Human genome facts

• The following is a brief list of facts regarding the human genome. .
• 
  The human genome is the complete list of coded instructions needed to make a human.
• 
  The human genome is composed of more than 3 billion nucleotide bases. There are 4 types of nucleotide base: A- adenine, T- thymine, C- cytosine, G- guanine.
• 
  The order of the nucleotide bases contains the instructions for making an organism. Every three bases codes for an amino acid.
• 
  There are 20 different amino acids that combined in different ways make different proteins.
• 
  The total number of human genes is estimated to be between 30,000 - 40,000.
• 
  Worms have 19,098 genes, fruit flies have 13,602 and yeast has 6,034.
• 
  Almost all nucleotide bases (99.9%) are exactly the same in all people.
• 
  Less than 2% of the genome codes for proteins.
• 
  The vast majority of the DNA in the genome (>97%) has no known function.
• 
  The functions remain unknown for over 50% of discovered genes.
• 
  Chromosome 1 has the most genes (2,968) and chromosome Y has the least (231).
• 
  Humans have about 3 times as many proteins as flies and worms. This is because different proteins can be produced by the same gene using the processes of mRNA splicing and protein post-translational modifications.
• 
  Our DNA is 98% identical to chimpanzees. The average amount of genetic difference between any 2 chimpanzees is 4 or 5 times more than the average difference between any 2 humans.
  There are 100 trillion cells in your body.
• 
  If unwound and tied together, the strands of DNA in one cell would stretch 6 feet.
  If all the DNA in your body was tied together, it would stretch to the sun and back over 600 times.
• 
  12,000 letters of DNA are decoded by human genome project computers every second.
• 
  The entire human genome requires more than 3 gigabytes of computer storage space.
• 
  If a person recited the genome at a rate of one nucleotide per second, 24 hours a day, it would take them a full century to complete.
• 
  To sequence the human genome, researchers collected a large number of blood samples from females and sperm from males. A few of these samples were then chosen at random for sequencing. The identities of the sample sources have never been disclosed, either to the donors or to the scientists.

ChandraMukhi --- Reloaded ( Part X )

Part X – Rajini’s – the mission possible

Rajini : As usual came to office late

Prabhu : was in high tension …..

Rajini : what happened Prabhu ?? why are you so tensed ??

Prabhu : Jyo dint return home yesterday.. Called all her friends.. But I could not trace her ..

Rajini : What do you say ??? I was here till 2 o clock .. I dint notice anyone working here

Prabhu : I am having headache .. Let me go and sleep at home. If I get any important call make a call to me

Rajini : OK Prabhu

Rajini went out for a break and say Jyo entering office at 2.

Rajini : hey jyo … why are you so late to office ???

Jyo : I was working in the office till today morning 2 . was very tired and was afraid to drive my car. So I stayed with my school friend’s flat.

Rajini : Prabhu called your mobile it seems .. But you dint pick up ??

Jyo : Mobile was in silent mode …

Rajini and jyo enters office and they work their tasks

During tea break

Rajini : hey jyo .. You havnt completed the tasks assigned to you it seems ??

Jyo : ME !!! Jyo ‘s eyes as it turned devilish for a moment and then returned to normal..

Rajini : Cool Jyo … you have completed your task …. Come lets go and see that Chandralekha’s system

Jyo : What ??? that system .. No .. I cant come .. I am very afraid .. already some are saying tat we are losing all the files cos of that. And I have once entered the room . It was really very dark. I was scared to enter and came back .. some say even they hear some sounds during night
Rajini : Even I heard the sounds when I was working alone !! ( Jyo was really surprised to hear the same from rajini )

Rajini and Jyo enters the room and Jyo was so happy to say that this was Chandralekha’ system and the system was dust free.

Without Jyo’s notice Rajini was about to login to the system and happened to see Jyo’s id in it ..

Rajini : Jyo come on .. very sultry here .. let us go !!

Jyo : Rajini I m very tired and I m going home today

Rajini : Ok Jyo.. Good night and sweet dreams …

The Climax :

Rajini : Was in that dark room … He logged on to the system of Chandralekha and when he logged in was able to see lots of games and songs in her system and was able to see lots of codes which can be used in the project .

( thinks to himself … wat an intellectual gal … IT world has missed such a talented person .. )

As Rajini was playing a song … he was able to see disturbance in the network and the access was cut in few minutes … He connected his laptop and was having the same in the same room … he was able to see all those …

When rajini shut down the system .. The network was up .. So Rajini concluded that the probs was due to this system.

Then Rajini tried to transfer some of the codes from the system to his laptop … While the transfer was about to complete his entire softwares was hacked and was attacked by virus and his computer got hanged !!

Rajin found that each time Jyo tried to transfer some of the code snippets we had the crash and I was having network breakdown at nights.

Rajini started to think very deeply and found a solution …

We all hear this music as BGM !!

Come on, Come on
Yeah Come on,
Hey Come on, Come on…… , Yo!!!!!
I am back to explore, Give the comp, give a few minutes now,
S.A (System admin) thatz what they say
C to the C to the N to the A
S.A thatz what they say…

Rajini planned a software such that when ever some one tries to transfer softwares or games or music files from Chandralekha’s system he programmed a code such that it plays a song ( Bhakthi song ) such that the when the song played the blackmagic from the Chandralekha system becomes inactive and loses its power to reach the other system.
Rajini deployed this concept successfully and was able to put off the system back to the same place and happily comes out of the room with a victorious smile…

The end !!

Bioinformatics and drug discovery 2

Sometimes we want to develop broad spectrum drugs that are effective against a wide range of pathogenic species while at other times we want to develop narrow spectrum drugs that are highly specific to a particular organism. Comparative genomics helps to find protein families that are widely taxonomically dispersed and those that are unique to a particular organism.For example, when we want to develop a broad spectrum antibiotic, we are looking for targets that are present in a large number of bacteria yet have no similar homologues in human. This means that the antibiotic will be effective against many bacteria killing them while causing no harm to the human.


In order to determine the role our potential drug target plays in a particular disease mechanism we use DNA and protein chips. These chips can measure the amount of transcript or protein expressed by a cell at different times or in different states (healthy versus diseased). Clustering algorithms are used to organise this expression data into different biologically relevant clusters. We can then compare the expression profiles from the diseased and healthy cells to help us understand the role our gene or protein plays in a disease process.


All of these computational tools can help to compose a detailed picture about a protein family, its involvement in a disease process and its potential as a possible drug target. Following on from the genomics explosion and the huge increase in the number of potential drug targets, there has been a move from the classical linear approach of drug discovery to a non linear and high throughput approach. The field of bioinformatics has become a major part of the drug discovery pipeline playing a key role for validating drug targets. By integrating data from many inter-related yet heterogeneous resources, bioinformatics can help in our understanding of complex biological processes and help improve drug discovery.

Personalised drug treatment using SNP's

99.9% of our genes are identical to anyone else's. The other 0.1% that makes us unique is made up of 3 million single nucleotide polymorphisms (SNPs) that occur one in every 1000 bases. A SNP is a variation of one nucleotide between the DNA sequences of individuals. Ten pharmaceutical companies and the Wellcome Trust have set up the SNP consortium to compile a SNP map of 300,000 SNPs. The rationale behind this giant venture is that the SNP map can be used in the mapping of disease associations and can also be used to unravel an individuals response to various medications. The most interesting SNPs from a pharmaceutical point of view are the coding-SNPs (cSNPs).

These occur in coding regions and are therefore themselves either directly responsible for the disease or a different drug response when they cause a non-synonymous change to a protein. Pharmacogenetics is the study of the genetic basis for the difference between individuals in response to drugs in order to tailor drug prescriptions to individual genotypes. SNPs can be used to distinguish between patients who will benefit from a particular drug against those who will not. This ability to divide the population into drug responders and non responders makes it possible to target a specific population that would benefit from a new drug more effectively. The result will probably be a significant increase in the chance of getting a new drug through to market. This new approach defines a new discovery paradigm that moves beyond genomics to personalised drug treatment. The information obtained from these polymorphic studies could be used in target validation. If a target is determined to be highly polymorphic, it could be abandoned.

Drugs that were abandoned because they caused severe side effects in a minority of people, could be revived. It is believed that in the future doctors will use "SNP-chips", tiny microarrays studded with the DNA sequences that bind to different SNPs. A patient's DNA would be washed over the chip and fragments that matched the sequence would bind to the chip and light up. With computer analysis, doctors would know which gene variations each person carried. Given this head start, they could intervene, long before the disease began to manifest or they could determine which medication would besr suit that individuals genetic makeup.

Bioinformatics and drug discovery

In recent years, we have seen an explosion in the amount of biological information that is available. Various databases are doubling in size every 15 months and we now have the complete genome sequences of more than 100 organisms. It appears that the ability to generate vast quantities of data has surpassed the ability to use this data meaningfully. The pharmaceutical industry has embraced genomics as a source of drug targets. It also recognises that the field of bioinformatics is crucial for validating these potential drug targets and for determining which ones are the most suitable for entering the drug development pipeline.

