Tough 60s chick disappoints woke young interviewer

Quanta — — always has science and math worth reading.   The following is worth reading for the contrasting mindsets of interviewer and interviewee —

Virginia Trimble — now 76 and in declining health, was once young, beautiful, brilliant and a grad student at Cal Tech in astronomy.  Now a prof a UC Irvine she was interviewed by a young woman, about her experiences.

The interviewer did her best to make her appear exploited, but Trimble was having none of it.

Q. So you get to Caltech, and you’re the only woman —

A. I wasn’t. There was this tiny little cluster of seven of us that went through all at the same time …

She was so gorgeous (see her picture in the article) that Feynman asked her to be a model as (presumably) he was learning to draw, paying her $5.50 an hour.

The interviewer couldn’t contain herself

Q. When you spoke to him, did he treat you collegially?

Trimble, never one to pussyfoot around, responds.

A. The obvious question, did we make love? As it happens, no, but not a big deal. It might just as well have been yes, and we would still have been good friends.

The intrepid interviewer persists.

Q: I want to talk about sexual harassment in academia.

I don’t particularly care for the word harassment.

Let’s go with “hanky-panky,” OK?


When I was young and beautiful, I engaged in a great deal of hanky-panky. I could never see anything very wrong with it. You may claim that if a very distinguished senior scientist engages in hanky-panky with a much younger scientist — never mind which gender, and make it a conductor and a violinist if you wish, instead of senior and junior scientists — if that results in real injustice to people not involved in the hanky-panky, then, yeah, you have to have a rule against it. But I’m not so sure that that happens very often.

Clearly not the sort of thing the interviewer expected.  She persists and gamely frames a question so she can get the answer she wants

Q: I just want to clarify, when someone in power makes someone who is subordinate feel that they have to engage in sexual activities for the sake of their job or the sake of their academic career, that is what angers so many people right now.

Trimble is having none of it

A: The step in that syllogism where I part company is the younger — or whatever — person feeling they “have to,” and let me say again that a young attractive female has a lot of power, where older, less attractive men are concerned.

Defeated, the interviewer changes the subject.

Q: What are you most proud of in terms of your scientific work?

There’s a lot of interesting science in the article, but the clash of mindsets interested me more.

Want to understand Quantum Computing — buy this book

As quantum mechanics enters its second century, quantum computing has been hot stuff for the last third of it, beginning with Feynman’s lectures on computation in 84 – 86.  Articles on quantum computing  appear all the time in Nature, Science and even the mainstream press.

Perhaps you tried to understand it 20 years ago by reading Nielsen and Chuang’s massive tome Quantum Computation and Quantum information.  I did, and gave up.  At 648 pages and nearly half a million words, it’s something only for people entering the field.  Yet quantum computers are impossible to ignore.

That’s where a new book “Quantum Computing for Everyone” by Chris Bernhardt comes in.  You need little more than high school trigonometry and determination to get through it.  It is blazingly clear.  No term is used before it is defined and there are plenty of diagrams.   Of course Bernhardt simplifies things a bit.  Amazingly, he’s able to avoid the complex number system. At 189 pages and under 100,000 words it is not impossible to get through.

Not being an expert, I can’t speak for its completeness, but all the stuff I’ve read about in Nature, Science is there — no cloning, entanglement, Ed Frenkin (and his gate), Grover’s algorithm,  Shor’s algorithm, the RSA algorithm.  As a bonus there is a clear explanation of Bell’s theorem.

You don’t need a course in quantum mechanics to get through it, but it would make things easier.  Most chemists (for whom this blog is basically written) have had one.  This plus a background in linear algebra would certainly make the first 70 or so pages a breeze.

Just as a book on language doesn’t get into the fonts it can be written in, the book doesn’t get into how such a computer can be physically instantiated.  What it does do is tell you how the basic guts of the quantum computer work. Amazingly, they are just matrices (explained in the book) which change one basis for representing qubits (explained) into another.  These are the quantum gates —  ‘just operations that can be described by orthogonal matrices” p. 117.  The computation comes in by sending qubits through the gates (operating on vectors by matrices).

Be prepared to work.  The concepts (although clearly explained) come thick and fast.

