Tuesday, December 30, 2008

Review: Everything and More

Everything and More: A Compact History of ∞ is the first (and thus far only) book by David Foster Wallace I have read. I thought that book was great. I loved the writing style, and the level of mathematical detail fit my background rather well. The book (or booklet, as Wallace insists) traces the development of maths treatment of infinity throughout western history. It includes metaphyscial/philosophical discussions (starting with the Greeks, of course). It focuses on math rather than on the biography of any individual. Importantly, it provides motivation for how particular ideas in math developed, and the intellectual context in which well known advances occurred. The first half or so of the book (say, up through Newton and Leibniz and the development of calculus) is more lucid than the second part. But, this is a consequence both of the relatively lower level of abstraction of the material, my own familiarity with these concepts and Wallace's ability to more successfully impose a grand narrative onto the events. Any one who has spent time pondering Zeon's Paradoxes should definitly give this book a shot.

Wallace's style is quit distinct. It is slyly informal, with the author's voice directly addressing the reader. It is also interrupted by a multitude of parentheticals and foot notes--devices which Wallace uses masterfully to inform and entertain. I can see how some would find this style jarring and difficult to get through. I can also see how the books level of detail could be overwhelming. Wallace claims that all that is required is some basic college level math background, but I think it is best targeted to a slightly higher level reader.

Some reviews for technical audiences focused on a number of errors Wallace makes in his presentation. I am uncertain how much this detracts--after all, this isn't my field, so I am very much an interested layman (and thus the target audience). I found it to be an amazing, literary depiction of important and abstract ideas--the type of communication that I'd love to read more of.

I agree with this review by Chad Orzel (the excerpt he gives pretty much sums up the writing style. If you can't handle that, then don't bother with the book, but if you are intrigued by this style and interested in how some of the most difficult problems and paradoxes dating back to the Greeks are handled, then give the book a read).

Sunday, December 28, 2008

Gene Conversion and Drosophila Duplications

The study of duplicated genes is an important topic in evolution and population genetics. A recent paper in PLoS Genetics by Osada and Innan (Duplication and Gene Conversion in the Drosophila melanogaster Genome) makes some interesting observations about the role of gene conversation in shaping patterns of sequence evolution in Drosophila segmental duplications. Osada and Innan discuss other topics in their paper, but I want to use this mostly as an opportunity to lay out some comments on gene conversion.

Gene conversion is one of the potential ways of resolving the Holiday structure intermediate formed between two DNA molecules during recombination or other repair process involving double strand breaks. A lot of the players involved are known, and if you have access I recommend this recent review by Chen et al.

Instead of considering gene conversion mechanistically, I am going to describe the consequences of gene conversation using a simple genetic example. Consider a diploid eukaryotic organism where the four meiotic products can be directly observed (eg, a fungus such as Saccharomyces cerevisiae). For some heterozygous locus (with the two alleles A and a) the expectation is that two of the gametes will carry the A allele and the remaining two will carry the a allele. This is depicted below, and is the situation taught in all of the intro textbooks, and is consistent with what is most often observed.

Meiosis without gene conversion:

Sometimes, though, an unexpected outcome may be observed. Instead of the expected 2:2 ratio, there may be 3 gametes with the A allele and only 1 gamete that carries the a allele.

Meiosis with gene conversion:

What happened? At some point following replication (so that each homolog is represented by two sister chromatids), there was a transfer of sequence information from one of the A chromatids to one of the chromatids that carried an a. This transfer was non-reciprocal and unidirectional. The end result is that the sequence of an a allele was converted to match that of an A.

It turns out that such a gene conversion process can occur whenever there is sequence homology between two different DNA strands (NB: although named gene conversion, this process can alter any sequences that have sufficient homology with each other. The altered regions do not have to be "genes".) Of course, this is clearly the case for corresponding loci on homologous chromosomes, but it also the case between paralogous sequences. Paralogs are simply the individual copies of a duplicated stretch of DNA that is found at multiple locations in the haploid genome. How this can work is illustrated below, where the flowchart schematically follows a single chromosome over many generations.

