Missing Brains Will Return!

Hello, dusty and abandoned wilderness of the internet!

Now, I know that Missing Brains, this blog that you have come to know, love, and depend on for guidance in your life, has not been updating for nearly two months now.  And I won't apologize for that.  Not only have I passed my first quarter of graduate school, but I've also found the time in the last couple of months to write an entire novel - in a month!

So, that's pretty awesome.

Unfortunately, the novel is nowhere near reading-quality yet - I have side characters wandering off and disappearing, and others somehow managing to completely shift and mutate their personalities as the book goes on.  I'm going to have to hew at this with an axe for a while before it's ready to see the light of day.

Also, when I do release it, it will probably cost money.  Gotta pay for my cardboard box and lentils somehow!

But what about our free content? I can hear you asking.  Missing Brains used to give me the occasional chuckle or groan for free, and I want that back!  Well, never fear!  Regular updates to Missing Brains will return in January.  One of my New Year's resolutions is invariably to write more - maybe one of your resolutions should be to read more!

Or even, if you're feeling like an especially awesome person, to donate to that favorite blog of yours and help out the author!  I'm sure he or she would totally appreciate it, and not just put the money towards booze.

So don't despair, and keep on checking back!  Like that burrito that you thought would be a good choice instead of a real lunch, Missing Brains will return!

Update and musings!

Hello, random spam and Google indexing bots that are still remaining loyal to my site!

First off, despite what the major media outlets are claiming, I'm not dead.  I am alive and well, kept busy by both work, working on my NaNoWriMo novel, and by the fact that Netflix has just released all five seasons of Chuck for online streaming.  Damn you, Chuck, and your silly everyman approach to being a super-spy.

If you're wondering about progress on my novel, as I am sure that you all are (thoughts of a search bot: "Yay, he's writing more stuff for me to index in hopes of coming across a tasty nugget of advertising!"), rest assured that I am meeting and exceeding my word targets.  It is currently day 8, which means that my novel is supposed to be at 13,333 words by the end of the day.

My novel is 20,000 words.  And I'll work on it more this evening.

Thank you, search bots.  Please, you can stop your electronic beeping.  Is that supposed to be applause?  You should work on that.

However, I don't just want to talk about all the congratulations that I'm receiving - no, I currently have a different train of thought passing through my mind-station.  And that train is named "The concept of intelligence."  Weird name for a train, I know.

If people were given the choice of any three qualities or characteristics for them to wish to possess, their choices would likely be something like "Rich, Popular, and Smart."  Actually, for some people they may replace "Smart" with "Beautiful/Handsome".  Fine, Smart is in the top four choices.

But saying whether someone is smart or not is quite difficult.  And, surprisingly, I feel that, just like wealth, intelligence is a trait that can be changed - unlike looks, you can work on being smart!

In talking to many people, and reading many accounts on the internet ("See, I'm not just on Reddit to goof off - I'm conducting important sociological studies!"), I've seen a tendency for people to consider themselves either "smart" or "dumb", and usually in a pretty static range.  They point at things like IQ tests, Mensa memberships, grade point averages, or college/job history to prove their intelligence.

I don't feel that this is a good measure, however, as plenty of Mensa members tend to be arrogant blowhards that could use a couple months with their jaws wired shut.  And at the same time, I've heard people who would consider themselves to be "stupid" make surprising flashes of brilliance.  Instead, I feel that intelligence should be defined in a couple of different ways:

1. Intelligence should be segregated by area.  Knowing about biology, genetics, and biochemistry, while admirable, does not mean that I should let you fix my car.

2. For each and any area, intelligence should be defined as such:
"the amount of factual information known"
multiplied by
"the ability to draw inferences, make connections, and bridge gaps in this knowledge"
multiplied by
"the ability to express ideas clearly, as a percentage"

This formula is simple: there are three ways to increase your intelligence in any area!

Approach 1: learn more.  Read books, practice a skill, watch others, ask questions, add to your mental library.
Approach 2: practice making connections.  This is probably the toughest to train (and thus, comes the closest to being intelligence that you are born with).  But the more knowledge is truly understood, including the reasoning behind it, the more connections can be made.
Approach 3: talk, talk, write, and talk again!  I know so many intelligent people that are mind-numbing bores when they speak.  If you can't communicate an idea clearly, you may as well not know it at all.  It is trapped in your head, unable to get out!

"But, Samwise, why do we even need to redefine intelligence at all?" you ask me.

"Spambots, it is very clear why this is necessary," I reply.  "And I shall provide a personal example.  I know a person who knows nothing about science, my chosen field.  Biology is a mystery to her.  I possess years of experience and factual information about things like DNA, RNA, recombination, and genetic analysis that she does not.

"However, when I explain concepts to her, as soon as she has the background, she is able to quickly and intuitively follow my leaps of progression!  In her formula, the first value may be low, but the second value is high.

"Does this mean that, even focusing on biology as an area of intelligence, that she is dumber than I am?  Well, yes, as a total value at the end of the formula.  But that is due not to a lack of brainpower on her part - merely the fact that she doesn't have as many facts as I do!  It's easier to win a race in a Lamborghini than in a Volvo, even if the Volvo has a racecar driver behind the wheel.  Looking at potential intelligence, the second value, she's just as smart as I am."

Of course, by this point the robots have long since stopped indexing the page, so I'm talking to myself.  But my point stands.  Our measures of intelligence are shoddy, and they need to be improved.

Temporary Hiatus

Attention, my dear readers: Missing Brains, the nearly-award-winning blog, is going to be going on hiatus for the next month.  Fear not, we will return, but for the next month, this blog will lie still and (mostly) dormant.

"But why!?" you might ask.  "Why would you forsake us, and stop providing us with free and mildly entertaining stories?"

Well, it certainly isn't because I'm going to stop writing!  On the contrary, in honor of NaNoWriMo, I'm going to be undertaking an entire novel.  In only thirty days!

I can just hear you all now.  "Nano-rhyme-o?  What the heck is that?"

Not quite, but good try on the pronunciation!  National Novel Writing Month, or NaNoWriMo, is every November, when thousands of budding novelists all around the world try to sit down and write a full-length novel in just November - in 30 days.

"That sounds next to impossible.  Writing a whole novel?  In just 30 days?  Isn't that, like, 5,000 words a day?"

Actually, it's just 1,667 words per day.  A novel can be as few as 30,000 words, or as many as 80,000.  Some novels are even longer, but those tend to drag on, and should either be pared down or should be split into two different stories.  50,000 words is usually a good standard to aim for.  And working with Times New Roman, 12 point font, double spaced, this works out to only about 4-5 pages per day.

Now that doesn't seem too hard, does it?

Actually, as a former NaNoWriMo survivor veteran, I can attest to the fact that it is quite difficult.  Plotlines change and evolve, new characters appear, and sometimes edits are needed.  And edits don't count towards length requirements.

Add in to this that I have plenty of other work that comes ahead of writing, and NaNoWriMo becomes quite the challenge.  But never let it be said that I will back away from a challenge, so I'm going to give it a shot.

Want to track my progress?  Check out my writer's profile here.  And wish me luck!  If anything, maybe consider becoming a participant in NaNoWriMo yourself!

Talk to you all at the end of the November?

How it works: Mendelian Inheritance!

Today in How It Works, we are going to take a step away from the molecular areas of genetics, and are going to instead talk about evolution!  More specifically, we are going to talk about this dude:

Look at those glasses.  Has to be a scientist.

This man, who lived back in the 19th century (1822-1884, to anyone who's interested), is named Gregor Mendel.  Growing up in Austria, he worked on a farm as a child, and chose to join the Augustinian monks to help afford his studies, as the monks would pay for his education.

At the university where he studied, Mendel chose to focus on heredity - a hot topic at the time!  He started off breeding mice together to track their traits, but the monks weren't comfortable with him observing animal sex (squeamish lot, those monks), so he switched over to plants.