Recently, there has been a change in the way that medicines are being developed due to our increased understanding of molecular biology. In the past, new synthetic organic molecules were tested in animals or in whole organ preparations. This has been replaced with a molecular target approach in which in-vitro screening of compounds against purified, recombinant proteins or genetically modified cell lines is carried out with a high throughput. This change has come about as a consequence of better and ever improving knowledge of the molecular basis of disease.

All marketed drugs today target only about 500 gene products. The elucidation of the human genome which has an estimated 30,000 to 40,000 genes, presents immense new opportunities for drug discovery and simultaneously creates a potential bottleneck regarding the choice of targets to support the drug discovery pipeline. The major advances in genomics and sequencing means that finding an attractive target is no longer a problem but finding the targets that are most likely to succeed has become the challenge. The focus of bioinformatics in the drug discovery process has therefore shifted from target identification to target validation.A lot of factors need to be taken into account concerning a candidate target from a multitude of heterogeneous resources.

The types of information that one needs to gather about potential targets include nucleotide and protein sequencing information, homologues, mapping information, function prediction, pathway information, disease associations, variants, structural information, gene and protein expression data and species/taxonomic distribution among others. Different bioinformatics tools can be used to gather this information. The accumulation of this information into databases about potential targets means that the pharmaceutical companies can save themselves much time, effort and expense exerting bench efforts on targets that will ultimately fail. The information that is gathered helps to characterise the different targets into families and subfamilies.

It also classifies the behaviour of the different molecules in a biochemical and cellular context. Decisions about which families provide the best potential targets is guided by a number of criteria. It is important that the potential target has a suitable structure for interacting with drug molecules. Structural genomics helps to prioritise the families in terms of their 3D structures.

Patterns of inheritance of disease

We have two copies of every gene (except for the genes on the X and Y chromosomes). One copy is inherited from our father and the other from our mother. The two copies of a gene may be exactly the same or slightly different versions, called alleles. The genes for eye colour and hair colour are alleles accounting for the variations that are seen in eye and hair colour. Most characteristics and diseases have a complex genetic and environmental basis. There are a few traits and diseases that result from different alleles of a single gene that are well understood. Alleles can be dominant or recessive. A dominant allele is one that influences the phenotype even if it is present in only one copy. This means that if you have one mutant gene that causes the disease, you will develop the disease. An example of an autosomal dominant disease is Huntingtons disease. A recessive allele will only effect the phenotype if its counterpart allele on the other chromosome becomes inactivated or lost. This means that individuals that have one copy of a mutant gene will not develop the disease but will be carriers - they have a 50% chance of passing the mutant gene to their offspring. If both parents are carriers, there is a 25% chance that their offspring will inherit two recessive alleles and therefore develop the disease. Cystic fibrosis is an example of an autosomal recessive disease. Mutations on the X chromosome show a third and fourth pattern of inheritance, namely sex-linked dominant and sex-linked recessive diseases. X chromosomal genes are different from the autosomal genes because the male only carries one copy of the X chromosome that he inherited from his mother. A recessive allele does not influence the phenotype in females if it is present in only one copy, because there is a second copy to block it. Of course there is no second gene copy in males and therefore the recessive allele will appear. An example of an X-linked recessive trait is colour blindness. Sex linked dominant traits are quite rare. Most diseases are not so simple. Cystic fibrosis can result from a number of different mutations in the same gene causing a range of different effects in individuals while Alzheimers patients can show an identical outcome as a result of mutations in several different genes. Some diseases are multi-factorial requiring mutations to develop in several different genes (heart disease). The phenomenon of imprinting determines which of a pair of genes, either the one from the mother or the father, will be activated. In some cases, an individual may have the mutated gene and not develop the disease. Penetrance is a measure of the likelihood that a given mutation will cause a disease.

Mutation case study : Cystic Fibrosis

Cystic fibrosis is a severe, genetically determined disease that involves both the lungs and the gastrointestinal tract. It occurs in about one in every two thousand births among white children and at a far lower rate in asian and black children. There are now more than 500 different mutations known to cause the disease. These mutations occur in a huge gene (>6000 nucleotides) on chromosome 7 that encodes a protein of 1480 amino acids called the cystic fibrosis transmembrane conductance regulator (CFTR). This protein transports chloride ions out of cells. People with cystic fibrosis must inherit two mutant genes to develop the disease but these mutations need not be the same. This disease results from a number of different mutations in the CFTR gene. The most commonly observed mutations that have been observed include deletion of a codon resulting in the deletion of the amino acid phenylalanine at position 508, a missense mutation resulting in an aspartic acid being substituted for a glutamic acid at position 551, a nonsense mutation at position 542 resulting in a stop codon instead of one that codes for glycine and hence a truncated protein and mutations at the splice sites of intron 8.

Other Types of Mutation

Insertions and deletions

Extra base pairs may be added or deleted from the DNA of a gene. The number of bases can range from a few to thousands. Insertions and deletions of one or two bases or multiples of one or two cause frameshifts (shift the reading frame). These can have devastating effects because the mRNA is translated in new groups of three nucleotides and the protein being produced may be useless. The picture on the right shows an example of a frameshift mutation, in the second codon the deletion of 'c' leads to a shift in reading frame and multiple amino acid substitutions in the subsequent protein.Insertions and deletions of 3 or multiples of three bases may be less serious because they preserve the open reading frame. However, a number of trinucleotide repeat diseases exist including Huntingtons disease and fragile X syndrome. In Huntingtons disease, the repeated trinucleotide is 'cag'. This adds a string of glutamines to the Huntington protein. The abnormal protein produced interferes with synaptic transmission in parts of the brain leading to involuntary movements and loss of motor control. Fragile X syndrome is caused when a locus on the X chromosome contains a stretch of nucleotides in which the triplet 'cag' is repeated (as many as 400 times). This causes a constriction in the x chromosome making it quite fragile. Males who inherit this X chromosome are mentally retarded. Females are only mildly affected.

Chromosomal mutations

A chromosome mutation is any change in the structure or arrangement of the chromosomes. Mutations to chromosomes happen most frequently during the crossing over stage of meiosis. There are many different types of mutation that can change the chromosome structure resulting in detrimental changes to the genotype and phenotype of the organism. Chromosomal mutations effecting essential parts of the DNA can result in the abortion of the foetus before birth.
Translocations - Translocations are the transfer of a piece of one chromosome to a non-homologous chromosome. They are often reciprocal, with the two chromosomes swapping segments with each other. In most cases of chronic myelogenous leukaemia (CML), the leukaemic cells share a chromosomal abnormality known as Philadelphia chromosome. This abnormality is the result of a reciprocal translocation between chromosomes 9 and 22. An abnormal hybrid gene is created leading to the production of a novel protein that is not normally found in the cell. This protein prevents normal growth and development, leading to leukaemia.
Inversion - A region of DNA on the chromosome can flip its orientation with respect to the rest of the chromosome.
Deletions - A large section of a chromosome can be deleted resulting in the loss of a number of genes.
Duplications - In this mutation, some genes are duplicated and displayed twice on the same chromosome.
Chromosome non-disjunction - During cell division, the chromosomes fail to successfully separate to opposite poles, resulting in one of the daughter cells having an extra chromosome and the other daughter cell lacking one. If this non-disjunction occurs in chromosome 21 of a human egg cell, a condition called Downs syndrome (DS) occurs. A person suffering with DS has 47 chromosomes in every cell instead of the normal 46. They suffer from heart defects, mental retardation and stunted growth. However, it must be pointed out that the distributions of IQs of people with DS overlaps considerably with the IQ distribution of 'normal' (non-DS) population, mainly due to changes in education policy in the last 30 years.

Types of mutations

Single base substitutions

A single nucleotide base becomes replaced by another. These single base changes are also called point mutations. If a purine (a, t) replaces a purine or a pyrimidine (c, g) replaces a pyrimidine, it is called a transition. If a purine replaces a pyrimidine or vice-versa, the substitution is called a transversion.

Missense mutations -


In a missense mutation, the new base alters a codon resulting in a different amino acid being incorporated into the protein chain. This is what happens in sickle cell anaemia. The 17th nucleotide of the gene for the beta chain of haemoglobin is changed from an 'a' to a 't'. This changes the codon from 'gag' to 'ggt' resulting in the 6th amino acid of the chain being changed from glutamic acid to valine. This apparently trivial alteration to the beta globin gene alters the quaternary structure of haemoglobin, which has a profound influence on the physiology and wellbeing of the individual.The picture on the right shows an example of a missence mutation, a substitution of 'a' in the second codon to 'g' leads to an amino acid substitution of glutamine (Q) to arginine (R).


