Other new summery/fall things

1. I got a bike! It's a Gary Fisher hybrid (between road and mountain bike) that goes easy over curbs and is easy on the eyes in a slick black and silver combination. I need to find a better helmet (the one I've got, free, makes me look silly) and a better lock (a little coil ain't good enough for HP).
2. I got (now president-elect) Barack Obama gear that I proudly wore during the Grant Park rally and which I proudly drink out of everyday.
3. I spent many hours reading about political news surrounding the conventions and all the election hoopla. A memorable moment from the Republican convention: the moderator (or whatever you call the speaker) asks if there are any other nominations besides John McCain, one man screams "Ron Paul!" and is quickly ignored as the moderator declares "with no other nominations..." Kinda  sad that a party so hellbent on protecting our freedoms should blithely ignore one of the fundamental ones. The man was clearly audible and yet not heard. How sad.
4. My laptop died and has since been replaced by a Lenovo SL400 Thinkpad. My old T40 may still be saved since the motherboard is apparently fried. After over five years of nearly unfailing service (only had to replace the fan and DVD drive once each), I will miss the machine that has traveled far with me and taken me places too numerous to count. Why so sentimental about a machine? Why do people weep when their cars finally die out on them?
5. Saket got me a really sweet new Nano!! It's a beautiful blue color and best of all, it comes with an inscription that only my brother would think of: "for Sapana, my favorite bear of all." ::tear::
6. B&J went on a semi-cross-country 10-day (and well-earned) vacation during which I successfully managed to keep all their plants (and myself) alive and not completely trash the apartment. Yay me! Funny too how my TV viewing increased dramatically during those days. As enthralling as the "boob tube" may be, it can never replace genuine company.
   
7. I saw WALL-E with Kevin and enjoyed the movie (though the fact that we saw the flick shortly before he had to leave for Champaign to attend his grandfather's funeral, may he rest in peace, did dampen my spirits more than a bit). Pixar continues to amaze me with the creativity and heart they put into their movies. I have seen them all except Cars which was the first to not excite my interest and, perhaps non-coincidentally, is also their worst-reviewed movie to date.
8. The Dark Knight was awesome. I only wished they had filmed some true IMAX shots of Batman swooping down over Gotham City. Alas.
9. I still can't believe I went skydiving.
10. I still can't believe my DAD went skydiving.
11. Nate came to visit! Totally awesome (something I really needed after my prelim experience), especially since the poor guy was sick most of the time, yet he was such a trooper. Hats off to anyone who can put up with my jabbering nonstop for an entire weekend. With a fever too. Oh, and we went to the temple by Obama's "mansion" for a brief yet interesting visit. The woman who let us in to another woman: "Can you show them around before service? Or maybe throw them out?" All this while we were standing there. Awkward! The temple is quite beautiful though and has an interesting history, much of which I've unfortunately forgotten. Oh well, as good an excuse as any to get past the security blockade in front of Obama's house!
    
12. Anything else? Only if I think of it.
    

Summer in the City

All right, so it's been quiet some time since I last updated this. Needless to say, I've been pretty tied up, but that's no excuse for not blogging, since blogging is what all the cool people are doing these days.

First I'll catch up on what's been going on since my family left Chicago back in June...in order of most recent to most...non-recent:

1) I completed my laboratory rotation with Dr. Ken Onel who I've discussed in an earlier post. The man is just awesome. I'll discuss my new lab mates in detail later, but just know they're a fun bunch and I look forward to working with them as long as they're in the lab.

2) I wrote and presented my prelim not just once, but twice since I wasn't exactly brilliant the first time. The second time went only a bit better, but rest assured I'm still in the program and will be just fine. It's nice to know i have such a supportive network of friends and colleagues to make sure I succeed. And it's really nice to know that I have an amazing advisor and supportive classmates who've always got my back.

3) I've discovered some new music (shocking, I know...I do listen to artists other than Sarah McLachlan). They're from different genres but some pretty neat stuff. Ken and I were talking about international music (I may have been discussing a Bollywood film) and he mentioned an artist named M.I.A. She was born in Sri Lanka but raised in the UK and has produced her albums from several different countries. I find it a little difficult to describe her music succinctly since it's definitely cross-genre material. It's rap/hip-hop based, with a dance infusion and hints of Bollywood drama and sounds. Anyway, you should check out her latest album "Kala." Another group I discovered through Pandora Radio (the "music genome project"; really a neat site that streams songs based on artists or genres you like. For example, I've created a "Sarah McLachlan" channel and so songs by Sarah and artists like her are streamed through there) is called Bond. I haven't looked much into them, but they're apparently a group of women who do classical music but in a rather funky modern way. A standout is "Shine" which has some Hindi lyrics (awesome). I like some modern classical-sounding stuff like E.S. Posthumous and Mythos, and these ladies fit in pretty well. The last new cool artist comes from the west side of Chi-town and his name is Lupe Fiasco. Saket attended a neat outdoor concert in SF to see Radiohead and got to hear this guy as well. A song of his, "Go Go Gadget Flow" made an impression on Saket by the craziness (and geekiness) of the lyrics and the energy with which Lupe and his band performed the song. So Saket sent me a YouTube link of his song and, impressed with his lyricism and sound, I downloaded his latest album off Ruckus. For someone who's not a big fan of rap, I was very impressed. Not only are the beats wicked, but most importantly the lyrics are so thoughtful and relevant it's hard not to like what you're listening to. How many rappers do you know can sing about AIDS in a way that's both tragic and beautiful (Streets On Fire) and also about child soldiers (Little Weapon)? Now this guy is definitely worth listening to.

4) I got to meet up with my aunt and cousins from India!! How cool is that? I found out just after my folks and sister left that my cousin Shweta, who's currently in her senior year at the University of Michigan at Ann Arbor (go Blue!). Finally, a chance to meet more family! As you may know, about 99% of our family lives in India still. The other 1% can be found in Canada (cousins of my mom and their families) and Houston (a niece of my dad's). We've only had a handful of chances to meet that 99% (and I've been lucky enough to see more of the folks in Canada than Saket or Sachi) due to the length and timing of the school year, my dad's work schedule, and the sheer expense and time committment it takes to make a family trip to India. Thankfully, now that we're no longer in traditional school binds, we can take trips more frequently. Nonetheless, our last trip as a family was nearly four years ago. But I digress.

You shouldn't need a special occasion to meet family, but we found a good one in any case. Shweta was working as an intern for Walgreens in Chicago for the summer and Archana Masi (aunt) and Shruti (Shweta's younger sister) were visiting her from India. The last time I remember talking to them was back in 2004 when Shweta was seriously considering coming to the US for college. I have to say I'm happy she decided to come, regardless of whether she'll consider settling here or moving back to India when she's got her degree in engineering/environmental studies. Since they were in Chicago (living in Evanston), and I am in Chicago, we decided to meet downtown at the Taste of Chicago. The Taste is a popular summer food festival featuring hundreds of local restaurants and eateries who give out "tastes" or small portions along with full servings of their iconic items. As you can imagine, there were lots of places serving deep dish pizza, hot dogs, and cheesecake, but a lot of ethnic food as well from Indian to Ethiopian and beyond. Despite a sky threatening rain, we enjoyed ourselves at the Taste eating tasty things (see what I did there?) and catching up on life since December 2004. I got to see them a couple more times before Masi and Shruti headed back to India when we saw The Dark Knight together at the IMAX theater at Navy Pier and when I came up to Evanston for pizza night at Kevin's place. I can't wait to see them again in India the next time we go (though who knows when that will be...)

Those are the main points of summer. Additional details in the next post.

Rest of Family Visit II: 19 Jun- 21 Jun

19 Jun: Thursday and it's time to visit more of the city. Dad had a meeting with a colleague for work so while he was at that, Sachi, Mom and I headed to the Sears Tower. Originally built by Sears Roebuck and Co. in 1973, the Sears Tower is one of the tallest buildings in the world (110 stories for 1450 feet, 1725 if you count the antennas) and home to the offices of dozens of companies (no longer Sears though, they moved to the suburbs). It offers one of the finest views of Chicago from the top although some areas, like my Hyde Park, are nothing more than a blur even on good days. It is possible to see Indiana nearly everyday and even Michigan on the clearest days. We spent some time taking lots of pictures, then headed down to meet up with Dad at lunch. We ate at a Potbelly's in the Loop and then caught a bus south to the Museum of Science and Industry in Hyde Park (maybe a dozen blocks from my university). The MSI complex was constructed as a temporary structure for the 1893 World's Fair, part of Chicago's famous "White City." Rain and the elements threatened to disintegrate the city until locals decided the buildings were worth maintaining and thus refurbished the structure into the museum it houses today. The classical Greek style of the columns and facade make the MSI a valued addition to Chicago's long history of architectural treasures.

