Tag: science

Molecular Machine Feasibility

Richard Jones lists 6 challenges for molecular nanotechnology:

  1. Stability of nanoclusters and surface reconstruction. Surfaces have a tendency to “reconstruct” – seek out stable equilibria in ways not necessarily predicted by molecular dynamics simulations.
  2. Thermal noise, Brownian motion and tolerance. Atoms on the nanoscale may be too wobbly to build complex machines out of. Drexler addressed this, but not in thorough detail.
  3. Friction and energy dissipation. Surface area becomes much larger as machinery scales down, and high functional densities will give rise to high power densities in molecular machine systems. The friction and heat may be so intense that molecular machine systems cannot be reliably constructed.
  4. Design for a motor. Richard is skeptical that the electrostatic motor as described in Drexler’s Nanosystems would actually work. More detail needs to be fleshed out and supported by experimental testing.
  5. The eutactic environment and the feed-through problem. For MNT systems to work, they would need to operate in ultra-high vacuum. But, interacting with the outside, they’d be exposed to a very atomically messy environment. Valves and pumps need to be around 100% efficient to exclude foreign molecules.
  6. Implementation path. How do we get there from here? If “soft” nanotechnology is all that works, how do we transition from there to hard?

These are all valid arguments, but some are a bit more interesting than others. To estimate them roughly in order of declining importance based on my own opinion, I’d list them as 3, 1, 2, 4, 5, and 6.

beats tracking down all the physical chemistry papers

Antibiotics

For all you antibacterial soap-using dummies.

Unlike (soap and other) traditional cleaners, antibacterial products leave surface residues, creating conditions that may foster the development of resistant bacteria. Alcohol-based hand sanitizers are just about as effective against germs as soap and water. They’re also easier on your skin than hand-washing, and unlike antibacterial soaps, they don’t breed antibiotic-resistant superbacteria.

The bottom line is that you shouldn’t live in fear of high-traffic surfaces. This type of contact simply isn’t the way people get sick.

2010-11-08: We are essentially back to an era with no antibiotics

This new resistance pattern has been reported in many different types of bacteria compared to previously and 10% of these NDM1-containing strains appears to be pan-resistant, which means that there is no known antibiotic that can treat it. A second concern is that there is no significant new drug development for antimicrobials.

2015-01-08: New Antibiotics Platform?

A lot of people have had similar ideas to this one, based on the fact that the overwhelming majority of bacteria in any given environmental sample can’t be readily cultured. These organisms may well be able to produce useful antibiotics and other natural products, but how will you ever be able to tell if you can’t fish any of them out? Using this on a soil sample from Maine and leaving the chip in situ for a month, a number of colonies formed. These were tested for their ability to grow outside the device in fermentation broth, and extracts of these were tested against pre-grown lawns of an S. aureus strain to look for useful antibiotic activity. Lo and behold, one extract cleared out a large spot – it turned out to come from a newly described bacterium (Eleftheria terrae, provisionally). The compound present has been named teixobactin, and here it is. So how useful is the compound? It’s active only against gram-positive organisms, which is too bad, because we could really use some new gram-negative killers (their cell membranes make them a tougher breed). But the mechanism of action turns out to be interesting: studies of S. aureus with labeled precursors showed that teixobactin is a peptidoglycan synthesis inhibitor, but extended exposure and passaging did not yield any resistant strains. That’s close to impossible if an antibiotic is binding a particular protein target – stepping on the selection pressure will usually turn up something that evades the drug. When you don’t see that, it’s often because there’s some nonspecific non-protein-targeted mechanism, which can be problematic, but teixobactin isn’t toxic to eukaryotic cells in culture (and has a favorable tox profile in mice as well). It turns out that it binds to some of the peptidoglycan precursors, lipid II and lipid III. Vancomycin has a similar mechanism (binding to lipid II), but teixobactin has a wider spectrum of activity against lipid II variants (and lipid III as well). This mechanism makes developing resistance not so straightforward – the selection pressure is more of a bounce shot than a direct hit.

