Cavalcade of Mammals

The CRISPR gene editing system is a major technical advance. It does open up the near term possibility of making a few small changes to a human embryo’s DNA, but I don’t find that particularly interesting or alarming.

What makes CRISPR better than previous tech for gene modification is that it works at high efficiency–1% to 60% with very high specificity. I read a recent paper testing CRISPR on human embryos that reported 50% effectiveness. Given a handful of embryos to work with, there is a very good chance of making a single change in one embryo.

We have very little knowledge or technology for making positive changes to animals which is a huge limitation to genetic ‘engineering’. Mostly what is understood are disease causing (or predisposing) genetic variants. So a single change (maybe in a few years, a handful of changes?) can be made to a human embryo. There are other limits to modifying human embryos apart from lack of knowledge. The more time an embryo or human embryonic stem cell is cultured, the more it is manipulated, the greater the chance of something going wrong, and the child being born with problems. This tech is great for manipulating animals in the lab. If many or most of them have the genetic change, great! If some are born with defects, cull them, or breed another generation and use those in experiments (often the first generation has non-genetic defects that breed away). But these are huge problems if you are working on humans, because things that increase the risk of getting a damaged child are not desirable.

Long term (100-1000 years), when increases in understanding of biology make improvements (or significant changes of any sort) in humans possible, I think what we’ll see is that the people with the least concern for child welfare will be the most willing to experiment on them.

The really exciting possibilities CRISPR opens up is in genetic treatment of human disease in the tissues of kids and adults. There is delivery tech (well tested viral vectors, and a host of other methods) that can get CRISPR into a good percentage of cells (10% to 50+%) in many tissues, and once there, CRISPR will edit a good fraction of those cells. For many diseases, fixing a genetic defect in 1%, 10% or 20% of cells is enough to treat the disease, so genetic treatment of host of diseases is now possible. Things like hemophilia, some muscular dystrophy, maybe Huntington’s Disease, metabolic diseases, Parkinson’s disease, and on and on. There will be a lot of exciting advances turning that ‘possible’ into actual treatments for different diseases over the next decade or two.

The other major effect of CRISPR tech is that it makes animal experimentation faster and cheaper, and will accelerate basic biological research. We still don’t know what the majority of indivdual genes do, let alone how they work in complexes and networks in cells.

Bizarre Paintings Of Mecha Robots And Werewolves Attacking East European Peasants Of The Early 20th Century by Polish artist Jakub Rozalski
2019 Sequencing Tech Speculations: Will We Actually See New Entrants?

Novel Benzodiazepine-Like Ligands with Various Anxiolytic, Antidepressant, or Pro-Cognitive Profiles, link.
-Improves mood and age-related memory loss.

Under the Boot: Max Boot’s conversion narrative proves one thing—he hasn’t changed a bit. by Lyle Jeremy Rubin

Kompromat: Or, Revelations from the Unpublished Portions of Andrea Manafort’s Hacked Texts. by Maya Gurantz

Is Sunscreen the New Margarine? by Rowan Jacobsen

It was already well established that rates of high blood pressure, heart disease, stroke, and overall mortality all rise the farther you get from the sunny equator, and they all rise in the darker months. Weller put two and two together and had what he calls his “eureka moment”: Could exposing skin to sunlight lower blood pressure?

Sure enough, when he exposed volunteers to the equivalent of 30 minutes of summer sunlight without sunscreen, their nitric oxide levels went up and their blood pressure went down.

A Brad DeLong explains why it’s time to give democratic socialists a chance
“The baton rightly passes to our colleagues on our left.”

Paul Krugman Asked Me About Modern Monetary Theory. Here Are 4 Answers: Deficit levels, interest rates and the tradeoff between fiscal and monetary policy. by Stephanie Kelton

Stephen Wolfram: Seeking the Productive Life: Some Details of My Personal Infrastructure

The MBA Myth and the Cult of the CEO
CEOs don’t play much of a role in driving stock price performance, and the “aligned incentives” of equity incentive pay don’t change behavior in any way that benefits shareholders. The “best and brightest” — those executives with the most dazzling CVs and track records — don’t perform any better than less credentialed executives.

Harmony of Means and Ends: “theory of politics” by Cosma Shalizi

Socialists Win Big in Chicago: In city elections this week, progressive candidates shocked the Democratic machine. by Miles Kampf-Lassin

Review of Whiteshift by Eric Kaufmann
Kaufmann focuses on the “ethno” part [in ethnonationalism], arguing that mainstream politicians need to more openly cater to white concerns about cultural and demographic change if they wish to beat back the far-right tide.