Linear algebra is basic to quantum mechanics.  Superposition of quantum states is nothing more than a linear combination of vectors.  When I audited a course on QM 10 years ago to see what had changed in 50 years, I was amazed at how little linear algebra was emphasized.  You could do worse that read a series of posts on my blog titled “Linear Algebra Survival Guide for Quantum Mechanics” — There are 9 — start here and follow the links — you may find it helpful —

From a mathematical point of view entanglement (discussed extensively in the book) is fairly simple -philosophically it’s anything but – and the following was described by a math prof as concise and clear–

The book is a masterpiece — kudos to Bernhardt

Technology marches on — or does it?

Technology marches on — perhaps.  But it certainly did in the following Alzheimer’s research [ Neuron vol. 104 pp. 256 – 270 ’19 ] .  The work used (1) CRISPR (2) iPSCs (3) transcriptomics (4) translatomics to study Alzheimer’s.  Almost none of this would have been possible 10 years ago.

Presently over 200 mutations are known in (1) the amyloid precursor protein — APP (2) presenilin1 (3) presenilin2.  The presenilins are components of the gamma secretase complex which cleaves APP on the way to the way to the major components of the senile plaque, Abeta40 and Abeta42.

There’s a lot of nomenclature, so here’s a brief review.  The amyloid precursor protein (APP) comes in 3 isoforms containing 770, 751 and 695 amino acids.  APP is embedded in the plasma membrane with most of the amino acids extracellular.  The crucial enzyme for breaking APP down is gamma secretase, which cleaves APP inside the membrane.  Gamma secretase is made of 4 proteins, 2 of which are the presenilins.  Cleavage results in a small carboxy terminal fragment (which the paper calls beta-CTF) and a large amino terminal fragment. If beta secretase (another enzyme) cleaves the amino terminal fragment Abeta40 and Abeta42 are formed.  If alpha secretase (a third enzyme) cleaves the amino terminal fragment — Abeta42 is not formed.   Got all that?

Where do CRISPR and iPSCs come in?  iPSC stands for induced pluripotent stem cells, which can be made from cells in your skin (but not easily).  Subsequently adding the appropriate witches brew can cause them to differentiate into a variety of cells — cortical neurons in this case.

CRISPR was then used to introduce mutations characteristic of familial Alzheimer’s disease into either APP or presenilin1.  Some 16 cell lines each containing a different familial Alzheimer disease mutation were formed.

Then the iPSCs were differentiated into cortical neurons, and the mRNAs (transcriptomics) and proteins made from them (translatomics) were studied.

Certainly a technological tour de force.

What did they find?  Well for the APP and the presenilin1 mutations had effects on Abeta peptide production (but they differered).  Both however increased the accumulation of beta-CTF.  This could be ‘rescued’ by inhibition of beta-secretase — but unfortunately clinical trials have not shown beta-secretase inhibitors to be helpful.

What did increased beta-CTF actually do — there was enlargement of early endosomes in all the cell lines.   How this produces Alzheimer’s disease is anyone’s guess.

Also quite interesting, is the fact that translatomics and transcriptomics of all 16 cell lines showed ‘dysregulation’ of genes which have been associated with Alzheimer’s disease risk — these include APOE, CLU and SORL1.

Certainly a masterpiece of technological virtuosity.

So technology gives us bigger and better results

Or does it?

There was a very interesting paper on the effect of sleep on cerebrospinal fluid and blood flow in the brain [ Science vol. 366 pp. 372 – 373 ’19 ] It contained the following statement –”

During slow wave sleep, the cerebral blood flow is reduced by 25%, which lowers cerebral blood volume  by ~10%.  The reference for this statement was work done in 1991.

I thought this was a bit outre, so I wrote one of the authors.

Dr. X “Isn’t there something more current (and presumably more accurate) than reference #3 on cerebral blood flow in sleep?  If there isn’t, the work should be repeated”

I got the following back “The old studies are very precise, more precise than current studies.”

Go figure.

Vaping — don’t do it until we know more

If you have kids, I’d advise them to stop vaping entirely until we know more. Here’s why — granted that there have been ‘only’ several hundred cases of ‘lung injury’ and a few deaths  in a 300+ million population, but in any new illness (AIDs, SARs, Legionnaire’s diseases) only the most severe cases are seen first.  

