'Code in Place', a computer coding course in Covid time

Learning during a grim phase of Covid Delta wave in India 

My log in page

When India was simmering with Delta wave of Covid-19, deaths were reported everywhere from one's neighbor to distant places, medical/social assisting system of every kind was disrupted completely, human dignity touched it's lowest point in our recent history; we sat in our homes with doors and windows closed and  mask on, isolating self in rooms possibly available, as if 'Covid-19 was in the air'. Hardly there was any home left where the family members were not with viral infective symptoms of some kind. People ran from one medical store to other in search of counter top medicine of some sort as there was no one to prescribe or guide to. This peak period ranged from mid April to the end of the May 2021. It was a period when 'Code in Place' came as rescue & refuge for many of us, here in India.

Shelter in Place vs Code in Place 2021 

OhYay for virtual Section

Phrase well suited to the situation when we all needed 'Shelter in place' and Stanford University provided us with 'Code in Place'. One can hardly imagine that how beneficial it was to us to engage us mentally for hours without any Covid-19 fear or isolation pressure from rest of our world. I sat transfixed to computer monitor, pouring attention to, unaware to the grim world outside, in my room at least for that much of the period. Thank you to all the distinguished team members of Stanford University for saving us from the rigorous pressure of the Covid Delta wave with unique opportunity of learning as well, a new skill set.

Coding in Places

Screenshot of a lecture video by Prof Mehran Sahami

It was a computer course in learning for coding and programming for Python language, based on Stanford University's CS106A, like the one they had in previous year in peak Covid-19 time of 2020. This was an online course, conducted for five weeks duration, requiring at least 10 hours per week, from April 19th to May 28th, 2021.

Karel commands from Karel Reader

For me it provided an unique experience of learning Coding in computer language Python. Each week with 3 days lecture videos, 1 day for 1 hour Section teaching, learning, problem solving activity with assigned  Section Leader of a Section around 10 students. Every week there were due assignments to solve and submit in due period. 'Karel' robot for initial learning of Python language, 'Ed' an online IDE hosting CIP community, 'OhYay' access for live Section for 1000+ section meetings around the clock across the globe engaging in virtual experiences were a huge shoutout. Hangout campfire by Section leaders was so useful to sort out and debugging of code written by any individual. Handouts, Lecture Videos, Lecture Slides, Files are still there for 'Life after Code in Place'.

While working on PyCharm IDE

Teaching by Mehran Sahami, Chris Piech, Julie Zelenski was a life time experience for the Coding. 

Meeka's design was selected by voting 

My experience was that the 'Content delivery' in teaching is a crucial part in communicating learning; while 'content', 'resource' and 'language-medium' matters little.

Final Project Showcase

  Learning Coding was like getting magical tool along with 12,000 students, 1125 Section Leaders from all across the globe in a Community Service gesture of Stanford University in the testing time of Covid-19.

Getting my final project published in the showcase of Code in Place 2021 was a real reward and a great opportunity of participation.

Thank you Mehran Sahami, Chris Piech, Julie Zelenski, Brahm Capoor and many more in the entire team of this project at Stanford University, expanding in all 7 continents and countries.

Map of Code in Place 2021, thankfully shared from 

Genetic code, Codon, Anti Codon, expression in Translation and Laws of heredity

--------------------------------------   

Basic molecular code of life:

--------------------------------------

Genes on Chromosome in the cell nucleus carry instructions for amino acids in the form of chemical alphabets. They are four nitrogenous bases: A, G, T, C; namely Adenine, Guanine, Thymine, Cytosine. U (Uacil) is found only in RNA, replacing T. 

These 4 nucleotides (A, G = Purines; T, C = Pyrimidines) of the DNA combine in various ways to form 3 letter code for any specific amino acid to the synthesis of protein.

Making of protein: Gene expression for the synthesis of protein is in two ways:

1. Transcription: Gene sequence of DNA strand is rewritten on mRNA with the help of transcriptase enzyme inside nucleus of the cell.

2. Translation: mRNA Nucleotide sequence is rewritten on tRNA with the help of polymerase enzyme, which in turn picks up a specific amino acid to form a polypeptide in Ribosome of the cell.

We encounter Codon and Anti Codon at the time of Translation.

Codon: A sequence of 3 nitrogenous Bases in a row on mRNA, as a message for the specific Amino acid.

