Incoming links: Biology
Check out: OurBigBook.com, the best way to publish your scientific knowledge. It's an open source note taking system that can publish from lightweight markup files in your computer both to a multi-user mind melding dynamic website, or as a static website. It's like Wikipedia + GitHub + Stack Overflow + Obsidian mashed up. Source code: github.com/ourbigbook/ourbigbook.
Sponsor me to work on this project: 100k USD = I quit me job and work on it one year full time. Status: ~144k / 200k USD reached: 1st year locked-in, 2nd year stretch goal open at 200k USD. 1M USD = I retire and do it forever. How to donate: Section "Sponsor Ciro Santilli's work on OurBigBook.com".
I reached 100k USD after a 1000 Monero donation, so I quit my job for 1 year starting 1st June 2024 to solve as many STEM courses as I can from a world leading university to try and kickstart The Higher Education Revolution. If I reach 200k USD, then I'll do it for two years instead. A second year greatly improve chances of success: year one I solve a bunch of courses, year two I come guns blazing with the content and expand further.
Mission: to live in a world where you can learn university-level mathematics, physics, chemistry, biology and engineering from perfect free open source books that anyone can write to get famous. More rationale: Section "OurBigBook.com"
Explaining things is my superpower, e.g. I was top user #39 on Stack Overflow in 2023[ref][ref] and I have a few 1k+ star educational GitHub repositories[ref][ref][ref][ref]. Now I want to bring that level of awesomeness to masters level Mathematics and Physics. But I can't do it alone! So I created OurBigBook.com to allow everyone to work together towards the perfect book of everything.
My life's goal is to bring hardcore university-level STEM open educational content to all ages. Sponsor me at github.com/sponsors/cirosantilli starting from 1$/month so I can work full time on it. Further information: Section "Sponsor Ciro Santilli's work on OurBigBook.com". Achieving what I call "free gifted education" is my Nirvana.
This website is written in OurBigBook Markup, and it is published on both cirosantilli.com (static website) and outbigbook.om/cirosantilli (multi-user OurBigBook Web instance). Its source code is located at: github.com/cirosantilli/cirosantilli.github.io and also at
cirosantilli.com/_dir and it is licensed under CC BY-SA 4.0 unless otherwise noted.To contact Ciro, see: Section "How to contact Ciro Santilli". He likes to talk with random people of the Internet.
GitHub | Stack Overflow | LinkedIn | YouTube | Twitter | Wikipedia | Zhihu 知乎 | Weibo 微博 | Other accounts
Besides that, I'm also a freedom of speech slacktivist and recreational cyclist. I like Chinese traditional music and classic Brazilian pop. Opinions are my own, but they could be yours too. Tax the rich.
Let's create an educational system with:
- no distinction between university and high school, students just go as fast as they can to what they really want without stupid university entry exams
- fully open source learning material
- on-demand examinations that anyone can easily take without prerequisites
- granular entry selection only for space in specific laboratories or participation in specific novel research projects
I offer:
- online private tutoring for:
- any STEM university course
- passionate younger STEM students (any age) who want to learn university level material and beyond. Can your kid be the next Fields Medalist or Nobel Prize winner? I'm here to help, especially if you are filthy rich! I focus moving students forward as fast as they want on and on producing useful novel tutorials and results
Let your child be my Emile, and me be their Adolfo Amidei, and let's see how far they can go! I will help take your child:and achieve their ambitious STEM goals!- into the best universities
- into the best PhD programs
- educational consulting for institutions looking to improve their STEM courses
- do you know that course or teacher that consistently gets bad reviews every year? I'll work with the teacher to turn the problem around!
- are you looking to create a consistent open educational resources offering to increase your institutions internationally visibility? I can help with that too.
My approach is to:For minors, parents are welcome to join video calls, and all interactions with the student will be recorded and made available to parents.
- propose interesting research projects. The starting point is always deciding the end goal: Section "Backward design"
- learn what is needed to do the project together with the student(s)
- publish any novel results or tutorials/tools produced freely licensed online, and encourage the student to do the same (Section "Let students learn by teaching", digital garden)
I have a proven track of explaining complex concepts in an interesting and useful way. I work for the learner. Teaching statement at: Section "How to teach". Pricing to be discussed. Contact details at: Section "How to contact Ciro Santilli".