Nonsense mutations -

In a nonsense mutation, the new base changes a codon that specified an amino acid into one of the stop codons (taa, tag, tga). This will cause translation of the mRNA to stop prematurely and a truncated protein to be produced. This truncated protein will be unlikely to function correctly. Nonsense mutations occur in between 15% to 30% of all inherited diseases including cystic fibrosis, haemophilia, retinitis pigmentosa and duchenne muscular dystrophy. The picture on the right shows an example of a nonsense mutation, where 'c' in the second codon is changed to 't'. In the normal nucleotide sequence the second codon 'cag' codes for glutamine (Q) whilst in the mutated second codon 'tag' codes for Stop leading to premature termination of the protein.


Silent mutations -


Silent mutations are those that cause no change in the final protein product and can only be detected by sequencing the gene. Most amino acids that make up a protein are encoded by several different codons (see genetic code). So, if for example, the third base in the 'cag' codon is changed to an 'a' to give 'caa', a glutamine (Q) would still be incorporated into the protein product, because the mutated codon still codes for the same amino acid. These types of mutations are 'silent' and have no detrimental effect.

Splice site mutations -


Introns must be spliced from mRNA to produce the correct protein. This process must be carried out very accurately and it is guided by the nucleotide signals at the splice sites. If a mutation alters these signals, the intron may not be removed and an incorrect protein will be produced.

ChandraMukhi -- Reloaded ( Part IX )

PART IX - RAJINI ON MISSION CHANDRALEKHA

Rajini arrived to LMRVSoft office from US, as soon as he got the SMS from Prabhu. Prabhu apprised him of the strange happenings that were happening over the recent few days at office. Staffs were under the impression that these could be the effect of the black magic of Chandralekha. Prabhu refused to buy this "black magic" logic...he He rather suspected this as Nayantara's handiwork in association with Neelambari to stop the organization's growth. However Rajini rubbished these claims by Prabhu, as he thought Nayan could have never thought of doing such things. Prabhu thought since Love is blind, Rajini did not want to look Nayantara as guilt.Rajini ran the latest virus scanners, anti-spyware in every system, but none of them showed any problems in the system. Rajini was clueless…. What could be the problem.... During day times the systems ran fine without any issues… but during nights, some weird things were happening from any of the system... The problem occurs only for a few while and there was no log or anything created in the system, for Rajini to analyze the reason behind such a behavior. Another thing Rajini noticed was a strange sound coming from Chandralekha's room in the nights.. If Rajini knocked the door of that room, the sound will stop..On a fine day, as Rajini was working in his laptop monitoring the company's network set up, suddenly he found a strange thing happening... A malicious application that bypassed the company's firewall system was transmitting through every systems... Alas!!, Rajini could not stop that application through any of his software... And it was actually going towards the company's Project server... God!! If it gains access to the project server, then it might erase the entire data in that server.... Rajini was quick to react to this danger... He ran to the server room where prabhu was working in the Project server system... Swiftly, he pushed Prabhu from the chair and unplugged the network cable... Every staff arrived at the server room hearing this huge noise that came as a result of Prabhu falling to the ground... A shocked Prabhu got off from the ground... Rajini apologized to him and explained to him why he disconnected the network cable from the server system... Prabhu was surprised... "From which system, this virus has originated, Any idea?", he enquired... Rajini paused for a moment and said... "Hmm... it has come Nayantara's laptop only"Everyone was surprised... Prabhu was very much angry... "I told u already rite... This girl is the reason for everything....".. Rajini replied... "O.K dont worry, I will take care of her".... Nayantara who was also present there,was shell shocked... "I did not do anything...Please believe me...", she requested everyone, but no one was believing her... Rajini took Nayantara along with her laptop and went inside the conference room... He locked the room from inside, so that people from outside could only hear some whip lash sound.... After a while.... Rajini came outside of the room, a worried Vijayakumar inquired "What happend, what happened to my dear daughter's laptop... Dude..dude.. She loves that laptop... she can't bear losing the laptop... ... I assure u, she had kept it protected from any virus or spyware.. Nothing would have entered it, Kindly dont do anything to her laptop or disconnect the internet connection... She can't live without G-Talk or orkut dude....", Vijayakumar broke into tears... Rajini looked at him with a straight face and replied... "Dont worry... I have just disconnected the network cable from that laptop and put her system in quarantine... Things would be alright now... O.K everyone get back to work", Rajini left that place as a confused Prabhu and Jyo look over..That night, the staffs in LMRVSoft left home early fearing Chandralekha effect, and so Rajini was alone in the office. He decided to take another look at the Chandralekha ‘s room…. The strange sound was coming again from Chandralekha’s room…. Rajini, this time, rather than trying to go inside or knocking the door, observed the room, the sound carefully…. After a while, he left the place and left for his home with a sense of having found something…. Next day morning Rajini comes to office late and Prabhu was highly tensed.

Rajini : hey Prabhu .. Good morning … Why are tensed ???

Prabhu : Everyone in our company started to resign …. They are very much afraid of the Chandralekha’s effect .. Got 10 resignation letters in the morning and had a call from the client

Rajini : What they were asking ??

Prabhu : I had put conference to u … where were you at that time ??

Rajini : Cool … Cool you have Jyo to do all the household chores .. for me I have to do myself. Went for having breakfast

Prabhu : He asked us to solve this issue …If we solve this problem they will make the payment it seems … Is the handwork of Antony ??? Is he involved in all these ??

Rajini : Silly … Antony doesn’t have that much guts to work on these

Prabhu : Then ….. is there anything called BLACKMAGIC ??

Rajini : Give me 2 days… I will work and solve the issue

Prabhu : ( Rajini laughs ) : Poruthuirunthu par

Rajini planned to stay in the office …

Everyone else in the office left …… Jyo was happily playing in the chandralekha’s system ….
Rajini tried to connect but he wasn’t able to do the same as there were some network problems.Rajini went near the room and happened to hear the clicks sounds from the keys …. He found out that some one has entered the room and started working in the system

( TO BE CONTINUED .... )

ChandraMukhi -- Reloaded ( Part VIII )

PART - VIII - ENTRY OF CHANDRALEKHA AND PROBLEMS FOR LMRVSOFT

On a fine Monday morning, Prabhu calls Rajini at his cabin and informs him about "Hey Rajini, you've got a mail from a top US company to solve a technical problem. Seems like you need to go there immediately".


Rajini feels peeved, not because he had to leave to US immediately, but, wat the hell, how could Prabu login into his official email account and check his mails without his knowledge.


Rajini : Prabhu, this is too much, I think you are crossing your limits, how can you peep into my mails?


Prabhu (replies with a smile): well… Monday morning, I didn't feel like working at all..Yesterday when u logged in my system and checked ur mail, you had set the option for remember password rite, so I was able to check ur mails :D. Hey come on, this is how it happens in the original ChandraMukhi also. After all Remakes shud not deviate much from the original


Rajini got irked, but knowing that this guy Prabhu can never be changed, so he left the issue there and started to leave for the immediate Onsite assignment. So he bid good bye to everyone in the office including his love Nayanthara.. "Any problem one SMS, Rajini will be right there", Saying this Rajini signed off in style


Business continued as usual at LMRVSoft with Prabhu and Jyo effectively managing the office. As Rajini and Prabhu had instructed, no one dared to enter the room where Chandralekha's PC was locked and other than that room, the entire office was kept clean and nice.


But Jyo was rather curious to browse thru Chandralekha's system. In her earlier office, after lunch time and during relaxed times, she used to spend time playing solitaire, mine sweeper and other PC games which gave her a refreshing break from the mind boggling work. Especially Jyo enjoyed the thrill of playing the games at office without getting noticed by the PM or PL. She missed all those now. In the hush-hush created by Neela while getting the relieving order, Jyo could not get the back up of her personal data from her old office machine. She heard from some old staffs who worked there earlier about Chandralekha, that she used to play Prince of Persia, Dave, Paratrooper and similar games during office hours..tjhey were telling that the buzzing sounds of such games were still ringing in their ears. Ever since hearing this, Jyo's curiosity to check out Chandralekha's system grew more.


So Jyo, ignoring her hubby's and Rajini's warnings, on one fine day, unlocked the Chandralekha room and stepped inside.......The room was covered with dust and Chandralekha's system was looking dirty and pale with all the dust on it... Jyo cleaned the room in quick time and switched on the monitor, as the system which was on standby mode all these days came back to life as she moved the mouse cursor.


At the same time, Prabhu who was typing google.com in his browser, accidentally missed out one of the letters and was taken to a porn site, while Accounts department aasha while doing online money transfer to one of the company's clients, entered an additional zero to the amount accidentally and pressed enter even before she realized it……


The effect of Chandralekha had thus started to haunt the LMRVSoft Office as Jyo, unaware of these things proceeded to browse thru Chandralekha's system. She was amazed at the amount of data in Chandralekha's system, thousands of DOS and Flash games, the Entire collection of Calvin and Hobbes, Tintin, Asterix and Obelix and so much more. And then there was a huge collection of MP3 songs, English, Tamil, Hindi and even Konkani. This PC was surely a treasure, she thought. Jyo was just wondering, how Chandralekha's PM even thought of firing such a hardworking, dedicated employee.


