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:PROPERTIES:
:ID: e5dc49a0-af4f-4546-b1d0-624fd54435ad
:END:
#+title: M13 Globular Cluster
#+filetags: :celestial_objects:
#+STARTUP: latexpreview
Messier 13 is one of the best-known globular clusters in the night sky.
Messier number: 13
New General Catalogue (NGC) number: 6205
Constellation: Hercules
Distance from Earth: 25,100 ly
Discovered by: Edmond Halley in 1714
* Physical Characteristics
- M13 contains several hundred thousand stars.
- The stars are metal-poor and densely packed in the center.
- Stars have low-,etallicity, which means they wre likely formed in environments which fewer heavy metals.
* Notable Features
- M13 has a diameter of about 145 ly.
- M13 contains many blue-stragglers, which are stars that appear hotter and younger than all the other stars.
- Contains many variable stars, especially RR Lyrae variables, useful for determining distance and properties of globular clusters.
- There is onginog research into whether or not M13 contains a central medium-sized black hole.
* Observation and Viewing
- Viewed best in Summer and early Fall.
- Seen in the nothern hemisphere
- Spans 22 arcminutes of the sky. For comparison, the Moon only spans 30 arcseconds of sky.
- Diameter of 145 ly calculated using distance, angular size, and simplifying using the small-angle approximation.

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:PROPERTIES:
:ID: d4ec4698-96e7-4cce-93a3-27e7b9eb5965
:END:
#+title: Genetics: DNA and the Molecular Structure of Chromosomes
#+filetags: :genetics:textbook_notes:
#+STARTUP: latexpreview
* Proof that DNA Mediates Transformation
- Frederick Griffith worked with the bacteria /Streptococcus Pneumoniae/ and tested it with mice. This bacteria has virulent strains (S type) and avirulent strains (P type).
- When injected with S type, the mice died and the bacteria cells were recovered from their corpses.
- When injected with R type, the mice survived, because the cells were avirulent.
- However, when Griffith heat-killed the S type, and then mixed those dead bacteria with the living ones, the mice still died. What happened?
- From the corpses, Griffith actually found living S type bacteria! Something from the dead S type must have transformed the living R type into living S type.
- The hunt for the "Transforming Principle" began.
- Several years later, a team led by Oswald Avery determined that DNA was the molecule that facilitated this transforming principle.
- They used *DNase, RNase,* and *protease* to reach this conclusion. When DNase was used, no living S type colonies were formed, because the DNase destroyed the DNA, the transforming principle.
- In 1952, Hershey and Chase determined that DNA was the source of genetic information to produce bacteriophages in the cells of /E. coli/.-
- They used radioactive sulfur and phosphorus to label the proteins and DNA respectively.
- Upon exposing the cells the phage coats toshearing forces in a blender and then centrifuging the results, it was clear that the substance inside the cell (and thus the substance that coded for new bacteriophages), was DNA.
* Nature of the Chemical Subunits in DNA and RNA
Nucleic acids are compososed of:
1. A *Phosphate Group*
O-
|
O- = P = O
|
O-
2. A five-carbon sugar (called a *pentose*).
In RNA it is *Ribose* and in DNA it is *Deoxyribose*.
In deoxyribose, the second carbon is missing a hydroxyl group and only has a hydrogen bound to it.
3. A cyclic, nitrogen-containing base.
There are *purines*, which have two rings, and *pyrimidines* which have only one ring.
The purine bases are Adenine and Guanine.
The pyrimidine bases are Cytosine, Thymine, and Uracil (usually only found in RNA).
Adenine and thymine form two hydrogen bonds with each other, while cytosine and guanine form three hydrogen bonds.
*Chargaff* found that concentrations of *thymine* was always equal to the concentrations of *adenine*. The same was true for cytosine and guanine.
The base pairs in DNA are stacked about 0.34 nm apart, with ten base pairs per 360 degree turn of the helix.
The two helical strands of DNA are complimentary and *antiparallel*, as well as *right-handed.*
The hydrophobic core of the stacked base pairs inside the DNA molcule offers it much stability.
The DNA described is called *B-DNA* and is the form it takes in aqueous solutions with low concentrations of salt. Most DNA in your cells take on this conformation.
In higher salt concentrations, DNA takes on an *A-DNA* form. A-DNA contains 11 nucleotides per turn instead of 10 and is shorter and thicker.
In addition, *Z-DNA* has been found. Z-DNA has left-handed helical structure and is very G:C rich. It also has 12 base pairs per turn. The purpose of Z-DNA in cells is unclear.
Most DNA in cells are *negatively supercoiled*, meaning that the DNA is cleaved at some attachment point by a specifric enzyme, then rotated 360 degrees /against/ the right-handed direction of its helix.
* Chromosome Structure in Viruses and Prokaryotes
- Most DNA in viruses and bacteria are *folded genomes*.
- they are also negatively supercoiled.
- Bacterial chromosomes contain circular DNA molecules organized into 40-50 loops or domains.
- Each domain can then be negatively supercoiled.
- DNase and RNase can be introduced to relax the folded genome, but in different ways.
* Chromosome Structure in Eukaryotes
- DNA is entangled with many proteins, a complex structure called *Chromatin*.
- *Histones* are proteins that assist in packaging DNA. There is Histone 1 (H1), H2a, H2b, H3, and H4.
- There is scientific evidence that suggests that each chromosome in a eukaryote is just one, masive DNA molecule.
- How do these massive molecules (sometimes measuring several centimeters long) manage to fit in a space half a micrometer in diameter?
*Nucleosomes* are small "beads" that have DNA coiled around them.
- 146 base pairs are wrapped around the nucleosome, which is made up of the histone proteins. This is known because this many base pairs survives the introduction of DNase.
- The DNA winds 1.65 times around this core.
- The core is actually an octamer of histones, two each of each type of histone (excluding H1).
- The width of these ellipsoidal "beads" is *11 nm*.
- Usually all that is required for interphase DNA.
*30 nm Fiber* arises from these necleosome cores being wrapped and stacked around each other.
- chromatin, and the fibers, and expand or contract based on chemical modifications of the histones.
- H1 is the linker histone and can link the nucleosomes together into a tight arrangement.
*Protein Scaffold* can package the fibers into the tightly wound chromosome.
- Forms negatively supercoiled loops and domains.
- happens during *metaphase.*
* Centromeres and Telomeres
- Much of a chromosome contains highly repetitive gene sequences.
- Some of these repititions can move throughout the chromosome, and these are called *transposons.*
- *Centromers* are the central portion of the chromosome which microtubules bind to during mitosis and meiosis.
- The region around the centromere, is the *heterochromatin* and is packaged more tightly than the surrounding *euchromatin.*
- Telomeres are the termini of chromosomes and they consist of highly repetitive sequences upwards of 500 - 3000 times.
- In mammals and vertabrates, the telomere sequence is TTAGGG.
- Telomeres are also known to form *t-loops* where the single-stranded, G-rich 3' end is inserted into the upstream telomeric repeats and displaces the DNA strand previously occupying that space.
- The DNA in t-loops are protected from degradation.

