Reviewers Workshop

How to Review Scientific Papers

Carl Schwarz Publishing Director

Campinas, 4 May 2011
Outline
Brazil, UNICAMP and Elsevier

How to Review an article

Why Peer Review
Reviewer, author and editor
Structure

Cases

2
Outline
Brazil, UNICAMP and Elsevier

How to Review an article

Why Peer Review
Reviewer, author and editor
Structure

Cases

3
MAP OF BRAZIL: STRONG FOCUS ON BIOLOGY

MATH & PHYSICS

COMPUTER SCIENCE

CHEMISTRY
SOCIAL SCIENCE
MULTI-DISCIPLINARY
RESEARCH AREAS
HUMANITIES
RESEARCH AREA
WITH GLOBAL STRENGTH ENGINEERING
BRAIN RESEARCH

HEALTH SCIENCE

EARTH SCIENCE
BIOLOGY
MEDICINE
BIOTECHNOLOGY

INFECTIOUS DISEASES 4
MAP OF UNICAMP: STRONG FOCUS ON ENGINEERING AND CHEMISTRY

RESEARCH AREA
WITH GLOBAL STRENGTH

MATH & PHYSICS

COMPUTER SCIENCE

MULTI-DISCIPLINARY
SOCIAL SCIENCE
RESEARCH AREAS CHEMISTRY

HUMANITIES

BRAIN RESEARCH ENGINEERING

EARTH SCIENCE
HEALTH SCIENCE BIOLOGY

BIOTECHNOLOGY
MEDICINE
INFECTIOUS DISEASE

5 5
 UNICAMP
Some popular journals (2009-2011)
Papers from UNICAMP
4,000 Quimica Nova
3,500 Journal of the Brazilian Chemical Society
Lecture Notes in Computer
3,000
Ciencia E Tecnologia De Alimentos
2,500 Physical Review B Condensed Matter and
2,000 Materials Physics
Journal of Applied Physics
1,500
Arquivos De Neuro Psiquiatria
1,000 Chemical Engineering Transactions
500 Computer Aided Chemical Engineering
0
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010

20% of articles from UNICAMP find a home in an

Elsevier journal Elsevier Editors from UNICAMP
5
4
3
2
1
0

6
Examples of our 1800 journal titles
Outline
Brazil, UNICAMP and Elsevier

How to Review an article

Why Peer Review
Reviewer, author and editor
Structure

Cases

8
Take-Home Lesson

The best reviewers tend to view themselves

as teachers rather than critics
 What do modern researchers want as authors?
Register a discovery as theirs and made by them on a
Registration certain date
Assert ownership and achieve priority
Get their research (and by implication, themselves) quality
Validation stamped by publication in a journal of known quality
Establish a reputation, and get reward

Dissemination
Let their peers know what they have done
Attract recognition and collaboration

Leave a permanent record of their research

Archive
Renown, immortality

10
 Certification Breakdown by Discipline

Subject variation

Small to Medium Scale Theoretical and very large scale experimental

Experimental/Empirical

Many Co-authorship
investigators low Small fields
where quality of
Theoretical paper, each researchers
Right or Wrong work is known
by inspection personally to peers
Peer review as methodological
and quality filter Co-authorship high

Very Very
Certification function
strong weak
Peer Review
The reviewer is at the heart of scientific publishing
the lynchpin in the whole business of Science

It is a testament to the power of peer review that a scientific hypothesis or

statement, presented to the world is largely ignored by the scholarly community
unless it is published in a peer-reviewed journal.
Reviewers, who are usually both authors and readers, make the editorial
process work by examining and commenting on manuscripts, often several
times to improve them prior to publication.
Reviewers are the backbone of this process, because both the quality and
timelines of published papers depend directly on the thoroughness and
promptness of the individual reviewer.
Peer Review
Why do reviewers review?
Give
Academic duty
Take
General interest in the area
Keep up-to-date with the latest developments
Helps with their own research and/or stimulate new ideas
Builds association with prestigious journals and editors
Aware of new research before their peers
Career development
Editors for journals

Usually selected from the list of

active reviewers.
Experience From Heritage
Science and medical communities around the world are
united through the highly organized and efficient system of
STM Publishing

