Switchblade Pisces Pt. 4

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We’re at a gas station, because apparently even motorcycles driven by crazy robot girls need gas occasionally. I’m leaning on one of the support columns, and Janis is filling the tank when I realize I have a way out of this situation.  I call to Janis to get her attention. She looks up, her purple irises regarding me with the same focus that she had previously applied to filling the tank. “Yes?”

“I’m not going to see this Eklund character of yours. I order you to take me to the cops or whoever you’re supposed to call in this situation, and for you to confess what you’ve done.”

“I will comply. This is not ideal, however.”

“I don’t care if it’s ideal! That’s what we’re doing.”

“You understand that you will be arrested if I do this?”

“I don’t believe you about that. All I know right now is you just killed two people and I just helped you blow up my apartment after you tried to kill me.”

Janis hangs up the nozzle, but she pauses just as she’s lifting her leg above the seat of the motorcycle. She shudders and starts to collapse. Without thinking I find myself diving forward to catch her. She is burning hot, her face is beet red. She opens her eyes and they look blood shot. “I need to rest. I don’t feel well. I think. I…think I am upset about something.” She closes her eyes and a droplet of moisture falls out of a corner of one of them.

Is she crying?

She’s running a high fever, and the fans on the boxes on her head are whirring like crazy. I feel the side of one of them and involuntarily jerk it away. Feeling again more carefully I estimate that it’s running about fifty degrees Celsius. That’s not too bad for a processor, but for something attached to a human?

I consider my options. I could just get on her bike and leave her, but that doesn’t seem like the right thing to do. Even though she did kill some people.

Just then a black sedan pulls up in front of us. A man who looks to be in his forties rolls down his window and addresses me. “Ethan Yates?”

“Yeah?”

“Please get in the car. Janis is overheating. She needs rest. You are only a few miles from Eklund’s compound. I’ve been tracking her on GPS.”

Crap. Reinforcements. He’ll probably kill me if I don’t go with him. “Janis. Go ahead into the car, alright? You don’t have to follow that last order I gave you.”

“Th…Th…” Janis tried. I could barely hear her over her fans. Damn it!

The guy in the car gets out. He’s wearing a shiny silver suit. It looks expensive, but I’m not an expert. I’ve been wearing jeans and t-shirt for most my life. The guy in the suit opens the back door and I help him get Janis inside.

“She’s burning up,” I say to the guy. “You have a hospital or something in this place?”

“She will be fine. She just needs to rest.”

I sit next to Janis feeling the temperature of her skin. Before I realize it, the car door is closed and the guy in the suit is in the driver’s seat again. ”I will take you both to Eklund now.” That’s when I see the two boxes on back of his head.

“You’re like her? You’re a Pisces?”

“Yes,” he says as he drives out of the gas station. “I will follow any order given to me. I lost more of my brain tissue before reconstruction, so I suffer less from emotional stress when compared with Janis. She has been like this before, when her birth mother came to visit. I believe that if you give her physical contact and say meaningless optimistic statements, it will accelerate her recovery.”

Janis sobs involuntarily. She is definitely crying now.

The man stops to wait for traffic at the entrance and reaches back to Janis while he’s stopped. “There. There.” He says as he pats her mechanically on the knee. “It will all be alright.”

Janis sobs again.

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Reading Your Blueprint: Karyotyping

DNA is  what makes us who we are. It identifies us. The government uses it to control us. Well, that last one isn’t quite true…yet. Still most of us, even those of us who should know better, treat DNA as if it were magical fairy dust that wizards in lab coats use to answer questions. But the only difference between the wizards and you is some knowledge and equipment. This blog will help with the knowledge part.

There are three main ways to use DNA to tell something about an individual: Karyotyping, DNA fingerprinting, and Genome sequencing. I’ll go over Karyotyping in this post and tackle the other methods later.  Karyotyping is basically looking at the chromosomes of a cell as it’s dividing. Cells divide to make new cells, but in order to make sure each new cell has everything it needs, everything has to be copied, including the genetic information. Unless the cell is a bacterium (or an archeum), it will keep its genetic information in a sort of ball of denser material called a nucleus. Most of the time this ball is all we see of the cell’s DNA, but if we add a dye and watch the cell divide, we can see several strange, threadlike structures, or bodies, that are colored by the dye. These “colored bodies” are the chromosomes, named after the Greek “chromo” for colored and “soma” for body. A chromosome is actually DNA wound up around proteins and then wound up again and again until it becomes a tight tangled mess, similar to what happens if you twist a coiled telephone cord.

As you look at  chromosomes under a microscope, in other words, you are actually looking almost directly at DNA.  Normally the chromosomes are haphazardly arranged around the nucleus of the cell, but after taking a picture of them, you can rearrange them so that they’re aligned the same way and in order from largest to smallest. This is a Karyotype.

Usually a lab worker who wants to karyotype a person’s blood, will look at some white blood cells, which are easier to work with for a variety of reasons, and wait for themto start dividing. Then, he or she will use a drug such as colchicine or vinblastin to stop the cell from dividing completely. This allows the technician to look at all the chromosomes under the microscope and analyze them using dyes that bind to different genes. The lab worker or another scientist or technician can then compare the karyotype of one individual to another to see what differences they are in where the dye shows up.

The drugs used to stop the cells from dividing have interesting histories. Colchicine started out as the active ingredient in an herbal remedy extracted from autumn crocuses to treat gout and inflammatory arthritis. Crocus extract was used as such as far back as 1500 BCE though it was only isolated from crocus extract in the late 1800’s. Colchicine is still used to treat severe cases of gout today, however, the difference between an effective dose and a toxic one is rather small, so takers of the drug have to be careful.