The Museum was quite crowded since it was celebrating its 25th anniversary and thus decided not to charge an admission price. We spent a couple hours admiring the chicks, checking out some DNA exhibits, meandering through some naval and space history, and leaving rather abruptly given the fact that we were a little fatigued and Dad was getting a headache from the crowd and noise. It took quite a bit of time to catch a bus that would take us downtown but finally caught one back to the hotel. After resting and freshening up, it was time for dinner. We visited the "Star of Siam" just off State Street and it proved to be a delightful little Thai restaurant. I was especially impressed with the cushions in the middle of the room. It looked as though the diners were seated with legs crossed on level with the table (as though on the floor), but in fact they were sitting as normal; it was just that the cushions had table-shaped square holes cut through them to the floor, creating a hollow space for legs. I guess it would help to see the place, so come visit me sometime and I'll show you.

After dinner we stopped at Kevin's favorite used bookstore that happened to be right next door, and then caught a cab for Buckingham Fountain (it's more fun to see this fountain at night). A light and music show is put on so of course we stayed for that and I took many pictures. After a pleasant evening by the fountain, we caught a cab back to the hotel for some rest.

20 Jun: It's Friday and we're going skydiving! It's also Dad's birthday! What a day for adventure! We headed out early due west for Hinckley, IL, a tiny town with a big love of flying. Our destination was the Chicagoland Skydiving Center where Sachi, Dad, and I had booked a day with destiny. The weather started nice but as we waited for our class to begin and our instructors to arrive (at my insistence we had arrived ludicrously early, but to good effect as you'll see later), the sky turned gray and before we knew it rain was falling. Uh oh! Finally, our team arrived and just in time too the sky cleared. We watched a video with the other divers and were shown briefly how to properly deploy the chute and jump (Sachi got to demonstrate some moves for us). Operating the chute was optional; if we didn't our tandem instructor would do so.

In what seemed like no time, we were suiting up for our jump. All three of us elected to have a videographer/cameraman accompany our jump to record our freefall for posterity. As a result, we were quite a crowd bundling into the little airplane (3 of us, our 3 instructors, 3 videographers, 2 pilots, and 2 other divers from CSC). The ride up didn't take too long, and we chatted with our fellow divers as best we could over the roar of the engine and wind. Although I appeared calm and excited on the outside, I was secretly fighting nerves within. I trusted my instructor and the equipment, but you just never know...

All of a sudden, we were at about 14,000 fight. Since I was first to board, I was last to jump and got to watch as Sachi first and then Dad were escorted out of the plane and into thin air. Shuffling awkwardly with Eddie, my instructor, I found myself poised on the brink of the aircraft. My videographer (I only remember his first name started with a J, so I'll call him J) was already hanging off the plane, and before I could think to have second thoughts, Eddie was counting down and rock forward, rock back, and OUT!!

The next minute is largely a blur, but I remember the sudden rush of cold air, the roar of the wind, my mouth turning dry in an instant, and sheer exhiliration. As J expertly manuvered around us, I smiled and posed the best I could. He distracted me from any fears that may have arisen and as a result I mostly looked ahead and around instead of down. Eddie was fun too and he pulled some delightful poses. The fall was both fast and slow and in my last moments of freefall, I remember J spinning around like a top and my downward velocity reversed in an instant as the chute opened above us. The air became calmer immediately, and after the second chute opened and we glided a bit, Eddie said I could remove my goggles and just relax. I still had my contacts in, of course, so taking off goggles at 6,000 feet made me a little nervous, but the air was still so it was fine. We drifted for a few minutes admiring the view of the Illinois countryside (Chicago alas was too far away). I landed in a bit of a heap and after freeing myself from Eddie, triumphantly walked back to the hangar. Although I was last out, I managed to barely beat Dad and Sachi. No fair!

After getting our DVDs and paying, we headed back to the city. The whole adventure took about 6 hours (driving to and from, waiting, and diving) so we were hungry by the time we got back into town. The rain that had passed us had passed into Chicago so navigating the streets was a little harrowing, but we managed to find India House, a fabulous Indian restaurant that Bonnie and I had gone to with her friends to celebrate her birthday last October. The food was wonderful and after we said it was Dad's birthday, our waiter brought out a delicious dessert of kulfi (Indian ice cream), light cake, and orange slices.

After dinner we drove back to my apartment where we chatted with B&J a bit before I packed up things to send home and we got ready for bed.

21 Jun: This morning we ate brunch at the Mellow Mushroom (not the pizza place in Raleigh) along 53rd street. It's an old-timey breakfast place that serves omelets, waffles, pancakes, etc. After the hearty meal, it was straight back to the apartment for some final packing, directions, and then goodbye. Such a delightful visit filled with memories I shall treasure for years to come. I didn't do much the rest of day except check in with the family occasionally to make sure they were doing fine. Next trip...December!

Rest of Family Visit: 16 Jun- 18 Jun

To keep things brief and reasonably current, I'm going to sum up the rest of my family's visit to Chicago.

16 Jun: It's Monday and we're greeted by the first bout of rain in days. Fortunately, we had planned a trip to Devon today and since we didn't leave the hotel until almost 11, we managed to miss all the showers. Devon Avenue is essentially Little India (and I guess Little Pakistan...how 'bout Little South Asia?) located south of Evanston and north of Lakeview/Lincoln Park. The street is lined with shops selling everything Indian from sarees to sweets, aliments to accoutrement, and Bollywood CDs to chapatis. The sights and smells assault the senses and for a brief moment one can imagine being on the streets of Mumbai or Bangalore. We strolled around for some time, eating lunch in a couple of different small restaurants and checking out some music and cooking utensils in various shops.

After lunch we decided to head out to the western suburbs to visit the IKEA store in Schaumburg. This adventure took up most of the remaining day and concluded at an Olive Garden in the mall complex near the IKEA. I managed to stock up on some new clothing and found some things for the apartment (some sweet glasses and an organizer). It was back to the hotel after dinner.

17 Jun: Tuesday and we're off to Wisconsin for a couple of days. The Wisconsin Dells are much heralded for their beauty and affinity for water parks, so thanks to some research by my mom and sister, we headed there for a spell. Given the recent flooding in the area, accomodations were easy to secure so we focused on lunch and entertaining ourselves first. Lunch was at a festive Mexican restaurant overlooking a lake. I had a strawberry-mango margarita that was about the size of my head and quite delicious. After lunch we booked ourselves a Duck tour and river boat ride. The "ducks" are amphibious vehicles that were employed during WWII to ferry soldiers to shore from the warships that could not approach the coast thanks to various obstacles such as mines and artificial barrier reefs. Many of these vehicles have since been co-opted into entertainment vehicles that allow civilians, like ourselves, to ride around in them on land and on the water. The river boat ride, although longer and more scenic, did not have the same novelty as an amphibious boat. Alas.

After our boating adventures, it was time for dinner. Thanks to our GPS, we selected a pizza place near the hotel. It quickly became apparent that this place was popular with the locals, though we were seated astonishingly quickly upon arrival, despite the crowd waiting in the foyer. Maybe it was my Indiana Jones hat. Dinner was delicious and a satisfying end to a long day.

18 Jun: Wednesday and it's time to head back to the city. On our way, we did what every real visitor to Wisconsin must do. Visit a cheese factory! (Green Bay Packers fans are not called "cheeseheads" for nothin'). The one we chose was both open to visitors, offered a tour, and was not too far out of our way back south. Perfect. The manager generously gave us about 40 minutes of his time to explain the cheesemaking process and though we didn't get a walk-around tour, he pointed out through the window step-by-step what was transpiring on the floor. Naturally, we bought about five pounds of the cheese including a few bags of "cheese curds", a favorite treat with locals (if it's not squeaky, it's not really fresh!).

Our Wisconsin experience was not complete without a stop at a Culver's restaurant. For those on the West Coast, Culver's is much like an In N' Out burger. I don't know the equivalent on the East Coast. Perhaps a Cook Out for you NC folks. In any case, it's a popular chain that serves comfort food from burgers to fries to various ice cream treats (ice cream is another thing you simply must try in Wisconsin. A state that has that many cows must have good cheese and ice cream. Beer factors in as well, but that's because there's so much leftover grain from feeding all those cows :) ). We ordered conservatively at first, but after some prodding from our cashier, our order rapidly expanded until she was convinced we'd order half the menu. It was delicious.

