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Member since: 2002
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Wow. Carbon dioxide concentrations measured at Mauna Loa on April 3 were 421.21 ppm.

Accessed April 8: Recent Daily Average Mauna Loa CO2

April 07: 418.46 ppm
April 06: 418.64 ppm
April 05: 418.71 ppm
April 04: Unavailable
April 03: 421.21 ppm

I never saw a number like that before there, but I will for sure see many more such numbers in the future.

Heckuva job humanity, heckuvajob.

Tonights cool tip from the ACS for cancer patients being treated with checkpoint inhibitors.

For various reasons, I've decided to focus much of my attention during this ACS meeting (which is virtual, but pays some attention to the fact that it was supposed to be in San Antonio) on glycomics, mostly because it's a subject I about which I know next to nothing.

I just listened to a real cool lecture by Howard Hang which indicates that non-responders to checkpoint inhibitors, a group of immunostimulatory drugs that are designed, just like it sounds, stimulate the immune system to fight cancer, may fail to respond because they lack the proper bacteria in their microbiome.

Here's a paper in a prepub form: Enterococcus peptidoglycan remodeling promotes immune checkpoint inhibitor therapy.

Cool, I think.

Some news on the variants of SARS-CoV-2 and the effectiveness of the Pfizer vaccine, (good news)!

Today at the virtual ACS meeting I attended two lectures, one by Phil Dormitzer of Pfizer and one from Melissa Moore of Moderna.

I don't have much time to discuss the details, but during Dr. Dormitzer's fascinating lecture some cool things came up.

It appears that the variants are fairly well removed from the target areas of the vaccines, which a good thing. They have nonetheless been completely mapped, and work is underway to address them if needed. In Dr. Dormitzer's lecture he specified them, if my notes are correct as D614G (Aspartic Acid replaced at the 614th residue of the spike protein by glycine), N501Y, replacement of asparagine at the 501st residue by tyrosine, and E484K, replacement of glutamic acid at the 484th residue by lysine.

There are some genetic differences between races in diseases and response to diseases; for example, women of Chinese origins are much less likely than women of European extraction to get certain forms of breast cancer because of a variant in the COMT gene (catechol O methyl transferase). African American men and women are less likely to respond to certain blood pressure medicines, (which makes it regrettable that omipatrilat was not approved, since it treated this hole in medicine.)

It turns out that African Americans are winners in terms of the ethnic profile of the Pfizer vaccine effectiveness. For them, according to the data shown in the talk and them alone, the Pfizer vaccine is 100% effective in preventing Covid infections.

Dr. Moore's lecture made me realize something that had not occurred to me in the development of these novel RNA drugs and vaccines. (I'm not a nucleic acid kind of guy.) They are a lot more difficult to make than one might think niavely. This is because of the multiplicity of codons for several amino acids. One has to be very careful in considering the availability of transfer RNA's corresponding to these codons, since they are not necessarily available in the same concentrations in organisms in which they are generated. Dr. Moore pointed out that for the SARS-Cov-2 Moderna vaccine there were actually 10^201 choices that could have been made in the codon sequence, which is a number larger than all of the atoms in the known universe! She briefly described the statistical methods used to manage this chemical space and make wise choices.

Nevertheless, Moderna has spent years learning how to choose the particular sequences of codons, and they are also ready to make changes FAST! FAST! FAST! as necessary.

Another thing: Both vaccines incur, according to the existing clinical trial data, a higher level of immunity than one actually obtains by having Covid. This suggests that even people who have had Covid might want to consider vaccination.

Very cool, very cool.

Pfizer has developed a protease inhibitor for the treatment of infected CoV-Sars-2 patients.

I attended a lecture today at the ACS meeting by Dr. Daffyd Owen of Pfizer about which I will make a brief comment.

