On the value of peer review

Just thought I'd post this comment that I excerpted from a message board. It discusses the value and limitations of the peer review process.

I don't think its the peer review that is the problem, but rather our perception of what it means.

Peer review is just a way of vetting an article to make sure it's not whacked out. The reviewers don't repeat experiments, recalculate all the data, etc.

Being published in a peer reviewed journal simple means that the author has made a respectable argument. Kinda of like a indictment.

The actual court case doesn't happen until after it's been published. When others may dispute the results, repeat the experiment, etc.

But the simple fact that the article has been published in a peer review journal does not make it inherently correct, just like being indicted for crime doesn't mean you are actually guilty.

Tobacco mosaic

Adapted from the book, Scientists and Discoveries:

In 1892, Dmitry Ovanovsky, a Russian botanist, investigated the sap from tobacco plants affected by mosaic disease. This is a condition that stunts the growth of tobacco plants and mottles their leaves in a characteristic mosaic pattern (hence the name). He passed the sap through filters so fine that they would trap all known bacteria. The sap retained its ability to produce the disease in new plants. Ovanovsky thought there was some flaw in his experiment, not realizing that viruses (which had not yet been discovered) were at work.

Bull snake

I captured a bull snake recently -- twice, in fact. It was a pet snake that had escaped, and I found it in my closet three days later. I placed it in a temporary travelling cage so that I could show him to some children, but after I brought him home, he managed to pop the lid off the cage overnight.

That does it. Next time, I'm placing him directly in his permanent cage. Ugh.

Inaccurate assay description

I just discovered that this site says, "ELISpot assays employ the sandwich enzyme-linked immunosorbent assay (ELISA) technique." That is not very accurate. To be sure, there are some undeniable similarities between the ELISPOT method and the ELISA assay technique, but it's a bit of a misrepresentation to say that the former uses the latter. I would certainly be extremely uncomfortable making such a claim.

Yeargh.

Originator of chaos theory dies

Edward Lorenz, the man who created the field of chaos theory, died on Wednesday at the age of 90. His name will be unfamiliar to most of the world, even among the well-educated, yet those of us who have studied his work will surely mourn.

As the cited article says, "His discovery of 'deterministic chaos' brought about 'one of the most dramatic changes in mankind's view of nature since Sir Isaac Newton,' said the committee that awarded Lorenz the 1991 Kyoto Prize for basic sciences. It was one of many scientific awards that Lorenz won."

Cytometers

Cytometers are used for counting cells. Biotech applications that involve various cell types use cytometers to keep track of the types and quantities of cells. For example, a hemocytometer is used in biotech applications that involve blood cells.

Traditionally, cytometry was performed using microscopes and special cytometry slides. This made it a tedious and laborious process. Even a skilled scientist can only count about 200 cells per minute.

Nowadays, much of cytometry is more thoroughly automated. For example, a flow cytometer employs monochromatic light (typically a laser beam) to enumerate, sort, and identify cells within a laminar flow of liquid.

Dysthymia

Dysthymia is basically low-grade depression, being less severe and pervasive than major depression.According to the APA, two or more of six possible symptoms must be present for a diagnosis of dysthymia. Symptoms can include the following:

Poor appetite or overeating
Insomnia or hypersomnia
Low energy or fatigue
Low self-esteem
Poor concentration
Difficulty in making decisions
Feelings of hopelessness.

For a proper clinical diagnosis, an individual must experience symptoms for at least two years and should have no longer than a two-month period without symptoms being present. These symptoms must result in clinically significant distress or impairment in social, occupational, academic, or other major areas of functioning (APA, 2000).

Microplate readers

The following has been excerpted from Biotechnology 101 by Brian Robert Shmaefsky. Some grammatical issues have been corrected. Also, please note that the description provided in this excerpt is a bit simplistic. It's accurate when it comes to ELISA assays, but not for assays in which specific structures are generated, such as FluoroSpot and ELISpot assays or colony counting applications.

