasoned criteria typically do not decide between them.

Arguments about theism are classics of Kuhnian paradigms. Each side has a completely different view of the world (taking atheism vs progressive theism as the pattern). The views are so different that people are reduced to vague formulations like "it makes everything else make sense" and the like. In the words of C. S. Lewis, "I believe in Christianity as I believe that the sun has risen: not only because I see it, but because by it I see everything else." Theism, at any rate, is not a logical deduction from observed phenomena, (as it used to be in Anselm's day), but a speculation about the unknown- unknown souls, unknown life after death, and the unknown god. All strongly felt, but not known. God is forever in the gaps of knowledge, not in what the atheist would call secure knowledge- that which has been nailed down about reality in empirical and / or logical terms.

Non-theists stick to what is known, but in their own way also assume a great deal- that the brain-mind connection is not what is called "supernatural", and that whatever that connections is can be understood, someday, through the normal course of scientific endeavor. And that any god worth the name would make itself far more manifest than has been the case in the past, and certainly is now. And lastly, that the whole theological edifice is far more efficiently explained by our rich psychological archetypes, weaknesses, and hopes than it is by its mystical discernment of an entirely alternate reality. These assumptions do not credit theists and theology with any special knowledge or modes of knowing, but rather assume that everyone has largely the same perceptions and immediate reality, though they may make of them quite different inferred realities.

Which model is more in accord with the real reality? Which is more humble- that is another intruiguing one. Is there an actual reality out there separate from what we make of it ... that is yet another one, in a more postmodern / Platonic vein.

As vastly different models of reality, they can also be called paradigms. Kuhn told us that communication between strongly contrasting paradigms can be extremely difficult, since the concepts, and even the language used, have meanings that depend on the edifices of their own respective paradigms and communities. They are non-commensurate. This is especially true for beliefs that are acknowledged to come by non-scientific means; by faith, by mystical deliverance, by community engagement, by one's "gut".

Occam's razor tells us to go with the simplest explanation, all else being equal. And that certainly would be theism. God is the answer for everything that we do not know, and much that we do. Why does lightning strike? That used to be (a) god's job, but is now generally regarded as not supernatural at all. Why does evolution happen? Even those who agree with natural selection and Darwinian evolution in general often, if they are theists to start with, see a hand of god in the mix, perhaps pushing sub-atomic particles around just so, weighing the scales in some way we can't see and certainly couldn't reconstruct historically, to make that all-important creature, us.

It is a very winning simplicity, sweeping all our questions, especially the most important ones, under a totemic rug, while reluctantly recognizing the mechanisms that scientific thought has constructed for whatever has been rigorously explained. That is, if you are a progressive religious person, rather than a fundmantalist home-schooler barring the doors & windows against a much wider gamut of profane knowledge. But how far does progressive theology go? To remain theology, it can never go "too far". It can not empty god out of the world completely. While the whole point of evolution is that it is a mechanistic process, blind and brainless, and therefore explanatory of biological change, that is anathema to theology, however tepid. So at least we humans must have been granted some kind of grace ... some special relationship with god that sponsors our moral nature, even if it did not meddle with our physical evolution. Or something like that.

Then there is psychology. Are we beset by various biases and defects that impair our reasoning and tend to lend more credence to supernatural theories than they are due? Do we have an intense need for social hierarchy and father figures that we map onto an imaginary cosmos? Or are we blessed with a sort of sixth sense, by which god approaches us, perhaps in dreams, or in quiet moments of meditation, or in the rousing community of worship? Religious people make a great deal of "discernment", which usually means a very non-scientific feeling of a god existing, inherent in the world, and also relating somehow to us personally. This helps to construct non-believers as *blind, and also construct religious group leaders as somehow gifted with special abilities or relations with the divine. As Tanya Luhrman demonstrates so well, (as William James before her), this discernment is most clearly a sign of imagination, or considerable mental self-management, but not necessarily something that a skeptic is obliged to credit as discernment of something real.

The very immensity of speculation required in religious belief constitutes another psychological factor, as it can be a method that draws forth commitment and social bonding. The greater the unbelievability of a doctrine, the more isolated its believers, the more they depend on each other, and the greater the psychological barrier to entry and to exit. Atheists are notoriously unable to form communities, perhaps because their beliefs, at least in the religious sphere, are rather modest and skeptical. Believing in a lack of life after death, in a lack of priestly charisma, a lack of divine sanction for their endeavors, etc. is not calculated to create great devotion. Truly it is curious how real riches, such as wealth and health, have so much less purchase on our psychology of personal meaning than do the highly speculative riches of the hereafter and the invisible.

But broaching the subject of psychological explanation for religion is highly offensive to those in the paradigm. "Are you calling us nuts? Or stupid? Is this the first step to locking us up?" and so forth. And are atheists immune from psychological biases? To judge from the internet comment traffic, that is not the case, though the biases at work do seem different. Richard Dawkins has not yet been canonized or described as divine.

Obviously, simplicity is not the entire standard of paradigm comparison. Simplicity purchased at the cost of deep explanation, indeed of the very motivation to approach the mysteries of reality in analytical fashion, may not be (philosophically) superior to complexity, or even to ignorance. In any case, the test is not internal to the paradigm, but in its correspondence to reality, in some empirical sense. If all those correspondences are, in the face of a god who resolutely remains hidden from clear view, fobbed off to mystical senses or speculations about what must have ultimately caused the universe and ourselves to appear, then all the clarity and simplicity can't make up for explanatory weakness.

It goes without saying that what one wants out of a paradigm does not serve to make it more or less true. Whether theism makes us more moral, or whether contrariwise it makes us kill each other, doesn't speak to its truth or falsity. Indeed, the personal attractiveness and psychological tenacity of religion can be taken as an argument against its truthfulness. Except, of course, if one resides within a theistic paradigm, in which case god made us religiously inclined and mystically receptive, in a wonderful, if somewhat fuzzy, circle of logical causation.