What Mendel observed, as he bred together pea plants while looking at certain traits, is that it was possible to create what were known as inbred lines - that is, lines that always showed a certain trait!  Back then, there wasn't a clear understanding of the existence of genes, so scientists could only observe the phenotype - that is, the physical appearance of the organism in respect to a specific trait.

Mendel, in true scientific fashion, tried to only focus on a single trait, figuring that the fewer variables he had to track, the better.  For this example, let's take pea pod color (which comes in two flavors: green and yellow).  If Mendel bred some wild-type plants together, he would get a mix of greens and yellows.  But if he kept on breeding only green or yellow plants together, he eventually found that all the offspring would be 100% green or yellow, matching the color of the parent.

Now, that's not too interesting.  If you keep on selecting for a trait, eventually you only see that trait.  Awesome.  But when things got really interesting was when Mendel decided that, after creating an inbred line of green peas and an inbred line of yellow peas, he was going to breed the two different inbred lines together.

The first generation of offspring from this cross (usually referred to as F1) was all green peas.  Pretty dull, although it's interesting that green seemed to dominate over yellow.  But not yet willing to give up, Mendel decided to go ahead and cross this F1 generation to itself.  The results from this cross were surprising.

Mendel saw that in this next generation (the F2 generation), he would see three green pea pods for every yellow one.  And no matter how many times he tried this F2 cross, he still saw this remarkably stable ratio of three to one.

From this, Mendel deduced that there were two alleles that represented these two colors.  The green allele made pea pods green, while the yellow allele made them yellow.  Whenever a plant had one of each allele, it would show green; the green allele is dominant to the yellow allele!

The big conclusion that Mendel drew, along with the existence of these alleles, is that these alleles were given to offspring independently.  This is known as the Law of Independent Assortment.  Here's a handy chart to show how it works:

In this case, the big G corresponds to the allele that makes the pea pods green, while the small g corresponds to the allele that makes them yellow.  As you can see, the F1 individuals each have one big G allele and one little g allele; because the big G is dominant, they are green.  When they are bred together, 3/4 of the resulting offspring will inherit at least one G allele, and will thus be green.  But the last 1/4 will inherit a little g from both parents, and thus will be yellow!

One way to think about Mendelian inheritance as a set of rules:

1. All genes have two forms: a dominant form, usually represented by a capital letter, and a recessive form, usually represented by a lower case letter.
2. If a dominant allele for a gene is present, that is the phenotype that will be shown by the organism.
3. The only time a recessive allele will create the phenotype is if there are no dominant alleles present for that trait!
4. There is an equal chance for a parent to pass on any allele that it has.  In the above example, each parent in the F2 cross has a 50% chance of passing on a big G allele and a 50% chance of passing on a little g allele.

Makes sense so far?

Now, there are a ton of other factors that can influence inheritance, things like co-dominance, suppression, partial penetration, and haploinsufficiency.  But these will come into play later.  Mendel's discoveries, although lost for many years, created a stir in the scientific community when they were rediscovered and shown to be correct.  

Ask Jackson Galaxy!

Do you recognize this man?  His name is Jackson Galaxy, and he is a part-time musician and full-time Cat Whisperer on the Animal Planet show, My Cat From Hell!  The editorial staff, here at Missing Brains, would love his input on several pressing topics of cat ownership that we have prepared here.

Yes, he IS the Cat Daddy.

• Dear Cat Whisperer, my cat won't eat his cheeseburger.  Are there certain toppings that he dislikes?

• Dear Cat Whisperer, my cat insists on creeping into my room and whispering to me at night.  How do I make him stop?

• Dear Cat Whisperer, I met an amazing guy on a date last night.  But when he came back to my house and saw my seven feline roommates, he turned tail and fled.  Should I call him right away or wait the customary day?

• Cats.  Why?

• Dear Cat Whisperer, my cat insists on bringing me dead animals - birds, mice, etc.  How do I get him to bring me my ex-wife?

• For removing unwanted cat hair, should I use wax, Nair, or a razor?

• Dear Cat Whisperer, my cat has the cutest little mask on his face like a bandit!  He also has lovely dark rings on his tail.  How do I discourage him from digging through my trash?

• Dear Cat Whisperer, my boyfriend keeps texting me how he wants to "punish my kitty."  Why does he want to hurt Snuggles?

• Dear Cat Whisperer, I think I'm not going to wait to call him.  I'm sure he loves me!

• Dear Cat Whisperer, I've heard stories of cats gnawing off people's faces.  Is there a flavor they especially crave?  Can I get a new, better face afterward?

• How do I improve my cat's grammar?

On behalf of the editorial board here at Missing Brains, we look forward to Mr. Galaxy's responses!

Out Beyond The Walls - writing short

No, this isn't connected to any other story yet.  Just a bit of post-apocalyptic character building.

As I gazed around the interior of the ruined building, uneasily noticing how the other members of Terry's crew seemed to occupy their spare time by using pointy objects to pick at their teeth or nails, or sharpen their blades, something nagged at the back of my mind.  Something about Terry's description of his allies.

"Wait a minute," I said, turning towards Terry.  He was still standing beside me, obviously enjoying my discomfort, thrust into this world with which I was totally unfamiliar.  "You said that you had four other people in your crew, right?"

"I did," he agreed, grinning at me.  His hands hung free, but I knew that, if I made the slightest aggressive move, he would have the pistol at his waist free in a heartbeat.  Although I doubt he'd waste a bullet on me.  Not when a knife would work just as well, and be much cheaper.

I glanced around the dusty, shadowed interior.  "I only count three," I said, my eyes roaming over each of them in turn.  Jhang was using a dagger to clean his nails, perched contentedly atop an overturned shelving unit.  Kali was using a whetstone to hone her many daggers; a small pile sat on the ground beside her, waiting to be sharpened before she would tuck them back up her sleeves.  And Wade, whom I had yet to hear utter a sentence more than three words long, was sitting cross-legged atop a small stool, his eyes closed in meditation and his long, straight-edged blade lying across his lap.

"We're a tight-knit crew, sure, but there's always more to be done around this place," Terry commented, spreading his hands wide to take in the disarray.  "So sometimes, while most of us are out on missions, like retrieving you, I'll send one or two of us off to get some real work done."  His eyes flicked away from my face, over my shoulder.  "Ah, and here he is now!"

I turned, and was stunned as I took in the newcomer.  I couldn't believe he had managed to get this close to me before I noticed him.

Approaching at a slow tread was the largest man that I had ever seen.  He stood well over seven feet in height, and had shoulders as wide as axe handles.  Each hand, hanging open loosely at his side, must have been as big as a dinner plate.  He was walking with his back slightly hunched, but I was still amazed that he was able to fit through a door frame.

"Our last member!" Terry declared loudly as the giant joined our rough, ragged circle.  "Meet Smasher.  Oh, it's an obvious name, to be sure, but it just suits him so well!"

The giant gave a slight grumble, a low-pitched rumbling noise deep in his throat.  Terry crossed in front of me, reaching up to pat the massive man's arm in a curiously dismissive manner.  "Smasher doesn't do much talking," Terry went on.  "Not really his thing.  But he's our go-to for the heavy lifting, and he certainly pulls his load!"

I looked back up at Smasher.  Now that I looked closer, I could see that his wide face was curiously childlike.  He had a protruding brow which, coupled with his wide, flattened nose, made him appear slightly as though he had walked face-first into a wall.  His eyes, nestled deep into his face, looked calm, unworried.  That made one of us, I thought darkly to myself.

"Wonderful," I said, directing my voice towards Terry as I surreptitiously took a step or two away from the group.  "So now you've brought me here, under the threat of violence-"

"Implied violence, mate!" Terry interrupted.

Behind us, Kali laughed, a sharp, harsh sound.  "As if there's any real difference," she spat out.  "No room for sneaky lies or fancy words in this world any more."