Just at that moment, Prabhu called for Jyo. So she quickly switched off the monitor, closed the door and left the room immediately to respond to Prabhu.


Next day... Everyone were busy working on a module that had to be delivered to onsite that day. Prabhu after attending a client call at the conference room was returning back to his cubicle. At that time he noticed Nayantara logging into a different system from that of hers and doing something. So he stopped and inquired Nayantara, "Hey Nayan, wat are u doing here, your job is in the front office..." Nayantara, who did not seem to expect Prabhu at that time, got tensed by his question and replied "yea..yea Prabhu, this is anita's system...she is on leave today and it seems she had forgotten to check in the files that she has modified yesterday. So she called me up today morning and asked me to just check in the files...as these are critical for today's drop. I am doing just the same". "O.K Fine", said Prabhu and proceeded to his cubicle.


The module was completed shortly and was packaged for the System testing. Prabhu thought he would just do a round of Sanity testing before the testers started BVT (BVT - Business value Testing, Testing of key functionalities which must be passed if it needs to be delivered) on it. He ran the application and it looked to run smoothly suddenly, the application crashed and the system hanged. Everyone were shocked. "how could this be" was the question in everyone's mind. Nasser, the Module leader quickly pointed out "the bug should be in the database module only. Anita was handling it, but she ran it in her machine yesterday..showed me also before she left for the day, it was working fine..somebody shud have screwed it afterwards..", he paused and raised his voice "Who worked on Anitha's system today"......... everyone's eyes fell on Nayantara.. She got terrified... "No..no..i did nothing at all. I just checked in whatever code Anita has entered into VSS".. Prabhu was puzzled at this sudden failure of application..But he did not mutter any thing rather looked at nayantara with a straight face..."Please go away from here to your cabin....", he turned to the developers "Folks, look at the root cause of this issue and get it solved immediately. "


From that day onwards, problems seemed to coming in plenty for LMRVSoft. Certain machines crashed for no reason, Programs threw memory out of exception error at times, some machines behaved very strangely. Prabhu and Jyo got upset by this and were worried about the business prospects if the problem continues. So Prabhu sent an SOS like SMS to Rajini to return to see what is haunting LMRVSoft of late.

( TO BE CONTINUED .... )

PART - VII - RAJINI Vs ANTONY


A tensed Prabhu rushes into Rajini's cabin.


Rajini : Hey Prabhu, why do u have to look so serious and tensed like V.V.S.Laxman?. I didn't say you will not be included in the next match, did I?


Prabhu : Oh come on Rajini, we have got a serious problem


Rajini : What is it?


Prabhu : We had been testing the software product by Antony Software Technologies as per our contract with MilliSoft rite? The company chairman Mr.Antony is on the line now. He is warning us to close the bugs that we have logged into Millisoft's defect tracker for their product… otherwise…


Rajini : otherwise?


Prabhu : Otherwise, he would influence Millisoft's top management to break our contract with them. Antony Software Technologies is a 10 year old company and had been the partners of Millisoft for more than 5 years now. Antony personally knows most of the top management guys there at MilliSoft. Thatz why I am more worried. What should I reply to him?


Rajini : hahaha, don't worry. I will take care of the issue. It is lunch time na. You go and have ur lunch..


Prabhu : So soon eh? Just now I had my breakfast. I will have it after an hour or so. Now I am having snakes


Rajini : (terrified) : What?????


Prabhu : snakes you don't know? the chips, biscuits, cakes stuff…


Rajini : oh snacks ah ? o.k o.k you continue having it. I would take care of this problem.


[Prabhu left the place]



Rajini : Antony…………


[Antony immediately recognizes Rajini's voice. Rajini had been Antony's arch rival for years.]


Antony : waare wah Rajini…………. So was it my old friend who logged in so many defects against our name

Rajini : Hey hey hey , don't see the defect count ah, see the effects on client.

Antony: Don't teach software management to me. You are a kid in the software business. I had been running a company for 10 years now. If you find defects, do you think you are a big Tester?

[Rajini just smiled]

Antony : (continues) Defects kandupidikkaravan ellam Tester aagida mudiyaathu. Just tell me whether you will close the defects or not.

Rajini : Sure, I will give u 7 days time. You fix all the reported bugs, I would close the defects in the defect tracker.

Antony : [in angry tone] Haaaa, you are setting time to me is it?, OK, I will close… I will close your chapter and your company contracts with Millisoft within the same 7 days time u gave………..

[Saying this, Antony angrily disconnects the phone]

(the next few days)

Scene : Antony and his team hacks into Millisoft Defect tracker and changes the status of the bugs

[Flash] Somebody takes a picture of it

Prabhu comes and tell to Rajini "Antony is hacking into Millisoft's Defect Tracking system"

Rajini : Let him hack

Scene : Antony bribes a LMRVSoft employee to get the contract documents pertaining to this project.

[Flash] Somebody takes a picture of it

Jyo rushes to tell Rajini, "Antony has got a copy of our official document"

Rajini : Let him have that

[ After a week]

Antony called up Rajini

Rajini : Hello, LMRV Soft

Antony : Antony……… Marc Antony…… You had given me 7 days time to finish off the bugs rite. I have taken enough steps to finish off your company as a whole.

Rajini : Ha ha ha…. Kanna, If there is a PC in front of you, just read the latest E-mail from MilliSoft,.

A shocked Antony logs into his PC, and read the E-mail that he had just received from MilliSoft. MilliSoft's Vice president for Asian operations have sent a mail that read "We are sorry to inform that our agreement stands cancelled in view of your fraudulent activities'" and attached were photos that showed Antony bribing LMRVSoft's employee and him hacking into Millisoft's website.

An angry Antony kicks the monitor infront of him………. Rajiniiiiiiiiiiiiiiiiiiiiiiiiiii

Rajini : Ha ha ha, Yeah yeah yeah Rajini………….. Super Star Rajini………….. What you told, what you told?

Defects kandupidikkaravanga ellam Testers aaga mudiyathu nu you told la . yea, quite true, ... Defects kandupidikkaravanga ellorum Testers aagida mudiyaathu…. But these are not the bugs that we had disconvered… These are bugs that were the result of ur negligence…… This is not a minor bug. High severity bug. We can do nothing about this.

Antony grumbled and moaned as Rajini continued

Rajini : hey hey hey……. GOD will give so many compiler errors to a good programmer... But he will make the code pass UAT successfully with zero defects...For bad programmer's code might seem to run perfectly in offshore environment. But during UAT, GOD will make the bad code fail miserably. Your code(points at Anthony) will fail in UAT phase…. Try to correct it…..

[ A dejected antony hangs up the phone... But since Rajini was the one who called, the connection is still active, After a few minutes silence, due to rajini's magic, automatically the speaker turns on in Antony's phone. Rajini delivers a punch line ]

Ennai pathi theriyum la "Intha Rajini oru idathula code change senja............... 100 bugs fix panna maathiri......" (Sshhk sshk sound..)

(BGM followed by Rajini disconnecting the phone)

( TO BE CONTINUED )

Mutation

A mutation is any change in the DNA sequence. Mutations can lead to genetic disorders or disease. Most mutations are recognised because the phenotype, that is the characteristics displayed by an organism, have changed. There are many different types of mutation. They can occur on a macroscopic level in the form of chromosomal mutations or they may be the result of a single base pair change in the DNA sequence. Mutations can occur within a gene preventing the synthesis of the correct protein, they may occur in gene promoter regions or in DNA regulatory regions changing the expression levels of the protein, or near the splice sites in introns causing disruption to the splicing process and production of an incorrect protein.

Mutations are rare events occurring at a rate of 1 in every 50 million bases added to the nucleotide chain. Most of the changes that happen are quickly repaired by our very efficient and accurate DNA repair system. However, this repair mechanism is not foolproof. Failure to repair all mutations has led to the introduction of some mutations that have made organisms fitter and better able to adapt to their environments. However, many mutations have detrimental effects for an organism and it is these mutations that are the basis of many human genetic disorders and disease.

A healthy body depends on the interaction between thousands of proteins, acting together in the correct amounts and in the correct places. Proteins are what perform all of the body's essential functions - fighting infections, growth and repair, detoxifying toxins, metabolising food and much more. Mutations in our genes can result in the production of a completely malformed protein that is unable to carry out its functional role or they may change the amount of a protein being produced.

The outcome of a particular mutation depends both on how it alters a proteins function and also on how vital that protein is to our survival. Failure to produce proteins in the correct amounts or at all can disrupt essential metabolic, regulatory or signalling pathways resulting in the development of disease.

Gene mutations can either be inherited from a parent or acquired. A hereditary or germline mutation is present in every cell of the body. They are called germline mutations because they are present in the germ cells or reproductive cells and in this way they can be passed from one generation to the next. These mutations are copied every time a body cell divides. Acquired mutations or somatic mutations are changes that occur during a persons lifetime. Somatic cells include all body cells except for the reproductive cells.