Gene Conversion and Duplicated Sequences:

The diagram starts be considering a single stretch of sequence on the p-arm (short arm) of the depicted chromosome. This stretch is indicated by the red box, and at this point is unique within this particular genome. At some time, an intrachromosomal duplication event occurs, and the indicated sequence is copied onto another location on the same chromosome (in this example). The red box is now duplicated. In a haploid genome that sequence is present two times.

From here things may unfold in several different ways. For this example, I'll posit that both copies of the duplication are retained, and that they each independently accrue sequence difference (mutations). This is indicated by the change in the color of the segments. Visually, initially there were two segments that were both identical, but over time one becomes orangish and the other yellowish. Now, if we knew something about how fast sequence differences (here, change in color) accumulate, we could compare the two sequences and make an estimate as to how long ago the sequences would have been identical, and thus estimate when the duplication event occurred. However, this estimate would be all messed up if a gene conversion event occurs--especially if such a possibility is not incorporated into the analysis.

The putative conversion even in the schematic has the effect of homogenizing the two copies--the "yellow" segment is converted to have the same sequence as the orange segment. Without any other information, one might observe that the two paralogs are very similar in sequence (nearly identical), and erroneously conclude that the duplication occurred recently, or that some other force (selection?) has acted to maintain the sequence similarity between the two copies.

In their paper, Osada and Innan try to get around this dating problem by using information from closely related Drosophilla species. Essentially, they count how many regions are found in two copies in the D. melanogaster genome but are only a single copy in D. simulans or D. sechellia. Knowing how long ago the melanogaster lineage separated from the others, the authors can then calculate a rate of duplication directly. Focusing on genes, they estimate that a duplication involving a single-copy gene (1 copy to two copies) occurs (and survives to be fixed) every 75 thousand years.

Based on sequence comparisons between regions duplicated in both melanogaster and another species, the authors also search for evidence of gene conversion. Using a gene-tree based approach, they find evidence for gene conversion in most (24 out of 28) of the duplicated segments they examined. This is an interesting finding, and if true, means that conversion is extremely important in terms of the evolutionary trajectory of duplicated genes.

The authors carry out additional analysis, but I'll end this post with another thought I had on this paper. For technical reasons working with duplications can be tricky. In this study, all of the duplications were identified using the genome assemblies. Although the D. melanogaster assembly is good, the others are essentially draft WGS assemblies. This means that duplications, particularly those with a high sequence identity or those present in a tandem configuration (duplicates adjacent to each other) may be missed. This could result in the incorrect conclusion that the duplication occurred after the melanogaster specialization. This should inflate the estimated rate of duplication specifically along the melanogaster lineage, but I'm not sure how it would bias the other analyzes in the paper.

Osada N, Innan H (2008) Duplication and Gene Conversion in the Drosophila melanogaster Genome. PLoS Genetics 4(12): e1000305 doi:10.1371/journal.pgen.1000305

Liu Y, West, SC (2004) TimelineHappy Hollidays: 40th anniversary of the Holliday junction
Nat Reviews Molecular Cell Biology
5, 937-944 doi:10.1038/nrm1502

Chen JM, Cooper DN, Chuzhanova N, FĂ©rec C, Patrinos GP (2007) Gene conversion: mechanisms, evolution and human disease. Nat Rev Genet. 8(10):762-75. doi:10.1038/nrg2193

Friday, December 26, 2008

Writing Contest: In the beginning...

The Book Bench blog at The New Yorker tipped me off to the first paragraph contest launched by literary agent Nathan Bransford of Curtis Brown Ltd. Entries to the contest were first paragraphs from novels in progress. The six finalists were announced here, and the winner chosen here.

Scanning through the many submissions I noticed a common thread: the overuse of adjectives. Maybe this comes about because we are all told to "paint a picture with words." But, good writing seems to build up this picture in an unobtrusive way--the reader comes to know the characters and the setting, almost without realizing it. In less good writing the brush strokes leave a trail across the image that can be seen a few steps away.

Based on the submissions Bransford defined three broad categories of common openings which I'll summarize alliteratively:

1. Surprsing Sentence followed by pedestrian prose
2. Delebriate Description followed by shocking statement
3. Purposefull Protagonist ignores wicked weather and propels plot

My main lesson from this contest: good writing (like good anything) is hard.

