From: Jeff Hansen <hansen@bioc02.uthscsa.edu>
  To  : rasmb@bbri.eri.harvard.edu
  Date: Tue, 3 May 94 12:28 GMT

Accomplishing long-term goals

Greetings from Texas -

This is both a specific response to Emory's message of 4/29, as well as a 
general commentary about how the XL-A community can work together to best 
accomplish our long-term goals and desires.

First Emory's message.  There is no question that investigators in the 
protein folding and stability fields are rapidly embracing the analytical 
ultracentrifuge, and in almost every case would like to perform experiments 
between 40-100*C.  For example, Andy Robertson (University of Iowa) and I 
are currently determining the influence of temperature and denaturants on 
the distribution of monomers and small aggregates of the CheY protein.  
Results obtained between 5-40*C are compelling, but we are hampered by 
our inability to extend the analyses above 40*C (where most of the action 
is).  Barry Nall in my department is in the same situation.  All three of us 
and I'm sure many others would wholeheartedly support development of high 
temperature capabilities of the XL-A.

I think this issue also illustrates two important general problems that must 
be addressed. First, simply deciding that a given modification is necessary 
isn't enough.  We must also figure out how to convince Beckman to actually 
do it.  Take the current inability to set the XL-A run temperature to 
anything less than whole degrees.  Speaking for a department that has 
performed over 500 sedimentation velocity runs in the last 18 months, we are 
ENORMOUSLY FRUSTRATED by this design oversight.  For almost two years, we 
have begged Beckman to modify the XL component of the XL-A to allow 
temperature settings at 0.1 degree intervals.  During this time, we have 
been told repeatedly that many other sedimentation velocity practitioners 
have said the same thing.  Nonetheless, despite the fact that such a 
modification is relatively trivial, nothing has been done and there has been 
no indication that anything will be accomplished anytime soon.  Another 
example that falls into this category is the user interface.  The lack of 
response has nothing to do with Don, Paul, Alan, Barney Hedges et al., who 
are clearly on our side.  Nonetheless, if corporate Beckman is unwilling (or 
unable) to correct such trivial design oversights, how are we going to 
convince them to develop much more sophisticated systems such as high 
temperature capabilities, etc.  I think Emory hit the nail on the head when 
he suggested that we present these suggestions to Beckman collectively.  If 
30 or 40 XL-A owners unite to make a request, we represent a group of 
individuals that has recently pumped 5-6 million dollars into Beckman's 
accounts.  I don't know if this will work, but the individual approach seems 
to have failed miserably.

Secondly, I think it is very important that the XL-A users worldwide take 
the next 3-6 months to develop a stategic long-term plan ("wish list") for 
the XL-A that encompasses ALL of the design  modifications that we would 
like to see made.  The problem with individual modifications that are strung 
out over a long period of time is one of finances, i.e., where is everyone 
going to get the money to continually upgrade our instruments with expensive 
modifications.  Our department is currently facing this problem with the 
interference optical system.  For example, one of our two XL-A's was 
purchased with an NIH shared instrumentation grant.  If interference optics 
and any other putative upgrades such as high temperature capabilities had 
been available from the beginning, we could have simply submitted a higher 
budget and obtained a "complete" instrument from this single source.  
However, because the NIH SIG program does not allow supplemental 
applications, we are scrambling to figure out how to come up with the many 
tens of thousands of dollars required to upgrade even just one of our 
machines.  For the sake of future XL-A purchasers, particularly those that 
are obtaining their funds through granting agencies, I think we should 
present Beckman with a COMPLETE list of design modifications that should be 
SIMULTANEOUSLY incorporated into the next generation of XL-A.

Well, if nothing else this has hopefully given everyone lots to think about. 
 I realize that there are no easy answers here, but that is why we should 
begin discussing these issues ASAP.  I'll be interested in hearing what 
y'all have to say.


Jeff Hansen
Department of Biochemistry
University of Texas Health Science Center at San Antonio