Daniel Lemire's blog

, 15 min read

Science and Technology links (April 7th, 2017)

Many people suffer from obesity. I am not sure we know how to combat this epidemic effectively. There is a never ending stream of wonder diets, but nothing seems to actually work. Or we just tell people to have more will power. New research suggests that inactivity is more a consequence than a cause of obesity. That is, while moving too little can contribute to making you obese, once you are obese, your body favors inactivity.

Some time ago, Amazon surpassed Walmart in market value: Amazon is worth (430B$) about twice as much as Walmart (225B$). Amazon has about 340,000 employees whereas Walmart has over 2 million employees. For some perspective, Apple is worth nearly twice as much as Amazon (800B$), but it has far fewer employees than Amazon (about 100,000). We have learned this week that Tesla, the electric car company, surpassed Ford in market value. Unlike Ford’s cars, all of Tesla’s cars have full self-driving hardware. Ford has 200,000 employees; Tesla has 30,000 employees. By the way, Amazon is worth about ten times as much as Ford.

Our cells produce their energy in its mitochondria. The mitochondrion is like a tiny cell (with its own DNA) that lives within our cells. (Red blood cells are an exception as they produce their energy by fermentation, like cancer cells.) Having lots of healthy mitochondria is critical. Cells that have a hard time producing energy don’t work as well. Our brain uses a lot of energy so it needs lots of good mitochondria. It is possible that neurological diseases (like Parkinson’s) could be tied to mitochondrial dysfunction. Anything from cancer all the way to skin wrinkles might be tied to mitochondria. So what harms mitochondria? We don’t know everything yet, but Toda et al. found that too much sugar may harm the mitochondria within our neurons.

What might you do if someone has too few good mitochondria? What about just injecting new ones? It seems that it might work:

Mitochondrial dysfunction is associated with a large number of human diseases, including neurological and muscular degeneration, cardiovascular disorders, obesity, diabetes, aging and rare mitochondrial diseases. Replacement of dysfunctional mitochondria with functional exogenous mitochondria is proposed as a general principle to treat these diseases. Here we found that mitochondria isolated from human hepatoma cell could naturally enter human neuroblastoma SH-SY5Y cell line, and when the mitochondria were intravenously injected into mice, all of the mice were survived and no obvious abnormality appeared.

If you care, however, about how many mitochondria you have, you should know that high-intensity training increases the mitochondria count of your muscles. This likely means that high-intensity training makes your muscles better at producing energy.

Quick: what operating system people use most to browse the Web? If you said Windows, you are wrong. Android is the Web’s most popular operating system. Android’s parent company (Google/Alphabet) is worth more than Microsoft. Stem cells are these specialized cells in our bodies that are in charge of generating all other cells. There is currently a race to produce therapies based on stem cells. We are developing cheap ways to generate stem cells for therapeutic purposes. The idea is that you just inject stem cells at the right place in just the right way, you might spur regeneration. What might you want to regenerate? What about injured tendons for example? Sadly if you just inject stem cells in an injured tendon, you do not get the kind of regeneration we need. For example, the stem cells may just go elsewhere, where you do not need them. However, Peach et al. found that if you just implant the stem cells within a synthetic matrix, that acts as a niche for the stem cells, they stay in place and do the work we expect, regenerating tendons.

Greg Linden reports that though 6.3 million VR headsets were sold in 2016, “almost all so far just the cheap toys where you slot your smartphone in to use as the screen”. As an anecdote, my wife got a free VR headset with her latest smartphone, and she just told the clerk to keep it. Greg also reports that tablet sales a falling.

Apple quietly released a new iPad, its famous tablet. It is inexpensive (for an Apple product), it has great processor performance, and a nice screen (albeit without reflective coating). I own an iPad Air and I won’t be upgrading.

Apple has been designing its own mobile processors (the Ax series) with great success. Apple’s mobile products have fast processors. The single-core performance of Apple’s latest iPhone is on part with Intel’s laptop processors. It now looks like Apple wants to design and own its graphics processors. Up till this point, Apple was relying on designs from a company called Imagination Technologies. Apple told them that it was over. It seems very likely that Apple has been developing its own technology quietly for some time and that they are ready to produce it. This comes at a time when graphics processors are increasingly used for artificial intelligence, in addition to graphics.

Whereas mitochondria provide the cells with energy, the lysosome collects and recycle the garbage (what scientists call “autophagy”). When either of those goes bad, the cell is in trouble. A Korean team found that some kind of product (“ataxia telangiectasia mutated inhibitor KU-60019”) can do some good when it happens:

In turn, this reacidification induced the functional recovery of the lysosome/autophagy system and was coupled with mitochondrial functional recovery and metabolic reprogramming.