Terry made a tutting sound, clicking his tongue at her.  "Oh, subtlety is alive and well!" he insisted.  "But yes, Ambassador, we have brought you here for a reason.  Oh, that is very certain."

"And what reason is that, pray tell?"

The leader of this villainous gang swung his hand wide, arcing around to indicate the dark recesses of the large building that held us, pointing off down the dim corridors.  "We may be some of the best out here in this God-forsaken wasteland, but look at our digs!" he exclaimed.  "This place isn't much more than a hovel.  No power, no light - basically every system that could break has done so."

I nodded.  "Sure, but I don't see what this has to do with me."

Terry's finger, previously taking in the decay, now swung around to point straight at my chest.  I noted uneasily out of the corner of my eye that Kali had stopped sharpening her blades, and that her and Jhang's eyes were locked on mine.  "You, my dear boy," Terry said, "are going to fix it."

How to Talk to Professors

Now that I've started graduate school, I've had to go and talk with lots of professors.  Discussing class topics, planning presentations, setting up rotations, asking for letters of recommendation, getting advice on projects, etc., I decided that it's time to share my thoughts on how to go about it, and what mistakes many people make.  So, without any further ado, let me present: How to Talk to Professors!

Before the meeting:

Get a notebook.  Even if you have an amazing memory, get a notebook.  And a pencil or pen.  Bring it with you.  Take notes in it.  It will keep you on track, help you remember anything interesting the professor mentions that you may want to look at later - and to the professor, it makes you look as though you really care about what they say.  Win/win.

Figure out what you're after.  Why are you even bothering to talk to this professor?  This should be pretty obvious, but make sure that you're aware of what you're after.  If you want a letter of recommendation, this should be your primary goal.  Want a rotation slot?  That's your goal.  Write this at the top of your notebook so you won't forget, should you be distracted or the topic veer off topic.

Read up on the professor.  This depends a bit on the professor, but the best way to seem smart and knowledgeable is to be prepared.  (Also, the best way to seem undesirable is to go in with no background, should your goal be to bomb the meeting.)  And I mean more than knowing the professor's name!

• Website bio.  Everyone has a website with a bio on it these days.  Find it by Googling your professor's name and give it a quick read.  Chances are good that it hasn't been updated since 2010, but check it out nonetheless.
• Their last 3-5 significant works.  Most professors write research papers, which are then published.  If they're in biological sciences, put their name into NCBI's database and see what comes up.  If they're in a different discipline, you may need to find a different database.
• Note: do not read the entire paper!  Do it if you've got time, but usually you don't need to bother.  Read the abstract, introduction, and conclusions/discussion.  That usually gives you enough to follow along in their talking without having to memorize too much.
• The syllabus.  Meeting with the professor for a class?  First, make sure your answer isn't in the syllabus.  If you show up and ask about something clearly stated in the syllabus, the professor will irrationally hate you for the rest of the class. 

Location, location, location.  Do you know where your professor's office is?  Are you sure?  Better double-check (good thing you found their website already!).  Figure out how to get there, and plan an extra 5-10 minutes to account for getting lost in the labyrinthine halls of these massive buildings.  Who decided that a Space Invader was the best floor plan layout anyway??

Was that a left or right at the antenna?

At the meeting:

Check yourself before you wreck yourself.  In terms of fashion, I mean.  Take a quick look down at what you're wearing.  Does your shirt have a beer logo on it?  Is that clever saying on your hat offensive to women, minorities, gerbils, and anyone who knows the difference between 'your' and 'you're'?  If so, take it off or cover it up.  You don't need to be wearing a suit and tie, but make sure you look presentable.  Button-up or polo shirt, no food stains, and comb your hair.

Don't talk, listen.  I've found that, at most of my meetings with professors, I tend to do between 25-40% of the talking.  That's right: I'm never talking even half the time.  People in general like to talk about things they know about, and the professor knows more about his topic than you.  Shut up and let him talk.  He feels good that you're listening to what he has to say, and you'll get to not have to worry about saying something really stupid.

Body language.  We've all seen that quote that says that 90% of communication is nonverbal.  Well, show it, you slacker.  Sit up, keep your eyes on the professor, write down little bits of what he says so that you can go back to it later, and give him/her an encouraging nod whenever he or she pauses.  Keep a smile on your face.

• Don't fidget.  I'm making a separate note here: if you're nervous, lace your fingers together and twiddle your thumbs inside this little finger-igloo.  Even better, do it under the table.  This way, the professor can't see that you're nervous.  

Don't fall asleep at the meeting.  Drink caffeine if necessary.

Rephrase.  Is the professor staring at you, waiting for you to say something?  Do you have no idea what answer he or she wants?  Instead of fumbling with lots of pauses and ums, simply say something like:

"Let me just make sure that this is clear: you're saying that if a pig has a wingspan greater than three times its body length, it should be able to generate sufficient upward thrust to at least leave the ground?"

Obviously, don't say that.  But take the last point the professor was stating, rephrase it slightly, and pose it as a question.  If you're wrong, the professor will assume that he or she didn't make the point clear enough and will repeat it.  If you're right, the professor will usually leap off of where you ended with that upward lilt, continuing on towards the point he or she was trying to get you to guess previously.  

The professor runs the conversation; you steer.  This is a lesson I had to learn through experience.  If you're sitting there doing the listening, the professor will be talking, and will be running the conversation.  But don't forget, you're there for a reason!  That reason should be written at the top of your notebook.  Glance down if you've forgotten it.  So just add a comment here or there, but keep on steering the conversation back towards your goal.  

• Want a rotation slot?  Mention your current rotation and how it's going, or ask about current lab research the professor is doing.
• Want a letter of recommendation?  Mention the scholarship/job opportunity/fellowship and comment on how you've been working really hard on the application and/or essays.
• Want a grade changed?  Well, good luck with that, but mention how you've been doing a lot of studying for their class, or how you felt that the recent test was very specific.

DO NOT disagree with the professor.  Or if you do, be extremely wary.  No one likes being told that they're wrong.  And if you say that they are, they will almost always dig in their heels against you.  Research on cognitive dissonance say that, even if the professor is in the wrong, they won't want to change their mind - they certainly don't want to be corrected!  If the professor is really, obviously, definitely wrong, pose your correction as a suggestion or question to give them a better avenue to correct themselves and save face.

At the end of the conversation, if you don't have your answer, ASK.  It is incredibly frustrating to walk away from a meeting with a professor without an answer.  If you go in to get a letter of recommendation, don't leave until you've asked for one!  Better for them to say no so that you can move on, than for them to not answer and leave you stuck in the lurch.  If they're wrapping up and you don't have an answer, say something like:

"Professor Boltzmann, thank you for taking the time to talk to me.  I really liked hearing about your work, and I would greatly enjoy the opportunity to help contribute by rotating through your laboratory this fall.  Would there be an available spot for me?"

Easy as that.  You've got your answer.

After the meeting:

Follow up.  Promptly.  Did the professor request anything from you, such as a CV, resume, essays to read, test to review, etc.?  If so, send it to him as soon as you get to your computer.  Don't delay.  If there are any materials they need, such as a link to click for submitting a letter of recommendation, make sure to send that to them as well.  Even if they don't need any other materials...

Thank them.  Even if they said no.  All it takes is a quick one-line email that says, "Dear Professor Boltzmann, thank you for taking the time to meet with me today - I enjoyed hearing about your research.  Sincerely, me."  Little details like thank-you emails can be the difference between a professor tackling your request right away, or tossing it on the bottom of their to-do pile.  It can also serve as a reminder about what you asked for, should it have slipped their mind already (which does happen).

Don't write a thank you in crayon though.  Even if your handwriting's this good.

