Disqus - Latest Comments for gsgs

Re: Simple Alpha Zero

gsgs — Sun, 28 Jan 2018 06:48:28 -0000

then maybe minichess on a 5x5 board ... and see, what happens when slowly expanding

the board, so we get an estimate how hard it is for normal chess
no e.p castling underpromote 3fold or 50move rule

Re: TWiV 446: Old sins die hard

gsgs — Tue, 11 Jul 2017 12:44:51 -0000

I do remember that paper and discussion about it in 2014
I think this is still unclear and there are some problems ...

35:30-1:08:15 1918-flu paper from 2014 paper , Worobey,Han,Rambaut

I think this is all very speculative, there are lots of problems with those explanations.

I feel that the 1918 age pattern is still unexplained.

The genealogy people do have lots of data but aren't interested in this.

Did people born just before outbreaks in 1889-1892 do worse in 1918,

than those born shortly after the outbreak ?

Same with seasonal outbreaks before 1889 , were they protective ?

In England (and some other countries) there was (almost) no flu in 1870-1889,

but still the age-pattern in 1918 was the same.

Flu in horses was common at that time and in 1918 the horses had it as well.

An original antigenic sin of similar dramatic effect as in 1918 has not been

demonstrated in the lab, nor did it happen in other outbreaks.

Re: Are viruses alive?

gsgs — Tue, 09 Aug 2016 03:19:21 -0000

and I thougt, the main argument were about evolution history,

the tree of life, the 3 domains

When you require "cells" , you are already somehow using that
evolution-history argument.

However, there are also bacteriophagues

viroids,satellites,prions

Re: Mosquito saliva enhances virus replication and disease

gsgs — Tue, 09 Aug 2016 01:42:48 -0000

let's help the virus in its evolution by making it harmless and reducing
the itching

so people are less motivated to use mosquito nets.
And let it attack those other evil viruses.

I'm waiting for these new smart micro-airplanes that chase mosquitoes ...

Re: Moving beyond metagenomics to find the next pandemic virus

gsgs — Sat, 19 Mar 2016 13:12:59 -0000

for a better understanding see here the 141 pages .pdf summary of the workshop on
"gain of function" on
2014/12/15-16

http://www.ncbi.nlm.nih.gov...

Re: TWiV 363: Eat flu and dyad

gsgs — Tue, 01 Dec 2015 08:35:55 -0000

D222G is the mutation that is believed to be associated with increased
virulence in mexflu, due to better replication in the lungs.
It was also observed in 1918-spainflu and speculated that it was the reason
for the bad 2nd wave ...

------------------edit----------

I found a link to an entry in the virology blog
http://www.virology.ws/2009...

Re: TWiV 351: The dengue code

gsgs — Sun, 29 Nov 2015 14:39:36 -0000

but you might adapt an avian flu to humans (mice first) this way ?!

Re: TWiV 354: The cat in the HAART

gsgs — Wed, 30 Sep 2015 10:07:44 -0000

sort of a poll. "Large majority out of 200". Well, that's what they say but
apparently the opponents

couldn't come up with better - or just other - estimates

http://www.cidrap.umn.edu/n...

Re: TWiV 351: The dengue code

gsgs — Thu, 17 Sep 2015 05:56:30 -0000

searching google-scholar for citations of that Wimmer et.al.
paper on influenza codon-de-optimization :
-----------------------------------------------------------------------------

http://www.nature.com/nrm/j...
[2014] Recent
progress in DNA manipulation and gene circuit engineering has greatly

improved our ability to programme and probe mammalian cell behaviour. These
advances

have led to a new generation of synthetic biology research tools and
potential therapeutic

applications. Programmable DNA-binding domains and RNA regulators are
leading to

unprecedented control of gene expression and elucidation of gene function.
Rebuilding

complex biological circuits such as T cell receptor signalling in isolation
from their

natural context has deepened our understanding of network motifs and
signalling

pathways. Synthetic biology is also leading to innovative therapeutic
interventions

based on cell-based therapies, protein drugs, vaccines and gene
therapies.

-------------------------------------------------------------------------------

http://www.sciencedirect.co...

Genetic design automation: engineering fantasy or scientific renewal?

------------------------------------------------------------------------------------

Large-scale de novo DNA synthesis: technologies and
applications
-------------------------------------------------------------------------------------

http://www.pnas.org/content...

A long-held dogma posits that strong presentation to the immune system of
the dominant

influenza virus glycoprotein antigens neuraminidase (NA) and hemagglutinin
(HA) is

paramount for inducing protective immunity against influenza virus
infection. We have

deliberately violated this dogma ... We conclude that the suppression of
HA and NA

is a unique strategy in live vaccine development.

