developer notes

2

so i heard that the sun and the moon are girlfriends

(i wonder if they meet in twilight or dawn)

6

A messy little comic where Otabek calls it out.

Part 6/Part 8

It only gets happier from here, I promise. Next part coming out next week 👍🏾

Notes on Function Maturity

Immature Si: I only seek details that make me comfortable while ignoring or downplaying important details that might require me to change course
Mature Si: I prepare myself to perform well by methodically learning and attending to every new or significant detail that each situation brings

Immature Ni: I believe I know how the world works though I can’t see myself accurately and don’t know how to live my own life meaningfully
Mature Ni: I make positive progress because I possess a deep and meaningful vision of who I should be and what I contribute to the world

Immature Ti: I follow my own rules and principles without really understanding exactly how my actions influence the world at large
Mature Ti: I seek precise knowledge of what impact my thoughts/behaviors produce so as to act coherently without harm, bias, or hypocrisy

Immature Fi: I can only see as far as my own values and suffering so I can’t formulate a factual and objective understanding of the world at large
Mature Fi: I seek deep understanding of human experience in order to act with integrity and work to prevent/alleviate suffering for myself and others

Immature Se: I simply react as circumstances dictate without enough consideration for whether the direction is the right one to take
Mature Se: I seek out new/positive learning experiences and fully appreciate that the unexpected can teach me to be more adaptable to life’s changes

Immature Ne: My mind is unable to conceptualize the best ideas or grasp the most promising opportunities for making progress in life
Mature Ne: I am confident in making continual progress because I can work out many viable paths to approach any situation or difficult problem

Immature Te: I utilize power to shape the world into what I want it to be and fail to realize that my actions do not produce universally positive results
Mature Te: I utilize my strengths to get positive results for all and work to improve my weaknesses so as to minimize negative or harmful behaviors

Immature Fe: I only care about others in terms of how they affect me and fail to treat them as individuals with their own unique needs/experiences
Mature Fe: I can see other people objectively and separately from myself and respond to their needs appropriately and compassionately

Les Miserables_ Les amis de l’ABC page ½

Keep working in my portfolio ~ I should have started with Valjean but… just watch me.

This is only the sketch and I’m already crying. Someone send help.

anonymous asked:

I know nothing about Jrey but I already love him

Is the youngest of 7. The ace of the class. competitive and cocky, has a heart of gold. Is rivals with Coran, over both serious and silly stuff. Also he and Coran dated for awhile. 

rival bf

Notes on Breaking Loops

aux Si: reflect on how to be content and prioritize accordingly
aux Ni: take time to understand every side of an issue accurately
aux Ti: acknowledge your flaws and improve systematically
aux Fi: reflect on whether your ideas/actions support well-being
aux Se: avoid assuming the worst to embrace new experiences
aux Ne: work hard to actualize better possibilities for your life
aux Te: change any beliefs that prevent success or cause failure
aux Fe: improve your relationships and value their feedback

“We learn from failure, not from success!” - Bram Stoker

Ben Tallmadge, in his Memoir: I have never received a dangerous wound, nor had a single bone broken. I seem to myself a singular instance of the Divine protection and care.

TURN Writers: it’s not inaccurate if we don’t break anything. define ‘serious’. let’s shoot him a couple of times and give him a bout of hypothermia.

Notes on Self-Reflection

Si+Ne: Does comparing this new moment to my past knowledge help or hinder me in appreciating the wonder and possibility of what is happening?

Ne+Si: Does this train of thought or imagined possibility help or hinder me in the process of reaching genuine gratification and contentment with life?

Ni+Se: Does this abstraction about the future help or hinder me in appreciating and making the best of what is happening at present?

Se+Ni: Will this action or experience help or hinder me in advancing towards my life goals or actualizing my greater potential?

Ti+Fe: Does this inference actually help or hinder me in understanding my place in the world and how to contribute something positive to it?

Fe+Ti: Does this approach to handling people/relationships help or hinder me in becoming a capable, confident, self-sufficient person in my own right?

Fi+Te: Does this moral judgment help or hinder me in doing my part to create the kind of world that better respects me and all individuals?

Te+Fi: Does this solution help or hinder me in addressing the actual problem and achieving results that do as much good as possible?

Quantitative Structure-Activity Relationship (QSARs) - Drug Development

QSAR modelling predicts the biological activity of a compound based off its physical properties. They are used to avoid synthesising and testing every possible version of a molecule to find the optimum for bioactivity. A small number of structurally similar molecules are synthesised and tested, and these results are used to mathematically predict other similar molecules on a computer.

Hydrophobicity 

This dictates the ease at which a molecule will pass through a cell membrane. Too hydrophobic and the molecule will be drawn to lipids and its bioactivity will be reduced, too hydrophilic and the molecule will be too polar to pass through the phospholipid bilayer and will not carry out its desired activity (will be excreted in urine)

LogP - a measure of the whole molecule’s hydrophobicity 

  • High logP = more hydrophobic
  • Low logP = more hydrophillic (polar)
  • Optimum for bioavailibility = 2-4.5

A regression equation can be formed with c=concentration for max activity

1/c = K1 logP + k2

If linear, values for other similar structures can be taken off the line. If parabolic = logP^2, indicating that after a max concentration bioavalibility will not increase as the drug becomes too hydrophobic and moves into fats.

Substituent hydrophobicity constant,  π

Measures the hydrophobicity of individual substituents in a compound.

π = logPX - logPH

X= partition coefficient for substituted compound 

H= partition coefficient for unsubstituted compound (Hydrogen (so if H was in place of the substituent of interest))

  • Compares how hydrophobic a substituent is compared to hydrogen
  • π = +ve –> X= more hydrophobic than hydrogen
  • π = -ve –> X= less hydrophobic than hydrogen

Note: can be used to calculate logP by adding substituents, rather than having to synthesise and test the molecule (clogP = calculated logP)

Electronics

Pharmacokinetics (administration, distribution, metabolism and excretion) rarely depends on hydrophobicity alone. The polarity of a compound dictates its passage through the patient and its binding at point of activity.

Hammett substituent constant, σ

The starting point  is a chemical equilibrium for which both the substituent constant and the reaction constant are arbitrarily set to 1: the ionization of benzoic acid (R and R’ both H) in water at 25 °C.

Provides K0.

RCO2H <–> RCO2- + H+

uses the dissociation constant

kH = [RCO2-][H+] / [RCO2H]

  • If X is electron withdrawing, it will stabilise RCO2- and shift the equilibrium to the right. kX will increase
  • eg NO2, CN, Cl –> +ve  σ
  • If X is electron donating, it will destabilise the RCO2- anion and shift equilibrium to the left, with a drop in kX.
  • eg alkyls, ethyls, methyls = -ve σ

σ = logkX - logkH

Steric properties 

Taft steric parameter, Es = rate of hydrolysis of XCH2CO2Me under acidic conditions

Es = logkX - logKH

If X is physically small, the rate of hydrolysis (time taken to reach tetrahedral intermediate) will be fast.

Here, the size of R affects the rate of reaction by blocking nucleophilic attack by water.

           H             1.24 +ve value: little steric resistance to hydrolysis
         Me             0.00 the reference substituent in the Taft equation
         t-Bu          -2.78 -ve value: large resistance to hydrolysis

Small X = large Es, large X = small Es

Accuracy of calculation decreases as the bulk and length of the chain increases.

Hansch equations put several of the parameters together to compare overall bioavailibility of different compounds.

Craig plots

  • Plots 2 constants
  • functional groups with similar activity will be in the same quadrant
  • the optimum quadrant, eg +ve σ and -ve π, will contain all the substituents worth investigating