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:PROPERTIES:
:ID: 3a5368b9-d120-40d0-907f-9b59cc53d653
:END:
#+title: Genetics: DNA Replication
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
Two important facts about DNA replication is:
1. It is *semiconservative*
2. It is *bidirectional*
Semiconservative means that when each strand is separated for replication, each strand is used as a template for a new strand.
This fact was determined by Messelson and Stahl. They grew /E. coli/ cells in an environment with heavy $^{15}N$ instead of the more naturally occurring, lighter $^{14}N$ isotope. This effectively makes the nitrogen on the DNA of the cells heavier than normal.
They put the DNA from the cells in a Cesium chloride density-gradient centrifugation process. The heavy DNA sits lower in the solution than lighter DNA.
After several generations in the heavy nitrogen, they transferred them to an environment with lighter nitrogen and they sat there for one generation of replication.
Once put in the density-gradient again, there appeared to still be some heavy DNA, as well as "hybrid" DNA, whicih sat in between the heavy position and the light position.
This essentially confirmed semiconservative replication.
Replication is also bidirectional. A "bubble" forms in the DNA and each replication fork grows away from each other.
* Origins of Replication
In /E. coli/ cells, the replication origin is called the /ori C/.
The /ori C/ has two elements:
- First is a 13 base-pair-long sequence that exists in 3 tandem repeats. They are very AT-rich, and because of having only 2 H-bonds, they serve to separate first, before the rest of the other DNA.
- Second is a 9 base-pair-long sequence that exists in 4 repeats with some other sequences interspersed within. These sequences facilitate the binding of proteins such as *DnaA proteins*.
In Yeast, and other eukaryotes, origin sites are referred to as *Autonomously Replicating Sequences, or ARS.*
In SV40 virus, the origin site is 64 bp-long sequence.
- It is very AT-rich.
- serves as a protein binding site
- T-antigen binds to palindrome 27bp long.
* Bidirectional Replication
- Shnos and Inman made features, almost like physical markers, on a bacteria plasmid, by heating the DNA to a point to where only the AT-righ regions denatured.
- They used these 'landmarks' to visually see which direction the replication fork was travelling.
- from these landmarks, they determined it was bidirectional.
* The Players
- *DNA Polymerase I*
* Also known as Kornberg's enzyme, after the person who first purified it.
* Needs a template and a primer
* Directions is *always* 5' --> 3'
* Utilizes 5' triphosphates of each deoxynucleoside. (dNTPs)
* 2 phosphates get cut off when attached to the backbone, releasing a lot of energy. (See [[id:d4ec4698-96e7-4cce-93a3-27e7b9eb5965][Genetics: DNA and the Molecular Structure of Chromosomes]] For more information)
* *Pyrase* recycles the phosphates.
This enzyme incredibly has 3 different functions:
1. 5' --> 3' polymerase
2. 5' --> 3' exonuclease, meaning it can remove objects in front of it that may be blocking it. Important for removing primers, which will be disussed below.
3. 3' --> 5' exonuclease, meaning it can clip out something incorrect that it placed. The base can drift away bit must receive 3 phosphates before it can bind again.
- *DNA Polymerase III*
* Also needs a template and a primer.
* Contains 20 different proteins.
* $\alpha$ subunits are responsible for polymerase activity.
* $\epsilon$ subunits are responsible for proof-reading.
* $\theta$ subunits bind with $\alpha$ and $\epsilon$ to create the *minimal core*. This in itself does not have function, but it is necessary for structure.
* t subunits link both of the domains together; they are responsible for dimerization.
* $\beta$ subunits physically grab the DNA template. This makes DNAP III much more stable on the strand than DNAP I.
- *Lagging Strand/Leading Strand and more Players*
* composed of *Okazaki fragments*.
* results in covalent breaks between the fragments (since DNAP III cannot remove things in its path like DNAP I, as long as it's in an environment with more than one strand).
* These breaks are remedied by *DNA Ligase.*
* Each fragment must also be primed.
* Leading strand does not have these fragments and thus must only be primed once (however, leading strand on side may be lagging strand on the opposite side. Remember that replication is bidirectional).
* *DNA primase* lays down this primer, *which is made of RNA*. These provide the 3' OH needed by DNAPs.
* DNAP I can go back and remove these primers afterword, using its exonuclease function.
* Unwinding the DNA Strands
- Before replication can take place, DNA must first be unwound, at an estimated rate of 3,000 revolutions per minute. This is accomplished by *DNA Helicase*.
- Opened DNA is kept open by *single-strand DNA-binding proteins, or SSB proteins*.
- *Topoisomerases* remove positive supercoils (also by introducing negative supercoils) created by the rapid unwinding of the DNA strand.
* These come in two classes: Class I and Class II
* Class I removes supercoils by nicking just one strand (no ATP).
* Class II breaks the double-strand and pulls each side out of the coil and reattaches them, thus solving two coils at once. It breaks the strand and literally pulls it through the coil.
* Eukaryotic Differences
- DNA replication restricted to S-phase.
- Multiple replicons per chromosome.
- Two or more polymerases at each fork; RNA primers have to be removed by *RNase H1/RNase FEN-1*. the polymerases lack a 5' --> 3' exonuclease activity.
* Problems with Telomeres
- Occurs on lagging strand.
- At the end of a DNA strand, when RNA primer is cleaned up, there is nothing there to build it up again.
- This creates a *3' overhang*.
- *Telomerase* makes the 3' end longer, using its very own RNA template.
- The RNA template is the same in every telomerase, making it a very repetitive and predictable sequence.
- The lengthening of the 3' end allows for a primer to be put in. Not as much real estate is lost.
- However, there will still be some sort of overhang left over in the end.

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:PROPERTIES:
:ID: 4a34f08a-c003-4d88-968c-10e298ef2793
:END:
#+title: Genetics: DNA Transcription
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
RNA is the vessel upon which transcription takes place.
An intermediary molecule must be needed since DNA never leaves the nucleus but protein synthesis occurs in the cytoplasm. RNA is the molecule that brings the message from DNA to the ribosomes, which contruct the protens. Thus, RNA is a /messenger./
Two scientists, Volkin and Astrachan, used radioactive Phosphorus to:
* Show a burst of RNA synthesis following bacteriophage infection.
* Labeled RNA degraded quickly.
Spiegelman saw that RNA could be made from a viral genome.
This brings us to the *Central Dogma of Biology:*
DNA
|\
v/ transcription
RNA
|\
v/ translation
Protein
There are also many types of RNA, each with specific functions that will be touched on in other notes.
* mRNA: Codes for proteins
* rRNA: structural component for ribosomes and other complexes
* tRNA: Responsible for facilitating the contruction of polypeptide chains
* snRNA: Responsible for assisting in pre-mRNA splicing
* miRNA: used to block the expression of mRNA
* Transcription Overview
- RNA is made first as *pre-mRNA*
- Then, it is spliced/cut/etc.
- Precursors for RNA synthesis are called *ribonucleoside triphosphates* or (RNTPs)
- Only *one* strand of DNA serves as the template for the new RNA
* RNA is complimentary to template only
* This means RNA is *identical* to non-template strand (but with uracil instead of thymine)
- RNA chains can be synthesized /de novo/ *they don't need a primer.*
- Synthesis is in the 5' --> 3' direction. (For more info see[[id:3a5368b9-d120-40d0-907f-9b59cc53d653][Genetics: DNA Replication]])
- The current base in question on a strand is labeled as +1. bases ahead of it (downstream) are +2, +3, etc. Bases behind (upstream) are -1, -2, -3, etc.
Transcription comes in these steps:
1. Initiation
2. Elongation
3. Termination
4. Splicing
5. RNA Editing
* Initiation (From Perspective of Bacteria)
- Binding of *RNA Polymerase*
* Holoenzyme contains 5 subunits
* $\alpha$ subunits are involved in assembly
* $\beta$ subunits contain rNTP binding site
* $\beta$' subunits contain template binding region
* $\sigma$ subunits recognize *promoter sites* (specific sequences that function as the anchor site for RNAP)
- Actual chain synthesis is not recognized to happen at least for another 5-9 base pairs after the promoter sequence. After 10 base pairs, much more stability is acheived. the length of the RNAP enzyme may also contribute to this.
- $\sigma$ subunits prevents random transcriptional initiation.
* -10 and -35 promoter sequence
* -35: TTGACA (non-template)
* -10: TATAAT (non-template)
* After these promoter sequences, there is a /range/ over which RNAP begins to polymerize (Transcription Start Site).
* /The actual RNA is usually begun with a purine, that is, an A or a G./
* So when there a lost of Cs and Ts...you can be confident that the polymerizing began at a conspicuous A or G. In reality it may be harder to visualize the start of an RNA molecule.
- There are four types of sigma factors, which are activated based on the nature of the external environment:
* $\sigma^{70}$: normal factor
* $\sigma^{32}$: heat shock response
* $\sigma^{54}$: nitrogen metabolism
* $\sigma^{23}$: viral infection
- Sigma is released after initiation.
* Elongation
- Unwinding and rewinding
- 2,400 nucleotides/min in /E.coli/
- RNA:DNA hybrid is very short.
- The single-stranded RNA is mostly "grown" off the DNA template strand, threaded through the RNAP.
* Termination
There is Rho-dependent and Rho-independent termination processes.
*Rho-independent:*
* Termination region in DNA
* G:C - rich region followed by a stretch of of T's
* For example: CGGCCCATTTTTTT (non-template)
* A hairpin can form from the strong, tighly-knit interactions between C's and G's. The T's form a weaker bond with A's.
* So essentially it is a strong hairpin region followed by a weak region.
* RNA folds sharply in on itself due to C:G interactions. And what's left (all those U's) is weakly bound to the DNA. Thus, it can detach and terminate easily.
*Rho-dewpendent*:
* 50-90 bp long stretch of C's
* *Rho* binds to the RNA and moves 5' --> 3'
* when Rho "catches" RNAP, it literally pulls the chain free
* Rho appears to chase the RNAP
* However, in prokaryotes, translation happens concurrently with transcription. Eventually the ribosomes encounter their stop sequences and disengage.
* This allows Rho to bind to it and engage the RNAP.
* Transcription in Eukaryotes
- There are multiple Polymerases
* 10 or more subunits each
* RNA polymerase I, II, and III
* RNAP I: Nucleolus, rRNA, not 5S rRNA
* RNAP II: Nucleus, nuclear pre-mRNA (does much of the process as the prokaryote RNAP discussesd above)
* RNAP III: Nucleus, tRNA, snRNA, 5S rRNA
- However, these RNAP's /cannot initiate by themselves./
* Uses transcription factors, TFIID, TFIIA, TFIIB, (Transcription Factor for polymerase II A, etc.)
* *TFIID* binds first. It contains *TBP* which searches for the eukaryotic promoter region called the "Tata-box" (found at -30)
* *TFIIA and TFIIB* then follow, helping TFIID bind more securely
* *TFIIE and TFIIH* then bind. TFIIH can use ATP.
* *TFIIB* defines the directionality of the transcription. If you think about this, this also mean it determines which strand is the template and which is the non-template. Sometimes, divergent transcription can happen. The purpose is not known, but it may actually serve to help the process. TFIIB also acts as a molecular "ruler" for RNAP II.
- RNAP I promoters are typically bipartite. Both are G:C-rich. These are not "Tata-boxes"
- RNAP III promoters are typically /downstream/ of the TSS. This means it binds to the DNA before its promoter sequence, meaning that sequence is actually included on the fabricated pre-mRNA strand.
* mRNA Processing
- 7-methyl guanosine cap
* Initiation of translation
* Protects growing mRNA strand
- Poly(A) Tail
* Protects mRNA from degradation]
* Aids in transportation
* Added /after/ transcription
* Splicing
- Removal of introns from pre-mRNA
- The recognizable features of introns are given below
5' GT........UACUAAC.........AG 3'
GT and AG can be thought of as "bookends" of the introns.
- These introns don't have caps or tails, so they are digested.
*Type 1 Splicing*
* Shape driven
* Requires endonuclease and ligase
* Enzymes recognize shape and clip intron by location, not by base-pair.
*Type 2 Splicing*
* No protein activity
* Requires guanosine with 3' OH end
* Two phosphodiester bond transfers
*Type 3 Splicing (Spliceosome)*
* Involves spliceosomes, which are RNA/protein structures
* U1, U2, U4, U5, U6.
* *U1* binds to 5' splice site (GT)
* *U5* binds to other end (AG)
* *U2* recognizes the UACUAAC sequence on the intron
* *U4* and *U6* do not make contact with the RNA but provide structure.