2015-02-24: Antibiotics market failure

we seem willing to pay $100K or more for cancer drugs that cure no one and at best add weeks or a few months to life. We are willing to pay 1$0Ks for knee surgery that, at best, improves function but is not lifesaving. So why won’t we pay $10K for a lifesaving antibiotic?

2015-03-31: Medieval salve kills MRSA. Impressive! Not all ancient medical knowledge is homeopathic nonsense.

Take cropleek and garlic, of both equal quantities, pound them well together… take wine and bullocks gall, mix with the leek… let it stand 9 days in the brass vessel

So goes a 1000-year-old Anglo Saxon recipe to vanquish a stye, an infected eyelash follicle. If the 9th Century recipe does lead to new drugs, they might be useful against MRSA skin infections such as those that cause foot ulcers in people with diabetes. These are usually antibiotic-resistant

2016-01-23: Antibiotics synthesis

Antibiotics are generally synthesized in nature by bacteria (or other microbes) as defenses against each other. We have identified antibiotics in the lab, and thus necessarily only those made by bacterial species that we can grow in the lab. Almost all bacterial species cannot be grown in the lab using practical methods. That hasn’t changed for decades. But those bacteria grow fine in the environment, typically the soil. So… can we isolate antibiotics from the soil?

2018-05-21: Phage Therapy

3 months earlier, Patterson had suddenly fallen ill, so severely that he had to be medevaced to Germany and then to UCSD. There were several things wrong—a gallstone, an abscess in his pancreas—but the core of the problem was an infection with a superbug, a bacterium named Acinetobacter baumannii that was resistant to every antibiotic his medical team tried to treat it with. Patterson was wasted, his cheekbones jutting through his skin. Intravenous lines snaked into his arms and neck, and tubes to carry away seepage pierced his abdomen. He was delirious and his blood pressure was falling, and the medical staff had sedated him and intubated him to make sure he got the oxygen he needed. He was dying. … “We are running out of options to save Tom. What do you think about phage therapy?”

2019-11-04: CRISPR Antibiotics

An alarming number of bacteria are now resistant to one or more antibiotics, so this new line of inquiry would certainly be welcomed if it proves effective.

In their recent study, Dr. Edgell and his colleagues successfully used a Crispr-associated enzyme called Cas9 to eliminate a species of Salmonella. By programming the Cas9 to view the bacterium itself as the enemy, Dr. Edgell and his colleagues were able to force Salmonella to make lethal cuts to its own genome.

As we discover more of the benefits of our microbiota, it would also be interesting to have a solution to bacterial infections which doesn’t create problems for our “good bacteria.

2020-02-22: Antibiotics ML

So overall, this is an impressive paper. The combination of what appears to be pretty rigorous ML work with actual assay data generated just for this project seems to have worked out well, and represents, I would say, the current state of the art. It is not the “Here’s your drug!” virtual screening of fond hopes and press releases, but it’s a real improvement on what’s come before and seems to have generated things that are well worth following up on. I would be very interested indeed in seeing such technology applied to other drug targets and other data sets – but then, that’s what people all around academia and industry are trying to do right now. Let’s hope that they’re doing it with the scope and the attention to detail presented in this work.

2020-07-24: SCH-79797

Researchers have found a compound, SCH-79797, that can simultaneously puncture bacterial walls and destroy folate within their cells — while being immune to antibiotic resistance. This is the first antibiotic that can target Gram-positives and Gram-negatives without resistance

2020-08-07: Maybe the non-profit route will work

If something isn’t done now, antibiotic-resistant bacteria could kill as many as 10M people a year by 2050. A little-known Boston nonprofit could be our best hope.

2021-07-28: Biofilms are nasty

This discovery underscores how important it is to include biofilms in any studies of antibacterial compounds because being able to kill planktonic cultures bears no relation to being able to break down biofilm.