I am particularly excited about pointing people to the potential next big things, my top picks these days are:I am also generally interested in:
- 20th century physics, notably AMO and condensed matter
- the history of science, and in particular trying to look at seminal papers of a field
Ciro Santilli's amazing Stack Overflow profile
. Ciro contributes almost exclusively by answering question he Googles into out of his own need, and never by refreshing the newest question of big tags for low hanging fruit! More information at: Section "Ciro Santilli's Stack Overflow contributions".Introduction to the OurBigBook Project
. Source. OurBigBook Web topics demo
. Source. The OurBigBook topic feature allows users to "merge their minds" in a "sort by upvote"-stack overflow-like manner for each subject. This is the killer feature of OurBigBook Web. More information at: docs.ourbigbook.com/ourbigbook-web-topics.OurBigBook dynamic article tree demo
. Source. The OurBigBook dynamic tree feature allows any of your headers to be the toplevel h1 header of a page, while still displaying its descendants. SEO loves this, and it also allows users to always get their content on the correct granularity. More information at: docs.ourbigbook.com/ourbigbook-web-dynamic-article-tree.OurBigBook local editing and publishing demo
. Source. With OurBigBook you can store your content as plaintext files in a Lightweight markup, and then publish that to either OurBigBook.com to get awesome multi-user features, or as a static website where you are in full control. More information at: docs.ourbigbook.com/publish-your-content.Top Down 2D continuous game with Urho3D C++ SDL and Box2D for Reinforcement learning by Ciro Santilli (2018)
Source. More information: Section "Ciro's 2D reinforcement learning games". This is Ciro's underwhelming stab at the fundamental question: Can AGI be trained in simulations?. This project could be taken much further.
-------------------------------------
| Force of Will 3 U U |
| --------------------------------- |
| | //////////// | |
| | ////() ()\////\ | |
| | ///_\ (--) \///\ | |
| | ) //// \_____///\\ | |
| | ) \ / / / / | |
| | ) / \ | | / _/ | |
| | ) \ ( ( / / / / \ | |
| | / ) ( ) / ( )/( ) \ | |
| | \(_)/(_)/ /UUUU \ \\\/ | | |
| .---------------------------------. |
| Interrupt |
| ,---------------------------------, |
| | You may pay 1 life and remove a | |
| | blue card in your hand from the | |
| | game instead of paying Force of | |
| | Will's casting cost. Effects | |
| | that prevent or redirect damage | |
| | cannot be used to counter this | |
| | loss of life. | |
| | Counter target spell. | |
| `---------------------------------` |
| l
| Illus. Terese Nelsen |
-------------------------------------Code 1. .
Artist unknown, uploaded December 2014. Part of Section "Cool data embedded in the Bitcoin blockchain" where Ciro Santilli maintains a curated list of such interesting inscriptions.
This was a small project done by Ciro for artistic purposes that received some attention due to the incredible hype surrounding cryptocurrencies at the time. Ciro Santilli's views on cryptocurrencies are summarized at: Section "Are cryptocurrencies useful?".
YellowRobot.jpgJPG image fully embedded in the Bitcoin blockchain depicting some kind of cut material art depicting a yellow robot, inscribed on January 29, 2017.
Ciro Santilli found this image and others during his research for Section "Cool data embedded in the Bitcoin blockchain" by searching for image fingerprints on every transaction payload of the blockchain with a script.
The image was uploaded by EMBII, co-creator of the AtomSea & EMBII upload mechanism, which was responsible for a large part of the image inscriptions in the Bitcoin blockchain.
The associated message reads:This is one of Ciro Santilli's favorite AtomSea & EMBII uploads, as it perfectly encapsules the "medium as an art form" approach to blockchain art, where even non-novel works can be recontextualized into something interesting, here depicting an opposition between the ephemeral and the immutable.
Chiharu [EMBII's Japanese wife] and I found this little yellow robot while exploring Chicago. It will be covered by tar or eventually removed but this tribute will remain. N 41.880778 E -87.629210
At twitter.com/EMBII4U/status/1615389973343268871 EMBII announced that he would be giving off shares of that image on Sup!?, a Bitcoin-backed NFT system he was; making. In December 2023, he gave some shares of the robot to Ciro Santilli.
2010 Wayback Machine archive of starwarsweb.net
. This website was used as one of the CIA 2010 covert communication websites, a covert system the CIA used to communicate with its assets. More details at: Section "CIA 2010 covert communication websites".
Ciro Santilli had some naughty OSINT fun finding some of the websites of this defunct network in 2023 after he heard about the 2022 Reuters report on the matter, which for the first time gave away 7 concrete websites out of a claimed 885 total found. As of November 2023, Ciro had found about 350 of them.
