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Yet another one of my geeky post.  Consider the national highway traffice safety adminstiration estimates that 20% of the motor vehicle crashes are due to over-worked (not drunk) and sleepy drivers, knowing how sleepy before you hit the gas may save other people’s lives (not yours).  If you ever wonder what might a series of tests a futuristic car would perform before the ignition is unlocked, this is certainly going to be one of them. 

An article in December issue of the Proceedings of the National Academy of Sciences of the USA (here PNAS or short) by L Seugnet, J Boero and colleagues suggests Amylase, a ubiquitous enzyme in your mouth, could serve as a biomarker for excessive sleep deprivation!  They first noticed in flies, increased sleep deprivation is associated with increase in mRNA expression of Amylase.  Then, they ruled out the possibilities of amylase being associated with just waking or it mechanistically is not a causative agent of sleepiness.  Finally, they were able to show humans with long hours of sleep deprivation also showed increase in Amylase activity (not total protein). 
Interestingly, they had to squash a bunch of fruit-fly heads to get the measurement and only easy swab for humans.  Talking about serious double standards here.  poor flies, sleep-deprived and headless…

Ref: Laurent Seugnet et al, 2006 Dec 26;103(52):19913-8.

We (humans) often think very human-centrically (no surprise given our
predisposition).  The universe must be surrounding us.  The sun is
circling the earth.  And, fruits got to be sweet for we won’t cultivate
it if it’s unpleasant.  But what is pleasant? Something pleasant for us
is simply a chemical reaction, a binding of the odor molecule to our
sensory nervous neurons that sends a signal to our brain’s reward center
and generates a release of "happiness" (similar to the breast
feeding sensation (oxytocin-driven) or getting a pat on the shoulder(dopamine-driven) behavior)…That’s pleasant my
friends.  Similarly, pleasant smell to bugs may not have to be flowery
or sweet… it could be rotten flesh… in fact many plants in the
southeast Asia do produce flowers that offer a offensive odor of rotten
meat.  Hey… doesn’t really matter if the flies or bees are doing the
pollination right?

But the real question is why do we have so little "stinky" flowers and lot of "pleasantly fragrant" flowers?  Is it because we’re the dominating species? not really for there are purely more insects than animals and a wide variety of habitats (some inhabitable by animals).  Why is this? Or did evolution just took a chance and decided this one form of smell is to dominate the planet?

Thomas Friedman’s recent Best Seller titled the World is Flat describes, in intrigue details, the process of globalization.  He further explores not only how this process occurred but also where are we heading in this post-globalization era.

These are some of my notes and gist for globalization:
1. Fall of Berlin wall and up with the windows initiated the first flattening event.
2. 8/9/95 windows Netscape created:
a. Internet browsing
b. Commercializing open standard (no walls between companies).
c. Dot com boom
Dot com boom bubble inadvertently created an over-investment of 1 trillion dollars in 5 years in fiber optics.  Many of those early fiber optics cable companies are no longer around.  but they left us an invaluable cocoon, a shell of almost infinitely expansive network that connects from shore to shore.
This process also has made global collaborations possible by driving down the cost of long-distance travel.  On 8/9/95 @28 closed at 56 WOA!

In history, the .com bust not the first time we over-invested.  Railroad for example, was also over-invested, and it made cheap cross-country travel available for the U.S. citizens.  The difference this time is that the beneficiaries are the Chinese, the Indians, and other s.e. Asian countries.
3. Open sourcing.  We all know Microsoft cannot undercut FREE!!
4. Three factors distracted us from seeing opportunities of globalization (or should I say the product).  They are the 911 tragedy, the Enron scandal, and .com bust: 911 has driven the priorities of this country to other parts of the world. Some people argue that we(the U.S.) is effectively missing a golden opportunity in out-sourcing and improving productivity.  Once this window of opportunity is gone, we’ll be left behind.  The Enron scandal unfortunately has made every CEO guilty until proven innocent (so their words are not taken seriously).  Friedman thinks while occasionally, CEO’s do commit unscrupulous deeds, they nevertheless should still be trustworthy.  Lastly, some believe that the .com bust had projected a false image that globalization is a thing of the past.  No, it’s only the beginning. 

