A perfect opinion poll

We are about to find out the political persuasions (and perceptions) of a large group of people without spending a cent. National Public Radio (NPR) claims to be unbiased politically. The new budget of the Trump administration proposes to cut out all federal funding. It will be fascinating to see who complains and fights against it. If they’ve established themselves as neutral honest brokers, the complaints should arise equally from left and right, Democrat and Republican.

Note the results are irrelevant to the question of whether NPR is actually unbiased. This is about people’s perceptions of NPR, those liking it finding it agreeable to their world view and more likely to protest its discontinuance.

Did these guys just repeal the second law of thermodynamics and solve the global warming problem?

Did these guys just repeal the second law of thermodynamics and solve the global warming problem to boot? [ Science vol. 355 pp. 1023 – 1024, 1062 -1066 ’17 ] Heady stuff. But they can put a sheet of metamaterial over water during the day in Arizona and cool it by 8 degrees Centigrade in two hours!

How did they do it? Time for a little atmospheric physics. There is nothing in the Earth’s atmosphere which absorbs light of wavelength between 8 and 13 microns (this is called the atmospheric window). So anything radiating energy in this range sends it out into space. This is called radiative cooling. It doesn’t work during the day because most materials absorb sunlight in the visible and near infrared range (.7 -2.5 microns) heating them up. Solar power density overwhelms the room temperature radiation spectrum shorter than 4 microns. So for daytime cooling you need a material reflecting all the light shorter than 4 microns, while being fully emissive for longer wavelengths.

This work describes a metamaterial– https://en.wikipedia.org/wiki/Metamaterial — in which small (average diameter 4 microns) spheres ofSiO2 (glass) are randomly dispersed in a polymer matrix transparent to visible and infrared light. The matrix is 50 microns thick. The whole shebang is backed by a very thin (.2 micron) silver mirror. So light easily passes through the film and is then bounced back by the mirror without being absorbed.

Chemists have already studied the Carnot cycle, which gives the maximum efficiency of a heat engine. This is always proportional to the temperature difference between phases of the cycle. That’s why the biggest thing about a nuclear power plant is the cooling tower (and almost as important). Well few things are colder than the cosmic microwave background (2.7 degrees Centigrade above absolute zero).

So while the entropy of the universe increases as the heat goes somewhere, locally it looks like the second law of thermodynamics is being violated. No work is done (as far as i can tell) yet the objects spontaneously cool.

Perhaps the physics mavens out there can help. I seem to remember Feynman and Wheeler once saying something to the effect that radiation is impossible without something around to absorb it. If I haven’t totally garbled the physics, it almost sounds like emitter and absorber are entangled.

Anyway beaming heat out into space through the atmospheric window sounds like a good way to combat global warming.

No wonder DARPA supported this research.

A book recommendation

If you’re Irish and your family looks like it’s been at a wake since 8 November or if you’re Jewish and your family has been sitting shiva since Trump won, I’ve got a book for them. They’ll hate it of course and reading it will be painful for them, but if they want to defeat him in the future they’d best buckle up and read it.

The book is called “How Trump Won” by Joel B. Pollak, and Larry Schweikart. Pollak is Breitbart Senior News Editor at Large, and Schweikart is an emeritus American history prof.

Why should the mourners read it? Simply this. If  you want to defeat Trump in the future you should know just how he beat you. The celebrators of his victory will need no urging.

It’s pretty well written, and the chapters alternate between the two with Pollak describing his experiences in the last days of the campaign starting 19 October and Schweikart covering American history starting with Martin van Buren to put things in context. It is disconcerting as Schweikart also covers the Trump campaign from its inception in 2015, so there are jumps in time from chapter to chapter.

Even though a political junkie I was as bamboozled by the press coverage of the election as anyone else, going to bed at 10PM election night because I knew it would be a rout of Trump — “Hispanics surging to the polls” etc. etc.

A few points to whet your interest. Giving the lie to Breitbart’s antisemitism, Pollak is a devout Jew,leaving the campaign trail each Saturday to observe the sabbath. He’s a Harvard Graduate.

The authors knew Trump would win Florida, based on the early voting. They knew how various counties reliably voted, and the panhandle was early voting heavily. They could see that blacks weren’t voting as much — down 3 – 4 % in Florida, 8% in North Carolina (apparently absolute absentee numbers by location are available long before the election, although not WHO the voters were for). So much for the theory that North Carolina was won because it was difficult for blacks to get the polls — there certainly is no obstacle for early voting.

Here’s another — why were the polls so wrong. People were afraid to say they were for Trump (particularly in liberal enclaves). One pollster (Trafalgar) figured out a way around this — they just asked people who they thought their neighbors would vote for.

On election night the media did what they authors expected, calling states for Clinton as soon as possible, and delaying calling any states for Trump for as long as possible.