2,000
STM publishers

23,000
peer-reviewed journals

1.4 million
peer-reviewed articles
Publication Process

Reviewers
Pre-Submission
Peer Review
Authors

Editor Produc-
tion
Readers

Publication
 The Elsevier Journal Publishing Cycle

1,000 new editors per year 800,000+ article submissions per year
20 new journals per year Solicit and
manage
40 90% of
submissions
articles rejected
9.8 million articles Archive and Manage
now available promote peer review
use 7,000 editors
70,000 editorial board
30 Million members
Researchers 300,000 reviewers
Publish and Edit and 1.6 million referee
180+ countries disseminate prepare reports/yr
4,500+ institutions 600,000 authors
480 million+ 6.5 million author/publisher
communications / year
downloads per year Production

250,000 new articles produced each year

185 years of back issues scanned, processed and data-tagged
17
Authors Deeply Care About Refereeing

Elsevier Author Feedback Programme

Refereeing Speed
Refereeing Standard
Reputation
Impact Factor
Audience/Readership
Production Speed
Editor/Editorial Board
Publishing Services
Final Quality

And thus also critically

important to editors
Role of Reviewers
The peer review process, which in essence determines the
public record of science, is based on trust
trust between authors and editors
trust between editors and reviewers

The quality and integrity of the entire scientific publishing

enterprise depends largely on the quality and integrity of
the reviewers
Reviewers Task
The reviewer should write reviews in a collegial,
constructive manner
This is especially helpful to new investigators
There is nothing more discouraging to a new investigator or
even to a more experienced one, than a sarcastic, destructive
review
Treat all manuscripts in the same manner as you like to
be treated yourself

The reviewer recommends, the Editor decides

Issues for Comment in Reviews
Importance and clarity of research hypothesis
Originality of work
Delineation of strengths and weaknesses of methodology,
experimental/statistical approach, interpretation of results
Writing style and figure/table presentation
Ethics concerns (animal/human)
Reviewer guidelines
Materials Science and Engineering A
Reviewer Checklist

1. Give a brief estimate of the scientific interests and originality of the paper.
2. Is it a new and original contribution?
3. Does it contain matter that might be omitted? If so, what?
4. Is it clearly presented and well organized?
5. Does it give adequate references to related work?
6. Is the English satisfactory?
7. Are all illustrations and tables necessary and adequate?
8. Is the abstract informative and does it cover the content?
9. Are the conclusions sound and justified?
10. Please, list any further comments or specific suggestions

Confidential checklist meant for editors eyes only.

International Journal of Pharmaceutics -
Reviewer Checklist Confidential checklist meant for editors eyes only.

Is the article within the scope of the journal? Yes/No

Would the article be more appropriately published in a specialist journal? Yes/No
Can the article be condensed? Yes/No
o If so, where: Figures // Figure legends // Tables // Text
Is the language acceptable? Yes/No
Are there portions of the manuscripts which require further clarification? Yes/No
o If so, where?
On a scale from 1 (poor) to 5 (outstanding), how do you rate
o New knowledge in pharmaceutics
o Experimental design
o Evaluation of data
o Discussion of results
o Clarity of presentation
The article should be:
o Accepted without change
o Accepted after minor revision
o Accepted after condensation
o Reconsidered after major revision
o Rejected
Confidential comments to the editor: [free text]
Purpose of Peer Review
Ensure:
quality, checking that no mistakes in procedure or logic have
been made
that the results presented support the conclusion drawn
that no errors or omissions in citations to previous work have
been made
that all protocols conducted follow proper review and approval
by appropriate institutional review committees
that the work is original and significant
Scientific Quality of the Work
Are the methods appropriate and presented in sufficient detail
to allow the results to be repeated?
Are the data adequate to support the conclusions?
Presentation of the Paper
Writing
Clear, concise, good English?
But no need for reviewers to act as language editor
Title
Specific, and reflecting the content of the manuscript?
Abstract
Brief, and describing the purpose of the work, what was done, what was
found, and the significance?
Figures
Justified? Clear? Sharp, with fonts proportionate to the size of the figure?
Clear and complete legends?
Tables
Can they be simplified or condensed? Should any be omitted?
Trade names, abbreviations, symbols
Properly used where indicated? Abused?
Confidential Comments to the Editors
Provide comments regarding the novelty and
significance of the manuscript
Provide a recommendation about the manuscripts
suitability for publication in the journal, usually
Accept / Minor revision / Major Revision / Reject

