theiconoclast.info

http://www.media.rice.edu/images/media/2007RiceNews/0503_gleevec.jpg

In traditional chemotherapy, the goal is to kill cancer cells. However, the drugs that do this operate by only two mechanisms: damaging DNA and damaging the cell skeleton (the cytoskeleton). However, since all cells have DNA and a cytoskeleton, chemotherapy is not very specific to cancer cells. Consequently, chemotherapy is essentially poison; many different cells other than cancer cells are damaged and killed by it, leading to horrific side effects, and potentially, secondary cancers that have been caused by the chemo itself. Also, many cancer cells learn to repair their DNA and cytoskeleton, or pump out chemotherapeutic drugs. This renders them useless, as the cancer out –evolves treatment. Soon however, a new type of drug may change all of this…

Inhibitors. Inhibitors are drugs designed to block the function of specific biomolecules (usually enzymes or receptors) in or on cells. Usually, inhibitors are small, low molecular weight compounds that fit into the activation site of an enzyme, thus preventing it from binding its substrate and carrying out its function.

Inhibitors may be useful cancer drugs, as many cancer cells express and require oncoprotiens (cancer inducing proteins, the products of oncogenes, cancer inducing genes) and enzymes that normal cells do not express and need, or they express them at higher than normal levels. If inhibitors could be developed to these oncoproteins or enzymes, then theoretically, the cancer cells would die while the normal cells would be relatively unaffected. So, what‘s been done with inhibitors so far?

First, there is already an extremely successful cancer drug on the market that is an inhibitor: Gleevec. Gleevec is a drug designed to treat Chronic Mylogeneous Leukaemia (CML). It works by blocking the fuction of the Bcr-Abl tyrosine kinase, an oncoprotein that is only expressed in CML cells and stimulates their excessive growth and extended survival (i.e. makes them cancerous). Gleevec is highly successful in treating CML (though in most cases the patients relapse as the cancer evolves to overcome Bcr-Abl inhibition or prevent the drug from binding).

Furthermore, researchers have been trying for years to develop a telomerase inhibitor. Telomerase is enzyme, which in adult humans is only expressed in germ cells, activated lymphocytes, and cancer cells, that repairs the telomeres of chromosomes. The telomeres prevent apoptosis by preventing chromosomes from fusing to one another, and they degenerate slowly as cells go through replication. Since cancer cells divide so frequently, they have to develop a mechanism for repairing their telomeres; and roughly 90% of them express the enzyme telomerase to do this. If the function of telomerase could be stopped with an inhibitor, then cancer cells would die, as they would be unable to repair their telomeres. Though pharmaceutical companies have been unable to develop a telomerase inhibitor as of yet, such a compound would be a highly successful cancer drug with applicability to almost all cancer types.

Finally, research is currently underway to develop inhibitors to other oncoproteins and enzymes, notably, tyrosine kinases. Kinases are essentially “on” switches in cells; they turn on other proteins by adding phosphate groups to them. Tyrosine kinases, of which there are about 90, are kinases that are often involved in causing cancer. Much research is in progress to develop inhibitors to them, in hopes that they will serve as effective and specific cancer drugs.

So, why will inhibitor therapy become common place in cancer treatment? Inhibitors are already being developed, and they offer two huge advantages over traditional chemotherapy. First, although they will likely not be entirely cancer cell specific, they will definitely be more so than traditional chemo, and thus they will have fewer side effects.  And, more importantly, they will provide a different method to kill cancer cells, thus making the probability that a cancer would be able to out-evolve ALL our current treatments less likely. In my opinion, this will be their largest benefit.

Sources:

·         http://www.oncologychannel.com/leukemias/types.shtml

·         http://www.nature.com/leu/journal/v19/n9/abs/2403881a.html

·         The Biology of Cancer by Robert A. Weinberg

http://www.psychometric-success.com/images/PC0201.gif

The Myers-Briggs Type Indicator (copyrighted, I don’t know how to type that little thing that symbolizes copyrighted-ness) is a personality test given to over two million people in the United States per year. If you are a high school student, your school probably uses it somehow to help you think about careers and college. The MBTI will break down your personality according to where you fall on 4 scales: (1) extraversion/introversion, (2) sensate/intuitive, (3) thinking/feeling, and (4) judging/perceiving. It all sounds very nice, and very scientific.