Well that’s enough. Either you will grit your teeth and read it or you won’t.

A few other points — I’ve never seen the Wall Street Journal, the New York Times, the Nation and the National Review agree on anything. But they were uniformly against Trump slanting the news against him, declaring his campaign imploding at various times. Fascinating that it had no effect. The National Review put out an entire issue in January 2016 titled “Against Trump.”

So if you find a biased article against your favorite politician (assuming you have one) — relax — it no longer matters.

The book is not abstract, filled with interviews by Pollak of those attending Trump rallies (along with interview of those there to protest him).

Back to the drawing board on knockouts and knockdowns

Nothing could be simpler than the distinction between the initial product of genes that code for proteins (mRNA) and genes that don’t (long non-Coding RNAs — aka lncRNA, lincRNA). Not anymore according to an exceedingly clever and well thought out piece of work.

[ Cell vol. 168 pp. 753 – 755, 843 – 855 ’17 ] We know that ultraviolet light damages DNA primarily by forming pyrimidine dimers. Naturally transcription of DNA won’t be as accurate, so the cell has ways to shut it down. Ultraviolet exposure results in an unusual type of restriction of transcription along with slower elongation, with the result that only the promoter proximal 20 – 25 kiloBases of a protein coding gene are efficiently transcribed into mRNA.

In addition, after ultraviolet damage there is a global switch in pre-mRNA processing resulting in a preference for the production of transcripts containing alternative last exons not normally included in the dominant mRNA isoform. Some 84 genes are processed this way.

ASCC3 is the strongest regulator of transcription following UV damage, acting to repress it after UV damage. It is a DEAD/DEAH box DNA helicase component. The ASCC3 protein interacts with RNA polymerase II (Pol II) and becomes highly ubiquitinated and phosphorylated on UV irradiation. It isn’t required to establish transcriptional repression, just maintainance. Disruption of the UV specific form — e.g. the short isoform containing the alternative last exon has the opposite effect, allowing transcriptional recovery after UV damage.

This explains why the human genes remaining expressed (or actually induced) after UV irradiation are invariably ‘very short’ (whatever that means).

The short and long isoforms constitute an autonomous regulatory module, and are related functionally, so the effect of deleting one can at least be partially compensated for by deleting the other.

The 3,100 nucleotide long ‘short’ isoform, codes for a protein, but the protein itself didn’t have the effect of the short form mRNA (see if you can figure out, without reading further how the authors proved this). The mRNA produced from the short isoform is found almost exclusively in the nucleus. The authors put in a stop codon immediately downstream of the start codon which ablated protein production but not transcription into the appropriate mRNA, but there was still rescue of the transcriptional recovery phenotype. So the functional form of the short RNA isoform is mediated by a nonCoding RNA encoded in the ASCC3 protein coding gene. The short ASCC3 isoform has an open reading frame of 333 nucleotides, but functionally it is a lncRNA (of 3.5 kiloBases).

So protein genes can produce functional lncRNAs. How many of them actually do this is unknown. When you knockdown a gene, how much of the effect is due to less protein and how much due to the (putative) lncRNA which also might be produced by the gene. That’s why it’s back to the drawing board for knockout mice (or even mRNA knockdown using shRNA etc. etc.)

The current definition of lncRNA is absence of protein coding potential in a gene.

Why have the same gene code for two different things — there may be a regulatory advantage — controlling the function of the protein. lncRNAs have the unique ability to act in close spatial proximity to their transcription loci.

Stay tuned. It’s just fascinating what we still don’t know.

How diverse are thy articles oh alumni magazines

College Alumni Magazines love to brag about the wonderful things their graduates are doing. The recent Jan/Feb issue of one they send to me bragged about the exploits of two of their business school alums in the sports business, one graduating in 1968 the other in 1997. They also had profiles of 7 alums receiving awards at the 2016 reunions.

I didn’t get one even though attending my 50th medical school reunion. There was a lot of congestion as Donald Trump was attending the graduation of one of his kids while running for president. Our med school classmate and Nobel Laureate addressed the graduation. He didn’t get an award either, they thought he had enough.

The issue also had room for a nice recipe for Chocolate Chip Banana Cookies.

There was also an article about the president of the school deciding what US laws the University would and wouldn’t obey, declaring the University to be a “Sanctuary”

In one of the Sherlock Holmes stories the following dialog appears

Gregory (Scotland Yard): “Is there any other point to which you would wish to draw my attention?”
Holmes: “To the curious incident of the dog in the night-time.”
Gregory: “The dog did nothing in the night-time.”
Holmes: “That was the curious incident.”

It wasn’t until I read the letters to the editor in the March/April issue, that I realized just what was curious about the Jan/Feb issue.

They failed to have an article about another graduate of the business school in 1968.

Donald Trump Wharton 1968.

The first US president from the University of Pennsylvania in its 227 years of existence.

