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Tyler O'Neal, Staff Editor ACADEMIA May 23, 2022, 12:00 pm

Jiménez-Osés lab's simulations show additional insights into the SARS-CoV-2 spike protein glycan shield

Never as these past two years manifested the importance of collaborative research in virology and immunology. Readiness of action when such striking pandemic events occur relies on decades of basic knowledge accumulated in time and constant technology development, which rely on stable scientific policies on a global scale. An unprecedented wealth of information has been gathered on SARS-CoV-2 in a very short period mainly focused on the cellular entry process and mechanism of antibody recognition where mainly protein-protein interactions occur. However, the SARS-CoV-2 spike protein is decorated by chains of carbohydrates (sugars) whose identity and flexibility have essential implications for antibody escaping, cellular proteins recognition and so for….

The groups of Dr. Abrescia and Dr. Jiménez-Osés at CIC bioGUNE in Spain, have combined high-resolution cryo-electron microscopy and supercomputer simulations to understand the correlation between sugar identity and flexibility in SARS-CoV-2 spike glycoprotein and published the results in Front Microbiol. on 15th of April 2022. Right: glycans showing very conserved geometries around crucial glycosidic bonds near to the protein. Left: Sugars located at the so-called S2 domain which is proximal to the viral membrane  CREDIT Nicola Abrescia, Gonzalo Jiménez Osés. Modified from Frontiers in Microbiology

Rapid and free access to high-end Krios microscopes at eBIC-Diamond LS (UK) by the Abrescia Lab has allowed a 3D reconstruction of the spike protein at 4.1 Å resolution with a minimal number of contributing particles (~23,000) in which the density for the decorating glycans is as clear as other maps at a higher resolution for which hundreds of thousands of particles were necessary.  The most ordered sugars are located in the so-called S2 domain which is proximal to the viral membrane (Fig. 1 left). Chemical variations of those glycans discovered by mass spectrometry were modeled on representative glycosylated amino acids by the Jiménez-Osés lab and showed no significant influence on either protein shielding or glycan flexibility. Mathematical methods were used to compare the cryo-EM density and the time-resolved full-atom supercomputer models. The best fits between the two techniques are characterized by glycans showing very conserved geometries around crucial glycosidic bonds near the protein (Fig. 1 right). Being able to predict glycan behavior is relevant because this S2 location on the spike is also the one mostly conserved across the other human coronavirus and the ideal target for a pan-ligand capable to neutralize the virus after cell entry. This study – also a result of collaborations with Jimenez-Barbero, Millet, and Connell labs - shows that experimental and computational tools combined can provide valuable insights into the conformational preferences of inherently flexible and complex glycoconjugates, advancing the discovery of new drugs able to evade the glycan shield of infectious viral proteins.

Keese’s modeling delivers insight into nuclear rocket engine heat transfer; wins the best student paper at NETS conference

Tyler O'Neal, Staff Editor ACADEMIA May 23, 2022, 11:01 am

A research paper about heat transfer inside the reactor of a conceptual liquid-fueled nuclear rocket engine by a University of Alabama in Huntsville (UAH) graduate student was hot stuff at the American Nuclear Society’s recent Nuclear and Emerging Technologies for Space (NETS) conference, winning the best student paper at the Cleveland event. Jacob Keese says the novel engine design could open the door for much more ambitious space missions.  Michael Mercier | UAH

Winner Jacob Keese, a native of Valley Center, Kan., is a second-year master’s student in mechanical engineering at UAH, a part of the University of Alabama System. Keese is advised by Dr. Keith Hollingsworth, chair of the UAH Department of Mechanical and Aerospace Engineering. It was the second consecutive year a UAH student won the best student paper at NETS.

Keese’s research was done as part of UAH investigations into a novel concept of nuclear thermal spacecraft propulsion called Centrifugal Nuclear Thermal Propulsion (CNTP), where uranium fuel is spun in a combustion chamber so the centrifugal force holds it to the walls. The fuel heats to the point of liquefaction at temperatures not far from those found on the sun, and then hydrogen gas is bubbled through it. The expansion of the hydrogen propels the spacecraft.

With UAH's eminent scholar in systems engineering Dr. Dale Thomas as the principal investigator, UAH is leading a collaboration of universities across the nation to investigate the feasibility of such an engine under a research contract for the Space Nuclear Propulsion Project Office at NASA’s Marshall Space Flight Center.

“My research has been to create a numerical model of the heat transfer and thermodynamic processes within the liquid-fueled reactor,” Keese says. “This is an advanced nuclear rocket concept that promises much greater performance than current rocket engines.”

Keese’s modeling provides insight into what temperatures can be attained within the reactor.

“That, in turn, will help us understand the performance potential of the rocket,” he says.

“My research has application primarily to advanced space missions that require very high-performance rocket engines,” Keese says. “The CNTP concept promises an enhanced specific impulse, which is basically the efficiency of a rocket engine, like miles per gallon in a car.”

The concept could deliver efficiency that is as much as three to four times that of traditional rocket engines and one and a half to two times that of the solid-fueled nuclear rocket engines currently under development, Keese says.

“This enhanced efficiency could be achieved without sacrificing a high thrust, which could open the door for much more ambitious missions,” he says. “Some of the missions which have been proposed are human missions to Mars with significantly reduced trip times, and robotic scientific missions to the far reaches of our solar system.”