So, in yeast, these scientists were able to “reboot” the cells so that both energy production and garbage collection were back in full strength. Though you may not care about yeast, it is possible that the same trick could work in mammals like us. I presume that these researchers must be working on mice as we speak.

Ethiopia is building a space programme.

How fast is JavaScript, the programming language used by your browser? Fast enough to run high-performance databases:

This demonstration explores the novel and unconventional idea of implementing an analytical RDBMS in pure JavaScript so that it runs completely inside a browser with no external dependencies. Our prototype, called Afterburner, generates compiled query plans that exploit two JavaScript features: typed arrays and asm.js. On the TPC-H benchmark, we show that Afterburner achieves comparable performance to MonetDB running natively on the same machine.

Sabine Hossenfelder comments in Nature about the current state of science:

We’re judged by our publication count — or at least it’s what we think we’re being judged by — and stricter quality measures in theory development would cut back productivity. (…) To me, our inability — or maybe even unwillingness — to limit the influence of social and cognitive biases in scientific communities is a serious systemic failure. We don’t protect the values of our discipline. The only response I see are attempts to blame others: funding agencies, higher education administrators or policy makers. But none of these parties is interested in wasting money on useless research. They rely on us, the scientists, to tell them how science works.

Optimizing productivity is important, but you have to produce the right things. Producing research papers in great quantities is hardly worth anything. It is not like research papers are scarce as it is. We have a glut of research papers: more than you could ever read. Obviously, what we want, what we need, is scientific progress. I believe that producing research papers can be part of a productive process… telling others about your work is a great way to help push things forward… but it should never be the end product. Here is an analogy. The goal of a programmer is not to produce software. If we started remunerating programmers by how many lines of code they write, we would sure get many lines of code. But that’s obviously not what we, the users, want. Yet, of course, producing lines of code is part of a useful process to serve users. So how do we fix the problem that Hossenfelder outlines? She is right that it is useless to complain about the pressure to publish. We are all under pressure to be more productive and that’s not a bad thing. What is missing, and somehow Hossenfelder fails to mention it, is more “skin in the game”. What I mean is that scientists need to profit when their research help us progress, and they need to suffer when their research (irrespective of how many papers are published) fails to help us or, worse, holds us back. We have to realize that the current funding practices simply do not provide these necessary incentives. If you are a scientist doing useless work as part of a large cohort of equally useless people, you will be, everything else being equal, more successful than a lone scientist trying to find more useful alternatives… because of peer review. Peer review ensures mediocrity. Scientists should be reviewed by people who have strong incentives to fight against cargo-cult science.

The bulk of medical research occurs in the United States, and much of it is funded by the US government through the National Institutes of Health (NIH). It looks like White House is planning to cut by 20% NIH’s funding which could have adverse consequences on scientific progress. My understanding of US politics is that the president in not in charge of the budget, the congress is, so I am not sure what to make of it all. Moreover, the bulk of the medical research, in the US, is privately funded (75% of clinical trials are privately funded), and an overwhelming majority of new drugs and therapies come from the private sector. So while I would favor massive increases in funding for research, especially medical research, I do not think that, in the current system, there is a strong correlation between scientific progress and government funding. Sadly. We need to fix the incentives. Moore’s law is the empirical observation that the number of transistors in processors doubles every two years. It was made in 1975 and it has held true for the last few decades. However, many people have proclaimed that Moore’s law is dead. Not so fast

If you divide the number of transistors in Intel’s current [processor] by the surface area (…), the rate of improvement still equals out to more than double every two years, keeping Moore’s law on track

What is certainly true, in my experience, is that successive Intel commodity processors do not generally make our software runs faster, much faster. That’s what leads people to call Moore’s law as being dead. But we should not conclude that the technology is stagnating just because one metric is plateauing (performance of Intel’s commodity processor).

Google is giving us more details regarding the hardware they use for machine learning. It seems to be between one and two orders more efficient than commodity processors. It is capable of 92 trillion 8-bit operations per second. For a company the scale of Google, it matters. Over time, it would be interesting to contrast these results with the evolution of Moore’s law. That is, can Google manage to keep on improving its custom processors at a rate that exceeds that of companies like Nvidia and Intel?

Another computer science professor warns us about technological unemployment:

“If you are a truck or taxi driver, you should be very concerned,” the Dalhousie University computer science professor [Stan Matwin] said in an interview Monday. “In five to 10 years, I think we will see a substantial amount of cars that will be driving automatically.”