This is exactly the way it was with AIDs, the first few cases seroconverting (showing they’d been infected with the virus) had their immune system collapse almost immediately after infection.  As time wore on, we’d see seroconverters who remained healthy for 1 year, 2 years, 5 years, because (for reasons we still don’t understand) they were resistant to the virus or had a stronger immune system.  But eventually they got sick and died as well.

So it is with vaping related lung illness.  How many more cases we’ll see in  more resistant individuals in the coming years isn’t known. Will we have a nation of 30 year olds crippled with chronic lung disease?  Unlike AIDS, SARS or Legionnaire’s disease where there is a single organism, there are thousands of vaping products, and what people are putting into the machines is completely unknown.  Perhaps it’s just one drug.  Perhaps it’s a contaminated drug.  Perhaps its the particular machine.  At this point we don’t know.  It’s just like the early days of the AIDs epidemic — plausible theories abound and reliable data is scarce.  I was practicing medicine when AIDs came out in the late 70s and it was scary as hell, not knowing what was causing it.  At least with this we’re pretty sure it’s the vaping, given the age distribution and the positive histories in all.

We have one excellent example of a genetic condition predisposing to lung disease — alpha1 antitrypsin deficiency predisposes to emphysema and chronic obstructive pulmonary disease  —  It would be useful  to see how many of the vaping cases have this deficiency.

This just in – according to the Wall Street Journal 2 hours ago 31 October ’19 ago the CDC says there have been 1,888 cases with 37 deaths.  Hopefully this is NOT the tip of the iceberg  — but probably it is.

Addendum 1 Nov ’19 I wrote this to a niece who has an 18 year old daughter entering college.  She is a teacher in a standard American high school (not in the ghetto, not filthy rich).  If any one has boots on the ground she does. Her response:  “Yes it’s very common in high school” — scary.

Addendum 8 Nov ’19  — The following comment by Peter Shenkin is so important that it belongs in the body of the blog proper —

It’s pretty impressive, but these are early times in the investigation.

If you have kids, I’d advise them to stop vaping entirely until we know more. Here’s why — granted that there have been ‘only’ …

You wrote: “Vaping — don’t do it until we know more”

We now know more; source of the following quote is at the end.

“CDC Announces “Major Breakthrough” that I Recognized and Reported Two Months Ago; Outbreak is Almost Certainly Not Associated with Legal Nicotine Vapes
Minutes ago, the Centers for Disease Control and Prevention (CDC) announced what they called a “major breakthrough” in its investigation of the vaping-associated respiratory illness outbreak. They tested lung tissue samples from 29 case patients and all 29 (100%) were found to contain vitamin E acetate oil.

This finding does represent a major breakthrough for four reasons:

1. The vitamin E acetate oil was detected in the actual lung tissue of the case patients.

2. The vitamin E acetate oil was detected in every single one of the lung tissue samples from these 29 case patients.

3. The samples came from 10 different states, confirming that the outbreak seems to have a common cause, rather than geographic variation.

4. Three of the patients whose lung samples revealed vitamin E acetate had reported using only nicotine-containing products, thus confirming that there is significant under-reporting which may explain why about 11% of the patients do not report vaping THC.”

The above quote is from:

Full disclosure: Michael Siegel, a Public Health and Epidemiology doc who writes this blog, is my first cousin once removed. In another blog entry, he lambasts the FDA for disallowing mint vaping liquids while giving cigarette companies a pass on mint-flavored cigarettes.

The Russian language

“The power of language is its ambiguity” sayeth I.  This came up because my nephew married a wonderful Russian expat a few weeks ago.  Plucky fellow that he is, he’s learning to speak Russian.  Like my wife’s friend of 50+ years ago he is amazed at how many words the language has.  Russian apparently has a word for everything so there is little ambiguity, which must make the language hard to pun in.

Someone Googled the number of words in Russian and English and they’re about the same.

Perhaps the lack of ambiguity makes Russian hard to learn (and use).  Computer languages (basic, C, pascal) are completely unambiguous.  Every reserved word and operator means exactly one thing, no more no less.