Coffee Talk (Mechanics)

I'm clearly a coffee addict. I'm shamed to report that my French press coffee maker broke earlier this week and I reacted with the expected horror.

I've used this model since May of 2007. My settled procedure was to use two scoops of ground coffee, fill it up to the upper black band with hot (nearly boiling) water, and wait for 3 minutes. This made two cups of coffee and rich and full-bodied coffee. I'd immediately drink one--a very enjoyable coffee experience. I would sometimes drink the second in rapid succession, but would often wait a bit and usually found that it needed to be warmed up for 45 seconds in the microwave. Other times the second cup went to waste. The French press made a superior cup of coffee, but it was a bit of a pain to clean. Many of the spent grounds ended up down the kitchen drain, a situation with unknown future consequences.

Even though it served me well during its time, I was seriously putout by the failure of my BonJour Hugo French press. The mortal wound was the failure of a plastic piece holding the filter apparatus together. As a replacement, I decided to try a simple manual drip coffee cone system. I purchased this one that comes with a mug but fits on top of any cup.

Despite its unfortunate name I purchased the Ready Set Joe single cup brewer because it was easily available (purchased at nearby convenience store) and I remembered once wanting to try out this method for coffee making (I've owned a standard drip coffee maker with carafe before, but never the single cup cone system). I like the ability to make a single cup at a time as well as the ease of cleanup (just toss the filter and grounds--you can even get filters that will decompose).

My first time I made several mistakes that are easily avoided. Here is some advice that seems obvious, but isn't so clear when you groggy and suffering withdrawal symptoms. First, be sure to fold the number 2 filters on the bottom and side as indicated. Second, don't just pour all the water in at once--even if you don't over top the filter, it will lead to an overly quick brew and weak coffee. After a few trials I've found that it works well to pour the water in agonizingly slowly, let the volume drop as it filters through, and then slowly pour in more. I try to obtain a dynamic equilibrium for several seconds (perhaps 10-20, maybe longer), then stop the pour to let the remaining water flow through the cone. It may take some trials to get the total volume right, as overflowing the cup is an unfortunate result.

I hope to get be able to compete with the quality I got out of the french press by increasing the amount of coffee used per cup (to say 1.5 scoops), and perfecting my pour rate. The ease of cleanup is a big benefit, as is the single cup brewing ability. So far, I am tentavily satisifed with this simple coffee maker.

Wednesday, December 24, 2008

Review: 1900 House

The basic idea of 1900 House is to see what happens when a middle class British family from 1999 is transported back in time to live using the technology and furnishings available to a rising middle class British family in 1900. The family lived in the house for three months and the series is only four episodes long. I found them all quite enjoyable.

The series includes the expected bits about struggling without modern technology, standards of cleanliness, and etc. Essentially all of the Woman of the House's time is spent cleaning and cooking--at least until a maid was hired. I enjoyed the show, and appreciated how it illuminated the past in ways I haven't considered:the darkness, the mind-numbing nature of household chairs, the physical closeness of people.

One thing that was lacking (and I'm not sure how to change this, really), was a better sense of the mentality of the times. The family physically was living a 1900 life style, but mentally they very much still had their 1999 values (giving those up would be both very difficult, and rightfully repulsive to our sensibilities). I think that trying to understand the social and cultural norms of a time is one of the more intriguing aspects of this type of history. The narrator and series experts would point out strong social transgressions by the family, such as taking pictures of people in their underwear (which came down to the ankles) or answering the door in the morning before being fully dressed. And the social status of women was a large part of the series. But I wonder if more could have been done?

The family received letters from experts describing how to do household activities and included things such as recipes, and suggestions for making shampoo and other items. It may have been interesting if these letters included some sort of "moral instruction" as well. It is comparably easy to understand what it would be like to go back in time in terms of physical amenities, but I find the social conscience aspect much more difficult to relate to. The relationship with the maid was the most interesting in this regard, but I wonder what would happen if one delved deeper into this aspect. Of course, I have no idea how to do that with real people living real lives and end up with an entertaining show.

This difficulty illustrates just how profound such changes have been. The series did make some points about the relationship between physical advances--cleaning equipment, ability to hire maids leading to more free time--and the increasing roles for women in society. This is a subject I am interested in learning more about.