2010 Wayback Machine archive of noticiasmusica.net
. This is another website that was used as one of the CIA 2010 covert communication websites. This website is written in Brazilian Portuguese, and therefore suggests that the CIA had assets in Brazil at the time, and thus was spying on a "fellow democracy".
Although Snowden's revelations made it extremely obvious to the world that the USA spies upon everyone outside of the Five Eyes, including fellow democracies, it is rare to have such a direct a concrete proof of it visible live right on the Wayback Machine. Other targeted democracies include France, Germany, Italy and Spain. More details at: USA spying on its own allies.
Diagram of the fundamental theorem on homomorphisms by Ciro Santilli (2020)
Shows the relationship between group homomorphisms and normal subgroups.
Used in the Stack Exchange answer to What is the intuition behind normal subgroups? One of Section "The best articles by Ciro Santilli".
Spacetime diagram illustrating how faster-than-light travel implies time travel by Ciro Santilli (2021)
Used in the Stack Exchange ansewr to Does faster than light travel imply travelling back in time?. One of Section "The best articles by Ciro Santilli".
Average insertion time into heaps, binary search tree and hash maps of the C++ standard library by Ciro Santilli (2015)
Source. Used in the Stack Overflow answer to Heap vs Binary Search Tree (BST). One of Section "The best articles by Ciro Santilli".
Top view of an open Oxford Nanopore MinION
. Source. This is Ciro Santilli's hand on the Wikipedia article: en.wikipedia.org/wiki/Oxford_Nanopore_Technologies. He put it there after working a bit on Section "How to use an Oxford Nanopore MinION to extract DNA from river water and determine which bacteria live in it" :-) And he would love to document more experiments like that one Section "Videos of all key physics experiments", but opportunities are extremely rare.A quick 2D continuous AI game prototype for reinforcement learning written in Matter.js, you can view it on a separate page at cirosantilli.com/_raw/js/matterjs/examples.html#top-down-asdw-fixed-viewport. This is a for-fun-only prototype for Ciro's 2D reinforcement learning games, C++ or maybe Python (for the deep learning ecosystem) seems inevitable for a serious version of such a project. But it is cute how much you can do with a few lines of Matter.js!
HTML snippet:
<iframe src="_raw/js/matterjs/examples.html#top-down-asdw-fixed-viewport" width="1000" height="850"></iframe> 100 Greatest Discoveries by the Discovery Channel (2004-2005) Updated 2024-12-15 +Created 1970-01-01
Hosted by Bill Nye.
Physics topics:
- Galileo: objects of different masses fall at the same speed, hammer and feather experiment
- Newton: gravity, linking locally observed falls and the movement of celestial bodies
- TODO a few more
- superconductivity, talk only at Fermilab accelerator, no re-enactment even...
- quark, interview with Murray Gell-Mann, mentions it was "an off-beat field, one wasn't encouraged to work on that". High level blablabla obviously.
- fundamental interactions, notably weak interaction and strong interaction, interview with Michio Kaku. When asked "How do we know that the weak force is there?" the answer is: "We observe radioactive decay with a Geiger counter". Oh, come on!
biology topics:
- Leeuwenhoek microscope and the discovery of microorganisms, and how pond water is not dead, but teeming with life. No sample of course.
- 1831 Robert Brown cell nucleus in plants, and later Theodor Schwann in tadpoles. This prepared the path for the idea that "all cells come from other cells", and the there seemed to be an unifying theme to all life: the precursor to DNA discoveries. Re-enactment, yay.
- 1971 Carl Woese and the discovery of archaea
Genetics:
- Mendel. Reenactment.
- 1909 Thomas Hunt Morgan with Drosophila melanogaster. Reenactment. Genes are in Chromosomes. He observed that a trait was linked to sex, and it was already known that sex was related to chromosomes.
- 1935 George Beadle and the one gene one enzyme hypothesis by shooting X-rays at bread mold
- 1942 Barbara McClintock, at Cold Spring Harbor Laboratory
- 1952 Hershey–Chase experiment. Determined that DNA is what transmits genetic information, not protein, by radioactive labelling both protein and DNA in two sets of bacteriophages. They observed that only the DNA radioactive material was passed forward.
- Crick Watson
- messenger RNA, no specific scientist, too many people worked on it, done partially with bacteriophage experiments
- 1968 Nirenberg genetic code
- 1972 Hamilton O. Smith and the discovery of restriction enzymes by observing that they were part of anti bacteriophage immune-system present in bacteria
- alternative splicing
- RNA interference
- Human Genome Project, interview with Craig Venter.