Nor does arrogance or humility really decide the question. Each paradigm thinks itself nobly humble and its adversary perversely arrogant. Believers bow before god and seek to obey (or at least understand) "His" teachings and dictates, while viewing atheists as believing themselves to be god, and having no god-given, objective morals into the bargain- a lost and dangerous tribe. Conversely, atheists suspect theists of making it all up anyhow, thus conjuring around the back door the laws and deities that they so conspicuously bow to in front of the temple, all demonstrated by the appalling failures of the theist's own social institutions. Which are, under this view, incredibly arrogant, fraudulently leading their people to believe they are communing with the creator of the universe, who cares whether they win the next bingo game. Or the next war.

The consideration of these radically different, yet each widely believed, paradigms is the first step of theology. Before one can make suppositions about what this god wants, or what our meaning is as humans, or what moral consequences we think derive from it all, we need to situate ourselves in a model of reality, either supernatural or not. As an atheist, I think the choice is clear, that inferring so much as a premise, and in such imaginative fashion, however attractive and justified on traditional, moral, or hopeful grounds, is no way to begin one's philosophy. It is to fall into psychological traps from the very start and to build on sand.

But how to communicate all this to anyone outside the paradigmatic echo chamber? Our ability to close our minds to foreign and inconvenient thoughts is monumental. In this case, each paradigm is not just incommensurate, but is built on active, explicit opposition to the other. The most basic tool we have is philosophical / intellectual integrity, that each party has the courage to understand opposing ideas and to be wrong, if evidence dictates that conclusion. Also, perhaps a dab of introspective psychological insight, but that is extremely treacherous territory. Of course, what counts as evidence is as contentious as anything else across these paradigms. And the length to which evidence can be discounted, and even "truth" redefined, is quite impressive.

At any rate, it takes a strong stomach to even listen to the opposing side, since not only is its paradigm contrary to one's own, but it will tend to be dismissive and scoffing (especially coming from the atheist side) if not outright insulting to what it regards as false, ill-informed, possibly immoral views. But that is the price of dialog. Making small talk over tea and crumpets may smooth the waters psychologically, but it will not address paradigmatic or philosophical issues. And dialog is unlikely to change anything anyhow. It is a private process where each person has to search within themselves for their intepretation of reality, and their place in it. Such searching is most intense in adolescence, and that is where hope lies- when childhood indoctrination meets reality.

  • Let's say nice things about religion, by Karen Armstrong.
  • Let's say mean things about religion, by John Loftus.
  • Mythos vs Logos.
  • What happened to the Muslim world?
  • What is the best safety net? Unemployment insurance, or basic income? How about real jobs?
  • The stimulus program, such as it was, was very successful.
  • Morality and the sciences ... women get a better shake.
  • The Ferguson library steps up. More notes on Ferguson.
  • Somebody is taking action against neonicotinoids, but not us.
  • A total failure of incentives and appropriate punishment.
  • Now for some corporate thanksgiving.
  • U.S. General on Iraq: "Washington hails Saudi Arabia as a key “moderate” Arab ally despite the fact that the kingdom exports an extreme, puritanical, sectarian interpretation of Islam that established the theological parameters taken to extremes by groups like ISIS." On the other hand, the Saudis are being very helpful against Iran and Russia.
  • Does everybody hate us?
  • Why did the Supreme Court throw out rights to equality before the law and due process?

Saturday, November 22, 2014

From Weed to Maize

A large-scale investigation on the evolution of corn finds lots of regulatory change.

When Darwin wrote his book on the origin of species, his strongest examples came from pigeons, which at the time were very popular domesticated animals. Just like dogs and cats, pigeons displayed a profusion of breeds and characteristics, all quite clearly descended from a single progenitor species, by way of artificial selection. The speed of artificial selection is amazing, but its relentless focus on desired, superficial traits can lead to problems in temperament, disease susceptibility, and subtle congenital defects.

As mentioned in a recent post, most evolutionary change takes place in regulatory relationships within the genome, rather than as structural changes in encoded proteins. Fine-tuning the binding site of some transcriptional regulator, or moving its site nearer or farther from a gene, tends to have smaller, graded effects on the organism than a change, for example, to that same transciption regulator's own protein sequence, which may affect its interaction with to thousands of sites all over the genome.

A recent paper took a deep dive into the changes that happened in the maize genome on its way to our tables as the king of American agriculture. They reiterate the power of small scale change in a gene's regulatory elements, which they term the cis elements, which is to say, mutations in the DNA local to the gene, typically in upstream sites that bind various regulatory proteins which promote or repress transcription.
"Changes in the cis regulatory elements (CREs) of genes with functionally conserved proteins have been considered a key mechanism, if not the primary mechanism, by which the diverse forms of multicellular eukaryotic organisms evolved. Variation in CREs allows for the deployment of tissue specific patterning of gene expression, differences in developmental timing of expression, and variation in the quantitative levels of gene expression. Furthermore, modification of CREs, as opposed to coding sequence changes, are assumed to have less pleiotropy and consequently have a lower risk of unintended deleterious effects in secondary tissues. The importance of CREs for the development of novel morphologies is supported by the growing catalog of examples for which differences in gene specific CREs between closely related species contributed to the evolution of diversity in form."

The authors sequenced a large crop of RNAs from the tissues of maize and from its ancestor teosinte, to see how their genes are expressed, and, in combination with knowing the genomic DNA that had been sequenced previously, whether changes in gene expression could be tied to specific genome mutations that happened during domestication. The maize genome has more genes than that of humans, 39,423, and 17,579 of them had sufficient expression in these tissues (the RNAs came from the immature ear, the seedling leaf, and the seedling stem) to be analyzed. To give an idea of the scale of current technology, they gathered roughly four billion sequence reads from their RNA libraries.

The majority of the genes they analyzed (82%) were expressed in each of three tissues, while about three percent each were specific to only one or two tissues. The main point of the paper was to attempt to figure out which genes had changed in expression between teosinte and maize, and further, what had caused this, either mutations local to the altered gene, (acting in "cis"), or mutations to DNA far away (acting in "trans") that encodes regulatory proteins whose alteration would affect many other genes as well.