Send reminders/thank you messages before the deadline.  Not after.  If there are five days until the letter of recommendation is due and the professor still hasn't uploaded it, send them a quick email thanking them for agreeing to write their letter.  This will both remind them of the upcoming deadline, and make them feel guilty for not doing it yet.  

Reward yourself, and then jump back in.  Congratulations, you talked to another human being without hyperventilating too badly, passing out, or throwing up on them!  Give yourself a brownie as a reward.  Now, eat that brownie quickly, because now you need to move on to the next professor.  Start prepping for your next meeting!

Disclaimer: if any of these tips backfires on you, well, you probably did it wrong.  I take no responsibility.

Reboot, Part V

Continued from Part IV.  Start from Part I here.

I gingerly made my way out of the control room, winding my way through the maze of hallways as I took my roundabout approach towards the power core.  As with most ships, the power core was located towards the rear, where it would be close to the engines for easier conduit access, and further away from the living quarters in case of meltdown.  Unfortunately, as the control room was at the bow of the ship, this meant that I had plenty of distance to cover.

As I hurried along, keeping my eyes peeled for potential dangers, I made sure to glance into each room that I passed.  I was moving through the crew's quarters, and normally these halls would be filled with bustling activity.  My men should be running about, each with his own task to accomplish.  Restocking, cleaning, checking levels for various internal systems within the ship - these were all vital jobs.  But the rooms were deserted.  I didn't even see any bodies.  The rooms looked neat, undisturbed, and spookily vacant.

At the end of this corridor, I reached a set of blast doors, pausing and gathering my wits.  This was the access point to one of the larger cargo holds.  The doors had sealed, but instrument readings claimed that the other side hadn't suffered a breach and was still accessible.  I had the override code.

I felt that nasty little sliver of doubt rearing its head inside my brain.  Were the sensors malfunctioning?  Was I going to open this door, only to be sucked out into the void of space?  Was that what had happened to my previous iterations, forcing repeated reboots?

As I stood there, my finger poised over the access terminal, I glanced down, and noticed that there was some dirt on the floor of the hallway.  For a moment I felt irritated, making a mental note to chastise whomever was on cleaning duty.  A moment later, however, the significance of this hit me.

Reaching down, I ran a finger through the dirt, noting how it loosely stuck to my finger.  There couldn't be vacuum on the other side of this door, or the dirt would have been sucked away!  Feeling more confident, I straightened up and keyed in the code on the access panel.

The door slid open with the slight whoosh of compressed air, and there was no sucking void on the other side.  I let out the breath that I didn't know I had been holding, and made my way inside.

There may still have been atmosphere inside the cargo hold, but the lights had gone out, and I carefully picked my way through the large stacks of crates in near-darkness.  I briefly considered turning around and looking for a handheld torch to light the way, but I had been through this cargo hold many times before, and was able to see just enough in the dim near-darkness to avoid any collisions.  In a few minutes, I had made it to the other side, poised to key in the code to open the blast door on the far side.

I raised my finger to the pad, feeling out the keys, but then paused.  As I had slid my hand over the frame of the blast door, searching for the keypad in the darkness, I had felt something else, slight grooves in the frame.  A moment later, my fingers found them again.  The grooves were very shallow, no more than scratches, but there were four of them, and I realized, with a thrill of horror, that they aligned perfectly with my fingers.

I pulled my hand away from the keypad as though it was burning hot.  In my head, I could see myself being sucked through the doorway as the blast doors slid aside, scrabbling uselessly at the side of the door to try and hold on as I was pulled out into the unforgiving void of space.

Sucking in a deep breath, I took a step back, away from the door and the void that must have waited on the other side.  This must have gotten at least a couple of those reboots; those grooves were too deep to have been left by only a single person.  I shuddered as I thought about that last minute of realization when, as they were being pulled out, the previous copies of myself must have felt the grooves and realized that this had happened to them before.

As my heart rate returned to some semblance of normal, however, I began taking stock of the situation once again.  The power core was still severely damaged on the ship, and this meant that there was no way to access it for repairs.

I was, well and truly, stranded.

Continued in Part VI.

How it works: miRNA!

So previously, I was talking about the DNA to protein pathway.  But in real life, things aren't nearly as simple as this; there are many different mechanisms for feedback, for controlling how, when, and how many proteins are made from DNA synthesis.  Keep in mind that the raw genetic code in all of your cells, from skin to muscle to bone to organs to brain, is the same!  And yet somehow, these cells are able to differentiate, taking on many different shapes and roles.  How do they do it?

One way is through micro RNA, or miRNA!

Previously, I talked about messenger RNA, or mRNA, which is the intermediate stage between DNA and proteins.  DNA is transcribed into mRNA, which is then translated into protein.  A fairly simple two-step pathway.

But there are other types of RNA!  At least three other types that are well known, at least.  The first type is known as rRNA, and forms a specialized structure called a ribosome, which turns mRNA into protein.  The second type is known as tRNA, and is the structure that carries individual amino acids to the protein as it is being built by the ribosome.  And the third type is called miRNA, and suppresses the formation of proteins, preventing them from being translated at all!

So how's it work?  It's simple!

miRNA starts off just like any other RNA - it's transcribed from DNA.  But remember how RNA is single-stranded, while DNA is double-stranded?  And the bases in DNA match up with each other, leading to complementary binding that holds the two strands together?

Well, miRNA starts off as a single strand of RNA, about 70-90 bases in length.  The bases at either end of the strand match up with each other, however, which causes the strand to fold in half and form a loop, similar to a hairpin!  (In fact, these loops are known as hairpins in scientific terminology.)  This hairpin structure can also be known as a stem-loop.

Once a stem-loop has formed, an enzyme called Dicer approaches, and slices off the "loop" part of the stem-loop.  After this piece has been sliced off, the miRNA appears as a short little sequence, about 20-22 bases, and is double-stranded.

The next step after this is the formation of the RISC (pronounced like "risk") complex, a group of proteins that latch on to the double-stranded little miRNA.  At this point, one of the two strands is discarded, so the RISC complex contains a single piece of RNA, about 20 nucleotides long, sticking out from the big mass of proteins like a comb.

Now, that little miRNA contains a specific set of bases, and 20 bases means that this miRNA will only bind to sequences that are complementary matches - balanced opposites.  And it just so happens that certain, specific mRNAs have that exact complementary sequence!  The RISC complex uses its miRNA as a key to find matching mRNAs, and then binds to them and prevents them from being translated.  Instead, they are degraded, and that protein is not produced by the cell!

And thus, miRNA is able to lower the amount of, or down-regulate, the amount of a very specific protein in a cell, by preventing it from being made in the first place by destroying the mRNA.  Seems easy enough, doesn't it?

Reboot, Part IV

Continued from Part III.  Start from Part I here.

I stumbled along as I ran for the bridge, climbing up the half-flights of stairs to access the upper deck of the ship.  On this higher level, I could see definite signs of damage.  Some of the lights, normally providing a pleasant underglow, had been knocked out and left dark areas in the corridor.  I guessed that they had been overloaded by a power surge.

As I hurried along, I suddenly was brought to a stop by another sight, something that sent a tremor of fear running down my spine.  The upper levels of my ship had been equipped with small portholes, granting the crew a limited view of what lay beyond, in the reaches of space.  Most of the time, I ignored them completely, as there was nothing to see outside.

But now, as I gazed at the small, thick window that offered a slightly smudged view of the starry expanse, I could see a faint white line, creeping up from the bottom of the window.  I reached out and tapped on the glass with a finger, only to watch as, with a screech at the far edge of hearing, the crack expanded another inch up the glass.

This was serious.  If that glass gave, we would all be dead, and no number of reboots would fix that.  I had to hurry.

Not bothering to exercise caution any more, I sprinted down the rest of the hallway until I reached the large door at the far end.  Unfortunately, I saw as I skidded to a stop, the door was closed, sealed shut and inaccessible without using the wall-mounted access panel.

