klmr

The eLife paper you link to discusses errors in RNA synthesis (transcription), not in tRNA-dependent protein synthesis (translation). The abstract mentions “translation”, but only as an amplifier of transcription errors: each mRNA transcript is translated into proteins thousandfold, so every error in a single mRNA molecule will be present in thousands of protein molecules.

Translation errors also exist, and some people hypothesise that there is selective pressure on protein-coding genes to reduce this source of errors by selecting codons in a way that reduces the error rate (potentially by slowing down the polymerase). This results in something known as “codon bias” but so far there is no good evidence that codon bias has an actual effect on error rate (it does have an effect on correct protein folding), or is selected for (http://dx.doi.org/10.7554/eLife.27344, http://dx.doi.org/10.1371/journal.pgen.1006024).

He isn’t (and never was) the owner of Spiegel. He’s the son of the Spiegel’s founder and former editor in chief.

I did mean Stansted but admittedly it’s probably the least convenient airport from Central London unless you live close to the Liverpool Street line — personal bias led me astray. London City is of course closer from many points within London but is much smaller. That said, London’s other airports are also relatively convenient, e.g. Gatwick and Heathrow via tube, Thameslink or dedicated trains.

Yes: As mentioned, I think this is excellent advice.

For what it’s worth the comment you’re replying to is completely right about what I meant. I see that my phrasing invites misunderstanding, and the distinction is subtle.

> If you have a favorite 1 hour weekly TV show, that's almost the same amount of time committed.

Right, but very few people watch the exact same episode/series over and over, at the exclusion of everything else. And people who do that are generally seen as more than just devoted. It also means that you have one hour less to discover something new. The Bible is a big book, but it’s limited. I’ve read all of it, and I’ve read parts multiple times (it is, after all, a central part in Western culture). But reading it again and again every day means I’d lose time in which I could be reading (and learning!) other things.

A commenter below mentions quiet time. This is a perfectly fine concept but those Christians (both Catholics and Protestants) that I know don’t spend it rereading the same text over and over. They spend it introspecting. Anyway, I don’t want to disparage the concept: All things said and done even if I’d consider this time completely wasted you’re right that it’s fairly short. I just found it hard to believe because, as mentioned, it doesn’t match my experience at all due, presumably, to cultural differences.

This is good advice, but

> they are probably used to read a chapter or two on a daily basis

This sounds mental. Reading the Bible on a daily basis? I’m pretty sure that this is not the norm for the vast majority of (devout) Christians (at least in Western/Central Europe).

Flying is cheaper and faster, but not necessarily more convenient. To find cheap flights you often have to get to inconveniently located airports (the great exception being London Stansted) at odd hours, often having to change transport on the way, and lose a lot of time due to checkin and security (which are in themselves massive inconveniences). And even when paying for a better ticket the flight is often too cramped to do anything effectively. All in all, you’d often not save all that much time by flying, and the time actually spent in transit is mostly wasted, whereas a train ride affords you the opportunity to work, read or watch movies.

Some people manage to read or watch movies at least on the flight itself but personally my head hits the pillow before the plane even leaves the runway. I’m not sure what soporific magic is at play here. Anyway, I avoid flying as much as possible as a consequence.

I know this isn’t the point of the article but the code shown there is the archetypal case where writing classes is an anti-pattern, as argued in “Stop Writing Classes” [1]. All the classes in that code can — should! — be functions. There’s no downside, and it’s less code (and otherwise identical).

[1] https://news.ycombinator.com/item?id=3717715

I wasn’t explicitly referring to that, it’s just one of many efforts. Anyway, you’re certainly right that none of the existing efforts are “elegant” but that’s hardly relevant. What matters is that the connectome is fully mapped, and that we can accurately simulate arbitrary behaviour. The issue with projects such as OpenWorm is that they have so far not been successful in generating new insight (this may be connected to your issue with lack of elegance) but this is distinct from being able to accurately simulate behaviour. Another issue is that of simulating the physical environment because — surprise, surprise — simulating the worm neurons without any realistic external stimuli is a pretty pointless exercise for most purposes.

But pick any set of stimuli you like, feed it into the models and you get a response that corresponds exactly with empirical observation. I’d therefore definitely call the neuronal model itself accurate and complete.