"The microplate reader works by shining a particular type of light at each of the samples in [a] microwell plate. It can be adjusted to[sic] in various ways. It can read a few to all [of] the samples in a particular sequence or it can read several samples at a time. A particular type of light is selected based on the type of analysis being done. Some chemicals absorb a particular color of light. Their presence or quantity can be determined by measuring how much of the light is absorbed by the sample. This is called absorbance detection. Hence, a scientist looking for the production of a particular chemical made by a cell would notice more and more light being absorbed by the reader as the chemical is produced. Some chemicals glow when exposed to a particular light. This is called fluorescence detection. The amount of chemical is measured by the intensity of glowing. Microplate readers feed the absorbance or fluorescence measures into a computer program that analyses the particular information being collected."

BTW, this guy could have used a better editor.

Groups of animals

I came across teh follwoing list of unusual names for animal groupings. Thought I'd post it here.

A convocation of eagles
A prickle of porcupines
A charm of finches
An unkindness of ravens
A skulk of foxes
A shiver of sharks
A troubling of goldfish
A pod of whales
A smack of jellyfish
A descent of woodpeckers
A mob of kangaroos
A zeal of zebras
A shrewdness of apes
An exaltation of larks
A battery of barracudas
A troop of monkeys
A kaleidoscope of butterflies
A parliament of owls
A quiver of cobras
An ostentation of peacocks
A murder of crows
A rookery of penguins

ELISA spot in a flash animation

I love using visual aids to educate myself. I wish that I had more of them available when I was growing up. Heck, I wish that I could use them more extensively in my current self-education.

That's why I like this little animated clip. It depicts a biological assay that's used to capture the secretory footprints of blood cells. Certain B cells will secrete certain antibodies, for example. Additionally, different T cells will secrete different types of cytokines. That's the kind of assay that's depicted here. It shows how many T cells responded with a given cytokine to a particular type of stimulus.

Smallpox

The National Institutes of Health (NIH) is attempting to develop a new, safer vaccine against smallpox. This is part of an ongoing attempt to protect the nation against the threat of bioterrorism and bioweaponry--that is, the use of weaponized pathogens. Similar research is being conducted to protect the populace against other diseases, such as the plague.

Various species of monkeys have been used to test the efficacy of the proposed vaccine (modified vaccinia Ankara, or MVA). Monkeys are inoculated with MVA, then exposed to the monkeypox virus, which closely resembles smallpox. The researchers then determine if the vaccine provides any protection against the virus. Unfortunately, this does result in the monkeys' deaths.

It would clearly be unethical to test the vaccine on humans in the same fashion. (I have a hard enough time thinking about these poor simians.) Fortunately, the ELISPOT technique allows immune response monitoring to be performed ex vivo; that is, without injecting any pathogens into a human host.

SciWeb

Nothing earthshaking, folks. I just wanted to plug the SciWeb website. It's pretty neat and a pretty good informational resource for life science research, equipment and so forth.

I especially like the SciJobs section. Oh, I'm not looking for a job, mind you. However, I wish I had known about this resource four years ago, when I was searching for employment. The company directory and press releases sections are also quite nice. So is the product announcements section, although some of the announcements appear to be kinda trivial.

I would kinda like to advertise this job opening that my employer has; however, I don't think we want to spend any money on these job ads.

Manipulator grasp classifications

Gripper and fixture grasps can fall under different categories. The two most important grasp classifications are known as form closure and force closure grasps. These terms were first used by Reuleaux in his studies of machine design, and were later applied to robotic grasping by Salisbury. However, recent inconsistent use of these terms has confused their meanings.

A fixed set of contacts on a rigid object is said to exhibit form closure if the object's equilibrium is maintained despite any possible externally applied wrench (i.e. a force, a torque, or a combination thereof). In other words, the geometries and relative poses of the object and the contacting body--a gripper or fixture, for example--suffice to hold the object in place with complete kinematic constraint. Form closure is therefore more preferable to force closure, in which the applied manipulator force is further required as a consideration.