Chromosomes of a cell. Vinblastin or colchicine used to keep them from separating.

Vinblastin also comes from a plant extract, this time from the madagascar periwinkle plant. The plant was originally crushed into a tea, and researchers noted that people who drank the tea had a lower white blood cell count, leading researchers to look into the active ingredient as a possible treatment for diseases that affect white blood cells.

White blood cells are primarily responsible for the body’s immune response, which causes inflammation, the primary complaint of gout and arthritis sufferers. These cells also  affect a number of diseases, including cancer. White blood cells use microtubules to initiate movement, and all cells use microtubules to separate chromosomes as they divide. Cochicine and vinblastin both inhibit the production of microtubules, which is why the drugs are useful in karyotyping as well as a number of other diseases.

The easiest thing you can do with karyotyping, after determining species, is determining sex. A normal human being has 23 pairs of chromosomes and sex is determined from the 23rd pair. Genetic females have two longer chromosomes, called “X” chromosomes here, while for genetic males one of the chromosomes is shorter and called a “Y” chromosome. Sometimes a person might have two or more X chromosomes along with a Y chromosome in a condition called Klinefelter’s syndrome. There are also a number of other possibilities, such as XXX or even XXXY. All these scenarios usually result in learning disabilities, and regardless of how many X chromosomes there are, if there is a Y chromosome the person will be physically male. These situations where there are more than two sex chromosomes are examples of aneuploidy.

Karyotype of a normal male. From biology.iupui.edu

The word “aneuploid” comes from four Greek words mashed together: “an-” for not, “eu” for good,”ploos” for fold, and “oidis,” which means form or type. So all together you have “not good fold type,” a set of chromosomes that is not correctly paired. This sort of situation can occur in other chromosomes as well, such as in the case of Down syndrome, the second most common inherited  form of mental retardation, where there is an extra copy of chromosome 21.

In biological terms, “-ploid” refers to how many complete sets of chromosomes there are. The normal number of copies for a set of chromosomes is two, so most cells are called diploid. Sperm and eggs only have half the normal amount of chromosomes, so they are haploid. Plants and some other organisms can have more than two sets of chromosomes, making them polyploid. While polyploidy can occur in human fetuses, it never results in birth. In fact no vertebrate animal can be polyploid.

A normal x chromosome on left, fragile x on right.

Fragile X is the most common inherited form of mental retardation, and while it is not a aneuploidy disorder, diagnosticians can also identify it using a karyotype. In fragile X one of the x chromosomes looks thinner in an area that has a long string of the same DNA sequence. Because of this repeated sequence, a protein required for normal development can’t be produced properly and the neurons of the brain cannot form the proper connections as a result.

Diagnosticians can tell that someone has Fragile X from the way a certain area of a chromosome is affected naturally, however they can also tell other genetic attributes by how the chromosome is affected by the dye they use. Giemsa, the most common dye used for karyotyping, will concentrate in different bands on the chromosome, which you can see in the picture of the normal male karyotype above. By comparing where these bands show up between different karyotypes, researchers can begin to find abnormalities and differences that may have something to do with how a person looks, acts, or feels.

Other labeling techniques have also been used to get more information from chromosomes. Especially exciting is the work done on telomeres, which can be labeled using a protein attached to a fluorescent marker. These are the ends of the chromosomes, which are made up of repeating patterns of DNA that act like the aglets of shoelaces, keeping the chromosome from shortening prematurely. Telomeres have been found to be  linked with the aging process. Although the telomeres will shorten and lengthen throughout life, various stresses can cause them to shorten more than usual. It seems the older we are, the shorter our telomeres get. If we can figure out how to lessen the shortening process, we may find a cure for aging itself.

TELOMERES cap the ends of chromosomes. Image: WIKIMEDIA COMMONS/NATIONAL HUMAN GENOME RESEARCH (user GIAC38)

Suggestions? Corrections? Questions? Observations? I’m trying to cover a lot of ground here without letting things get too complicated, so I’m bound to make some mistakes. Please feel free to comment on this post or email me at zorknot (at) gmail.com about what I’ve written.

Switchblade Pisces Pt.3

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“Please do not attempt to have sex with me.”

I hold my hands up and back off a little. “Okay, you got it. Can you tell me why you were about to kill me?” I walk over to the kitchen area of my apartment and open the refrigerator for a beer.

“Yes.”

I pull the tab on the beer and take a swig, waiting for Janis to tell me what she knows.

“Well?” I ask finally.

“Oh. I was not aware that was a request. I am still learning intonations and intention monitoring. My neuroplasticity has been heightened, but learning is still difficult as I am no longer in the growth phase of my development. I was about to kill you because I was ordered to kill you. I do not know why I was ordered to kill you. I suspect however, that it is for the same reason the FBI wants to kill you.”

“Why?”

“I do not know. Only that you have recently appeared on their most wanted list without any information describing your crime.”

My apartment is on the first floor of a two story complex. I have two windows looking out on the parking lot. One of those windows has my air conditioner in it and I usually have black out curtains on the other one to keep the sun from making the place hotter than it already is, but the curtains are parted now to keep the place from seeming too gloomy.

That’s how we know when the FBI arrives. Well, it’s either the FBI or a black sedan got separated from a funeral procession. “Shit!”After taking a precious second to weigh my options,  I run out of the door. Of course the black sedan has my Tracer blocked, and the two guys in black suits and sunglasses are getting out and pulling out their pistols and giving me conflicting orders.