What? Ants don’t have general intelligence, and even ant colonies’ decision making (= simple swarm intelligence) is readily replicable in a programmed system, and has been, for a while.

I don’t think a gradual scale is very helpful because I don’t think that the progression from current-generation AI to AGI is going to be gradual (it will require at least one paradigm shift). That said, if you want to compare AI progress to actual animals then our current-gen AI way beyond ants. Note that, while we haven’t fully mapped the neurons/connectome of ants yet, this is unnecessary to emulate their decision-making power. And we have mapped (and can simulate) the full connectome of simpler animals (e.g. C. elegans, P. dumerilii) so we’re definitely a long way beyond single molecules.

Noncoding DNA ≠ junk DNA! In fact, the latter is a subset of the former. Confusing the two is understandable since even scientists occasionally play fast and loose with the terms but scientists nevertheless understand that they are different. To cite from the same article you’ve cited:

> When there is much non-coding DNA, a large proportion appears to have no biological function, as predicted in the 1960s. Since that time, this non-functional portion has controversially been called "junk DNA".

And this is by no means a new discovery, functional noncoding DNA has been known for as long as junk DNA.

Ah, I misunderstood your commend as saying that you’re currently working on the thesis.

Well my own research has focused completely on noncoding DNA. So yes. It exists.

Junk DNA has already been studied before whole-genome sequencing existed, and evidence from NGS not only hasn’t overturned that research, it has largely corroborated it. And as for personal biases, I’m a staunch defender of the ENCODE research so I’m certainly not biased in favour of the concept of junk DNA.

> To say that massive portions of our DNA “have no benefit” without having proof of such, seems naive to me.

What makes you think scientists have no proof? The whole reason we know junk DNA has no important function for cell biology is that there’s good evidence that says so. There’s some wiggle room with the details but the general picture of this won’t change, and this has been studied for a long time and is fairly well understood.

What you were taught in college 15 years ago is still correct. Junk DNA does not have “a very important function”. The “subsequent discoveries” were, by and large, just a failure in science communication. Junk DNA is still non-functional, very little has changed. We know this because it’s not preserved evolutionarily. By contrast, “important” DNA is preserved from mutation (this is called “negative” or “purifying” selection) because mutating it is almost always bad for the individual. What has changed is twofold:

* We have a better handle on what constitutes noncoding, non-junk DNA. The proportion of DNA thus labelled has grown slightly (but only slightly!). We were always aware of its existence but we previously couldn’t study it easily. There are very good reasons to think that the proportion won’t grow much further. The rest is still junk DNA.

* We know more about how new genetic function can evolve using the raw genetic material in junk DNA, and how junk DNA might interfere with the proper function of cells, in particular in the presence of pathogens. But, again, the principle of this was already known (or, partially, at least strongly suspected) decades ago. It was just not studied, and we’re now able to study it better.

But our fundamental understanding of junk DNA hasn’t changed.

> labeling something as non useful and leaving it out of the majority of DNA sequencing as a result has made large swathes of the scientific community unaware of how non coding DNA works within the DNA ecosystem

This is simply not true. Noncoding RNA and in particular regulatory regions have been known and studied for many decades. The reason we know less about them than about genes has multiple reasons, foremost the difficulty in studying them (large-scale studies have only recently become possible). But it has nothing to do with “ignorance”, or with the label “junk DNA” (the SciAm article you link to is utterly wrong to claim otherwise).

Furthermore, although I also think the name has issues (but mostly in science communication), scientists don’t just “assume” that intergenic, non-regulatory DNA regions are unimportant. They have good reasons, backed by evidence, to think so. I’m actually in the camp that thinks that stochastic biochemical function is potentially important (and I used to study repeat elements) but even so there’s almost certainly very little “exciting … unknown science” in junk DNA.

> some types of diets seem to help with autism

Sorry, the actual evidence for this is essential nil. The anecdotes are all explainable by confirmation bias. https://skeptics.stackexchange.com/a/43957/82

You could broaden your definition of gene to include proximal regulatory elements. If you take that unit and translocate it the answer is much less obvious.

