Is that mutation significant?

Face it, our genomes are a real mess. A study of just the parts of the genome coding for amino acids (2% at most) in about 2,500 people found an average of 205 variants which change the amino acid coded for IN EACH PERSON. Each person also had an average of 3 termination codons in the 15,000+ protein coding sequences they studied. So they are wandering around with 3 abnormally short proteins. You can read more about it in this old post –https://luysii.wordpress.com/2012/07/31/how-badly-are-thy-genomes-oh-humanity/

Here’s the problem — these people were healthy. Obviously, not a problem for them, but a big problem for physicians attempting to do genetic counseling. For how it affected epilepsy counseling see — https://luysii.wordpress.com/2011/07/17/weve-found-the-mutation-causing-your-disease-not-so-fast-says-this-paper/.

This brings us to Lynch syndrome (aka Hereditary NonPolyposis Colorectal Cancer — HNPCC). It is a familial cancer syndrome, and we now know what the problem is — mutations in any of four genes involved in a type of DNA mutation repair (there are many). The genes are called MSH2, MSH6, MLH1 and PMS2 (acronyms all whose names you don’t need to know) and the type of repair is called MisMatch Repair (MMR).

This isn’t academic at all. Suppose your aunt comes down with colon cancer and you get tested for mutations in one of the four, and a mutation is found. You’re fine now. The question before the house is — should you have your colon out? Colonoscopy won’t help because this kind of colon cancer doesn’t arise from polyps (which is what colonoscopy is looking for).

The problem is that the 4 genes are ‘peppered’ with missense variants (change the amino acid coded for). They are called VUS (Variants of Unknown Significance). The following paper [ Proc. Natl. Acad. Sci. vol. 113 pp. 3918 – 3820, 4128 – 4133 ’16 ] used a clever way to test a VUS for significance. This would have been impossible 5 years ago. What they did was use CRISPR to introduce the variant into the appropriate protein in mouse Embryonic Stem cells. Then they tested the manipulated stem cells for defects in MisMatch Repair. They tested 59 (yes fifty-nine) such VUSs and found that about 1/3 (19) produced MMR defects.

Fascinating time to be alive and reading about all this stuff.

Activating a proto-oncogene without mutating it

Many proto-oncogenes have to be mutated to cause cancer. Not so the TAL1, LMO2 genes. They drive blood formation, and are aberrantly activated (e.g. more proteins made from them is expressed) in T cell Acute Lymphoblastic Leukemia (TALL). [ Science vol. 351 pp. 1298- 1299, 1454 – 1458 ’16 ] activated them experimentally using the CRISPR technique, and therein hangs a tale.

Addendum 11 April — LMO2 is well known to gene therapists as early work (2002) using retroviruses inserted randomly in the genome to cure SCID (Severe Combined Immunodeficiency) resulted in TALL in 4kids.  The problem was that the vector integrated in multiple sites all over the genome and one such random site  turned on expression of LMO2.

I’ve written a series of six posts trying to imagine the incredible mass of DNA in a 10 micron nucleus on a human scale — we take it for granted, but it’s far from obvious how this is accomplished — here’s the link to the first — https://luysii.wordpress.com/2010/03/22/the-cell-nucleus-and-its-dna-on-a-human-scale-i/. — just follow the links to the rest.

[ Cell vol. 153 pp. 1187 – 1189, 1281 – 1295 ’13 ] Hi-C and 5C (Carbon Copy Chromosome Conformation Capture) allow determination of chromatin organization and long range chromatin interactions in an unbiased genome wide manner at the megaBase scale. Topologically associated domains (TADs) are the way the genome in the nucleus is organized into megabase to submegaBase sized interacting domains. TADs are conserved between species and are invariant across cell types. [ Call vol. 156 p. 19 ’14 ] They average 700 – 800 kiloBases and are said to contain 5 – 10 protein coding genes and a few hundred enhancers. The expression of genes within a TAD is ‘somewhat correlated’. Some TADs have active genes, while others have repressed genes. Genomic interactions are strong within a domain, but are sharply depleted on crossing the boundary between two TADs.

Well TADs have to be separated from each other. The current thinking is that the boundaries are formed by sites in the DNA which bind the CTCF protein, and possibly cohesin proteins as well. CTCF is a large protein (although maddeningly I can’t seem to find out how many amino acids it has) with a molecular mass of 80 kiloDaltons. It’s DNA binding is quite specific as it contains 11 zinc fingers (each of which can specifically bind a 3 nucleotide stretch of DNA). In addition to binding to DNA it can bind to itself, forming a perfect way to form loops of DNA.