I stared at the keypad on the wall, my mind going blank.  I knew the combination, I was sure of it - but I couldn't remember what it was!  I reached out, flipping down the cover on the panel.  After a moment, I peered closer - something seemed to be scratched on the inside.

2875
     -CR

It looked as though the numbers had been scratched down with the tip of a knife.  I wondered why a previous version of myself had known the code, when I didn't remember it now.  Maybe, I briefly considered, this had been carved by the original version of myself, before I had first been hit by something enough to trigger a reboot, which would then wipe the information from my memory.

There wasn't much point in thinking about it too much now.  I reached up and punched in the letter sequence.  For what felt like an eternity, the screen continued to glow baleful red at me, and then finally:

Code Approved; Access Granted

With a hiss, the door began to slowly slide open.  At first, I was about to rush forward and try and slip inside, but then I remembered those fourteen slash marks on the paper in the mess hall.  I restrained myself instead, keeping one hand on the access panel, my finger poised over the close button should I be greeted by a dangerous sight.

As the door opened, however, I saw no immediate danger.  What I did see, however, was the glowing, blinking, furious red of a control panel where many, many things were going wrong.  As soon as I was sure that there was no other danger, I hurried in, staring down in dismay at the confusion before me.

"Computer, run diagnostics!" I commanded, my fingers flying over the keys.

After a moment, one of the few remaining undamaged screens flickered to life:

Voiceprint accepted.  Welcome back, Captain Reynolds.
Running diagnostic scan...
...
...
...
Warning: scan reveals multiple issues at code three or higher:
 -Extensive damage detected to Reboot™ system.  RealScan system software is unable to function; hardware damage is critical.  
 -Ship's power core is offline.  Connection to power core has been severed.  Unable to reactivate.
 -Multiple hull breaches detected.  No repair process is possible at this time due to lack of power.

I groaned, running a hand through my hair.  I was definitely in trouble.

I keyed in a few more lines of code, pulling up the few security cameras that were still functioning.  The bottom deck, down by the cargo hold, looked as though it had been breached in multiple locations.  Fortunately, it looked as though the blast doors leading up to the main and upper levels had successfully sealed, their automatic circuits detecting the loss of atmosphere and closing to protect the rest of the vessel.  But this meant that I had very few options for accessing the power core.

Nonetheless, I knew that I wouldn't be able to get anything else done, be able to escape to safety, without the ship functioning, without the ship having power.  There looked like there was still one route open.  I didn't doubt that in my previous visits, before being rebooted, I would have seen this option.  But I had no other choice - I had to take it.

Continued in Part V...

Missing Brains' One Liners - the master list!

Ever noticed that there are incredibly witty one-liners at the top of this blog, just under the title, and they change every time you refresh the page?  "How does he do that?" you ask.  "Does he put a new one up there every time, just for me?"

Yes.  Yes, it's just for you.  Because you're special.

But if you're curious and don't want to refresh the page a million times, here is the full list so far:

0.  Probably not the worst blog you've seen

1.  Before publishing: insert meaningful statement here

2.  Sometimes when I close my eyes, I can't see

3.  A duck's opinion of me is influenced largely by whether I have bread

4.  Luckiness: being run over by an ambulance.

5.  Intelligence is chasing me, but I'm beating it so far

6.  Careful where you point that

7.  If you don't succeed at first, hide all evidence you tried

8.  To make time fly, throw your watch out the window

9.  Wear short sleeves support your right to bare arms!

10.  What's the speed of dark?

11.  I like big butts and I lie all the time

12.  I like my women how I like my coffee: hot and bitter

13.  Lick your computer right now. Do it

14.  A runway model for sweatpants

15.  Better than unlimited juice, if only slightly

16.  Yay, beers! Taste like tears!

17.  Why settle for Mr. Right, when you could have Mr. Restraining Order?

18.  Your hair smells like roses. Dirty, dirty roses

19.  Imagine if there were no hypothetical situations

20.  Those who live by the sword get shot by those who don't

21.  Internet: all of the piracy, none of the scurvy

22.  Santa knows where all the bad girls live

23.  Every zoo's a petting zoo if you're man enough

24.  If the world didn't suck, we'd all fall off

25.  I put the sexy in dyslexic

26.  Putting laughter back into manslaughter

27.  Atheism's a non-prophet organization

28.  Life is like an analogy

29.  Tornado rips through cemetery, hundreds dead

30.  Coffee just isn't my cup of tea

31.  I used to think I was indecisive but now I'm not so sure

32.  I miss your absence

33.  I broke up with my gym. We just weren't working out

34.  I overthink underthinking

35.  Every warning label has an awesome backstory

36.  So far out of your league I'm playing for the other team

37.  In a battle with words, I'm ready to mumble

38.  My wife and I laugh at how competitive we are, but I laugh more

39.  The best thing about telepathy is . . . I know, right?

40.  I'm counting on you, fingers.

41.  How dare you incinerate that I don't know big words

42.  Measure once, panic twice

43.  It's all shits and giggles until someone shits and giggles

44.  If I agreed with you, we'd both be wrong

45.  I played sports until I realized you could buy trophies. Now I'm good at everything.

46.  These are my principles. If you don't like them, I have others.

47.  I was born at a very young age

48.  Either this man is dead or my watch has stopped

49.  Whiteboards are remarkable

50.  Camping is intense

51.  Procrastination - working tomorrow for a better today

52.  Nobody drives in New York. Too much traffic.

53.  I'm against picketing, but I don't know how to show it

54.  I'm good friends with 25 letters of the alphabet, I don't know Y

55.  You can't trust atoms, they make up everything

56.  I have an inferiority complex, but it's not a very good one

57.  I love the word frequently, and try to use it as much as possible

58.  It's been swell, but the swelling's gone down

59.  Like a midget at a urinal, I needed to stay on my toes

60.  What's the hardest thing about a joke? timing

61.  Dead batteries for sale, free of charge!

62.  Have any naked pictures of your wife? Want some?

63.  I wish I shared your point of view, but my head doesn't fit up there

64.  Eating a clock is time consuming

65.  I was shocked to find out my toaster isn't waterproof

66.  A plateau is the highest form of flattery

A Word of Advice

Psst!  Hey you!  Yes, you, right there, looking at the screen.  Come in close, would ya?  I've got something to tell you.

Look, I know you.  No, don't try and shake your head at me.  I know you.  You seem pretty well put together at first glance, make a pretty decent first impression.  Or at least a second impression.  You're not a bad person, you've got some natural talents, some gifts, you're not the dullest tool in the shed.  And hey, you know this.  So then, why are you so... what's the word...

Ordinary?

Yeah, that's it.  And I know that, deep down inside, you don't want to be ordinary.  You want to excel, be unique, stand out from the crowd, have something about you that no one else has.  Because hey, don't we all.  Look around.  Everyone wanted to be normal as a kid, and now they want to be unique as an adult.  Paradoxical, ain't it?

But no, you want to excel.  At something.  And hey, don't we all.  But we've tried, and I can certainly attest to it, it's damn hard.  Trying to be good at something takes work.  And to be great?  Good luck, there's always someone out there who's further ahead, further down the line.  And at some point, you stop and say to yourself, might as well give up now, huh?  Call it, not waste any more effort?

So here, I'll help you out.  Lay a little truth on you.  You see everyone else around you, all those people who are better than you, who can somehow always have the right thing to say, to do, for whom everything always seems so damn easy?  See them?  The people who somehow seem to have it all figured out?  See them?  Know them?

It's a lie.

Everyone, every single person around you, is scared, paralyzed, in mortal fear that you can see through the chinks in their armor.  They're all projecting out shells of knowledge, of confidence, trying to seem impenetrable, while inside they cry and mewl in helpless despair.