Most people find programming far from intuitive.  It’s hard to express our sloppy ideas in unambiguous computer language.  Given it’s difficulty giving concrete form to your ideas, computer languages aren’t as powerful (in the sense of being easy to use) as your sloppy sentences.

Why should language be so ambiguous?  My guess is, that it has to be this way given the way we perceive the world (and the way the world probably actually is — ontology if you want to impress your friends).

We don’t live in Plato’s world of perfect forms, but in a world of objects that only partially and rather poorly instantiate them.  This is as true of science as anything else — even supposedly well defined terms change their meaning — are the giant viruses really viruses?  What do we really mean by a gene?  It used to be a part of DNA coding for a protein, but what about the DNA that controls when and where a protein is made.   Mutations here can cause disease, so are they genes?

Language, to be useful, must express our imperfect ways of rigidly classifying the world (perhaps because such a classification is impossible).

Socially, I never thought of our family as inhibited, but the Russians I met seemed more alive and vibrant than our lot (this without them living up to their reputation of hard drinking).

How does ketamine lift depression?

The incredibly rapid improvement in depression (hours) produced by ketamine is unprecedented and surely is telling us something vitally important about depression.  If only we could figure out what it is.  Clinicians were used to waiting weeks for antidepressants of all sorts to work.  As a neurologist, I’d see it work in a week or so in my MS patients depressed due a relapse.

Two recent papers show just how hard it is going to be [Neuron  vol. 104 pp. 182 – 182, 338 – 352 ’19 ]. First off you have to accept the idea that even though animals (usually mice) can’t tell us how they feel, we still have reasonable animal models of depression (tail suspension test, forced swim test).  We can at least get a handle on anhedonia using the sucrose preference test.

Throw ketamine at an animal and measure the biochemical or the neurophysiologic effect of your choice. There are zillions of them.  Throw just about anything at the brain, and all sorts of things change.  The problem is showing that the change is relevant.  Is the known blockade of NMDA receptors by ketamine how it helps depression.  Give enough and you get out of body experiences and all sorts of craziness, not an antidepressant effect.

Homer1a is a protein found at the synapse, and like all scaffold proteins, it interacts with a bunch of different proteins. It links another type of glutamic acid receptor (mGluR1 and mGluR5) to inositol 1, 4, 5 trisphosphate receptors (IP3Rs) on the endoplasmic reticulum.  It also links mGluR1 and mGluR5 to NMDARs and other ion channels.

So what?

Other work by the authors showed that knockdown of Homer1a (using small interfering RNA – siRNA) in the medial prefrontal cortex (mPFC) abolished the antidepressant effects (in animal models) to ketamine.  Well that’s good, but even better is that knockdown also abolished the antidepressant effects of a tricyclic antidepressant (imipramine).

The present work showed that increasing the expression of Homer1a (the protein comes in various isoforms) in the frontal cortex reduced depression in the various models.

Pretty good — all we have to do is increase Homer1a expression to have a treatment of depression.

Don’t get your hopes up, and this is why depression research is so — well depressing.

Increasing Homer1a expression in another brain region (the hippocampus) has exactly the opposite effects.

50 years later . . .

50 years ago, I was a US Air Force physician taking care of the maimed and wounded at Fitzsimons Army Hospital in Denver.  It was the first in a series of military adventures foisted on our soldiers by ‘the best and the brightest’ (aka our elites). None have gone well — Desert Storm, regime change in Libya, Afghanistan, you name it.

Presently President Trump is taking heat from congress and just about the entire mainstream press (right and left) for pulling our soldiers out of Syria, and ‘letting Putin win’.  Never questioned is why we were there in the first place.  We should equip anyone  in the press who wishes to defend the Kurds with a rifle (never call it a gun if you live in the barracks) and send them over.  I doubt that many have served (or would serve now)

74 years ago as a boy I saw firetrucks and cars parading around town making as much noise as possible.    It was Victory in Europe day (VE day).  It meant that one of the four uncles in our families could come home although I didn’t understand it at the time.  The other three were island hopping in the Pacific as a marine, helping guerillas in the Philippines, and running a company of MPs in China.

