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yeah so for those of you I haven't met

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yet my name is Thomas Campbell come from

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st. Louis University and I'm in Paul

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Brockers lab he's a new assistant

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professor so this is kind of the first

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let's say coherent story that we have to

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talk about and so I'm excited to share

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that with you guys and we're interested

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in fundamental questions that have been

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around for a long long time back in

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biblical times matthew was pondering if

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salt loses its saltiness how can we make

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it salty again and even today on the

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Today Show we're still asking questions

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of salt and thankfully these questions

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have almost nothing to do with my

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research but at least I got your

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attention so we are interested in salt

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though specifically salts of sodium and

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potassium and the reason we're

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interested in these salts is because we

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see a universal enrichment of potassium

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across all of modern biology so all

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cells today spend a tremendous amount of

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energy enriching potassium and expelling

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sodium and we won't understand why these

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selective gradients are universally

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conserved we work under the assumption

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that something that's ubiquitous like

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this developed early on is conserved

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throughout evolution because it's

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important and it's probably fundamental

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in nature which is what leads us to

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prebiotic chemistry so we want to

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understand how do these ions impact

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reactions their relative relevant to

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prebiotic chemistry and we want to start

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with the simplest systems we can pretty

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much possibly imagine so that brings us

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the peptides we've talked a little bit

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about peptides over the past couple days

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but why why peptides first their obvious

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prebiotic relevance second their

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relatively well understood by that I

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mean we have a lot of information to go

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off of they've been studied for a long

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time both in the context of prebiotic

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chemistry and other context

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and why hydrolysis so this is something

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that Becky just touched on a little bit

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obviously the goal is to drive

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condensation that's that's what we need

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to build complexity but these reactions

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are in competition and in order to

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understand the more messy condensation

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we first want to understand hydrolysis

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because that's going to be going on in

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the background all the time and again

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it's simpler we have one reactant one

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product in the case of a homodimer at

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least and so I'll highlight again the

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emphasis on fundamental reactions so

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hopefully we can just understand the

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basics first and then then apply what we

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observe to kind of messy your systems

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down the line okay that got pretty

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blurry but this is just a couple notes

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on our methods we are doing the

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hydrolysis of dipeptides we do

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everything with NMR so it pretty simple

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just measure the integration of the

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peaks of the reactants and the products

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over time get the rate constant but what

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I wanted to point out is that you can't

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see it but we have one more HCL that's

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key because the half life of a peptide

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bond neutral pH is painstakingly slow

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and I want to graduate eventually so we

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use an acid catalysts and we have an

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excess of acid which is important

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because then we observe a pseudo

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first-order reaction kinetics so kind of

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simplifies things they're a little bit

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also so when we do this experiment for

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we did for dipeptides all the all the

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possible combinations of glycine and

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alanine so glug lie gly ala ala gly and

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then ala ala so these are the two most

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simple amino acids the most prebiotic ly

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abundant amino acids that they're kind

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of the obvious choice there and when we

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measure this in the presence of sodium

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chloride and potassium chloride in every

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case the hydrolysis proceeds faster in

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the presence of sodium and slightly

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slower in the presence of potassium so

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this was cool we're excited about that

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and you know it's it's definitely

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interesting but it gets a little bit

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more interesting and that's we got to

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talk about cyclic dimers now so whenever

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we talk about peptides in the context of

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prebiotic chemistry we have to also

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consider cyclic dimers because this is

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the reactions general reaction scheme of

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prebiotic long-chain polypeptide

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synthesis the linear dimer will readily

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cycle eyes and you get the cyclic dimer

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here there's a little bit of debate

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about what the role of this is in this

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schematic but suffice it to say that

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generally researchers will consider the

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cyclic dimer to be a problem for

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prebiotic synthesis of long-chain

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polypeptides within in like a miller

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type experiment you see typical ratios

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of the cyclic dimer to the linear dimer

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somewhere between 10 to 12 20 21 ok so

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we wanted to then measure the hydrolysis

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of this cyclic dimer basically doing the

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same experiment again so we did that and