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:PROPERTIES:
:ID: 0a889e6f-d7d5-4c7a-b8d6-e983d6f37d45
:END:
#+title: Organic Chemistry: Structure and Stereochemistry of Alkanes
#+filetags: :organic_chemistry:textbook_notes:
#+STARTUP: latexpreview
* IUPAC or Systematic Names
To name and Alkane we follow 4 general rules:
1. Find the longest continuous chain of carbon atoms, and use this chain as the base name.
2. Number the longest chain, beginning with the end nearest a branch
3. Name the substituents on the longest chain (as alkyl groups). Give the location of each substituent by the number of the main-chain carbon atom to which it is attached.
4. When two or more substituents are present, list them in alphabetical order. When two or more of the /same/ alkyl group is present, use the prefixes /di, tri, tetra, etc./ (ignored in alphabetizing) to avoid having to name the alkyl group twice.
* General Alkane Properties
- Alkanes are nonpolar and generally are not too reactive.
- Most alkanes are refined from petroleum by distill fractions.
- *Catalytic Cracking* can break down larger, less-useful hydrocarbons into smaller, more useful ones. Hydrogen gas is used in the process.
* Newman Projections
- Newman's projections are used to analyze the different *conformations* of a molecule, and in this context, alkanes.
- Newman projections look head-on through a particular carbon-carbon bond. Based on the angles between substituents on the molecule, the energies and thus the stabilities of each conformation can be analyzed
- *totally eclipsed* conformation have the highest energy (and are less stable) because the substituents are all aligned.
- *gauche* confomration is 60 degrees offset from totally eclipsed.
- *eclipsed* is when a substituent and a hydrogen are aligned, instead of two substituents being aligned.
- *anti* is when the substituents are offset from each other as much as possible. This represents the lowest energy and thus the highest stability.
- It is important to note that at room temperature, molecules have enough energy to move through all of the possible conformations, but for the majority of the time, the bonds would be in the anti conformation.
- Another useful concept is the *torsional energy*, which is the energy needed to break free from high-energy conformations. It is usually measured in kJ/mol.
- When molecules are in a totally eclipsed conformation, something called *steric strain* happens. This strain arises from the electron clouds of the hydrogens on the substituents that are so close to each other that they begin to repel one another. Steric strain is responsible for how many molecules align themselves in space. It also has an effect of the reactivity of molecules.
* Cycloalkanes
- Cycloalkanes have many factors that determine their stability.
- These are *angle strain* and *torsional strain* (which arises from differences in torsional energy)
- Both of these aspects contribute to the total *ring strain* of the cycloalkane molecule.
- In cyclopropane and cyclobutane, the angles of the sp3 hybridized orbitals are forced to 60 and 90 degrees respectively. This literally reduces the contact between each carbon's sp3 hybrid orbital in relation to the next. Additionally, the bonds experience a totally eclipsed conformation.
- Larger cycloalkanes like cyclohexane have less angle strain and are arranged in staggered conformations.
- The combustion energy can be determined through bomb calorimetry and then that value can be divided by the number of *methylene groups* (CH2 groups) to determine how unstable each group is and thus the total instability or stability of the molecule.
- The most stable form of cyclohexane is the *chair formation*. Slightly less stable but still often found is the *twisted boat formation*
- The molecule fluctuates between these formations many times in a fraction of a second.
- In these formations, there are *axial bonds* and *equatorial bonds*.
- when these cycloalkanes have substituents, it is preferred that these substituents occupy equatorial bonds so as to limit the steric strain between themselves and the molecule.
- The molecule can cycle through the chair-formation and the twisted-boat formation to accomodate this.