Finally, back to the city. We stopped in Evanston to pick up Kevin since it's a tradition that we always have to take him out for food when the family's in town. Works out well for him, eh? We moved from our hotel out in the burbs to one right smack in downtown that we got at a deep discount thanks to it's grand opening. After settling down, we walked out to catch a trolley to Navy Pier. Navy Pier, as the name implies, was originally established as a commerical enterprise that also served military purposes during the Second World War. Since it's on a great lake (and not the ocean like naval bases in Maryland and Virginia), the utility was necessarily limited and Navy Pier is long past it's naval days and now the most popular destination in all of Chicago. Taking about 40 minutes to walk up and down, the Pier is a treat for the senses. Lined with food stalls and entertainment options, it's a great place for kids and adults alike on a sunny summer afternoon. There's a Ferris Wheel for those who want a nice view of the Chicago skyline and an IMAX theater for those who prefer to soar to new heights more passively.

After a stroll along the pier, it was time to think dinner. Kevin recommended Khyber Pass, an Indian restaurant he and his Northwestern friends had visited some time earlier. The food was decent, but the service rather deplorable considering we were some of the only guestst that night. Oh well. The real treat came after dinner as we caught the fireworks display from the Pier. The show is put on every Wednesday and Saturday and is beautiful if rather (understandably) brief. We bid Kevin farewell by the river and then headed back to the hotel.

Sunday, 15 Jun cont

So now we're at Second City. Before we left the field, Sachi made an important discovery. She realized that she had only purchased 3 tickets for the show instead of 4 after being used to counting in terms of three for so long. Oops! While she was on the phone, my folks and I discussed who would get left behind while the others watched the show. Turns out, we didn't have to resort to drawing straws since Sachi was able to acquire one more ticket. Disaster averted!

On to the show. The troupe was hilarious as expected, regaling us with funny takes on what it's like to live in Chicago (from the Lakeshore Drive "rollercoaster" to the different attributes of Chicago neighborhoods) as well as some digs at politicians and entertainment celebrities (most notably R. Kelly). At one point, in a song discussing how our stereotypes tend to be confirmed whether we like them to or not, the singers reached their "Indians always smell like curry" line. The four of us were seated rather conspicuously near the front and naturally the singers looked at us significantly during that line. It was hilarious (and you know we do, that stereotype is totally true. Along with Indians being super smart and able to break into song and dance on a whim).

After the show, we caught a belated dinner at a little Mexican place in Lincoln Park that was fortunately still open. From there it was back to the hotel for some rest.

Congratulations Michael Phelps!

I will return to my story (related belatedly) shortly. First, a quick Olympic update and tribute to a man many are calling "the greatest Olympian of all time".

Citius, Altius, Fortius.

During this past week, I have been fortunate to watch Olympic history being made in Beijing, China. Ever since the 1994 Winter Olympics in Lillehammer, Norway, I have been a huge fan of the Olympic Games (hence referred to as OG for simplicity's sake). I have diligently watched every OG: Atlanta, Nagano, Sydney, Salt Lake City, Athens, Torino, and now Beijing, whether I've been in Round Rock (TX), Cary (NC), London (England), or Chicago (IL). Not being very athletic myself, excellence in sport is something I have long admired in my friends, countrymen, and fellow human beings. The OG offers a chance every two years to witness arguably the highest form of such excellence in sport in the world and I don't want to miss a minute of it if I can help it. I love how the Olympics brings the world together and asks all of those participating and watching to seek the best in themselves. For these all-too-brief fortnights, conflicts can (mostly) be put on hold, disputes delayed, and patriotism rekindled.

Faster, higher, stronger. These adjectives, the motto of the OG, also embody the goal of each Olympic athlete to achieve the superlative of each: fastest, highest, and strongest. This week in Beijing the world has witnessed what may be considered the greatest single performance at an OG:

American swimmer Michael Phelps winning eight gold medals in eight events (5 individual and 3 team), 7 of those in world-record time and the last in Olympic record time.

Yes, he is perhaps the most overexposed athlete so far of these Games. We know what he eats, when he sleeps, what he wears, and how he trains. But we still don't know how he did it. How he made history for the most number of gold medals won at a single Games, winter or summer. How they were all in record time. How they all took place over the course of just nine days. And most of all, how he made many of them look so easy. Was it the new LAZR suit from Speedo? Was it the "faster" pool in Beijing? Was he sent from the future to compete with mere mortals today? Whatever it was, however he did it, we know one thing for sure: Michael Phelps is an incredible athlete and has set a new benchmark many will admire and others will aspire to surpass. Congratulations Mr. Phelps. I hope to see you shine again four years from now in London.

On the Olympics in general:

The modern games, begun in 1896 in Athens, Greece, involve the traditional Olympian events such as the marathon, wrestling, and running, and also include various point-based sports such as soccer, basketball, handball, water polo, etc, as well as more subjective events such as gymnastics and figure skating.

The latter two, as much as I (and millions of others) enjoy watching them, should not be Olympic sports in their current form. Although these athletes are superb at what they do, from leaping into the air and performing dizzying spins to pulling an "iron cross," the ultimate gymnastics feat-of-strength, the judging and subjectivity involved in determining the best performance is just too much to be called a "sport." Real sports are by and large objective; the most (or least) points, the fastest time, the highest height, the heaviest weight, etc. The only subjectivity permissible should come from judging penalties. (For that matter, cheerleading is an athletic activity too, but not a sport).

If I had it my way, the IOC would determine fixed routines of different levels, say "easy," "medium," and "hard." For example, of the four apparatus on which the women gymnasts compete (floor, balance beam, uneven bars, and vault), only the floor would be open to "free expression" or a routine entirely of the athlete's choosing (this would encourage and reward creativity). Athletes can pick any combination of difficulties, from all easy to all hard and everything in between. By having everyone compete from the same pool of routines, each performance can be compared more objectively with the others. For some people, such a competition would be more boring (most likely current gymnasts and former gymnasts who are commentators for gymnastics events). Frankly, most spectators cannot tell the difference between the skills of one routine and the next, but can usually tell the difference between a well or poorly executed routine. Given this observation, people viewing these events will still be entertained and the athletes will be judged more fairly. This system could also be implemented for the men's gymnastics and both men and women's figure skating for the winter Games.

But after all, who am I to judge how Olympic events should be run? I am no gymnast, figure skater, swimmer, skier, hurdler, luger, wrestler, bobsledder, pole vaulter, or athlete period. I do love the Olympic Games, however, and believe that such displays of amazing athleticism should be rewarded with as little bias as possible.

Sunday, 15 Jun

All right, enough of the present tense. I'm writing about past events and will thus tense my sentences appropriately. Note, pictures of the trip can be viewed on my Facebook page until I find the time (if I ever do) to eventually move everything to flickr as Saket has done. At least I made a flickr account before he did!
Today was Father's Day, and to celebrate we spent the morning and afternoon downtown at the Museum campus, followed by a show at Second City up in Lincoln Park. Three of Chicago's finest museums/learning centers, the Field Museum (natural history), Shedd Aquarium (duh), and the Adler Planetarium (more duh), are located on a beautiful part of the lake shore within easy access by foot or car from downtown. Not only are the grounds well kept and the buildings stately and grand, but to walk to the end of the pier on which the planetarium sits is to be rewarded with one of the finest views of the Chicago skyline in the entire city. The only view that rivals it, according to locals, can be found on the South Side at "The Point." But I digress.

We started first at the Field Museum since it's my favorite museum in Chicago so far (granted, I've only visited four as of this post and there are many more) and the one I really wanted to show off. We arrived around 11 and after parking took a nice stroll alongside Soldier Field (which also happens to be right next to the Museum campus whose parking lot is conveniently co-opted during Bears' games). Soldier Field, as the name implies, is a dedication to the armed servicemen and women of the United States who served our nation bravely through many a conflict. It is also home to the Chicago Bears, the only professional football team of the state of Illinois and one Chicagoans (yes, that's the right term to refer to a resident of Chicago, not "Chicagoite," "Chicagan," "Chi-towner," etc...) hold near and dear to their hearts (especially last year when they faced the Colts in the Super Bowl yet sadly lost despite an incredible opening kickoff touchdown run by Devin Hester which was the first of its kind). Back to the museum.