To be fair they did have an extremely wimpy note from the editor concerning why they didn’t have an article about Trump.

Ah diversity of thought and opinion in the Ivy League

Res ipsa locquitur

It’s been over 50 years since McLuhan noted “the medium is the message”.  It’s still very true

The humble snow flea teaches us some protein chemistry

Who would have thought that the humble snow flea (that we used to cross country ski over in Montana) would teach us a great deal about protein chemistry turning over some beloved shibboleths in the process.

The flea contains an antifreeze protein, which stops ice crystals from forming inside the cells of the flea in the cold environment in which it lives. The protein contains 81 amino acids, is 45% glycine and contains six  type II polyProline helices each 8 amino acids long (https://en.wikipedia.org/wiki/Polyproline_helix). None of the 6 polyProline helices contain proline despite the name, but all contain from 2 to 6 glycines. Also to be noted is (1) the absence of a hydrophobic core (2) the absence of alpha helices (3) the absence of beta turns (4) the protein has low sequence complexity.

Nonethless it quickly folds into a stable structure — meaning that (1), (2), and (3) are not necessary for a stable protein structure. (4) means that low sequence complexity in a protein sequence does not invariably imply an intrinsically disordered protein.

You can read all about it in Proc. Natl. Acad. Sci. vol. 114 pp. 2241 – 2446 ’17.

Time for some humility in what we thought we knew about proteins, protein folding, protein structural stability.

20,000 NanoSensors under the Cell (apologies to Jules Verne)

Too bad Jules Verne isn’t around to read PNAS vol. 114 pp. 1789 – 1794 ’17 where 20,000 fluorescent nanoSensors were placed under a single PC12 cell. PC12 cells are derived from a pheochromocytoma, a tumor which secretes catecholamines like dopamine and norepinephrine. So they’re almost neurons, and they contain vesicles containing dopamine, just like neurons, but they don’t form synapses.

The pictures they show of the cells shows the cell bodies sitting on a slide to be about 100 microns in diameter, with multiple protrusions so how are you going to get 20,000 sensors underneath them. Assuming them to be circular that’s about 3 per square micron. A micron is 10,000 Angstroms. The authors used Single Walled Carbon NanoTubes (SWCNTs) — e.g. rolled up graphene. They have a diameter of from 5 – 20 Angstroms, so there’s plenty of room for many in a square micron.

Here’s what they did. “Previously we found that the corona phase around SWCNTs can be engineered to recognize certain small analytes––a phenomenon we termed Corona Phase Molecular Recognition (CoPhMoRe) (7, 25, 26). Specifically, DNA-wrapped SWCNTs were found to increase their near InfraRed fluorescence in the presence of catecholamines . Here, we synthesized and characterized different DNA/SWCNT com- plexes and identified the best candidates for dopamine detection.

What they found is less remarkable than having the guts to try something like this. They could stimulate the cells to release dopamine using potassium (maddeningly I couldn’t find the concentration anywhere). Then with the density of sensors they could find out where it was released (the edges of the cell) with a time resolution of .1 second. It wasn’t generally released, but in hotspots — what you’d expectd if it were being released due to vesicles containing dopamine fusing with the cell membrane.

Remarkable — hard to see how they’re going to get this sort an array into a living organism, but their use in the study of brain slices can’t be far away.

Go see The Great Wall

There’s a nice weekend coming up in the states. Go see “The Great Wall” at your local multiplex. It isn’t doing that well in the USA and might not be there for long. Apparently it is doing well in China. Netflix just won’t cut it, as the movie must be seen on a big screen to be appreciated.

It is simply a visual feast. It is beautifully shot and many of the scenes could be paintings. The choreography of the action is excellent. It is one of the most beautiful pictures I’ve ever seen. It is an action picture however, and somewhat brutal and gory.

I find it remarkable that it has been criticized by both left and right. Some call it jingoistic propaganda for China, other saying that it is basically anti-immigrant. They should all calm down and just go and see a great flick.

Although I know more about Chinese culture than most Americans (with a Chinese daughter in law and two grandchildren over there), I’m sure there are tons of cultural references that I’ve missed. The monsters being fought look like much of the statuary in the forbidden city. I remember watching a Chinese movie back in grad school in the 60’s with two Chinese guys, when one of them said — they’re playing the War Song of China (something I couldn’t find on Google).

Norbert Weiner

In the Cambridge Mass of the early 60’s the name Norbert Weiner was spoken in hushed tones. Widely regarded as a genius tutti the assembled genii of Cambridge, that was all I knew about him aside from the fact that he got a bachelor’s degree in math from Tufts at age 14. As a high school student I tried to read Cybernetics, a widely respected book he wrote in 1948, and found it incomprehensible.

Surprisingly, his name never came up again in any undergraduate math courses, graduate chemistry and physics courses, extensive readings on programming and computation (until now).

