Thursday, August 3, 2023

Thursday Night Links

  • Knowledge and productivity are like compound interest. Given two people of approximately the same ability and one person who works ten percent more than the other, the latter will more than twice outproduce the former. The more you know, the more you learn; the more you learn, the more you can do; the more you can do, the more the opportunity - it is very much like compound interest. I don't want to give you a rate, but it is a very high rate. Given two people with exactly the same ability, the one person who manages day in and day out to get in one more hour of thinking will be tremendously more productive over a lifetime. [Richard Hamming]
  • I praise Oppenheimer strongly even though I don’t particularly like Nolan’s penchants and predilections. For instance, Nolan has practically no sense of humor. Despite his flair for self-dramatization, J. Robert Oppenheimer himself recognized that playing up his 1954 star chamber security clearance hearing as a historic cataclysm was overblown: “The whole damn thing was a farce, and these people are trying to make a tragedy out of it.” The Coen brothers could have done more with the extensive political passages in Oppenheimer, which revolve around Oppenheimer’s Stalinist 1930s and the revenge the right-wing Jews Edward Teller and Lewis Strauss took upon him in the 1950s. The Anglo-American Nolan doesn’t bring any particular insight into the conundrum of why Jews came to be associated with nuclear weapons in the 20th century, rather like Germans and rockets or WASPs and eugenics. If anything, the movie is overly critical of Oppenheimer, choosing to probe his contradictions and flaws relentlessly when it could have devoted more time to showing how a theoretician in his late 30s suddenly turned himself into the recruiter and manager of the most famous assemblage of talent in history. What made Oppenheimer the Danny Ocean of physicists, the leader whose judgment of their skills the other sages found nearly foolproof? Oppenheimer was to physicists what Johnny Carson was to comedians: their rightful St. Peter, worthy of judging them. [Steve Sailer]
  • The hero of the film is midcentury American society. The system works. It makes use of Oppenheimer's talents to win WWII, and then discards him, after a fair hearing, when he becomes an annoying primadonna after the war, as he seeks policy influence that his ego and awful judgment make him clearly unqualified for. The film makes you think it's going in the direction of a standard Hollywood sob story about McCarthyism. But those deciding on Oppenheimer's security clearance actually use good investigative procedures to get to the truth, and know that he's a loyal American. They tell him that, but also that he can't be trusted because he has awful judgment. And how can anyone think they're wrong? [Richard Hanania]
  • In a traditional debate round, students argue over a topic assigned by the tournament — for example, “The U.S. should adopt universal healthcare.” One side is expected to argue in favor of the motion (the affirmation side), and one against (the negation side). However, in recent years, many debaters have decided to flat-out ignore the assigned topic and instead hijack the round by proposing brand new (i.e., wholly unrelated to the original topic), debater-created resolutions that advocate complex social criticisms based on various theories — Marxism, anti-militarism, feminist international relations theory, neocolonialism, securitization, anthropocentrism, orientalism, racial positionality, Afro-Pessimism, disablism, queer ecology, and transfeminism. (To be clear, traditional feminism is out of fashion and seen as too essentialist.) [Slow Boring]
  • We enter life dependent on others, we exit life dependent on others, and if we do not create others in between, it all comes to an end. This is the point that Alasdair Macintyre makes so clearly in his book Dependent Rational Animals, from which he derives communitarian or republican ethics rather than libertarian ethics. Rand, however, ignores this entire aspect of human existence. She was herself childless. Of the major characters in her three major novels, not a single one, not Dagny Taggert, not Hank Rearden, not John Galt or Francisco D’Anconia, not Howard Roark, Peter Keating, Dominique Francon, or Gail Wynand, not Kira Argounova, Leo Kevalensky, or Andrei Taganov, has or shows any interest in having children. As a teenager flush with the vigor of youth, this is easy to miss. As an adult, it is a blinding oversight. The good life for man qua man must incorporate reproduction — or there will very soon be no men to qua. But as soon as reproductive interests are entered into the moral system, the easy libertarian answers get much harder. [Contemplations on the Tree of Woe]
  • Laster said he doesn’t subscribe to the idea of “minimalist judging.” The issues raised by those cases kept coming up, he said, and needed to be addressed. “Once something clusters like that,” Laster said, he begins to realize an area of law could use more clarity. “If next year, in the course of two months I see defendants in, you know, three or four different cases making the exact same argument, it’s going to flag that in my mind,” he said. [Bloomberg Law
  • A key hallmark of a cancer cell is replication stress and genome instability, and some of the leading chemotherapies exploit this hallmark, by introducing further DNA damage that results in catastrophic consequences for the cancer cell. The high incidence of transcription replication conflicts (TRC) is a major contributor to genomic instability within cancer cells, and TRCs likely provide a potential, but not yet utilized target for chemotherapy development. Directly testing this hypothesis of targeting TRC for selective killing cancer cells has been difficult, largely due to a lack of small molecule tools that can target the resolution of TRC. Here, we report a small molecule inhibitor, AOH1996, of a cancer-associated isoform of PCNA (caPCNA), which notably, almost completely inhibits the growth of xenograft tumors without causing any discernible toxicity to experimental animals. Mechanistically, AOH1996 stabilizes the interaction between chromatin-bound PCNA and the largest subunit (RBP1) of RNA polymerase II (RNAPII) and leads to degradation of the intracellular RPB1. AOH1996 selectively dissociates PCNA from actively transcribed chromatin and causes DSB accumulation in a transcription-dependent manner, without affecting the presence of PCNA in the heterochromatin region. This indicates that inhibition of caPCNA activity by AOH1996 leads to transcription-associated collapse of DNA replication. [Cell]

1 comment:

Anonymous said...

"Knowledge is good."

Emil Faber
Founder, Faber College