Hi Colin,
Yes I agree, see eg page 7 of 
https://www2.physics.ox.ac.uk/sites/default/files/2011-06-08/optics_notes_and_slides_part_5_pdf_63907.pdf
 (and there maybe better weblinks). 

The resolution of cryoEM imaging varies locally and so the “local scaling in a 
complex way” is what we have to get into in practice......

Greetings,
John

Emeritus Professor John R Helliwell DSc



> On 17 Feb 2020, at 21:57, Nave, Colin (DLSLtd,RAL,LSCI) 
> <[email protected]> wrote:
> 
> 
> Hi John
> I agree that neutrons have a role to increase the contrast for certain atoms. 
> The “water window” for x-ray imaging also fulfils a similar role. The 
> “locally scaled in a complex way” is a bit beyond me.
>  
> The relationship between “ diffraction” errors and “imaging” errors is  based 
> on Parseval’s theorem applied to the errors for electron densities and 
> structure factors.  See for example 
> https://www-structmed.cimr.cam.ac.uk/Course/Fourier/Fourier.html and scroll 
> down to Parseval’s theorem. Admittedly not a primary reference but I think 
> Randy (and Parseval, not to be confused with Wagner’s opera), are unlikely to 
> have got it wrong.
>  
> Imaging (with both electrons and x-rays) can be lensless (as in MX, CDI and 
> variants) or with an objective lens (electron microscopes have nice objective 
> lenses). The physical processes are the same up to any lens but MX, CDI etc. 
> use a computer to replace the lens. The computer algorithm might be imperfect 
> resulting in visible termination errors. With a decent lens, one can also see 
> diffraction ripples (round bright stars in a telescope image) due to the 
> restricted lens aperture.
>  
> Good debate though.
>  
> Colin
> From: John R Helliwell <[email protected]> 
> Sent: 17 February 2020 16:36
> To: Nave, Colin (DLSLtd,RAL,LSCI) <[email protected]>
> Cc: [email protected]
> Subject: Re: [ccp4bb] FW: [ccp4bb] [3dem] Which resolution?
>  
> Hi Colin,
> Neutrons are applied to the uranyl hydrides so as to make their scattering 
> lengths much more equal than with X-rays, and so side step ripple effects of 
> the uranium in the Xray case, which obscures those nearby hydrogens.
> In terms of feature resolvability the email exchange (and there may be better 
> ones):- http://www.phenix-online.org/pipermail/phenixbb/2017-March/023326.html
> refers to “locally scaled in a complex way”. So, is the physics of the 
> visibility of features really comparable between the two methods of cryoEM 
> and crystal structure analysis?
> Greetings,
> John
> Emeritus Professor John R Helliwell DSc
>  
>  
> 
> 
> On 17 Feb 2020, at 13:59, Nave, Colin (DLSLtd,RAL,LSCI) 
> <[email protected]> wrote:
> 
> 
> Hi John
> I agree that if I truncate the data at a high information content threshold 
> (e.g. 2 bits)  series termination errors might hide the lighter atoms (e.g. 
> the hydrogens in uranium hydride crystal structures). However, I think this 
> is purely a limitation of producing electron density maps via Fourier 
> transforms (i.e. not the physics). A variety of techniques are available for 
> handling series termination including ones which are maximally non-committal 
> with respect to the missing data. The issue is still there in some fields 
> (see https://onlinelibrary.wiley.com/iucr/itc/Ha/ch4o8v0001/ ). For protein 
> crystallography perhaps series termination errors have become less important 
> as people are discouraged from applying some I/sigI type cut off.
>  
> Cheers
> Colin
>  
>  
>  
> From: John R Helliwell <[email protected]> 
> Sent: 17 February 2020 12:09
> To: Nave, Colin (DLSLtd,RAL,LSCI) <[email protected]>
> Subject: Re: [ccp4bb] FW: [ccp4bb] [3dem] Which resolution?
>  
> Hi Colin,
> I think the physics of the imaging and the crystal structure analysis, 
> respectively without and with Fourier termination ripples, are different. For 
> the MX re Fourier series for two types of difference map see our 
> contribution:-
>  
> http://scripts.iucr.org/cgi-bin/paper?S0907444903004219
>  
> Greetings,
> John 
>  
> 
> Emeritus Professor John R Helliwell DSc