[cited by 21 at google scholar]

--------------------------------------------------------------------

Efficient manipulations of synonymous mutations for controlling translation
rate:

an analytical approach

------------------------------------------------------------------------

Species-specific codon context rules unveil non-neutrality effects of
synonymous
mutations
--------------------------------------------------------------------------

Many ways to make an influenza virus–review of influenza virus reverse
genetics
methods
-----------------------------------------------------------------------

Slow fitness recovery in a codon-modified viral
genome
--------------------------------------------------------------------

Pandemic influenza A virus codon usage revisited: biases, adaptation and
implications

for vaccine strain development

-----------------------------------------------------------------------

Synthetic genomics and synthetic biology applications between hopes and
concerns
http://www.ncbi.nlm.nih.gov...

-------------------------------------------------------------------

http://jvi.asm.org/content/...

[they have an algorithm to de-optimize, they detect variants that are
likely less optimal.

You can use the same for optimizing. If you know which variants are likely
less

optimal, then you also know which variants are likely more optimal]

----------------------------------------------------------------------------

Codon usage in vertebrates is associated with a low risk of acquiring
nonsense
mutations
---------------------------------------------------------------

Synthetic genomics: from synthesis of prokaryotic genomes to synthesis of a
fully

functional eukaryotic chromosome

... It also raises concerns about the risks of its use in bioterrorism.
...

-----------------------------------------------------------

Event report: SynBio Workshop (Paris 2012)–Risk assessment challenges of
Synthetic
Biology
-------------------------------------------------------------

live attenuated influenza vaccine (LAIV)
mimics natural virus
infection, which consequently has risks and benefits [37]

--------------------------------------------------------------------------------

http://jvi.asm.org/content/...

[Aug.2015] converting its codon usage ... to avian ... gave a new H1N1
attenuated

in humans but not in eggs

[as well you could start with an avian flu virus and convert its codon
usuage to human.

[[There you have your possible Frankenvirus]

use reassortments and assaging to improve the process. Make a statistics,
figure out

which start-viruses lead to most virulent end-results. Find the
patterns]]

[[[ loss of function research can be abused for gain-of-function ]]]

------------------------------------------------------------------------------

Large-Scale Nucleotide Optimization of Simian Immunodeficiency Virus
Reduces Its

Capacity To Stimulate Type I Interferon In Vitro

------------------------------------------------------------------------------

Re: TWiV 354: The cat in the HAART

gsgs — Thu, 17 Sep 2015 05:53:13 -0000

thanks for replying here. I think open internet discussion

is more productive than the typical debating in conferences

or writing papers or articles. You can rethink,edit,

correct,add links and there is direct feedback and discussion.

I'm missing this in the important GOF-debate, the

main "players" (Osterholm-term) won't do this.

profvrr wrote:

> How do you know that these methods can be used to

> create 'worse' viruses?

> Worse for whom? Where is the evidence? There is none -

> it is all threatening, apocalyptic scenarios created

> by the anti-GOF crowd which can only think of fear.

--------------------------------------------------------------------------------

## I "know" -- it seems likely from what we know. (There is

much evidence, I'd bet, that most experts would agree )

## "Worse" -- more virulent, more transmissable in humans.

Greater pandemic risk,

## Worse for -- mankind, global health, global economy.

## evidence --

We know, that these pandemic flu viruses are out there

in the giant search space of 13000^4 combinations and

are found by nature every ~40 years with an evolutionary

algorithm of point mutation and reassortment,

purely step by step, one at a time.

We know, there are better algorithms for such "problems"

and computers are more powerful than nature for that.

We also know that (many) viruses can be assembled from

just knowing the sequences.

This is becoming ever cheaper and easier.

And we know, that lab-reassortment and passaging can

often create more transmissable better host adapted

and sometime more virulent viruses in the lab,

starting from some other (artificial) virus.

Luckily probably we didn't yet get pandemic-capable

viruses from that. (so far)

Worse viruses have been created by these methods,

viruses that are being generally (including you, afair)

considered more dangerous than the original,

unmanipulated ones and require higher safety levels.

There is evidence that they are more dangerous,

although they didn't yet create a pandemic.

There are legal hurdles to fully create these,

so we don't really know what is currently possible.

There could also be some fundamental problems,

which however I don't see and which have not

been outlined yet. There is "no evidence" for

fundamental problems using your language.

------------------------------

## apocalyptic scenarios creaed by the anti-GOF crowd --

I remember how the apocalyptic scenarios were

"created" in 2005f by the "H5N1 crowd"

(WHO,UNO,CDC,Webster,Osterhaus,etc.)