I’m standing there, trying to decide whether to freeze or put my hands up when I hear Janis.

“Please run to my motorcycle,” she requests loudly, “And hurry.”

“But… they have guns…”

Just then, Janis moves in front of me as one of the agents shoots.

Janis’s arms become a blur. There is a rush of wind and a clang. Something hits a car window, causing it to shatter. “I am aware of their weaponry,” she says holding her blades in her hands. The fans in the black boxes she has on her head are whirring loudly now. “Please run to my motorcycle. It is at the South exit.”

I swallow and do my best to follow her advice. Her motorcycle, looks a bit larger than the ones I’ve seen before, while still seeming utilitarian. I notice as I’m climbing onto it that the license plate has a single letter on it. H. The Feds are shooting at me now, but Janis seems to be able to knock out their bullets. It’s getting difficult for her though. And I start to worry until Janis throws a small, dark object at them that arcs onto the ground at the men’s feet, bouncing a little metallically.

There’s an almost comical moment when they look down and realize what it is.  Then I’m temporarily blinded and deafened as the grenade explodes me.

“Holy crap!” I yell. Janis just killed those guys! Four men paid with taxpayer money, and this crazy girl with boxes on her head just blew them up!

Janis gets sits on the driver seat of the motorcycle. I get off immediately not wanting to go wherever this psychopath is going. The floating colors in my vision are slowly fading away. I can smell the smoke from the grenade. Smells like fireworks and burnt plastic.

“The apartment is about to explode. We are in the blast radius. Please get back on.”

I move mechanically, sitting behind Janis and grabbing the hand rails beside me. She speeds away from the apartment just as the window without the air conditioner in it blows out and orange flames reach out to the heavens.  It isn’t that large of an explosion, really but what if someone gets caught in the fire?

And what about those four FBI agents? They weren’t bad people, were they? They were just doing their jobs, serving their country. And here I am sitting behind the woman that killed them, as everything else that I own goes up in smoke.

I could jump off right now even while the road is speeding underneath me. I’d get a few broken bones, but I’d get away from her.

We zoom past a white mustang on one of the wider city roads. The wind is tugging at my clothes with alarming strength. We’re going too fast. I’m stuck.

Might as well relax and enjoy the misery.

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Switchblade Pisces Pt. 2

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“I am a Pisces,” the woman says as if that explains everything.

“You’re kidding me. So am I.” I laugh.

“When were you made?” the Pisces girl asks with a tilt of her head.

“I was born February twenty first. I just missed being an Aquarius by two days,” I tell her. Not that I believe in all that mumbo jumbo, but it’s always bothered me that I was a Pisces. I mean Scorpios are supposed to be the worst I think, but whenever I see a description of Pisces it seems like the most wishy washy of signs. Worse, it fits me pretty good in some places.

The girl closes her eyes and turns her head back and forth in three movements. “You are not a Pisces in the way that I am a Pisces.” She opened her eyes. “I was ordered to kill you. In the event of my failure, I was ordered to tell you that your services are requested by Baxter Eklund and to take you to his base of operations. Would you like me to repeat the message?”

“Who is Baxter Eklund?”

“He is my guardian.”

“Oh.Did you grow up in a mental institution or something? That would explain a lot.”

The girl looks down and rubs her right wrist with the thumb of her left hand. “The AI of my prosthetic cortex was developed in an institution of learning, a laboratory. Also, I have been training with my optogenetic interface for three years in the same environment. In this sense it can be said that I grew up in a mental institution. However, I did not grow up in a mental institution in the derogatory sense you seem to suggest.”

Although she doesn’t have a discernable accent, she says all the syllables of the word “laboratory.” La-bo-ra-to-ry. It’s kind of cute and creepy at the same time. Like a levitating puppy.

“Are you supposed to be a robot or something?”

“I told you. I am a Pisces.” She’s taken to rubbing her other wrist now.

I rub the bridge of my nose. “Just so we’re clear, you don’t mean Pisces as in the astrological sign, you mean something else?”

“I am a human female, partially controlled by computer through an optogenetic interface. I am distinguished from other human females from my programming, which requires me to answer any question truthfully and to follow any order that I can physically obey. Humans with this programming are called Pisces.”

I don’t know what an “optogenetic” interface is, but there are things I’m more concerned about at the moment.“Okay. So you aren’t going to kill me if I turn my back to you or something?”

“Not unless you want me to,” the Pisces girl releases her blades and tilts her head.

“Thanks, but no. I think I’ll pass.” I look around my apartment, trying to think of what to do now. I should probably phone the police, but, well look at it another way, I’ve got a beautiful girl in my apartment. Sure she’s a psychotic nutjob who might kill me anyway no matter what she says, but that kind of adds to her mystique. “So, uh what’s your name?”

“Janis” She says, retracting her blades once again into her smooth, lightly tanned wrists.

That’s a neat trick she’s got. “Janus? As in the two faced Roman god of doorways and financial fortune?”

“No. My name is Janis because Janis Joplin’s name was Janis. I admire the passion she exhibits in her music, perhaps because I do not understand it. I hope to someday.”

I nod and get up from the floor. “Nice to meet you, Janis.” I hold out my hand. “My name is Ethan. Ethan Yates.”

She extends her hand and grasps mine. Her hand is unexpectedly warm. Almost too warm. Her grip is firm for a woman, but not unnaturally so. I release her hand and she seems to look me over. “You are attracted to me, yes?”