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:PROPERTIES:
:ID: cf824a5f-d7a6-45c5-82e5-d5de3241d3fa
:END:
#+title: Organic Chemistry:The Study of Chemical Reactions
#+filetags: :organic_chemistry:textbook_notes:
#+LATEX_HEADER: \usepackage{chemfig}
#+STARTUP: latexpreview
For more general information discussing chemcial reactions see[[id:0856b9fd-822f-4cc7-9ec4-cdcc38c01b5e][Chemistry the Central Science: Chemical Kinetics]]
[[id:410d2780-127b-4972-ae22-34d9cdbb750b][Chemistry the Central Science: Chemical Equilibirum]]
[[id:a8356651-4155-4ed4-8129-d13ca9b448f7][Chemistry the Central Science: Additional Aspects of Aqueous Equilibrium]]
* Reactions Involving Free Radicalis
What is a free radical? /A free radical is a very reactive species with an odd number of electrons./
Often, free radicals can be made from halogens, using heat and light.
Then, these free radicals can literally /abstract/ a hydrogen from a hydrocarbon. Hydrogen abstraction is different than protonation, because in protonation, the proton itself is all that leaves the substance.
However, in hydrogen atom abstraction, both the proton and its respective electron is taken from the species. Thus, there is a single electron left at with the carbon in the hydrocarbon, creating a free radical.
Consider the overall reaction:
$\chemfig{H-C(-[2]H)(-[6]H)-H} + \chemfig{Cl-Cl} \longrightarrow \chemfig{H-C(-[2]H)(-[6]H)-Cl} + \chemfig{H-Cl}$
Reactions involving free radicals follow a specific pattern:
1. Initiation
2. Propagation
3. Termination
Within the context of these steps, let's analyze the reaction given above:
*Initiation:*
\begin{equation*}
\chemfig{Cl-Cl} \longrightarrow \chemfig{\charge{0=\.}{Cl}} + \chemfig{\charge{0=\.}{Cl}}
\end{equation*}
In this step, heat and light are used to break a chlorine molecule into two free radicals.
*Propagation:*
\begin{equation*}
\chemfig{H-C(-[2]H)(-[6]H)-H} + \chemfig{\charge{0=\.}{Cl}} \longrightarrow \chemfig{H-\charge{0=\.}{C}(-[2]H)(-[6]H)} + \chemfig{H-Cl}
\end{equation*}
\begin{equation*}
\chemfig{H-\charge{0=\.}{C}(-[2]H)(-[6]H)} + \chemfig{\textcolor{green}{Cl-Cl}} \longrightarrow \chemfig{H-C(-[2]H)(-[6]H)-\textcolor{green}{Cl}} + \chemfig{\textcolor{green}{\charge{0=\.}{Cl}}}
\end{equation*}
We can see from the two propagation steps that free radicals are always being created in a type of chain reaction.
*Initiation steps* generate a reactive intermediate.
*Propagation steps* see the reactive intermediate react with a stable molecule to form a product and another reactive intermediate, allowing the chain to continue until the supply of reactiants is exhausted.
*Termination steps* are side reactions which destroy reactive intermediates and end the process
*Homolytic cleavage* occurs when a bond breaks and each atom retains one electron from the bond. Thus, homolytic cleavage yields free radicals.
*Heterolytic Cleavage* occurs when a bond breaks and one of the atoms takes all the electrons. Thus, heterolytic cleavage yields ions.
* Transition States
- Transition states represent the highest energy that the components of a reaction go through.
- In transitions states, bonds are being dissolved at the same time bonds are being formed.
*Hammond's Postulate* says that /related species that are closer in energy are also closer in structure. The structure of a transition state resembles the structure of the closest stable species./
Hammond's postulate can be used to explain the behavior of alkane halogenation. For example, Flourine is very reactive, and so is chlorine, but bromine is more selective about where it froms bonds on an alkane and the reaction happens very slowly. Iodonation (with iodine) rarely happens in this manner (via free radical halogenation) if not at all.
If we look at chloronation, the reaction is very exothermic. This means the transition state is actually closer in energy to the reactants. Thus, there is not much energy difference between the two transition states. This then means that chlorine cannot be as selective.
However, with bromonation, the reaction is endothermic, which means the transition state resembles the products. This means that the hydrogen bond is nearly broken in the transition state. This allows bromine the "chance" to be selective about where it forms its bonds (i.e. the most substituted) since highly substitued carbons form more stable free radicals.
* Reactive Intermediates
- These are short-lived species that react quickly when they are formed. Thus, they never exist in high concentrations.
*Carbocations*
\begin{equation*}
\chemfig{H-C^+(-[2]H)(-[6]H)}
\end{equation*}
* Compounds with a carbon that has a positive charge.
* No nonbonding electrons
* /sp2/ hybridized
* Trigonal planar geometry
* Since it has one completely empty p-orbital, it is a very stron electrophile
* Stabilized by alkyl substitutions
- 3 > 2 > 1 > methul
- tertiary > secondary > primary > methyl
* This happens through the *induction effect* and *hyperconjugation*, which arises when adjacent alkyl groups' hybrid orbitals align so they overlap with the carbocation's p-orbital.
* Unsaturated carbocations are stabilized by resonance.
*Free Radicals*
\begin{equation*}
\chemfig{H-\charge{0=\.}{C}(-[2]H)(-[6]H)}
\end{equation*}
* Compounds with only one electron occupying the p-orbital
* /sp2/ hybridized
* Stabilized by alkyl substitutions
- 3 > 2 > 1 > methyl
* Can also be satisfied by resonance in unsaturated compounds
*Carbanions*
\begin{equation*}
\chemfig{H-\charge{0=\:}{C^-}(-[2]H)(-[6]H)}
\end{equation*}
* Trivalent carbon with nonbonding electrons, giving it a negative charge
* Since it is electron-rich, it acts as a nucleophile.
* /sp3/ hybridized
* trigonal pyramidal geometry, resembling tetrahedral but with lone-pair
* Order of stability is opposite from the previous two. Less substitution is more stable.
- methyl > 1 > 2 > 3
* Stabilized by resonance. Carbonyl groups and pi bonds adjacent to carbanion serve to delocalize the nonbonding electrons
*Carbenes*
\begin{equation*}
\chemfig{\charge{0=\:}{C}(-[3]H)(-[5]H)}
\end{equation*}
* Uncharged, divalent carbons, with a pair of nonbonding electrons
* /sp2/ hybridized
* trigonal planar geometry
* unshared pair of electrons occupies one of the /sp2/ orbitals.
* Since it has a lone pair of electrons and an empty p-orbital, it can act as a nucleophile or an electrophile.

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:PROPERTIES:
:ID: 409e700e-e5de-402d-8e46-a063de488216
:END:
#+title: Organic Chemistry: Isomers and Stereochemistry
#+filetags: :organic_chemistry:textbook_notes:
#+LATEX_HEADER: \usepackage{chemfig}
#+STARTUP: latexpreview
Stereochemistry is the study of the three-dimensional structure of molecules and atoms in space.
For more information on stereochemistry for alkanes, see: [[id:0a889e6f-d7d5-4c7a-b8d6-e983d6f37d45][Organic Chemistry: Structure and Stereochemistry of Alkanes]]
There are *constitutional isomers* and *stereoisomers*.
Constitutional isomers differ only in the bodning sequence of the carbons in the chain. Stereoisomers differ in the arrangement of atoms in space.
* Chirality
Chirality is defined by taking the mirror image of an object. If the mirror image of an object is nonsuperimposable on the original object, the object is said to be *chiral.*
Chirality can also be defined as "handedness" (like right hand versus left hand)
In chemistry, nonsuperimposable mirror-image molecules are known as *enantiomers*.
A chiral compound /always/ has an enantiomer.
*Assymetrtic carbon atoms* are carbons that are bonded to four different, unique groups. An assymetric carbon atom is a type of *chiral center*, which is the name of any atom bonded to four groups that form a nonsuperimposable mirror-image. Chiral centers are then part of an even broader category called *stereocenters* which are atoms at which the interchange of any two of its groups results in a stereoisomer.
/Any molecule that has an internal mirror plane of symmetry cannot be chiral,/ even though it may contain assymetric carbon atoms.
* (R) and (S) Nomenclature of Isomers
How do we distinguish between stereoisomers? We use the *Cahn-Ingold-Prelog* system. Here's how it works:
* Assign a relative priority to each group bonded to the carbon atom.
- Atoms with higher atomic numbers have higher priority.
- Heavier isotopes have higher priority.
- In the case of ties, use the next atoms along the chain to determine priority.
- Treat double and triple bonds as if each were a bond to a separate atom.
* Using a drawing, place the fourth priority group in the back. Drawn an arrow from the first priority group, through the second, and to the third.
* If the arrow is clockwise, the assymetric carbon is called (R), /rectus/, latin for "upright."
* If the arrow is counterclockwise, the assymetric carbon is called (S), /sinister/, latin for "left."
* Plane Polarization
Different isomers can shift the plane of polarized light. If one isomer shifts light 5 degrees clockwise, the anantiomer will shift the light the same amount, 5 degrees, but counterclockwise. This is called *optical activity.*
A *polarimeter* meausers the shift of the plane of polarization due to isomers. The light travels through a reaction cell and cast through a filter. Optical activity depends on the length of the reaction cell and the concentration of compounds within the cell, according to the following equation:
\begin{equation*}
[\alpha] = \frac{\alpha (observed)}{c * l}
\end{equation*}
Where c is the concentration and l is the length of the cell in /decimeters./
Compounds that rotate light clockwise are labelled as "d" while those that shift light counterclockwise are labelled as "l."
* Racemic Mixture
- Racemic mixtures are mixtures that contain precisely equal amounts of R and S isomers of the same compound.
- Racemic mixtures are thus not optically active.
- Optically inactive reactants cannot produce optically active products. Any chiral products must be yielded in a racemic mixture.
We consider a molecule to be achiral if its chiral conformations are in rapid equilibrium with their mirror-image conformations. For more information on conformations of cyclic alkanes see[[id:0a889e6f-d7d5-4c7a-b8d6-e983d6f37d45][Organic Chemistry: Structure and Stereochemistry of Alkanes]]
* Fisher Projections
- These projections allow for the easy determination of stereoisomers.
- Imagagine that you are looking at an assymetric carbon atom from below.
- Fisher projections appear like a cross, with the vertical bond going away from the viewer and the horizontal bonds coming towards the viewer.
- 180 degree rotation of projections is allowed.
- 90 degree rotation is not allowed, because of the convention stated above.
- If the Hydrogen is on a horizontal bond (coming towards the viewer), then whatever isomer that assymetric carbon is /in the fisher projection/ (R or S), then the actual orientation is /the opposite/ of that.
* Diastereomers
- *Diastereomers* are stereoisomers that are not mirror images of each other. Therefore, they are not enantiomers.
- A common example of diastereomers, are /cis and trans/ isomers.
- diastereomers with compounds with more than one chiral carbon are easily seen in fisher porjections. They usually arise from one interchange of groups on one chiral carbon atom.
- Unlike enantiomers, diastereomers have differing physical properties, usually in boiling point and dipole moment. Therefore, they can be separated by distillation, recrystallization, and chromatography.
* Meso Compounds
- *Meso compounds* are achiral compounds that have chiral centers in them.
- Most of the time, meso compounds contain an internal plane of symmetry.