The Field Museum boasts a first-rate collection of natural and historical artifacts from around the world. One of the highlights is a nearly complete (and largest ever found) fossilized skeleton of a Tyrannosaurus rex known affectionately as "Sue" (named after the archaeologist, Sue Hendrickson, who found her decades ago in South Dakota). Appropriately, Sue greets visitors to the museum almost as soon as they walk in, much like the way the famed Rosetta Stone is kept front and center at the British Museum in London. Sometimes it pays to put the best first instead of last. Along with Sue, the Field has a whole suite of exquisitely preserved dinosaur bones and an excellent display regarding evolution. Instead of presenting this well-supported scientific theory as a bunch of facts on placards, the museum has constructed a "walk through time" in which visitors start at the beginning nearly 4.6 billion years ago and literally move through the ages as they walk through exhibits explaining concepts from tectonics plates and climate change to speciation and extinction. This type of presentation not only conveys evolution as a logical progression of events but explains much of the rationale behind the theory and why its conclusions are so relevant today. A relatively new addition to the exhibit, which is possible due to the efforts of the provost of the museum, and a professor at my university, Dr. Neil Shubin, is known as Tiktaalik and represents one of the long sought-after "transitional forms" both evolutinists (and their "foes" creationists/IDers) have been yearning for as support/proof for the theory of evolution.

Why are there so few fossils like Tiktaalik? Why don't we see more transitional forms if evolution is a gradual process by which one species can become another? Simply put, the answer is far from simple. A large part of the evidence for evolution (both human and non-human) comes from fossilized or otherwise preserved remains that allow scientists to link present and past forms together and see what has changed and what has remained the same. Fossils are great evidence because they can be quantified in terms of size, weight, physical condition (tooth marks, burn marks, boiling, relative age, etc) and age in terms of how long ago the fossil was created (usually by dating the rocks in which the bones are found). They can also help reconstruct extinct species and give us an idea of what older creatures looked like, how they moved, what they ate, etc. In short, fossils open a wide window to the past. These windows, however, are hard to find largely because making them requires special conditions and finding them is largely the work of sheer luck. Windows are also easily dirtied by the elements and fossils are no exception. Contamination from recently dead material can lead to sometimes disastrous misdating of remains which muddies timelines and casts doubt on both evolution and the validity of radiometric dating methods. It is due to all these difficulties that the finding of Tiktaalik is such a big deal. All we need to do now is find more of them. Good luck Dr. Shubin!

The Field kept us occupied for a couple hours and then it was a quick bite to eat at the Corner Bakery in the museum (quite delicious actually). After our brief rest we headed further out onto the pier to the Adler Planetarium which was free that day. Unfortunately, our time there was all too brief since we had to make our way up to Lincoln Park in time to catch our Second City show. I mean to go back there at some point. I've always been a space geek and this planetarium, though geared towards young people, ain't half bad.

The Second City is an improvisational comedy club whose reputation stems from the fact that many well-known and beloved comedians (from Jim Belushi to Tina Fey) got their start/big break by being on the SC cast. "Second City" is also a nickname for Chicago since, for the longest time, Chicago was "second" after New York City in terms of population and size. Currently, Los Angeles holds the title of "second city" though Chicago could reclaim the name if it wins the bid for the 2016 Olympic Games.

As this post is getting rather lengthy, I'll continue the rest of the story in the next one.

Would you believe they put a man on the moon?

A brief departure from the story that still needs telling...

Today, July 20th, 2008, marks the 39th anniversary of the Apollo 11 moon landing (July 20, 1969). The mission accomplished what John F. Kennedy dared the country to achieve over 9 years earlier in 1960. The mission was historic on many levels (first human landing on an extraterrestrial body being perhaps the most significant of them), and yet it saddens me that many people doubt it ever happened and believe that our presence in space is now just fulfilling some antiquated and somewhat misguided dream.

What about all the problems here on Earth? some will argue. Shouldn't we be more concerned with ending poverty, curing infectious diseases, stopping wars, etc than spending tax dollars to send up yet another space shuttle, yet another satellite, yet another telescope, yet another human being on the greatest adventure our species has ever undertaken.

To leave one's home is a universally recognized sign of maturity and independence. Species that travel around in troops (chimpanzees for example) routinely send out either male or female members once they "come of age" to find another troop to join, thus keeping the gene pool well mixed and reducing friction at home. For mankind to leave Earth's land, sea, and air is a feat achievable by no other extant species and one accomplished by no extinct species either. Nature abhors a vacuum and thus no known living thing can exist in the harshest of all environments. Even Thermus aquaticus, a hardy bacterium whose ability to thrive and survive in water at temperatures between 160 and 175 degrees Fahrenheit allowed for the development of polymerase chain reaction technology (discussed in a an earlier post) that has revolutionized modern biology could not survive in a vacuum. Even the phantasmagoric creatures that inhabit the darkest depths (miles down) of the ocean where pressures can be hundreds of times what we feel at the Earth's surface could not survive in a vacuum.

But lauding the merits of the manned space program is a topic for another day. For now, the 39th anniversary of the moon landing should be a reminder that even the seemingly impossible can be achieved in a short amount of time if there are enough dedicated minds, hearts, hands, and dollars to the cause. This week, ex-Vice President Al Gore delivered a challenge reminiscent of JFK's proclamation to the nation nearly 50 years ago.

Gore delivered his address at a time of impending economic recession, two wars without end, a presidential election year, a disastrous housing crisis, long-delayed recognition of the crumbling infrastructure throughout the nation, genocide in Darfur, nuclear fears in Iran and North Korea, possible war between Thailand and Cambodia, increasingly armed and friendly China and Russia, and the weakest dollar in decades. In spite of all these ills, Al Gore wants us to save...the environment? Now why on earth should be worried about the Earth's health and condition when our own health and standard of living is being threatened by so many forces? Why? Because of a simple idea few seem to recognize with any immediacy or profundity: without a healthy planet there can be no healthy life or adequate standard of living for any of us, no matter how rich or entitled we may be.

If people in America think gas prices are bad now (~$4 a gallon), imagine how they'll feel when those oil reserves start drying up and everyone, including people in China, India, and Africa once disregarded as potential consumers in older calculations, is still clamoring for more and more oil. But if we can free ourselves from the chains of petroleum we can not only avoid that kind of energy crisis, but more importantly remove the yoke of OPEC and its member dictatorships from around our neck and breathe the air of freedom certain individuals in our administration are trying so hard to instill in many of those nations.

So how does the environment factor into all this? It's no coincidence that "environmentally friendly" practices (from waste disposal to energy generation to transportation, etc) use fewer resources of all types, including energy. The best way to eventually do away with our dependence on fossil fuels is to reduce that dependence first. Reduce, reuse, and recycle. Those simple three R's that everyone's heard but few truly heed. For far too many people:

#1 unthinkable--> I want more stuff, not less.
#2 distasteful--> I want new stuff, not old stuff.
#3 inconvenient--> I can't spare the time or effort to sort my trash, and there are no recycling bins near me.

Al Gore is leading a movement to change this way of thinking, because without a new trend of environmentally conscious behavior the planet and all its inhabitants will turn into the dystopia pictured in WALL-E.

Enough ranting. The moral of my story: let's do for the Earth what we did for man in space. If we succeed in this venture, future generations won't have to doubt that our mission was ever accomplished. They will be living proof it did.

Saturday, 14 Jun

I woke up earlier this morning than usual for a very special reason....the family was going to arrive soon! No sooner do I get out of the shower and am ready to wash my hair I get a phone call from Sachi saying they're about a half hour away from the city and would call again to clarify directions as they needed them. I quickly dried my hair, got dressed in my brand new UChicago shirt and after informing Bonnie and Jeffrey to expect my fam, I skipped down the steps to wait outside. Fortunately, it was a glorious day. Now the definition of "glorious' weather obviously varies from person to person, but I feel few could have argued with my definition today. Fluffy, sculpted clouds drifted lazily across and otherwise perfectly empty azure sky; a gentle breeze stirred the leaves whose whispers were frequently interrupted by chirps from robins to cardinals and other species I couldn't recognize. The temperature was perfect in the lower 70s F. In short, it was truly a glorious day and quite a pleasant change from the 90+ temps they were leaving back in Cary, NC.

I scan the streets in all cardinal directions for our gray Odyssey and after a few minutes spot one a block over heading too far north. I'm sure it's them and laugh because they clearly missed their turn but will realize it soon. Sure enough, a few seconds later I get a call from Sachi informing me they went a little far and am heading back down to me. Finally, the van cruises down Greenwood Ave and grinning from ear to ear I guide them to a good parking spot. Reunited at last!! I'm engulfed in a succession of bear hugs from everyone and then it's time to unload and head upstairs. So much stuff! It feels like I'm moving in all over again. B&J give my folks a warm welcome and while they all chat, I drag the goodies into my room to start unpacking. Chuckrie, shrikhand, kofta, paneer, nuts of all kinds, my Indiana Jones hat!, the treats just keep coming...