“Jacob’s model allows us to examine the influence of such parameters as cylinder size, rotation rate, hydrogen flow rate, and the level of controlled nuclear decay of the uranium,” says Dr. Hollingsworth, who is a co-author of the paper entitled "One-Dimensional Steady-State Thermal Model of CNTP Reactor."

“The right balance of these variables will keep the cylinder walls cooled down to a survivable temperature while giving us the desired level of thrust from the motor,” Dr. Hollingsworth says. “Jacob’s best paper award recognizes both his extraordinary talent as a graduate student presenter and the quality of his contribution to the field.”

Intriguing conceptually, the CNTP idea has been around since the 1960s, but the engineering challenges involved have kept it from getting off the drawing board, Dr. Thomas says.

Uranium has a high melting point, so it’s a fine line between an ultra-high performance rocket engine and a radioactive hot mess, according to Dr. Thomas.

The UAH team is attempting to walk that line and Keese’s research has contributed to the effort, he says.

“Jacob’s work on the heat transfer between the cold gaseous hydrogen and the very hot liquid uranium is foundational to establishing the engineering viability of this high-performance rocket engine concept,” Dr. Thomas says.

Keese says he was deeply honored when his name was announced for the award at the conference.

“I had been blown away by the presentations at the conference, and I was not at all expecting to receive the best student paper award,” he says. “I also felt thankful for being given the opportunity to work on such an ambitious and interesting project.”

Scottish built simulations show new spin on galaxy rotation saves controversial gravity theory

Tyler O'Neal, Staff Editor ACADEMIA May 20, 2022, 4:00 pm

An international group of astronomers, led by a physicist at the University of St Andrews, has revived an alternative gravity theory.

Headed by Dr. Indranil Banik of the School of Physics and Astronomy at St Andrews in Scotland, the study revealed a high predicted rotation speed of gas in a dwarf galaxy consistent with the previously debunked theory known as Milgromian Dynamics (MOND).

An earlier study of the rotation speed of gas in the dwarf galaxy AGC 114905 (Mancera Pina et al, 2022) found that the gas rotated very slowly and claimed the MOND theory was dead.

Such theories are essential in understanding our universe because, according to known physics, galaxies rotate so quickly they should fly apart. MOND, a controversial alternative to General Relativity, the prevailing Einstein-inspired understanding of the phenomenon of gravity that requires dark matter to hold galaxies together; does not require dark matter. As the dark matter has never been detected despite decades of very sensitive searches, various theories have been put forward to explain what holds galaxies together, and debate rages over which is right. The very low rotation speed reported in the Mancera Pina et al study is inconsistent with predictions in a universe governed by General Relativity with large amounts of dark matter.

Dr. Banik’s group argues that the high predicted rotation speed in the MOND gravity theory is consistent with observations if the inclination of the galaxy is overestimated. Gravity 59557

The rotation of stars and gas in distant galaxies cannot be measured directly. Only the component along the line of sight is known from precise spectroscopic measurements. If the galaxy is viewed almost face-on, then it would mostly rotate within the plane of the sky. This could mislead observers into thinking that the galaxy is rotating very slowly, which would require them to overestimate the inclination between disc and sky planes. This inclination was estimated from how elliptical the galaxy appears (see image).

The new study explored this crucial issue using detailed MOND simulations of a disc galaxy similar to AGC 114905 made at the University of Bonn by Srikanth Nagesh and instigated by Pavel Kroupa, Professor at the University of Bonn, and the Charles University in Prague. The simulations show that it can appear somewhat elliptical even when viewed face-on. This is because stars and gas in the galaxy have gravity and can pull themselves into a somewhat non-circular shape. A similar process causes the spiral arms in disc galaxies, features which are so common that these are often called spiral galaxies.

As a result, the galaxy could be a lot closer to face-on than the observers thought. This could mean the galaxy is rotating much faster than reported, removing the tension with MOND.

Dr. Banik, the lead author of the new study, said: “Our simulations show that the inclination of AGC 114905 might be significantly less than reported, which would mean the galaxy is actually rotating much faster than people think, in line with MOND expectations.”

Dr. Hongsheng Zhao, of the School of Physics and Astronomy at the University of St Andrews, said: “The very low reported rotation speed of this galaxy is inconsistent with both MOND and the standard approach with dark matter. But only MOND can get around this apparent contradiction.”

The new study also argues that a similar ‘fake inclination’ effect is unlikely to arise in the standard dark matter approach because the galaxy is dominated by the smooth dark matter halo. The stars and gas contribute little to the gravity, so the disc is not ‘self-gravitating’.

This means it is likely to look very circular if viewed face-on, as confirmed by simulations carried out by another group (Sellwood & Sanders, 2022). As a result, the observed ellipticity must be due to a significant inclination between the disc and sky planes. The rotation velocity would then be very small, implying that the galaxy has very little dark matter. It is not possible in this framework that an isolated dwarf galaxy would have such a small amount of dark matter given how much mass it has in stars and gas.

Pavel Kroupa, Professor at the University of Bonn and Charles University in Prague, said of the broader context of these results: “While MOND works well in the tests conducted so far, the standard approach causes very severe problems on all scales ranging from dwarf galaxies like AGC 114905 all the way up to cosmological scales, as found by many independent teams.”

  1. South Korean prof develops neuromorphic memory device that simulates neurons, synapses​
  2. Chinese scientists show why meridional heat transport is underestimated

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