> https://www.crcpress.com/The-Whats-of-a-Scientific-Life/Helliwell/p/book/9780367233020
>  
>  
> 
> 
> 
> On 17 Feb 2020, at 11:26, "[email protected]" 
> <[email protected] wrote:
> 
> 
>  
> Dear all.
> Would it help to separate out the issue of the FSC from the value of the 
> threshold? My understanding is that the FSC addresses the spatial frequency 
> at which there is a reliable information content in the image. This concept 
> should apply to a wide variety of types of image. The issue is then what 
> value of the threshold to use. For interpretation of protein structures 
> (whether by x-ray or electron microscopy), a half bit threshold appears to be 
> appropriate. However, for imaging the human brain (one of Marin’s examples) a 
> higher threshold might be adopted as a range of contrasts might be present 
> (axons for example have a similar density to the surroundings). For 
> crystallography, if one wants to see lighter atoms (hydrogens in the presence 
> of uranium or in proteins) a higher threshold might also be appropriate. I am 
> not sure about this to be honest as a 2 bit threshold (for example) would 
> mean that there is information to higher resolution at a threshold of a half 
> bit (unless one is at a diffraction or instrument limited resolution).
>  
> Most CCP4BBers will understand that a single number is not good enough. 
> However, many users of the protein structure databases will simply search for 
> the structure with the highest named resolution. It might be difficult to 
> send these users to re-education camps.  
>  
> Regards
> Colin
>  
> From: CCP4 bulletin board <[email protected]> On Behalf Of Petrus Zwart
> Sent: 16 February 2020 21:50
> To: [email protected]
> Subject: Re: [ccp4bb] [3dem] Which resolution?
>  
> Hi All,
>  
> How is the 'correct' resolution estimation related to the estimated error on 
> some observed hydrogen bond length of interest, or an error on the estimated 
> occupancy of a ligand or conformation or anything else that has structural 
> significance?
>  
> In crystallography, it isn't really (only in some very approximate fashion), 
> and I doubt that in EM there is something to that effect. If you want to use 
> the resolution to get a gut feeling on how your maps look and how your data 
> behaves, it doesn't really matter what standard you use, as long as you are 
> consistent in the use of the metric you use. If you want to use this estimate 
> to get to uncertainties of model parameters, you better try something else.
>  
> Regards
> Peter Zwart
>   
>  
>  
> On Sun, Feb 16, 2020 at 8:38 AM Marin van Heel 
> <[email protected]> wrote:
> Dear Pawel and All others ....
> This 2010 review is - unfortunately - largely based on the flawed statistics 
> I mentioned before, namely on the a priori assumption that the inner product 
> of a signal vector and a noise vector are ZERO (an orthogonality assumption). 
>  The (Frank & Al-Ali 1975) paper we have refuted on a number of occasions 
> (for example in 2005, and most recently in our BioRxiv paper) but you still 
> take that as the correct relation between SNR and FRC (and you never cite the 
> criticism...). 
> 
> Sorry
> Marin
>  
> On Thu, Feb 13, 2020 at 10:42 AM Penczek, Pawel A 
> <[email protected]> wrote:
> Dear Teige,
>  
> I am wondering whether you are familiar with
>  
> Resolution measures in molecular electron microscopy.
> Penczek PA. Methods Enzymol. 2010.
> Citation
> Methods Enzymol. 2010;482:73-100. doi: 10.1016/S0076-6879(10)82003-8.
>  
> You will find there answers to all questions you asked and much more. 
>  
> Regards,
> Pawel Penczek
>  
> 
> Regards,
> Pawel
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> 
>  
> --
> ------------------------------------------------------------------------
> P.H. Zwart
> Staff Scientist
> Molecular Biophysics and Integrated Bioimaging &
> Center for Advanced Mathematics for Energy Research Applications
> Lawrence Berkeley National Laboratories
> 1 Cyclotron Road, Berkeley, CA-94703, USA
> Cell: 510 289 9246
>  
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