However, I’ve always been skeptical of the Myers-Briggs test. I have three reasons for this. First of all, I have taken the test multiple times, and each time I have gotten different results. Second, how is one supposed to accurately answer some of the questions on the test? I would think that your response to such questions as “often you prefer to read a book instead of going to a party”, would be highly influenced by your mood and the context. Also, wouldn’t it depend upon which book and which party were being considered?

The final reason I’m skeptical about the Myers-Briggs test is the Forer effect. The Forer effect refers to people’s tendency to rate vague statements that could apply to anyone as uniquely descriptive of them. This is why people often believe that they meet the description of “their sign” in astrology. In personality tests such as the Myers-Briggs test, I believe that the description one receives of their type is so vague that it could really apply to anyone. For a more thorough and referenced debunking of the Myers-Briggs test and description of the Forer effect, check out my main sources below.

http://www.skepdic.com/myersb.html

http://www.skepdic.com/forer.html

http://www.healthsystem.virginia.edu/internet/hematology/images/AML-M4e3-website.jpg

An extremely unexpected thing will happen over the next few decades of cancer research: more types of cancer will emerge. Fortunately however, this will not be the result of pollution, novel genetic mutations, or any increased disease incidence. In fact, it will be a consequence of something that will lead to new treatment strategies and thus save many lives: better classification.

In the 1950s, researchers began to suspect that acute leukemia may come in more than one form, as some cases responded much better to treatment than others. However, most leukemia samples looked the same under the microscope, so scientists reasoned that the only difference must be biochemical. And, after roughly 40 years of research, research revealed that acute leukemia did in fact come in two forms: AML and ALL.

The distinction between AML and ALL has had a vast amount of therapeutic benefit, as ALL patients and AML patients must be given different treatments to ensure the best response to therapy. This raises the possibility that if doctors could classify other types of cancer into more specific sub-groups, then they may be able to provide more effective treatment for them as well. And indeed, this is what is already beginning to happen today…

Recently, scientists have learned that classic ALL can be broken down into two types of cancer. The first type carries a mutation in a gene known as MLL, and it is associated with infant leukemia, as well as a poor prognosis, while the second type of leukemia does not have a mutation in the MLL gene and is associated with a better prognosis. Furthermore, doctors believe that the first type of leukemia should be sensitive to a drug that inhibits the Flt kinase (I’ll cover the potential for inhibitors as a cancer treatment strategy in the next article), while the second type will not. Flt kinase inhibitors are currently in clinical trials. However, the key point is that identifying Flt kinase inhibitors as a potential drug would not have been possible without better classification. This is the type of research that will continue in the future. Furthermore, lymphomas, breast, ovarian, and colon cancer have all been further classified as of yet. There is no doubt that investigation in this area will continue, and hopefully many new drugs will be produced as a result.

Sources:

http://www.ncbi.nlm.nih.gov/pubmed/18282363

http://www.ncbi.nlm.nih.gov/pubmed/15680584

http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A65007

http://www.nature.com/leu/journal/v19/n9/abs/2403881a.html

http://www.innovations-report.com/html/reports/life_sciences/report-110666.html

http://www.oncologychannel.com/leukemias/types.shtml

MIT Open Courseware: Eric Lander’s Lecture #34 on Human Polymorphisms and Cancer Classification (in Course 7.012: Introduction to Biology, Fall 2004)

http://bizbox.slate.com/blog/google.jpg

I had planned to make this post titled “How to Cause an Earthquake”. But as I began my research, I had a different idea. The earthquake post is coming, but since I’m strapped for time today, I thought I’d go with my new idea.