Years ago, when the protease inhibitors for HIV were being developed, one interesting thing about them was that they were designed to dock in a protease - a protein which cleaves larger proteins - at a specific sequence, bonds between the amino acid aspartic acid (ASP) and phenylalanine (Phe). Interestingly there are no mammalian enzymes that cleave at this sequence, making targeting much easier.

The SARS-CoV-2 RNA transcribes a protease also not found in mammalian species, which cleaves exclusively at residues of glutamine, (Gln). A widely used enzyme in analytical chemistry and mammalian stomachs is trypsin, which cleaves are arginine (ARG) and lysine Lys residues.

Dr. Owen walked us through the medicinal chemistry for the development of PF-7321332, which is designed to block the pocket of the unique SARS-CoV-2. It was simply beautiful. The work involved 210 Pfizer scientists working around the clock to produce a compound entering the clinic in 11 months, unprecedented speed!

The work built on work conducted at Agouron - a company acquired by Pfizer - to develop one of the protease inhibitors for HIV, nelfinavir. (I was involved in the scale up of this compound, peripherally.)

What is interesting is that the dose (tid, 3 times a day) is "only" on the order of 300 mg, making scale up somewhat simpler than it was for the HIV protease inhibitors which had higher doses.

Interestingly, to prevent CYP metabolism, the drug may be administered with ritinovir, a treatment for HIV, to saturate the CYP enzyme.


I've been attending ACS lectures all day about the development of Covid treatments.

Just recently there was a cool talk on screening a few billion compounds in silicon at Oak Ridge NL.

These tools weren't around when I was a kid!

Good news: American science survived Trump.

New Weekly Record Set at the Mauna Loa Observatory for CO2 Concentrations: 418.03 ppm.

As I've indicated several times I somewhat obsessively keep a spreadsheet of the weekly data at the Mauna Loa Carbon Dioxide Observatory, which I use to do calculations to record the dying of our atmosphere, a triumph of fear, dogma and ignorance that did not have to be, but nonetheless is.

This week's reading is the first in the history of weekly average readings, going back, to 1975 posted by the Mauna Loa is the highest ever recorded at the Mauna Loa carbon dioxide observatory, 418.03.

Generally, each year, these measurements peak in May or early June. I expect we will see 420 ppm this year, less than 10 years after we first saw 400 ppm.

Up-to-date weekly average CO2 at Mauna Loa

Week beginning on March 28, 2021: 418.03 ppm
Weekly value from 1 year ago: 415.95 ppm
Weekly value from 10 years ago: 393.88 ppm

The increase in carbon dioxide concentrations when compared to the same week in 2020 is "only" 2.08 ppm, unusually low for these times. (If one keeps track as I do, there is a fair amount of statistical noise in these measurements, but the trends are consistent.) The highest weekly increase over 2020 this year, 2021, was 3.90 ppm, observed in the week beginning February 28, 2021.

In my spreadsheet, I keep records of the increases over 10 year periods, in this case, a comparison of the reading this past week, with the last week of May in 2011. Using Excel functions, I can sort them by values high to low and do a lot of other things.

The 12 month running average for increases over a ten year period, week to week, 2021 to 2011, is 24.15 ppm, 2.41 ppm per year.

If any of this troubles you, don't worry, be happy. You can always head over to the E&E forum and read that "renewable energy is growing 'exponentially.'" I've been hearing that, of course, my whole damned life and I'm not young, but again, don't worry, be happy.

But with respect to the most recent data point at the Mauna Loa observatory, so much for Bill McKibben's "350.org." Bill is another one of those putative "environmentalists" who has trouble mouthing the word "nuclear." He certainly wouldn't want to offend anyone by saying that word. Many of his supporters say things like: "Nuclear is 'too expensive,'" and "Nuclear is 'too dangerous,'" even while 18,000 to 19,000 people die every damned day - more than have died worldwide on Covid's worst day., from air pollution, precisely because we don't embrace nuclear energy.

By contrast, climate change is apparently not "too expensive." Climate change is also apparently not "too dangerous."