Medicine:
- blood circulation
- anesthesia
- X-ray
- germ theory of disease, with examples from Ignaz Semmelweis and Pasteur
- 1796 Edward Jenner discovery of vaccination by noticing that cowpox cowpox infected subjects were immune
- vitamin by observing scurvy and beriberi in sailors, confirmed by Frederick Gowland Hopkins on mice experiments
- Fleming, Florey and Chain and the discovery of penicillin
- Prontosil
- diabetes and insulin
These are the best articles ever authored by Ciro Santilli, most of them in the format of Stack Overflow answers.
Ciro posts update about new articles on his Twitter accounts.
A chronological list of all articles is also kept at: Section "Updates".
Some random generally less technical in-tree essays will be present at: Section "Essays by Ciro Santilli".
- Trended on Hacker News:
- CIA 2010 covert communication websites on 2023-06-11. 190 points, a mild success.
- x86 Bare Metal Examples on 2019-03-19. 513 points. The third time something related to that repo trends. Hacker news people really like that repo!
- again 2020-06-27 (archive). 200 points, repository traffic jumped from 25 daily unique visitors to 4.6k unique visitors on the day
- How to run a program without an operating system? on 2018-11-26 (archive). 394 points. Covers x86 and ARM
- ELF Hello World Tutorial on 2017-05-17 (archive). 334 points.
- x86 Paging Tutorial on 2017-03-02. Number 1 Google search result for "x86 Paging" in 2017-08. 142 points.
- x86 assembly
- What does "multicore" assembly language look like?
- What is the function of the push / pop instructions used on registers in x86 assembly? Going down to memory spills, register allocation and graph coloring.
- Linux kernel
- What do the flags in /proc/cpuinfo mean?
- How does kernel get an executable binary file running under linux?
- How to debug the Linux kernel with GDB and QEMU?
- Can the sys_execve() system call in the Linux kernel receive both absolute or relative paths?
- What is the difference between the kernel space and the user space?
- Is there any API for determining the physical address from virtual address in Linux?
- Why do people write the
#!/usr/bin/envpython shebang on the first line of a Python script? - How to solve "Kernel Panic - not syncing: VFS: Unable to mount root fs on unknown-block(0,0)"?
Figure 2. Path from init/main.c until bzImage in the Linux kernel 4.19. Source. From: What is the difference between the following kernel Makefile terms: vmLinux, vmlinuz, vmlinux.bin, zimage & bzimage?- Single program Linux distro
- QEMU
- gcc and Binutils:
- How do linkers and address relocation works?
- What is incremental linking or partial linking?
- GOLD (
-fuse-ld=gold) linker vs the traditional GNU ld and LLVM ldd - What is the -fPIE option for position-independent executables in GCC and ld? Concrete examples by running program through GDB twice, and an assembly hello world with absolute vs PC relative load.
- How many GCC optimization levels are there?
- Why does GCC create a shared object instead of an executable binary according to file?
- C/C++: almost all of those fall into "disassemble all the things" category. Ciro also does "standards dissection" and "a new version of the standard is out" answers, but those are boring:
- What does "static" mean in a C program?
- In C++ source, what is the effect of
extern "C"? - Char array vs Char Pointer in C
- How to compile glibc from source and use it?
- When should
static_cast,dynamic_cast,const_castandreinterpret_castbe used? - What exactly is
std::atomicin C++?. This answer was originally more appropriately entitled "Let's disassemble some stuff", and got three downvotes, so Ciro changed it to a more professional title, and it started getting upvotes. People judge books by their covers. notmain.o 0000000000000000 0000000000000017 W MyTemplate<int>::f(int) main.o 0000000000000000 0000000000000017 W MyTemplate<int>::f(int)Code 1.. From: What is explicit template instantiation in C++ and when to use it?nmoutputs showing that objects are redefined multiple times across files if you don't use template instantiation properly
- IEEE 754
- What is difference between quiet NaN and signaling NaN?
- In Java, what does NaN mean?