Have you ever noticed that Google now tries to guess what you are typing before you finish? The interesting thing about this is that you can get an idea of what “other people” spend their time searching. Here are a few of my favorites:

Also, as result of this blog, Google now guesses my name before you can finish typing it. Of course a website about Polish plumbers also comes up… Ah well.

http://www.news-medical.net/images/breast%20cancer%20cell.jpg

In any movie that involves cancer, the story always ends with the patient, “doing well and in remission”. They never say cured. Why? Well, the sad truth is, most people diagnosed with cancer will relapse (the cancer will return) within five years after the cancer is no longer detectable. Even worse, the cancer often is now resistant to chemotherapy and radiation, and has begun to metastasize (spread). Tragically, as a result of this, death often follows shortly after relapse.

As horrible as this sequence of events is, it raises several interesting questions. First, why are some cancer cells able to survive the original treatment (chemotherapy, radiation, or surgery)? Also, why does the cancer return in a resistant and metastatic form?

Both of these questions have a similar answer. When doctors treat a tumor, with a chemotherapy drug for example, there will be a small number of neoplastic cells that will be resistant to the drug, and those cells will survive. How are the cells resistant? There are a variety of ways. Perhaps the drug works by damaging DNA, and a few cells happen to have mutations in genes that code for DNA repair enzymes, thus making DNA repair more efficient.  Or perhaps the drug works by targeting a specific cellular antigen (like Herceptin does), and certain cancer cells do not have this receptor. There are many other mechanisms that can grant cancer cells drug resistance as well. Whatever the case, the important fact is that small numbers of cancer cells often survive the initial chemotherapy and/or radiation regimen. (In the case of surgery, the surgeon may miss some cancer cells during surgery, which is why surgery if often followed by radiation/chemo.)

Once some cells have survived the initial treatment, they will begin to grow again. However, this time, the entire new tumor will be resistant to treatment, as it has originated from cells that were themselves resistant. The cancer has, in a sense, evolved to overcome the therapy. Furthermore, evolution favors any mutations in cancer cells that make them survive better. The ability to metastasize is such a mutation. Since any cancer cells that survived the initial treatment have had the chance to replicate far more often than the cancer cells that existed pre-treatment, they are far more likely to have acquired the necessary mutations for metastasis. This explains why tumors that recur after therapy are often metastatic.

So, what can we make of all this? Surgery, radiation, and chemotherapy can be successful in curing cancer. But often they cannot achieve durable cures, as they are selecting for any cancer cells that are resistant to them. For instance, there has been one case where a man’s CML (chronic mylogeneous leukemia) was kept in remission for eleven years, using a highly successful drug known as Gleevec. However, his cancer eventually developed resistance to Gleevec, and he died.

Since the development of resistance is such a common and deadly problem, what can be done about it? Well, first, it helps to think about the cancer cells in a person’s body in evolutionary terms. All the cancer cells vary slightly in their genotype and phenotype, and those that are best suited for survival (i.e. those that have mutations conferring therapy resistance and metastasis) will survive and reproduce the most. The cancer therapies of the future will utilize this knowledge to their advantage, and thus be better designed to eradicated all neoplastic cells and prevent relapse. They will likely do this in some of the following ways:

1.      A wider variety of chemotherapy drugs will be developed that work by many different mechanisms and are chemically distinct from one another. They will be chemically distinct and act by different mechanisms to prevent cancer cells from being resistant to both of them. This is already occurring today, and it is the reason that chemotherapy protocols involve more than one drug. Theoretically, any cancer cells that survive a chemotherapy regimen must be resistant to all the drugs it includes. Since the probability that a cancer cell will be resistant to two or more drugs is much less than the probability that it will be resistant to a single drug, cancer cells are less likely to survive, and thus relapse is also less likely to occur.