After driving so long, I knew they wouldn't mind some exercise so I take them on a jaunt around campus and my lab (the one I was officially leaving but still had a key, and permission, to give a tour). I forgot this was also graduation weekend and so the quad was filled with students in black gowns, parents in their Sunday best, and lots of food and drinks under tents. Thinking that usually big crowds = full restaurants I hurry us over to Noodles, Etc to beat the people I'm sure would be hot on our heels. Fortunately, the place was only half full and we get a nice spot by the window. Sure enough, no sooner do we get our orders then the place starts filling up with all the grads and their families. Whew! That was a close call. After eating, I thought walking down to the lake might be nice so we take a nice stroll along 57th street until we cross over to the greenbelt.

We relax on the rocks for a bit and then head back home along 53rd this time so they could see one of the other major commercial streets in Hyde Park. It's tea (and nap for Mom) time at home so we brew up some refreshments and sit around chatting for a bit. At the same time, my neighbor (and professor) Marcus Peter was having a celebration downstairs to mark his son's graduation, daughter's birthday, and his and his wife Andy's new US citizenship. After everyone was rested, we head downstairs for a little while so that Marcus could meet my folks. I see a couple other professors (including one of my favorites, Kay MacLeod) there and introduce them to my folks. It's nice to see them in a completely non-academic context.

After hanging out at the party for a bit it's time to pack my things and head into town before going to our hotel (six people in a two-bedroom, 3 person place for a week would have been a bit much, and it will give B&J some time alone that they haven't really had since I moved in). Sachi found a placed called The Italian Village in downtown Chicago that was a bigger deal than I think any of us realized until we got there. The layout was spectacular: lots of little booths and alcoves that both created a sense of space and made the restaurant feel more intimate...rather paradoxical but it worked. We are promptly led to a little alcove and enjoy a fine meal without the crowd and noise one is used to in restaurants. This place takes the idea that ambience and decor can make or break a dining experience seriously and to wonderful effect.

Dinner over, we drive out to our hotel which is about 30-40 minutes from the city. We're pretty beat from a long day so tuck in early and call it a night.

End of Term and the Family (most of it) Visits

Finally, spring quarter officially ended for me on June 13th. Although classes were over the week before, as I mentioned I spent exam week in lab so technically my quarter didn't end until I finished that last real-time. Grades-wise I fared pretty well; two passes, one A, one B, and one (the rotation) I don't have the results for yet. B's are common, A's are rare, so we'll see.

But let's forget about school work for now...and until September (except for research which I'll be discussing periodically). The following posts will chronicle the week from June 13th to the 21st that I spent with most of my family, i.e. Sachi and my parents, in and around Chicagoland [Saket, that poor guy, was starting his first full week at Apple, Inc out in the Valley at a sweet internship with their iPod hardware division...yes, let's all feel very sorry for him :)].

Success at last!

If you recall, on my last post I had said that none of my experiments had really worked. Well, as of Friday the 13th, all of that changed...

In my final week in Dr. Dolan's lab, which also coincided with finals week (which wasn't a big deal since I only had one take home final to work on), I decided that it would be worthwhile to repeat my knockdown experiment one last time, except with a few changes: 1) shorter time point of 6 hours vs. 24 hours, 2) added the siRNA to the nucleofection 96-well plate before adding the cells+NFS mixture, 3) allowed the cells to rest for 10 minutes at room temperature in the hood before adding pre-warmed media after the nucleofection, and 4) pooled four wells per sample instead of two.

On top of changes to the protocol, my technique was solid on the RNA isolation, RT-PCR, and real-time PCR. My RNA yield was the best it'd been all quarter, and my real-time results were not only beautiful but more importantly were believable because the standard curves (for the standards and samples) had a slope of about -3.4 which is much closer to the ideal -3.3 that's expected for totally pure cDNA.

So what was the final result? At the highest concentrations tested (40 and 60 pmol), I saw an almost 80% decrease in CYP1B1 RNA for both cell lines after 6 hours of transfection. These results are very exciting since it shows that transfection is possible with these LCLs (otherwise considered a very difficult system in which to transfect siRNA) and that the vector system we've chosen (96-well, the particular program and NFS) are workable, if not necessarily optimal, choices.

The next step is to carefully note any and all the changes to the protocol I made (some of which were really just reverting back to what Amaxa, the supplier of the transfection stuff, recommended) and then explain those to others in the lab. Woohoo!

Real-time PCR

So I've taken you from cells to RNA to DNA, now it's time to find out whether my siRNA knockdown experiment actually worked. What real-time PCR does is implied in the name; it provides information about the quantity of a particular gene (or genes) at the time the assay is performed. The PCR part comes from the fact that while during the reverse-transcription step we use random primers to amplify all the RNA in our sample, this time we want to only amplify particular genes so we use special primers for them. What makes these primers special? Let's say they give the reaction a special glow.

A company, Applied Biosystems, has developed a system (or perfected it), in which a special probe with a colored dye and a quencher (a compound that masks the dye) is affixed to one end of the primer (a small stretch of DNA that will anneal to one end of a gene of interest) such that when the DNA polymerase enzyme that adds DNA nucleotides together runs into it, the probe is cleaved and the dye and its quencher are separated such that when the sample is excited, light is emitted which is read by a detector. This cleavage, excitation, and light emission occurs during each cycle, so the more of the target DNA there is, the more light will be emitted and thus read by the machine. Make sense? Multiple dyes for multiple genes can be added to each sample. In our case, we want to know the levels for our gene of interest, CYP1B1, and a housekeeping "standard" gene (HKG), huB2M, that lets us know the quality of cDNA we're testing and to control for any extra high overall gene expression in our cells (which is a frequent issue with tumor cells, though our LCLs are from normal, healthy individuals).

Once the samples are read, fold-change is assessed by dividing the amount of CYP1B1 by the amount of the HKG, and then dividing our concentrations by the 0 pmol (control) sample. If things work as they should, we expect to see a dose-dependent decrease in CYP1B1 in cells receiving the siRNA such that the higher the concentration of siRNA added, the lower the resulting gene expression.

My experiments, unfortunately, did not work. I got crazy fold-change numbers such that for one cell line I first saw a knockdown of about 40% and then two weeks later saw a 1×10^7 (that's 10 million fold) increase in expression! Crazy. Naturally, I repeated the experiment and will get my results tomorrow. Later!

RT-PCR

"Reverse transcription polymerase chain reaction" is a five-word mouthful for something more easily said in four simple words: "turning RNA into DNA." The polymerase chain reaction (PCR) single-tubedly revolutionized molecular biology and changed the pace of research in the field forever. It was such an important development that like many other important scientific techniques (including electron microscopy and centrifugation (here called "disperse systems)), it won the Nobel Prize in 1993 and rightfully so. In short, what PCR does is turn a very small amount of DNA into a lot of DNA, still microscopic of course but enough that scientists can actually work with and manipulate it. Here's a video of the process.

The "reverse transcription" means a lot of what it implies. Just as I said how transcription was turning DNA into RNA, the reverse of that process turns RNA into DNA. Viruses are unique in terms of "living" things (viruses are technically not considered living because they need a host in which to reproduce) because some of them use RNA (single stranded or double stranded) as their genetic blueprint instead of DNA (like we and every other organism in every kingdom of life do). HIV is one such example of an RNA-virus. As suggested, these viruses have the natural ability to turn RNA into DNA, a process they need to do in order to integrate their genetic material into that of their hosts'. To do our research, we borrow the special enzyme they use called "reverse transcriptase." It's actually quite remarkable how many uses scientists have for viruses and their products.

So for RT-PCR, instead of the normal DNA polymerase (an enzyme that joins DNA nucleotides together), we use reverse transcriptase. And since we want to convert all of our RNA into DNA (all of the genes), we use random primers (short sequences of nucleotides that specific a part of the genome to amplify) instead of specific ones (those come into play later when we hone into one gene).

Unlike the laborious process of RNA isolation, RT-PCR is quite simple and is just me making up a mix, aliquoting it into tubes with my RNA, then throwing all those tubes into a machine that does the heating and cooling (cycling) for me according to a program a lab mate set up. All I have to do is come back in a couple hours and boom, collect my DNA. Kinda like magic. Then again, a lot of science seems like magic....

Next up: Real-time PCR!

RNA Isolation

So I left off talking about we artificially reduce protein levels (be reducing levels of the template) and what we hope to see from that. Now, briefly, I'll describe how we can tell those protein levels have gone down to the extent that we want them to.