All the Science paper did was to delete a few CTCF binding sites using the CRISPR technique around the two oncogenes and bang — expression increased. Why?  Because the insulation between the TAD containing the genes and adjacent TADs was broken, allowing control of the genes by enhancers in the new and larger TAD that had been previously sequestered in an adjacent TAD.  The deletions were thousands of basepairs away from the coding sequence of the genes themselves.  All very nice, but it’s fairly artificial.

However the paper notes that across a large pan-cancer cohort, there was a 2 fold enrichment for boundary CTCF site mutations.

High level mathematicians look like normal people

Have you ever had the pleasure of taking a course from someone who wrote the book? I did. I audited a course at Amherst from Prof. David Cox who was one of three authors of “Ideals, Varieties and Algorithms” It was uncanny to listen to him lecture (with any notes) as if he were reading from the book. It was also rather humbling to have a full professor correcting your homework. We had Dr. Cox for several hours each weak (all 11 or 12 of us). This is why Amherst is such an elite school. Ditto for Princeton back in the day, when Physics 103 was taught by John Wheeler 3 hours a week. Physics 103 wasn’t for the high powered among us who were going to be professional physicists (Heinz Pagels, Jim Hartle), it was for preMeds and engineers.

Dr. Cox had one very useful pedagogical device — everyone had to ask a question at the beginning of class, Cox being of the opinion that there is no such thing as a dumb question in math.

Well Dr. Cox and his co-authors (Little and O’Shea) got an award from the American Mathematical sociecty for their book. There’s an excerpt below. You should follow the link to the review to see what the three look like along with two other awardees. http://www.ams.org/publications/journals/notices/201604/rnoti-p417.pdf. Go to any midsize American city at lunchtime, and you’d be hard pressed to pick four of the five out of the crowd of middle aged men walking around. Well almost — one guy would be hard to pick out of the noonday crowd in Williamsburg Brooklyn or Tel Aviv. Four are extremely normal looking guys, not flamboyant or bizarre in any way. This is certainly true of the way Dr. Cox comports himself. The exception proving the rule however, is Raymond Smullyan who was my instructor in a complex variables course back in the day– quite an unusual and otherworldly individual — there’s now a book about him.

Here’s part of the citation. The link also contains bios of all.

“Even more impressive than its clarity of exposition is the impact it has had on mathematics. CLO, as it is fondly known, has not only introduced many to algebraic geometry, it has actually broadened how the subject could be taught and who could use it. One supporter of the nomination writes, “This book, more than any text in this field, has moved computational algebra and algebraic geometry into the mathematical mainstream. I, and others, have used it successfully as a text book for courses, an introductory text for summer programs, and a reference book.”
Another writer, who first met the book in an REU two years before it was published, says, “Without this grounding, I would have never survived my first graduate course in algebraic geometry.” This theme is echoed in many other accounts: “I first read CLO at the start of my second semester of graduate school…. Almost twenty years later I can still remember the relief after the first hour of reading. This was a math book you could actually read! It wasn’t just easy to read but the material also grabbed me.”
For those with a taste for statistics, we note that CLO has sold more than 20,000 copies, it has been cited more than 850 times in MathSciNet, and it has 5,000 citations recorded by Google Scholar. However, these numbers do not really tell the story. Ideals, Varieties, and Algorithms was chosen for the Leroy P. Steele Prize for Mathematical Exposition because it is a rare book that does it all. It is accessible to undergraduates. It has been a source of inspiration for thousands of students of all levels and backgrounds. Moreover, its presentation of the theory of Groebner bases has done more than any other book to popularize this topic, to show the powerful interaction of theory and computation in algebraic geometry, and to illustrate the utility of this theory as a tool in other sciences.”

State functions, state equations, graphs of them and reversibility

Thermodynamic States are all considered to be continuous variables (the fact that Internal Energy (U) is a state variable is half of the first law).

A continuous function of state_function_1 in terms of state_function_2, . . . . state_function_n produces a graph which is an n dimensional surface in n + 1 dimensional space. If this seems rather abstract, we’ll get concrete shortly. Consider the classic calculus 101 function y = x^2. Write it like this

f : R^1 –> R^1
f : x |–> x^2

This does seem a bit stuffy, but the clarity it provides is useful, as you’ll see. R^1 is the set of real numbers. The first line tells you that f goes from the real numbers to the real numbers. The second like gives you what f does to a point in the domain. What about the graph of f? It is the parabola, which lives in the x – y plane, a 2 dimensional space. The graph of f is just a curved line with dimension 1, living in a space one dimension higher (e.g. dimension 2).