2.      The “Sucker’s Gambit” approach may become useful. This is an extremely theoretical approach at the moment, and it is just now being evaluated in cell culture. In the Sucker’s Gambit, those cancer cells that are not resistant to chemo and radiation would be somehow given an evolutionary advantage over those that are. For instance, perhaps those cells would be given a nutrient or growth factor that the resistant cells would not respond to. The nonresistant cells would then grow more than the resistant cells, and eventually out-compete them for resources, causing the resistant cells to eventually die off. The patient could then be given chemotherapy and/or radiation treatment, and relapse would be less likely, as resistant cells have already been killed off by evolution. See this link for a more thorough explanation of the research: http://www.wistar.org/research_facilities/maley/research.htm

3.      Certain cancers may one day be treated less aggressively but longer, in an attempt to keep resistant cells from proliferating too much. The goal would be to turn cancer into a chronic disease, like HIV infection, and to keep a tumor at a certain size instead of eradicating it. See this article for a longer explanation: http://www.sciencebasedmedicine.org/?p=518#more-518.

As always, just some speculation…

Brad Rybinski

Black Hole

“Black holes have no hair.” So said physicist John Wheeler. This statement seems obvious: a black hole is a region of space time that contains so much matter that its gravitational field is intense enough that not even light can escape from it. So why would a black hole have hair? But what Wheeler really means is much more interesting. Black holes may really just be giant elementary particles (elementary particles: proton, neutron, electron, etc.).

To begin with, what makes one type of elementary particle, say a proton, different from another, say an electron? There are really only three characteristics that differentiate them. The first is mass: the proton is bigger. The second is charge: the proton has a positive charge, while the electron has a negative charge. The third is spin: some electrons spin clockwise, others spin counter clockwise.

Now for a similar question: what makes one black hole different from another? It turns out that, like elementary particles, black holes have only three distinguishing characteristics: mass, charge, and spin. These are the exact same distinguishing features of elementary particles! (This is what Wheeler means when he says black holes have no hair: they are relatively similar to each other, and lack complicated hair dos to differentiate themselves.)

So, if black holes have the same distinguishing characteristics as elementary particles, are they the same thing. At first thought one may assume not; black holes are massive and elementary particles tiny. However, physicist believe that microscopic black holes the size of elementary particles do exist. And the other traits: charge and spin, can also be exact. So if one had a microscopic black hole that matched the exact size, charge, and spin of a specific elementary particle, might the black hole actually be that elementary particle? Who knows? For a more in depth look at this topic, check out: The Elegant Universe by Brian Greene.

Brad Rybinski

The Iconoclast: Imaginary Time

Most people know that Albert Einstein was a great physicist. What they do not know is that he was so much more than that. Einstein not only revolutionized physics, but he also helped avert a civil war, was a wise philosopher, offered the presidency of Israel, and, as a young man, had multiple girlfriends. Indeed, most people don’t know that Einstein was in fact more of a god than Jesus Christ. But I digress…

One of the things Einstein discovered is that space and time is essentially the same thing. The phrases “far away” and “long ago” actually have the same meaning in the language of the universe. There is not “space” and “time” in the universe, there is only “spacetime”.

For instance, as I write this, it is Sunday, August 9, 2009, at 1:54 AM, and I am in my basement, typing on my computer. Now, let’s ask an interesting question. Where was I a year ago (August 9, 2008) at this time, 1:54 AM? I was at the University of Delaware Campus, and I was taking Marine Biology Camp. Now for a better question. “What” separates the Brad Rybinski typing this blog from the Brad Rybinski that was at the University of Delaware?

Well, you might say 1 year. But that’s not exactly true. If it were just 1 year, I would have been sitting at my computer on August 9, 2008. So you must also account for distance. The University of Delaware is roughly 20 miles from my house. Therefore, one could say that the Brad Rybinski at Marine Biology camp is one year and 20 miles away from the Brad Rybinski typing this article.

But remember, space and time are actually part of the same thing. So is it possible to calculate how much space time separates the current Brad Rybinski from the one in the past? In other words, can we convert two measurements, the measurement of distance and the measurement of time, into a single measurement of spacetime? We can. The physicist Hermann Minkowski showed how.  Lets roll…

1.      Everything in science is done in metric. So first, convert 1 year to seconds, and 20 miles to kilometers.  1 year = 31,556,926 seconds                20 miles = 32.18688

2.      Take the time difference (31,556,926 seconds) and multiply it by the speed of light (300,000 km/second). This will convert time units to units of distance.       