That speaker, confidently giving his presentation?  He's spent months slaving over this topic, and is scared to death that someone will ask him a question he doesn't know, or he'll blank on the answer and be booed off stage.  That guy effortlessly chatting up the babes at the bar?  He's been rejected so many times, and he remembers every one of them, each with its own unique, exquisite sting of failure.  That girl strutting down the street, dressed in high fashion and making every man's head twist to follow her figure?  Just this morning, she stood in the mirror, observing every minuscule flaw and hating herself for them.  They all seem so sure of themselves, but inside, they're just as fragile as you or me.

So, what's the difference?  If we're all the same inside, why are they able to pull it off?  How can they step forward when everyone else hesitates or steps back?  What do they have, that you and I lack?

Really, it's rather a chilling answer.  They know that they will fail.  They have failed before, have taken those wounds, sustained those scars.  And they kept on going.  It's not natural talent, or trained skill, or confidence, or poise, or ability, luck, happenstance, or fortune.

No, it's raw, bloody, dogged determination.  They refuse to hide away, to stay safe from rejection, failure, disappointment and sadness.

It's the reductionist approach to life: if you keep it small, you'll keep it under control. If you don't make any noise, the bogeyman won't find you. But it's all an illusion, because they die too, those people who roll up their spirits into tiny little balls so as to be safe. 
Safe?! From what? Life is always on the edge of death; narrow streets lead to the same place as wide avenues, and a little candle burns itself out just like a flaming torch does. I choose my own way to burn.

-Sophie Scholl

How it works: The DNA to Protein Pathway!

In this installment of How it works, where I talk about various different aspects of science, I am going to focus on micro ribonuclease, also known as miRNA!  These tiny molecules have often been confusing to scientists - for clarity, read on!

One of the most important, if not the absolute most important, pathway in a cell is the creation of proteins.  Proteins are the building blocks of life, and make up most of your cells, carrying out various functions, providing structure, support, helping to create new molecules, digest food, fight off disease, and many more functions!  But where do they come from?

First an introduction: we all know about DNA, the building blocks of life, the code that contains the instructions for creating any organism, the double-stranded helix that looks like an incredibly long and twisted ladder.  But how does DNA turn into a baby, or a dog, or a palm tree?  Well, it needs to go through some conversion!

The first conversion step is the creation of RNA, which is very similar to DNA.  While DNA is double stranded and made up of the bases A, T, G, and C, RNA is only single stranded, and instead of using T (thiamine), it uses U (uracil).  The creation of RNA from DNA is known as transcription, while the conversion of the RNA into proteins (which make up the various parts of the cell and are what makes it 'tick') is known as translation.

This may seem confusing, so let's use an analogy!

Think of DNA as the blueprints of a skyscraper.  These blueprints are very valuable, since they contain all the instructions for how to build this massive building!  Also, because they include every single detail of the construction, there are a lot of pages of blueprints.  There's only one copy of these blueprints.  Now, if all the construction workers building the skyscraper had to keep on handing off this giant book of blueprints to each other, things would very quickly get disorganized and not much work would be accomplished.

So, what if we made things a little easier on our construction workers?  Instead, let's just make photocopies of the relevant pages, and give each worker the pages for his specific assignment, copied out of the blueprints.  This way, you can have tons of copies of the blueprints floating around, each one short and to the point, and the workers can destroy their copies when they're done, keeping the original blueprints intact.

In this case, all of those copies are like RNA!  This RNA is actually referred to as messenger RNA, or mRNA, because it carries the message of how to build a protein.  So, there's a guy sitting next to the blueprints in the main building making photocopies - what he's doing is known as transcription.  All the workers that get the copies then go on to build parts of the building - just like mRNA leads to the creation of proteins.  This is known as translation.

Still with me?  Good!

As I mentioned, there's only one copy of the DNA.  In humans, this isn't quite true - there are two copies, one copy coming from each parent.  Sorry to lie to you about that.  But still, 2 copies for an entire cell is not a lot, so the DNA remains inside the nucleus of the cell, where it is safe and protected.  Inside this nucleus, a protein known as RNA polymerase (remember this from our discussion of PCR?) is responsible for reading along an exposed strand of DNA and synthesizing the single-stranded RNA copy.

That single-stranded RNA copy isn't ready to be turned into a protein yet, however.  It needs to have some modifications made to it!  One step is that some parts of the code may be unnecessary, and certain protein complexes will chop out these unnecessary sections (known as introns) and reattach the two ends of the RNA.  Also added on to the RNA is a "cap" at one end, that helps keep the RNA from being prematurely broken down by enzymes.  At the other end of the RNA is a "tail", which contains instructions about how the RNA should be processed, as well as sites for miRNA binding (more on that later).

After the newly made mRNA has had these edits made to it, it is considered to be a mature mRNA, and is ready to be sent out into the big, wide world outside the nucleus!  So out it goes, into the cytoplasm.  Here, it floats around until it encounters a large protein complex known as a ribosome.  The ribosome attaches onto this RNA and, like a computer program, reads its code!  I will talk more about DNA code in another update, but the code specifies a specific order of amino acids.  As the amino acids are assembled in this order, they coil together and become a specific protein.  So this ribosome reads the RNA code and assembles the amino acids in the specified order, thus creating a protein.  This is translation.

Now, that mature mRNA hangs around for a while outside the nucleus, constantly being used by ribosomes to make copy after copy of protein.  But it can't stay forever, or else the ribosomes would waste all their energy making extra copies of the protein that it specifies!  So, over time, that tail is shortened more and more.  The tail is representative of the mRNA's age - the shorter the tail, the older the mRNA.

Eventually, that mRNA has such a short tail that its code is exposed!  At this point, another protein, known as RNase, steps in.  This enzyme, RNase, is designed for the specific purpose of destroying RNA without a tail.  It latches on to the mRNA and chops it up into pieces, which are then recycled and brought back inside the nucleus, where they will be reused to make new mRNA!

And that, ladies and gentlemen, is the pathway for making proteins, from the DNA (the blueprints) to immature mRNA (the unedited blueprint copies) to mature mRNA (the copies with proper notes for the workers) to protein (the actual product specified on the blueprints).  Not that bad, is it?

Reboot, Part III

Continued from Part II.  Start from Part I here.

As I turn away from the computer terminal, a sobering thought suddenly worms its way into my head: what if I've already discovered this before?  What if I've already awoken, found out what I know now, and gone to the terminal, only to die and be rebooted, with no memory of what had just happened?

As I explore this thought, it grows in intensity, worming into my thoughts and leaving me feeling discomforted and unsure.  What would be a good way to avoid this?  After a minute, an answer comes to me; in case something does happen to me, I should leave behind a message!

Still standing in the mess hall, I look around for something with which to leave a message.  Aha!  There's a piece of paper sitting on top of a nearby table, held in place by a mug with a pen sitting inside.  Perfect.  I reach over, picking it up, but the blood in my veins runs cold as I look at what's written on the paper.

Captain Reynolds,

This is me.  Well, you, now, I suppose.  Whatever.  Look, I've found out that somehow, our memory module has been compromised, so the reboot system can't save the most recent memories.  I'm headed down to fix it now, but I just realized that there's a chance that, if I die, the rebooted version of me won't remember doing this before.  So, I'm leaving this note.  

Signing off, 
Captain Reynolds

I set the note down.  So my suspicions were correct.  I have done this before.  At least once, since I've written myself a note.  Glancing at the pen, I suppose that maybe I should leave a count, to make it clear that I've been here once before.  I look down at the note and then flip it over.  As I see the backside, however, I gasp, and feel the blood pounding in my head.

Number of times I have read this note:
|||/| \||/| ||\|

Fourteen times.  Fourteen times, I've read this!  With shaking fingers, I add another slash mark on to the tally, and then carefully put the note back.  After sucking in a deep breath, I square my shoulders and try to muster my courage.  I must be cautious.  