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:PROPERTIES:
:ID: 6f237745-5dcb-49d2-a5ba-1125d2003e4d
:END:
#+title: Genetics: The Cell Cycle
#+filetags: :genetics:lecture_notes
The cell cycle consists of several phases called *G1, S, G2 and Mitosis*.
The first three cycles belong to *interphase*.
Human cells have 46 individual chromosomes that come in pairs. Therefore, we have 23 pairs.
However, we are *diploid* in that there are only 23 /types/ of chromosomes but they are /duplicated./
In addition to this, each of the 46 chromosomes have a *sister chromatid*, resulting in 92 "sticks" of DNA.
Chromosomes are numbered by length.
They are distinguished by location of the *centromere* the central point where the two sister chromatids of a chromosome meet.
There are 22 *autosomes* and 1 *sex chromosome* in the human genome.
* Mitosis
Mitosis consists of *prophase, metaphse, anaphase, and telophase*.
DNA is replicated in interphase to prepare for mitosis.
*Prophase*:
* Centrosomes (the structures that build microtubules and spindle fibers) duplicate and begin to move apart.
* Replicated chromosomes begin to condense and are held together by centromere.
* Nucleolus disperses
*Metaphase*:
* Nuclear envelope begins to break down.
* Chromosomes move to *metaphse plate*
* Kinetochore and polar microtubules form from centrosomes
* Polar microtubules brace spindle poles so that they don't flow towards each other when the kinetochore microtubules pull chromosomes apart.
*Anaphase*:
* Kinetochore microtubules shorten while polar microtubules lengthen.
* Results in *chromatid disjunction*.
*Telophase*
* Neclear envelope reforms
* Chromosomes decondense
* Undoing of prophase
Meiosis is similar to mitosis except that in the first step, it's not the sister chromatids that are separated, but whole chromosomes. They arrange im pairs along the metaphase plate.
Additionally, recombinants form prior to this step. This is when DNA is mixed between homologous chromosomes.

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:PROPERTIES:
:ID: 7a74d2b5-50ff-4eb8-bfdb-2d07b0ce1585
:END:
#+title: Genetics: Mendelian Genetics
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
Mendel was a monk who experimented with plants such as the pea plant.
From his experiments, he determined several characteristics of inheritance. In fact, he postulated three key principles:
*Principle 1:* /In heterozygotes, one allele may conceal the presence of another./
*Principle 2:* /Two different alleles segregate from each other during the formation of gametes./
*Principle 3:* /Alleles of different genes assort independantly of each other./
- Mendel crossed pure-breeding tall pea plants with pure-breeding dward pea plants.
- It turned out, that when he did this, /all/ of the progeny were tall. These progeny were then self-fertilized.
- The offsrping of the self-fertilization resulted in both tall and dwarf plants. The ratio of tall to dwarf was 3:1
What Mendel did here was a *monohybrid cross*.
The phenotypic ratio for a monohybrid cross is *3:1*
Likewise when a *dihybrid cross* was performed, i.e. a cross that tested two genes (each being heterozygous), a ratio of 9:3:3:1 was observed.
The phenotypic ratio for a dihybrid cross is *9:3:3:1*
The 9 dominant phenotypes often have differing genotypes.
The absolute frequencies of the phenotypes are found by dividing by the total (in this case 16.)
It is important to note Mendel's assumptions while performing these experiments:
1. Genes segregated into alleles
2. These segregations are not linked to each other
Mendel was wrong in the second assumption. Some genes are in fact linked. (see[[id:8c1675c6-1b10-4fb4-9d77-25cd03a373cd][Genetics: Gene Linkage]])
* Test Crosses
Test crosses are performed to test whether a dominant phenotype contained a heterozygous or homozygous genotype.
Test crosses always use an individual that is /double recessive./
If the results include a 1:1 ratio of heterozygote dominant:recessive, the individual being tested must have been a heterozygote.
For example, if an individual has the genotype G g W w and is crossed with g g w w, the resulting phenotypic ratio will be *1:1:1:1*
* Chi-Square Test
A simple test that is done to measure if the error in an experiment is expected or above expected and in that case, not accepted.
It is given by the following formula:
\begin{equation*}
X^2 = \sum \frac{(observed-expected)^2}{expected}
\end{equation*}
As long as the value of the Chi-sqaure method is less than the 5% critical value of the experiment, the error is considered acceptable.
The 5% critical value depends on the *Degrees of Freedom* of the experiment. This can be found as shown below:
\begin{equation*}
Degrees of Freedom = Number of Phenotypes - 1
\end{equation*}
If there are 4 possible phenotypes for a given procedure, then there are 3 degrees of freedom.
Degrees of Freedom|5% Critical Value
1 | 3.841
2 | 5.991
3 | 7.815
* Binomial Probability
Only for *2* phenotypic classes
Takes into account birthing order/all possible patterns
Let's say that there is a family of 4 children. What is the probability that 2 kids will be dominant and 2 will be recessive?
Do a fraction for /every kid./
The odds of being dominant are 3/4 (because of the 3:1 ratio)
The odds of being recessive are 1/4.
The method of getting number of patterns is shown below:
\begin{equation*}
\frac{4(kids)!}{2(dominant)! 2(recessive)!}
\end{equation*}
This expression simplifies to 6.
Thus,
\begin{equation*}
\left(\frac{3}{4}\right)^2 \times \left(\frac{1}{2}\right)^2 \times 6 = \frac{54}{256}
\end{equation*}
If a problem deals with an "at least" type of language, do each case separately. Then, add up all the results to get the answer.

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:PROPERTIES:
:ID: 71224ae5-3568-453a-a33f-14c2e8fa4f34
:END:
#+title: Genetics: Expansion of Mendelian Genetics
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
Mendel set the stage for the foundations of the study of genetics. However, not everything is so simple, and many exceptions have been found to Mendel's principles.
These will be discussed here.
For more information on Mendelian genetics see[[id:7a74d2b5-50ff-4eb8-bfdb-2d07b0ce1585][Genetics: Mendelian Genetics]]
* Incomplete Dominance
This is where the heterozygote actually has a different phenotype than the homozygote, or, true-breeding.
This shows up when crossing red and white flowers: The het will actually have pink flowers.
Explained by the concept of *gene product.* If just one allele is enough to make the necessary proteins neede to have the phenotype, then the phenotype will look normal. This is *Haplo-sufficient*.
However, if one allele does not make enough proteins to produce desired phenotype, a /mix/ forms. This is *Haplo-defficient*.
* Codominance
Heterozygous alleles each display a dominant phenotype.
Common example is blood type.
For example, both $I^AI^A$ and $I^Ai$ produce blood type A. The same can be said but for type B.
$I^AI^B$ produces blood type AB.
$ii$ produces blood type O.
* Epistasis
Genes can interact in a linear or parallel pathway.
A gene is said to be epistatic if it conceals the presence of another mutant allele.
for example:
\begin{equation*}
\overrightarrow{Gene A}\;\;\;\overrightarrow{Gene B}\;\;\;\overrightarrow{Gene C}
\end{equation*}
Even if Gene C is dominant, if Gene B is 'broken' or double recessive, Gene C will /never be reached./
Take a look at the below pathway:
\begin{equation*}
White\;\;\;\overrightarrow{Gene A}\;\;\;Pink\;\;\;\overrightarrow{Gene B}\;\;\;Orange\;\;\;\overrightarrow{Gene C}\;\;\;Red
\end{equation*}
Let's say that a flower with the genotype A a B b C c is self fertilized.
We can determine the odds for each flower color phenotype.
White: Gene A must be broken, so all we need is $aa$
The odds are then 1/4 (once again because of the basic 3:1 ratio)
Pink: We can have either $Aabb$ or $AAbb$.
The odds are 3/4 times 1/4 which equals 3/16
Orange: We can't have Gene C working, so we need $A-B-cc$
The odds are 3/4 times 3/4 times 1/4 which equals 9/64
Red: We need all genes working, so $A-B-C-$
The odds are 3/4 times 3/4 times 3/4 which equals 27/64
* Penetrance and Expressivity
Incomplete penetrence is when a trait doesn't fully show up in an individual with the appropriate genotype.
Expressivity refers to when traits are not manifested uniformly (or to the same extent) in affected individuals.