As for "too expensive:"

The earliest nuclear plant ever built in the Western World produced electricity for half a century. It was built on 1940's and early 1950's technology. Modern nuclear plants are designed to last 60 years or more. After they are amortized they are cash cows, they produce electricity only requiring trivial low fuel costs and maintenance costs.

By contrast, every damned piece of so called "renewable energy" on this planet will need replacement in 25 years or less - a few wind turbines, very few, as reported at the comprehensive Master Register of Wind Turbines from the Energy Agency of that off shore oil and gas drilling hellhole, Denmark, lasted 30 years; almost all of them were landfill in 25 years or less, with an average lifetime of under 20 years. Wind turbines will be greasy rotting hulks requiring diesel trucks to haul the blades to landfills before most babies born in 2021 graduate from college. Pretty much every damned solar cell now on this planet will all be more already intractable electronic waste in 25 years.

Nuclear energy is too expensive for whom? Certainly not for future generations, but we certainly don't give a rat's ass about their lives. When it comes to providing for them, we couldn't care less. We all turn into Ayn Rand when discussing nuclear energy; we only care for ourselves and those babies born today will have to deal with the shit we leave behind on a planet choking to death on dangerous fossil fuel waste, leaking fracking fields, destroyed ground water, abandoned depleted mines dug so we could be "green," with all of the world's best ores completely depleted etc.

History will not forgive us; nor should it.

I trust you are having a pleasant and safe Sunday.

Conspiracy: As if the Ghost... ...was me.

Laser Cooling of Antihydrogen.

The paper to which I'll point in this post is this one: Laser cooling of antihydrogen atoms (Baker, C.J., Bertsche, W., Capra, A. et al. Laser cooling of antihydrogen atoms. Nature 592, 35–42 (2021))

Beyond an inordinate interest in neutrons, I'm not much for deeper particle physics. My kid won a medal in the 5th grade science project for a poster on the subject and some of the other parents of kids in the competition accused me of doing the project, but to be perfectly honest, I actually had no idea what he was talking about.

Nevertheless, chemists are aware that on a molecular level life is asymmetric, and one theory that's floated by my consciousness from time to time is the asymmetry of beta decay of neutrons (the Wu experiment) was involved in the mysterious origins of molecular asymmetry. As I understand it, this has been difficult to prove.

I am also vaguely aware that physicists have wondered why the universe seems to have excess matter, that is, why wasn't as much antimatter created as matter was created.

Antimatter can be prepared in the laboratory, and positrons are actually pretty easy to get: Proton bombardment of stable nuclei yields, upon proton capture, neutron poor atoms that decay by positron emission. When positrons interact with electrons, they are annihilated, releasing intense gamma radiation.

The paper cited at the outset is about isolated anti-hydrogen, a hydrogen atom with an anti-proton with a positron (an anti-electron) in its orbital; not only has it been synthesized, but it has been supercooled, which makes this a cool paper or perhaps an anti-cool paper.

Happily, it is open sourced, and anyone can read it by clicking on the link above.

Some excerpts:

The antihydrogen atom, the simplest example of atomic antimatter, offers unique opportunities in challenging the foundational framework of contemporary physics. Precision comparisons of antihydrogen’s properties with those of the well studied hydrogen atom allow tests of fundamental symmetries such as charge–parity–time invariance and Einstein’s equivalence principle, which underpin quantum field theory and the general theory of relativity. The field of antihydrogen studies has seen tremendous advances in recent years. Techniques have been developed to produce15,16,17,18, confine19,20,21 and interrogate cold antimatter atoms with microwaves13,22 and lasers10,11,12,23. In addition, experiments are being built to measure the gravitational properties of antimatter14,24,25. The finite kinetic energies of the anti-atoms impose substantial limitations on the precision of many of these measurements. Therefore, preparation of antihydrogen at the lowest possible kinetic energies is an important objective in the field.