To do that, they used hybrids between teosinte and maize, sampling their RNA as well. In these hybrids, versions of the same gene (alleles) from each parent co-habit in the same cell. So if their expression remained different, it could be chalked up to local effects on each allele's DNA. Conversely, if their expression became similar, (while being different in the parental strains), then the parental difference is likely to be due to regulators that are encoded elsewhere and affect the sampled gene similarly, whatever its origin and local sequence. A very clever scheme, one has to say.

Master graph of genes (dots) assigned to categories of regulatory change, either local to the gene sequence (cis, in black), or due to changes in a non-local regulator (trans, in red). The conclusion is based on the gene's respective behavior when co-housed in the same plant, i.e. the hybrid progeny of a maize X teosinte cross. The logs on each axis refer to logs of the ratio between maize and teosinte, in either the parents (X axis) or in the hybrids (Y axis).

The identity / parentage of the alleles in the hybrids could be kept straight by way of minor DNA variations sprinkled throughout the sequences of their expressed RNA. Teosinte and maize have been separated by about eight thousand years, enough time for quite a few (mostly silent) mutations to accumulate in each genome. But the interesting differences between them would be those that were specifically selected in maize to make it into the dramatically different plant it is today- stalk branching, ear size, ear morphology, growing speed, hardness of the seed, etc. What were those mutations and how can they be found? This paper unfortunately does not get to that detail. They note that 70% of all the genes showed significant changes in expression, and that the sets of differently expressed genes were ~70% different in each of the three tissues. All of which is quite remarkable.

What they are more interested in is defining large sets of genes that might be interesting as ingredients of the special properties of maize. To start, they assume that genes under selection pressure would have had local changes to their regulatory DNA. This is not entirely correct, though. Some far-away change might have been selected for if it had strong effects regulating some target gene / trait, without having too many side effects. While this is difficult to imagine and likely rare, it is by no means impossible or without precedent. Nevertheless, they bundle up all the genes with local or local + distant changes, and call them their "CCT" set (for cis and cis+trans changes in regulation profile). These are the black and purple dots on the graph above, and amounted to about 5500 genes.

They further filtered that set by asking for high consistency and high expression over all their samples, (or different parental and hybrid cross strains), and came up with sets of varying stringency, from very few (69) genes to a much less stringent set (~2326) genes. This had the defect of discounting genes whose expression was very low, either before (in teosinte), or after (in maize). Anyhow, it was a rough-and-ready method to whittle down their data to some interesting candidate genes, depending on how stringently they set the dials. One problem was that gene expression is naturally more variable in teosinte, being a genetically diverse and wild plant, (despite their using inbred strains, which must not have been quite as inbred as they thought), than it is in maize, being heavily in-bred and virtually clonal.

The larger the expression difference of a gene between teosinte and maize (X axis), the more likely that difference is due to local "cis" regulatory effects (Y axis). This is reflected also in the previous graph of genes with higher expression differences on the higher slope lines.

The rest of the paper, unfortunately, is a litany of woe, as they find that their sets of specially selected genes do not agree very well with those that other researchers have isolated using other methods. For instance, one group used a micro-chip based method with fixed DNA samples detect RNAs that are expressed differentially between modern maize and teosinte, and found their own list of such genes:

"However, the absolute level of correspondence between the two studies is rather low. For example, of the 350 leaf genes identified as DE [differentially expressed] by RNAseq [the current paper's method], only 24 (7%) were also identified by the microarray study [the other paper's method]. Thus, while the overlap between our two studies is statistically significant, the two methodologies resulted in largely different lists of DE genes."

It is somewhat depressing that this many years into the genomic age, the large-scale technologies being touted and used to gather presumably quantitative gene expression data of this sort can generate such divergent results. Technically, I believe this is due to their need to have high expression under all conditions, which is contrary to most of the other methods used, which prize very high contrast, i.e. very low expression in one sample vs higher expression in another, to identify candidate genes. Nevertheless, each collection of genes must have some gold amongst the placer and thus this paper is surely the career-building effort of some post-doc who will give job interviews on the ambition of panning through these genes to find ones that have individually significant effects on the unique properties of maize.
"This study shows cis and trans regulatory differences account for ~45% and ~55% of regulatory divergence between maize and teosinte, respectively (Table S1). These values suggest relatively equal contributions of these two mechanisms to regulatory divergence. However, this ignores the contribution of cis effects to large expression differences where cis accounts for nearly 80% of the expression divergence."

A final interesting point is that roughly half the expression differences were traceable to the "trans", or non-local, mechanism. This might seem to go against the assumption outlined above that local mutations in gene regulatory sequences should predominate, but it may take only a few individual changes in regulators or their networks to cause changes in the expression of many of the genes assayed here, while each expression change classified as "cis" or local requires a separate change to that gene's sequence. So the overall number of local regulatory changes in this data set will vastly outnumber individual changes elsewhere, and the authors note additionally that the expression changes that were quantitatively highest were virtually all due to local mutations.

  • Similar story for the deeper divergence between mouse and human.
  • Has religion outlived its usefulness?
  • Reza Aslan: No, and let me present a diatribe about that.
  • A notable podcast on the role of philosophy, relations to science, and ... is there progress?
  • Inheritance ... another feudal, antisocial practice.
  • Perjury- the new frontier in mortgage fraud.
  • Banking is a immoral industry. Perhaps a proper target of vice squads?
  • CO2 visualized, world-wide.
  • Target zero for carbon emissions.
  • Some power companies are on board.
  • Just what was China promising?
  • Britain has internet service competition, we do not.
  • Just what is wrong with the muslim world? Why the torpor, humiliation, and tragedy?
  • Why is the Fed backing off?
  • Democracy may require some kind of revolt.
  • This week in the WSJ- the 1% "earners" are OK.
  • But Bill Black thinks otherwise:
"Cochrane admits in the final paragraph that one of the “secrets of prosperity” is a well-functioning “rule of law.” He doesn’t tell you that his institution, the University of Chicago’s law, finance/business, and law faculty, have led the systematic attack for the last 40 years that successfully eviscerated that rule of law and allowed the banksters to lead the fraud epidemics that Cochrane admits drive our recurrent, intensifying financial crises."