Without subnormals: +---+---+-------+---------------+-------------------------------+ exponent | ? | 0 | 1 | 2 | 3 | +---+---+-------+---------------+-------------------------------+ | | | | | | v v v v v v ----------------------------------------------------------------- floats * **** * * * * * * * * * * * * ----------------------------------------------------------------- ^ ^ ^ ^ ^ ^ | | | | | | 0 | 2^-126 2^-125 2^-124 2^-123 | 2^-127 With subnormals: +-------+-------+---------------+-------------------------------+ exponent | 0 | 1 | 2 | 3 | +-------+-------+---------------+-------------------------------+ | | | | | v v v v v ----------------------------------------------------------------- floats * * * * * * * * * * * * * * * * * ----------------------------------------------------------------- ^ ^ ^ ^ ^ ^ | | | | | | 0 | 2^-126 2^-125 2^-124 2^-123 | 2^-127Code 2.Visualization of subnormal floating point numbers vs what IEEE 754 would look like without them. From: What is a subnormal floating point number?
- Computer science
- Algorithms
- Is it necessary for NP problems to be decision problems?
- Polynomial time and exponential time. Answered focusing on the definition of "exponential time".
- What is the smallest Turing machine where it is unknown if it halts or not?. Answer focusing on "blank tape" initial condition only. Large parts of it are summarizing the Busy Beaver Challenge, but some additions were made.
- Algorithms
- Git
| 0 | 4 | 8 | C | |-------------|--------------|-------------|----------------| 0 | DIRC | Version | File count | ctime ...| 0 | ... | mtime | device | 2 | inode | mode | UID | GID | 2 | File size | Entry SHA-1 ...| 4 | ... | Flags | Index SHA-1 ...| 4 | ... |tree {tree_sha} {parents} author {author_name} <{author_email}> {author_date_seconds} {author_date_timezone} committer {committer_name} <{committer_email}> {committer_date_seconds} {committer_date_timezone} {commit message}Code 4.Description of the Git commit object binary data structure. From: What is the file format of a git commit object data structure?- How do I clone a subdirectory only of a Git repository?
- Python
- Web technology
- OpenGL
Figure 8. Example of a texture atlas containing glyphs. Source.Image by Nicolas P. Rougier, author of Freetype GL.Used on Ciro Santilli's answer: How to draw text using only OpenGL methods?- What are shaders in OpenGL?
- Why do we use 4x4 matrices to transform things in 3D?
Figure 10. . Source. - Image Processing with GLSL shaders? Compared the CPU and GPU for a simple blur algorithm.
- Node.js
- Ruby on Rails
- POSIX
- What is POSIX? Huge classified overview of the most important things that POSIX specifies.
- Systems programming
- What do the terms "CPU bound" and "I/O bound" mean?
Figure 12. Plot of "real", "user" and "sys" mean times of the output of time for CPU-bound workload with 8 threads. Source. From: What do 'real', 'user' and 'sys' mean in the output of time?+--------+ +------------+ +------+ | device |>---------------->| function 0 |>----->| BAR0 | | | | | +------+ | |>------------+ | | | | | | | +------+ ... ... | | |>----->| BAR1 | | | | | | +------+ | |>--------+ | | | +--------+ | | ... ... ... | | | | | | | | +------+ | | | |>----->| BAR5 | | | +------------+ +------+ | | | | | | +------------+ +------+ | +--->| function 1 |>----->| BAR0 | | | | +------+ | | | | | | +------+ | | |>----->| BAR1 | | | | +------+ | | | | ... ... ... | | | | | | +------+ | | |>----->| BAR5 | | +------------+ +------+ | | | ... | | | +------------+ +------+ +------->| function 7 |>----->| BAR0 | | | +------+ | | | | +------+ | |>----->| BAR1 | | | +------+ | | ... ... ... | | | | +------+ | |>----->| BAR5 | +------------+ +------+Code 5.Logical struture PCIe device, functions and BARs. From: What is the Base Address Register (BAR) in PCIe?
- Electronics
- Raspberry Pi
Figure 13. . Image from answer to: How to hook up a Raspberry Pi via Ethernet to a laptop without a router? 
Figure 14. . Image from answer to: How to hook up a Raspberry Pi via Ethernet to a laptop without a router? 
Figure 15. . Image from answer to: How to emulate the Raspberry Pi 2 on QEMU? 
Figure 16. Bare metal LED blinker program running on a Raspberry Pi 2. Image from answer to: How to run a C program with no OS on the Raspberry Pi?
- Raspberry Pi
- Computer security
- Media
Video 2. Canon in D in C. Source.The original question was deleted, lol...: How to programmatically synthesize music?- How to resize a picture using ffmpeg's sws_scale()?
- Is there any decent speech recognition software for Linux? ran a few examples manually on
vosk-apiand compared to ground truth.