These somatic mutations are changes in the genomic sequence of individual cells and they are only passed to cells that are directly derived from the original cell. These mutations are often a result of the failure of the cells DNA repair mechanism to correct a mistake that has occurred during cell division. The body's repair machinery is highly accurate most of the time (uncorrected errors occur at the rate of about 1 in every 50 million nucleotides added to the chain) becoming a little less efficient with age. Somatic mutations can also be the result of environmental stresses such as cigarette smoke, over exposure to the sun, radiation, car fumes, pesticides and many more.

ChandraMukhi -- Reloaded ( Part VI )

PART - VI - NAYANTARA FIGHTS AND THEN LOVES RAJINI

(Few months later)

[Location : LMRVSoft Office]


Business at LMRVSoft had been smooth and steady. With the expertise of Rajini and the management skills of Prabhu combined with diligence of Jyothika, the company was doing enormously well. Also the recruitment had yielded some best talents for the company. Within few months after resuming its operations, LMRVSoft earned a good reputation as service oriented company. Owing to Rajini's efforts, the US Software giant MilliSoft certified LMRVSoft as its most valuable partner and made LMRVSoft as the official Testing center for all of their software products that were outsourced to the Indian vendors.


Watchman Vijayakumar's daughter Nayantara was made the receptionist for the company. Even though she did not like them, as they occupied this building much against her father's wishes, she took the job, since she had no other job.


Vijayakumar once arranged for a special lunch for Rajini, Prabhu and Jyo at his home. Nayantara was assigned the task of getting the menu for the same.. When she inquired them about their food preferences, Jyothika and Rajini chose vegetarian, while Prabhu who had a liking for variety in foods replied


"Nirpathuve, Nadappathuve, Parappathuve neengalellam thinner thaane, en veetin dinner thaane, "

implying he would eat any kind of living being. Nayantara realized that Prabhu could turn out to be a threat to animal kingdom in Siruseri, and so immediately chased away all the birds and animals that were roaming in the nearby vicinity,

(Song is adapted from "Kokkku para para from ChandraMukhi)

" Kokku para para (Translation : Crane, fly fly)

Kozhi para para (Translation : Hen, fly fly)

Mynah para para (Translation : cuckoo, fly fly)

Mayilae Para.. (Translation : Peacock, fly fly)"


Her hatred for them increased but nevertheless she decided to maintain silence and was doing her work sincerely.

One day Morning, Rajini was going through the company's Bulletin Board hosted on their Intranet for a technical doubt. Since he could not find any help in any of the forums, he was browsing through other forums. He was surprised to see all the forums except the Sports forum, inactive. There was a huge discussion going on in the Sports forum as to whether Sachin or Lara was the best ever player. Most of the postings were from Nayantara and she was posting all technical, statistical and personal failures of Sachin in comparison with Lara. Rajini got very much irritated over whatever that was going on, and he asked the moderator to delete all the posts immediately in the Sports forum and disallow any further activity there.


After some time, a visibly angered Nayantara came to Rajini's room.


Rajini ( coolly) : Hey ten thara

Nayan (angrily) : Nayanthara....

Rajini : yeah yeah nayanthara... watz the matter

Nayan : Why did you block access to Sports forum

Rajini : Ha ha ha, you are supposed to be a receptionist and not a sports columnist.

Nayan : What do u know about cricket or any other sports? You know only about coding, networking blah blah. You know I had been a cricket captain in my college women's team.


Rajini : Haan….


Nayan (Embarassed ) : You can only block acc...acccess to the sports forum...(stutters) but..but..you cant block my spo..spo...sports knowledge.........


Saying this Nayanthara walks away angrily from the room. After moments of silence, Rajini started singing at her ( no no not athinthom song , he is a national hero boss :), so he sang in a hindi tune :) ).

[ Tune : Yeh Tara woh Tara from Swades]

Yeh Tara Woh tara, Nayanthara,

Cricket se, dekho, mein brian lara

Yeh tara woh tara Nayanthara

Cricket se, dekho, mein brian lara



Woh young days le,

simply superb i played!!

have to see my batting skills u tara.........


Batting, bowling… all I do… and win too, u know that? tharaa tharaa…….


Everybody in the office joined the dance too… Nayantara came to know that Super star had been a good cricketer and also one whom John Wright and Greg Chappell consulted for some technical methods in batting and fielding setup. She felt bad about mistaking Rajini and also realized in Tamil films no one can be and is allowed to be more talented than the hero. Hence as per Tamil cinema Grammar, Nayantara immediately fell in love with Rajini.


Rajini : hahaha, Remember, a bulletin board shud not be used as a bullet board to hurt others' feelings and thatz precisely why we blocked the access. I hope you would have understood. Go ahead, the access would return.

[A happy Nayantara returned to her cabin]

(To be continued...)

Few days later]

ChandraMukhi -- Reloaded ( Part V )

PART - V - RAJINI'S ADVICE TO S/W ENGINEERS AND RAJINI RESCUES JYO

[ Next day evening at Neela's office ]

A grand farewell was arranged at the Office. Keeping in with the office custom, the party started with a song sequence

(Tune : Ra..Ra. ramaiyah)

As Computer first sang in Java language, a singer translated it in plain English

[computer] Public final ContentMarkupLanguage HTML;

[singer]Only one HTML - All around the Web

[computer] Public final float SalaryHike;

[singer]Only one Salary Hike - Around the year

[computer]Public final SuperStar Rajini;

[singer]Only One Super star for the entire world........

Only....... One....... Super star for the entire world........

After some drum beats, Rajini enters the scene singing

E..E... E.... Engineer.......

Four phases in your software career.

Listen here, E..E....E.... Engineer

Four phases in your software Career...

Four phases in software career,

Which phase you are in now, think Dear,

[ E..E..Eee Engineer....]

In the First phase, you will be put into training,

Boring lectures will leave ur mind draining,

Second phase , you will start to test or fixing,

Slogging for a dumb work, will be taxing,

Third phase , you will take up management and team leading,

Slowly you would realize, that ur IT skills are fading,

Fourth phase will be when u realize, this life is boring,

But u wud never dare to escape it, with money pouring.

Four phases in software career,

Which phase you are in now, think dear.......

Listen here E..E..E.... Engineer

Four phases in software career.

As the song ends, they hear a huge explosion. System Engineer Naren came running

Neela : naren, What happened?

Naren : Nothing maa'm. Jyothika's system crashed.

Neela : oh, but it sounded like the World Trade Center crashing.?

Naren : Since jyo has not switched off her system for decades , the motherboard got overheated and the harddisk got burnt. Luckily for us, except for the hard disk and the data in it, other parts of the PC are not much damaged…

Neela : Oh, I see (turning to Jyo) What jyo, All the tasks assigned to you was in that system only rite? You are yet to finish some tasks and I noted that you have not checked in the code to the server machine too.

Jyo (worried) : Yes maa'm. But a system crash is not my fault

Neela : We had sent so many mails requesting you ppl to switch off the systems atleast once in a week. You had never listened… and since you always kept it on, even the auto update and system back up could not happen correctly…. Now you see the result of all those negligence….a system crash…

Jyo : But..but….

Neela : (with a wicked smile) Never mind, take your own time, complete the pending tasks assigned to you and then collect your documents

Jyo : Maa'm pleaseeee. I need to start the work in our company tomorrow.

Neela : (smilingly) I can do nothing about that dear. This is company rules…….

Jyo starts crying. To redo all the pending tasks that went with the crash would definitely take another 2 months. Every employee in the gathering felt sorry for jyo. They knew this was Neela's handwork. Rajini pacified Jyo…

Rajini : Hey jyo, cool, why do u cry. Just wait and see

Smilingly Rajini walked towards Jyothika's system, Build up music started

Come on, Come on

Yeah Come on,

Hey Come on, Come on…… , Yo!!!!!

I am back to explore, Give the comp, give a few minutes now,

S.A (System admin) thatz what they say

C to the C to the N to the A

S.A thatz what they say…

Yo, I am about to service,

Here I come, I work without any fees

[Rajini reached the system as the beats continued. He replaced the hard disk in the system with the one that he had in the bag, and restarted the machine]

Yo ! I am about to login,

For the justice I will win,

Can you stop me you cannot

I'm the admin and you are not

Do you expect me to be here?

Lemme tell u that none has to fear,

I am a magical man,oh yeah

I am a man on the machine with a mission as I have clear vision,

Well, they try to make the system work

The name is S.A , yeah thatz me

The name is S.A , yeaaaaaah thatz me...............

To everyone's surprise, the hard disk Rajini replaced actually contained all of Jyothika's data in perfect condition. Jyo could not believe her eyes. Tears were rolling from eyes and she could not utter a word. Neela on the other hand was shocked.

Rajini : (victorious smile) Ha ha ha, This is the actual hard disk of Jyothika's machine and the one that got crashed was the duplicate hard disk I replaced yesterday in this machine

Neela turned towards the junior programmer Madhu with anger

Rajini : ha ha Neela, why are you looking at Madhu. I will narrate, whatever that happened yesterday

[ FLASH BACK ] Time : Yesterday night

Madhu was returning from Neela's room all smiles. She straightly went to Jyothika's system and logged into it, with Jyo's user id and password. Madhavi her fellow colleague came up there..