Saturday, November 15, 2014

Wave of in-Attention

The visual system uses rhythmic synchrony to gate data to higher levels.

While it is clear that the brain creates our mind, the vast mechanism linking the two remains mysterious in many respects. The connection is attested by countless conditions and experiments, more or less tragic, but while the science has been progressing well, the brain is an inscrutible organ, and much remains to be done.

A recent paper describes coordinated fMRI and EEG experiments on humans to tell whether top-down attention uses the mechanism of brain waves to filter visual processing coming up from the sensory system, so that we can look at what we want. The attention system is very interesting and perhaps not commonly understood. The executive areas of the brain reach back into all the sensory areas and elsewhere, such that information processing is a two-way street. Signals from the senses do not just all flood into consciousness at the same time, but we attend to one or another, and that requires not only filtering against all the other streams of incoming data, but also management of the active stream, to focus on what we are "interested" in. Indeed, with no sensation at all, we can, though the attention process, imagine a sensory stream, which actually animates the sensory regions involved to create an attenuated, but physically accurate, stream of internally-generated "sensation" information.

The researchers here were interested in the correlation between mental activity, particularly in the visual areas, and brain wave activity. They were looking at alpha waves, (7-12 kHz), not the gamma wave activity that has been associated (loosely) with consciousness. Alpha waves are known to be associated with relaxed, non-processing, but ready, states. The primary example is the visual (occipital, rear) area of the brain, with eyes closed and the subject relaxed but awake. The waves then decline in power / coherence when eyes are opened and a visual scene is being actively processed. Other forms of the alpha wave are strong in specific areas and kinds of sleep.

"... several studies using transcranial magnetic stimulation and visual entrainment of 10-Hz activity have demonstrated that the alpha rhythm plays a causal role in the allocation of attention, perception, and working memory maintenance."

Not surprisingly, the researchers found an inverse correlation between alpha waves and the attention someone is paying in a part of a visual scene. This suggests that alpha waves are used to quiet the waters in unattending areas, rather than to synchronize or convey data, as has been thought for other wave patterns. The unattending areas are still working and processing their visual fields, but they are closed off from attention and consciousness, more or less.

Visual processing pathway, showing how visual hemifields map to the respective occipital cortex hemispheres.

The setup was to place human subjects in an MRI machine, with EEG electrodes attached as well. They were shown visual images that had two parts, a left side and a right side. The left side (coming from each eye) maps in the brain to a left "hemifield", which is processed in the right side of the brain. The researchers instructed the subjects to pay attention to one or the other side, though images were presented to both sides. The attention was enforced by asking/testing whether the image was the same or different than a previous one.

Example of images presented to the subjects, where attention was directed to one or the other side (hemifield; arrows). This implies that the subject's eyes were kept straight ahead, focused on the center "X".

So the subjects were staring at a full visual field, but spent a couple of seconds attending (mentally) to one or the other side, either a face or a landscape. The MRI showed increased activity (i.e. blood flow) on the corresponding side of the brain's visual processing area, the occipital lobe at the back. It also showed increased activity in the facial recognition area (for faces; fusiform face area) or in a place recognition area (for landscapes; parahippocampal place area).

But the alpha wave pattern in the EEG consistently showed lower power in the areas active above, and higher power in the corresponding areas in the other hemisphere- the hemisphere where attention was not being focused.

Alpha wave power during directed visual attention, reflected by higher MRI signal on the R side, corresponding to attention to the Left visual hemifield. Alpha power is dramatically reduced as attention is being paid.
MRI signal simultaneous with the image above, with higher activity on the attending side (R).

What do they make of all this? They note that "Our findings add support to the notion that alpha band activity serves an active role in the allocation of resources." But not exactly in the way I had expected. As a last project, they look at something called the dorsal attention network, which is thought to be a mechanism where the frontal executive areas reach back to focus attention. This set of regions show similarly inverse MRI correlation with the alpha wave power in the visual area.

"We have demonstrated that the suppression of unattended information is reflected by active inhibition via increased alpha band activity in the unattended visual stream. Our findings add support to the notion that alpha band activity serves an active role in the allocation of resources." 
"We suggest that the mechanism of this gating by alpha activity is via phasic manipulation of higher frequency oscillations in the gamma band. In particular, the increase in alpha activity is important for the routing of information by depressing irrelevant processing of sustained stimulation, which is in stark contrast to the view that posterior alpha activity reflects idling or drowsiness."

Sadly, the work seems quite weak. They basically find that if one directs a person's attention to some item in a visual scene, the corresponding visual region in the brain shows dampened alpha wave activity, while the contralateral area in the other hemisphere shows heightened activity. That part was quite clear. The attention network result was not very strong. And the interpretation of all this is very unclear. Do some waves have something to do with attention and consciousness in some areas of the brain, while other waves at other frequencies and places relate to the opposite? That seems to be the lesson, which thus leaves us waiting for more work and insight into the matter.

  • What worries you masters you.
  • On the false consciousness of capitalism. "The capitalist marketplace generates a huge amount of anger".
  • Same old fraud, same old Citi.
  • "The oceans have become 30 percent more acidic over the past 200 years as a result of human activity."
  • Which fosters more violence- Hollywood or Islam?
  • Amazon goes evil.. towards coal.
  • Eco-collapse by neonicotinoids.
  • Inflation and growth still needed in Germany.
  • Religion vs the internet.
  • More on bankers, fraud, corruption, recurring economic catastrophe, etc.
  • Why have a legitimate government at all?
  • On the Takata story.

Saturday, November 8, 2014

We Are the Adaptable Ones

Climate change is about other species, not us.

While all the attempts to calculate the economic costs and benefits of climate change are well-meaning, I think they are mostly beside the point. Of all species on earth, we are the most adaptable, and can readily, if not easily, adapt to climate change. Even if adapting to it eventually costs more than solving it. While other organisms are fated to adapt on evolutionary time, by mutation and selection, (or die), we can adapt in cultural time. Cultural time is hugely compressed vs evolutionary time, as our last century of technical progress, and biosphere destruction, attest.