Potluck Economics from Existential Comics

Number of unauthorized immigrants in the U.S. declined over the past decade

Conversion of the solar fuel from norbornadiene to quadricyclane uses sunlight, reversed by a catalyst to release heat. ref, news.

Sleep is still a mystery.

Mac OSX Bash Profile

Recent US election results:
2016 President:
Donald J. Trump 63.0 million votes
Hillary R. Clinton 65.8 million votes

In 2018, Americans got some of what they want:
Democratic House candidates 59.0 million votes
Republican House candidates 50.3 million votes

Video of house
Gear design: Gearotic
Bike horse clopping
National Association of Watch & Clock
Watchmaking info
Cardboard Dinosaur PuzzleT-Rex Dinosaur Puzzle With Different Sizes and Positions
Bacteria In Worms Make A Mosquito Repellent That Might Beat DEET
How to Close the Democrats’ Rural Gap by Claire Kelloway

How Russian Money Helped Save Trump’s Business. After his financial disasters two decades ago, no U.S. bank would touch him. Then foreign money began flowing in. By Michael Hirsh

Sequencing an Ashkenazi reference panel supports population-targeted personal genomics and illuminates Jewish and European origins

Shai Carmi et. al., Nature Communications volume 5, Article number: 4835 (2014)

Abstract

The Ashkenazi Jewish (AJ) population is a genetic isolate close to European and Middle Eastern groups, with genetic diversity patterns conducive to disease mapping. Here we report high-depth sequencing of 128 complete genomes of AJ controls. Compared with European samples, our AJ panel has 47% more novel variants per genome and is eightfold more effective at filtering benign variants out of AJ clinical genomes. Our panel improves imputation accuracy for AJ SNP arrays by 28%, and covers at least one haplotype in ≈67% of any AJ genome with long, identical-by-descent segments. Reconstruction of recent AJ history from such segments confirms a recent bottleneck of merely ≈350 individuals. Modelling of ancient histories for AJ and European populations using their joint allele frequency spectrum determines AJ to be an even admixture of European and likely Middle Eastern origins. We date the split between the two ancestral populations to ≈12–25 Kyr, suggesting a predominantly Near Eastern source for the repopulation of Europe after the Last Glacial Maximum.

pdf, suppl

Pan-cancer network analysis identifies combinations of rare somatic mutations across pathways and protein complexes
Mark D M Leiserson et. al., Nature Genetics volume 47, pages 106–114 (2015)

Abstract

Cancers exhibit extensive mutational heterogeneity, and the resulting long-tail phenomenon complicates the discovery of genes and pathways that are significantly mutated in cancer. We perform a pan-cancer analysis of mutated networks in 3,281 samples from 12 cancer types from The Cancer Genome Atlas (TCGA) using HotNet2, a new algorithm to find mutated subnetworks that overcomes the limitations of existing single-gene, pathway and network approaches. We identify 16 significantly mutated subnetworks that comprise well-known cancer signaling pathways as well as subnetworks with less characterized roles in cancer, including cohesin, condensin and others. Many of these subnetworks exhibit co-occurring mutations across samples. These subnetworks contain dozens of genes with rare somatic mutations across multiple cancers; many of these genes have additional evidence supporting a role in cancer. By illuminating these rare combinations of mutations, pan-cancer network analyses provide a roadmap to investigate new diagnostic and therapeutic opportunities across cancer types.

pdf, suppl

Frank Wilhoit: The Travesty of Liberalism
Conservatism consists of exactly one proposition, to wit:
There must be in-groups whom the law protectes but does not bind, alongside out-groups whom the law binds but does not protect.

Silicon Valley’s Chinese Dream: Tech elites, weary of democracy, look to the East by Jacob Silverman
Trump Fans Sink Savings Into ‘Iraqi Dinar’ Scam

An Alternative History of Silicon Valley Disruption
   “Temp: How American Work, American Business, and the American Dream Became Temporary’ by Louis Hyman
   “The Value of Everything: Making and Taking in the Global Economy” by Mariana Mazzucato
   “Winners Take All: The Elite Charade of Changing the World” by Anand Giridharadas

Create a living will without a lawyer

Interpreting 23andMe, Ancestry SNP array results: Promethease, SNPedia
Four Days Trapped at Sea With Crypto’s Nouveau Riche by Laurie Penny
How to Convince MAGA Cretins to Fear Climate Change
Paper craft, including two by Haruki Nakamura
Kamikara – Mechanical Origami, book by Haruki Nakamura, in Japanese — Kami no karakuri – Kamikara de Asobo!
Wood clock plans and kits
Clayton Boyer Clock Designs
Aleksandar Hemon: Fascism is Not an Idea to Be Debated, It’s a Set of Actions to Fight
   In the comments: Bertrand Russell’s 1962 letter to fascist Sir Oswald Mosley

