Monday Links

• In Macklin’s patients, semaglutide reduces the drive to engage in a wide spectrum of dopamine-fueled behaviors, including drinking alcohol and shopping. “People say they’re on Amazon way less,” observes Macklin. The animal research backs this up, reporting that semaglutide and similar drugs reduce alcohol intake in alcoholic monkeys and the use of a variety of dopamine-spiking addictive drugs in rodents. So one reason why semaglutide is so effective may be that it curbs food intake from two angles: our brain’s perceived need for calories (hunger), and our tendency to be seduced by food even when we aren’t hungry (reward). [Stephan Guyenet]
• EIA reported an overwhelmingly bullish oil storage report this week. The most important figure in the release today was the material jump in implied oil demand. The increase of 3.354 million b/d w-o-w to 23.191 million b/d makes it the highest demand ever recorded. And on a 4-week basis, this is the highest demand for this time of the year. In the product demand breakdown, you can see a large spike in propane and propylene demand. Distillate fuel oil is also very strong with residual oil moving higher as well. Gasoline is right at the norm and jet fuel demand remains below the historical averages. This indicates to us that if jet fuel demand recovers, we will be well above where we were historically on demand. There are profound implications from this, because IEA, at the moment, is assuming global oil demand from the OECD countries to be below that of 2019 on the foundation that jet fuel demand is below the norm. While that is factually accurate, it doesn't take into account that the aggregate demand is already at the 2019 level even in the absence of jet fuel demand recovery. [HFI Research]
• Rapamycin known in the clinic as Rapamune or Sirolimus, was unlucky from the start, however. Twenty years ago, it was labeled an immunosuppressant and used to treat renal transplant patients. If rapamycin had been labeled an immunomodulator and anti-inflammatory drug instead, it would sound much more appealing now. At anti-aging doses, rapamycin “eliminates hyperimmunity rather than suppresses immunity” or, more figuratively, it “rejuvenates immunity”. This enables rapamycin and everolimus, a rapamycin analog, to act as immunostimulators, improving immunity in cancer patients and the elderly. For example, rapamycin reduces the risk of CMV infection in organ transplant patients, improves antipathogen and anticancer immunity in mice, prolongs lifespan in infection-prone mice and protects aged mice against pneumonia. Rapamycin also inhibits viral replication. As a noteworthy example, rapamycin inhibits replication of the 1918 flu virus (the deadliest flu virus in history) by 100-fold, and also protects against lethal infection with influenza virus when administered during vaccination. Still, as Dr. Allan Green advises, patients taking rapamycin should be carefully monitored for skin and subcutaneous bacterial infections, which should be treated with antibiotics. [NLM]
• Blake Masters: Capitalism works. It’s a really good system for generating wealth. The problem with capitalism is that can work too well in a sense, it can create the conditions for people to grow complacent, which ultimately, as Ross Douthat has written, contributes to the sort of decadence we’re experiencing today. Capitalism’s an incredible engine of material progress, but it’s not a self-contained moral system. It has its own incentives, but those incentives aren’t always necessarily correlated with a conception of the good. Companies under capitalism just respond to profit incentives. If you act on them you’ll generate a lot of wealth, but it won’t tell you what to do with that wealth, which is why a parasite like Wokeness can basically spread and take over. An example is offshoring. Maybe it’s good for GDP, but if you have too much of it, that’s clearly really bad for the country and most people living in it. It crushes the middle class by sending jobs overseas by the millions. But such are the incentives that the capital owners are responding to. So I think problems like Woke Capitalism, or ‘globalization’, are actually much older and bigger problems than people think. Because you can’t just be a capitalist country, because a country is not just an economy. You also need a conception of yourself as a nation, as a people, and as a culture. And that’s what America is increasingly lacking today. [Mark Granza]
• Omicron Spike protein mediates deficient cell entry and is inefficiently cleaved compared to Delta spike. We tested viral entry mediated by Wild Type, Delta and Omicron spikes using a pseudotyped virus system, infecting primary 3D lung alveolar organoids. Omicron Spike protein induces relatively poor cell-cell fusion compared to WT and Delta. We expressed spike in cells stably expressing split GFP, so that Green signal could be measured over time upon cell-cell fusion and syncitia formation. The difference is significant. What does this all mean? Efficient infection of lung cells could correlate with severity of lung disease. Syncitia or fused cells are often seen in respiratory tissues taken following severe disease. Delta was very good at both, in contrast to Omicron. Further work is needed. We also tested how well antibodies from vaccinated individuals neutralised Omicron v Delta. We found that Omicron was poorly neutralised after two doses of mRNA or Ad vectored vaccine compared to Delta, but that the third dose (mRNA vaccine) rescued this at an early time point. In summary this work suggests that Omicron does appear to have become more immune evasive, but that properties associated with disease progression *may* be attenuated to some extent. The significant growth of Omicron nevertheless represents a major public health challenge. [@GuptaR_lab]