Earth has gone though very warm epochs in the past, where there were no ice caps, and Alaska had palm trees. And there were great changes to life as a result. But it was all very slow, giving time to the ecological network to adjust. Truly catastrophic events, like the end-Cretaceous asteroid impact, devastated the biosphere to a state that we would never want to see if we can possibly help it. If we have to move to Siberia to farm within a hundred or a few hundred years, we can do so, burning yet more fossil fuel to get there. Other species don't have it so easy.

So I think it is important to avoid, or at least go beyond, the economic, cost vs benefit calculus that many seek to put on the climate change debate. Our current biggest benefit is always to do nothing and hope for the best. The "discount" put on future human generations with respect to benefits they might get from our responsible behavior today is variable and highly subjective. If we feel like doing something for future humans, great. But in any case, we do not face extinction. Other species do.

"A large fraction of species face increased extinction risk due to climate change during and beyond the 21st century, especially as climate change interacts with other stressors (high confidence). Most plant species cannot naturally shift their geographical ranges sufficiently fast to keep up with current and high projected rates of climate change in most landscapes; most small mammals and freshwater molluscs will not be able to keep up at the rates projected under RCP4.5 [an intermediate mitigation scenario] and above in flat landscapes in this century (high confidence). Future risk is indicated to be high by the observation that natural global climate change at rates lower than current anthropogenic climate change caused significant ecosystem shifts and species extinctions during the past millions of years. Marine organisms will face progressively lower oxygen levels and high rates and magnitudes of ocean acidification (high confidence), with associated risks exacerbated by rising ocean temperature extremes (medium confidence)."
"Many terrestrial, freshwater, and marine species have shifted their geographic ranges, seasonal activities, migration patterns, abundances, and species interactions in response to ongoing climate change." 
- the IPCC
Future hothouses on earth, under two different scenarios, first a stringent mitigation scenario, and second a business as usual, high emissions scenario- also from the IPCC.

Saturday, November 1, 2014

Islam is Not a Religion of Peace

Nor is it a religion of war. A review of the Quran.

Muhammed is the Apostle
Of God; and those who are
With him are strong
Against Unbelievers, (but)
Compassionate amongst each other.
As scripture, the Quran stands head and shoulders above its relatives in some respects. It is clear, (if tediously long and repetitive), not given to parables and riddles. Nor is it given to obscure genologies and mythical tales (other than a few retold from the Jewish and Christian traditions). It is explicit on many points, giving rules for behavior and hammering home its points about who and what are good and bad. Its general world view is also refreshingly simple. The world's beauty and gifts, especially the wonders of biology, are clear signs of the one god, and one would have to be an idiot or worse to doubt them and thus the Apostle's message, which comes directly from god.
And among His Signs
Is the creation of the heavens
And the earth, and the variations
In your languages
And your colors: verily
In that are Signs
For those who know.
(The version I am using dates from sixty-eight years ago, well before the political correctness that beset the field since 2001. It is also a version that reads very well and is abundantly annotated. The text runs to 1800 pages.)

The Quran's provinance is also far more secure than those of the other scriptures, being assembled within twenty years of Muhammed's death by order of the rulers of the community. The ancillary Hadith is less secure, but that is another matter. Muhammed's existence is also far better attested than that of the other prophets, from Jesus back to Moses, Abraham, Noah, Adam, and into the mists of time, many of whom, if not all, are mythical, or very heavily mythicised. Muhammed had a very active and well-recorded life, full of commerce, revelation, warfare, and preaching. Indeed, he took special exception to the deification of Jesus, making it a tenet of Islam that Jesus as one of the prior apostles was a normal man with (some) divine inspiration. One might note in passing, however, that the seemingly universal practice of Muslims to never refer to Muhammed without wishing peace be upon him amounts to a furtive deification / sanctification of the apostle. He is most certainly in the finest possible position of heaven by this doctrine, and hardly needs assistance of any kind from the sinners here below.