LEGO Star Wars Ultimate Millennium Falcon 75192 Building Kit (7541 Pieces)
Ramesh Ponnuru: Recession Is a Far Larger Threat Than Inflation
Commented:
We’re in the strange situation where the Fed, Republican economists, and related commentators all want to keep the economy juiced and growing for another year and a half to two years. I expect that will be the unspoken factor in Fed decisions and the wonkosphere, they’ll all sound more reasonable than normal for the period. I expect the Fed will begin to think a Democrat in WH is likely in 2020, and will steer the next recession to 2020-2021.

The Woman Who Cared for Hundreds of Abandoned Gay Men With AIDS by David Koon

Functional medicine: Reams of useless tests in one hand, a huge invoice in the other. by David Gorski

REVIEW ESSAY: Principles for Dummies by Matthew Walther
Principles: Life and Work by Ray Dalio

On the first page of his best-selling memoir, Ray Dalio unburdens himself of the opinion that he is “a dumb shit.” Nothing in the ensuing six hundred or so pages convinced me that I should dissent from this verdict.

Chicago police search arrests
Chicago Police Department BAIL BOND MANUAL

Shetland sheep
“A Shetland ram was kept by United States President Thomas Jefferson for several years in the early nineteenth century. Unlike modern Shetlands (but like some related breeds) this ram had four horns. He was kept with about 40 other sheep on President’s Square in front of the White House. In the spring of 1808, it attacked several people who had taken shortcuts across the square, injuring some and actually killing a small boy.[8] Having been moved to Jefferson’s private estate at Monticello, the ram was eventually killed after having killed several other rams: it was described by Jefferson as “this abominable animal”.[8] Such aggressive Shetland rams, however, are unusual.[9]”

Candice Delmas, A Duty to Resist: When Disobedience Should Be Uncivil (2018)
QAnon’s true believers are devastated as the conspiracy theory goes down in flames
How to Stock a Biology/Genetics Lab
Justin Teng’s Personal Go Book Collection and Guide
Timothy Denevi, author of “Freak Kingdom,” details how Hunter S. Thompson “is really good at trying to see what’s necessary and not, in terms of justice.” by Erin Keane

STAR-Fusion is a program that detects RNA fusions events in RNA-Seq data. According to the paper describing the program, STAR-Fusion is much better than the dozen or so other callers under active development.

Still, reading the paper left me with some questions. As descried by the authors, STAR-Fusion is not just a good caller, but the best caller by a wide margin. See Fig 3A. The next nine best callers have AUC values of 0.5 to 0.3, but STAR-Fusion has a value of 0.8 in the author’s testing.

And what is the source of this incredible result? The authors are silent on the subject. They don’t know, or perhaps didn’t notice how remarkable their achievement is, and so don’t remark on it. The description of the STAR-Fusion algorithm seems very similar to the algorithms used by every other RNA fusion caller. Some do better than others, so details of implementation must matter.

So what is the critical advance STAR-Fusion makes? Is better sequence alignment key? Is the filtering approach? The paralog handling seems like it cuts down on false positives, is this key? Discovering the critical factors for RNA fusion calling would be an important result.

Or are the performance results in the paper dependent on the synthetic test data set the authors use? Will subsequent papers comparing STAR-Fusion to other methods find that it is only average, or sub-par?

Video of tagged individual mouse cells during embryo development. The video gets good at 2:20. It even includes a TARDIS (of sorts).

Conservatives’ self-delusion on race: How the right created the illusion of colorblindness. By Joshua Tait
House GOP Bill Cuts Legal Immigration By 1.4 Million Over 20 Years
Trump-era GOP cares more about the national origin and race of immigrants than how they got here.
Presidential Campaign Slogans
Trump’s Caravan Hysteria Led to This by Adam Serwer

Archaeorhynchus spathula, a dinosaur that is an early ancestor of birds, had bird-like lungs! In bird lungs, air makes a circuit rather than going in and out like in mammals. link, bird lungs

Wisconsin’s $4.1 billion Foxconn boondoggle

Debunking Yet Another Misleading John Lott Gun Study
Dishwasher with good reviews, Bosch SHS63VL5UC, $720, review
Tamron SP 150-600mm F/5-6.3 Di VC USD
ContraPoints youtuber
Graph of world language use.
It Can Happen Here by Cass R. Sunstein
Federal Spending as a Percent of GDP