- Eclipse
- Computer hardware
- Scientific visualization software
Figure 17. VisIt zoom in 10 million straight line plot with some manually marked points. Source. From: Section "Survey of open source interactive plotting software with a 10 million point scatter plot benchmark by Ciro Santilli"
- Numerical analysis
Video 3. Real-time heat equation OpenGL visualization with interactive mouse cursor using relaxation method by Ciro Santilli (2016)Source.
- Computational physics
Figure 18. gnuplot plot of the y position of a sphere bouncing on a plane simulated in Bullet Physics. Source. From: What is the simplest collision example possible in a Bullet Physics simulation?
- Register transfer level languages like Verilog and VHDL
- Verilog:
Figure 19. . See also: Section "Verilator interactive example"
- Verilog:
- Android
Video 4. Android screen showing live on an Ubuntu laptop through ADB. Source. From: How to see the Android screen live on an Ubuntu desktop through ADB?
- Debugging
- Program optimization
- What is tail call optimization?
Figure 21. gprof2dot image generated from the gprof data of a simple test program. Source.The answer compares gprof, valgrind callgrind, perf and gperftools on a single simple executable.
- Data
Figure 22. Mathematics dump of Wikipedia CatTree. Source.
- Mathematics
Figure 23. Diagram of the fundamental theorem on homomorphisms by Ciro Santilli (2020)Shows the relationship between group homomorphisms and normal subgroups.- Section "Formalization of mathematics": some early thoughts that could be expanded. Ciro almost had a stroke when he understood this stuff in his teens.
Figure 24. Simple example of the Discrete Fourier transform. Source. That was missing from Wikipedia page: en.wikipedia.org/wiki/Discrete_Fourier_transform!
- Network programming
- Physics
- What is the difference between plutonium and uranium?
Figure 25. Spacetime diagram illustrating how faster-than-light travel implies time travel. From: Does faster than light travel imply travelling back in time?
- Biology
Figure 27. Mass fractions in a minimal growth medium vs an amino acid cut in a simulation of the E. Coli Whole Cell Model by Covert Lab. Source. From: Section "E. Coli Whole Cell Model by Covert Lab"
- Quantum computing
- Section "Quantum computing is just matrix multiplication"
Figure 28. Visualization of the continuous deformation of states as we walk around the Bloch sphere represented as photon polarization arrows. From: Understanding the Bloch sphere.
- Bitcoin
- GIMP
Figure 29. GIMP screenshot part of how to combine two images side-by-side in GIMP?.
- Home DIY
Figure 30. Total_Blackout_Cassette_Roller_Blind_With_Curtains.Source. From: Section "How to blackout your window without drilling"
- China
Co-founder of PowerDNS, an open source dNS implementation.
Homepage: berthub.eu/ says:.
All stuff Ciro cares about too! Cool dude! In particular Ciro loved his quote of I should have loved biology.
All stuff Ciro cares about too! Cool dude! In particular Ciro loved his quote of I should have loved biology.
He's writing a fun-sounding book about molecular biology as of 2022: berthub.eu/dna-book. Appears to be closed source though. Ciro wonders if he really needs to sell the book for money after all those years though, rather than just publishing it online for free.
Looking at Bert just brings the Dutch Golden Age, and more in particular Antonie van Leeuwenhoek to mind. Epic.
How life is Digital by Bert Hubert (2021)
Source. Just a "boring" overview of the central dogma of molecular biology ;-)Chemistry is fun. Too hard for precise physics (pre quantum computing, see also quantum chemistry), but not too hard for some maths like social sciences.
And it underpins biology.
100 Greatest Discoveries - Chemistry by the Discovery Channel (2005)
Source. Pretty good within what you can expect from popular science. The discovery selection is solid, and he interviews 3 Nobel Prize laureates, only one about stuff they invented, so you can see their faces. The short non-precise scenes of epoch are also pleasing. Part of 100 Greatest Discoveries by the Discovery Channel (2004-2005)."De novo" means "starting from scratch", that is: you type the desired sequence into a computer, and the synthesize it.
The "de novo" part is important, because it distinguishes this from the already well solved problem of duplicating DNA from an existing DNA template, which is what all our cells do daily, and which can already be done very efficiently in vitro with polymerase chain reaction.
Many startup companies are attempting to create more efficient de novo synthesis methods:
Notably, the dream of most of those companies is to have a machine that sits on a lab bench, which synthesises whatever you want.