Madhavi : Hey madhu, what are u doing yaar, in Jyo's system? Are u gonna take over this system after Jyo leaves?

Madhu : haha no no, I am going to install this Trojan in Jyo's machine that would screw up her machine leading to a system crash.

Madhavi (shocked) But why?

Madhu : Mhmm.. Neela madam wants to hold Jyo's resignation so as to distrupt their new company's operations. This is the only way by which we can hold her back legally.

Madhavi : But but Jyo is our good friend, she had helped us a lot during critical times and guided us when we entered as freshers.

Madhu : haha, But you know in a Corporate life, ppl will accept you as a professional only when you are selfish and think only about ur growth..... And I am a true Professional. Madam assured me that I would get an onsite opportunity and a good hike during the next quarter..

Madhu inserted the CD containing the malicious software in Jyo's PC and told Madhavi, Come on Let us crash Jyo's system now.

[ At the moment, they both hear a clap sound. Rajini was coming down the stairs]

Rajini : Lets crash..yea Let's crash [smiles]

Is Crashing a system difficult…., No, recovering from the Crash is…..,

Is finding a bug difficult?, No fixing the bug is…..,

Is Infecting a system with Virus difficult? No, to remove it is…...

Wherever there is a Hacker, there would also be a System Admin [ Saying this, Rajini dives in air and lands near Madhu]

[Both were shocked]

Madhavi : Sorry Rajini, I am very sorry. Only Madhu was trying to do something silly.

Rajini [gets angry] : To get an Onsite opportunity or a salary hike, there are 1000 ways, 1000 places, Please don't do it at the expense of your colleague.

[Madhu immediately changes heart]

Madhu : I am very very sorry for my behavior. I will never repeat this. Kindly forgive me

Rajini : O.K, get Jyo's hard disk to me and replace it with this faulty one…. (hands over a hard disk to Madhu) Now go ahead installing the software that Neela gave u.

Madhu : Yes pa

[ END FLASH BACK ]

Rajini : (victorious smile) Ha ha ha I hope, now there is no problem in getting Jyo's documents rite?

[ A heavy BGM is played in the back as an apparently fuming Neela handed over the documents and papers to Jyothika. They both left the Office]

Genes & Disease

Genes introduction

The human genome is composed of three billion base pairs of DNA. These three billion base pairs are divided up among the 46 chromosomes that are present in every human cell. We inherit 22 autosomal (non-sex) chromosomes and one sex chromosome (X or Y) from each parent. These chromosomes vary in length from 50 million to 250 million base pairs. These 46 chromosomes are found in the nucleus of every one of the bodies trillions of cells. Each chromosome contains many genes, the basic physical and functional units of heredity.

Each gene contains the instructions of how to make a protein or proteins. The exact protein that is made is determined by the order of the DNA bases within the gene. It is believed that there are between 30,000 - 40,000 genes within the human genome. This is far fewer than the number that was predicted originally and only about twice the amount of genes that are present in the fly. Less than 2% of the human genome contains genes (coding regions). The rest of the genome is believed to be involved in providing chromosomal structural support and in regulating the amount of proteins produced in the different cells of the body and at different times. Although each cell in the body contains a full complement of the bodies 3 billion base pairs of DNA, they use the genes selectively.

The genes that make proteins that are needed for basic functions (called housekeeping genes) are active in most cell types. Genes that code for proteins that have more specific functions are only activated in cell types where that protein is needed. It is by expressing different genes and hence producing different combinations of proteins that the different cell types can fulfill their various roles eg. the genes expressed in a brain cell differs from a skin cell which differs from a liver cell. So at any one time a normal cell will activate only those genes that code for the proteins it needs and it will actively suppress all the other genes. Proteins are in fact what perform all of life's essential functions.

Changes in the DNA sequence of our genome - both coding and non coding - can have disasterous consequences. These changes can lead to the production of faulty malformed proteins that are incapable of performing their correct function or over or under production of a protein resulting in the complete disruption of certain cellular processes. These disruptions to protein structure and regulation are what cause many of the common diseases that we observe today (cancers, heart disease, diabetes).For these reasons scientists are excited that for the first time ever they can begin to explore the DNA sequence of our genome, search for the genes and attempt to pinpoint the DNA mutations that lead to common disease states.

ChandraMukhi -- Reloaded ( Part IV )

PART - IV - LAUNCH OF LMRV S/W COMPANY


[ A month later.... At the launch of LMRV Software Company rechristened as LMRVSoft. Only close associates were invited to this simple celebration of the launch.. Jyo's PM Neela and her father, the MD, were called as special invitees. Jyo and Prabhu welcomed them with glee. ]


Jyo : Welcome madam, it is a real pleasure to have you here with us. Please make urself comfortable inside.


[ Neela and her father went inside]


Prabhu ( to jyo) : Hey, Why did u ask them to make themselves comfortable. What would you do if they go and take a nap at the Duroflex cot in the guest room.


Jyo : Oh c'mon prabhu, Don't be stupid!! Go and serve them drinks….


Prabhu: O.K leave it. Have u collected all the documents pertaining to your work in her company? Hope that doesn't become a problem


Jyo : oh never prabhu.... All formalities has been completed, Neela had assured she would get me the papers latest by the End of this week.


[Just then Rajini arrived in his own style]


Jyo : Hello Rajini, We had been expecting you for so long. And you come so late (shows false anger)


Rajini (turns towards the monitor) : I may be a late fix, but I am always a hot fix.


Prabhu : you just keep delivering dialogues. Those who were lesser talented and popular than you, had planned in advance and had started their own organization. But you are still lagging behind.


Rajini : Ha ha ha. Some ppl code by example (searching from Google etc.,)…. But I always lead by example…. I don't follow others…… OK that much for the punch…now shall we go inside?


[ Everyone went inside the company, The Formal inauguration got underway]


M.D (of Jyo's company) : Hey Jyo. You and your hubby can make this new venture a grand success. Good Luck (shakes hands with Jyo)


Jyo : Thanks a lot sir.


[ Neela and MD were about to leave just as Jyo calls Neela ]


Jyo : Maa'm ....


Neela : Yes, Jyo, tell me whatz the matter?


Jyo : Regarding my relieving order and other documents...


Neela : (smiles...) hmm...yes Jyo, I had forgotten to tell that. To honor your commitment and long standing service to our company, we had arranged a grand farewell at our office tomorrow. You must attend that. Rajini, you are welcome too there… I would get your documents at the end of the function, Jyo.


Jyo : oh thanks a lot maa'm. But why all these fanfare?


Neela : [with a cunning smile] oh you deserve it Jyo. I wanted to hold a function for you. You are a marvel. You are a treasure…


[ Neela continued as Rajini stopped her ]


Rajini : Wait maa'm wait. Why are u praising unnecessarily… Tell our good things during Appraisal meeting, tell our problems in a personal meeting…


[ A visibly annoyed Neela walks away ]


Prabhu : Why did you stop her Rajini?


Rajini : Kanna, always understand . If somebody praises someone at their face, it means they are planning a ditch for them.


Prabhu : So do you think she is planning something against us tomorrow?


Rajini : Ha ha ha . Let us wait and see.

(TO BE CONTINUED ..... )

ChandraMukhi --- Reloaded ( Part III )

PART - III - RAJINI vs NEELA

Jyothika patted on Prabhu's shoulder… "Hey Prabhu…. wake up. The flashback is over. Come lets go inside. See him (Rajini), how nicely he is pretending to listen to the story, yet day dreaming. Wake him up also..." She turned to vijayakumar, Sir your story was very nice, but now please give the keys, we need to go inside"

Vijayakumar shrugged his shoulders. "O.K it is up to you to believe or not. Whatever I said were true to the best of my knowledge... " Rajini interrupted, "Ok ok Vijay, cool down, Now don't start writing resumes with declaration statement. letz go inside dude" Vijayakumar accompanied them with the keys, as they went inside the company. There were dusts all around the place. All the systems wore a dirty look. It seemed as if the place was abandoned for years. Rajini went through all the rooms including the room where Chandralekha's condemned system was kept.
Prabhu : The company interior is fine except for the dusts and dirt all around. I think once we clean this place would look great. (turns to Vijayakumar) Sir , can you please arrange for people to clean this place, We would be occupying this by the end of this Aadi** month

[Aadi * - Tamil month, considered generally inauspicious for any new events, occasions such as marriage, house warming etc.,]

[Vijayakumar looks unhappy]

Vijayakumar : Sir, so you have decided to occupy this place. Isn't it? I think you would have got this company at Aadi special discount price. Havent u read papers regarding the frauds related to Aadi purchase?

Rajini : ok ok vijay. Cool down. Do what Prabhu says. Come on Prabhu let's go. I think Joe has to slog today in office. Is it not Joe? So let's hurry

Prabhu : Hey jyo, have u put urur papers at your office?