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:PROPERTIES:
:ID: 82f37229-e178-4881-88a1-b9ee229b339d
:END:
#+title: Genetics: Sex-Linked Chromosomes and Traits
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
Thomas Morgan worked with the eye-color gene in fruit flies, which is on the X-chromosome.
He crossed red-eyed females with red-eyed males.
To his surprise, /all/ the females had red eyes but only 50% of the males had red eyes.
He concluded that eye-color was a *sex-linked trait* because it only occurs on the X chromosome. The cross can be depicted as $w^+w \times w^+$
Since male fruit flies only have one X chromosome 50% owuld get the $w^+$ and the other 50% would get $w$
His assistant, Calvin Bridges, then crossed white-eyed females with red-eyed males and found red-eyed male offspring and white-eyed female offspring.
These outcomes were not expected, and he called them *exceptional flies*.
The white-eyed female offspring could be explained with the fact that the females kept both recessive alleles. This resulted from *anueploidy.* (see[[id:7c91735d-5d8a-41d6-afac-058361daf3ad][Genetics: Types of Ploidy]])
* Sex-linked genes in Humans
A common example is red/green color blindness.
Affected individuals are male. Results from a $X^cY$ genotype.
Since the Y chromosome does not have many genes, it does not contain a gene that could potentially be dominant.
Therefore, the male is *hemizygous.*
* What Determines Sex?
Usually, XX means female and XY means male.
Specifically, the *SRY (Sex-Determining region of Y)*
- If missing, improper development occurs.
- Contains *TDF (Testes Determining Factor)* a gene that contributes to the growth of testes.
- *Tfm (Testicular feminization)* is a condition that only affects people with testes. It causes them to not be fully developed, sometimes even causing a female phenotype.
In insects, *denominator proteins* can inhibit *numerator proteins*. This relationship affects the sex of the organism. This is why it is a /ratio/ of chromosomes that determines sex in this case.
* Gene Dosage
*X-inactivation*
- X chromosomes inactivate and form *Barr Bodies* until there is only one active X chromosome.
- All cells that come from a given parent cell will have the same X chromosome inactivated as that parent cell.
- Inactivation is random to start with, however.

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:PROPERTIES:
:ID: 7c91735d-5d8a-41d6-afac-058361daf3ad
:END:
#+title: Genetics: Types of Ploidy
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
Here we discuss the nature of different types of ploidy, such as polyploidy and anueploidy.
* Cytogenetics
Chromosomes are identified by size, shape, and banding pattern.
There are short and long arms on chromosomes. The short arm is labeled /p/ for /petite/ and the long arm i referred to as /q/.
Location of the centromere is also considered: *Metacentric* (in the middle), *submetacentric*, *acrocentric*, and *telocentric* (at the very end).
* Ploidy
- Euploid = Complete set of genome; "normal"
- Polyploid = Having multiple sets of genome; more than 2
* Too many copies of DNA result in inability to split cell to make gametes (infertility)
* Fertile polyploids are rare, but can occur in certain plants.
- Aneuploidy
* Refers to numerical change in the number of chromosomes in a certain part of genome.
* *Hypoploid* means that a chromosome is underrepresented in a cell.
* *Hyperploid* means that a chromosome is overrepresented in a cell.
* *Trisomies* (when there are three copies of a chromosome in a human genome) can occur for chromosomes 13, 18, 21, and sex chromosomes.
* All other trisomies are embryonic lethals!
* Anueploidy results from *nondisjunction*.
* Anueploid Conditions of the Sex Chromosomes
Klinefelter Syndrome (XXY)
- Usually sterile, because there is "traffic jam" along metaphse plate (see[[id:6f237745-5dcb-49d2-a5ba-1125d2003e4d][Genetics: The Cell Cycle]] )
- Caused by nondisjunction in either mother or father.
- X inactivation occurs (see[[id:82f37229-e178-4881-88a1-b9ee229b339d][Genetics: Sex-Linked Chromosomes and Traits]] )
Triplo-X (XXX)
- Limited fertility
- Hyperploid condition
Turner Syndrome (X)
- Almost always sterile
- Reduced viability in the womb
- This actually means that the normally inactivated X chromosome is actually needed or helpful in some way.
- Problem with development leads to infertility.
Somatic *mosaic* Turner females can have cells that are normal and cells that are Turner.
- There are no Barr bodies.
* Chromosomal Rearrangements
Inversions
- *Pericentric inversion* includes centromere. Changes length of chromosome arms.
- *Paracentric inversion* does not include the centromere. Chromosomes loop themselves to line up with homologous pair in this case.
Translocations
- Genes moved between chromosomes.
- DNA exchanged between nonhomologous chromosomes; can cause a problem.
- Still technically euploid, no ploidy issues
Triplo-X (XXX)
- Limited fertility
- Hyperploid condition
Turner Syndrome (X)
- Almost always sterile
- Reduced viability in the womb
- This actually means that the normally inactivated X chromosome is actually needed or helpful in some way.
- Problem with development leads to infertility.
Somatic *mosaic* Turner females can have cells that are normal and cells that are Turner.
- There are no Barr bodies.
* Chromosomal Rearrangements
Inversions
- *Pericentric inversion* includes centromere. Changes length of chromosome arms.
- *Paracentric inversion* does not include the centromere. Chromosomes loop themselves to line up with homologous pair in this case.
Translocations
- Genes moved between chromosomes.
- DNA exchanged between nonhomologous chromosomes; can cause a problem.
- Still technically euploid, no ploidy issues.
- Because of how chromosomes line up, anueploidy can occur in daughter cell after mitosis/meiosis (see[[id:6f237745-5dcb-49d2-a5ba-1125d2003e4d][Genetics: The Cell Cycle]] )

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:PROPERTIES:
:ID: 8c1675c6-1b10-4fb4-9d77-25cd03a373cd
:END:
#+title: Genetics: Gene Linkage
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
We know come back to the topic of Mendel's assumption regarding genes: That they are not linked together in any way. It turns out that many genes in fact are linked together.
Independent assortment may not always be the case.
* Linkage
Linked genes can be separated by "crossing over"
* Cytologically - To form *chiasmata*
* Genetically - To form *recombinants*
Much of our analysis will be to determine how linked together certain genes are and thus how likely it is for them to crossed/swapped/separated.
What if the observed is so different from the expected, that the Chi-Squared analysis does not work? (see[[id:7a74d2b5-50ff-4eb8-bfdb-2d07b0ce1585][Genetics: Mendelian Genetics]])
This is probably the result of gene linkage.
We can determine the degree of how much certain genes want to stay linked together.
For these analyses, it can be assumed that linked genes are on the same stick of DNA.
When crosses happen with linked genes, less than 50% of the offspring are *recombinants*.
Most of the genotypes observed contains the same unaltered chromosomes from one of the parents. These are referred to as *parental*.
A *low frequency* of recombinant offspring suggests gene linkage.
For 2 linked genes the frequency is:
\begin{equation*}
Frequency = \frac{Recombinants}{Total}
\end{equation*}
This yields the frequency in units of *Morgans*. If the frequency was 0.18 Morgans, that means the genes will be separated 18% of the time.
Use notation such as $AB/ab$ to denote genes linked on DNA.
When offspring receive these chromosomes it is refered to as *coupling*.
When offspring receive separated/recombinant chromosomes, $Ab/aB$, it is referred to as *repulsive*.
* Three Linked Genes
There are now 8 chromosomal possibilities with 3 linked genes.
If sex-linked, and father has recessive, that is the only chromosome he can give. Most of the offspring will receive chromosomes from the mother /as is./
Two biggest observed numbers are the parental classes.
The rarest event is a *double* crossover in the gene. Sometimes, it is important to note, that /none/ of the offspring have this genotype.
1. Determine the order of the genes on the DNA since gene order is often not certain.
* Can be found by comparing the double crosses with the parental chromosomes. The only different gene when comparing them is the gene that come in the /middle/. The order is then found.
2. Calculate distances between genes in Morgans
* Only look at two genes at a time. /Ignore/ the other one.
* Add up numbers of observed genotypes where the two observed genes are the same as they are on the parental chromosome. Divide by the total to find the Morgans.
* To find total distance, add up all values from preceeding step.
3. Find *theoretical rate* of double crosses by multiplying the two rates together for each single cross (from step 2)
4. Find the *actual rate* of double crosses. Do this by:
\begin{equation*}
Actual\;Rate = \frac{double\;crosses}{total}
\end{equation*}
You will find that the actual rate is /always/ less than the theoretical rate.
This is because of *interference.*
5. Find interference by the following formula:
\begin{equation*}
Interference = 1 - \frac{actual\;rate}{theoretical\;rate}
\end{equation*}
Thus concludes the topic of gene linkage. I hope you can see how Mendel was revolutionary and successful in his hypotheses, yet did not account for certain cases in which certain genes are very close to each other on a given segment of DNA.