TODO current de novo synthesis costs/time to delivery after ordering a custom sequence.
The initial main applications are likely going to be:but the real pipe dream is building and bootstraping entire artificial chromosomes
- polymerase chain reaction primers (determine which region will be amplified
- creating a custom sequence to be inserted in a plasmid, i.e. artificial gene synthesis
News coverage:
- 2023-03 twitter.com/sethbannon/status/1633848116154880001
AnsaBio created the world's longest DNA oligo produced using de novo synthesis! 1,005 bases! 99.9% stepwise yield
- 2020-10-05 www.nature.com/articles/s41587-020-0695-9 "Enzymatic DNA synthesis enters new phase"
Nuclera eDNA enzymatic de novo DNA synthesis explanatory animation (2021)
Source. The video shows nicely how Nuclera's enzymatic DNA synthesis works:- they provide blocked nucleotides of a single type
- add them with the enzyme. They use a werid DNA polymerase called terminal deoxynucleotidyl transferase that adds a base at a time to a single stranded DNA strand rather than copying from a template
- wash everything
- do deblocking reaction
- and then repeat until done
The half-life of radioactive decay, which as discovered a few years before quantum mechanics was discovered and matured, was a major mystery. Why do some nuclei fission in apparently random fashion, while others don't? How is the state of different nuclei different from one another? This is mentioned in Inward Bound by Abraham Pais (1988) Chapter 6.e Why a half-life?
The term also sees use in other areas, notably biology, where e.g. RNAs spontaneously decay as part of the cell's control system, see e.g. mentions in E. Coli Whole Cell Model by Covert Lab.
Ciro Santilli feels it is not for his generation though, and that is one of the philosophical things that saddens him the most in this world.
On the other hand, Ciro's playing with the Linux kernel and other complex software which no single human can every fully understand cheer him up a bit. But still, the high level view, that we can have...
For now, Ciro's 2D reinforcement learning games.
Whatever it is that biology studies.
As of 2019, the silicon industry is ending, and molecular biology technology is one of the most promising and growing field of engineering.
42 years of microprocessor trend data by Karl Rupp
. Source. Only transistor count increases, which also pushes core counts up. But what you gonna do when atomic limits are reached? The separation between two silicon atoms is 0.23nm and 2019 technology is at 5nm scale.Such advances could one day lead to both biological super-AGI and immortality.
Ciro Santilli is especially excited about DNA-related technologies, because DNA is the centerpiece of biology, and it is programmable.
First, during the 2000's, the cost of DNA sequencing fell to about 1000 USD per genome in the end of the 2010's: Figure 2. "Cost per genome vs Moore's law from 2000 to 2019", largely due to "Illumina's" technology.
The medical consequences of this revolution are still trickling down towards medical applications of 2019, inevitably, but somewhat slowly due to tight privacy control of medical records.
Ciro Santilli predicts that when the 100 dollar mark is reached, every person of the First world will have their genome sequenced, and then medical applications will be closer at hand than ever.
But even 100 dollars is not enough. Sequencing power is like computing power: humankind can never have enough. Sequencing is not a one per person thing. For example, as of 2019 tumors are already being sequenced to help understand and treat them, and scientists/doctors will sequence as many tumor cells as budget allows.
Then, in the 2010's, CRISPR/Cas9 gene editing started opening up the way to actually modifying the genome that we could now see through sequencing.
What's next?
Ciro believes that the next step in the revolution could be could be: de novo DNA synthesis.
This technology could be the key to the one of the ultimate dream of biologists: cheap programmable biology with push-button organism bootstrap!
Just imagine this: at the comfort of your own garage, you take some model organism of interest, maybe start humble with Escherichia coli. Then you modify its DNA to your liking, and upload it to a 3D printer sized machine on your workbench, which automatically synthesizes the DNA, and injects into a bootstrapped cell.
You then make experiments to check if the modified cell achieves your desired new properties, e.g. production of some protein, and if not reiterate, just like a software engineer.
Of course, even if we were able to do the bootstrap, the debugging process then becomes key, as visibility is the key limitation of biology, maybe we need other cheap technologies to come in at that point.
This a place point we see the beauty of evolution the brightest: evolution does not require observability. But it also implies that if your changes to the organism make it less fit, then your mutation will also likely be lost. This has to be one of the considerations done when designing your organism.