I recommend this series to anyone interested in Victorian times, or just how much things have changed in our daily lives over the past 100 years.

Monday, December 22, 2008

Review: Time Crimes

Time travel is a creativity trap. It often simply doesn't make sense and is frustrating for the audience. Movies specifically about time travel are even harder to pull off. Exploring the consequence of time travel isn't a new idea in science fiction.

Is there anything original left to say? Maybe not. But
Time Crimes (Los CronocrĂ­menes) sure says it well. I was pleasantly surprised by this film. It was smart, and unexpected.

I don't want to give away anything about the plot, but will say that if you enjoy sci-fi, or like thinking about causality and determinism, then this is one movie worth checking out.

Sunday, December 21, 2008

Review: Alpha, Omega

Alpha, Omega is a novel written by Lori Stephens and self-published via BookSurge. The novel revolves around a quasi-religious cult and the mysterious power of its holy book, the Librah Vae-ta.

Spoiler Alert!

The story is an engaging enough action/adventure: mysteries are solved, people are hurt, people fall in love, relationships are broken but ultimately everything is happily resolved, etc. While reading (I read most of the novel over dinners at a nearby bar/restaurant) I found myself wondering how things would end (clearly a critical requirement for any suspenseful yarn), but was bothered by some basic aspects of the plot. Let's accept that language can set up some kind of neural resonance and impact people as depicted. And that taking random words/characters from an assortment of languages can have some discernible meaning. But, how does this work in only one direction? How can people (such as Gatsby) speak words that cause this reaction in others without experiencing the effects themselves while they are speaking?

Also, it is unclear to me what the organization really wants/desires? Total control of the world? Power and Money? Omega comes across as a somewhat empty vessel of malevolent evil, without any real motivation. Their motiviation is unclear. Just how old are they? The same sense of incompleteness applies to Woodie Sanderson and his mysterious journey to find himself in religion. What's up with him? No deep insight is related to the reader from his years of soul searching. Just some weird stalker-emails and a My Heart Will Go On style reunion (Kama). Mechanically, he was useful for the fancy brain monitoring seen, but the character seemed under developed.

The novel also lacks a sense of place. The action unfolds in London, but other than references to the tube and to lifts, I did not get a sense of the city. Why London instead of elsewhere? I believe that Stephens is from the Seattle area--why not set the story in that city so that it could be more easily anchored into a fleshed out setting?

At times the writing seemed a bit clunky. Some passages gave a sense of: I'm standing over here, and I need to be over there, so let me just walk slowly across and look, there I am. This is in contrast to times when the events of the story appear to naturally follow from the set up, without any forceful writing to propel things along.

Since my pedantic side is on full display, I'll mention that I found the use of exclamation points to be a little wearing. For example, the first sentence of the book is:
The fate of my soul!!

Is that second exclamation point really necessary? There are some additional minor textual/low level things that bothered me while reading.

As I said up top though, I found the actual story to be engaging, but feel the novel would benefit from greater depth and character development. But then again, I think this was intended to be a quick read thriller, and my choices for fiction tend to go more toward the engrossing, expansive, all encompassing style.

Group Dynamics

I wonder if I'm a good group member. Sometimes I know I am a bit of a jerk--especially when I'm bored with what's going on, or when I get frustrated with others about a topic. I should work on this both as a group member, and especially when I'm helping to organize whatever activity is occurring. I bring this up because I just listened to this weeks episode of This American Life (episode 370: Ruining It for the Rest of Us).

The episode began with Ira Glass talking with Dr. Will Felps about the effects of "bad apples" on group dynamics. Felps's research seems to indicate that one "bad" group member can severely derail a group's progress. Additionally, the group member's behavior actually changes the outlook/disposition of others in the group. If this is a general observation that holds for more long term situations (such as project teams at work, small departments, and even the boards of non-protifs), then it is more importnat for me to think about how best to behave as both a group member and as an organizer. Definitly an idea worth thinking some more about.