First step, isolating the total RNA from the cells. Think of this step as a lot like panning for gold. You're standing in the middle of the river, with your pan in hand, and scoop up a good mound of the river bed. In it are pebbles, sand, tiny microorganisms, some plant matter, maybe some pieces of pollution, and of course some tiny nuggets of gold. The quality of the gold doesn't matter right now, you just want everything with Au atoms in it. So how do you separate the yellow stuff from everything else? First you shake the pan rather vigorously, then as more and more of the junk falls out you sift more slowly and carefully, occasionally washing the pan with water. Finally, after shaking and washing, you see clinging to your netting tiny little nuggets of gold that you then store into well sealed containers for later analysis.

And now back to RNA. Much like the example, RNA isolation is a process that ranges from the rough and tumble to soft and gentle. Cells from the nucleofection plate are pipetted up, put into tiny centrifuge tubes, spun down at about 100g until they form a pellet, and are dropped into liquid nitrogen where they are flash frozen. (By the way, liquid N2 remains hands down the coolest reagent in science. Though I've handled it many times now, it never gets old).

After the cells are frozen (in which all the liquid around them gets frozen or evaporated off too), they are resuspended in a solution that breaks up the cells to release all their contents. The tubes are spun again so all the heavy stuff (proteins, etc) sink to the bottom while the light stuff (DNA, RNA), stay at the top. The tubes we use are two-chambered in that the bottom chamber collects eluent that flows down from the top chamber. Near the middle of the top chamber is a special filter to which nucleic acids (DNA and RNA) can cling but nothing else can. This way it is easy to discard everything but the nucleic acids throughout the process.

Once protein and nucleic acids are separated, it's time to get rid of DNA since we're not interested in it. We use a tube that has a specific filter for DNA that traps it while letting RNA through. Keep in mind none of these steps are perfect, but these macromolecules are different enough such that these separation methods really work quite well. To get just RNA, it's a matter of washing with various solvents and spinning the tubes many times in a centrifuge. At the end, we get about 2.5 or more micrograms of RNA (that 2.5 millionths of a gram). Very, very small amounts of material here. Once we've got our RNA suspended in water, we throw into the freezer at -80 C until we're ready for the next step: reverse-transcription polymerase chain reaction, also known as RT-PCR.

What I Do in Lab, continued

It's interesting, but sometimes I feel as though the New York Times and I are strangely in sync with one another, especially in regards to their articles about science topics. Just yesterday I found these two articles, Genes Explain Race Disparity in Response to a Heart Drug and A Genetics Pioneer Sees a Bright Future, Cautiously
that made me pause for a moment. It was pharmacogenomics in mainstream news. Hooray! See? What I'm working on isn't so obscure after all. For current "real-world" applications of the kind of stuff I'm working on, please read these articles.

Anyway, back to my work. So I talked about how we aim to decrease the levels of a particular drug-clearing enzyme to make the cells we treat more sensitive to our chemo agent. The next thing I should explain is how we actually go about manipulating levels of said enzyme.

First, a brief lesson in molecular biology. DNA, or deoxyribonucleic acid, is considered to be the "code of life" as it prescribes nearly all the information required for organisms in all five kingdoms of life to fulfill the requirements of life, i.e. grow, reproduce, survive, etc. Living things, however, are not made of DNA alone (obviously). The information coded in DNA proceeds along the path to proteins (what we actually see and feel in living things, i.e. skin, hair, etc) through an intermediary molecule known as RNA, or ribonucleic acid. DNA and RNA are very closely related but have significantly different properties which suits them for their particular roles. RNA is much less stable (it's single-stranded instead of double-stranded) and is usually rapidly degraded after it's produced (compared to DNA which lasts until the cell dies). The type of RNA I'm interested in in particular is messenger RNA, or mRNA. The "messenger" bit comes from a famous molecular biologist who likened that molecule to a "messenger from God" for it's role in transducing DNA's message (so much for all scientists being determinedly irreligious!). What does the RNA send its divine message to? Structures called ribosomes which are synthesis stations in which mRNA is used as a template off of which proteins are built.

If you consider the percent composition of living things, we are possibly 99.9980% protein, 0.0015% RNA, and 0.0005% DNA. Do not take these percentages for fact; I literally made them up just for a sense of scale. But I digress.

If we want to knockdown protein levels, there are three conceivable ways we can go about doing that. One is to alter the gene (DNA) to make a substandard protein that doesn't do its job so well. Another would be to break down the final protein or inhibit its activity somehow by making it stick to another protein or small molecular (this is actually how many new fancy drugs work). A final way, and the way we're using, is to go after the mRNA and reduce its levels such that the protein isn't made in normal quantities in the first place.

Back in the early 1990s, two labs headed by molecular biologists Craig Mello and Andrew Fire discovered an incredibly potent viral defense mechanism in the roundworm C. elegans in which foreign RNA (many viruses have RNA instead of DNA as their primary "code of life"; bit of a misnomer here since viruses are technically not considered living things) was rapidly degraded by a unique type of RNA produced by the worm's cells. This defense mechanism had already been identified in plants, but what made Mello and Fire special (and eventually Nobel laureates) was their insight that could harness that natural defense mechanism to attack any RNA of their choice. This technique, called RNAi (short for RNA interference), won them the Nobel Prize in 2006 (just over a decade after their discovery) and is an extremely common and invaluable laboratory technique. (If you care to find an earlier post I made back in winter 2007, you can read about my experience of actually meeting Dr. Mello at the Field Museum here in Chicago).

Back to the lab. The siRNA experiment is actually quite simple:
1) I siphon off the volume of cell suspension I'll need from the flasks in which they grow (the cells we use, lymphoblastoid cells, do not grow flat on plates but suspended in media...think Guild Navigators for you Dune fans, except these cells fortunately can't bend space).
2) I then spin down the cells to form a tiny pellet that I then wash with a simple pH neutral solution to remove any remaining media.
3) Spin again to make a new, cleaner pellet.
4) Now I add in a "nucleofection solution" which basically makes lots of tiny holes in the cells such that stuff can get in, but they still stay alive.
5) I carefully plate these hole-ridden cells onto a dish full of tiny wells.
6) Quickly, else the cells will die, I add in my siRNA solution that is full of those attacking RNA molecules. Since I wish to knockdown the CYP1B1 protein, the siRNA I use is specific for the mRNA for that protein.
7) Once the cells have been dosed with the siRNA, I place them in a machine where they are "zapped" with an electric pulse to make the cells take up the siRNA. This takes seconds.
8) Once the cells are zapped, I give them some warm media and stick them in the incubator for some minutes to let them recover from the shock (a pun, haha).
9) Once they've relaxed a bit, I plate them out onto a new dish and add some more media so that they will be happy.
10) At a predetermined time point, in my case 24 and 48 hours after plating, I'll scoop up those cells and go on to the next experimental step: RNA isolation.

All in all the nucleofection takes approximately 2 hours from start to finish. Not too bad, considering I performed an RNA isolation today which took approximately 4.5 hours, so I'm not exactly in the mood to describe that right now...but I will do so tomorrow! Stay tuned!

Spring Quarter Rotation, or What I Do in Lab

Over the course of the next seven weeks, I will frequently post "in lab" as an away message or respond as such if I am called during working hours on Monday, Wednesday, and Friday. So what am I doing in lab? Allow me to explain (both the why and what such a question might address):

As a first-year cancer biology grad student at the University of Chicago, I am required to complete two 10-week (whole quarter) rotations or time-periods in a research laboratory run by a professor on the cancer biology committee (though not necessarily exclusively so). Shortly before I arrived on campus last September, I was surfing through faculty research pages in search of a potential PI (principal investigator) to rotate with. I found Eileen Dolan's page and just needed to see "identify genetic determinants contributing to cellular susceptibility to chemotherapeutic agents" before I was hooked. I immediately emailed Dr. Dolan and set up an appointment with her just two days after I would arrive in Chicago. Our meeting went well, and she agreed to let me rotate with her in the spring.

The months passed amazingly quickly and before I knew it, spring break was over and spring quarter was starting! The week before break I attended lab meeting (for those who don't know, these are weekly sessions in which a lab member or members present their work and receive feedback on it from the rest of the lab, especially the PI) and learned that I would continue a project started by another grad student who was just finishing her rotation. I owe much already to Nora for doing a lot of the grunt work (optimizing a protocol...more on that later) and letting me have all the fun.

My, rather our, project is to decrease the expression of a particular drug metabolizing enzyme, CYP1B1, in lymphoblastoid cell lines that highly express that enzyme and see if these cells become more sensitive to the chemotherapy agent daunorubicin. The hypothesis is that high expression of this drug clearing enzyme allows these cells to render the chemo useless (breaking it down very quickly, etc) and thus escape cell death. If we can decrease the amount of the enzyme in these cells (by decreasing the mRNA which in turn would decrease protein levels), then these cells should die more readily (at lower drug concentrations) than they do otherwise. I'll go later into the science specifics of how we decrease expression and dose with the drug.

