forgive my indulgence but 2020's been a big year for @shmuplations, so here's a look back at everything that went up over the last twelve months—there's a lot of stuff I'm sure you all read & other things you'd be forgiven for missing, so let's recap (thread)
https://t.co/orlgPTDsKK
https://t.co/QnQl8KI9IX
More from Software
Developer productivity, y'all. It is a three TRILLION dollar opportunity, per the stripe report.
Eng managers and directors, we have got to stop asking for "more headcount" and start treating this like the systems problem that it is. https://t.co/XJ0CkFdgiO
If you are getting barely more than 50% productivity out of your very expensive engineers, I can pretty much guarantee you cannot hire your way out of this resourcing issue. 😐
(the stripe report is here:
Say you've got a strategic initiative that 3 engineers to build and support it. Well, they're going to be swimming in the same muddy pipeline as everyone else at ~50%, so you're actually gotta source, hire and train 6, er make that 7 (gonna need another manager too now)...
...which actually understates the problem, because each person you add also adds friction and overhead to the system. Communication, coordination all get harder and processes get more complex and elaborate, etc.
So we could hire 7 people, or we could patch up our sociotechnical system to lose say only 25% productivity to tech debt, instead of 42%? 🤔
By my calculations, that would reclaim 3 engineers worth of capacity given a team of just 17-18 people.
Eng managers and directors, we have got to stop asking for "more headcount" and start treating this like the systems problem that it is. https://t.co/XJ0CkFdgiO
When people often have to spend weeks just to get a local development environment up, there is a lot to improve. \U0001f641
— Daniel Schildt (@autiomaa) December 20, 2020
If you are getting barely more than 50% productivity out of your very expensive engineers, I can pretty much guarantee you cannot hire your way out of this resourcing issue. 😐
(the stripe report is here:
Say you've got a strategic initiative that 3 engineers to build and support it. Well, they're going to be swimming in the same muddy pipeline as everyone else at ~50%, so you're actually gotta source, hire and train 6, er make that 7 (gonna need another manager too now)...
...which actually understates the problem, because each person you add also adds friction and overhead to the system. Communication, coordination all get harder and processes get more complex and elaborate, etc.
So we could hire 7 people, or we could patch up our sociotechnical system to lose say only 25% productivity to tech debt, instead of 42%? 🤔
By my calculations, that would reclaim 3 engineers worth of capacity given a team of just 17-18 people.
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Keep dwelling on this:
Further Examination of the Motif near PRRA Reveals Close Structural Similarity to the SEB Superantigen as well as Sequence Similarities to Neurotoxins and a Viral SAg.
The insertion PRRA together with 7 sequentially preceding residues & succeeding R685 (conserved in β-CoVs) form a motif, Y674QTQTNSPRRAR685, homologous to those of neurotoxins from Ophiophagus (cobra) and Bungarus genera, as well as neurotoxin-like regions from three RABV strains
(20) (Fig. 2D). We further noticed that the same segment bears close similarity to the HIV-1 glycoprotein gp120 SAg motif F164 to V174.
https://t.co/EwwJOSa8RK
In (B), the segment S680PPRAR685 including the PRRA insert and highly conserved cleavage site *R685* is shown in van der Waals representation (black labels) and nearby CDR residues of the TCRVβ domain are labeled in blue/white
https://t.co/BsY8BAIzDa
Sequence Identity %
https://t.co/BsY8BAIzDa
Y674 - QTQTNSPRRA - R685
Similar to neurotoxins from Ophiophagus (cobra) & Bungarus genera & neurotoxin-like regions from three RABV strains
T678 - NSPRRA- R685
Superantigenic core, consistently aligned against bacterial or viral SAgs
Further Examination of the Motif near PRRA Reveals Close Structural Similarity to the SEB Superantigen as well as Sequence Similarities to Neurotoxins and a Viral SAg.
The insertion PRRA together with 7 sequentially preceding residues & succeeding R685 (conserved in β-CoVs) form a motif, Y674QTQTNSPRRAR685, homologous to those of neurotoxins from Ophiophagus (cobra) and Bungarus genera, as well as neurotoxin-like regions from three RABV strains
(20) (Fig. 2D). We further noticed that the same segment bears close similarity to the HIV-1 glycoprotein gp120 SAg motif F164 to V174.
https://t.co/EwwJOSa8RK
In (B), the segment S680PPRAR685 including the PRRA insert and highly conserved cleavage site *R685* is shown in van der Waals representation (black labels) and nearby CDR residues of the TCRVβ domain are labeled in blue/white
https://t.co/BsY8BAIzDa
Sequence Identity %
https://t.co/BsY8BAIzDa
Y674 - QTQTNSPRRA - R685
Similar to neurotoxins from Ophiophagus (cobra) & Bungarus genera & neurotoxin-like regions from three RABV strains
T678 - NSPRRA- R685
Superantigenic core, consistently aligned against bacterial or viral SAgs
@EricTopol @NBA @StephenKissler @yhgrad B.1.1.7 reveals clearly that SARS-CoV-2 is reverting to its original pre-outbreak condition, i.e. adapted to transgenic hACE2 mice (either Baric's BALB/c ones or others used at WIV labs during chimeric bat coronavirus experiments aimed at developing a pan betacoronavirus vaccine)
@NBA @StephenKissler @yhgrad 1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
@NBA @StephenKissler @yhgrad 2. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2
@NBA @StephenKissler @yhgrad B.1.1.7 has an unusually large number of genetic changes, ... found to date in mouse-adapted SARS-CoV2 and is also seen in ferret infections.
https://t.co/9Z4oJmkcKj
@NBA @StephenKissler @yhgrad We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the ... Thus, this mouse-adapted strain and associated challenge model should be ... (B) SARS-CoV-2 genomic RNA loads in mouse lung homogenates at P0 to P6.
https://t.co/I90OOCJg7o
@NBA @StephenKissler @yhgrad 1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
1. From Day 1, SARS-COV-2 was very well adapted to humans .....and transgenic hACE2 Mice
— Billy Bostickson \U0001f3f4\U0001f441&\U0001f441 \U0001f193 (@BillyBostickson) January 30, 2021
"we generated a mouse model expressing hACE2 by using CRISPR/Cas9 knockin technology. In comparison with wild-type C57BL/6 mice, both young & aged hACE2 mice sustained high viral loads... pic.twitter.com/j94XtSkscj
@NBA @StephenKissler @yhgrad 2. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2
1. High Probability of serial passaging in Transgenic Mice expressing hACE2 in genesis of SARS-COV-2!
— Billy Bostickson \U0001f3f4\U0001f441&\U0001f441 \U0001f193 (@BillyBostickson) January 2, 2021
2 papers:
Human\u2013viral molecular mimicryhttps://t.co/irfH0Zgrve
Molecular Mimicryhttps://t.co/yLQoUtfS6s https://t.co/lsCv2iMEQz
@NBA @StephenKissler @yhgrad B.1.1.7 has an unusually large number of genetic changes, ... found to date in mouse-adapted SARS-CoV2 and is also seen in ferret infections.
https://t.co/9Z4oJmkcKj
@NBA @StephenKissler @yhgrad We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the ... Thus, this mouse-adapted strain and associated challenge model should be ... (B) SARS-CoV-2 genomic RNA loads in mouse lung homogenates at P0 to P6.
https://t.co/I90OOCJg7o