Jyo : Not yet, I would do that on Monday pa.

[And so they leave the place..But none of them noticed Vijayakumar's eyes as it turned devilish for a moment and then returned to normal]

At this point let us take a break and get to know something about Prabhu – Jyothika 's flash back for a moment.

Both Prabhu and Jyothika were software engineers working in different companies. Jyothika as u know was working for VBA company while Prabhu was working in XYZ company. XYZ company was a client to VBA Company and had been outsourcing some of its works to VBA. Once when Jyothika was on a visit to XYZ company for deploying their application, she also deployed her heart into Prabhu's. Inspite of both working in Software companies for a number of years, without proper planning, they decided to get married as soon as they fell in love. Only after marriage they came to realize the problems that could be faced by a software couple, especially when they were working in different companies. In order to solve some of those problems, Jyothika proposed an idea to start their own firm for a better future.... Prabhu accepted that idea and hence with the help of his influential father, he bought stakes in LMRV Software Company and owned it. Rajini was their family friend and a leading network specialist graduated from Massachusettes Institute of Technology (MIT) in America. He was an Independent Network security consultant for many leading companies including VBA Software Company. His job was to give consultation and ideas regarding network setup, educate network administrators of the company for a stable and secure network and help them related to network issues. Neela , the other character we had seen, was a Sr. Manager in VBA Software company. Being the daughter of the company's CEO , her position , was definitely not a hard earned one.

Location : VBA Software company, Monday Evening

Rajini, scheduled to work in night shift, walked in to office at 6 pm, just as Neela was coming out for the day.

Neela : Hey Rajini, I would like to have few words with you

Rajini : Oh sure, what is the matter

Neela : Rajini, you are very lucky.

Rajini : (confused) : Why?

Neela : I myself am admiring u la, thatz why....

Rajini: (Smilingly.) Oh!!!..

Neela : Looking at our company's market value, salary figures, many ppl, more talented and experienced than you, have applied for the prestigious Sr.Network Admin position. Not only from Chennai but also from US and UK. But I don't want to take any one of them. Our company needs a Network Admin like you. I went through your career profile and was very much impressed. People told me, somewhere in our earlier part of our career when we were juniors, without knowing each other, we had worked together in a project. I don't remember all that. In the rapidly changing IT field, only back up admins would be storing the old data.
(Rajini smiled as Neela continued)

Neela : I don't know why…When you swiftly found out the problem the other day, when everyone of us were thinking it is a software bug, I liked your ability to think quickly.. When you stepped into help for Jyo, I liked ur team spirit, When you took the responsibility in your hand and argued on behalf of other employees, I liked your leadership skills, When u dared to talk straightly to me and even advised me, I liked your communication skills. Above all I liked the enthu with which you fix the problems. Five characters.. These five characters had impressed me a lot. (Pauses and then continues)

I want everything best for our company. From the security we employ at the gate to the software to secure the network I want everything as best. You are one and the best. Having a productive guy like you in our company, we can proudly show to our clients abroad about what we can do. I would like to have you as Sr.Network Administrator working full time for our company. Now tell , aren't u lucky. Even I am appreciating you. Come and collect your offer letter from my dad tomorrow. Probably you would feel shy. I would get the offer letter for you and get it to you tomorrow. O.k? Good boy..

Neela started to leave, saying this. Rajini waited for a moment, then clapped his hand and called "Maa'm.". Neela stopped and waited.

"Just a minute.", Rajini said and walked stylishly towards her.

Neela : What?

Rajini: (softly but firmly) You had told about your wish. Havent asked me yet? (pause) I don't want to join your company as Network Admin…

Neela was shocked as she dropped her company ID down which swiped her out. Just as her card swiped off, a smiling Rajini take out his employee ID and swipes in (BGM and this action is done in a slight slow motion)

Rajini: (smiled and continued) You want a productive employee for your company….. I want a productive company as my employer (in terms of salary). Your company….is not one such.

Neela gets angry and frustrated.

Neela : you don't know about our company. If we plan to employ one we will go to any levels to hire them.

Rajini : (laughs) Babe.., you had listed my 5 characters. I have another character too. Sixth character. This Rajini's sixth character. Don't try to see that. You would feel sorry for that. Neela : Rajini...Rajini : You don't know about me. My Network........... Isolated Network........ Never try to breach it.

Neela : Can I ask you if you are planning to join any other company for full time

Rajini went near her, and said Yeahhhhhhhhhhhhhhhh. and walked into the office.

An upset neela grumbled "Having rejected my offer, let's see how you or the company you are gonna join survive".

(TO BE CONTINUED...)

How genes encode proteins

The sequence of base pairs in a gene determines the protein product that gene can encodeThe genes are located on the DNA which is found in the nucleus of the cell. Protein synthesis happens outside the nucleus in the cytoplasm on the ribosomes. The processes that are involved in making proteins from our genes are called transcription and translation and the molecules that are involved in these processes are called DNA, mRNA, tRNA and proteins. The order of information transfer is DNA to mRNA to protein.

Transcription

Transcription is the process where messenger RNA (mRNA) molecules are synthesised from DNA molecules. Transcription takes place in the nucleus. During transcription only one of the strands of DNA corresponding to a gene (template strand) is copied into mRNA. This mRNA molecule will be complementary to the bases that compose the template strand. The mRNA molecules have short lives. They travel out to the cytoplasm where they direct the synthesis of a protein and then they are destroyed. Transcription depends on complementary base pairings. A pairs with U, T with A, C with G and G with C. Only one of the DNA molecules is transcribed and therefore the resulting mRNA molecule is single stranded. The amount of transcription of any given gene can be directly controlled by the cell. Once the mRNA molecules leave the nucleus and enter the cytoplasm, they are loaded onto the ribosomes. It is at the ribosomes that protein synthesis occurs by a process called translation. The ribosomes are composed of ribosomal RNA (rRNA) proteins and ribosomal proteins.

Translation

Translation is the process where mRNA molecules are translated into proteins at the ribosomes. The nucleotides of the mRNA molecule are read by the ribosome so that each set of three nucleotides called a codon, specifies a single amino acid. Therefore, the first three nucleotides of the mRNA will encode the first amino acid, the second three bases the second amino acid and so on. The rules by which the base sequence of the mRNA molecule is translated into the primary amino acid sequence of a protein are called the genetic code. There are 64 different possible codons (this is because there are 4 bases: A, U, C, G, and each codon has 3 bases, so 43 = 64) and 20 amino acids. Some codons code for the same amino acid and therefore the genetic code is said to be degenerate. No codon codes for more than one amino acid.Three of the codons do not specify the incorporation of any amino acids. These are known as the stop codons - UAA, UAG, UGA. They are found at the end of the mRNA coding sequence and they tell the ribosome to stop translating the message and release the protein. The mRNA is translated from the 5' end and read one codon at a time to the 3' end. Translation usually starts at a start codon (AUG) which codes for methionine. Each successive codon is read and the amino acid incorporated into the protein chain until a stop codon is encountered. The codons in a mRNA molecule do not directly recognise the amino acids that must be incorporated. Instead this process is directed by a group of adapter proteins called transfer RNAs (tRNAs). Every codon, except the stop codons, has its own tRNA molecule. A tRNA molecule has an anti-codon end, which is made of a set of three base pairs. These base pairs can base pair with the complementary codon in the mRNA. The 3' end of a tRNA molecule is attached to an amino acid. In the translation process, a ribosome reads a mRNA molecule codon by codon. At each codon, a tRNA molecule with an anti-codon complementary to that codon attaches to the mRNA. It brings with it the appropriate amino acid that is then incorporated into the growing polypeptide chain. Once the amino acid has been added, the tRNA molecule is released and the ribosome moves onto reading the next codon in the mRNA chain. This process continues until the ribosome reads a stop codon. At this point the ribosome releases the mRNA molecule and the completed protein. The tRNA molecule functions as an interpreter reading codons in the mRNA molecule and translating them into amino acids. In this way, the sequence of base pairs in a given gene determines the amino acid sequence of the protein.

ChandraMukhi -- Reloaded ( Part II )

PART - II - HISTORY OF CHANDRALEKHA
(At the food court)

Jyothika : Hey Rajini, it was a surprise to see u here today. We tried to reach your mobile yesterday but could not get you.. How you came here at the right time?

Rajini : hahaha... (laughs and turns to the screen and tells), When I come, how I come, nobody can guess, but whenever needed I would be right there".

Jyothika : OK OK, I know, Prabhu would have sms-ed you about the new venture we are upto.
Rajini : yeah yeah, i got his message.I have come to help you to set up the new office. I have a small work to be completed here, let's go to Siruseri today evening. Prabhu too would be there at that time

Jyothika : Anyway, Thank god u saved my code, otherwise they would have spoiled my entire work

Evening time..Prabhu, Jyothika and Rajini arrived in a car to inspect their newly acquired office, LMRV Software company. Since the doors were locked, Rajini went to the security cabin and asked for the key from the Chief Security, Vijayakumar. Vijayakumar inquired why he needed the key. Rajini informed him that Prabhu had acquired the company and soon he would resume the operations at LMRV Software Company. Vijayakumar was shocked. "LMRV Company???.......... You mean you had bought that one". Rajini "Yea yea..you are right...What is the matter?". Vijayakumar replied "Sir, that company is haunted. ".