Next on the episode was a story about a measles outbreak and anti-vaccine parents. The reporter seemed to dance around this basic point: of course having everyone vaccinated is the best for society as a whole, resulting in a reduction in overall disease, and undeniable benefits of everyone being vaccinated. The idea of "herd imunity" is even discussed. However, at the margines, there is a non-zero risk (because nothing is perfect, and some people will have reactions, etc) to any individual child. And--and this is key--as long as everyone else is vaccinated, one can get all of the benefits without accuring any of the risk. So, of course, some parents will make the cost-beneift calculation weighing their child infinitly more than anyone elses. But, in the intermediate to long term, that of course would lead to a worse situation for everyone else and for society as a whole. This is why the governemnt steps in and essentially forces everyone to participate. Such partiicpation (and the loss of the assoicated invidual autonomy) is part of the price demanded for reciving the larger benefits of organized public health policy.

This topic reminds me of a New Yorker article from 2002. In this article, Atul Gawande talks about the training of doctors, and how patients with "insider knowledge" can get better care by refusing to be treated by less expereinced physiciancs or physicians in training. However, as Gawande concludes, this would destroy the way University teaching hosptials work. Any person who knows would choose the more experienced practioner--and this is precisly why the ability to make that choice should be denied (or so the arugment goes).

Anyway, I enjoyed the episode, but wished there was a clearer statment about the benefits of vaccines, and why/how government coerciion works in these situations. Not only because it would help (maybe) dampen the growing anti-vaccine movement, but would also because these examples show how liberterianism doesn't really work and how collective action is needed to achieve "larger good".

The rest of the episode, atlhought entertaining, wasn't directly related to these deeper subjects.

I've noticed online that some people were having trouble finding more info on Will Felps. Dr. Felps is currently at the Rotterdam School of Management at Erasmus University. More info about the study mentioned on the show can be found in this press release. The research discussed appears to be published as a chapter in Research in Organizational Behavior vol. 27 (available from google books here)

Thursday, December 18, 2008

Review: Our Mutual Friend

Charles Dickens is funny!

Our Mutual Friend
was the first of his books I've read, and I was surprised by the level of humor which colors his social commentary: Podsnappery, the Lammle's marriage, Jenny Wren turning around the doll. Why didn't anyone ever tell me how humorous Dickens's writing is?

Our Mutual Friend, the last novel he finished, appears to be rather unknown. The main plot focuses on a the fate of a large inheritance whose heir is murdered. The real joy comes from the many side stories and characters that get weaved together into the main plot.

The ending seems forced--there is a twist that I found to be unbelievable and inconsistent with the previous depictions of some of the characters. Also, the way Bella reacts to things at the end didn't seem true to me.

If you've never read any Dickens (or, even if you have), I highly recommend this as a place to start.

Monday, December 15, 2008

Review: My-HiME

My-HIME hits all the targets one expects from a certain type of anime:

  • school girls in uniform with super powers
  • hot outsider girl with a motorcycle
  • tension between saving the world and the fierce urgency of adolescent love
  • filler episodes that are both hilarious and annoying
  • non-sequitor skits at the end of the credits
  • at least one character who constantly stumbles into "perverted" situations
My only complaint has to do with the DVD. The English subtitles are printed in yellow text on top of the bottom of the image. On my screen, they were not legible whenever the background was light or yellow in color. At times this was annoying, but tolerable.

Sunday, December 14, 2008

Review: Rachel Getting Married

I saw Rachel Getting Married today--it was an odd film. The camera work at times was like a documentary, featuring shaky, zoomed in close ups and sometime rapid cuts. The plot as well had a documentary feel, as it focused on two days in the life of the main character (who just got out of rehab and is attending her sister's (Rachel) wedding). Bits of backstory are slowly revealed, but much of the film is just an accounting of the rehearsal dinner and wedding. This is also done in a documentary style--it feels as if we are watching the "wedding tape" made of the event.

My opinion of the film is rather mixed. There are aspects of Anne Hathaway's performance that are intriguing, and aspects of forgiveness, remorse, jealousy and the mundane, daily evils of family relations are depicted in a refreshingly realistic way. Some reviews raise interesting points about this film, but overall I preferred I've Loved You So Long (Il y a longtemps que je t'aime). Although, I now think that the two movie are trying to do very different things. Perhaps in film I just prefer more of a an established structure?