Other cool topic include:
- computational biology: simulations of cell metabolism, protein and small molecule, including computational protein folding and chemical reactions. This is basically the simulation part of omics.If we could only simulate those, we would basically "solve molecular biology". Just imagine, instead of experimenting for a hole year, the 2021 Nobel Prize in Physiology and Medicine could have been won from a few hours on a supercomputer to determine which protein had the desired properties, using just DNA sequencing as a starting point!
- microscopy: crystallography, cryoEM
- analytical chemistry: mass spectroscopy, single cell analysis (Single-cell RNA sequencing)
It's weird, cells feel a lot like embedded systems: small, complex, hard to observe, and profound.
Ciro is sad that by the time he dies, humanity won't have understood the human brain, maybe not even a measly Escherichia coli... Heck, even key molecular biology events are not yet fully understood, see e.g. transcription regulation.
One of the most exciting aspects of molecular biology technologies is their relatively low entry cost, compared for example to other areas such as fusion energy and quantum computing.
Ciro Santilli often wonders to himself, how much of the natural sciences can one learn in a lifetime? Certainly, a very strong basis, with concrete experimental and physics, chemistry and biology should be attainable to all? How much Ciro manages to learning and teach in those areas is a kind of success metric of Ciro's life.
Mission: to live in a world where you can learn university-level mathematics, physics, chemistry, biology and engineering from perfect free books that anyone can write to get famous.
Live website: ourbigbook.com
Further information and rationale: Section "OurBigBook.com"
The project's mission is one of, or perhaps the most important, life objective of Ciro Santilli. Reproductive goals aside. These two types of goal are incommensurable. This is one of the great challenges of life.
This is ongoing project.
Ciro's goals in advertising this half done project are is partly to obtain some feedback, and partly to give the idea to someone else who might help push it further, be it in this stack or not.
Better editing support is a must, likely WYSIWYG.
But besides that, it is already in broad strokes the best approach Ciro Santilli can come up with to try and reach the mission statement only with technical advances, i.e. without large amounts of money or political influence which Ciro Santilli does not have.
Maybe that website isn't enough of a technical advance to reach its mission. Maybe there is some further not yet imagined technical insight that would push it into viability. Maybe not. But one must try. Only God can know the answer to these questions.
As of 2022, Ciro has spent about 2.5 years full time working on this project. First he spent about 1 year in 2014 on the first iteration: github.com/booktree/booktree, a GitLab fork, but then decided it was not the way to go.
Then around 2021 he put in some more 1.5 year of full time work, now with a possibly overly complicated (or perhaps just insane/immature) Next.js/Sequelize from scratch website stack.
It makes Ciro a bit ashamed to see that "so little user visible stuff was achieved in so much time". It is partly because he and many people underestimate the difficulty of web development. Perhaps there were some bad stack/useless feature choices issues. And a good dose of indulging in studying the natural sciences to bootstrap content and have fun. But really trying is the only way to learn.
How to use an Oxford Nanopore MinION to extract DNA from river water and determine which bacteria live in it Updated 2024-12-15 +Created 1970-01-01
This article gives an idea of how this kind of biological experiment feels like to a software engineer who has never done any biology like Ciro Santilli.
Physics (like all well done science) is the art of predicting the future by modelling the world with mathematics.
And predicting the future is the first step towards controlling it, i.e.: engineering.
Ciro Santilli doesn't know physics. He writes about it partly to start playing with some scientific content for: OurBigBook.com, partly because this stuff is just amazingly beautiful.
Ciro's main intellectual physics fetishes are to learn quantum electrodynamics (understanding the point of Lie groups being a subpart of that) and condensed matter physics.
Every science is Physics in disguise, but the number of objects in the real world is so large that we can't solve the real equations in practice.
Luckily, due to emergence, we can use uglier higher level approximations of the world to solve many problems, with the complex limits of applicability of those approximations.
Therefore, such higher level approximations are highly specialized, and given different names such as:
As of 2019, all known physics can be described by two theories:
Unifying those two into the theory of everything one of the major goals of modern physics.
xkcd 435: Fields arranged by purity
. Source. Reductionism comes to mind.
Physically accurate genie by Psychomic
. Source. This sane square composition from: www.reddit.com/r/funny/comments/u08dw3/nice_guy_genie/.Understand and explain amazingly every single Nobel Prize in physics, chemistry and biology. Since in particular the Nobel Foundation is unable to do that for any at all, especially of the key old ones, e.g. www.nobelprize.org/prizes/physics/1965/summary/. Hopeless.
To be fair, those in theoretical physics at least basically come down to reading a bunch of books. But perhaps anything slightly more experimental could have