I step out into the hall, carefully advancing down towards the control room.  At the slightest noise, I freeze, ready to spring backwards or turn and flee, but I see nothing out of the ordinary.  Indeed, a few minutes later, I've reached the entrance to the control room without incident.  I reach up and key in my sequence, unlocking the door.  With a soft whoosh of compressed air, it slides open, revealing the dim lighting and blinking LEDs of the ship's main computer.

I quickly move through the towers of computer equipment, but stop short.  "That's definitely the problem," I say aloud, staring at the ruin of a computer tower in front of me.  Some sort of electrical fire must have broke out; the entire tower is scorched and black, and the plastic and metal of the wires has melted into a streaky puddle at the floor.  There's no way that anything this severe can be repaired.  No wonder the computer was malfunctioning so much.

As I step closer, I notice another note, this one held haphazardly pinned to the ruined tower with a twisted piece of wire.

To myself:

Man, writing these notes is weird.  As you can see, the tower's beyond repair; this part of the system controlled the reboot scanning equipment, so we can't save recent memories without it.  No idea why the engines are malfunctioning, though.  I'm headed to the bridge next.

Reynolds

Well, at least I know where to go next.  I glance at the back of this note, but there's no similar, disturbing tally.  Not that I've encountered any problems yet.  I need to remember to stay on my highest alert.

Continued in Part IV...

Reboot, Part II

Continued from Part I.

"Berlman?" I call out again, my legs gaining strength as I force them to continue carrying me forward.  I make it out of the medical bay, heading down through the metal, meshed walkways that lead throughout the ship.  I still feel a little woozy, but that's not what's bothering me the most.

Warning: Attempt to access most recently written memories failed.  Memories were likely corrupted due to improper upload or transfer.

Attempting to repair files...
Repairing...
Repairing...
Repair failed.  Files cannot be repaired from available data.

Attempting to restore files from earlier backup...
Restore failed.  No earlier backup is present.

The system in the ship was top-of-the-line, capable of keeping a constant real-time profile of every crew member's brain in the synthetic matrix of the computer.  Whenever massive damage was detected to a crewman, the real-time profile on the computer was simply saved, ready to be uploaded to a new, rebooted body.  

I knew that the system worked.  On previous voyages, several of our more accident-prone members of the crew had managed to injure or kill themselves through various circumstances.  In every case, their profile had been successfully saved, and they had stepped out of the reboot chamber a couple of hours later, after their new body had been constructed, shaking their head at their stupidity.  

It had even progressed to the point where Barry, one of the more enterprising crewmen, kept a pool going on who would be the next person to need rebooting.  As the captain, I had to discourage such behavior, of course, but occasionally I'd sit down and consult with him in private.  He was able to provide a good insight into how the crew felt - something invaluable to a captain.

But my point was that the ship's computer was able to keep a full brain profile up until the last microsecond of that person's life before the reboot.  There should not be any memory gaps.  So why can't I recall why I had been rebooted?

The corridors are suspiciously quiet.  The only noise that I can hear is the banging of my own steps against the metal gratings.  Wait a minute.  I pause, straining my ears.  It isn't just my imagination - the sounds of the ship itself, the steady purr of the warp drive beneath my feet, is different.  I've commanded this ship long enough to tell when it's gone wrong.  And something is definitely off.  No crew, malfunctioning reboot system, and now something different with the ship's engines; there's a sinking feeling in the pit of my stomach.

I lean forward, releasing the railing and pushing myself forward into a half-stumble, half-run down the corridor towards the nearest terminal interface.  I duck around the corner, into the mess hall (which is also completely empty.  This is very bad, my brain's crying out to me), and grab for the terminal keyboard.  I key in my access code to the ship's mainframe, my fingers trembling slightly. 

Access code accepted.  Welcome, Captain Reynolds.

>Run diagnostics

Running full-system diagnostic scan...
...
...
Warning!  Extensive damage detected.  Multiple detection pathways are currently offline.  Extent of damage cannot be determined at this time.

Warning!  Damage detected to Reboot™ system.  Memory save function corrupted.  Real-time protection module has been disconnected and must be manually repaired.  Any Reboot™ that occurs will be drawn from most recent saved profile.

Ah, so that explained part of what was wrong.  The computer system, for some reason, had been damaged and was no longer able to save the up-to-date copies of brain scans for new reboots.  This explained why I couldn't remember what had gone wrong when I had awoken; those most recent memories must not have been preserved.

Although the idea of not being able to save my memories fills me with concern, I know what I have to do next; I have to head to the computer room.  Hopefully, I'll be able to repair the computer system.  But I'll have to be alert as I do so. Any mistakes I make won't be remembered if I reboot...

Continued in Part III...

How it works: SDM!

Welcome to How it works, a new and (hopefully) illuminating series on many of the techniques that I, as a biologist, am familiar/somewhat familiar/not at all familiar with!  Read on, but be prepared to learn!

So, in the last How it works, I talked about PCR.  PCR, as you may recall, stands for Polymerase Chain Reaction, and is a way of making a lot of copies of DNA, very fast!  Seriously, once you know your sequence and have a couple strands of the DNA, you can go from 2 strands all the way up to 20,000 strands, all identical, in an hour or less.

But wait!  What about if you want to make a couple small changes to your DNA?  In order to explain this, I'll lay out a nice, hypothetical example:

You're a researcher, working on, for example, fingers!  You go out and take a bunch of DNA samples from six-fingered people (this condition is actually called polydactyly), and compare the DNA sequence to that of normal, five-fingered people.  You compare the DNA using sequencing, which will be explained in another episode.

Now, you find that the DNA is almost identical - except in one spot, instead of there being an A in the DNA, you find a T instead!  (Remember, DNA is made up of only 4 bases, A, T, G, and C, combined in long strings, a bit like computer code.)

So, you hypothesize, if a person has a T in this spot on their DNA, instead of an A, they grow six fingers instead of five!  But you can't just call it quits now - you don't have any experimental proof, nothing to show that this isn't just coincidence.  So you decide to do an experiment!

Now, first off, you can't go around giving people extra fingers (unless you're a mad scientist or something, in which case feel free).  So instead, you look at mice, and notice that they have this exact same gene.  Great - there's no problem with giving mice extra toes!

So, you now have 2 different directions your research could take.  You could:

1. Search through millions of mice until you find some that have extra toes, and extract their DNA and see if it shows that same mutation A -> T.
2. Take normal mice, use a technique called Site-Directed Mutagenesis, or SDM, to change DNA from them to have the T instead of the A, and see what happens when you put it back into new mice.

Do you know which path is best?  Here's a hint: we want the method that doesn't involve searching through millions and millions of mice, counting toes.  We're taking door number 2!

As you recall, PCR works by separating the two DNA strands, attaching primers to each strand as starting spots, and then synthesizing the rest of the DNA in the complementary strand, building off the primer.  SDM works almost exactly the same way - but with one difference.  Another primer is included!

This third primer is made to cover the spot where the mutation should occur.  Remember, primers are usually 7-10 bases long, so even with one base in the middle altered (to create the mutation), it will still bind very strongly to the DNA.  It might look something like this: 

On this picture, ignore the red circles, but look at the two strands of DNA (black lines) with the SDM primers (blue lines) attached.  See how the blue lines have one base that is incorrect, making them kink away from the DNA?  That's intentional!  

Now, after the first round of DNA synthesis, the new strands, made from these primers, will have that mutation, that single changed base, as a part of them!  And because every DNA strand will be made with these altered primers, 99.9% of the DNA from the reaction will be mutated, just as you wanted, instead of containing that original A instead of T.

(Can you see why this process isn't 100% effective?  If you guessed that it's because of the original strand of DNA, you'd be right!  That strand is unchanged, and so it will still have the A instead of the T.  Since we've made thousands of copies, though, the chances of that original strand being the one used is very low, however, so we don't worry about it much.)

So after reading this, hopefully you're starting to see a bit of the power of PCR - not only can it make thousands of copies of a single piece of DNA, but it can also be used to introduce very specific changes at exact locations!  And all of this can happen while you take your lunch break, you productive researcher, you.