Why is this project relevant, you might ask? The vast majority of chemotherapy agents must be processed by the liver in order to become biologically active. Many over-the-counter and prescription drugs work the same way. When the drug enters the body, it reaches the bloodstream through intestinal lining (unless administered intravenously) and then travels through the liver before continuing on to the rest of the body. The liver is such an important organ (and not surprisingly the largest internal organ) because it processes all the circulating blood in the entire body. It detoxifies and cleanses blood continuously (which is why the only solution for a hangover is time; the liver can only process all that alcohol, i.e. toxin, so fast). There is a superfamily of enzymes found primarily in the liver known as the Cytochrome P450 (CYP450) family. These enzymes handle the vast majority of toxins and foreign agents the liver processes, including drugs.

Proper drug formulation is crucial for its activity since these enzymes modify the compounds in certain ways and in short try their best to inactivate or destroy them (hard for the body to distinguish friend from foe: while you can train your eyes to tolerate contact lenses you can't train your liver to be nice to certain things and attack others). Knowing this, drug companies formulate their drugs such that they usually must be modified in some way to actually work. Just popping the pill in your mouth does nothing; it must travel through the liver and then reach its target through the bloodstream. You can determine how long this takes by measuring the time between you take a painkiller and when you start feeling relief (it takes me about an hour with Advil, but I have no idea if that's typical...) Anyway, chemo agents must be processed by the liver to work.

The catch, however, is that not all livers can process drugs the same way because each person has a slightly different set or variation of the CYP450 enzymes. This variation is caused by the genetics that make us 99.97% alike and yet still 0.03% different. As a result, while some people can process a particular drug well such that it gains proper activity, others cannot process it and that drug does not work for them and can potentially build up to unsafe concentrations in their body (chemo agents in particular are very nasty; you don't really want them at the therapeutic concentration much less anything higher, especially when they're not really working anyway!) The enzyme we're working on, CYP1B1, is a member of this family and studies have implicated its role in conferring resistance to daunorubicin. Thus, we postulate, if we can lower the activity of this enzyme we can let the dauno be processed the way it should to properly kill the cell. Make sense?

Ok, so that's a good bit of background. On my next post I'll explain how I will go about testing our hypothesis. Cheers!

To catch up: Finals Week(s)

Losing Eve six weeks ago hurt, a lot. That loss along with being truly and insanely busy with finals (enough that I probably lost about five pounds and made myself sick), rather took blogging further off my mind than unfortunately it normally is (unfortunate for those few yet faithful readers). In return, I promise to be more diligent and keep this updated every few days.

So, how did winter quarter end? I survived, to say the least, and managed to pull out a few surprises for myself. I scored two A's and one B, which is an improvement over my one A and two B's from last quarter. Guess what I plan to get this spring J? The B came from Fundamentals of Molecular Biology, which is actually quite sad considering how relatively elementary that class was compared to Cell Biology of autumn quarter (what I consider quite possibly the hardest class I've ever taken, period, except perhaps orgo one and two). The A's were in Cancer Biology II, in which a B would have been not only downright embarrassing but pathetic! My A was a pretty good one nonetheless, certainly one of the top three in the class (a rare statement from me about a science class since high school; to be fair I've done but seldom superlatively well unlike in some of my English classes).

The second A was in Signal Transduction which went from being possibly the easiest to the scariest to the easiest class on Earth all in the space of a few short weeks. To begin with, the three cancer biology students in that class (myself, Kelly, and Tanmayi) were there because we were told there would only be one exam and a take-home at that. Score! This is what we thought for about the first half of the quarter, a thought that allowed me to guilt-free zone out a bit during some of the more tedious lectures. Then, after checking with the TA that "this class really is just going to have a take-home final, right?" We're told, "no, we're changing it this year since so many people skipped class last year." Frak! The next few weeks went by in a bit of a panic that was accompanied by furious and diligent note-taking. Now comes the week before finals. Tuesday is the review session and Thursday the in-class final. I bring with me all 8 weeks of notes which were derived from the wood pulp of an entire acre. Instead of our usual classroom, we find ourselves in a conference room with a video from a Nobel Prize-winning lecturer ready to begin. What was going on? To allay our fears, our professor informs us that due to "excellent attendance", they've decided to make the final take-home after all. A collective sigh of relief exhaled from the students and suddenly the day become a whole lot brighter. I was saved! The final ended up being five questions and required just five lectures (out of 16) to answer. All in all it probably took me just over two hours, and most of that time was spent flipping through pages to find the pathway I needed. Total length? Just fewer than three pages (compared to the eight of my cancer biology take-homes). I don't know the final distribution for that class (there were only eight of us in it), but I must say I am grateful for my A despite not being as attentive (or smart) as most of the other people in there.

As for my other classes, Can Bio II wrapped up well yet rather hectically. My poster presentation went fine (I could have been more prepared, but still did well) though getting my final in nearly gave me a heart attack. The Friday before we were informed that our final would be due no later than 9 a.m. on Tuesday, March 18 (the poster session was the 17^th). Since I mostly worked on the poster/studied for Mol Bio over the weekend, I didn't devote much time to the final except doing some background research on the questions. So I get home on the 17^th around 1:15 to find an email from my TA asking that our finals be sent in no later than 3 p.m. so she can distribute them to our professors. Needless to say, I almost had a cardiac infarction and immediately informed my TA of what our professor said. I went on to spend the next nearly 12 hours typing away almost without break. The final product wasn't my best, but at least it was done. Considering I headed into the final with almost the highest grade in the class, I wasn't too worried…

Anyway, enough about classes. Next post: spring break!

Blogging with Microsoft Word…

Who would have thought that two huge rivals, Google and Microsoft, could team up (at least on some level) to let users of both companies' products do something fun and useful? Blogger, a very popular blogging resource owned by Google is compatible with a new "Blog Post" feature in Microsoft Word 2007. This means I can type any document I want in Word (like what I'm doing right now), click "publish," and voila! My doc gets posted to my Blogger page smoothly and beautifully.

Why does this matter? For one, it lets me write and save blog posts before I publish them in a secure and familiar program. Instead of a normal Word doc, something I've used before, now when I'm ready I can post from Word directly instead of copying my text into Blogger's "add post" feature. Probably the best part of this feature, though, is my ability to publish anything I can normally put into a Word doc to my blog. By this I mean an Excel spreadsheet, Powerpoint graphics, Word tables and graphics, equations, other images, you name it, all without formatting troubles you often get by moving between different programs.

Why I am excited about this? It's because I'm a total geek and increasingly big fan of the new Microsoft Office 2007 suite. Vista, from what I've heard, was pretty much a total bust but Office '07 carries the day in my book…

Eve Marie Carson, 1985-2008

On Wednesday, March 5, 2008, in the early hours of the morning, the University of North Carolina at Chapel Hill and the world at large lost a soul whose light burned with the fierceness and warmth of a thousand suns. Eve Marie Carson, beloved daughter, sister, friend, mentor, colleague, peer, and human being, was shot and killed in an unspeakable crime that awaits resolution. Here's a press release from the university.

I found out about Eve from my sister, Sachi, who called me with the awful news this afternoon as I was heading home from class. I had about 10 minutes to digest the information before reaching my computer. It wasn't until I saw her picture on UNC's main page that the horrible, horrible truth became real for me. While I cannot claim to have known Eve Carson particularly well, we did speak on several occasions during the three years we both attended UNC.

I met Eve during an event about science hosted by the Honors Program. While I do not remember the specifics, I remember the impression Eve, just a freshman new to the university, made on me at the time. I could tell, literally in just minutes, that she was someone special and capable of a great things. It wasn't her charming smile or intelligence that made itself known the moment she opened her mouth. It was her exuberant enthusiasm to be wherever she was at the moment that really struck me. Fearless, she questioned a well-known professor about the event immediately afterward. Her actions made me wish I had been so bold the year before.

As a fellow biology major, I was lucky enough to have Eve in one of my classes, Ecology and Population Genetics (Biol 54 at the time and some other number now). Ever the engaged student, Eve asked numerous intelligent questions throughout the course. While her attentiveness to detail and willingness to challenge ideas impressed me, it clearly annoyed my professor (who I shall not name out of professional courtesy) who behaved increasingly disdainful and rude toward Eve during the course of the class. One day I remember particularly well: I was in the restroom after class and heard a girl walk in talking on her cell phone. I recognized Eve's voice immediately. I could tell she was practically in tears and no wonder given how exceptionally rude the professor had been that day. How could he have been so blind to what I could clearly see in her? That this was a young woman who would excel in everything she attempted, that she was a gem among rocks who would shine in just a short amount of time. I hated the professor for the rest of the year and have thought back on those days with lingering ire, especially since I watched how far Eve rose in the following years.