Anti Codon: A sequence of 3 nitrogenous Bases in a row on tRNA on it's anti codon loop. They also have pseudo bases apart from the regular bases. These codon recognize the correct codon on mRNA by its complementary sequence.

Amino acid activation:

Amino acid + ATP --------> Amino acyl AMP +2Pi

Amino acyl + tRNA  --------> Amino acyl tRNA +AMP

                                               (tRNA loaded with Amino acid)

                                                   (cognate or charged tRNA)

Correct amino acid recognisation here by tRNA base (3' 5'), with complementary match with the base sequence on mRNA (5' 3').           

-----------------------                                       

Code crackers:

-----------------------
1. Physicist George Gamow in mid 1950s proposed the triplet hypothesis, this insight was mathematically suitable to code for essential 20 amino acids. 

This three nucleotide triplet code was the minimum to cover all the amino acids, later proved correct.

2. American biochemists Marshall W. Nirenberg, Robert W. Holley, Hargobind Khorana in 1960s did the pioneering work.

Nirenberg in 1961 with mRNA consisting poly-U, synthesized Phenylalanine (concluding UUU code for Phenylalanine) and later with poly-C mRNA translated to Proline (concluding CCC code for Proline).

Later Khorana experimented with poly-UC mRNA generated Serine and Leucine (concluding UCU code for Serine and CUC for Leucine).
In 1965 this code researcher  team deciphered the entire genetic code, including stop code, initiation code and received Nobel Prize in 1968. (above modified image from nobel.org, in public domain)

----------------------------------------------------------------------------

Gregor Johann Mendel (1822-1884), Father of Genetics

-----------------------------------------------------------------------------

Mendel (Czech) did his experiments on 10,000 pea plants for eight years (1856-1863), published his results in 1865. He concluded that genes come in pair and inherited as distinct units, one from each parent. He tracked the segregation of parental genes and their appearance as dominant or recessive traits in offspring.

He clearly recognized the mathematical pattern of inheritance from one generation to the next.

Mendel's Laws of Heredity are:
1, The Law of Segregation,

2. The Law of Independent Assortment,

3. Law of Dominance.

After his death, most of his personal papers and documents were burnt by the monks except few which remained in the archive of monastery.

Mendel on a postal stamp

      His laws were not understood until 1900 when independently three Botanist namely Hugo de Vries (Netherland), Correns (Germany) and Tschermak (Austria) rediscovered the findings of Mendel. 

      So Mendel put a blue print of things to come in the field of Genetics by deducing the laws of inheritance. 

       Meiosis, Chromosomes, Crossing Over, Genes, Linked Genes, Triplet Code were unknown in his time but his finding explains all this. His experimental results were rediscovered 16 years after his death and 34 years after he first published it. Triplet code came to be known only 100 years after his publication. Such was his genius as if he foresee all that. A friar, abbot who became 'Father', leaving no descendants behind, died at the age of 61 due to kidney ailment.

Reverse Transcriptase Polymerase Chain Reaction for Covid-19 and Zika testing

PCR 

Polymerase Chain Reaction is an in vitro diagnostic technique. This is being used to amplify the DNA or RNA sequence of any source material. 

In the PCR process a target DNA sequence and DNA Polymerase enzyme is used in lab conditions, usually passing with following cycles in stages:

1. Converting dsDNA to single stranded DNA,  

2. formation of new dsDNA  with one old strand and one new strand,

3. using new dsDNA as an template to for synthesis in next cycles.

RT-PCR 

Reverse Transcriptase Polymerase Chain Reaction is also an in vitro diagnostic technique with a variation of PCR. In this process a mRNA sample with reverse transcriptase enzyme, a cDNA copy is obtained. Here onward a standard PCR process is followed in sequence to obtain the dsDNA sequence. 

RT-PCR and Covid-19 

Often RT-PCR is combined with the real time PCR (qRT-PCR) to quantify the transcript levels in cells/tissues.

Originally radioactive isotopes were used in this nuclear derived method; now replaced by the isotopic labelling with special markers like fluorescent dyes.

Conventional RT-PCR allows to see the result at the end of the process while in qRT-PCR one can see result immediately while the process is still on going. This technique has been used successfully in diagnosing Ebola and Zika virus and is now adapted for testing the Covid-19 virus.