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:PROPERTIES:
:ID: e43a2223-ffee-4372-81c6-9520ca97450d
:END:
#+title: Genetics: Techniques of Molecular Genetics
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
* Cloning
1. Inserting gene into self-replicating chromosome
2. Amplifying the DNA (cloning)
- This is facilitated by using *RENS (Restriction Endonucleases)*
* These enzymes bind at a *restriction site* along the DNA
* Usually, it is a 4 or 6-mer *palindrome*
* RENS bind as dimers. Each side cuts one strand. This is why a palindrome is needed.
* When looking for palindromes, search for adjacent bases that are able to bind with each other if they were on complimentary strands:
\begin{equation*}
CAATTG
\end{equation*}
* *sticky cuts* create overhangs. *Blunt cuts* cut down the middle of the palindrome. It is more difficult to paste blunt ends together.
* Bacteria use RENs to protect themselves from outside (viral) genes.
* To protect its own genes, the bacteria methylates its own genes. The methyl groups protect the bacteria's genome from its own RENs.
- * Vectors are what the gene is inserted into.
* Contains Origin of replication
* Contains selectable markers
* Contains unique restriction endonuclease sites
All of the restriction sites on plasmid can be cut with the respective REN. If the target gene is also cut with the same REN, it will bind onto the respective site on the plasmid.
Multiple sites are preferred because that forces the desired gene to insert a certain way.
Plasmids support up to 10kb inserts
Bateriophages support 10-15kb inserts
Cosmids support 35-45kb inserts
A *shuttle* contains plasmids and ARS. Thus, it can be used in prokaryotes and eukaryotes
Plasmids must be mutated to remove undesired sites.
* PCR
- Replication, but in a test tube.
- Need dNTPs, ions, and polymerase. (For more info see[[id:3a5368b9-d120-40d0-907f-9b59cc53d653][Genetics: DNA Replication]])
- Primers must be designed based upon the sequence to be amplified.
- Can use polymerase without 3'- 5' to encourage errors. This is done to figure out what a sequence does when working properly.
- PCR is done in three steps:
1. Denature
2. Anneal
3. Extension
- Denaturing allows primers to bind and polymerase to operate
- Extension can be as long as needed. Length of this phase depends on the length of the segment of DNA being amplified. Extension is stopped by another round of denaturing.
- The temperature of the steps is dependent upon the G-C content of the DNA.
* DNA Libraries
- Genomic DNA Library: Series of DNA clones collectively containing the entire genome.
- cDNA library: Contains only the coding regions of the expressed genes.
* Very /functional/
* Collects RNA
- Foreign DNA can be precisely excised from the vector DNA using the same RENs.
- In cDNA libraries, Poly(T) oligomers are bound to polyA tail. Using *Reverse transcriptase* to create DNA transcripts, a *transcriptome* is made.
* Analysis of DNA
*Southern Blotting*
- Can use nylon blotting paper. Cause DNA to run through gel and buffer, all the way to the surface of the paper on top.
- Paper is heated to get DNA single-stranded, then dried or immobilized with UV irradiation.
- Then, a single-stranded radioactive probe can be used to bind to a standard, known, and non-mutated sequence. The result is subjected to X-rays to visualize the hybridized probes. All else is washed away.
- If the probe does not bind and stick, there is a mutation in the sequence. Thus, this method is often used to test for diseases.
*Northern Blotting*
- Same method can also be done on RNA.
- RNA must be kept denatured as it moves throughout the gel, since RNA has complex secondary structure.
- Denaturing accomplished by adding formaldehyde to the gel buffer.
- This method is very helpful in studies regarding gene expression.
- However, it provides no information about why the accumulation of the given RNA transcripts has occurred.
*Western Blotting*
- Proteins run through a polyacrylamide gel.
- Adhered to nitrocellulose paper.
- Antibodies are used to target specific proteins, instead of a single-stranded DNA probe as in Southern Blotting.
* Restriction Maps and Sequencing
- These are done to learn where restriction sitea are in a given region of DNA.
- Different RENs cut the DNA in different lengths; thus a gel will show this result.
- Location of restriction sites can be deduced by observing the length of the digested DNA fragments.
- In *sequencing*, "poisoned" dNTPs are used. These dNTPs are missing a 3/ OH /as well as/ the 5' OH. Therefore they are *dideoxyribonucleic acids*.
- These compounds act like *chain terminators*.
- In a polymerization reaction, the process can be terminated by adding, for example, ddGTP. When it is terminated, we know that it ends on a "poisoned" G.
- Upon adding all 4 ddNTPs, the sequence can be determined when loaded onto a polyacrylamide gel by comparing the lengths of each fragment that is terminated by one of each of the 4 "poisoned" bases.

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:PROPERTIES:
:ID: 3c1042b7-41e6-4830-a7b9-68a8d1d3b46f
:END:
#+title: Genetics: Genomics
#+filetags: :genetics:lecture_notes:
#+STARTUP: latexpreview
* Structural Genomics
- Deals with the *location* of genes:
* Genetic maps -- Shows distance between genes in Morgans. Only good up to 50 Morgans, because beyond this, independent assortment can be assumed and thus no actual distance can be attributted.
* Cytological maps -- Uses flourescence to locate genes on a chromosome.
* Physical map - Displays the actual bases.
* Restriction Fragment Length Polymorphisms (RFLPs)
- Mutations that change the length of DNA fragments produced from REN digests. The mutation happens within the sequence that a particular REN recognizes.
- They are small nucleotide polymorphisms (SNPs).
- They segregate as codominant alleles.
- They are a useful tool in creating genetic maps.
* Variable Number Tandem Repeats (VNTRs)
- Large areas of tandem repeats.
- The number of times it repeats is different in each person.
- Happen at different *loci*.
- They are not genes.
- They can produce a genetic fingerprint when all loci are analyzed.
* Contiguous Regions
- Using different clones, they can be overlapped to form the gene to form a contiguous map.
* Large DNA regions are fragmented so that they are easier to work with. BACs or YACs are often used.
* Fragments are analyzed for overlapping regions, acheived by looking at restriction sites.
* Once all overlapping positions are determined, they can be put together to create a complete map, giving the positions of genes on the chromosome.
* Sequencing the Human Genome
- Collin's team mapped clone by clone.
- Venter used whole-genome sequence using computer software.
- 30-35K genes were found ot be in the genome.
- Exons are only 1.1% of the genome while introns are 24%.
- About 75% of the genome is intergenic space.
* Functional Genomics
- Study of gene products: mRNA and proteins
- Microarray technologies examine expression of entire genomes (transcriptome) (see[[id:e43a2223-ffee-4372-81c6-9520ca97450d][Genetics: Techniques of Molecular Genetics]])
* A gene chip is used. gene-specific oligonucleotide probes are added to the chip.
* RNA is extracted from experimental and control tissues.
* RT-PCR is used to create cDNAs. The cDNAs are dyed with flourescence.
* The binding of a cDNA to a probe in the microarray chip means that a the specific template RNA was present, which in turn means that particular gene was being expressed.
- Can answer questions such as: What is normal? What is abnormal? What has changed based on the conditions?
* Comparitive Genomics
- The word *homologous* can refer to common ancestry *or* to analog proteins in prokaryotes vs. eukaryotes, or different species.
- Bioinformatics provides information from DNA sequences:
1. Can provide protein data/identify similar proteins with known functions.
2. Hints to crucial amino acids
3. Can provide exon data. Sheds insights on those that show high *conservation*, which usually is found in exons.
* conservation means that mamy different species have the same DNA sequence. This means that the sequence must be important and have a specific function.