From PNAS vol. 114 pp. 1281 – 1286 ’17 –“In their seminal theoretical work, Norbert Wiener and Arturo Rosenblueth showed in 1946 that the self-sustained activity in the cardiac muscle can be associated with an excitation wave rotating around an obstacle. This mechanism has since been very successfully applied to the understanding of the generation and control of malignant electrical activity in the heart. It is also well known that self-sustained excitation waves, called spirals, can exist in homogeneous excitable media. It has been demonstrated that spirals rotating within a homogeneous medium or anchored at an obstacle are generically expected for any excitable medium.”

That sounds a lot like atrial fibrillation, a serious risk factor for strokes, and something I dealt with all the time as a neurologist. Any theoretical input about what to do for it would be welcome.

A technique has been developed to cure the arrhythmia. Here it is. “Recently, an atrial defibrillation procedure was clinically introduced that locates the spiral core region by detecting the phase-change point trajectories of the electrophysiological wave field and then, by ablating that region, restores sinus rhythm.” The technique is now widely used, and one university hospital (Ohio State) says that they are doing over 600 per year.

“This is clearly at odds with the Wiener–Rosenblueth mechanism because a further destruction of the tissue near the spiral core should not improve the situation.” It’s worse than that because the summary says “In the case of a functionally determined core, an ablation procedure should even further stabilize the rotating wave”

So theory was happily (for the patients) ignored. Theorists never give up and the paper goes on to propose a mechanism explaining why the Ohio State procedure should work. Here’s what they say.

“Here, we show theoretically that fundamentally in any excitable medium a region with a propagation velocity faster than its surrounding can act as a nucleation center for reentry and can anchor an induced spiral wave. Our findings demonstrate a mechanistic underpinning for the recently developed ablation procedure.”

It certainly has the ring of post hoc propter hoc about it.

The New York Times Parodies itself

I have a conservative friend who is becoming increasingly exercised by what he regards as the antiTrump bias of the Times. I’ve told him to calm down as the Times was turning into a parody of its former self. Today the NYT obliged by doing just that.

Here’s what so exercised my friend in today’s Times (19 Feb ’17). “For $200,000, a Chance to Whisper in Trump’s Ear”, Membership at Mar-a-Lago Gives Titans Easier Access to Political Power.” This appeared on the front page taking up the twomost right columns above the fold. All of page 13 inside is devoted to the article.

Here’s how the Times parodied itself “Around the World by Private Jet: Cultures in Transformation ” This took up the entire back page of the Style Section (New England Edition at Least) “Privately chartered Boeing 757 26 day/9 countries/50 travelers/$135,000” You will ride with 5 members of the Times staff (lilywhite) — Arthur O. Sulzberger Jr. Alan Riding, Nicholas Kristof, Elaine Sciolino and Elizabeth Bumiller. You will not have to share the air with the Times’ minority editorial contributors, Charles Blow (Black) and Ross Douhat (Conservative). They don’t appear to have a Latino.

Imagine the joy of access for the cut rate price of 135K (who said the Times didn’t care about the little man), while cruising at 35,000 feet exuding both virtue and carbon dioxide.

Here’s part of what my friend had to say about the article (unfortunately he doesn’t blog (he should ) so I can’t supply a link).

Back in the early 18th Century William Congreve wrote:

” Heaven has no rage like love to hatred turned
Nor hell a fury like a woman scorned”

You would think he was talking about the venerable “Gray LADY”, aka New York Times. Indeed the paper has jettisoned any pretense of professional journalistic ethics – any pretense of journalism purpose. A week after the election, after flagrantly shilling for Clinton and smearing Trump in previous months, the editor of the Times issued in writing to the papers readers an apology of sorts by admitting the paper had lost its way and promised to return to reporting news. Evidently atonement to its readers is in the words not the performance. The Gray Lady is profoundly stunned by the rejection by most of the country of the paper’s vision of how the world should be.

—-

Since the election the scorned and enraged Gray Lady has fill page after page , day after day , with disgrace as represented by the article below. The paper has flooded us with conjecture about things that have not happened and gossip of any sort that could denigrate and damage Trump.

The relentless attacks on Trump and his playing golf with dangerous cohorts etc is in marked contrast to how it suppressed any conjecture about Obama’s rise through the notoriously crooked Chicago political machine. Not a whisper of how he was dependent on other graduates of the Chicago cesspool, such as Axelrod and Jarrett. There was dismissal of Obama’s friendship with Ayers, a principal in a murderous urban terrorist group.

The august “paper of record” never conjectured how Obama could spent 20 years listening to Rev. Wright vicious racist rants and kept listening to them, but later said he hardly knew the man.

One final thought — could this be fake news, an ad bought by the Koch brothers to embarrass the Times. Possible, but unlikely.