All and all, the core thesis of the book is obviously about globalization.  But Friedman also cautious us about our lack of communication to our kids, the next generation.  How do we teach out kids that we no long possess the competitive edge in physically being close to the job.  Is used to be common to used the old adage "finish your meal because kids in China are starving."  Now is more or less "finish your homework so you won’t lose your job to the kid in China or India."  Are we ready?  ARE WE READY? Is our education prepared?  The adults (educators) aren’t even prepare.  sigh..

What we call the beginning is often the end
And to make an end is to make a beginning
The end is where we start from.
–T.S. Eliot

Strange it may seem, life itself is a circular argument.  Most people ask why we have to die, but never thought about why we were born.  Too many have wondered how the universe was formed but never seek to understand how one would end.  I’ve seen the history of mankind beyond what was recorded.  The hardships our ancestors have to endured to create new beginnings were incredible.  The paths they took to reach the continents were audacious ones and they were clairvoyant.  The stories are all there.  They’re coded in our DNA…
Do you want to know?
Image taken from www.illumina.com

I was fortunate enough to go visit Singapore this winter on company’s dime.  My first impression of this country (city) is how much diversity is harboured here.  People with different ethnic backgrounds, religions, and languages have all gathered here to celebrate this wonderful metropolitan city. 

It is a beautiful city, although plagued with similar number of seven elevens as other major metropolitan South East Asian cities. The average number of seven elevens is … every block.  I walked a 1/4 mile radius and was able to discover as much as 6 seven elevens.  The story doesn’t end there, I also found 3 Gucci stores, 2 Prada, and 4 cartier… isn’t this strange or what?  99 degrees F and walking into the same stores selling the same stuff  couple time a day isn’t what I really imagined how  someone would like to spend their vacation days. 

Anyhow…that’s just my take.   I was able to find wonderfully diverse food courts… OH YES!! FOOD COURTS… since I travel light, I just don’t have room to buy material goods… but food… hehehe is an entirely different story. I’ve already checked out the most glamorous places and the most ghetto huts/basements.  Price ranges from 3.50 to 35SGD. 
Here is my report:
Day 1: SG style rice noodle beef soup (4.50), New Zealand natural frozen yogurt (3.50).  Sorry no pictures(I ate it too quickly).
Day 2: um… I fell asleep due to jetlag.
Day 3: Colleague treated dinner.  Very nice restaurant in Biopolis.
Day 4: Ding Tai Feng.  Now I have visited Ding Tai Feng in 3 locations. TPE, LA, and now SG.
Day 5: switched Hotel to Marina Mandarin (was at Orchard street Crown Plaza) and wow~ the friggin hotel is spectacular! It has left a good impression.  Oh…it is also connected to a huge mall.

Day 6: Supposedly, the best buffet in Singapore is in the Marina Mandarin.  I had it.  But since I need to give my presentation right afterwards… it was tasteless at the time… boy did I regret that

Day 7: Hopped on a plane to Kansai, Japan.  and then right on a express JR train ("Haruka") to Osaka and then to Kyoto.  It’s a very pretty city.  Whatever people are doing, they’re very meticulous and focused (this include janitorial workers cleaning the train).  I am impressed the level of professionalism and craftsmanship.  Anyway, about food.  I had some very good sushi… no surprises.  Oh… the Sneaker candy bar is equally sweet as the U.S. version.

For a long while(past 20 years), the field of genetic-immuno-cancer therapy was just an idea, a theoretical "guess" that some how immune cells (T-lymphocytes, or these killer cells that protect us from virus and bacteria etc) can be "reprogrammed" to recognize tumor and eliminate them.  People have been able to extract tumor cells and "train" the progenitor white-blood cells to recognize, expand (multiply), and eliminate the metastatic tumor cells.  The challenge is how to "pre-warn" the cells for a potential future risk of having cancer.  Also, it is also a major undertaking to identify preexisting tu
mor-reactive white-blood cells.

