Escola da Ponte by Ciro Santilli 40 Updated 2026-01-30
Video 1.
Aprender em Comunidade by Prof. José Pacheco
. Source. In Portuguese. Title translation: "Learn in community".
Video 1.
Transmission Electron Microscope by LD SEF (2019)
Source. Images some gold nanopraticles 5-10 nm. You can also get crystallographic information directly on the same machine.
University by Ciro Santilli 40 Updated 2025-09-09
One major issue is that teachers don't have the right incentive to, nor are selected to, teach well. Thus the existence of Rate My Professors! But we can do better...
Which is why Ciro Santilli wants to destroy its current format with OurBigBook.com. He believes that we can find a more efficient organization to achieve both the social and research functions of university, by first doing as much as possible online
This technique has managed to determine protein 3D structures for proteins that people were not able to crystallize for X-ray crystallography.
It is said however that cryoEM is even fiddlier than X-ray crystallography, so it is mostly attempted if crystallization attempts fail.
By looking at Figure 1. "A cryoEM image", you can easily understand the basics of cryoEM.
We just put a gazillion copies of our molecule of interest in a solution, and then image all of them in the frozen water.
Each one of them appears in the image in a random rotated view, so given enough of those point of view images, we can deduce the entire 3D structure of the molecule.
Ciro Santilli once watched a talk by Richard Henderson about cryoEM circa 2020, where he mentioned that he witnessed some students in the 1980's going to Germany, and coming into contact with early cryoEM. And when they came back, they just told their principal investigator: "I'm going to drop my PhD theme and focus exclusively on cryoEM". That's how hot the cryo thing was! So cool.
Figure 1. . Source. This is the type of image that you get out of a raw CryoEM experiment.
Video 1.
The structure of our cells by Matteo Allegretti
. Source. The start is useless. But the end at this timestamp shows an interesting technique where they actually cut up cells in fine slices and image them, that's cool.
Super-resolution means resolution beyond the diffraction limit.
First you shine a lot of light which saturates most fluorophores, leaving very few active.
They you can observe fluorophores firing one by one. Their exact position is a bit stochastic and beyond the diffraction limit, but so long as there aren't to many in close proximity, you can wait for it to fire a bunch of times, and the center of the Gaussian is the actual location.
From this we see that super-resolution microscopy is basically a space-time tradeoff: the more time we wait, the better spacial resolution we get. But we can't do it if things are moving too fast in the sample.
Tradeoff with cryoEM: you get to see things moving in live cell. Electron microscopy fully kills cells, so you have no chance of seeing anything that moves ever.
Caveats:
  • initial illumination to saturate most fluorophores I think can still kill cells, things get harder the less light you put in. So it's not like you don't kill things at all necessarily, you just get a chance not to
  • the presence fluorophore disturbs the system slightly, and is not at the same Exact location of the protein of interest
Free university by Ciro Santilli 40 Updated 2025-07-16
Related projects:
Leeuwenhoek microscope by Ciro Santilli 40 Updated 2025-07-16
Figure 1. Source. This is a microscope, I kid you not. TODO photo of what you can see with it.
X-ray crystallography by Ciro Santilli 40 Updated 2025-07-16
One of its main applications is to determine the 3D structure of proteins.
Sometimes you are not able to crystallize the proteins however, and the method cannot be used.
Crystallizing is not simple because:
  • you need a considerable amount of the protein
  • sometimes it only crystallizes if you add some extra small chemical that stabilizes it
Cryogenic electron microscopy can sometimes determine the structures of proteins that failed crystallization.
X-ray diffraction by Ciro Santilli 40 Updated 2025-07-16
Often used as a synonym for X-ray crystallography, or to refer more specifically to the diffraction part of the experiment (exluding therefore sample preparation and data processing).
cyclotrons produce the better images, but they are expensive/you have to move to them and order a timeslot.
Lab-based just use some X-ray source from the lab, so it is much move convenient e.g. for a pharmaceutical company doing a bunch of images. The Wikipedia image shows such a self-contained lab system: en.wikipedia.org/wiki/File:Freezed_XRD.jpg
The image of an university is basically their only real asset, which they extract money out of via undergraduate students in some countries like the USA, and by getting funding.