The "GOF-crowd" then just applied it to lab-viruses.

I think that without the H5N1 crowd there may not have

bee an anti-GOF crowd. (too small for a crowd)

======================================

But for a reasonable risk estimate it doesn't matter

so much which crowd thinks what and how they spread it,

what media and headlines they use.

I'm not happy with the GOF-crowd either, FVR etc.

Both sides in the controversy are party agenda-driven,

they have professional interests un the decision.

How safe current American labs are, what happened

in 1977 or whether GOF-research is useful, that's

not the main point, IMO.

The main point is estimating the risk created by

current technological non-GOF advances.

---------------------

## GOF-crowd --

By calling them "crowd", you presumably want to

compare them with the (uninformed) "anti-vaccine

crowd" (another term used by TWiV) or the

"climate-change-denier-crowd" or such.

But it doesn't work. There are many reknowned and

accepted scientists, nobel-laureates and such,

in the crowd and indeed most non-flu experts are

reportedly against those GOF-experiments.

Re: TWiV 351: The dengue code

gsgs — Tue, 15 Sep 2015 14:08:01 -0000

As for the codon-bias, I remember that Wimmer also used codon
de-optimization for
flu (PR8,1934), see TWiV236,10:00-26:20.
I first saw
it in a 2006-paper by Rabadan (Columbia,who was also in TWiV, afair) who
showed
that Avian and Human flu can be distinguished by their Nucleotide-bias
:
human ones have more A,T which was astonishing to me at that time.

Wimmer et.al. use this for de-optimization and vaccine, but it is clear
that the same could
be used for optimization. TWiV didn't mention this ...

It will probably be more difficult to optimize than to deoptimize, but
eventually they might
get the patterns and use computers to effectively
optimize viruses.
Similar to what was done with reassortment until it was
"stopped".

23:00

I couldn't find the letter on TWiV 353 which led to discussion of the
mechanism

BTW., I get this error here:
https://wordpress.org/suppo...

Re: TWiV 351: The dengue code

gsgs — Tue, 15 Sep 2015 12:53:39 -0000

24:00 table 2 irrelevant to the argument. Even if it were true that some
group used

publication "tricks" (or bad newspaper headlines, Vincent's favourite) to
get more attention,

that doesn't tell us anything about the correct,reasonable judgement of the
issue.

24:50 Frankenstein does not apply. This is not a public (artificial fear)
debate,

but rather an experts discussion.

25:55 lots of laughter (I didn't understand, somehow about the origin of
science-fear)

27:00 Pittsburg center = origin of (evil) GOF-critics

[ if they become right, TWiV will enter history as the center of
GOF-dangers ignorism ?! ]

[ attacking the arguers, not the argument ]

27:30

1977 is no longer an argument ?

Why would a vaccine trial that went wrong be _any_ better

than a lab escape wrt. that science-distrust - Frankenstein theme

or the other examples that gave you so much laughter ?

There was a danger that the scientists didn't consider enough

in their research. It can't happen again, because now we know

about that danger and such trials won't be done ? (in humans)

What's the logic ?

Besides that, I think the paper does bad science.

When you consider all the segments, not just HA, then it's clear

that the common ancester is in summer or fall 1976.

And the 4-places virus became extinct while the Hongkong virus

did spread worldwide. They also don't mention the earthquake

and the political trouble in 1976. Looks agenda-driven to me.

Re: TWiV 354: The cat in the HAART

gsgs — Tue, 15 Sep 2015 11:20:22 -0000

(I remember Kawaoka on TWiV saying he didn't understand why people still
were

opposed after he had exlained why the research was useful. I didn't
understand that.)

45:50

As I understand it, the GOF-argument is, that those methods may also be
used by

evildoers to create more dangerous flu-viruses. While those people (Kawaoka
and earlier

also Wimmer's de-optimization) are doing this for vaccine production, it is
clear that

these methods can also be used to create worse viruses. Evildoers may learn
from it

"mechanistically", as Vincent would say.

Could they do the research while keeping the results secret ?

Apparently not, the system is not designed for that research.

Maybe the military could do that. You must control and lock up these
researchers

And let me say, that the TWiV team is traditionally biased here.

It's a controversial discussion and most non-flu scientists are against it
and that's

why we have the moratorium. So, how likely is it that all TWiVers are soo
clearly

on one and the same side here ? I'm not sure how it started, maybe the
"nasty"

Osterholm discussion, maybe because Palese benefits from GOF-research,

maybe because they are too concerned about the science,research,teaching

community and their funding and too less concerned about the general
public.

It goes more and more into riduculing than debating.

I call it agenda-driven science as opposed to curiosity-driven
science.