Just under 75 years ago the other uncle was in the Battle of the Bulge fighting against Germany.

Why in the world are we still defending Germany 3/4 of a century later?  President Trump has been criticized for offending our European allies by asking them to pay more for their defense.  They will not be sufficiently offended to stop taking our money.  It’s welfare dependency on the national level.

Defense against what?  Russia — a third world country with a first world army and educational system which is barely maintaining its population.  Europe has 3 times the population and GNP.  As Franklin said “We must all  hand together, or assuredly we shall all hang separately” (1776). If European nations won’t, so be it.

President Trump is asking questions that should have been asked long ago.  He is doing exactly what he was elected to do.

Why it is sometimes good to read the preface7

“the (gravitational) field equations are derived  . . .  from an analysis of tidal forces.”  Thus sayeth p. xii of the preface to “The Geometry of Spacetime” by James J. Callahan.  This kept me from passing over pp. 174 –> on tides, despite a deep dive back into differentiating complicated functions, Taylor series etc. etc. Hard thinking about tidal forces finally gave me a glimpse of what general relativity is all about.

Start with a lemma.  Given a large object (say the sun) and a single small object (say a satellite, or a spacecraft), the path traced out by the spacecraft will lie in a plane.  Why?

All gravitational force is directed toward the sun (which can be considered as a point mass – it is my recollection that it took Newton 20 years to prove this delaying the publication of the Principia , but I can’t find the source).  This makes the gravitational force radially symmetric.

Now consider an object orbiting the sun (falling toward the sun as it orbits, but not hitting the sun because its angular momentum carries away). Look at two close by points in the orbit and the sun, forming a triangle.  The long arms of the triangle point toward the sun.  Now imagine in the next instant that the object goes to a fourth point out of the plane formed by the first 3.  Such a shift in direction requires a force to produce it, but in the model there is only gravity, so this is impossible meaning that all points of the orbit lie in a plane containing the sun considered as a point mass.

You are weightless when falling, even though you are responding to the gravitational force (paradoxic but true).   An astronaut in a space capsule is weightless because he or she is falling but the conservation of angular momentum keeps them going around the sun.

Well if the sun can be considered a point mass, so can the space capsule.  Call the local coordinate of the point representing the capsule point mass x.  The orbit of x around the sun is in the x — sun plane.

Next put two objects 1 foot above and below the x — sun plane.


x  ——————————sun point mass


Objects 1 and 2 orbit in a plane containing the sun point mass as well.  They do not orbit parallel to x (but very close to parallel).

What happens with the passage of time?   The objects approach each other.  To an astronaut inside the capsule it looks like a force (similar to gravity) is pushing them together.  These are the tidal forces Callahan is talking about.

Essentially the tidal are produced by gravitational force of the sun even though everything in the capsule floats around feeling no gravity at all.

Consider a great circle on a sphere — a longitudinal circle on the earth will do.  Two different longitudinal great circles will eventually meet each other.  No force is producing this, but the curvature of the surface in which they are embedded.

I think that  what appear to be tidal forces in general relativity are really due to the intrinsic curvature of spacetime.  So gravity disappears into the curvature of spacetime produced by mass.   I’ll have to go through the rest of the book to find out.  But I think this is pretty close, and likely why Callahan put the above quote into the preface.

If you are studying on your own, a wonderful explanation of just what is going on under the algebraic sheets of the Taylor series is to be found pp. 255 –> of Fundamentals of Physics by R. Shankar.  In addition to being clear, he’s funny.  Example: Nowadays we worry about publish and perish, but in the old days it was publish and perish.

Why don’t serotonin neurons die like dopamine neurons do in Parkinson’s disease

Say what ?  “This proportion will likely be higher in rat dopaminergic neurons, which have even larger axonal arbors with ~500,000 presynapses, or in human serotonergic neurons, which are estimated to extend axons for 350 meters” – from [ Science vol. 366 3aaw9997 p. 4 ’19 ]

I thought I was reasonably well informed but I found these numbers astounding, so I looked up the papers.  Here is how such statement can be made with chapter and verse.