In developing a gripper or fixture, one should therefore strive for form closure. In certain important instances, however, this would be is impossible. For example, any part which is axisymmetric (such as a sphere) cannot be kinematically constrained in form closure. Under such circumstances, a robotic manipulation strategy should strive for frictional form closure (a type of force closure) instead. Under frictional form closure, friction contributes to immobilize a grasped part which is otherwise not fully kinematically constrained by a gripper.

Multiple sclerosis

Disseminated sclerosis is a chronic, inflammatory disease that affects the central nervous system. It is more commonly known as multiple sclerosis. Its symptoms include changes in sensation, visual problems, muscle weakness, cognitive impairment, dysfunctions in balance, speech and muscular coordination, severe fatigue, depression, overheating, and pain.

Multiple sclerosis is believed to be an autoimmune disease in which some unknown trigger initiates an immune response against brain proteins. This is known as an autoaggressive response, and according to this hypothesis, it causes the breakdown of the myelin sheaths that protect nerve axons. This leads to impaired nerve conduction and subsequent neurodegeneration, both of which are characteristic of MS.

Epitope mapping has applications in understanding multiple sclerosis. This mapping can be performed using ELISPOT assays.

Revisiting ELISA Spot assays

ELISA spot assays are used for the quantitative determination of single cells secreting a specific cytokine. They are known as ELISA spot assays due to their similarities to the ELISA method, but nowadays, they are more commonly referred to as ELISPOT assays.

Kits are available which contain the basic components and protocols required to perform colorimetric assays wherein one spot marks one cell to be identified.

Blood, plasma and serum

Well all know what blood is, of course. It's that red stuff that circulates through your body. More specifically though, blood is composed of plasma and blood cells suspended in plasma, a clear, yellowish fluid that makes up more than half the volume of blood.

Blood cells can be categorized as erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets). These are suspended in the plasma with other particulate matter.

Serum is the clear, cell-free fluid that is left over when the cells and clotting factors are removed.

Leonardo and science

Leonardo da Vinci is often applauded as a great scientist, in addition to being a great artist. He was a Renaissance man in every sense of the word.

But a scientist? Not in a strict sense. He dabbled, but he generally (if ever) did not draw firm conclusions, as a true scientist would. His methodology was more observational than anything else.

Oh, and please don't call him "da Vinci." That's not his name. "Da Vinci" is Italian for "from Vinci," and simply denoted where he was from. Check out any encyclopedia and you'll see that they refer to him as "Leonardo." So do art historians. Anyone who calls him "da Vinci" is simply speaking out of ignorance.

Curse you, Dan Brown, for perpetuating that bit of misinformation (along with the many other falsehoods recorded in your book)!

Cytokine production by different blood cell types

Spot size and morphology frequently allow researchers to distinguish cytokine production by different cell types within mixed cell populations. For example, when IL-10 production by human peripheral blood mononuclear cells (PBMC) is measured in ELISPOT assays, most of the “antigen-induced” spots are not T cell derived (as would be expected), but are produced by macrophages in response to LPS contamination of the antigen. Such macrophage-derived IL-10 spots are considerably smaller than the IL-10 spots generated by antigen-specific T cells. While the LPS-induced macrophage-derived spots provide no information on specific immunity, the antigen-induced T-cell-derived IL-10 spots do, since they indicate the presence of T regulatory cells. In order to measure the latter, the former need to be excluded from the counting results by setting appropriate size thresholds. ELISPOT image analysis must therefore be capable of distinguishing different spot sizes and morphologies to provide information relevant for T cell diagnostics.