You would pick only the evidence that supports you agenda while
ignoring

the contras. You won't acknowledge and accept any argument of the
other

side and do some weighting of pros and cons.

In my opinion the lab escapes from official lab is not the main argument,

but the danger that others will secretly do the research in less safe
labs

illegally or in countries with laxer regulation.

Re: Your viral past

gsgs — Sun, 07 Jun 2015 05:12:22 -0000

> Now you can find out with just a drop of your blood and about
$25.

not really.

>> The test is currently used as a research tool and is not
commercially available.

Re: A new cell receptor for rhinovirus

gsgs — Sun, 03 May 2015 01:51:34 -0000

cadherin = kathrin or katrin ?
I remember, one of the methods how influenza enters was
by katrin mediated metapinocytosis (or such, afair)
..................................
googling ...
clathrin mediated endocytosis (CME)
Filamentous Influenza Virus Enters Cells via Macropinocytosis
Influenza virus has been described to enter host cells via clathrin-mediated
endocytosis
Influenza Virus Can Enter and Infect Cells in the Absence of Clathrin ...
...............................................
http://en.wikipedia.org/wik... (cadherin = calcium-dependent adhesion)
http://en.wikipedia.org/wik... (clathrin = like a lattice)

Re: Big-Data Project on 1918 Flu Reflects Key Role of Humanists

gsgs — Wed, 25 Mar 2015 08:24:02 -0000

what I think what should (and could) be done :
get the death-certificates from Oct.-Dec. 1918 and type the exact birthdates
into the computer ! Cooperate with the genealogy people, to collect the data.
Then we might conclude, whether birth before a seasonal wave in the 1880s
protected better in 1918 than birth after the wave was over.

Re: Big-Data Project on 1918 Flu Reflects Key Role of Humanists

gsgs — Wed, 25 Mar 2015 08:03:44 -0000

Copeland's role, is it important ??
When I saw "big data", I was hoping for death certifates scanning etc.
to resolve the mystery of the unusual age-distribution in 1918.
If it was indeed immunity from a similar virus before 1890, as most
experts think, then we were just lucky in 1918 and the same
may happen again, but with the same death rate in people >40y ! ...

Re: Hat der Westen nach dem Mauerfall Russlands Interessen zu wenig berücksichtigt?

gsgs — Sun, 09 Nov 2014 08:42:52 -0000

seit wann vertritt Gorbachev (oeffentlich) diese Auffassungen ?
Er hat doch Buecher geschrieben (die ich allerdings nicht gelesen habe -
jemand hier ?) etc., ich hab's noch nicht vorher gehoert

Re: The Wild Types

gsgs — Thu, 30 Oct 2014 15:27:39 -0000

evil viruses
the kooaint that make you sickk

Re: TWiV 307: Ebola aetiology

gsgs — Mon, 20 Oct 2014 03:56:52 -0000

why do people write letters and emails instead of discussing here directly ?

Re: TWiV 307: Ebola aetiology

gsgs — Mon, 20 Oct 2014 03:50:01 -0000

I couldn't understand Tara Smith so well.
Vincent's voice is best for me to understand
(as a German)

Re: TWiV 307: Ebola aetiology

gsgs — Mon, 20 Oct 2014 02:10:58 -0000

they are still checking the contacts (almost) each day for 21 days,
as can be seen in the (almost) daily situation reports:

Sierra Leone: http://health.gov.sl/?page_...
Liberia: http://www.mohsw.gov.lr/con...

total contacts currently being followed in Sierra Leone: 10205
contacts seen and healthy in the last 24h in Sierra Leone: 9946
contacts seen and ill in the last 24h in Sierra Leone: 32
contacts currently under follow-up in Liberia: 7052
contacts seen on Oct.13 in Liberia: 6750
5.6 contacts per suspected case in average in Sierra Leone
3.9 contacts per suspected case in average in Liberia

Re: New Yorkers like their science from scientists

gsgs — Sun, 12 Oct 2014 10:47:09 -0000

most deaths are from cardiovascular causes
http://www.who.int/mediacen...

Re: TWiV 304: Given X, solve for EBOV

gsgs — Mon, 06 Oct 2014 03:19:29 -0000

the numbers look better now, just look at the WHO-charts at
http://www.who.int/csr/dise...

yet at http://cpid.iri.columbia.ed... I still read

Update 10/01/2014
... Overall, for the combined forecast, the exponential growth of the outbreak is consistent
with the previous week.

which I don't quite understand.

Re: Could the Ebola virus epidemic have been prevented?

gsgs — Fri, 03 Oct 2014 09:48:11 -0000

but should we invest in research or in surveillance and
epidemiological intervention by WHO, as Gostin said ?