The Muslim doctrine, aside from a few defects that I will get to, is also a highly moral one, which repeatedly invokes a very simple formula for community membership- belief in god and obedience to his apostle, virtuous moral action, modesty and circumspection in all affairs, and charitable giving to the poor. There are other incidental tasks, such as praying, food restrictions, and the hajj, (incidentally, Islam is about the only modern religion still employing animal sacrifice, which takes place during the hajj), but the basics are admirably simple and doubtless contribute to the attraction of this religion to so many people, and to their self-understanding that it is an almost self-evident doctrine. The Quran also enjoins believers to give charity with open arms and a positive attitude- something that our current Republicans might do well to emulate, our tax system being, in essence, precisely the kind of alms and charity distribution system (plus a little jihad) that Islam envisions.
But some of the desert Arabs
Believe in God and the Last Day,
And look on their payments
As pious gifts bringing them
Nearer to God, and obtaining
The prayers of the apostle.
Aye, indeed they bring them
Nearer (to Him): soon will God
Admit them to His Mercy:
For God is Oft-Forgiving,
Most Merciful
Unfortunately, Muhammed was faced with a lot of disbelievers in his time, as is reiterated on virtually every page. They are assigned to hell in innumerable ways, sometimes mild, sometimes excruciating. But the repetition of this theme is striking, seeming to signify some insecurity about the clarity and confidence otherwise expressed. Its endless repetition also functions as a sort of hypnotic mantra. Sometimes he takes the mild approach, assuring listeners that, despite the apparent success of unbelievers in this life, with riches and sons, god will mete our their just deserts in the afterlife. But frequently, hatred gets the better of him, and unbelievers are reviled where they are, threatened with various horrible fates in this world, and subject to terror by the (always virtuous) believers. He recurs frequently to the tales of Noah, Moses, Lot, et al. to make clear that unbelievers stand a very good chance of being struck down in this life, en masse, God-willing.
Those who reject
Our Signs, We shall soon
Cast into the Fire;
As often as their skins
Are roasted through,
We shall change them
For fresh skins,
That they may taste
The Penalty: for God
Is Exalted in Power, Wise.
There is also an odd lack of certainty sometimes, as though the speaker, though being god, isn't entirely sure of some facts or events events. He recounts (18:22) an old Christian story of boys who happened upon a cave and fell asleep there, for a few centuries, only to find on waking that the Christianity that was reviled by the Roman authorities before is now the state religion. Only, the teller of the tale isn't sure whether there were three boys, or five, or seven. It doesn't inspire confidence, frankly. Likewise, he retells the immaculate conception story of Mary having been impregnated by god, but later claims that Jesus was a normal man like all others, not in any way a deity. And that nor did god ever have a son. Logically, it doesn't quite make sense, especially as told by an omniscient being, but makes more sense as a sop to tradition.
Have We not created
You from a fluid
(Held) despicable? 
The which We placed
In a place of rest,
Firmly fixed, 
For a period (of gestation),
Determined (According to need)? 
For We do determine
(According to need); for We
Are the Best to determine (things). 
Ah woe, that Day!
To the Rejectors of Truth!
More generally, the book claims to be full of truths, but the information communicated is meagre. Belief is extolled ad nauseum, as is truth, but no scintilla of knowledge not commonly known at the time is related. This is especially notable in its celebration of biology and the heavens, which are given repeatedly as strong signs of god and his beneficence. Where is the knowledge of breeding, of evolution, of development, and of genetics? (Hey, how about a funny biology song?) The author claims simply that god has made everyone, and can make or unmake people at will. Where is the knowledge of the history of biology and scale the universe? The birth of Adam is recounted as the origin of humanity, in the story of the garden of Eden. As a source of knowledge, the Quran comes off poorly indeed. Imagine how mind-blowing it would have been for an ancient scripture to tell the true story of our origins and nature, taking it as a lesson on the great preciousness and rarity of our existence, and the momentous stewardship we have been granted.
Praise be to God,
Who hath sent to His Servant
The Book, and hath allowed
Therein no Crookedness: 
(He hath made it) Straight
(And Clear) in order that
He may warn (the godless)
Of a terrible Punishment
From Him, and that He
May give Glad Tidings
To the Believers who work
Righteous deeds, that they
Shall have a goodly Reward, 
Wherein they shall
Remain forever:
There are also some theological confusions. God is free of all wants (14:8, and elsewhere), but at the same time wants all kinds of adulation and submission, wants unbelievers to spend eternity in Hell, wants moral behavior in peace and martial behavior in war, indeed, has transmitted a book full of wants.

Pagans and unbelievers are assigned to hell on virtually every page. But they also are promised ill fortune in this life, though sometimes they might do just fine, as god is just staying his hand till some more convenient moment. Indeed, sometimes they are so rich with money and sons that it drives believers positively apoplectic, and to doubt that they are on the right side after all. The Quran tries its best to quiet such doubts, asserting time and again that whatever the current situation, (and however detestable the unbelievers, and whether they may be crushed and destroyed in this world as many other whole tribes have been before by earthquake, flood, or fire, or the sword, or ...), god sees all and will send them to the fire when they die. If not before.

The Santa Claus nature of all this is unmistakable. Charming in its simplicity, but intellectually not at a very high level. God sees all, and will balance all accounts in the final judgement. All the good actions of this life will be rewarded. Except that unbelief seems to cancel them all out. Unbelievers in the Quran can never be good. They are perverse, lying, deceitful, blind, arrogant, mocking ... the list is endless. So the doctrine never has to grapple with the problem of positive moral behavior among non-Muslims. This applies apparently both to the time of death, and to a final judgement, which is mentioned, along with bodily resurrection of the believers, as an evident bow to the Christian system, but is not very well fleshed out, if you will excuse the pun. I could never tell whether I, for example, would go to hell immediately upon death, or whether that would await a general judgement day. The whole thing is, theologically, a jumbled mishmash of past beliefs, and looks much more like a psycho-mechanical contrivance for belief propagation than it is a search for, or convincing explanation of, truth.
O ye who believe!
Ask not questions
About things which,
If made plain to you,
May cause you trouble.
But if ye ask about things
When the Quran is being Revealed,
They will be made plain to you,
 For God is Oft-forgiving,
 Most forbearing.

 Some people before you
 Did ask such questions,
 And on that account
 Lost their faith.
This god is also the most passive-aggressive character in all literature. The signs of his existence are no more than the mundane / glorious / mysterious conditions of nature, which admittedly in Muhammed's day, merited virtually unlimited awe. But if you don't believe in him, (and, notably, obey his humble Apostle), he will get you when you are least aware, and haul you off to everlasting hell fire. On the one hand, the whole Apostle thing comes off as a ego trip without parallel, while on the other, if god were so merciful and powerful, why would Satan (Iblis) be given leave to mislead so many hearts for so much time- why would anyone listen to him and not to god? It makes little sense, other than as a mapping of psychological archetypes onto an imaginary cosmic drama.

This brings up a significant moral point, which is that one would think that with such a fate in store, unbelievers would merit more compassion than they seem to get in the Quran. Why indulge in so much hatred if their fate is so sure and terrible- if they are building in this world their furnace in the next, by all their immoral deeds, unbelief, and mockery? Again, one gets the distinct sense that the theology is not really all that secure, and that the hatred is a very this-world phenomenon oriented to the oldest trick in the book, convincing people to believe in invisible beings, unbelievable doctrines, and the goodness and success of one's own group, led & ruled by God's representative on earth. All for the most admirable reasons, of course, but in a contemporary world that is so dense with other beliefs, yet at the same time contains a billion and half Muslims typically in communities with no contact with unbelievers at all, such attitudes are unhealthy, to say the least. Muhammed himself practiced precisely what he preached and lived a blood-soaked life, killing his enemies right and left, in Medina (expelling all the Jews along the way), Mecca, and in the larger conquests through the Arabian peninsula up to the end of his life.

