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Archive for December 2010

eat me protein

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Cancer patients the world over take heart. We  may be on the cusp of a seminal breakthrough in cancer research and treatment. A few days ago, researchers from Stanford University reported that they have discovered a protein in abundance, on the surface of cancer cells. What is remarkable about this protein (calreticulin) is that it signals the immune system to engulf them and destroy them (hence the name “eat me” cells). But cancer cells also have a second molecule, CD47, which signals “don’t eat me”. Macrophages do not destroy cancer cells because CD47 counteracts Calreticulin.

In normal cells, Calreticulin is expressed when the cell is damaged, thus allowing the macrophages  to clean them up.

The same researchers found in a previous study that CD47 antibodies were very effective in curing leukemia and other cancers induced in mice, without affecting normal cells (ie., no side effects)!!

The thinking here is that by blocking the CD47, the eat me signal is stronger in the cancer cells, allowing the macrophages to clean up.

Key developments in cell biology related to this research can be found in this article

Apopstosis:eating sensibly

 

 

 

 

 

 

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Written by asterix98

December 27, 2010 at 11:15 pm

Posted in cancer, Oncology

Book List

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I found these references in a WSJ article on cultural classics that teach us important life lessons( I picked two topics of interest to me but the article itself has more).

How to face death

Consolation in the face of death – Samuel Johnson

My last sigh – Luis Bunuel

The year of magical thinking – Joan Didion

How to fill  the God-shaped hole

Dialogues concerning natural religion – David Hume

If I get to read them I will update this post with some reviews.

I also came across a couple of other interesting forums

Onbeing.org – also a weekly show on public radio which deals with issues of  “faith and moral imagination”.

the stone –  a blog on NYtimes.com where contemporary thinkers from various disciplines write about philosophical issues.

This next one should be a fun read

Sleights of mind: What the Neuroscience of magic reveals about Our Everyday Descriptions  – Sptephen L Macknick, Susana Martinez- Conde and Sandra Blakeslee

Written by asterix98

December 26, 2010 at 6:30 am

Anniversary

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December 15th will always be a day of intensely mixed emotions.

Intense joy because 11 years ago Lechi and I officially became man and wife. Intense sadness because we learned on this day (exactly a year ago) that we had exhausted all conventional treatments for Lechi’s malady. Lechi’s own emotions surrounding both of these events are captured vividly on film for posterity.

I used to joke with Lechi that our wedding was the last great event of the millenium. I tried to cheer her up with this same joke, last anniversary, but there was much on her mind. (It is ironic that of all the days available in a year, Lechi had her second surgery on Mahati’s 5th birthday and this piece of news on our anniversary. Go figure!)

I remembered her a lot this morning on the way to work and choked up.I wanted to thank her for the time spent together (I also wondered if it really mattered now.) I learned so much from our journey together. We take so much for granted, focus on the wrong things, get caught up in keeping up with the Jones’es, keep up pretenses, and frankly, indulge in extremely petty minded behavior. It takes enormous mental discipline to continually monitor the above and clean up your act. I have some ways to go in some of these areas. I will get there.

Sometimes there is confusion on how best to honor and remember Lechini. Is moving on a sign of disrespect? A case of “out of sight, out of mind”? At times there is guilt in the enjoyment of everyday things. I am told these are natural feelings for someone who has lost a spouse, a partner, a friend.

And of course, there is Mahati. The poor darling is going through an intense range of emotions, at times, that she is not able to articulate very well. It has been a challenge as I am trying to figure out how to help her cope with it and fill the void, the best I can. She has come a long way but a longer road remains. The loss of a nurturer and protector looms large (it is abundantly clear why nature made moms the way they are).

Nevertheless, the cards have been dealt. We have to make a game of it. I take immense comfort in the fact that Lechi made it a point on a couple of occasions, in her final days, to communicate that I had made a difference in her life. To me that is worth everything and will always be.

Agony and Ecstasy. December 15th. Happy Anniversary Lechi!

Written by asterix98

December 16, 2010 at 8:21 am

global baby

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We do live in interesting times.

This weekend I read an article in the Wall Street Journal on “global babies”. Apparently, couples  (infertile, gay) around the globe, who want to have kids, turn to outfits like PlanetHospital(PH). PH has an international network of surrogates, egg and sperm donors. They offer “packages” to families – “India bundle” being a low cost option. This international market is a lower cost alternative to US surrogates ($200K per baby) vs. $32k to $68K in other nations. What is even more interesting is the value-added option : being able to determine the sex of the baby upfront. PH has been offering these services since 2002!

To me, this article was interesting, because it is so far out compared to traditional baby making models. Outsourcing gone extreme!  It is even classified as, I think, the reproduction industry (nascent) and there is demand for this sort of product, made by baby making machines (in most cases to support the future of their own babies).

It also reminded me of the insurance industry, which profits from the terminally ill, by buying up their life insurance, in return for immediate gratification (the insured is paid some portion of their policy). In a way, this is a win-win situation for both parties, but the “blech” feeling seems to be anchored around the idea of profiting from death (funeral homes are another example of selling “packages” for the send off).  Should we marvel at the endless creativity of human beings or worry about this anything goes trend?

In all this, I forgot to mention, where there is money to be made, enter the bad guys. Somebody told me there are kidnappings, etc., to harvest sperms from good looking women, sometimes even ending in death for these women. Oh well, I digress….