For this reason, universities will sacrifice basically any principle in order to give themselves a good image.
Although for profit companies also do this, it is simply on another level for universities.
You can always learn pure theory later on for free or very cheap from books.
And above all, you can always learn software engineering later on for free, because the programming community is so much more open than any other so far, notably e.g. with Stack Overflow and GitHub, see also: Section "Ciro Santilli's Open Source Enlightenment". Ciro Santilli is trying to change that with OurBigBook.com, but don't hold your breath. But it is increasingly hard to understand why there isn't an university that forces teachers to publish all their notes and lecture videos (which should be mandatorily recorded) with a Creative Commons License, and then let anyone take whichever exams they want for a small fee or for free.
Actually, there is a good chance you will learn to program, like it or not, because chances are that you won't be able to find as decent a job doing anything else.
But there is one thing you cannot learn for free: laboratory work. Laboratory work is just too expensive to carry out outside of an institution.
Basically, if you don't do laboratory work in undergrad, you will very likely never be able to do so in your entire life.
Because laboratories are so rare and expensive, it is laboratories that put you in the best most unfair position at creating world changing deep tech startups, which is why when in doubt, choose the course that has the most experimental work. Yes, you won't be able to achieve those insanely concentrated equities of the early-Internet, as you will need more venture capital to run your company, but those days are over now, deal with it.

Pinned article: Introduction to the OurBigBook Project

Welcome to the OurBigBook Project! Our goal is to create the perfect publishing platform for STEM subjects, and get university-level students to write the best free STEM tutorials ever.
Everyone is welcome to create an account and play with the site: ourbigbook.com/go/register. We belive that students themselves can write amazing tutorials, but teachers are welcome too. You can write about anything you want, it doesn't have to be STEM or even educational. Silly test content is very welcome and you won't be penalized in any way. Just keep it legal!
We have two killer features:
  1. topics: topics group articles by different users with the same title, e.g. here is the topic for the "Fundamental Theorem of Calculus" ourbigbook.com/go/topic/fundamental-theorem-of-calculus
    Articles of different users are sorted by upvote within each article page. This feature is a bit like:
    • a Wikipedia where each user can have their own version of each article
    • a Q&A website like Stack Overflow, where multiple people can give their views on a given topic, and the best ones are sorted by upvote. Except you don't need to wait for someone to ask first, and any topic goes, no matter how narrow or broad
    This feature makes it possible for readers to find better explanations of any topic created by other writers. And it allows writers to create an explanation in a place that readers might actually find it.
    Figure 1.
    Screenshot of the "Derivative" topic page
    . View it live at: ourbigbook.com/go/topic/derivative
  2. local editing: you can store all your personal knowledge base content locally in a plaintext markup format that can be edited locally and published either:
    This way you can be sure that even if OurBigBook.com were to go down one day (which we have no plans to do as it is quite cheap to host!), your content will still be perfectly readable as a static site.
    Figure 2.
    You can publish local OurBigBook lightweight markup files to either https://OurBigBook.com or as a static website
    .
    Figure 3.
    Visual Studio Code extension installation
    .
    Figure 4.
    Visual Studio Code extension tree navigation
    .
    Figure 5.
    Web editor
    . You can also edit articles on the Web editor without installing anything locally.
    Video 3.
    Edit locally and publish demo
    . Source. This shows editing OurBigBook Markup and publishing it using the Visual Studio Code extension.
    Video 4.
    OurBigBook Visual Studio Code extension editing and navigation demo
    . Source.
  3. https://raw.githubusercontent.com/ourbigbook/ourbigbook-media/master/feature/x/hilbert-space-arrow.png
  4. Infinitely deep tables of contents:
    Figure 6.
    Dynamic article tree with infinitely deep table of contents
    .
    Descendant pages can also show up as toplevel e.g.: ourbigbook.com/cirosantilli/chordate-subclade
All our software is open source and hosted at: github.com/ourbigbook/ourbigbook
Further documentation can be found at: docs.ourbigbook.com
Feel free to reach our to us for any help or suggestions: docs.ourbigbook.com/#contact