I broadly agree with your point but careful when saying “no obvious phenotype”. As my former boss likes to say about work in C. elegans: “Worms can’t talk. They seem healthy but maybe they’re extremely unhappy.” Less flippantly, we know that biological systems in general have huge plasticity to buffer environmental changes. The environment is controlled under lab conditions, so loss of robustness due to genetic changes will almost never be detected. We have no good estimate — not even a ballpark! — of how many of these 95 “no obvious phenotype” cases actually have no phenotype, and beliefs widely vary.

It seems this study focuses on regulatory regions of coding genes (i.e. regions of DNA that’s in proximity of coding genes, or in introns), rather than on noncoding RNAs. This doesn’t exclude the possibility of noncoding RNAs also having an effect though.

Nice explanation but you seem to be saying that at most 3% (being generous) of DNA would be functional (if the rest is “random noise”). This number is over twice as small as the lowest estimate (~ 8%) of even the most fervent critics of ENCODE’s number. I’d love to hear a brief break-down of your reasons, if possible.

> Would this mean gene-therapy could potentially undo autism?

Almost certainly not. Autism is caused by developmental changes. This means that any gene therapy would have to start before the embryo development is even finished, i.e. in the mother’s womb. After that, it’s essentially too late. Think of it this way: Could gene therapy make an adult person taller or smaller? Despite the fact that height has a large genetic component the answer is obviously no, since skeletal growth stops after puberty.

> I believe it's now actually agreed upon that autism rates actually ARE increasing

You’re jumping the gun there. It’s plausible that there are factors that are causing an increase of autism rates (e.g. ageing parents) but so far there’s no positive evidence that this is indeed the case, or that diagnostic changes aren’t the sole reason (see https://en.wikipedia.org/wiki/Epidemiology_of_autism#Changes...).

Teaching research is unfortunately fairly balkanised and my brief stint in the science of teaching was in German, so I could, for the most part, only offer references to German text books. However, it’s established that active learning increases student performance significantly [1], and systematic active learning was only introduced into curricula fairly recently (and not yet pervasively). Where this was done this has by necessity caused an at least partial “grade inflation” but I’ll admit that its adoption is far from satisfactory so (as my comment already noted!) it might not be sufficient to explain grade inflation.

[1] https://www.pnas.org/content/111/23/8410.full

The essay is very light on evidence. Pathological cases (such as buying grades) aside, maybe grades have generally increased because teaching has gotten better? I certainly wouldn’t posit this as an absolute truth but research into teaching methods has gotten better. 50 years ago teaching wasn’t the least bit scientific. Modern research into teaching methods is a proper science, even if it’s hindered by many false starts and slow adoption. Modern technology also offers vast potential for better teaching and learning.

I’m not sure how useful grades are when everybody gets an A. But if the reason is a phenomenal teacher (and better teachers reproducibly produce better performing students [e.g. 1]) then maybe grades are simply an unhelpful metric. “Stopping grade inflation” isn’t just not a solution, but actively counter-productive. “Grading on a curve” when every student has mastered the curriculum (which, in higher education, is entirely achievable) is bogus.

[1] https://onlinelibrary.wiley.com/doi/full/10.1002/jae.2539

This is a good heuristic for advanced logic, but not when the main purpose of the script is to encode a workflow of coding other tools. I’m using other languages for that too, but shell scripting languages are consistently superior to all of them (including Perl and Ruby, IMHO; workflow languages might help but pull in tons of dependencies).

It’s also really limited. I do a lot of shell programming and I lean heavily on Bashisms to get any work done. Even in Bash I’m hitting the wall constantly. Sh-only is utterly impractical: Reading code from big projects that try to stay compatible (e.g. automake) really show-cases these limitations. For instance, performing proper argument quoting of variables without arrays is next to impossible.

Unfortunately that link to the Rust FAQ is broken.

The vast majority of experts in this field are not affiliated with Monsanto and don’t make a dime from it. They are the “general public”, except well informed, and have studied years to understand the relevant (complex) background to make an informed assessment. Non-experts may be dedicated but they simply don’t match years or even decades of rigorous studying on the subject.

This “all experts are in the pockets of big X corporation” is inaccurate and insulting. It’s just getting really tiring.