Doppler cooling, the type of laser cooling used in this work, takes place via the velocity-dependent absorption of near-resonant photons by atoms. The atoms moving towards the photon source are selectively excited by setting the photon frequency slightly below the resonance for the atom at rest (red detuning), resulting in a net force opposing the motion2,3. The spontaneous emission of a photon from the excited atom occurs in a spatially symmetric manner in free space, resulting in a null average recoil force. In the case of (anti)hydrogen26, by exciting the 1S–2P Lyman-α transition, a net velocity change of 3.3 m s−1 can be exerted on average by each 121.6-nm photon scattered. In principle, repeating such scatterings only a few dozen times should slow (anti)hydrogen atoms, initially trapped in a well depth of about 50 μeV (corresponding to a maximum speed of about 90 m s−1), down to submicroelectronvolt energies.

In practice, however, laser cooling of antihydrogen presents a number of technical challenges. First, generating and transporting radiation at 121.6 nm is difficult. There are no convenient lasers or nonlinear crystals at vacuum ultraviolet wavelengths, and the light is readily attenuated in air and in optical components...

A picture:

Fig. 1: The ALPHA-2 apparatus schematic and antihydrogen energy levels.

The caption:

a, Central parts of the ALPHA-2 apparatus are schematically shown. The field for the magnetic minimum trap is produced by five mirror coils for longitudinal confinement and one octupole coil for transverse confinement. The trap has a depth of about 50 μeV with an axial length of 280 mm and a diameter of 44.35 mm. The magnetic trap is superimposed on a cryogenic Penning trap (the electrodes are shown in yellow). An external solenoid, not shown, provides a 1-T base field for charged particle trapping and cooling. The solenoids at either end of the trap further boost the field in the preparation traps to 3 T for more efficient cyclotron cooling of electrons, positrons (e+) and antiprotons (p¯), before antihydrogen synthesis. The atom trap is surrounded by a silicon vertex annihilation detector made of three layers of double-sided microstrip sensors. The pulsed Lyman-α light at 121.6 nm, generated in a gas cell immediately outside the ultrahigh vacuum chamber, is introduced through a magnesium fluoride window with an angle of 2.3° with respect to the trap axis to allow particle loading on axis into the Penning trap. The intensity of the 121.6-nm pulse is recorded by a solar-blind photomultiplier (PMT) placed after the trap. A cryogenic optical cavity serves to both build up the 243.1-nm laser light needed to drive the 1S–2S transitions, and to provide the counter-propagating photons that cancel the first-order Doppler shift. Microwaves, used to drive hyperfine transitions, and to perform electron cyclotron resonance magnetometry, are injected through the microwave guide. According to the coordinate system shown, we define the longitudinal kinetic energy to be 1/2mHv2z, and the transverse one to be 1/2mH (vx2+vy2), where mH is the mass of antihydrogen, and vx, vy and vz are the velocity components in the x, y and z directions. b, Magnetic field profile on the axis of the trap. The shaded region illustrates a volume in which the field on axis is uniform to 0.01 T, corresponding to a Zeeman shift of 140 MHz in the 1S–2Pa transition. Immediately before reach run, the magnetic field at the centre of the trap was measured via electron cyclotron resonance and the laser frequencies were adjusted accordingly. The measured magnetic minimum field, averaged over the pre-run measurements, was 1.03270 ± 0.00007 T, where the error is the standard deviation from the set of measurements. c, The energy levels of the antihydrogen in the n = 1 and n = 2 states are depicted as a function of the magnetic field. On the vertical axis, the centroid energy difference, E1S–2S = 2.4661 × 1015 Hz, has been suppressed. The dotted vertical black line represents the field at the magnetic minimum of our trap, 1.0327 T (see above). Details of the energy levels near this field and their state labels are shown on the right of the figure. The first value in the ket notation represents the quantum number of the projection of the total angular momentum of the positron, mL + mS, where L is the orbital angular momentum (L = 0 for the S state and L = 1 for the P state, respectively) and S is the spin (S = 1/2). The double arrow shows the antiproton spin (up or down). Initially, both the 1Sc and 1Sd states are trapped in our magnetic trap. The grey arrow indicates the microwave-driven 1Sc → 1Sb transition to eliminate the anti-atoms in the 1Sc hyperfine state and prepare a doubly spin-polarized antihydrogen sample in the 1Sd state. The solid and broken red (cyan) arrows indicate the cycling transition for laser cooling (heating) with red (blue) detuning −δ (+δ?. The purple arrow represents the probe laser excitation to the 2Pc– level. Note that the 2Pc state at a magnetic field of about 1 T is a superposition of the positron spin-up (mL = 0, mS = +1/2) and spin-down (mL = +1, mS = –1/2) states. Owing to this superposition, upon de-excitation from the 2Pc state, the anti-atom can either go back to the original 1Sd state, or undergo an effective ‘spin flip’ transition to the 1Sa state. In the latter case, the anti-atom is forced out of the trap and detected via its annihilation signal. The black arrows show the two-photon excitation from the 1Sd state to the 2Sd state.