This speculation, however, came to a realization today when scientists from the NIH have used genetically modification techniques to activate normal peripheral blood lymphocytes to target and kill metastatic tumor cells.  They were able to delivery the recognition machinery of the T-cell (killer cells), something called T-Cell receptor that specifically recognizes different tumor types, to the peripheral blood lymphocytes using a genetically engineered RNA retrovirus.   They first took out some white blood cells, gave them the recognition machinery, and reintroduced these cells (now called autologous cells) back into the patients.  In 2 cases of 15 very agressively advanced and metastasized tumor patients (who had prior treatments and unsuccessful), the population of circulating "updated" white-blood cells are at a sustainable level, and their tumors have regressed  to an undetectable level.  They’re cancer free!

Above: note the dark area (tumor) is regressing starting from pre-treatment -> 10 months later.  Liver size of this one patient also reduced by 89%!!! All you alcoholics… pls thank modern genetics/immuno therapy.  It may safe your liver one day.

source: Morgan, Dudley, Wunderlick…and Rosenberg, Science Oct 6, 2006 314: 126-129

We all know the story of Lucy, the first uncovered ape-human like Australopithecus Afarensis.  It’s the first evidence that beginning 3.3 million years ago, our ancestors slowly was becoming more human like. They stood up and got out of the trees.  They started to use voices to communicate and tools to help themselves etc.  Never has anyone seen a child, until today when Dr. Zeresenay Alemseged (a native to Ethiopian) at the Max-Planck Institute unveiled the first A. Afarensis child.  After years of digging (since 2000), Alemseged and team members were finally able to complete the story of a young girl. 

The key feature that he and his team discovered include evidence for bipedalism (foot), a evidence of a voice box (hyroid) that support the tongue, and scapula that’s very gorilla like. The discovery of the hyroid is the first evidence that A. Afarensis can produce some kind of sound, though we don’t know if they could "talk."  The discovery of a gorilla-like scapula (shoulder blade bone) certainly raises question about whether Afarensis lived a dual arboreal and terrestrial life.

Ever wonder why some people are always so agressive and so hard to get along? well… researchers have recently identified an agression gene in Fruit Flys Drosophila melanogastar (not so fruity after all huh?). See below:

Researchers Herman Dierick and Ralph
Greenspan of The Neurosciences Institute in San Diego, California, set
out to see if they could breed high levels of belligerence back into
lab strains and to learn what genes might be implicated. They designed
a cage in which 11 small containers of fly food were evenly spaced to
serve as distinct "territories" for the insects.  120 Males+ 60 females were introduced to this environment.  Only the
males deemed most aggressive–as judged by behaviors such as charging,
lunging, holding, and tussling–were removed and mated (score!).

After 20
generations, the aggressive insects scored more than 30(!) times higher
than the controls did on a "fighting index" that measured how
ferociously they fought, Dierick and Greenspan report. To see what genes might be involved in
this increased aggression, the team used microarrays to look for
differences in gene expression in fly brains. Several dozen genes were
expressed differently in the superaggressive flies, compared to
controls, but flies with mutations in one gene called Cyp6a20
were especially combative. This gene encodes one of a group of enzymes,
called cytochrome P450s, which are involved in a number of biological
processes including development, reproduction, and detection of
pheromones.

Source: Dierick and Greenspan Nature Genetics, August 13, 2006.  Also see Trudy MacKay in a similar study from PLOS Genetics on August 2nd, 2006

To what extend are we different from primates? what makes us human and others just animals, albeit sharing 96% of our genome?  Prof. David Haussler, a revolutionary thinker, a computer scientist, and now a self-taught geneticist used aligned sequences from many animals and compared with human sequences.  He was able to identify regions with large number of changes within humans but virtually none in all other species, which are closedly related with humans, and he indicated these human lineage-specific changes. 

In particular, he discovered an RNA-gene that is highly expressed with reelin, a regulator of brain (cortical) development.  This gene is expressed in a type of cells called Cajal-Retzius cells of the subpial granular layer, a layer thought to contain the Cajal-Retzius neurons and their precursors migrating tangentially from the outside the neocortex (unique in human).  It is also present in the upper cortical plate, presumably representing the cells that are finishing up their radial migration.

source: Pollard et al, Nature 2006 (august 16th) doi:10.1038/nature05113, advanced publication online.