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Genetic Mosaicism, Lending Club, and Genomics


Kelly Clancy, The New Yorker, The Strangers in your Brain, here. First, reverse cell division across the biosphere then have really smart people figure out the hard stuff like autism, mosaicism, evolution, and consciousness. For starters, assume the DNA is just object code for a C program and the cell division hardware is a printed circuit board by an unnamed manufacturer. Find the source code and the circuit within some error bounds TBD. Make a spec sheet and put it on the internet. Extra Credit: write bgdb ( biosphere gdb) and bspice (biosphere spice).

Each of us is the product of trillions of successful divisions, and so our cells are remarkably good at silencing transposons. (In humans, the majority of these nomadic genes are known technically as retrotransposons.) Until recently, in fact, they were thought to be dormant in most areas of the body. This turns out to be true almost everywhere but in the brain. Fifteen years ago, the neurobiologist Rusty Gage and his colleagues at the Salk Institute, in La Jolla, California, were studying neurogenesis, the development of adult brain cells from immature stem cells. When they ran a survey of all the genes being expressed in these stem cells, compared with mature neurons, they were puzzled to find that transposons were the most active. Far from being silenced, they were singing.
For some time the finding floated around the lab as a sort of curiosity. It was hard getting anyone to work on the project, Gage told me, because the results were unexpected, even a little disturbing. If transposons were tampering with the DNA of every future neuron, then they were endowing each one with a slightly different genome. Even neurons that budded from the same mother would behave differently. This phenomenon, which is known as genetic mosaicism, doesn’t happen much in other tissues. The cilia that guard our lungs are genetically identical to the blood cells that circulate in our arteries, even though one looks like a sea anemone and the other looks like a cough drop. The two appear different only because they express various genes differently, in developmentally predetermined ways. Although neurons are similarly programmed, the Salk study suggested that transposons were giving them the ability to ad-lib. Several years after the initial discovery, members of Gage’s lab sequenced hundreds of individual neurons from human cadavers and found this to be true. Cells in the same brain are, indeed, genetically distinct from one another.

Matt Levine, Bloomberg, Lending Club Can Be a Better Bank Than the Banks, here. Nice place for NIMo.

If Lending Club was a bank, it would look like a pretty risky bank!

But of course it’s not a bank. There are a lot of ways in which it is not a bank, but the big one is that basically all (95.6 percent) of its liabilities are “notes and certificates,” that is, just unsecured structured notes tied directly to specific underlying loans. Banks, on the other hand, are funded mostly by deposits and repo and other short-term senior borrowing. So:

Lending Club’s assets and liabilities are perfectly matched in duration: Those notes and certificates mature when the corresponding loans mature. A bank, on the other hand, is in the business of borrowing short to lend long.
Lending Club’s assets and liabilities are perfectly matched in loss bearing: Every dollar that a borrower doesn’t pay back to Lending Club is a dollar that Lending Club doesn’t pay back to note holders. The note holders know going in that they bear the entire risk of loss on the underlying loans. A bank depositor expects to get her money back even if the bank makes some bad mortgage loans.

Anna Azvolinsky, Princeton Alumni Weekly, Biology: Mapping the Body, here. Olga (from dobbo’s Dillon bball game) is mapping genomic experiments. They are going to track experiments that reverse the PDP 10 and figure out supersonic flow simulation simultaneously.

But not all tissues are accessible, and many can’t be manipulated well in the laboratory. To fill in these knowledge gaps, the lab of computer science professor Olga Troyanskaya recently achieved an extraordinary feat — compiling 38,000 sets of genomic experiments done by others to create a tool that shows how the genes in 144 human tissues work. Putting together and analyzing this amount of information is a huge step forward — no one has been able to create such maps before.

Making sense of large computer-generated datasets is Troyanskaya’s bread and butter. Her laboratory, part of the Lewis-Sigler Institute for Integrative Genomics, uses statistical and computational analyses to manipulate vast amounts of information generated by biologists. Her latest work is an example of an innovative and ever more computationally sophisticated way to make the most of the data. The sheer amount of data from both healthy and diseased samples that Troyanskaya studied allowed the team to deduce the gene maps for several difficult to study but important tissues.


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