Dear Sasha, I was taught that 'scientist' was best translated into German as 'Naturwissenschaftler' rather than the general term 'Wissenschaftler'. Mathematicians were philosophers and e.g. economy belongs maybe to humanities. I thought this distinction was also made at the Imperial College were my English learned at school settled further.
I am not a native speaker, if I am wrong I would like to apolgise - I meant no offense. Best, Tim On 11/29/2014 01:47 PM, Alexandre OURJOUMTSEV wrote: > Dear Tim, > > as you know I avoid making public comments and prefer enjoying the comments > done by others, however this time is hard to resist :-) > > I was surprised by your mail : do you mean that mathematicians are NOT > SCIENTISTS ?! Do you mean that they are nasty persons who fight against > "normal biologists", do not let them developing new techniques and prevent > them from achieving their holy goals ? > > I think (hope) all of us are a sort "natürphilosophes" (is it a right term in > German ? "estestvoispytatel'" = "естествоиспытатель" in Russian), all of us > trying to solve the same Global Problems, looking on them from different > sides and applying the best of our individual knowledge. This diversity is a > force of our community, and there is a very nice article by Kathleen Lonsdale > dated by September 1953 (!!! more than 60 year ago! ) in Acta Cryst, 6, > 874-875, entitled "The training of modern crystallographers". She is talking > exactly about "chemists, biochemists, physicists, geologists, engineers or > mathematicians" (we can make this list much longer); a short and excellent > text. > > Each of us has a "center of gravity of individual knowledge" in different > domains, and professional points of view are useful to contribute into > development of the respective parts of our Global Project (not only Global > Phasing :-). Then I see nothing wrong if an expert in methods (Pavel in this > case; I think he deserves this word) gives a general point of view to a > person who "wants to improve crystallographic methods" because without such > general points of view (usually based on a profound experience of many other > experts) the improvements we are waiting for may not come or will come with a > pain (cannot resist from citing Arthur Conan Doyle: "All refinement is > through sorrow"). > > I hope that it was just an unfortunate phrase in your mail and that everybody > understands what exactly you had in mind :-) During my life I was lucky > seeing fantastic collaborative projects of biologists and mathematicians. > > With best regards, > > Sacha Urzhumtsev > > Prof. of Universities of Lorraine and of Strasbourg > > ________________________________________ > De : CCP4 bulletin board [CCP4BB@JISCMAIL.AC.UK] de la part de Tim Gruene > [t...@shelx.uni-ac.gwdg.de] > Envoyé : samedi 29 novembre 2014 11:16 > À : CCP4BB@JISCMAIL.AC.UK > Objet : Re: [ccp4bb] Free Reflections as Percent and not a Number > > Hi Pavel, > > I think your email highlights one of the differences between us and one > of the reasons for this discussion: > > I am a scientist, not a mathematician - I want to improve > crystallographic methods because people who solve crystal structures > want an answer to a biological or chemical or physical question rather > than because they enjoy watching the realisation of a mathematical > definition. I like Ken Follett's definition of a physicist, for whom > reality is a poor approximation to theory, but the motivation for my > research runs the other way round. > > Cheers, > Tim > > On 11/29/2014 05:12 AM, Pavel Afonine wrote: >> Hi Tim, >> >> your examples are valid and valuable, and clearly exemplify existing >> problems, limitations as well as common misconceptions. >> >> However, if you follow mathematics and strict definitions thereof, then >> crystallographic structure refinement is nothing but an optimization >> problem that, fundamentally, to be defined requires: a) definition of model >> parameterization, b) definition of a function that relates experimental >> data and model parameters, and c) definition of a method that changes model >> parameters in a such a way that optimizes (most of the time minimizes) the >> chosen (at step "b") function. >> >> Please don't think that I've just made up or invented these "a)-b)-c)" >> steps above.. In fact, this has been published, for example, in >> *Acta Cryst.* (1985). A*41*, 327-333, >> and then reiterated using modern jargon, for example, in >> *Acta Cryst.