My active involvement with Hunger Lunch, now Nourish International, had diminished by the time Eve rose to prominence within that group, so I cannot comment on her accomplishments firsthand, but know that she certainly invigorated the group with an enthusiasm that she brought to everything she did.

The last conversation I had with Eve occurred my senior year during an event in which a writer and producer from the show "The Office" was giving a talk to students. The room was crowded but I managed to get a nice seat up front. Eve was in the middle of a run for Student Body President at the time which made her a very recognizable face to everyone and a major draw of attention. Just my luck, she sat down in the open seat next to me. I congratulated her on her successes to that point and thought that, poor girl, she can barely enjoy herself without dozens of people watching her every move. I asked about summer plans and the usual chit-chat given the semester was almost over. I also, to my regret, asked her what separated her from the other candidates. She had been making her case for weeks so why did I have to hear it personally? Maybe because I wanted to listen to her again, almost three years later, and see if the diamond I found before still sparkled. Maybe I wanted her to sound good for any eavesdroppers. Maybe I should have been nicer, more considerate, and treat her like a normal person instead of a candidate.

But Eve was not just another normal person: she was extraordinary in ways that cause paradigm shifts, in ways that restore one's faith in humanity, in ways that make you feel proud to have known her. A friend of mine remarked how incredible it was that her death, though one day surely her life would have too, became a cover story on CNN. How many of us, hubris aside, claim the same? Not that "CNN-making" be one's goal in life (or in death), but it should be one's goal to touch lives, be involved, make a difference, brighten at least one corner of this vast landscape we call the world in some way. To lead, inspire, teach, assist, encourage, sympathize, sacrifice...these are all things each of us can do to make the world around us just a little better, a little less dark.

The warmth and light of an extraordinary human being was cruelly extinguished this week. Eve Marie Carson, my condolences to your family and friends, and to every heart and mind you ever touched. You left an indelible impression on me, and for that I am grateful and honored. Thank you.

The Next Three Weeks

I may post sporadically during the next three weeks. The end of the quarter is all too rapidly approaching and I've got lots on my plate, including:

1) Discussion paper for Fundamentals (March 3)
2) Science Olympiad regional tournament (March 8)
3) 20+ page (dbl space) paper due for Cancer Biology II (March 10)
4) Discussion paper for Fundamentals (March 10)
3) Final exam for Signal Transduction (March 13)
4) Poster presentation for Cancer Biology II (March 17)
5) Final exam for Cancer Biology II (March 17)
6) Final exam for Fundamentals of Molecular Biology (March TBD)

So, yeah, it's going to a rough fortnight and half, but you know what, this is part of what graduate school is all about. At least the bright light at the end of my tunnel is coming home to Mom whom I haven't seen since September 3rd!!! Not to mention it'll be nice to escape the tundra and get some Carolina (a little North and South) sunshine before spring :).

In other news, Megha Bisarya (dear little Megha), will be moving to Chicago in July! Hooray! Also, the WaterPLUS project got 2nd place at a entrepreneurship competition at the University of Washington. Huzzah!

All right, back to work. Cheers!

Oh my it's been a while!!

I am sorry for not posting in what, three months now? How oh how will you, dear readers, ever forgive me for such a travesty? I guess I can win back your love and trust by posting a recap to make up for time lost:

Dec:
1. Took my first finals and finished my first quarter as a UC graduate student. Huzzah! In celebration of my last exam, I wandered around campus for about an hour taking pictures of the snow and ice that covered the ground. You can find those on Facebook.
2. Flew back to NC to spend a wonderful break with my family. It was ~70 degrees when I got off the plane, compared to the 26 degrees I left. Glorious!
3. Anna graduated from CH. Congratulations!!!
4. Visited some friends at CH for a crazy (not really) night out the same day Saket came home from San Fran. I was just tipsy (Greg) and NOT drunk: I have never been "drunk" in my life, and certainly don't plan on becoming so anytime soon!
5. Dad came home from India the day before our birthday. Such goodness!
6. Turned 23 and was treated to a delightful birthday by some dear friends.
7. Discovered the deliciousness of pita chips + hummus.
8. I read a LOT: Quicksilver (Neal Stephenson), Les Miserables (Victor Hugo, the unabridged version), The Amber Spyglass (Philip Pullman), Heretics of Dune (Frank Herbert), Atonement (Ian McEwan), The Omnivore's Dilemma (Michael Pollan)...totally ~4,000 pages of text. Woohoo!
9. Attended "First Night Raleigh" for the first time since living in Cary for almost nine years. Got my picture taken next to a giant acorn (which was later featured on CNN, no less) and listened to an excellent Beatles cover band before watching an amusing though underwhelming improv comedy show.

Jan:
1. Went out to dinner with some friends in med school at CH and others around Cary at La Hacienda in Chapel Hill. What an amazing group of individuals! Shannon lent me some books which I'm slowly but surely working through. Thanks Mahoney!
2. Flew back to Chicago to spend a few days getting used to the Windy City before the start of winter quarter on the 7th.
3. Went to see a "Star Wars" exhibit at the Museum of Science and Industry here in Chicago. I love how that museum is just a twenty minute walk from where I live. I think I posted about the show earlier, but let me tell you, it was spectacular! This is me letting my geek flag fly real high, I know, but I'm just such a "Star Wars" nut. It was delightful to get to see actual props from the movies, including the original Han Solo and Chewie outfits, along with the original C-3PO and R2-D2 costumes. Amazing!! Not to mention the scaled models of the famous ships, from Luke's X-wing to Imperial Star Destroyers. The attendees were mostly middle-aged people with lots of little kids who grew up with the new trilogy instead of the old. I felt like I had more in common with the 40-somethings who actually knew and loved the old movies than the teenagers who looked like they would rather be anywhere else. If they only knew what they were missing! You can see pictures of the exhibit on Facebook.
4. Classes started the next day (Monday). A new quarter, another chance to shine. Bonnie was away in India for a couple weeks in December and flew back to NY on the 1st. She got in late on Tuesday (I think). I had spent a good bit of the weekend cooking (enchiladas, lasagna, stir fry = delicious!) so she didn't have to worry about food for a bit. It was nice catching up on our respective breaks and I was dying to hear about her impressions of India. Sounds like it was a pretty positive trip overall (except for the inevitable bout of illness) and of course wonderful for her to visit her beloved betrothed Jeffrey who's studying in Rajasthan.
5. School's going fine. My cancer biology class is great (molecular mechanisms), my cell bio is all right, though Ursula Storb is a fantastic lecturer, and signal transduction is useful though not terribly exciting.

Feb:
1. Went on a fantastic ski trip with Kevin and his friends at Northwestern. Got to meet some great new people, and discovered another ERS opponent! Enjoyed the best day of skiing I've ever had, despite having not skied since high school...I even took down a black diamond (ok, it was a Wisconsin black diamond, but it still counts in my book). Only fell once, but in line for the BD, not on the slopes: exceptionally embarrassing given the fact that I literally just toppled over without anyone/anything touching me, and that Kev and I had said just seconds before that the folks in this line were the better skiers on the slopes (the line was only for blue square and black diamond). I guess I proved us wrong! Had a great time cooking food and talking with everyone. Thank you so much NU Mat Sci people for such a great time!
2. The Giants won the Super Bowl! I'm sure everyone knows this already, but I was super excited to see them win: not because I'm a huge Giants fan (though my mom is) but more because I could not bear to watch a cheating team win football's biggest prize. I don't hate the Patriots because they win, but because they cheated and tried to hide evidence. As a non-athletic person, I have tremendous respect for athletes and the feats they accomplish in sports. I also have no tolerance for cheaters, which is why Floyd Landis deserved to be stripped of his Tour de France win, which is why Marion Jones deserved to lose all her Olympic medals, which is also why the Patriots should have lost the Super Bowl just inches away from "perfection."
3. School's rolling along as usual. I did find out that I got the highest score in my CanBio class on our midterm. Rather shocking (but obviously immensely gratifying), since that hasn't happened in a science class since I left high school! Maybe I really can be a cancer biology rock star, but only if I redouble my efforts and be excellent in all my classes on all my assignments. Unlike some people, I'm not a natural genius and know that I really have to work extra hard for my successes. Alas, a rougher road but a sweet finish at the end!
4. It's still February now, so I promise to post again before March. Thanks for reading, and cheers!