2021-10-14: Another approach is to modify bacteria to destroy the MSRA biofilms

Bacteria present a promising delivery system for treating human diseases. Here, we engineered the genome-reduced human lung pathogen Mycoplasma pneumoniae as a live biotherapeutic to treat biofilm-associated bacterial infections. This strain has a unique genetic code, which hinders gene transfer to most other bacterial genera, and it lacks a cell wall, which allows it to express proteins that target peptidoglycans of pathogenic bacteria. We first determined that removal of the pathogenic factors fully attenuated the chassis strain in vivo. We then designed synthetic promoters and identified an endogenous peptide signal sequence that, when fused to heterologous proteins, promotes efficient secretion. Based on this, we equipped the chassis strain with a genetic platform designed to secrete antibiofilm and bactericidal enzymes, resulting in a strain capable of dissolving Staphylococcus aureus biofilms preformed on catheters in vitro, ex vivo, and in vivo. To our knowledge, this is the first engineered genome-reduced bacterium that can fight against clinically relevant biofilm-associated bacterial infections.

2023-05-23: Odd that phage therapy only made progress in former soviet republics

“Phages” are little known outside the former countries of the Soviet Union, which did the most to develop the idea. In Georgia they have been part of the local pharmacopoeia for decades. (Indeed, 2023 marks the Eliava’s centenary.) Little vials containing stale-tasting liquid full of anti-bacterial viruses can be bought at pharmacies across Tbilisi. Now, as worries about antibiotic resistance build, Western firms are taking a second look.

Interstellar

Multi-Generation Space Ships

the motivations, technology, and prospects for interstellar flight, while the balance deals with anthropological, genetic, and linguistic issues in crew composition for a notional mission with a crew of 200 with a flight time of 2 centuries.

2007-06-15: On the infeasibility of interstellar travel

We require the equivalent energy output to 400 megatons of nuclear armageddon in order to move a capsule of the gross weight of a fully loaded Volvo V70 automobile to Proxima Centauri in less than a human lifetime. That’s the same as the yield of the entire US Minuteman III ICBM force. Our entire planetary economy runs on 4TW. So it would take our total planetary electricity production for a period of 5 days to supply the necessary va-va-voom.

2009-02-01: Tau Zero Foundation

The Tau Zero Foundation is a volunteer group of scientists, engineers, entrepreneurs, and writers who have agreed to work together toward practical interstellar flight and to use this quest to teach you about science, technology, and our place in the universe.

2010-05-07: Project Icarus

To design a credible interstellar probe that is a concept design for a potential mission in the coming centuries.

2011-01-06: No Interstellar Travel Before 2200. About 10^18 Joules required, more than a Kardashev type I civilization.
2011-05-20: Star Children. It might make sense to start a religion to ensure long term space travelers retain their goals.

We are seeking ideas for an organization, business model and approach appropriate for a self-sustaining investment vehicle. The respondent must focus on flexible yet robust mechanisms by which an endowment can be created and sustained, wholly devoid of government subsidy or control, and by which worthwhile undertakings—in the sciences, engineering, humanities, or the arts—may be awarded in pursuit of the vision of interstellar flight

2013-04-25: Starship Century

Is this the century we begin to build starships?

yes

2014-03-12: Starship Century

Starship Century is a symposium coordinated by the new Arthur C. Clarke Center for Human Imagination in collaboration with Gregory and James Benford, presenting ideas from their anthology of science and science fiction. First 8 minutes most of them agree the era of interstellar starships will be 100-300 years away after there is lot of solar system development.

2015-10-21: Black hole drive

The petawatt Hawking radiation of γ-ray laser-created subatomic black holes (Schwarzschild Kugelblitzes or SKs) has been proposed as a propulsive and power source for interstellar starships. Production of a black hole requires concentration of mass or energy within the corresponding Schwarzschild radius. In familiar 3D gravity, the minimum such energy is 10^19 GeV, which would have to be condensed into a region of approximate size 10^-33 cm. This is far beyond the limits of any current technology; the Large hadron collider (LHC) has a design energy of 14 TeV. This is also beyond the range of known collisions of cosmic rays with Earth’s atmosphere, which reach center of mass energies in the range of 100s of TeV. It is estimated that to collide 2 particles to within a distance of a Planck length with currently achievable magnetic field strengths would require a ring accelerator ~1k light years in diameter to keep the particles on track.