9.4670778 x 10^12 km

3.      3. Square the distance in space. 32.18688^2 = 1035.995244

4.      Subtract the number from step 2 from the number in step 3. 9.4670778 x 10^12 km - 1035.995244 = - 9.4670778 x10^12 (My calculator apparently lacks sufficient resolution to get the exact answer, but we can proceed nevertheless.

5.      Take the square root. This will produce the distance in spacetime, in kilometers.

(- 9.4670778 x10^12)^(1/2) = (3076861.68) i kilometers

Hmm… So we’ve calculated distance in spacetime, only to get an imaginary number. What does this mean? Math teachers constantly remind students that negative distance has no meaning. So what on earth would imaginary distance mean? I have no idea, and physicists don’t have that many great ideas. The only thing that physicists know for certain is that the presence of i tells us that space and time, though part of the same thing, are still different in some fundamental way; space is still space and time is still time. This obviously agrees with our experience in the world. Oh physics…

Brad Rybinski

Sources:

About Time: Einstein’s Unfinished Revolution by Paul Davies

http://blogs.discovermagazine.com/cosmicvariance/files/2008/11/time-flies-clock-10-11-2006.gif

The Iconoclast: The Rise of Immunotherapy

I am by no means an expert or doctor, but cancer and molecular biology are my two favorite areas of science. So I read papers, listen to lectures, and study textbooks in these fields. Though I have an incredible amount left to learn, I definitely have accumulated some knowledge and opinions over the years. With that caveat, I’ve decided to write a four part series (it will be posted every Sunday) describing what I believe the future of cancer treatment will look like. Most of what I say will be speculation (duh), but it will be based on facts and current research trends. So, here we go…

“Immunotherapy, the use of the immune system to attack a patient’s cancer, will rise to the level of surgery, chemotherapy, and radiation as a fourth major treatment strategy for cancer.” Current cancer therapies include the use of surgery to remove tumors and the use of either chemicals (chemotherapy) or radiation to kill neoplastic (cancerous) cells. However, immunotherapy will harness the cells of the body’s immune system, and get them to recognize cancer cells as foreign, and eventually destroy them.

First, what evidence do scientists have that the immune system can kill cancer cells? After all, if the immune system could recognize and kill cancer cells, wouldn’t cancer patients eventually fight off their cancer, just as people regularly fight off and recover from the flu? Though this is a valid question, and its answers have hindered the development of immunotherapy as of yet, there is strong evidence that the immune system can recognize and kill cancer cells to some extent. Amplifying this ability will form the core of immunotherapy.

The first piece of evidence that the immune system can fight cancer comes from a depressing statistic: people who have received organ transplants are significantly more likely to get cancer than members of the normal population. How significantly? It varies for different cancer types, but we are not talking about small numbers. People who have received transplants are 14.3 times as likely to get thyroid/endocrine cancers, 13.8 times as likely to get some form of mouth cancer, 10.3 times as likely to get Non-Hodgkin’s lymphoma, 9.1 times as likely to get kidney cancer, and 5.5 times as likely to get bladder cancer. The incidence is dramatically increased in other cancers as well. (Source: The Biology of Cancer by Robert A. Weinberg, page 680). Why is this the case? As it turns out, most patients who receive organ transplants must take immunosuppressant drugs in order to keep their immune system from attacking their new organ. The thinking is that, since a suppressed immune system seems to correlate with an increased risk of cancer, then the immune system probably plays some role in preventing cancer development. The same increased cancer risk is found in AIDS patients. Correlation does not ensure causation, but such strong correlation is extremely suggestive. There have also been many experiments in mice that show that a reduced immune system makes them more easily develop cancer.