I feel a little heat rise to my cheeks. “Yeah…uh sorry.”

“Please do not attempt to have sex with me.”

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A Story of Glowing Maps

The Japanese didn’t have GPS during World War II, at least not in the form that we’re familiar with today.  If ground troops in the Pacific wanted to look at a map, they had to shine a light on it, and that was rather detrimental to their survival prospects if they needed to know where they were while conducting a secret night time operation.

Luckily for the Japanese soldiers, one thing the Japanese knew a good deal about was ocean life. In particular, a crustacean they call an umi hotaru or “sea firefly”  has the unique property that if you prod it, it glows. If you crush a bunch of these little guys up, and pour water on them, you can create a glowing sludge that you can put on your hands. A glow that is dim enough to not be noticed in the field, but bright enough to read a map by.

When the atomic bombs fell on Hiroshima and Nagasaki, it effectively ended the Japanese soldiers’ need for glowing maps. But a young man who had been working at a factory only 15 miles away from Nagasaki when the bombs dropped, would ensure the sea firefly retained its place in human history. A decade and a lustrum after the war, this man, Osamu Shimomura, was studying at Nagoya University when his mentor,  Yoshimasa Hirata, gave him the task of figuring out how the sea firefly glowed.

Sea fireflies. Image from http://mytechnologyworld9.blogspot.com/2010/11/sea-creatures-used-as-light-for-reading.html

Sea fireflies, similarly to the fireflies we’re more used to, glow, in part, because of a protein named luciferin.  When oxygen binds to luciferin in the presence of another protein, an enzyme called luciferase, the molecule glows. Even though the sea firefly had been studied for a number of years, no one had been able to purify its luciferin because it was so unstable. If you’ve ever had a firefly splat on your windshield, you’ve observed this instability first hand. The firefly guts glow, but they quickly fade to nothing. When the firefly splats, its luciferin binds with oxygen in the air, causing it to glow as it degrades, but it’s used up after only a few moments. In order to purify the luciferin from the sea fireflies, Shimomura had to take powder from the crushed creatures and distill it using a complicated apparatus (pictured at right), then get it to crystallize in a special solvent, all before too much of it degraded into uselessness. It was tough work, but Shimomura finally did it, and published his results in a scientific journal that got the attention of Frank Johnson, a professor at Princeton University in the U.S.

At Princeton, Johnson and Shimomura worked on figuring out how jellyfish glowed. At the time, the popular theory was that every living thing that glowed used some form of luciferin and luciferase, but try as they might to purify luciferin  from the jellyfish, they weren’t able to do it. The problem was that the jellyfish they were looking at didn’t use luciferin at all, but a completely different protein.

Jellyfish glowing mechanism. Image from http://www.conncoll.edu/ccacad/zimmer/GFP-ww/shimomura.html

Shimomura suspected this might be the case and looked into the possibility on his own even while Johnson obsessively pursued the luciferin angle. After a tense period of disagreement, Shimomura discovered that the glowing was actually caused by two different proteins: one, which Shimomura and Johnson named after the jellyfish they were studying, (aequorin) and another, present only in trace amounts, which they called simply “Green protein,” because it glowed green when placed under an ultraviolet light.

Thing was, although the green protein was present in only trace amounts, it had a dramatic effect on the bioluminescence of the jelly fish. Aequorin, the more numerous protein, glows blue in the presence of calcium ions, but instead of glowing blue, as one might expect, the jellyfish glow green.  What is happening here is that the blue glow from the aequorin was making the green protein fluoresce green. This was a very interesting property for a lot of researchers and so the green protein was studied in several other labs, and was soon officially renamed “Green Fluorescent Protein” or GFP.

Shimomura and his colleagues spent many years gathering enough of the protein from the jellyfish near Princeton to properly analyze GFP, isolating  the part of the protein (the peptide) that was responsible for its fluorescence. Such fluorescent peptides are called chromophores.

GFP is unique among fluorescent proteins in that its chromophore is within the actual protein, as opposed to being in a compound attached to the protein. This means that if you can copy the DNA that’s responsible for making the protein, you can recreate the protein in all its glowing glory in just about any animal you care to genetically modify , and indeed,  Douglas Prashar and his colleagues  managed to do  just this in 1985, “cloning” the protein so that other, animals could produce the protein. This allowed research on GFP to continue, even as  the jellyfish it originally came from became much harder to work with due to decreased populations.

The nematode worm C. Elegans

In 1989, a marine biologist who spent many of his summers studying at the same research facility that Shimomura worked at, was giving a lecture on fluorescent proteins and bioluminescence when one of the scientists in attendance, Martin Chalfie, had the idea that he could maybe use GFP in his research on nematode worms.

Nematodes have bristles on their bodies, which normally make them very touch sensitive. The system that allows them to feel touch is governed by a very fast molecular motor, operating at least ten times faster than the molecules responsible for vision in humans and other animals. Chalfie was studying how this touch system worked by comparing normal worms with worm mutants that lacked the gene that produced the molecular motor. The problem was that the only way to distinguish between the mutant worms and the regular worms was to either kill them, which would make it impossible to check their touch sensitivity, or to tickle them with a hair, which kind of defeated the purpose.  He wanted to know which worms were touch sensitive, not just that some were and some weren’t.

One thing that nematodes have going for them is that they are transparent. Chalfie realized that if he could get a fluorescent protein to show up wherever the molecular motor was produced, he could easily distinguish between the mutants and the normal worms without having to kill them, because the worms that had the fluorescent protein would glow.