Which brings us to jihad. This struggle against unbelief is fundamental to the message of the Quran (indeed, one wonders about some influence from Zoroastrianism, with its relentless black-white outlook) and one question is whether it is formulated in military terms in the text itself, or only in the ancillary Hadith. There are many sections about war, usually focused historically on the early battles of Muhammed which are plainly life or death struggles for the faith. War is definitely the answer, and the pagans are reviled and attacked in the most absolute terms. God expresses himself through the success of his believers in arms.

But the Quran also claims to be a very general text, being the last and final revelation, so its lessons are not simply confined to their historical moment, but apply to all the faithful still today. This makes for a messy theology. The practice of going out hunting for unbelievers to forcibly convert is not explicitly promoted, as far as I could read, despite all the hatred directed at them. Indeed, Muslims are instructed to live in community with each other and to leave areas where they are a minority (i.e. Mecca during the exile in Medina). At the same time, the struggle against unbelief is to be unremitting, so the more explicit directive to military jihad that one finds in the Hadith is very consonant with the Quran in this respect. And of course the historical record of Muhammed's career and the ensuing centuries, when Muslim armies swept the known world, makes the point more eloquently still. Overall, it supports the idea that jihad is properly understood in the original sense, to be a military conquest of unbelievers until the whole world takes up the one true faith.
Be not weary and
Faint-hearted, crying for peace,
When ye should be
Uppermost: for God is
With you, and will never
Put you at a loss
For your (good) deeds.
The Quran, for instance, promotes terrorization of unbelievers, as though the theology of hell were not already disquieting enough. It also allows polygamy, which, in my opinion, leads inexorably, if indirectly, to war by the excess males of a society. Females captured on battle were, and, if one is to believe reports about ISIS, remain, fair game to jihadists. In Muhammed's day, one can put a somewhat more generous construction on this policy, as a way to provide for widows in a violent, militaristic age. But then his marriage to Aisha (one of his thirteen wives) suggests something quite different ... a Koreshean zeal for a more youthful additional wife.
If ye fear that ye shall not
Be able to deal justly
With the orphans,
Marry women of your choice,
Two, or three, or four;
But if you fear that ye shall not
Be able to deal justly (with them),
Then only one, or (a captive)
That your right hands possess.
That will be more suitable,
To prevent you
From doing injustice.
Incidentally, married life was not without its problems. In one chapter, he complains about wifely insubordination and threatens to divorce them all:
It may be if he [Muhammed]
Divorced you (all),
That God will give him
In exchange Consorts
Better than you,-
Who submit (their wills),
Who believe, who are devout,
Who turn to God in repentence,
Who worship in (humility),
Who travel (for Fiath) and fast,-
Previously married or virgins.
But back to the main theme of what to do about unbelievers:
Therefore, when ye meet
The Unbelievers (in fight),
Smite at their necks;
At length, when ye have subdued them,
Bind a bond
Firmly (on them); thereafter
(Is the time for) either
Generosity or ransom:
Until the war lays down
Its burdens. Thus (are ye
Commanded): but if it
had been God's Will,
He could certainly have exacted
Retribution from them (Himself);
But (He lets you fight)
In order to test you,
Some with others.
But those who are slain
In the way of God,-
He will never let
Their deeds be lost.
There are various mercies and controls put on war against unbelievers, such as the acceptance of conversion on its face, and the directive to not be vindictive in victory, and to attack only in defense, not in offense. But the plastic nature of victimization narratives is such that, as we observe all over world, groups can always construct some way in which they are under attack and thus justify attack. Christians in the US moan constantly how victimized they are by those arrogant atheists, etc. Indeed the insufferable arrogance of the unbelievers is a constant (and rather ironic) theme in the Quran.
Your God is One God:
As to those who believe not
In the Hereafter, their hearts
Refuse to know, and they are arrogant. 
Undoubtedly God doth know
What they conceal,
And what they reveal;
Verily He loveth not the arrogant. 
When it is said to them,
"What is it that your Lord
Has revealed?" they say,
"Tales of the ancients!" 
Let them bear, on the Day
Of Judgement, their own burdens
In full, and also (something)
Of the burdens of those
Without Knowledge, whom they
Misled. Alas, how grievous
The burdens they will bear!
The Quran is an interesting blend of Jewish and Christian theology (Mostly Jewish, however, which accords with Muhammed's principal influences). Muhammed comes off as something of a Paul-like character, reshaping the somewhat foreign theology of Judaism for a new audience, language, and age with forceful, confident, and ceaseless proselytizing. The schizophrenic, two-faced nature of god is extreme, as he is called terrible, awful, and judgemental in the same breath as he is the most merciful. Clearly the audience for this message was intensely tribal, and the transposition of the old family & tent tribalism into a new religious tribalism of believer vs unbeliever was as historically momentous as it was psychologically astute and intellectually vacuous. In our own day, it continues to be the nail upon which multitudes of Muslims, disaffected as they routinely are by their own defective systems of civil society and government, hang their hopes and hatreds.

But there was one enormous oversight in all of Muhammed's hundreds of pages of detailed directives and repetitive trash talk, which was the matter of succession. Muhammed never revealed the identity of, or method of choosing, the next leader, let alone all the successive leaders of the community. This despite the huge significance he placed on the community, its coherence, and its leadership. This failure has haunted Islam from the day of his death, when the wrangles and ultimately civil wars over Ali, Abu Bakr, and Shiism began. The founders of the United States, in contrast, stand head and shoulders over Muhammed in that they authored a durable mechanism of peaceful succession and of government in general. A beneficent god could surely have managed as much for Muslims.
"The Kharijites argued a true believer would have trusted his fate not to diplomacy but to ongoing warfare and God will decide." .. from a Western commentary.