Reboot, Part I

Warning: Damage at critical levels. 
Shutting down non-vital systems.
Diverting power to core processes.

Wait, what?  No, hold on!  I can almost reach the switch . . .

Warning: Damage at critical levels.
Overriding higher subroutines.
Beginning memory dump.

No!  I can't.  Hold.  Fight back.  Cannot.  Memory...

Memory dump complete.  
Final upload initialized.
Transferring...
Transferring...
Transfer complete.

Shutting down.

Rebooting in 5...
4...
3...
2...
1...

Core systems online.  Running boot diagnostics...
System is stable.

Booting secondary subroutines.
Secondary subroutines are active.
Booting primary subroutines and personality core.

Ow... oh man, my head is killing me.  What happened?

All systems active.  Performance nominal.

Ugh.  I hate waking up like this.  When I've watched the old movies, the main character sometimes sits up, clutching his head, on the morning after a hard night of drinking.  I don't drink, of course, and the alcohol wouldn't have much effect even if I did.  Thanks, super-efficient liver.  Thanks for not letting me get drunk for more than ten minutes or so at a time, at the cost of an entire bag of booze.

But anyway, I imagine that those old people, after their heavy nights of drinking, felt something like how I do now.

Anyway, let's see.  Time to see if the muscles in this body are any good.  I'll just reach up for the handle to the pod that I'm in, and ta da!  One push, and the door is open.  My muscles feel a little wobbly, but nothing too bad.  I should be able to walk.

Thud.  Freaking ow.  Okay, maybe the neurons are still compensating a little, and I don't yet have full control.  Luckily, there was this hard metal med bay floor to break my fall.  Let's try this: I'll reach out for the operating table, anchored in the middle and fortunately unoccupied, and use it to pull myself up.  There, that works great!

Now that I'm sitting here in the middle of the med bay, waiting for my new brain to get acquainted with my new body, I wonder where the doctor is.  Ugh, memory's still fuzzy, long-term connections aren't all there yet, but I can picture his face.  Bearded fellow.  A little tall, for a crewman, but doctors are always in high demand, and he can get on a ship even though he stretches the acceptable size limits.  I can't quite recall his name, though.  Beard-man?  Beerman?  Berlman?  I think that last one's it.

"Berlman?" I call out, my voice still a little raspy.  Yeah, definitely still need more connections to finish wiring themselves inside my head.  All reboots are supposed to be perfect copies, up until the last few seconds, but nothing's ever quite as good as it sounds.

No answer.  That's really odd.  Now, I can remember Berlman a bit better, including his belligerent attitude.  He rules over this sick bay like a lord, and he'd never leave it alone this long.  Especially if someone's rebooting.

Speaking of which, I can't remember why I rebooted.  This is really strange.  Fortunately, my legs seem to be working all right now.  

Time to go find some answers.

Continued in Part II...

How it works: PCR!

Author's note: This is part of an installment on how many methods and techniques in biological sciences work, written for educational purposes!  Hopefully, this blog will rise to be something more than silly short stories.

If you've ever worked in a biology lab, you've probably heard professors, researchers, or even other students talking about PCR.  But what in the world is this strange acronym?

PCR stands for Polymerase Chain Reaction, and is a method for amplifying DNA!  This process can take a few strands of DNA, or even a single strand, and turn it into thousands of (nearly) identical copies! Although it has a few limitations, it is a very rapid, powerful tool, and has many different uses.

So, you may be wondering, how does PCR work?  It's simple, and all depends on temperature.  But first, a little refresher on DNA.

DNA is made up of two strands, each of which is complementary to the other.  Because they are perfectly complementary, they fit together, bonding perfectly.  Think of it like ripping a piece of paper in half - the two pieces of paper will perfectly match up together, unlike any other ripped piece of paper!  Same thing with DNA.  Once enough complementary bases are in a strand of DNA, it will only fit perfectly with its exact match.

Even though DNA normally sticks together, it does separate - when heated up!  In order to separate the DNA, the solution containing the DNA is heated up to between 95 to 98 degrees Celsius, near-boiling.  At this point, the DNA peels apart into the two different strands, but doesn't fall apart quite yet.

Now, the enzyme that copies DNA is known as polymerase, and it's a big, complex protein.  Polymerase attaches on to an exposed single DNA strand, and builds the complementary strand of the DNA.  Bam, DNA copied!  Unfortunately, it's not quite that easy - there are a couple requirements of polymerase, however, that make it a little tricky to work with.  

The first issue, which made PCR impossible for a long time, is the fact that polymerase is heat-sensitive.  If you heat the protein up too much, it acts a bit like a spaghetti noodle - it falls apart, and no longer performs its DNA-copying function.  Even if you cool it back down, it is still broken.  Now, when you have to heat up the DNA to separate the strands, this becomes an issue.  

The way to solve this problem is actually rather ingenious, in terms of biology.  In some hot vents, such as those found in hot springs in Iceland or at the bottom of the ocean, certain bacteria (known as thermophilic bacteria) are able to thrive.  In order to survive in the boiling-hot water, they have evolved special forms of enzymes that remain stable at very high temperatures.  The polymerase used in PCR comes from one of these bacteria, T. aquaticus, and is thus known as Taq polymerase.  It doesn't break down in hot water!

The other issue with polymerase, however, is that it can't start on just a single strand - it needs to start on a double strand.  This means that if you chop a bit out of a double-stranded piece of DNA, the polymerase can copy that area missing its complementary strand.  If you have a single strand by itself, however, there's no place for the polymerase to attach.

Now, in order to get around this problem, two different short pieces of DNA, known as primers, are added to the mix for PCR.  These primers are usually 8-10 bases each in length, and are specially selected to perfectly fit the DNA strands at either end.  This means that the primer forms a very short section of double-stranded DNA, allowing the polymerase to attach!

The last thing needed for a PCR to work successfully is the raw ingredient - the bases that DNA is built from!  These are easily synthesized, and are added to the mixture so that the polymerase has raw materials to use to build its strands.

So, PCR goes through three steps - denaturing (where the DNA separates into single strands), annealing (where the DNA is cooled off enough for the primers to bond to either end of the single DNA strands), and elongation (where the polymerase attaches to the DNA at the double-stranded primer, and then builds the second strand down the rest of the length of the strand).  Each of these steps is performed at a different temperature, so a PCR machine, also called a thermocycler, rotates a sample between the three temperatures.  Although temperature can vary, denaturing is usually around 96 degrees, annealing happens around 58 degrees, and elongation is generally at 72 degrees.  The thermocycler simply keeps on cycling the temperature of the sample between the three programmed temperatures.

Because the primers/Taq polymerase combination makes a copy of every single-stranded DNA molecule, each cycle should, in theory, double the amount of copied DNA!  Here's a quick example:

Start with 1 strand.

After 1 cycle, you have 2 strands.

After 2 cycles, you have 4 strands.

After 3 cycles, you have 8 strands.

After 4 cycles, you have 16 strands.

After 5 cycles, you have 32 strands.

As you can see, the amount of DNA grows very rapidly!  Of course, this growth stops if you run out of primer pieces of DNA or raw bases, but in general, this method allows for millions of copies of DNA to be synthesized in a half hour or less.

PCR has a couple other limitations.  Because polymerases don't copy DNA instantly, there is a limit on how long the copied DNA strands can be.  The maximum length of DNA that can be copied by PCR is about 10,000 base pairs, although some methods can go up to 40,000 base pairs.  PCR also has occasional errors, as the Taq polymerase has an error rate of about 1 in 10,000 bases.  Sometimes, the copied DNA strands aren't perfect - and that, of course, means that future strands copied from those are also flawed.  

Despite this, however, PCR is a very powerful tool, and is used all the time in biology labs!  And now, you know how it works!