BC SCIENCE
Saved by @Alex1Powell

With @franklowery our new study on attributes of T cells that contribute to successful cell therapy in cancer patients in @ScienceMagazine today w/ colleagues @slgoff_SB, @NCI_CCR_SB @theNCI a TL;DR thread on key findings with caveats :) 1/10

 @NCI_CCR_SB has a long history of using tumor infiltrating T cells (TILs) to treat cancers since well.. before I was even born. We analyzed our most successful melanoma ACT trial for cell surface phenotypes in TIL infusion products of patients (aPD1/immunotherapy naive) /2
Surprisingly we found a CD39- TIL subset (CD39-CD69-, DN) associated with ACT-response. TBH we were expecting the opposite (CD39+). We only included CD39 bcz multiple groups (e.g. Simoni et al, 2018) had reported CD39+ as enriching for anti-tumor/neoantigen reactive T cells. /3
CD39- DN TILs RNA/epigenetics resemble stem-like memory progenitors, and in vitro were able to self-renew, and give rise to other CD39+ subsets. OTOH the most dominant subset of patient infusion products were CD39+ CD69+ (DP) and these guys were terminally differentiated.. /4
So, to clarify we specifically analyzed tumor-specific mutation-reactive Tcells. Turns out, ACT-responders had pool of neoantigen-reactive TILs in the CD39- phenotype, while non-responders did not (despite other irrelevant CD39- Tcells) -> not all CD39- T cells are bystanders /5
But previous studies aren’t wrong! Even in responders, we find most neoantigen-reactive TILs are CD39+CD69+ (DP). So, we find the same and agree: CD39 does enrich for mutation reactivity. The nuance is those T cells don’t seem to contribute to response at least in this cohort. /6
In this subgroup, we found no differences btwn resp. vs nonresp. in total # of neoag-specific TILs infused or CD39+ neoag TILs infused. By single cell tracking of mutation-reactive TCRs in patient blood, we found DN TCRs tended to persist longer than DP (they crash faster!). /7
We confirmed this in NYESO-TCR responder by tracking TCR clones over 5yrs! and in Pmel mouse model. In sum: we think stem-like T cells causing ACT response are different from TIL subsets enriched with tumor-reactivity. Recent ICB studies suggest this too (e.g. Kurtulus et al) /8
Caveats: Unsure if neog stem-like Tcells true in other tumor, immuno/cell therapy. We study TIL infusions -> probly diffnt from ex vivo TIL. We can’t comment on PRs/SDs (excluded). In 3 CRs, TIL-infusion was exclusively CD39+DP term diff. Tcells: so.. what’s happening there..? /9
These and many more questions to answer. This is the first in hopefully a series of studies we @NCI_CCR_SB have ongoing with respect to TIL phenotypes, so stay tuned :/ Finally, big thanks to my mentors Steve Rosenberg and Paul Robbins. ~fin

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Currently, one of the most economic forms of carbon capture is called "amine-based" capture.

An "amine" is a special liquid chemical which selectively grabs on to CO2 molecules.

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Recently I learned something about DNA that blew my mind, and in this thread, I'll attempt to blow your mind as well. Behold: Chargaff's 2nd Parity Rule for DNA N-Grams.
If you are into cryptography or reverse engineering, you should love this.
Thread:


DNA consists of four different 'bases', A, C, G and T. These bases have specific meaning within our biology. Specifically, within the 'coding part' of a gene, a triplet of bases encodes for an amino acid


Most DNA is stored redundantly, in two connected strands. Wherever there is an A on one strand, you'll find a T on the other one. And similarly for C and G:

T G T C A G T
A C A G T C A

(note how the other strand is upside down - this matters!)


If you take all the DNA of an organism (both strands), you will find equal numbers of A's and T's, as well as equal numbers of C's and G's. This is true by definition.
This is called Chargaff's 1st parity rule.
https://t.co/jD4cMt0PJ0


Strangely enough, this rule also holds per strand! So even if you take away the redundancy, there are 99% equal numbers of A/T and C/G * on each strand *. And we don't really know why.
This is called Chargaff's 2nd parity rule.
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10-K Diver
10-K Diver
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1/

Get a cup of coffee.

In this thread, I'll help you understand the basics of Binomial Thinking.

The future is always uncertain. There are many different ways it can unfold -- some more likely than others. Binomial thinking helps us embrace this view.


2/

The S&P 500 index is at ~3768 today.

Suppose we want to predict where it will be 10 years from now.

Historically, we know that this index has returned ~10% per year.

If we simply extrapolate this, we get an estimate of ~9773 for the index 10 years from now:


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What we just did is called a "point estimate" -- a prediction about the future that's a single number (9773).

But of course, we know the future is uncertain. It's impossible to predict it so precisely.

So, there's a sense of *false precision* in point estimates like this.

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To emphasize the uncertainty inherent in such predictions, a better approach is to predict a *range* of values rather than a single number.

For example, we may say the index will return somewhere in the *range* of 8% to 12% (instead of a fixed 10%) per year.

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10 years from now, this implies an index value in the *range* [8135, 11703]:
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"We have purposely avoided directly confronting the issue of masks because it is such an emotional and political issue. Like waving a red flag in front of a bull, the topic elicits strong emotions which overwhelms

We wear a mask in the hospital and don a N95 mask, gown and gloves when we see a patient known to have COVID-19. Masks are used for source control when patients are admitted with various types of infectious respiratory diseases

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After the visit, we dispense of the gown, gloves and change into our regular surgical mask to continue patient rounds. In public, we wear a cloth mask to comply with executive orders and as a courtesy to others who feel afraid and uncomfortable.
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In truth, we wish masks worked. If they did, it would be a cheap, and easy way to control the spread of Covid.

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The idea that they protect not only their wearer, but also those people around them seems noble. We wished masks worked because citizens are spending billions of dollars on them.

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The last Hindu king of Pakistan.

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They have always maintained friendly relations with the rulers. The Mughal court and the Rana of Amarkot had special respect because Emperor Akbar was born in the shelter of Amarkot Raj. They did not even have to attend court regularly.

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