So what exactly is immunotherapy? Immunotherapy currently comes in three main forms:

1.      Cancer vaccines. See this previous Iconoclast interview for an explanation: http://theiconoclast.info/?p=102.

2.      Passive immunization. Passive immunization consists of injecting a patient with an antibody to their cancer cells. Certain neoplastic cells have an abnormal pattern of antigens on their surface. Abnormal antigens may be present, or normal antigens may be present in increased numbers. Passive immunization consists of injecting an antibody to such an antigen, thus causing the antibody to bind the cancer cell and (1) prevent it from growing and replicating and/or (2) target it for destruction.

3.      Bone marrow transplantation. The immune system is generated by cells in the bone marrow. A common treatment for many hematological cancers, such as leukemia, is to give patients what is known as a bone marrow transplant. This usually results in a cure. In a bone marrow transplant, the patient’s own immune system is either partially or completely eradicated (using drugs and radiation). They are then given new bone marrow from a completely different person (known as a donor). This bone marrow then regenerates the immune system, and the patient ends up with a replica of the donor’s cancer free immune system.

The original intent of bone marrow transplantation was to cure cancer by simply replacing the cancerous immune system with a noncancerous one. However, though cures were being achieved, scientists soon realized that the cures were not entirely a result of simply “replacing the bad with the good”.  There was a much more exciting phenomenon going on…

The graft versus tumor effect. As it turned out, some cancer cells still remained inside the body after the attempts to destroy the immune system. However, the newly generated immune system of the donor recognizes these cells and destroys them. This results in a long term cure. Though the graft versus tumor effect does not cure solid tumors (large tumor masses create an environment near them that renders many killing cells of the immune system useless), research is currently underway to understand exactly why this is, in hopes that one day the graft versus tumor effect may be used to treat solid cancers.

So, has immunotherapy been tried yet in humans? Has it been successful? The answer to both questions is yes. Passive immunization is already in clinical use. The vaccine Herceptin is being used to treat some forms of breast cancer, specifically those that over-express the HER-2 antigen. Many more passive immunization procedures are being investigated. The other type of cancer vaccine, the kind described in the interview with Dr. Parcells that relies on immunostimulatory molecules, is currently in clinical trials for a variety of cancers. And finally, researchers have begun to report preliminary evidence (just a few case studies) in which bone marrow transplants have caused remission in solid cancers (breast and ovarian so far). Though there is much work left to do, and still huge obstacles to overcome, I believe that one day immunotherapy will be a common and effective type of cancer treatment.

Brad Rybinski

Sources:

·         The Biology of Cancer by Robert A. Weinberg

·         http://www.herceptin.com/pdf/AdjuvantCorePatientBrochure-NEW.pdf

·              http://cancerres.aacrjournals.org/cgi/content/full/68/8/2561

·         http://www.ncbi.nlm.nih.gov/pubmed/12531922

·         http://jco.ascopubs.org/cgi/content/full/22/19/3846

·         http://annonc.oxfordjournals.org/cgi/content/full/18/10/1751

·         http://www.nature.com/bmt/journal/v25/n6/full/1702206a.html

·         http://www.centocor.com/centocor/images/immunology.jpg

A few weeks ago, I met a girl who informed me that, if I want an interesting experience and have some free time, I should deprive myself of sleep and see how I feel. She told me that, if you haven’t slept for 72 hours, you are classified as legally insane. Furthermore, she said she tried it and kept a journal of her experiences. Obviously, I hang out with interesting people.

Never the less, I took her world for it. I wanted to try this, and write about my experience here. But my parents wouldn’t let me. So I decided to do the next best thing. Research it and see if I could find a sleep deprivation report to post here.

First of all, it turns out that there is no objective law that states “Anyone who has not slept for 72 hours is considered legally insane.” This is an urban myth. However, sleep deprivation has many affects on the body, and may be a possible reason for insanity if argued in court. Instead of listing and describing the affects of sleep deprivation, here is a journal of someone who deprived themselves of sleep for five days:

It is

1:00 PM, Saturday, March 27.

I haven’t slept in 5 hours.

I’m feeling normal right now. I slept ~8 hours last night.

———————- It is

2:00 PM, Sunday, March 28.

I haven’t slept in 29 hours.