Different state functions apply to different physical systems at which point they are called equations of state, with every point on their graph representing a collection of state variables at which the system is at equilibrium (e.g. not changing with time)

The simplest state function comes from the ideal gas law PV = nRT, which was promulgated in 1834 by Claperyon. You may regard it as

T : R^2 –> R^1
T : (P, V) |–> P*V/R == T

This is Temperature (statefunction1) in terms of P (statefunction2) and V (statefunction3). What is its graph — something 2 dimensional living in 3 dimensional space — e. g. a surface.

If you’ve studied PChem, you’ve probably met the Carnot cycle. Here’s a link https://en.wikipedia.org/wiki/Carnot_cycle.  It is represented by  a bunch of curved lines in the PV plane, but each line in the diagramreally represents a line on the 3 dimensional graph of T. You can think of this like a topographic map of a mountain, but not quite. The top and bottom lines represent constant temperature (altitude) but the (semi)vertical lines are paths up and down the mountain. Just looking at the flat PV diagram is pretty misleading.

Any combination of P, V, T not satisfying PV = RT is not on the surface, and is not in equilibrium.  You won’t see any of them on the diagram of the PV plane, which is why it’s so misleading. 

P, V and T will change so they approach the surface (either by minimizing internal energy or maximizing entropy or a combination of both — these are the driving forces of Dill’s book — Molecular Driving Forces.

The definition of surface given above is quite general and applies to more complicated situations — which is why I went to the trouble to go through it. For instance, in some systems Internal Energy (U) is a function of 3 variables Entropy (S), Volume (V) and the number of molecules (N). This is a 3 dimensional surface living in 4 dimensions. It’s just as much of a surface as that for T in terms of P and V, but I can’t visualize it (perhaps you can) Note also that when you go to higher magnification N is not a continuous variable, any more than concentration is.

Any point on the surface can be reached reversibly from any other — what does reversibility actually mean?

Berry Physical Chemistry 2nd Ed 2000 p. 377. Reversibility of changes in equilibrium means 3 things.

l. The change occurs almost infinitesmally slowly (a very large class of real processes have work and heat values very close to reversible processes)

2. Changes remain infinitesmally close to equilibrium (e.g. they stay on the surface. At equilibrium, thermodynamic variables still fluctuate. If movement on the surface is slow enough that the thermodynamic variables are within 1 standard deviation of the average values of the thermodynamic state variables, no observation can show that the stat eof the system has changed

3. Intensive variables corresponding to work being done (e.g. pressure, surface tension, voltage) are continuous across the boundary of the system on which work is being done.

Objects off the surface aren’t in equilibrium and maximization of entropy or minimization of internal energy drive them toward the surface. This implies that the surface is is an attractor. Now that chaos is well known, are there thermodynamic attractors — I’ve written Dill to ask about this.

Hopefully this will be helpful to some of you. Putting it together was to me. As always, the best way to learn something is trying to explain it to someone else.

Sn2 — It’s a gas

Sn2 reactions are a lot more complicated than as taught in orgo 101 (at least in the gas phase). The classic mechanism is very easy to teach to students, it’s just an umbrella turning inside out in the wind. A current article in Science (vol. 352 pp. 32 – 33 1 April ’16) shows how complicated things can be when the reaction is carried out in the gas phase. Mechanisms illustrated include rebound stripping, frontside attack, ion-dipole complex, roundabout, hydrogen bond complex, frontside complex and double inversion.

Why study Sn2 in the gas phase? One reason is to sharpen computational and theoretical methods to be able to predict reaction rates (in gas phase reactions). I was surprised on looking up Rice-Ramsperger-Kassel-Marcus theory to find out how old it was. Back in the 60’s it was taught to us without any names attached. One assumes that before and after reaction the ion molecule complexes are trapped in potential wells. It is assumed that vibrational energies in the complex are quickly distributed to ‘equilibrium’ in the complexes so that detailed computation of rates can be carried out.

Is this of any use to the chemist actually reacting molecules in solution? Other than by sharpening computational tools, I don’t see how it can be given the present state of the art.

