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Monthly Archives: May 2013

Making decisions from limited data

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Daniel Kahneman was profiled on NPR’s Science Friday Desktop Diaries segment last week. In this segment Flora Lichtman interviews scientist / researchers and used desktop trinkets to get a personal view of the human being behind the science. Daniel Kahneman, who won the 2002 Nobel Memorial Prize in Economic Sciences for his work in psychiatry including 1974’s Judgment under uncertainty: Heuristics and biases published in Science, which helped establish an understanding of people’s predictable irrationality (sounds like another book I enjoyed) in decision making stemming from the belief that severely limited data can provide predictive power. In his own words, he describes this as, “regressive prediction, that is that people make absurdly, extreme predictions on the basis of very weak evidence. If I tell you about this graduating senior and I call her Julie that she read at age four. And I ask you what’s a GPA? You have an answer. An answer comes to mind. I mean, you know, that’s ridiculous. And somehow, it’s a very narrow range of answers, and it’s that sort of answer that comes to everybody’s minds.”

I was struck by something in that and have been trying to find some data on it for a couple hours. The problem is that I’m not sure how to search for it. What I want to know is, ‘is this really so ridiculous?’ That is, has anyone ever gotten data on this? And if so, do we know that it doesn’t correlate?

Because if it does, maybe we (all humans, apparently) are not so silly for believing this. His assumption only makes sense if he is sure that what we are jumping to a conclusion about it wrong. If it’s right, maybe the connection isn’t so spurious.

Perhaps I am making too much out of a short remark, but it did interest me to know whether or not there has been data collected that could answer this question at all. 

My wife has recommended his book, Thinking Fast and Slow, to me several times. Perhaps I should pick it up. 

Please, if you know of any data about this one question (reading age vs academic success) please forward it to me here and I will take a look at it. Or, better yet, write it up on your own blog and we can link to one another.Image

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Posted by on May 24, 2013 in Uncategorized

 

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Jony Ive’s new look for iOS 7: black, white, and flat all over

I’m conflicted about the imagined designs for iOS7 shown here. I really think my iPhone is perfect as it is, but I also know that really good, simple design is very compelling and, let’s face it, Jony kind of has a decent track record.

 
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Posted by on May 24, 2013 in Uncategorized

 

Penicillin

A great old government film touting the discovery and promise of Penicillin:

Penicillins are a group of drugs naturally produced by penicillium molds. The antibiotic activity of penicillium was first observed by Alexander Fleming in 1928. He recognized the value of what he was seeing, but was unable to isolate the molecule that mediated the activity and therefore could not perform appropriate trials. It was not until Howard Florey and a team of researchers including Ernst Boris Chain and others from the Sir William Dunn School of Pathology, University of Oxford managed to isolate and purify the substance that its great promise became evident. (later Fleming, Florey and Chain shared the Nobel Prize in Medicine for their work)

Alexander_FlemingA number of naturally occurring penicillins exist, each characterized by a beta-lactam ring joined to a variable R-group. These drugs may be effective in the treatment of certain, susceptible (mostly) gram positive bacteria. The mechanism of action is the inhibition of peptidoglycan crosslinks in the bacterial cell wall, such that organisms cannot produce new cell wall and wind up shedding the wall during division. Without the cell wall, the bacteria is highly susceptible to immunological mechanisms and is readily killed.

ImageUnfortunately, many otherwise susceptible bacteria produce an enzyme (penicillinase / beta-lactamase) that cleaves the beta lactam ring structure leaving it ineffective. This single enzyme can be easily passed from one bacteria to another via a sex pilus or transformation rendering them non-susceptible to the antibiotic.

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This enzyme breaks the β-lactam ring and deactivates it’s antibacterial properties. Because beta-lactam is central to the activity of penicillins, cephamycins, and carbapenems, all of these antibiotics can be rendered ineffective by organisms possessing this enzyme.

To counter this beta-lactamase activity, Clavulanic Acid can be used as an inhibitor of this enzyme. Clavulanic acid acts as a competitive ‘suicide inhibitor’, covalently bonding to the active site of the β-lactamase and irreversibly inactivating it. Compounds of the drug (Penicillin) and the enzyme inhibitor (Clavulanic Acid) are available as Amoxicillin under a number of brand names.

 
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Posted by on May 21, 2013 in Uncategorized

 

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The Haemopoietic Stem Cell

An excellent post looking at hematopoietic stem cells and the work done with them over the years. And even a bit of a FACS cheat sheet at the end.

All About Blood

The Discovery of Haemopoietic Stem Cell

 

Blood was regarded as an important tissue, but till the mid 1800s it was not known how blood cells were made. Three discoveries lead to the modern concept of haemopoietic stem cell.