* (2012). D*68*, 352-367. >> >> (I say "for example" above just to stick to the context and also point out >> that you can find more examples in crystallographic literature as well as >> in totally different disciplines such as economics, aerospace science etc.) >> >> Anyways, once all the above (a-b-c) are set and defined, then your only >> goal is as "simple" as finding the global minimum of the function that you >> have chosen to optimize. >> >> Anything else beyond that are either technical details or various >> inefficiencies related to improper model parameterization, improper target >> choice or using limited optimization tool. >> >> All the best, >> Pavel >> >> >> On Fri, Nov 28, 2014 at 11:40 AM, Tim Gruene <t...@shelx.uni-ac.gwdg.de> >> wrote: >> >>> Dear Pavel, >>> >>> there is a beautiful paper called 'Where freedom is given, liberties are >>> taken' by Kleywegt and Jones, but also a wide variety of articles that >>> (fortunately) fought hard for the introduction of Rfree to the >>> (macro-)crystallographic community. >>> >>> In there is mentioned the threading of an amino acid chain backwards >>> into the density achieving (by refinement) a lower R-value than the >>> original one. Since this was achieved with refinement, the former >>> structure was closer to the global minimum than the latter one. >>> Apparently none of these authors had an idea how to modify the target >>> function so that this would not happen - whyfore they suggested to use >>> cross validation to avoid it. >>> >>> If you don't like this line of thought, I can offer a different one: >>> >>> there is a vast number of sets of parameters that ideally fit your data: >>> fill your asymmetric unit randomly with atoms so that your data to >>> parameter ratio is 1 or lower. Refine unrestrained and your are going to >>> end up with an R-value of 0. For unrestrained refinement, the formula >>> for the R-value corresponds (maybe not for maximum likelhood based >>> target functions, you may have to do some translation here) to the >>> target function, which usually has a lower bound of zero, hence this >>> vast number of "structures" all reached the global minimum. Note that >>> the deposited structure has an R value much greater than 0, i.e. it is >>> far away from the global minimum. >>> >>> In order to improve the situation, one modifies the target function by >>> adding restraints. They increase the target value of all "structures", >>> but in general those for the arbitrary solutions increase so much more >>> than that for an acceptable solution that most of those are lifted above >>> that of an acceptable solution. >>> As an example, one of the structures for the yeast polymerase I contains >>> about 34,500 atoms, i.e. the target function is minimised in a 138,000 >>> dimensional space. I don't think there is a proof that any set of >>> restraints is ever so ideal that all false solutions are lifted above >>> the target value of the accepted solution. In fact, without being able >>> to proove it, I doubt that this the case, which lead me to the below >>> claim that we don,t necessarily want to reach the global minimum of the >>> target function. >>> >>> Of course an acceptable structure actually may have a target value >>> representing a global minimum, but I don't think this is always true. >>> >>> Best, >>> Tim >>> >>> On 11/28/2014 05:42 PM, Pavel Afonine wrote: >>>> Hi Tim, >>>> >>>> you don't necessarily want to find the global minimum (...) >>>> >>>> >>>> this contradicts the definition of crystallographic structure refinement. >>>> If finding the global minimum is not what you ultimately want then either >>>> the refinement target or model parameterization are poor. >>>> >>>> Clearly, given complexity of refinement target function profile (in case >>> of >>>> macromolecules) we unlikely to reach the global minimum; however, >>> reaching >>>> it is what we aim for (by definition and construction of refinement >>>> program) . >>>> >>>> Pavel >>>> >>> >>> -- >>> Dr Tim Gruene >>> Institut fuer anorganische Chemie >>> Tammannstr. 4 >>> D-37077 Goettingen >>> >>> GPG Key ID = A46BEE1A >>> >>> >> > > -- > Dr Tim Gruene > Institut fuer anorganische Chemie > Tammannstr. 4 > D-37077 Goettingen > > GPG Key ID = A46BEE1A > -- Dr Tim Gruene Institut fuer anorganische Chemie Tammannstr. 4 D-37077 Goettingen GPG Key ID = A46BEE1A
signature.asc
Description: OpenPGP digital signature