Right now I’m feeling drowsy. I’ve been drinking a cup of coffee every now and then, and it’s working well. Through the night, I kept myself occupied as best as I could with movies and computer games. Staying awake wasn’t a challenge. I have no change in mood at the moment, although I am starting to feel slightly sluggish. I’m not quite as enthusiastic as I usually am about day to day activities. Overall, nobody I associate myself with has been able to tell I’m lacking sleep.

———————-

It is

5:00 PM, Monday, March 29.

I haven’t slept in 56 hours.

Right now I’m starting to get extremely apathetic towards everyday things. My performance in day-to-day dealings and events is extremely uninvolved. I’m starting to get slightly irritable and impatient with people who make mistakes/act stupid around me. Staying up is increasingly difficult. I find that if I do anything aside from quickly blinking, I nod off to sleep. This has happened 5-6 times, but I’ve snapped out of it. Caffeine is becoming a major factor in staying awake. I can’t perform complex literary/mathematical functions without many careless errors. Through the night I no longer watched TV - I was in danger of falling asleep. I must keep myself involved… busy to stay awake. My eyes are becoming slightly red, and slightly pained. This pain can only be relieved by closing them, which I simply cannot do. My reflexes are beginning to slowly dwindle.

It took me a while to correct grammatical and spelling errors in this update. There may still be some, but I don’t have the patience to fix them.

———————-

it is

8 pm, wed march 30′

i haven slept in 83 hrs

i can barely keep my eyelids open. i have to fight so hard not to just lose it and fall asleep. will power is is starting to become i bigger part of staying awake. ive abandoned any sort of activivty to requires intense attention because i just get frustrated- i lash out at people that get in my way and i find myself to be really irritable whn i can muster up enough energy and will power to yell at someone. caffeine is constantly coming into my body, and ive taken severla nodoze tablets. im not going to try anything illegal like meth because i decided this should be fairy level stated when awake this is really fucking difficult. i feel extremely apathetic to all sorts of things right now and generally dont give a shit. my eyes are extremely sore right now, and very red on top. at hour 70-72 somewhere i developed a dull headache that has been grwing in tension. i feel terrible and am close to mentally giving up and sleepng

-phlab,

———00000000

it is 6pm wednesd mar 31

havent slept in 105 hrs

my eyes are burnng horribly an seem to be bloodshot. as far as reaction time goes, its almost nonexistant. i had friend throw something at me, and didnt even bother flinching. needless to say it hurt, but felt duller and insignificant to if i was rested. nothing but incoherent thoughts ar ronning through my head, i cant concentrate on a thing. when i do talk i ramble nmeedlesly, mumbling notbhing but jibberish. my sense of taste is dwindlng, althoy i think i may just be imagining it. i try to keep myself busy drinkng coffee and other diuretics to keep myslf busy and pissin so i cant sleep with full bladder. as im writin this, im in danger of sleeping because this chasir is padded. i must stay in unconfortable positions endlessly to stay awake. my muscles are aching and sore all over my body from not gvng them a break. asi attemtp to watch tv, im tryng to listen and comprehend but its extremely unclearand i dont understand dont understand. i think i may be hearing things, auditory hallucinations, but im gambling thats its simply a placebo effect because thats what im expecting. i cnst explain myself right now ,this is so full of errors but i cannot allot my concrentration tow fixing thm,. if these auditory hallucinations continue and i can confirm that theyy rre actully hapnign, im stang up 6 dyas. hah. i doubt that somehow. i just want o sleep, its all i can hthink about. im feeling delirious-