 

Written by asterix98

December 14, 2010 at 3:26 am

Emperor of all maladies

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Book Review : The Emperor of all Maladies

To use a contemporary metaphor, Cancer is the Voldemort of diseases, what with it vast array of Horcruxes and Death Eaters. Mukherjee’s narrative is lyrical, the language exquisite (here is a sample sentence from the book “..The gibbet and the graveyard – the convenience stores for the medieval anatomist-… “.) What an image! It is also a tale of innovation, creativity, serendipity, passion, and motivation on the part of a few key individuals driven to make a difference, where breaking the rules to advance the status quo is the norm.

Most of you know I lost my wife to this dreaded disease. I had been looking for such a book since her diagnosis and could’nt find one. I wish we had it then. Nevertheless, as Mukherjee traces the history, it is heartening to note that the fight to conquer this disease has made slow but steady progress. I hope, as many of you out there, as possible, can read this tour de force of science writing.

Much awareness raising is required for the more lethal forms (pancreatic cancer and metastatic melanoma, to name a couple). I hope after reading this book you are spurred into action to support the Harry Potter oncologists of the world in their fight to rid the earth of this dreadful malady.

This book is a keeper.Buy it, gift it, spread the word.

Written by asterix98

December 8, 2010 at 7:20 am

Google and the brain

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Google’s page ranking algorithm solves two fundamental issues in search: how to represent the universe of web pages to yield meaningful search results, and equally important, how to rapidly retrieve this information in response to a query.

Google achieves the first by assigning a number (importance) to each page based on the number of incoming and outgoing links. Each of these incoming and outgoing links are assigned “weights”. However, this number is also modulated by the salience of the linking pages.  The importance of each page can then be represented as a simple summation of all pages linking to it (including itself). Each summation term is the product of the link weights and the importance of each page.

A column vector, constituting the universe of all web pages, can be now be derived, as the product of a giant NxN matrix, representing the weights of all links to every page, and the column vector itself. This giant matrix, then captures, all of the relationships, amongst the universe of web pages.

In the general case, the above discussion has to be expanded to a multi-dimensional space. Rapid retrieval, in this high dimensional space, requires other mathematical techniques such as finding a projection that will reduce the dimensionality of this space while still retaining the interrelationships. This is important to retain accuracy in the retrieved results.

A key idea embedded in this formulation is that representation and retrieval are not separate mechanisms but fundamentally intertwined processes that have much in common.

For mathematical convenience, as well as to handle corner cases, there are numerous modifications to this fundamental formulation. But they are not completely germane to the current discussion so we can ignore them for now.

It turns out that evolution needed to solve the same fundamental issues – representation and retrieval- to facilitate the rich panoply of cognitive processes evident in our brain. If we recast this as a search problem, the mathematics behind Google’s page ranking algorithm, seems to offer a simple and elegant solution to the problem.  

In brain science, numerous theories have been put forth, addressing these issues, but fall short mechanistically.  We can think of the universe of neurons akin to the universe of web pages. Neurons have incoming and outgoing links (remarkably dense).  Importance of each neuron then is a function of its “tuning/content” (things it responds to in the environment) and “context” (incoming/outgoing links). The “search terms” are derived from the statistics of the impinging stimuli (which has the benefit of gravitating towards solutions that naturally preserve salient features thereby reducing dimensional complexity). A second mechanism, for reducing the dimensionality of the external environment, can potentially be achieved through a divide and conquer strategy. In other words, the brain uses modularity.  Pruning (strengthening/weakening) of links is accomplished by mechanisms such as Hebbian learning/temporal synchrony/ correlated firing. Such a distributed representation, also allows for graceful degradation, in case of damage to portions of the neural machinery. Simply put, our brain is a giant matrix!!

Written by asterix98

December 8, 2010 at 7:03 am

Posted in Brain, google

Resilience

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Today I thought of Lechi a lot. I am not sure what triggered it.

It may have been the blanket I still have on my passenger seat in the car. This blanket (incidentally from Stanford Hospital) was in use to make the bucket seat level so that she could slide into position on a level surface instead of having to scoot over the elevated perimeter of the seat.

It brought back a flood of memories around how excruciatingly painful, ordinary (to most of us) movements, became for Lechi. Getting down the stairs, the “short walk” to the car, and then getting into the car. This sequence of movements were greatly exaggerated in time, required minute maneuvers, and great effort to get into position for each activity.

Our frequent hospital visits (a short ride by most measures) were pretty dreadful as it seemed like every small pebble, crevice, and undulation on the road surface, came alive and caused unbearable shooting pain in her lower back. There were days,when I had the hazards on, and drove slowly on busy streets.

(Incidentally, there is a side story here about reactions of the general public viewing us as a nuisance on the street. It is a sad commentary on how self-absorbed and impatient our society has become. )

It may also have been because I heard about the passing of Elizabeth Edwards, also of cancer, (wife of John Edwards – this dickhead was having an affair when his wife was terminally ill. I wonder if such people are evolutionary anomalies.) on NPR. She wrote a book called “Resilience”. When I look back, Lechi was the embodiment of this spirit. One way she demonstrated this by her resolve to brave the pain associated with the commute to UCSF, walker, or wheelchair notwithstanding (I can’t quite convey how extraordinary this is having witnessed every moment of it). I can cite so many other examples. Lechi was grace personfied even under enormous distress.

No matter how I think about it, it just feels wrong that Lechi had to suffer this much. All of us wellwishers could not do much more than be helpless bystanders. It reminds me of a tale in the Bhagavatam, where an elephant, inspite of being surrounded by his herd, suffers alone, when trapped in the jaws of a crocodile.

Written by asterix98

December 8, 2010 at 6:52 am

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