• How often do you hear back from the subjects of your impressions? RB: We did a thing with Michael Caine at the Albert Hall, and he was very nice. You can see it. Anthony Hopkins I met in Los Angeles and he said, [does an Anthony Hopkins voice] “I loved The Trip. Loved The Trip.” This was after we’d done the first one and the Italian one hadn’t come out. And I said, “Well, in this new one, the Italian one, we’re on a yacht and we do you in The Bounty.” And he started doing it! He started going, “Turn your back away, Mr. Fryer!” And then I was doing it back to him. We were in a car and I got rather giddy. Hopkins! [Vulture]
• Self-actualization is, of course, different from empathy. And while some forms of empathy are surely teachable — there are books, meditations, soup kitchens, hospices and family members that offer great opportunities for empathetic practice — it feels very unlikely that watching impressive people talk about their lives is going to do it. The selling point here seems to be more about comfort and validation. The course is as cozy as reading a picture book about Ruth Bader Ginsburg to a child at bedtime, as righteous as planting an “IN THIS HOUSE WE BELIEVE NO HUMAN IS ILLEGAL” sign on an upscale suburban lawn overlooked by security cameras. [NY Times]
• It has especially clever use of well-chosen music – at the Circus Christmas party, everyone sings along to ‘The Second Best Secret Agent in the Whole Wide World’ (the theme song to Lindsay Shonteff’s License to Kill!) and the Soviet national anthem sung in Russian, while Cumberbatch’s Guillam invades the Circus to steal a crucial record book to the tune of George Formby’s ‘Mr Wu’s a Window Cleaner Now’ (which makes even a surveillance eavesdropper’s foot tap), while the entire climax of sniper retribution is similarly played out as a music video clip (‘Beyond the Sea’). [link]
• Nuclear fusion, says Klinger, is “the only primary energy source left in the Universe” that we have yet to exploit. Ever since the process that powers the stars was harnessed in the 1950s for hydrogen bombs, technologists have dreamt of unlocking it in a more controlled manner for energy generation. Existing nuclear power plants use fission: the release of energy when heavy atoms such as uranium decay. Fusion, by contrast, produces energy by merging very light nuclei, typically hydrogen, which can happen only at very high temperatures and pressures. Most efforts to harness it in reactors involve heating the hydrogen isotopes deuterium (D) and tritium (T) until they form a plasma — a fluid state of matter containing ionized atoms and other charged particles — and then fuse (see ‘Fuel mix’). For these isotopes, fusion starts at lower temperatures and densities than for normal hydrogen. D–T fusion generates some radiation in the form of short-lived neutrons, but no long-lived radioactive waste, unlike fission. It is also safer than fission because it can be switched off easily: if the plasma is brought below critical thresholds of temperature or density, the nuclear reactions stop. What makes it so difficult to conduct in a controlled manner, however, is the challenge of containing electrically charged plasma that is undergoing fusion at temperatures of around 100 million kelvin — much hotter than the centre of the Sun. Generally, researchers use magnetic fields to confine and levitate the plasma inside the reactor. But instabilities in this infernal fluid make containment very difficult, and have so far prevented fusion from being sustained for long enough to extract more energy than is put in to trigger it. [Nature]
• From the time he was twenty until he was fifty-five, Old John drank steadily, but throughout the last thirty-two years of his life he did not take a drop, saying, “I’ve had my share.” Except for a few experimental months in 1905 or 1906, no spirits ever have been sold in McSorley’s; Old John maintained that the man never lived who needed a stronger drink than a mug of stock ale warmed on the hob of a stove. He was a big eater. Customarily, just before locking up for the night, he would grill himself a three-pound T-bone, placing it on a coal shovel and holding it over a bed of oak coals in the back-room fireplace. He liked to fit a whole onion into the hollowed-out heel of a loaf of French bread and eat it as if it were an apple. He had an extraordinary appetite for onions, the stronger the better, and said that “Good ale, raw onions, and no ladies” was the motto of his saloon. [New Yorker]
• Our sample of OTC-listed banks is 2100 bps cheaper on tangible book value than our sample of publicly traded banks despite earning a significantly higher ROE, having higher capital, having lower non-performing assets, a touch better demand deposits, and buying back more stock year over year. Note that both sets (which number a couple dozen banks each) are very small banks with average market capitalization under $500 million. We find this really fascinating because for the first time, using sets of companies in the same industry that are highly comparable, we are demonstrating a discount that is stemming from not being public – or, conversely, from being OTC listed. If the Oddball Stocks Newsletter stands for anything, it is for harvesting this OTC valuation discount. [Oddball Stocks]