with l ove

phlab

—————————————————

its 3pm, thurs. april 1

i haven not slept in 126 hrs

my mental aptitude is completely shot. words that come out of my mout are completely random ; nonsensicle. i have found a good way of keepng myself awake and active is wlaking around the neighbordhood. the fresh air, sun, and public environment somehow tells me brain it is not appropriate to fall asleep in the outdoor public setting, which somehow is relieving some of the severe urges to sleep. in addition to complete mental exauhstion, i am physically deprived. i cannot eat a thing, only takng in liquids. my appetite is completely gone, i havent eaten in 14-16 hours or so. time is beginning to drag, an percetion of it is slightly more difficult. my entire body is sore and the pain in my eyes is at a peak as im writing. the headache has gradually increased and is making is difficult to to stay much mawake more. in additon, i am developing a slight stomach ache that is more of a nuisance than anything. when all physical ailments are combined with complete mental emptyness this makes for an awful experience. i am certiain i am hearing audioty hallcunations - i hear a cat mewo despite thatfact thast i own no cats. i also hear a weird series of bleeps in different tones - i cannot find the sourceo f them. i snap in and out of an almost trancelike state wher i look at a random object an space out. ifeel delirious, a frien came over to check on me asi told him to, and he thought it was funny that my statements were halfbaked nonsensical jibberish. i no longer simply walk - it is more of a staggerlike lurchin g. my balance is also off. out of the corner of my eyes i believe im seeing visual disturbances an interruptions. no hallucinations - i imagin thos come muhc later - just ripples an slight distortions in my periphial. it may not even be a true hallucination, just delerium. i am so fatigued tha if sonmeone offered me to sprint around a track once for 100 grand, i most likely couldnt. when i fill my head with thoughts of going to sleep and curling up in bed under a blanket, i get a dumb smuile on my face. for all i know, it could be my brain releasing positive chemicals of some sort to will me into sleepng. i hope what i’m saying is makng sense. i have little attention span and my short term memory seems to to be weakened so i wrote thi update over about half an hour. i hav reached my goal an will stay up slightly longer to futrher explor auditory hallulcinations and see if the visuals increas. if not, im going to go to bed. i have a grin on my gesicht jsyt thinking about it,.

thansk for readng. it will be interesntg to go over this log when ii ma fully rested an analy it a little after sleepngm.for the record the only stimulant usedd was caffeine, wich i stope usng 12 hrs ago becauee the comedown was killin g me./

goodnight. dropping into bed will be GOOD FEELNGI..

Phlab-

Source: http://www.modrs2.info/en/fringe/fringe_science/effectsofsleep173704.html

The Iconoclast: Protein Videogame

Chances are, if you read this blog, you are pretty fluent in the ways of a protein.  If not here’s the basics.  Proteins are made of a series of molecules called amino acids.  The sequence of amino acids in a protein determines that proteins unique shape.  The shape of the protein determines its function in the human body. 

            The process by which an amino acid chain twists and contorts itself to produce the final protein shape is known as folding.  Here’s the problem: scientists do not completely understand the process of protein folding.  A protein folds so quickly that it is pretty much impossible to observe.  Knowledge of the process of protein folding could lead to the ability to predict protein structure and ultimately be used to design proteins to combat various diseases such as cancer and Alzheimer’s.  

The inability to observe the process of protein folding did not halt its study.  Armed with the knowledge of the basic principles behind folding, biologists used supercomputers to try to reproduce the shapes that actual proteins had.  The results were close, but not perfect. 

Then came a distributed computing network known as Folding@home (folding.stanford.edu).  Developed by Stanford University, the program draws on the computing power of home computers and Playstation 3’s to simulate protein folding.  If you so feel, download the program from the website and start making a contribution to science, though if you keep reading, you’ll see there is a better way to do this. 

I’d now like to introduce you to the game Foldit, downloadable from the website: fold.it (it’s a pretty nifty URL).  The idea of the game is simple; a computer generates a rough color-coded model of what a series of amino acids will fold into.  Then you, using your mouse and keyboard, tweak the protein into better, more fitting shapes according the basic rules of protein folding.  If you download the game, you’ll be greeted to a tutorial that explains how to do it much better than I can.  Proteins designed by Foldit users have proven to be better than those conceived by the best computers out there.  So give it a try, play some Foldit!

Sources:

http://fold.it/portal/info/science

http://www.wired.com/medtech/genetics/magazine/17-05/ff_protein?currentPage=all

http://flowtv.org/wp-content/uploads/2009/02/fold.jpg (picture)

The above article was graciously contributed by Rohit R. .