Gas phase kineticists are starting to try, but they’ve got a very long way to go. “Stepwise addition of solvent molecules to the bare reactant anion offers a bottom up approach to learn more about the transition of chemical reactions from the gas to liquid phase. To investigate the role of solvation in Sn2 reactions Otto et al. have performed crossed molecular beam studies of the microsolvated” Sn2 reaction (e.g. the approaching anion solvated with all of one or two waters). “The results show that “the dynamics differ dramatically from the unsolved anion.”

That’s not a bug — that’s a feature

Back in the early days of computers you could own (aka personal computers) it wasn’t point and click, but hunt and peck, where commands in the early operating systems (DOS, etc.) had to be typed onto the command line using a keyboard. The interfaces were far from intuitive, to say the least, and the unexpected was always expected. When things went south software designers quickly learned to say “That’s not a bug, thats a feature ! ”

Essentially the same thing has happened to the latest and greatest tool in genetic engineering, the CRISPR system. It’s fascinating that it has been hiding in plain sight for FOUR decades. In med school in the mid60s the basic book about hereditary and DNA was “Sexuality and the Genetics of Bacteria” (1961) by Francois Jacob. No one had any idea that DNA would be sequenced. Viruses were studied (called bacteriophages back then).

No one had any idea that bacteria could defend themselves against viruses, but defend they do by their CRISPR system. It’s only been known for a decade, earlier papers on the subject by 3 different authors Mojica, Gilles Vergnaud, Alexander Bolotin were rejected before eventual publication.

Briefly, when a bacterium is infected by a virus, it makes a copy of fragments of its DNA, and pastes it into its genome. On subsequent invasions, it uses the DNA copy to make RNA, which along with a complex enzyme binds to the genome of the new organism, and destroys it.

It turns out that a PAM (Protospacer Adjacent Motif) is crucial for the whole system to work. The bacterial DNA doesn’t have such a sequence of DNA, and searches for it in the invader. The PAM isn’t large (just 3 nucleotides in a row) and the system looks for it in invading viral DNA double helices.

But where does it look? On the side of the double helix with the least information — the minor groove

Look at the following http://pharmafactz.com/wp/wp-content/uploads/2014/11/watson-crick-base-pairing.jpg

It shows classic Watson Crick base pairing — the major groove is a lot bigger taking up 210 degrees (hardly a groove) with more chemical information) than the minor groove. So binding to the major groove is likely to be far more accurate (as well as easier because it’s a larger space)

So why does E. Coli do this? Because different viruses contain different PAM sequences. [ Nature vol. 530 pp. 499 – 503 ’16 ] This is the crystal structure of the E. Coli Cascade complex (the business end of CRISPR) bound to a foreign double stranded DNA target. The 5′ ATG PAM is recognized in duplex form, from the minor groove side, by 3 structural features in the Cse1 subunit of cascade. The promiscuity inherent to minor groove DNA recognition explains how a single Cascade complex can respond to several distinct PAM sequences — this is a feature not a bug.

Types of variables you need to know to understand thermodynamics

I’m been through the first 200 pages of Dill’s Book “Molecular Driving Forces (2003)” which is all about thermodynamics and statistical mechanics, things that must be understood to have any hope of understanding cellular biophysics. There are a lot of variables to consider (with multiple names for some) and they fall into 7 non mutually exclusive types.

Here they are with a few notes about them

l. Thermodynamic State Variables: These are the classics — Entropy (S), Internal Energy (U), Helmholtz Free Energy (F), Gibbs Free Energy (G), Enthalpy (H).
All are continuous functions of their Natural Variables (see next) so they can be differentiated. Their differentials are exact.

2. Natural variable of a thermodynamic state variable — these are defined as continuous variables which when an extremum (maximum, minimum) of the state variable using them is found, the state function won’t change with time (e.g. is at equilibrium). Here they are for the 5 state functions. T is Temperature, V is Volume, N is number of molecules, S and U are what you think, and p is pressure

State Name State Function Natural Variables
Helmholtz Free Energy— F —T, V, N
Entropy —S —U, V, N
Internal Energy —U — S, V, N
Gibbs Free Energy— G —T. p, N
Enthalpy — H —S, p, N

Note that U and S are both state variables and natural variables of each other. Note also (for maximum confusion) that Helmholtz free energy is not H but F, and that H is Enthalpy not Helmholtz Free energy

3. Extensive variable –can only be characterized by how much there is of it. This includes all 5 thermodynamic state variables (F, S, U, G, H) alone with V volume, and N number of molecules.  Extensive variables are also known as degrees of freedom.