Further reference for:

Virus, genome and Covid-19

Mutation and Strain Biology of Covid-19 Virus

Spanish flue of 1918 

World is still fighting with the third wave of Covid-19 pandemic. Humans do have short memories as we forgot Spanish flu pandemic; a 100 year ago with fatalities in tens of millions at that time. Mutation in influenza, the RNA virus was behind the infamous pandemic. Understanding how virus mutates is critical for making decisions about the vaccines. RNA viruses mutate relatively quickly because they lack a proofreading mechanism to look for and repair errors during replication.

Actually there was no learning from that history, as our initial reaction with this new Covid-19 virus was of utter amazement. Still a lot lessons could be learned if we could visualize the after effects of the last pandemic of 1918.

Viruses fall on the borderline of living and non living.

They are strange as:

1. Do not have cell, a basic structural & functional unit of life to claim it as living organism,
2. Do not have their own metabolism of any kind, as do not possess any cell organelle,
3. Do not reproduce by any form of cell division,
4. Do self assembly only in a host cell, creating their multiple copies on the expense of host cell,
5. The only living characteristic they possess is gene, either in RNA or DNA strand form. They can not synthesize protein as they lack Ribosome, a cell organelle for the translation of viral mRNA,
6. The nucleic acid in RNA or DNA form alone is capable of infecting host cell even after being crystallized and stored for years in abiotic conditions. If and when that comes in contact with any host cell, starts behaving as a copy machine, producing of their own kind and consuming/killing the host cell.

Virus name in various Indo-European languages like Latin, Ancient Greek, Avestan means poison or poisonous substance, originating from Sanskrit root 'Visa'. 

Much before the discovery of structure of virus, it was identified as the poisonous substance rather than some biological entity.

Some specific features of viruses:

1. Viruses are submicroscopic in structure, shape ranges from helical to icosahedral to many more complex forms, invisible in the light microscope, as they are one-hundredth of the size of bacteria.
2. In nature their number is 10 times higher than the Bacteria.
3. Bacteriophage is a virus infecting to bacteria. 
4. Tobacco Mosaic Virus was the first virus discovered by Dmitri Ivanovsky in his 1892 experiments just at the end of the nineteenth century.

Wendell Stanley later studied the virus, managing to extract it in the form of pure crystals and show that it is composed of protein and ribonucleic acid (RNA) in 1935 and was awarded Nobel Prize in 1946.

Viruses consist of a long chain of either DNA or RNA, a protein coat Capsid surrounding and protecting the central genetic material and in some cases a lipid envelope surrounding the nuclear capsid.

Genomics of Viruses:

Of all the viruses found, about 70 percent are of RNA types genome. Due to possible higher rate of error in enzymes responsible for replication in RNAs type, they show much higher rate of mutation than to DNA viruses. That causes much higher rate of variant and that means the great adaptability to the new host.

The viral RNA may be of two types:
Single stranded (ss) or Double stranded (ds), they further vary as occupying on single RNA segment or two or more segments.

Genomes on single stranded RNA may further be of 2 types:

1. a sense strand (plus strand), which can function as mRNA; they alone can replicate if injected into host cell.

2. anti sense strand (minus strand), a complementary to sense strand, can not function as mRNA, no translational function, can not produce viral component.

The retrovirus genome comprises two identical plus-sense ssRNA molecules.
Most DNA viruses contain a single genome of linear dsDNA.

SARS-CoV-2, a corona virus causing Covid-19, is a RNA virus, and it must infect a host cell to replicate itself.
Error during the replication of viral RNA resulting in similar but not exact copies of the original, causing mutation. These mutant viruses called variants, which differ by single or many mutations.
A variant is called strain which shows distinct physical properties, behaving differently from the parent virus.

 
Following are the common variants of Covid-19 which are also strain; each containing several different mutation:

1. UK variant (B.1.1.7)

2. South African variant (B.1.351)

3. Brazilian variant (P.1)

Delta plus variant of Covid-19 is a warning that SARS-CoV-2 is continuing to evolve.

 

When new organisms enter the human race, they learn and adapt quickly to us. Unless we learn and adapt too, we're going to have more problems in the coming months and years. The virus is not done with us yet.

WHO says: 'When a virus is widely circulating in a population and causing many infections, the likelihood of the virus mutating increases. The more opportunities a virus has to spread - the more replicates and the more opportunities it has to undergo changes.'

Note: On the site of  WHO , this has been explained with a nice illustrative video to understand the mutational change in Covid-19 virus genome to form the newer variant. 

Following screenshots are shared thankfully from the above said video put in public domain to understand the possible change in four bases of the RNA's; i.e. Adenine, Guanine, Uracil, Cytosine.