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remarkably we found the exact opposite

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trend of what we what we saw before so

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in this case all the possible

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combinations of glycine alanine all

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three of them and in each case they

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hydrolyze faster in the presence of

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potassium than in the presence of sodium

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and this I mean when admittedly when I

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first did this experiment I was like a

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kind of upset that you know it didn't go

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right but then it's actually pretty

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interesting for for a number of reasons

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so if we look over here this is

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basically we're just comparing the rates

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of sodium sodium and potassium so

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anything that goes up hydrolyzes faster

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in sodium anything that goes down

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hydrolyzes faster and potassium so if we

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this is kind of a cartoon model of the

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reaction scheme I just showed you but if

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we're in a potassium rich environment

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then relative to a sodium rich

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environment you're going to have

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higher proportion of the linear dimer

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which then can go on to react to form

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longer chain polypeptides and so this

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these results kind of raise the the

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possibility emphasize possibility that

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life may have needed potassium rich

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environments to optimize these kinetics

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because although admittedly their modest

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changes in kinetics you know given

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millions of years a small change good

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could kind of be what's needed to tip

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the kinetic scales let's say so also i

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call it the flip so the the flip in the

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relative rates it's useful for a number

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of reasons one it rules out the effect

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of cations on the structure and

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reactivity of water this was our initial

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hypothesis that there would be some

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difference like for example the activity

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of water of a sodium chloride solution

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is different than a potassium chloride

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solution and that's pretty reasonable we

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would think that would expect that would

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impact the rate of hydrolysis since the

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rate determining step of hydrolysis

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involves attack of water so if you lower

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the activity of water you should lower

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the rate of hydrolysis but if that were

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simply the only effect in play then that

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would be the case across the board

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regardless of which substrate you're

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looking at it also rules out any sort of

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systematic errors from reagents or our

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methods if we're say we're weighing out

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a lot of we have a lot of water in our

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potassium chloride and so we're not

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actually putting as much potassium

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chloride in there as we think we are

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then that would again present itself as

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the same change across all substrates

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what it does do is necessitate a direct

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role between the ions and the substrates

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themselves in the mechanism which a you

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know beyond the origin of the

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application to the origin of life I

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think this is a super interesting

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observation because if you ask an

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organic chemist that to draw the

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mechanism for pepto

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hydrolysis even in a sodium chloride

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solution not I don't think anyone would

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enlist the ions in in that mechanism so

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but these results suggest that we should

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so the next step for us is how can we

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probe that interaction we've we've done

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some work to try to do that but so far

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all of our studies have been

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inconclusive there so i won't i won't

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talk more about that but if you have any

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ideas about this I'd be happy to hear

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them so lastly not to be outdone by

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everybody who has these amazing you know

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field sites all over the world this is a

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picture of the Mississippi River that I

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took from just outside my lab it's it's

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a really nice place so lastly I just

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like to acknowledge my group

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specifically Annie and Mark are two

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really awesome undergrad surprisingly

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great undergrads Rio and Matt are the

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other two grad students in the lab they

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work on some other stuff and then

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funding sources so yeah that'll take

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questions thank you hi I for your rate

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of cyclization versus the rate of

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hydrolysis are they competitive or I

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couldn't see so we don't measure the

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rate of cyclization that's been done

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it's I can't recall the exact rate I

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mean it when we have a one more HCL it's

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not cycle izing you know it's only

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hydrolyzing for the most part does that

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answer your question yeah and my other

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question is it's safer like it was a

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kinetic rate you know if you have a

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equilibrium where like the hydrolysis is

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faster than the cyclization what about

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the do you know the rate of going from

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years linear chain to the polypeptides

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Oren uh I don't know that again in acid

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that's not really happening you're not

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condensing at all

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you know there's a lot of that's there's

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a lot of work on peptide condensation in

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general we and that's where we're going

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to go next is looking at that in the

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presence of sodium and potassium does

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that answer your question yeah yeah

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there is in more mild conditions but

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what you know we're trying to drive it

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that direction so that we can so we can

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measure that specifically all right that