In 1992  when Chalfie and a graduate student of his found out that Prasher had been successful in cloning the gene for GFP,  they contacted him and worked out how to express the GFP gene in bacteria. To their delight, GFP didn’t require any other molecules to get it to glow after it was produced from the gene. All Chalfie had to do was insert the gene into the bacteria, and it made the bacteria fluorescent. That meant that GFP could be used in other organisms easily.

Chalfie’s wife, Tulle Hazelrigg, gave the next contribution to the study of GFP by showing that fusing the molecule to another protein causes that other protein to be fluorescent as well. This meant that rather than simply labeling mutants versus normal animals, researchers could see exactly where the proteins showed up in the animals they studied.

Finally, Roger Y. Tsien, a Chinese-American biochemist working at Berkeley, California improved the GFP molecule by mutating the gene so that the GFP that was produced was brighter and could be seen with the fluorescent scopes that were already widely available in many different labs. He also was able to make GFP mutants that glowed red or yellow instead of green, allowing several different proteins to be viewed at the same time. This gives scientists a glowing map of where all the proteins they want to look at are showing up in their samples.

One of the most remarkable uses of this technology is in the Brainbow technique, developed by Jean Livet, Joshua R. Sanes, and Jeff W. Lichtman, which labels each neuron in the brain of a research animal individually with a separate color formed by a combination of fluorescence molecules.

An image of a rodent brain using the brainbow technique

So we’ve gone from glowing maps of battle grounds, to glowing maps of the brain all in the span of some sixty years.

Osamu Shimomura, Martin Chalfie, and Roger Y. Tsien all received the Nobel prize in chemistry in 2008 for their work on GFP. Shimomura has retired to emeritus status, but Chalfie still works on worms, and Tsien still works on sub-microscopic molecules. They have all changed the world.

My information for Osamu Shimomura came primarily from his 2008 Nobel Prize lecture.I got Martin Chalfie’s story from an interview conducted with him on the podcast Futures in Biotech. I left quite a bit out for simplicity’s sake, so I suggest giving these sources a look if you’re interested.All other sources are available through the hyperlinks I have provided in text.

Big Dumb Aliens

The alien Mo-Ron from the show Freakazoid

Last night I watched yet another movie with big dumb aliens in it, Cowboys and Aliens. Don’t get me wrong, C&A was a pretty good movie. I’d give it a 7/10. It’s fun, and it turns out Olivia Wilde is a sexy alien, which I always kind of suspected. But it seems that if an alien isn’t humanoid, they have to be some kind of horrible beast that kills people for some inadequately explored reason. Just listing some recent ones there’s Cowboys and Aliens, Super 8 (7/10 I’ve downgraded it from a previous score), Battle: Los Angeles (6.5/10), and the tv-series Falling Skies (4/10). Not so recently there was Independence day, and who can forget the aquaphobic aliens in Signs. Basically ever since the movie Alien, there’s this trope of big dumb aliens attacking us, that kind of has me peeved.

In Alien it made sense. The Giger alien monster didn’t come to us, we came to it. It was a creature, not an intelligent being, at least not in the first movie or so. But in all the movies I listed, to a greater or lesser extent, all the aliens come from innumerable light years away using technology we can only dream of, and when we see them we are distracted by how coldly they are separating our heads from our torsos using their serrated appendages.

There are other cases where this makes sense. I included Battle: Los Angeles because the aliens are big and burly and are attacking us, but in that movie they were just the soldiers sent to Earth by the weaker, presumably nerdier ruler aliens. In fact for all we know in the movie the soldiers might even be another species conscripted into battle by their previous conquerors.  I still call Big Dumb Alien in B:LA, though,  because there’s something missing in it that’s missing in all of them. Communication. You can’t really develop any advanced level of technology without communicating. You can’t organize the concerted invasion of a planet without it either. And yet we hardly see the aliens communicating at all in Big Dumb Alien movies. Not to themselves, and certainly not to the humans.

Super 8 is a little bit of an exception here. The alien does eventually communicate with a human and vice versa, but, I still include it, because the alien acts like a savage animal throughout most the movie. It can make people understand it if it touches them. Fine, but as my brother asked after he watched it, why doesn’t it just touch everybody then? Why not do that instead of killing people, or tying them up in some cocoon thing?

The aliens in Falling Skies might also be considered an exception because some humans eventually find out they communicate on radio frequencies. And they can also use children as cyranoids, speaking through them against their will. But why not do this all the time from the start? Their goal is to rape the Earth of its resources, fine. But it isn’t exactly working out that well if your operations keep getting attacked by the indigenous population. The idea is that they’re supposed to act like European colonists, but the European colonists had Indian guides. They didn’t start out mindlessly attacking natives. They ate with them, traded with them, gave them small pox that decimated their population, and THEN they killed them.

The other thing I don’t like about Big Dumb Aliens is that they aren’t just dumb, but big too. It just seems to me that any creature that can kill other creatures easily probably has little incentive to develop an advanced civilization. We humans have got opposable thumbs and our brains and that’s pretty much it as far as physical advantages go out in the wild. We have martial arts, but that’s a developed skill requiring technology. We have weapons, but that’s already technology right there. Just us, by ourselves, we ain’t much. That’s why we had to use our heads and work together to survive.