The antigen dose affects the cytokine secretion rate of T cells. Stimulation of a T cell clone with a high dose of the nominal antigenic peptide induces stronger cytokine production in the individual T-lymphocytes (that is, it triggers larger and/or denser spots) than does the stimulation of the same clone with low dose peptide. Therefore, when stimulated with a single antigen dose, as is frequently the case in ELIPSOT assays, high-avidity T-lymphocytes within the PBMC produce larger spots than low-avidity clones. Confirming this notion, increased T cell costimulation was shown to result in increased per cell productivity. In diseases such as HIV, the per cell cytokine productivity can be reduced, resulting in smaller spots. One advantage of ELISPOT assays is their ability to determine whether decreased net cytokine production in disease states is caused by a decreased number of cytokine-secreting T cells or from reduced per cell productivity by unchanged frequencies of T cells. In order to compensate for physiological and pathological variations in per cell productivity, ELISPOT image analysis tools must therefore be versatile, with the ability to permit fine-tuning of the image processing parameters.

More about the limitations of science

Continuing the previous discussion about the limitations of science...

I mentioned that some people insist that the scientific method is the only way through which truth can be discerned. I also mentioned that when they say that, I ask "so what scientific methodology did you use to determine that to be true?"

Unfortunately, that doesn't stop some people from insisting on that claim. Instead of re-examining that belief, some of them say "But it's true! It's obvious!" or words to that effect. The thing is, unless one can demonstrate it to be true [em]using the scientific method[/em], that claim remains unsubstantiated.

Indeed, how would one even begin to test this claim? I ask people that sometimes. Some of the more hard-headed ones say, "Well, you design an experiment to test this belief, and then you conduct the experiment. That's how science works!" However, this answer completely glosses over the question of HOW someone would design such an experiment -- or even if such an experiment is possible.

Some go a bit further, and say "Well, you take all the possible methods of learning knowledge, and then you test every single one of them. That will prove that science is the only means to knowledge." This answer is a bit more complete, but still unsatisfactory. For one thing, it ignores the question of HOW one would identify all the possible paths to knowledge. And second, it dodges the question of how one would test all these methods.

Indeed, how would one know that one has identified all paths to knowledge? For that matter, how would one know that ANYTHING is a means of discerning truth? If the claim is true, then one must first conduct a scientific experiment to establish these things to be true.

What's more, if someone is to claim that science is the ONLY way through which knowledge can be truly obtained, then one must test ALL possible methods under ALL possible circumstances. For if there is even a single situation in which one of these methods can work, then the scientific method is not the sole means to truth.

This is why I'm severely disappointed when people claim that only science holds the keys to truth. It's a statement that sounds neat, but which people often don't examine closely. It has no basis in reality.

The limitations of science

Every now and then, I hear people claim, "The scientific method is the only way that truth can be known!" The problem is that this is a self-refuting claim. It also betrays great naivete about the nature of science.

Self-refuting, you say? Yes indeed. Consider this: If the scientific method is the only way by which truth can be known, then what scientific methodology would one employ to arrive at that truth? The people who make this claim clearly have not performed any such experiment, and so their claim remains unproven. What's more, it CANNOT be demonstrated to be true, since one would have to identify all possible alternatives to science and then demonstrate that none of them are ever valid.

"But it's obvious!" some exclaim. Well, if you claim that it's true by virtue of being obvious, then you're not using the scientific method. Rather, you are claiming that something is self-evident. Ergo, you have implicitly demonstrated that science is not the only means by which truth can be discerned.

I know one guy who says, "The methodology that I use is observation. It's science!" Um, no. Observation is merely the first step in applying the scientific method. It is not an example of scientific methodology. Without the subsequent phases of hypothesis-forming and experimentation, one does not have a scientific method.

Indeed, there are things that science implicitly assumes, and thus, cannot prove. It assumes that the laws of logic and mathematics are valid, for example. As such, attempting to prove these tenets using science would amount to circular reasoning. Now, I'm not about to deny that the laws of math and logic are valid; however, my point is that one cannot use science to prove their validity. That would be begging the question, pure and simple.