2016-02-20: Interstellar Propulsion. A 100kg robotic craft could be sent to Mars in 3 days with the power levels that large rockets produce (50-100 GW)

2016-04-12: Starshot. This makes me proud of our civilization: We do stuff like this.

Milner wants his $100M to fund research that will culminate in a prototype of a probe that can beam images back to Earth. The images would arrive less than 5 years after the probe reached the star.

There are no official specs yet, but the probe would have a 2-megapixel camera, along with star-finders to help it get its bearings, after it boots up on the approach to Proxima Centauri. The probe will target one of the system’s 2 sunlike stars. It will be aimed at a planet (or planets) in the star’s habitable zone, the temperate region where oceans don’t boil or freeze, but instead flow, nurturing the kind of complex chemistry that is thought to give rise to life.

2018-08-14: Propellantless interstellar travel

Researchers propose a new mode of transport which relies on electric-field moderated momentum exchange with the ionized particles in the interstellar medium. While the application of this mechanism faces significant challenges requiring industrial-scale exploitation of space, the technological roadblocks are minimal, and are perhaps more easily addressed than the issues presented by light sails or particle beam powered craft. This mode of space travel is particularly well suited to energy efficient space travel at velocities less than 5% of light speed, and compares exceptionally well to light sails on an energy expenditure basis. It therefore represents an extremely attractive mode of transport for slow (~multi-century long) voyages carrying heavy payloads to nearby stellar neighbors. This could be very useful in missions that would otherwise be too energy intensive to carry out, such as transporting bulk materials for a future colony around Alpha Cen A, or perhaps a generation ship.

2020-02-21: Interstellar Probe, weighing a few grams, and getting there in 20 years.
2020-09-03: Mach Effect Propulsion. Jim Woodward is investigating mach effect thrusters as part of NASA NIAC. If successful, this will get us to .xc, making humanity interstellar.
2022-08-05: Bow Shock Deceleration

Deceleration at the destination system is a huge problem for starship mission planning. A future crew, human or robotic, could deploy a solar sail to slow down, but a magsail seems better, as its effects kick in earlier on the approach. Looking at the image below, however, suggests another possibility, one using the interactions between stars and the interstellar medium to assist the slowdown. The bow shock produces 3D structures, surfaces within which one can move while shedding speed, perhaps braking via a magsail. Each star would produce its own unique deceleration environment, allowing us to brake where possible along the bow shock, the astropause (cognate to the heliopause) and the termination shock.

Research is false

There is increasing concern that in modern research, false findings may be the majority or even the vast majority of published research claims. However, this should not be surprising. It can be proven that most claimed research findings are false.

Ioannidis presents a Bayesian analysis of the problem which most people will find utterly confusing. Here’s the idea in a diagram.


Suppose there are 1000 possible hypotheses to be tested. There are an infinite number of false hypotheses about the world and only a finite number of true hypotheses so we should expect that most hypotheses are false. Let us assume that of every 1000 hypotheses 200 are true and 800 false.

It is inevitable in a statistical study that some false hypotheses are accepted as true. In fact, standard statistical practice guarantees that at least 5% of false hypotheses are accepted as true. Thus, out of the 800 false hypotheses 40 will be accepted as “true,” i.e. statistically significant.

The groupies of science

for the last 4 years … has attended graduate physics seminars, used the offices reserved for doctoral and postdoctoral physics students and for all intents and purposes made the Varian Physics Lab her home. The only problem is that Okazaki appears to have no affiliation with Stanford and no real reason to be there.

When we discover a stowaway on the great Ship of Science, why throw her overboard when we could make her swab the decks?