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…