I just have a hard time believing that something with razorblades coming out of its armpits would ever try using a rock to kill something. The whole premise of these naked creatures being intelligent enough to travel through space seems off to me. It’s possible, but it just doesn’t seem likely. The whole reason we wear clothes is because we’re vulnerable. I just tend to think that if we didn’t have to wear clothes, we would have never invented the internet.

One of the best things about Cowboys and Aliens is the alien technology. There’s a nifty alien gadget that melts gold and floats it, dripping, up to receptacles that move it to the core of their ships, presumably giving them power somehow. Their ships aren’t just slightly tweaked versions of our aircraft, they look completely different and yet move how you might expect them to move. There’s a strange feeling I got while watching where I forgot that what I was watching was impossible. The mother ship is buried in the earth (which also seems to be a running theme in these movies now that I think about it) with a large part sticking out of the ground that looks similar to the rock mesas around it in the desert. When the camera first showed it, my eye just sort of took it in with everything else. There’s the plain, the sun, part of a mesa, an alien space craft, another mesa, a horse…wait what? The arm band thingy too, was different, yet it worked so naturally I wouldn’t have been that surprised to find out Steve Jobs or somebody designed it.

But all that care that went into the tech is rather wasted on the big dumb aliens that use it. A human gets a hold of one of their arm guns. Do they organize a group to go after that human and retrieve the weapon? Nope! They just carry on, tra la la, business as usual, kidnapping humans, making them watch television until they forget who they are and then cut them up and kill them for no real reason.

Of course in the movie, the humans are equally stupid. Okay, you know the aliens have these nifty arm guns that are the only things that seem to do them any noticeable harm. You manage to kill a few of the aliens that have the arm guns by luck and guile. What do you do? Keep shooting bullets so you can watch them ricochet off their impenetrable armor… WRONG! Cut their arms off and get their freaking arm guns! What’s wrong with you people!

…But I digress.

Basically the point I’m trying to make here is that if you’re going to write a movie where aliens are going to invade earth, take a few moments to think on things from the aliens’ perspectives. Yes, having a smaller alien body part come out of a larger alien body part is creepy, but how does that help the alien? Is it being creepy on purpose? Is that the alien’s way of saying hello? How about showing that the alien uses the smaller body parts for sophisticated tasks requiring a lot of dexterity or something? Anything. If you can let us know something about where the aliens come from and especially if you can show them working out some form of counter strategy to what the humans dish out instead of them just being evil, that will make the story so much better.

Just a thought.

Switchblade Pisces pt1

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There’s a beautiful woman in my apartment. Unfortunately, she’s about to kill me. I suppose you got to take the good with the bad. The only reason I’m not already dead is that the floors of my crappy efficiency apartment are so squeaky they’re pretty much ninja proof. The woman’s on the other side of the room right now wearing khaki shorts and a light blue sleeveless top. She has a utility belt and her milky blonde hair is in a braid. The odd thing is that she’s got these two small, black boxes on the top of her head. That and she’s wielding two knives in her hands.

I’m probably going to die.

She advances on me slowly. I’m still sitting in my swivel desk chair, turned around from my laptop. I wonder what James Bond would do in this situation. He’d grab the girl’s wrists and seduce her into a kiss, and then she’d tell him everything as she languished beside him on silk sheets. And in the next morning she’d be conveniently dead.

Well that sounds nice, even if it seems a little like retroactive necrophilia. I stand up, my hands out like I’m about to catch a beach ball, and I clear my throat, preparing my best Bond impression. “Um…could you stop please?”

Yes, I’m afraid that was more or less entirely unlike James Bond. Particularly the “um.” I’m pretty sure he never ever said “um” in his whole made up life. Then again, whatever I said seems to be working.

The beautiful woman has stopped.

Her skin is perfect, except for a thin, barely visible scar across her right cheek. Her eyes are an enchanting shade of purple, and they are dilated. I read somewhere that if a girl’s eyes are dilated, it means she likes you.

What does it mean if a girl has purple irises? Oh yeah, that she wears contacts. I haven’t seen colored contacts much since the late nineties though, and while I’ve heard of platinum blondes before, the girl’s hair seems more soft and liquid than shiny. I’ve never seen hair like that. It definitely isn’t bleached, or at least I don’t think it is. Who knows maybe there’s some new product out there that I don’t know about.

I’m not sure what to make of the two black boxes protruding out of her skull on either side of her braid. I could almost convince myself they were decorative bows, except for the blinking LEDs and the little computer fans whirring on the sides of them.

“Could you, ah, drop those knives?”

“No,” the girl says in a melodious soprano, “I cannot.” There’s an uncomfortable pause. Then the girl says. “They are surgically attached to my body.”

“Huh?” I ask, intelligently.

By way of answering my question, the girl straightens and lowers her weapons. Then, in a motion so quick I almost don’t catch it, she retracts the blades and the handles into her wrists.  “What the… who the hell are you?”

“I am a Pisces,” the woman says as if that explains everything.

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Aquamarine

The general thrust himself into the lab, marching past the intern who had greeted him at the entrance of the building. He had two aids with him, one male one female, both of them looking like they had been manufactured somewhere, despite being perfectly human. They wore nondescript suits and were perpetually muttering things into their devices. The man himself had silver hair cropped in a military style and shoulders that spread out from his head like the wings of some bird of prey. He wore his uniform from his days as a general festooned with medals in the manner of someone you didn’t want to mess with.

Charles Gentry waited for the man and his entourage to approach from inside his clean room suit. He could hear his own breathing, feel the humidity of it as it threatened to fog the clear plastic of the helmet. The plastic was treated, so it would be fine, but there was still the feeling that condensation would form at any moment.