  1. Neumann and Bizzozero separately, in 1868, proposed that the bone marrow was the site of blood production throughout the postnatal life.
  2. Improvement in staining techniques lead to the discovery of a spectrum of cells in the bone marrow.  Pappenheimer organized these cells into a tree with the most mature cells being at the leaves. He proposed that at the trunk was a cell that was so primitive that it could not be typed into any lineage. Ehrlich and Schilling differed from Pappenheimer in the existence of a single precursor for all blood cells. They proposed that there were two (Ehrlich) and three (Schilling) different precursor for blood cells respectively.
  3. The stem…

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Posted by on May 16, 2013 in Uncategorized

 

Dark Night of the Scarecrow : after 30 years of nightmares

Have you ever been haunted by an old movie existing in the shadows of your mind? Something youImage shouldn’t have seen? Perhaps hiding behind the couch when your parents thought you were in bed sleeping? 

I can think of several films I saw that way when I was young. Films that gained special power because my memory was incomplete and my mind filled in the gaps with things a lot scarier than the film itself. 

I was too afraid to keep watching that night and left scared out of my wits early on to stew in my own imaginings.

It must have been thirty years ago, and I never even knew what the movie was until just recently, when Netflix found it for me: Dark Night of the Scarecrow, Directed by Frank De Felitta in 1981, starring more familiar faces than you’d believe.

The film opens introducing us to Bubba, a man from the mold of Lenny from ‘Of Mice and Men’, a big man with a small mind. Not five minutes in, Bubba is (wrongly) accused of doing harm to a young girl who he plays with regularly.

The good old boys in town form up a quick posse to bring street justice to the man that they have already decided was a menace to their town. Soon, they corner the simpleminded man as he hides in plain sight as a scarecrow near his house.

 From then on, everything goes so predictably, Bubba could have written it:

 The men learn of Bubba’s innocence with their guns hot in their hands, there’s a trial but the men get off (they appear to have benefitted from a ‘stand your ground’ law that strongly favors the survivors of an interaction. But as the trial ends, they are cursed by Bubba’s old crone of a mother. One by one, over the next several days, the men see the scarecrow in their fields, panic and get themselves killed in ways that are arguably accidental.

There are some moments of tension once in a while, but this is not the kind of movie that will make you jump. Ever. I would not say that it’s a very good film, but it’s not terrible either. And Bubba will haunt your children’s dreams for years if you let they get a glimpse.

A la the ‘They’re Coming to get you Barbara’ movie review site (may it rest in peace), I’d give it two severed thumbs up.Image

 
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Posted by on May 16, 2013 in Uncategorized

 

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Wrapped in Plastic

 
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Posted by on May 13, 2013 in Uncategorized

 

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B Cell Activation (The Basics)

B cells, along with T cells, are lymphocytes that bear antigen receptors that have been randomized for their binding specificity during development (see my earlier post). On the B Cell, the antigen receptor is aptly named: B Cell Receptor, or more commonly, BCR.

Like the T cell Receptor (TCR) on T Cells, the BCR is a transmembrane protein expressed on the plasma membrane, where it can bind by antigen. Unlike the TCR, B Cells are not ‘presented’ antigen by other cells in the context of an MHC molecule. Instead, B Cells ‘see’ antigens in their native state – imagine these as soluble toxins or cell-surface antigens on bacteria of viruses.

APC : T Cell Interaction   vs  Native Antigen : B Cell

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Another difference between T Cell and B Cell activation is that T Cells become activated, but do not change their expression of their antigen receptor. B Cells, on the other hand, may react in one of several different ways.  In general terms, this means differentiation into either Memory Cells or Plasma Cells.

Memory B Cells proliferate, but retain their membrane-bound receptors. This makes sense because the purpose of these cells is to lie in wait until antigen is seen again, so they need their receptors to ‘see’ it.

c18Plasma cells lose their membrane-bound receptors, but continue to express the same molecule in a soluble form called Antibody. In fact, they grow in size and fill with ER and Golgi Apparatus to handle the extreme output of protein that they begin producing (~2000 molecules / sec according  to  Molecular Biology of the Cell. 4th edition. Alberts B, Johnson A, Lewis J, et al. New York: Garland Science; 2002. ).

ImageAntibody comes in a number of varieties, but all share a similar core structure as the one pictured to the right. It consists to two heavy chains and two light chains, creating two unique binding sites for antigen.

Events following B Cell Activation

Once cells become activated, they may either immediately become short-lived plasma cells (SLPCs) that secrete antibody identical to the BCR for a short time and then die off, or they may enter into Germinal Center (GC) Reactions. In the GC, B cells get T Cell help and compete for antigen in a poorly understood manner whilst undergoing hypermutation of the BCR’s antigen-binding site.  This results in BCR / Antibodies with higher affinity (greater binding ability) for antigen that may then differentiate into either Long-Lived Plasma Cells (LLPCs) of memory cells. These several differentiation paths can be seen in the illustration below.

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To Summarize:

1. B Cells are activated as a result of crosslinking BCRs by native antigen

2. B cells do require help from T Cells to enter germinal center reactions and produce LLPCs and memory cells (although getting help was not discussed here)

3. B cells become activated and either start producing antibody right away as SLPCs or enter genrminal center reactions.

4. Once in a germinal center, B cells undergo hypermutation of the antigen-binding section of  their BCR/Antibody.

5. Following the GC reaction, B cells bearing high-affinity BCR/antibody will differentiate into LLPCs or memory cells.

 
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Posted by on May 12, 2013 in Uncategorized

 

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