Have a nice weekend, and if you are a Christian, happy Easter.

"I am resonant...organic chemistry taught me to fully inhabit my mixed identities."

I came across this quote the other day in my Nature Briefing:

Quote of the day
“When I really take a moment to see these bonds for what they are—a union of atoms in three dimensions—I also witness my sense of self, split between mixed identities, scooch to a sweet spot in the center that is a space all its own.”

Science writer Ariana Remmel’s moving personal essay considers how organic chemistry helped to illuminate the complexities of their racial and gender identity.

It links here:

"I am resonant...organic chemistry taught me to fully inhabit my mixed identities."

This is just a beautiful piece of writing.

Some excerpts:

The splashes of children playing in the pool echo through the hot summer air. I’m not allowed in the deep end yet, not without my floaties. Even then, I am afraid that a shark will sneak up and eat my toes because Dad told me that this is what happens to little girls who go to the deep end without a grown-up. I am five years old.

My brother has just turned one. He toddles with the help of my mother’s hand. Normally, she would have dressed him in a swim diaper that swells like a balloon once he submerges in the kiddie pool. Today, Mom has put him in a pair of baby-blue swim trunks.

“I want to wear swim trunks,” I tell my mother.

“Swim trunks are for boys, honey. You get to wear a one-piece.” She is curt because my brother is crying. He has thrown his chupón onto the concrete and she is trying to find a clean one.

“But I want to wear swim trunks.”

“Sweetie, girls have to cover up. You can’t walk around bare chested. It’s just not right.” She is trying to be reasonable, but my brother has begun to remove the swim trunks altogether...

...I hate going to church. Dad never comes, so it is just me, my siblings, and my mother at St. Edward’s Cathedral. The Mass is entirely in Spanish. I do not speak Spanish. No one speaks Spanish to me...

Mom tried to teach us when we were little, but I am twelve now and I’ve learned to hate the sound of it. It is the sound of a priest who tells me that a woman’s hair is her glory. I...

...I am cramped into one of those chairs with a tiny desk that slides out, used for standardized tests. This is one of the big ones—a college-admissions test that will decide my future. But I am stuck on the very first page. Sex: Female or Male. I check “Female” with some remorse, but I still don’t have the words to describe my sadness. Race: White, Black, Latino, Pacific Islander, Asian. The instructions say to check one. Only one.

When I look in the mirror, I think I look white. That is, until I gaze into my dark-brown eyes, which are my mother’s and my Lita’s and her mother’s before her. I have my father’s pale skin and my mother’s round features. If I choose white, no one will bat an eye. I will only feel the guilt of erasing my mother and abuelos and the sacrifices they made for me to be here...

I just chatted with customer service at Delta airlines to...

...assure them that given their support for over suppression in their corporate statement, as a one time (precovid) and perhaps future business traveler I will be avoiding their airline like the plague.
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