“Good morning, Dr. Gentry,” growled the general, all pleasantness stripped from the pleasantry, “Is there a safety issue I wasn’t informed of?”

“No, sir.” Charles studied the general’s two assistants, who were scanning the room continually but not appearing to see anything. “This isn’t a hazmat suit, it’s for the clean room. I’m in and out of there a lot today, so it’s easier just to keep it on. I just decontaminate the outside of the suit before I go in. You’ll see some of the other researchers doing the same. It’s uncomfortable, but it keeps things moving.”

The general raised his head up slightly in a half nod. The man valued efficiency, especially if it came at the expense of comfort. “Let’s be quick about this then. You say you have a prototype ready?”

It was Charles’ turn to nod. “We keep it in a sort of airlock between the wet lab and the clean room. It’s in a stable form, so you don’t need a clean suit to work with it, but both sides of the lab need access to it for experiments.” He walked, inviting the general to follow him. “ I appreciate you coming down here. Our funding is about to run out and we can’t run the risk of going through the usual channels.”

“I understand your research may prove a security risk. I’m warning you, though, this better be good, Dr. Gentry.”

“Oh it’s good alright,” Charles said as he reached the door to the antechamber. He couldn’t help but smile as he continued, “It might just mean the end to all war.”

The general’s thick eyebrows came together in a frown. “What do you mean? Is it a bomb of some sort?”

Charles realized he let out more than he had intended. He glanced at the general’s assistants. “What’s their security clearance?”

The general studied Charles for a moment, seeming to weigh the risks. He took a percussive breath. “Michaels, Chamberlin, wait here for me. I have a feeling this won’t take long.”

The two assistants rolled their eyes in tandem and stepped back as if security clearances were the bane of their existence and life would just be so much easier if they could just be allowed to follow their boss indefinitely.

“Five minutes at the most,” Charles reassured the general. “And you will be impressed; I can guarantee it.”

The general gave his half nod again and Charles yanked open the door to the antechamber, pulling against the negative pressure caused by the air being sucked out of the chamber and through the filtration system. Charles hoped the general didn’t notice. Then he realized the man probably wouldn’t realize the implications even if he did. It was too late anyway. He was in the antechamber with Charles, alone.

“It’s not a bomb,” Charles pulled open a fume hood and withdrew a vial of a dark, syrupy, aquamarine substance to show the general. He unscrewed the plastic top. “Some would call it a namcub.”

“A what shrub?”

“A self-fulfilling prophecy, an incantation that affects the minds of those who experience it.  It’s basically liquid hypnosis.” Charles could tell he wasn’t getting through, so he tried one more explanation. “With this substance, you can hack somebody’s brain.”

The general immediately seemed to lose all interest. “We already have drugs for that sort of thing. Brainwashing techniques have been around since the nineteen-fifties.”

Charles shook his head, but the movement wasn’t that visible while he was inside his suit. “No sir, not like this. Look at it. Look how clear it is, how it moves just like water.”

“Yes it is clear. It looks just like water. But that’s not the point. We’ve tried these mind drugs in the past. They don’t work.”

Charles lifted the vial. “This isn’t a drug, sir. It’s billions of synthetic organisms and nanomaterials in a nutrient bath. Smell it.”

The general brought the vial to his nose and sniffed. He scrunched his nose at the sharp scent of sulfur and alcohol that burned his nostrils.

“No odor at all, right?”

“Right,” the general agreed as if it were obvious, “The problem is even if it works, it’s still not as effective as a spy with their brain intact. Drug induced sleeper agents have a bad habit of staying asleep.”

“But, if you could get control of specific people in power, if you were smart about it, and remained hidden …”

The general laughed, took the vial and drank the contents in one gulp. “Go ahead, Son. See if you can do it. See if you can convince the president, congress, the American people, that they’ve been a bunch of idiots and they need to listen to you. See if you can change one thing for the better and not have it get corrupted, perverted and spat back into your face. Go ahead, show me how to rule the world. Because I sure as hell haven’t been able to figure it out.”

Charles took a breath as the enormity of what he was trying to do hit him. Then he let it out with slight chuckle. “I hear what you’re saying, sir. It is a difficult problem to solve. That’s why I feel education is so important.” Charles put an arm around the wide shoulders of the older man. “It’s our children who need to learn to rule the world after all. In fact, I think education is the most important issue facing our country. Don’t you agree?”

“Yes,” the general said, “I agree.”

Charles smiled and patted the man on the back before opening the door and letting him out of the antechamber. He told himself he was being responsible, making sure his technology wasn’t used by the wrong people. And maybe the government would concentrate a little more on education.

What could be wrong with that?

Charles tried his best not to answer that question.

Immunohistochemistry

Diagram of how an atomic force microscope works

So there’s this amazing protein you want to study, and it might very well change the world, but you have a problem: how do you study the protein when its too small for even a microscope to see?

There have been a number of solutions to this problem over the years, many of which are still being used. You could, for instance, study the protein’s effects by adding controlled amounts of it to a sample, or you could keep an organism from producing the protein  through surgery, drugs, or geneticsand see what what happens when it isn’t there. More directly, the obvious solution is to get a better microscope. What do I mean by a “better” microscope? Well, although there are some drawbacks, there are some microscopes that can give much higher resolution and/or provide added information about what you’re looking at.