“The validity of the single-cell axon length measurements for dopaminergic and cholinergic neurons can be independently checked with calculations based on the total volume of the target territory, the density of the particular type of axon (axon length per volume of target territory), and the number of neuronal cell bodies giving rise to that type of axonThese population analyses are made possible by the availability of antibodies that localize to different types of axons: anti-ChAT for cholinergic axons (also visualized with acetylcholine esterase histochemistry), anti-tyrosine hydroxylase for striatal dopaminergic axons, and anti-serotonin for serotonergic axons.

The human data for axon density and neuron counts have been published for forebrain cholinergic neurons and for serotonergic neurons projecting from the dorsal raphe nucleus to the cortex, and cortical volume estimates for humans are available from MRI analyses; forebrain cholinergic neuron data is also available for chimpanzees. These calculations lead to axon length estimates of 107 m and 31 m, respectively, for human and chimpanzee forebrain cholinergic neurons, and an axon length estimate of 170–348 meters for human serotonergic neurons.”

H. Wu, J. Williams, J. Nathans, Complete morphologies of basal forebrain cholinergic neurons in the mouse. eLife 3, e02444 (2014). doi: 10.7554/eLife.02444; pmid: 24894464

How in the world can these neurons survive as long as they do?

Not all of them do–  At birth there are 450,000 neurons in the substantia nigra (one side or both sides?), declining to 275 by age 60.  Patients with Parkinsonism all had cell counts below 140,000 [  Ann. Neurol. vol. 24 pp. 574 – 576 ’88 ]. Catecholamines such as dopamine and norepinephrine are easily oxidized to quinones, and this may be the ‘black stuff’ in the substantia nigra (which is latin for black stuff).

Here are the numbers for serotonin neurons in the few brain nuclei (dorsal raphe nucleus) in which they are found.  Less than dopamine.  A mere 165,000 +/- 34,000 — › pubmed

So being too small to be seen with a total axon length of a football field, they appear to last as long as we do.  Have we missed a neurological disease due to loss of serotonin neurons?

Why should the axons of dopamine, serotonin and norepinephrine neurons be so long and branch so widely?  Because they release their transmitters diffusely in the brain, and diffusion is too slow, so the axonal apparatus must get it there and release it locally into the brain’s extracellular space, no postsynaptic specializations are present in volume neurotransmission — that’s the point.  This is one of the reasons that a wiring diagram of the brain isn’t enough —

Just think of that dopamine neuron with 500,000 presynapses.  Synthesis and release must be general, as the neuron couldn’t possibly address an individual synapse.

The more we know the more remarkable the brain becomes.


At a wedding . . .

I was a wedding last weekend which was the first Jewish wedding in the bride’s family in 100 years, the parents having emigrated from Russia 28 years ago where such things were banned. It shows what progressive secular religion can do if given a chance and the power to do it.

Like all religions, it seeks to dominate others.

The parallels between progressive secular religion and others are so uncanny and complete, they’re not even parallels.

Example1  — sinecures — a device used by the clerisy to support incompetent progeny — Hunter Biden and Burisma and the Chinese fund.

Example 2 — indulgences — buying forgiveness for sin by donating to the church — Jeffrey Epstein’s contributions to Planned Parenthood and NOW.  Martin Luther would have no problem recognizing this as such.

Example 3 — good works buying absolution for sin.  Clinton’s rape and abuse of women forgiven by legislation on reproductive rights.

Those are just the low hanging fruit.  Moving on to actual theology, social guilt and white privilege is simply original sin in modern garb.  You need do nothing to acquire it, and you can’t get rid of it.

Moving on to the old testament — there are sins which can not be forgiven, for which the punishment is personal destruction — wearing blackface as an adolescent, writing against homosexual marriage decades ago etc. etc.  Here comes the twitter mob.

Then there is heresy.   One such is admiring conventional religion.  This calls forth the twitter mob experiencing the rush that comes from expressing their moral superiority.

The worst (recent) example is the opprobrium heaped on Botham Jean for hugging his brother’s murderer.  The harpies were in full cry, but it is impossible for me to watch that video without being moved.  Viewed through the narrow lens of race it is disturbing, but viewed in the much wider and more appropriate lens of human emotion it is incredibly powerful.

Progressive secular theology (for that is what it is) gives no quarter.