4. Intensive variable — temperature, pressure, and ratios of State and Natural variables (actually the derivative of a state variable with respect to a natural variable — temperature is actually defined this way ( partial U / partial S)

5. Control variables — these are under the experimenter’s control, and are usually kept constant. They are also known as constraints, and most are intensive (volume isn’t). Examples constant temperature, constant volume, constant pressure

6. Conjugate variables. Here we need the total differential of a state variable (which exists for all) in terms of its natural variables to under stand what is going on.

Since U is a continuous function of each of S, V, and N

we have

dU = (partial U/ partial X) dS + (partial U / partial V) dV + (partial u / partial N ) dN

= T dS – p dV – mu dN ; mu is the chemical potential

So T is conjugate to S, p is conjugate to V, and mu is conjugate to N ; note that each pair of conjugates has one intensive variable (T, p, mu) and one extensive one ( S, V, N). Clearly the derivatives ( T, p, mu) are intensive.

7. None of the above — work(w) and heat (q)

Thermodynamics can be difficult to master unless these are clear. Another reason is that what you really want is to maximize (S) or minimize (U, H, F, G) state variables — the problem is you have no way to directly measure the two crucial ones you really want (U, S) and have to infer what they are from various derivatives and control variables. You can measure changes in S and U  between two temperatures by using heat capacities. That’s just like spectroscopy, where all you measure is the difference between energy levels, not the energy levels themselves. But it is the minimum values of U, G, H, F and maximum values of S which determine what you want to know.

There’s more to come about Dill’s book. I’ve found a few mistakes and have corresponded with him about various things that seem ambiguous (to me at least). As mentioned earlier, in grad school 44 years ago, I audited a statistical mechanics course taught by E. Bright Wilson himself. I never had the temerity to utter a word to him. How things have changed for the better, to be able to Email an author and get a response. He’s been extremely helpful and patient.

Too funny to pass up

This is 95%+ a scientific blog, but the following is simply too funny to pass up. None of the people receiving it had heard of it, and liberals and conservatives alike think it’s a riot. I don’t know who wrote it, but it isn’t me. Would the real author step forward? I googled the title but came up with nothing similar.

Subject: Canadians on illegal immigrants

The flood of Trump-fearing American liberals sneaking across the border into Canada has intensified in the past week, sparking calls for increased patrols to stop the illegal immigration. The Republican Presidential primary campaign is prompting an exodus among left leaning citizens who fear they’ll soon be required to hunt, pray, and live according to conservative ideas about the Constitution.

Canadian border farmers say it’s not uncommon to see dozens of sociology professors, global warming activists, and “green” energy proponents crossing their fields at night. “I went out to milk the cows the other day, and there was a Hollywood producer huddled in the barn,” said Southern Manitoba farmer Red Greenfield, whose acreage borders North Dakota. “The producer was cold, exhausted and hungry. He asked me if I could spare a latte and some free-range chicken. When I said I didn’t have any, he left before I even got a chance to show him my screenplay, eh?” In an effort to stop the illegal aliens, Greenfield erected higher fences, but the liberals scaled them. He then installed loudspeakers that blared Rush Limbaugh across the fields, but they just keep coming.

Officials are particularly concerned about smugglers who meet liberals near the Canadian border, pack them into electric cars and drive them across the border where they are simply left to fend for themselves after the battery dies.

“A lot of these people are not prepared for our rugged conditions,” an Ontario border patrolman said. “I found one carload without a single bottle of Perrier drinking water. They did have a nice little Napa Valley cabernet, though, and some kale chips.”

When liberals are caught, they’re sent back across the border, often wailing loudly that they fear assassination from Trump high hairers. Rumors have been circulating about plans being made to build re-education camps where liberals will be forced to drink domestic beer and study the Constitution.

In recent days, liberals have turned to ingenious ways of crossing the border. Some have been disguised as senior citizens taking a bus trip to buy cheap Canadian prescription drugs. After catching a half- dozen young vegans in blue-hair wig disguises, Canadian immigration authorities began stopping buses and quizzing the supposed senior citizens about Perry Como and Rosemary Clooney to prove that they were alive in the ’50s. “If they can’t identify the accordion player on The Lawrence Welk Show, we become very suspicious about their age,” an official said.

Canadian citizens have complained that the illegal immigrants are creating an organic-broccoli shortage, buying up all the Barbara Streisand c.d.’s, and renting all the Michael Moore movies. “I really feel sorry for American liberals, but the Canadian economy just can’t support them,” an Ottawa resident said. “How many art-history majors does one country need?”