All of them were surprised. "What do you mean" asked a puzzled Prabhu. Vijayakumar continued "yes sir, that company is haunted by some black magic. Dont you see that company remaining locked for months. There is a story behind it. ". Vijayakumar started narrating the story of the mystery behind the LMRV software company.”

"This is a MNC company which had its corporate head office at US. Some years ago, Mr.Babu was appointed Divisional Manager for Chennai office. Babu was a good administrator and an excellent manager. The company's profit increased multi fold under him and the company was getting some plum projects from major US companies.. While looking for a C resource, Babu came to know of one talented girl called Chandralekha…who came first place in the World level conference of Programmers held two years ago. She was just brilliant when it comes to 'C' and PERL programming. If she started coding in C, one can watch it the entire day, (the complexity of the code, very hard to understand for any others). Babu wanted to employ Chandralekha in his company, who he thought would be the best resource for a high risk project he got. But she was already working for HPTR Software Company though at a lower pay. Babu tried all his tricks to get Chandralekha in our company but Chandralekha was steadfast in her decision. Finally Babu pressurized the consultancy through which Chandralekha got into her company and made her join LMRV software company. Chandralekha was unhappy, but unable to do much about that, she started working here. At nights she would stay in the company, secretly doing coding for her old company and send it through internet to them. Babu found it one day when he was analyzing why there were so many Night Taxi requisitions from Chandralekha. He called the old Project Manager of Chandralekha, Mr.Arun to his company, and infront of Chandralekha he made the MD of HPTR company dismiss Arun. Chandralekha was also fired from LMRV Company and both of their names were blacklisted so that they would not be able to join in any other software company. The project that Chandralekha was involved in here was dropped and her computer, in which the entire code she had written was locked and shifted to the godown. Soon after this incident Babu went onsite, But those who were working here began to get affected by many problems, frequent virus attack, hacking attack etc., It was rumored that Chandralekha, as a measure of revenge, had employed some black magic here and the employees working in that company or the computers there would be get affected. It was beginning to show, as almost everyone encountered some or other serious problems in their official and personal life. Gradually, the employees shifted to other companies, and hence the head office was forced to shut down its operations in Chennai. The black magic of Chandralekha was still haunting the company. It could cause problems to anybody who enters this office".Vijayakumar finished this lengthyyyy flashback as Rajini and Prabhu completed another yawn. But Jyothika was keenly listening to this story.........

( TO BE CONTINUED .... )

Chandramukhi -- Reloaded ( Part I )

PART – I – INTRO OF RAJINI

Scene - 1

IT village,Siruseri, Chennai.

The camera flashes at the sign board of the company which read "LMRV Web Technologies". The company wore a deserted look. The doors of this World Wide Web technologies company were locked and upon the ceiling one could see a company wide web, woven by some spiders. It had been 2 months since the company's top management decided to close the operations temporarily and sell the shares of the company . But why would anyone think of selling a profit making company? Thatz a secret...shhhhhhhhhhhhhhh........Come on, let's go inside the room. The door opens (Graphic Effects) and the camera takes us into each of the rooms. Inside one dark room, suddenly a PC switches on automatically and shows up some fearful screensavers with terrorizing musical effects. (Scene ends)

Scene-2 opens with a light music

Prabhu was driving a car. His mobile ringed and he attended the call. At the other end was his P.A, Mr. Thyagu. "Sir, as u desired, I had successfully completed the dealing. LMRV Software Company would be merging with us soon. We had got 75% stake in the company". Prabhu smiled. "Wow, That was a real good news Thyagu. My Jyo would be very happy to hear this news. She was the one who advised me to take over this software company". A delightful Prabhu switched off the call and the scene ends.

3rd Scene opens

"VBA" Software company in Ekkaduthangal, Guindy. All employees were busy working on a Friday morning. Jyothika a.k.a Joe was one among them. You could hear typing sound everywhere which should imply people were busy working. The company's Senior Project Manager Neelambari was also busy with her daily work, i.e playing NFS IV in her system. Things were going smoothly, when suddenly a group of testing people, Guru, Shree and Deva, came running into Neelambari's cabin. As Neela did not expect this, she lost control over the car she was driving and was pushed to second place in the game. She got irritated and shouted at them. "Don't you folks have any manners? Is this the way to come to a PM's cabin?..... Tell me, what is the fuss all about?" One of them replied, "Sorry Madam, we just found a major bug in the Banking project that threw a javascript error. Thatz why we rushed to inform you...." Guru promptly reproduced the bug at Neela's machine. Neela's face grew red in anger upon seeing the bug. "O.K, so track down the bug immediately and fix it at once." Jyotika, whose cubicle was next to Neelambari's, came running to her place, and hold Neela's hands, pleading to her "Maa'm… How would the testing team know about the error or where to fix… Please dont ask them to tamper with the code, I had written. The bug they refer might have caused due to other reasons and not because of the code… Allow me to debug the code, Please..". Before she could stop, Neela slapped jyotika. "Afterall you are a software engineer working under me and you dare to advice me", she shouted and turned to the Testers and said, "What are you waiting for?. Go and do necessary code changes to fix the bug".

So the testers sat down at Neela's system and debugged the application to find out why the bug was occurring. After some time, Guru says, "Madam, the bug is likely due to this particular function in the security module. If I comment the line that calls the function, the bug does not recur"… Neelambari thought for a while and then responded "Go ahead, either delete the function or delete the line that calls the function… I just want the application to work without errors and give an impression to client that all is well with our product". The testers hesitate, "Maa'm this is legacy code. It had been part of previous releases also and worked without errors.. If we break this, it might lead to other problems also." Neelambari shouts, "I don't care about all that... Just go ahead and do what i say".

And hence Deva proceeded to delete a piece of code which he thought would have caused the bug. Jyothika who was witnessing all these incidents happening was sincerely praying that the code change should not happen. Afterall, it was she who coded that module, slogging in the nights, weekends to complete it. As Deva was about to press the DEL button, a hand grabbed Deva's hand and pushed it away. An Intro music with heavy beats started playing. The hand took the network cable that was lying in the floor and fixed it in the server machine that was hosting the database. Apparently it was unplugged while Neelambari was busy playing NFS. The bug did not recur when it was rerun. As the camera moves from his hand to the face we find it was none other than our Superstar Rajini. He flashed a smile into the webcam at the audiences (whistles and claps) and bang, started the intro song.

[ Tune : Padaiyappa starting tune...]

"Work hard and go to onsite..........

Already onsite? (then) work for ur sight*...."

*sight - one's boy friend or girl friend (in Tanglish)

A brief pause and there was silence everywhere. Superstar waited for somebody to ask "who are you man?" so that he could continue the song. But everybody seemed to know our superstar and hence nobody asked anything. At that moment in some other room an interview was taking place and interviewer was asking the candidate. "Tell the simplest form of datastructure in C"

[ Rajini leaves Padaiyappa tune in the middle and picked Devuda Devuda tune]

[Tune : Devuda Devuda tune]

"Array...Array....Array...Array"

"Chicago, Florida,

Software means India..

Java or .NET

we are the king yaar....

English is stronger

We can work longer..

You please continue outsourcing..

(chorus -- REPEAAAATU)

knowledge - vast (u)

less is our cost (u)

We are the IT super power

(chorus -- Sabashuuu)

Intro song ended thus and Rajini went to meet Jyothika .

A visibly peeved Neela who was waiting for the song to finish, started to shout at Jyothika now, realizing Rajini had come to meet Jyotika......... "How many mails do u need me to send reminding the guidelines regarding Personal visitors. Dont u know that Visitors should not be allowed to enter office premises at all...Where is that security", she called out for security "Security....Security.." . Rajini stopped her, "Relax Relax...Neela, why are u getting so angry.. I am not a visitor, I am the Network security expert coming at the behest of ur company chairman for consulting on ur company's network issues. Here is my visiting card". Neela glanced at the visiting card and realized what Rajini said was indeed true.

Rajini continued, "Why were u getting too much irritated, For a Project Manager, commitment can be there, but not commotion , pressure can be there, not panic, should know to talk soft, not shout like this........ On a whole a manager should be a manager and not a damager. You know one thing? A Faulty Design document is the root cause for all Bugs. One should know how to control it. Otherwise the project would be a big failure. Good Bye!!!..Rajini started to leave the place but turns once again (Whiskkk..... special effect)

LAST BUT NOT THE LEAST!! ... A Highly tensioned Project Manager or a lengthy coding Programmer can never be able to complete a project successfully". Whissshkkkk, Rajini salutes in his own style and leaves the place amidst a roaring BGM. Jyothika also used this opportunity to escape the place and they both met at the Food Court.

(TO BE CONTINUED .... )