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:PROPERTIES:
:ID: 6b3d2dbb-7c50-4ebf-b66c-4b0d1f20cdd1
:END:
#+title: Physics 231 Calculus and Vectors
#+filetags: :physics:textbook_notes:
#+STARTUP: latexpreview
A vector is *a mathematical entity with both a direction and a magnitude.*
* Vectors and Complex Numbers
it turns out that vectors are methematically awkward in 3D space. Dimensions such as 1, 2, and 4 allow for multiplication, addition, and division to make sense, as well as magnitudes such as distance to have meaning. Thus, 3D vectors can lead to awkward methematics.
complex numbers can be added to the x-axis to create a vector that gives the location of a point (let's say r). There is the real number part and the imaginary number part. The distance (or magnitude) of this vector can thus be found using the *pythagorean theorem*. Then, the angle could be found by taking the inverse tangent of the two components of the vector.
In this way, we could use complex numbers to describe physics in 2D, since 2D vectors have similar characteristics to that of complex numbers.
The 3D vectors we use today are imaginary components of William Hamilton's *quaternions*. These quaternions had 4 components to them and were a "sum" of a scalar and 3 imaginary components.
The vector portion of this concept was later extracted and used to describe the laws of physics such as E&M and gravity in an effective way. However, few people bothered to explore any further with quternions to see if they were more efficient. That being said, the paradigm of today is to use vectors, and they still are quite powerful.
* The Vector
In the modern vector, all of the parts are real numbers, but they still cannot be added together because they are each multiplied by a specific *unit vector* which points in a specific direction.
With vectors *components can be negative, but vectors themselves can never be negative.*
Any vector can be thought of as its own magnitude multiplied by its own direction, such as
\begin{equation*}
\vec{a} = |\vec{a}| \hat{a}
\end{equation*}
By rearranging this equation, one can find the direction of the vector by dividing each component of the vector by its magnitude. this gives the unit vector.
*unit vectors have no units in a dimensional sense.*
* Direction Cosines
Any unit vector can be described by:
\begin{equation*}
sin(x) = cos(\frac{\pi}{2} - x)
\end{equation*}
Thus, if the x-component of a unit vector is 3/5, then the cosine of the angle with respect to the x-axis equal 3\5.
Thus, direction cosines can be written as:
\begin{equation*}
\hat{a} = cos(\theta_x) \hat{i} + cos(\theta_y) \hat{j} + cos(\theta_z) \hat{k}
\end{equation*}
Direction cosines can be used to find how much of a vector point along one of the coordinate directions.

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:PROPERTIES:
:ID: 2a02b387-4fd0-4f83-9eac-131887b7abc8
:END:
#+title: Physics 231: Kinematics
#+filetags: :physics:textbook_notes:
#+STARTUP: latexpreview
Before diving into the topics of kinematics, we must ponder the questions that are raised when we think of an object all alone in the universe.
Imagine a rock in space that is far enough away from any star or planet, that it can interact with nothing. Answering the following questions will allow us to understand what will happen when the object is /not/ alone:
1. Could the rock speed up or slow down on its own?
2. Could it turn?
3. If the rock is observed to have motion, what would the properties of this motion be?
The laws of nature say that the rock's motion will be constant. Where it is going now, it will continue to go forever, unless acted upon.
This is referred to as the /inertia/ of an object.
This is Newton's first law of motion: *To the extent that objects are unaffected by external influences, objects at rest remain at rest, and objects in motion remain in constant-speed, straight-line motion.*
A deep implication that this hints towards is that there is fundamentally no difference between an object at rest and one that is in motion. This provides some of the underpinnings of Einstein's Theory of General Relativity.
*Motion can only be defined relative to another object.*
* Position
A definition of position: *The position of an object is a vector that describes the object's location with respect to some agreed-upon coordinate system. Both the location of the origin and the orientation of the axes must be known to make any sense of a position vector.*
The position vector is usually denoted as $\vec{r}$
The change in position is referred to as *displacement* and is denoted by $\Delta \vec{r}$
For more information regarding the basics of vectors see[[id:6b3d2dbb-7c50-4ebf-b66c-4b0d1f20cdd1][ Physics 231 Calculus and Vectors]]
Oftentimes, position vectors are functions of time, t.
* Velocity
Velocity is the derivative of the position vector with respect to time.
\begin{equation*}
\vec{v} = \frac{d\vec{r}}{d t}
\end{equation*}
To determine the direction, just divide the vector by its magnitude to find the *unit vector*.
To find the velocity vector from position, simply take the derivative of each component.
It is also very important to realize that the integral of a velocity vector does not result in the position vector but the *change in position* or the displacement.
We can find the latter position by adding the change to the first position, quite simply:
\begin{equation*}
\vec{r_2} = \vec{r_1} + \Delta \vec{r}
\end{equation*}
But notice that the first position is a piece of information that cannot be attained from the velocity vector!
To find the average velocity over a specific range, simply employ this calculus technique of dividing the result of an integral by its range:
\begin{equation*}
\vec{v}_{avg} = \frac{\int_{t_1}^{t_2} \vec{v} dt}{t_2 - t_1}
\end{equation*}
It is also important to note that the magnitude of the average velocity can be /different/ than the average speed. This is because the average velocity vector takes into account the direction of the straight-line path from point A to point B, while the average speed is dependent on the actual path that is different.
For example, if you run one lap around a running track, you should end up right where you started. Thus, the magnitude of your average velocity is 0, but of course, your average speed was definitely not 0 (hopefully).
* Acceleration
Acceleration can then be difined as the derivative of the velocity vector.
\begin{equation*}
\vec{a} = \frac{d \vec{v}}{d t}
\end{equation*}
And, like with integrating velocity, we can get:
\begin{equation*}
\vec{v}_2 = \vec{v}_1 + \Delta \vec{v}
\end{equation*}
We can continue to find information about the displacement as well:
\begin{equation*}
\Delta \vec{r} = \int \vec{v} dt = \int (\vec{v}_1 + \Delta \vec{v}) dt
\end{equation*}
Now, describing acceleration in terms of both change in speed /and/ direction is very useful and is given by (derived by the first equation in this sections and using the product law of derivatives):
\begin{equation*}
\vec{a} = \frac{d v}{d t} \hat{v} + \frac{d \hat{v}}{d t} v
\end{equation*}
We can see that the first term describes a change in speed only, which we know from natural observation, takes place in the direction of the velocity, such as a car speeding up or slowing down without changing direction.
The second term describes acceleration as a change in the direciton of the unit vector with time (radians per unit time) at constant speed.
The direction of the acceleration is perpendicular to the velocity vectors, just like the velocity vectors are perpendicular to the position vectors. This gives acceleration a direction in the $-\hat{r}$
* Eliminating the Time Variable
We now seek an expression that relates velocity to position, but contains no time variable.
If we want to eliminate the time variable, we must use the chain rule:
\begin{equation*}
\frac{dv_x}{d x} = \frac{d v_x}{d t} \frac{d t}{d x} = a_x \frac{1}{v_x}
\end{equation*}
Simplifyling, we have:
\begin{equation*}
\frac{d v_x}{d x} = \frac{a_x}{v_x}
\end{equation*}
From this simple equation we can create a host of kinematic equations that model physical systems with:
1. Constant acceleration
2. Position-dependent acceleration
3. Velocity-dependent acceleration
For *constant acceleration* applications, we can simply separate the terms and then integrate, ultimately leaving us with this equation (after some simplification):
\begin{equation*}
v_x^2 = v_{x0}^2 + 2 a_x(x - x_0)
\end{equation*}
However, it is very important to realize that these equations do not have a built-in sense of the correct passing of time (after all, we have eliminated the time variable). So, according to these equations, there are two values for time. However, only one is correct given the context. For example, the two time values express the time it takes for a ball to fall from a point and hit the ground, and the time that it would take for the ball to climb upwards from the ground to the point at which it was thrown, respectively.
For *Postion-dependent* accelerations, we can have an expression that depends on the slope:
\begin{equation*}
a_x = -g(slope)
\end{equation*}
Where g is the gravitational acceleration.
If we simply plug this expression in for the acceleration and separate and integrate like we have been doing before, we get an equation like this (after simplification):
\begin{equation*}
v_x^2 = v_{x0}^2 - (slope(x))g(x - x_0)
\end{equation*}
Where slope is a function of x, the position.
For *velocity-dependent* accelerations, let us give an example. Let's say that a car is rolling to a stop and its acceleration is a function of its velocity (since friction and air drag depend on velocity). Let's say this is:
\begin{equation*}
a_x = -0.2 v_x
\end{equation*}
\begin{equation*}
\frac{d v_x}{d x} = \frac{-0.2 v_x}{v_x}
\end{equation*}
From this, we see how easy this calculation can be, especially after cancelling out the velocity term.
Then, after separating and integrating, we arrive at this simple equation for velocity-dependent accelerations (ignoring air drag).
\begin{equation*}
v_x - v_{x0} = -0.2(x - x_0)
\end{equation*}
* Drag-free Projectile Motion
Using what we know about position, velocity, and acceleration, and what it means to take their derivatives and integrals, we can combine all of these things to create a glorious, complete equation.
\begin{equation*}
\vec{r} = (r_{x0}+v_{x0}t)\hat{i} + (r_{y0} + v_{y0}t-\frac{a_g t^2}{2})\hat{j}
\end{equation*}
/This equation does not account for landing or impact with the ground./
After solving for the time of flight using the y-component of the position equation given above, one can use it to find the range, or the distance in the x-direction the object goes before it hits the ground. The velocities in the x and y directions are just simply the components of the overall velocity vector. After doing this (substiuting the time of flight into the equation) we find that the range is:
\begin{equation*}
r_x = \frac{v_0^2 sin(2\theta)}{a_g}
\end{equation*}

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