=

The narrative rolls on

Let’s play spot the narrative and then, being scientific types, look at the numbers and see what they are telling us. The following is a direct quote of the headline and first few paragraphs of the following ‘news’ article appearing today followed a link to it.

Poll: Majority of American voters blame Donald Trump for violence at rallies

More than two-thirds of American voters hold Donald Trump responsible, in part, for the recent violence that has surrounded his Republican presidential campaign rallies, a new poll has found.

According to the Quinnipiac University national poll released this week, 37 percent of voters surveyed said they believe the GOP front-runner is “very responsible” for violent incidents involving supporters and protesters at his campaign rallies, while 27 percent said he’s “somewhat responsible.”

Less than a quarter said they believe he’s “not responsible.”

More than three-quarters of respondents, meanwhile, also blamed protesters at Trump rallies for being “very responsible” or “somewhat responsible” for such violence, while 70 percent said supporters of the businessman are very or somewhat responsible, the poll found.

Quinnipiac University Poll Assistant Director Tim Malloy contended that the results come somewhat in contrast to claims Trump has made about the origin of such incidents at his campaign events.

http://www.masslive.com/politics/index.ssf/2016/03/poll_majority_of_americans_bla.html#incart_most-comments

A Slanted headline at its best.

It should read

Poll: American voters think protesters at Trump rallies are more responsible for violence at his rallies than Trump.

This fits the facts as stated, if not the narrative. It’s right there in the numbers: 27 + 37 = 64% say it’s Trump’s fault while over 75% (why don’t they say just how far over) say it’s the fault of the protestors.

The higher drivel – II

From the obituary of a leading philosopher at an Ivy League institution. He proposed the following thought experiment to resolve the question of whether objects and relationship exist in the world independently of how we perceive them. This is what bothered Einstein about quantum mechanics, and he is said to have asked Bohr (I think) ” do you think the moon is not there if we don’t look at it”. The thought experiment is a brain placed in a vat by a mad scientist (I’m not making this up). So the brain in the vat — call him Oscar –could not formulate the sentence of “I am a brain in vat” because Oscar has no experience of a real brain or a real vat.

For this they’re currently paying 60K+ a year? It’s the higher drivel.

I read a book by Nozick with similar impossible situations he worried about after a rave review in the New York Times book review a few years ago. It had questions of the order ‘would bubblegum taste the same on the surface of the sun’.

The higher drivel series will appear from time to time — here’s the first one (published 5 years ago)

“The predicament of any tropological analysis of narrative always lies in its own effaced and circuitous recourse to a metaphoric mode of apprehending its object; the rigidity and insistence of its taxonomies and the facility with which it relegates each vagabond utterance to a strict regimen of possible enunciative formations testifies to a constitutive faith that its own interpretive meta-language will approximate or comply with the linguistic form it examines.”

From p. 35 of the NYTimes book review 16 October’11

You could actually major in this stuff (Semiotics) at an Ivy League university (Brown) in the 80’s. According to the article, Semiotics was the third most popular humanities major there at the time.  One son got in in ’86, but (fortunately) didn’t go there.  Nonetheless he was quite interested in Semiotics, hence the name of this blog.  Fortunately the author of the above quote recovered and notes “I now spend more time learning from the insights of science than deconstructing its truth claims.”

What a gigantic waste of time.  Think what Brown could have done by abolishing the department and using the funds for chemistry or mathematics.  The writer tries to salvage something from the experience noting that ‘a striking number of semiotics students have gone on to influential careers in the media and the creative arts.’  Unfortunately this explains a lot about the current media and ‘the creative arts’.

Students were being conned then, and they’re being conned now.  It might not have mattered what you majored in 50+ years ago at an Ivy League university, the world seemed to want us regardless.   A friend majored in Near Eastern studies, was hired by a bank, never saw the MidEast and did quite well.  Not so today.  The waitress serving us last Wednesday at a local bar was a graduate of one of the seven sisters in 2010.  She majored in Sociology and Psychology, is in debt for > 20K for the experience and is unable to find better work.   It isn’t clear what such a major prepares you for other than what she’s doing.  Finding out the distribution of majors of the jobless 20 somethings participating in OWS would be interesting

For a taste of the semiotics world of the 80’s, Google Alan Sokal and read about the fun he had with such a journal — “Social Text”.  Should you  still have the stomach for such things read “The Higher Superstition” by Gross and Levitt, which goes into more detail about Derrida, Foucault and a host of (mostly French) philosophes and what they tried to pull off.

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