One example of this is an atomic force microscope. How this works is that a small needle on a cantilever connected to a computer is dragged across what you want to look at. The computer then measures all the bumps that the needle encounters and gives a visual representation on the screen. As you might suspect this method has a number of drawbacks, (the cantilever is fragile, samples have to be specially prepared, etc) but it is possible to identify single atoms using this method.

Another type of microscope that can help you find a protein is an electron microscope. The idea here is to use electrons instead of photons to look at a sample. There are a number of drawbacks to this idea as well, for one thing, samples usually have to be “fixed” with a chemical such as Osmium tetroxide  and this can sometimes change the way things in a sample look. However, here the drawback can also be a good thing. What “fixed” means in this case, is that the molecules are attached to the things around them, and so aren’t going to move around all over the place like they would normally. If you want to see stuff moving around, you’re out of luck, but often you want to see where something is at a particular time and you don’t really want it to be free to wander.

There is another benefit to using electron microscopes. Parts of a sample will be darker depending on how electron dense they are after they’ve been fixed.  the electrons that the microscope uses to scan the sample will bounce off of that part of the sample, causing there to be a dark region. It isn’t always easy to tell which molecules will be more electron dense than others, but there are ways of making it easier. For one thing, if you have a molecule that you know is electron dense that you also know will form a bond with the protein you are looking for, you can add that to your sample and then you can compare the dark regions in the treated sample to how an untreated sample looks. The dark regions that appear in the treated sample but not in the untreated will most likely be your protein.

How confocal microscopy works

This trick also works with fluorescent and confocal microscopes. These microscopes shoot  beams of light at a constant, controlled frequency on the sample, causing some molecules to fluoresce, emitting light at a slightly different frequency. Confocal microscopes have the added benefit of being able to control where exactly the lasers focus so that it can show not only where something is in terms of up, down, left, and right, but also where it is in terms of depth. Once again, if you know a molecule is fluorescent and that it binds to the protein you’re looking for, you can add it to your sample and then check it out in the fluorescent microscope to find your protein. That’s great, but how do you find a fluorescent molecule to bind to your protein?

Diagram of antibody production

Well, your body has a ready-made system for finding molecules that will bind to proteins that has been tested over millions of years of trial and error. The immune system. If a virus or a bacterium enters your body and starts causing problems, your immune cells will start producing antibodies for the proteins that are present on the surface of the intruder, so that if it shows up again, it will be dealt with before it can cause any damage. Antibodies are large (by protein standards), y-shaped molecules produced by white blood cells. There are binding sites at the ends of the smaller arms of the y that bind to specific parts of a molecule. The binding sites act as a sort of lock, where the key is the part of the molecule the antibody binds to. There are a huge number of different binding sites that are available due to the genetic information encoding the antibodies getting shuffled and mutated all the time. When a cell in the body gets stressed, it sends out a signal that a white blood cell(a macrophage to be specific ) can respond to. This white blood cell then invites another cell (a T-cell) to take a look.  This T-cell will then go out and talk to another cell (a B-cell), which has a catalog of antibodies available for production that the T-cell can peruse by seeing if the peptide, or protein part, that’s in the stuff the macrophage ate, is also in the B-cell. If any antibodies from the B-cell  bind to something in the T-cell saw in the macrophage, then the B-cell knows to produce more of that kind of antibody. After that, wherever an antibody encounters its target, it triggers a response from other white blood cells.

Sometimes a cell might be stressed, but the antibodies will bind to something that isn’t the cause. Molecules, from peanuts, pet hair, pollen or just about anything might happen to be present in greater quantities than the thing that’s really causing the problem. This is how allergies happen.

That’s the bad news. The good news is that because antibodies can be found for almost any kind of molecule around, scientist can used lab animals to produce antibodies to the proteins they want to study. Furthermore, by manipulating the genetics of the animal, they can cause each antibody to be attached to a fluorescent molecule. The antibodies can be stored in a vial in a freezer and transported cold to labs all over the world. All a scientist needs to do then, is bathe whatever he or she is studying in a dilution of the antibodies, and then look at the sample with a fluorescent microscope. Wherever the sample fluoresces, that’s where the protein is.

This process is called immunohistochemistry. Immuno- because it deals with antibodies from an immune response, histo- from the Greek for tissue, and chemistry because it deals with the binding of molecules.

Antibody production diagram is from A Positron Named Priscilla: Scientific Discovery at the Frontier (1994) National Academy of Sciences (NAS) ( http://www.nap.edu/openbook.php?record_id=2110&amp;page=69 ) all other images from wikipedia.

Super8review and excuse

I recently saw Super 8 at the theater. It was great, like a mix between E.T. and Godzilla, I give it a 8.5 out 10.Watching it gave me the same feeling as riding a ride at Disneyland or Universal Studios. I always felt like there was something else going on. There’s practically a war going on through out most of the movie, but the camera focuses on the children who are the main characters. You see a lot of the effects of the war without ever seeing what caused them. In one scene the wall of a room explodes away from the kids unexpectedly. Surprising, and it keeps things interesting. At first the alien didn’t seem very intelligent. It acts like some kind of monster through most of the movie, which I find a little annoying, but the movie makes up for it by the end.

I originally wrote a more extensive review of Super8 as well as some other movies, but it got lost when I hit ctrl-c instead of ctrl-v. My family and I got back late today from garage sale-ing. We ended up going all the way (about an hour) to Brentwood to go to an estate sale, which, it turns out, wasn’t going to happen until tomorrow (my brother’s fault:-)). We went to some other places though, so it wasn’t too bad. I got a bunch of old books, a portable tape player and a CD holder.

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