Unfortunately, Islam has vacillated between legitimacy by blood and legitimacy by battle, per the most ancient template. It is incidentally odd that the theocratic model we find in Iran has been so rarely employed, in light of Muhammed's example. In any case, this continues to be a glaring weakness of the Muslim world and especially of ISIS, Al Qaeda, Taliban, and other fringe groups that send up fatwas and set up caliphates that get nothing but scorn from mainstream Muslims (unless they succeed ... nothing succeeds like success!). The charisma of the moment, yoked to fanaticism, fundamentalism, and terror, may be able to scatter a dysfunctional and totally corrupt government as found in Iraq or Syria, but its staying power against well-functioning, legitimate, (not to mention open, truth-seeking, and democratic) societies is going to be extremely modest.
They will recline on Carpets,
Whose rich inner linings
Will be of rich brocade: the Fruit
Of the Gardens will be
Near (and easy of reach). 
Then which of the favors
Of your lord will ye deny? 
In them will be (Maidens),
Chaste, restraining their glances,
Whom no man or Jinn
Before them has touched; 
Then which of the favors
Of your Lord will ye deny?
In the end, we have to ask how much Islam per se is responsible for the features of the Muslim world that keeps it in the news on such a regular basis. Many argue that religion has no significant effect, for it can and is interpreted quite flexibly depending on the material circumstances of the society. We would have to look to our own actions from the Crusades, colonialism, and recent US foreign policy to locate the reasons why some Muslims are so bitter about modernity and ready to take up arms anywhere they can fight infidels or set up fly-by-night caliphates.

Obviously, there is some truth to that view. The spectrum of Islamic interpretation is vast, from the Sufis to the Salafists. The Quran supports numerous views, and offers some compassion in amongst the rest. But I think that ideology is also critically important. We do not absolve the Nazis by accusing the Versailles treaty of driving Germans to  world war and genocide. Ideology drives world affairs, as the narrative force that shapes our responses to material conditions. No ideology, no Inquisition, no cold war, no racism in the US, no Crusades, no "holy land", no patriarchy, etc. ad infinitum. As the Quran exemplifies, people will find ideologies to suit them, (or have them forced down their throats), but if those ideologies claim to be rational, yet are not rational, the seeds of their own critique, if not destruction, can be sown. At least one can hope.
Fighting is prescribed
For you, and ye dislike it.
But it is possible
That ye dislike a thing
Which is good for you,
and that ye love a thing
Which is bad for you.
But God knoweth
And ye know not.
For instance, one of the momentous issues in Islamic ideology is its stance towards the modern world. Which is not easily compatible with traditional Islam. Globalism breaks down cultural borders, infecting everyone with consumerism, liberal political philosophies, women's liberation, and religious skepticism. The commerce and especially the oil-addiction of modernity has made some Muslim nations unimaginably wealthy, while more generally, the advent of colonialism, interacting with the technological and intellectual power of the West, has put Islamic culture in a poor, embattled, even subservient, position. The Egyptian philosopher Qutb came to a shocked and fundamentalist conclusion- that modernity is the mortal enemy of Islam. Quran and Sharia must be the sole answer to all of mankind's problems.
"The concept of the imperceptible is a decisive factor in distinguishing man from animal. Materialist thinking, ancient as well as modern, has tended to drag man back to an irrational existence, with no room for the spiritual, where everything is determined by sensory means alone. What is peddled as 'progressive thought' is no more than dismal regression."
Let not the Unbelievers
Think that they can
Get the better (of the godly):
They will never frustrate (them). 
Against them make ready
Your strength to the utmost
Of your power, including
Steeds of war, to strike terror
Into (the hearts of) the enemies,
Of God and your enemies,
And others besides, whom
Ye may not know, but whom
God doth know. Whatever
Ye shall spend on the Cause
Of God, shall be repaid
Unto you, and ye shall not
Be treated  unjustly.
The Saudi rulers in particular have blended this ideology with their wealth and Wahhabist religious structure into a globe-straddling ideological machinery of fundamentalist madrassas that groom the cannon fodder of jihad. Yet Attaturk, a generation before, came to the opposite conclusion, frog-marching Turkey into a quasi-secular, modernizing state. What is it to be? A great deal depends on the fairness and decency the rest of the world can bring to the table. But more depends on the readings that Muslims give themselves of their central text, history and traditions. The war for the ideological / theological soul of the Muslim world is highly consequential. And the core text is not, on the face of it, particularly helpful towards a tolerant, cosmopolitan, and peaceful reading.
It may be that God
Will grant love (and friendship)
Between you and those whom
Ye (now) hold as enemies.
For God has power
(Over all things); And God is
Oft-Forgiving, Most Merciful. 
God forbids you not,
With regard to those who Fight you not for (your) Faith
Nor drive you out
Of your homes,
From dealing kindly and justly
With them: For God loveth
Those who are just.

  • An Islamic theologian on the value of theology and the fundamentalist turn. "Islamic theology is based on an ethical rather than speculative imperative. Many Qur’anic verses and hadiths show that iman or “true faith” is obligatory and rewarded by paradise, and that kufr or “unbelief” is wrong and punished by hell." This shows, unsurprisingly, that a search for truth is not really part of the program.
  • An advanced discussion of ISIS and the Muslim world, on POI.
  • Shiite cleric sentenced to crucifixion in Saudi Arabia.
  • Christianity ... can be taken several ways as well.
  • Maher on Islam. And more, more, more, more, more.
  • What do regular Muslims think?
  • Is the Quran an example of "derp"?
  • And now some very peaceful news, from Indonesia.
  • The unending irony that is Pakistan: "An anonymous senior Pakistani security official stated: 'It is a worrying development that the TTP is regrouping close to the border right under the nose of the Afghan security forces.'"
  • Wesley Clark on policy: "We just can’t believe that we were responsible for creating it. We weren’t. The money that went into ISIS came from Saudi Arabia and Qatar, and it came particularly from the work of the Saudi leadership trying to find an opposition to Bashar Assad in Syria."
  • Fear is a political act, and a media goldmine.
  • Gosh- what happened to the middle class?
  • GOP heads to new lows. Suppression or outreach, that is the question.
  • What is the nature of our current form of capitalism? And of our political economy?
  • And what's the problem with Europe? "The Eurozone’s current problem arises because one country - Germany - allowed nominal wage growth well below the Eurozone average, which undercut everyone else.... Within a currency union, this is a beggar my neighbour policy."
  • Krugman on Japan- now is no time for false fiscal responsibility.
  • Notes and data on inequality.
  • The Fed can set long as well as short rates.
  • Economic graph of the week. Our economic prospects continue to decline.