We have been told for decades that salt is the silent killer, causing high blood pressure and leading to heart attack. Nah.

the consumption of a high salt diet is not the cause of hypertension and that there are other factors, such as added sugars, which are causative for inducing hypertension and cardiovascular disease

We have learned that it is useless to load up on antioxidants through supplements, and it might even be harmful. So taking vitamin C supplements is probably not good (but eating oranges is fine). However, that’s only true in general. Scientists have found that massive doses of vitamin C could be helpful for cancer patients. It seems that the effect is related to the fact that cancer cells tend to have dysfunctional mitochondria. These generate lots of active iron molecules that react with vitamin C to create nasty stuff damaging cancer cells specifically:

we verified convincingly that increased redox active metal ions in cancer cells were responsible for this differential sensitivity of cancer versus normal cells to very high doses of vitamin C

So maybe we shall treat cancer patients to megadoses of vitamin C in the future. Linus Pauling would be happy. To be clear, the point here is not that vitamin C can cure or prevent cancer, but rather that it can do a lot more harm to cancer cells than to rest of the body, thus complementing other treatments.

Maybe Earth is not a planet. But Pluto might be officially a planet again. It seems like astronomers have a lot of time on their hands.

We might be able to cure allergies using nanoparticles.

Last week, I reported how scientists they could, maybe, partially reverse aging by reversing the decline of nicotinamide adenine dinucleotide (NAD). Young mammals have lots of NAD, older mammals have little of it. NAD helps keep your cells healthier and having less of it means that your cells are more fragile. You can’t eat NAD, but you can convince your body to get more by consuming its precursors: nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Both of these should be available at a health store near you, and you can order them from Amazon if you want. (Note: I do not recommend doing so, and I am not taking this stuff.) I thought it was early to go to the press and claim that a cure against aging was around the corner. As it turns out, according to this article in Nature, NAD-precursor clinical trials are already ongoing in Japan. So it is further along than I thought. Still, I think expectations should be modest. Given that NMN is freely available, if it turned back the clock in an obvious manner, we would know by now. It is certainly not going to make wrinkles and gray hair go away. However, we could hope for it make older people healthier. Maybe. Hopefully. So why Japan? I’d like to know. Here is something nice I’d like to stress… if these trials show that NMN is helpful… makes us healthier as we grow older… we can all go Amazon and order the stuff. So even if the impact is modest on each individual, the overall impact could be huge given that it is relatively cheap and widely available. But, again, please wait for the science to come in before you eat the stuff or put it on your face. We still know too little.

Need to get a surgery that you can’t get in your country? China wants you to come over as a tourist to get your nifty medical treatments. This could give the “made in China” statement a whole different meaning.

Looks like the next generation of PC memory chips (coming out in 2018) could have twice the speed. This could be a big deal. Getting access to the data is often half or more of the work. A slower processor with faster memory can sometimes be faster.

Though you might think that you can see all colors, in reality, we only see blue, red and green colors. Researchers have found a way to fool our eyes into seeing more colors with special filters.

The thymus in an organ responsible for producing new white blood cells. As you age, your thymus shrinks to nothing and stops doing its work. Younger people can also have a damaged thymus due, for example, to cancer. So your immune system becomes ineffective. In particular, it means that you lose much of your ability to fight cancer through your immune system. There are ongoing clinical trials to regenerate the thymus, with the hope that it will give people better health (fewer cancers, fewer diseases). In a Nature article, researchers explain how they were able to construct an “artificial thymus”. So if you have cancer, instead of relying either on donated white blood cells or on your own blood cells, we could create custom white blood cells using organoids that are engineers to fight particular diseases like cancer. Senescent cells are cells that our bodies accumulate with time. They are supposed to die, but they just stay there, causing trouble. The more you get, the more trouble they cause, and since they won’t die, you get more and more over time. Clearing senescent cells is all the rage right now. There is a wonder drug called rapamycin that’s used as an immunosuppressant for transplant patients. It was first discovered on Easter Island, kept in a scientist’s personal fridge somewhere in Montreal after his employee shut down, and later commercialized. Rapamycin is not something you’d want to normally take, as it has several bad side-effects, like increasing your risk of diabetes and suppressing your immune system… However, it also seems to ramp up your body’s natural defenses through the Nrf2 pathway. It seems protective against cancer, for example. Incredibly, it looks like rapamycin is a senolytic, that is, a drug that helps clear out senescent cells. This makes rapamycin a very interesting subject of investigation. If only we can minimize its side-effects, maybe by altering it somehow, we could have a powerful drug that keeps us healthy.

It is now understood that the bacteria in your gut play a key role in keeping you healthy. They found that by injecting young poo into old fishes, they could make these old fishes live older. The equivalent process in human beings would be mind boggling. Close your eyes and imagine rejuvenation clinics where older people can receive, on a routine basis, transfusion of teenager’s poo. Hmmm… Multiple sclerosis is a terrible degenerative disease. There is no therapy right now that can even slow the progression of the disease. However, there is renewed hope as a new drug, ocrelizumab, seems to do just that. It completed phase III clinical trials and it seems to work. Hopefully, it will be commercialized soon. It is not a cure yet for multiple sclerosis, but slowing down the disease is important.