These confidential comments will not be revealed to the

author(s)!
Comments for Authors
Provide specific comments, preferably numbered, on the
design, presentation of data, results, and discussion
Do not include recommendations for publication in this
section
Ensure that that the comments to the author(s) are
consistent with your recommendation to the editors
Privileged Document
This manuscript is a privileged communication. The data are
and remain the exclusive property of the author(s)
should not be disclosed to others who may use the information in their
research
If you have printed the manuscript
it must be kept confidential until the review process is complete,
and then be destroyed
If you have shared responsibility for the review of this manuscript
with a colleague, please provide that persons name and
institutional affiliation to the editors
Reviewers
Should only accept to review manuscripts
in their areas of expertise
when they can complete the review on time
Should always avoid any conflicts of interest
If in doubt, consult with the editor
Are not allowed to plagiarize the data
Should provide an honest, critical assessment of the research
Must analyze the strengths and weaknesses of the research, and
provide specific suggestions for improvement
Oversight Function
The reviewer also has the unpleasant responsibility of reporting
suspicion of
duplicate publication
fraud
plagiarism
ethics concerns
etc.

These problems are normally followed up by the Editors and the

Publisher.
Publish AND Perish! When authors break ethics rules

International scientific ethics rules have evolved over centuries.

Scientific ethics are not considered to have national variants or

characteristics there is a single ethical standard for science.

Ethics problems with scientific articles are on the rise globally.

The article of which the authors committed plagiarism: it
wont be removed from ScienceDirect. Everybody who
downloads it will see the reason of retraction
Ethics Issues in Publishing
Scientific misconduct
Falsification of results
Publication misconduct
Plagiarism
Different forms / severities
The paper must be original to the authors
Duplicate publication
Duplicate submission
Appropriate acknowledgement of prior research and
researchers
Appropriate identification of all co-authors
Conflict of interest
Reasons for Rapid Rejection without Review
The Editor-in-chief evaluates all submissions, and
determines whether they go into the review process
Criteria
Example: Rules-of-Three
Out of scope
Too preliminary each with specific examples
Lack of Novelty
English language is inadequate
Evidence of prior publication or multiple
simultaneous submissions
Review process (I)
Regular articles are initially reviewed by at least two reviewers
When invited, the reviewer receives the Abstract of the
manuscript.
The editor generally requests that the article be reviewed within
two weeks
limited extensions sometimes negotiable
Articles are revised until the two reviewers agree on either
acceptance or rejection, or until the editor decides that the
reviewer comments have been addressed satisfactorily
The reviewers reports help the Editors to reach a decision on a
submitted paper
The reviewer is the reviewer; the editor the referee.
Review process (II)
If a report has not been received after 4 weeks, the Editorial office
contacts the reviewer
The final decision concerning a manuscript lies with the Editors
If there is a notable disagreement between the reports of the
reviewers, a third reviewer may be consulted
The anonymity of the reviewers is strictly maintained
unless a reviewer asks to have his/her identify made known to the authors
Review process (III)
Reviewers should not communicate directly with authors
All manuscripts and supplementary material must be treated by
Editors and Reviewers as confidential information.
The manuscript should not be distributed outside this small group
The aim is to have a first decision to the authors within 2-4
weeks after submission of the manuscript
Meeting these schedule objectives requires a significant effort on
the part of the Editorial staff, Editor and Reviewers
If reviewers treat authors as they themselves would like to be
treated as authors, then these objectives can be met.
Role of the Reviewer
General impression and Abstract
General impression
Before commenting on parts of the manuscript, add a short summary of
the article,
indicating a general comprehension of the article, its importance, reviewers
enthusiasm, language/style/grammar
Avoid remarks personally hitting the authors, or excessive or pointlessly
clever and sarcastic remarks
Reviewer comments are not meant to hurt the authors
If you must vent, add such remarks to Comments to Editor

Abstract
Is it a real summary of the paper, including key results?
Not too long?
Long abstracts are truncated in Abstracting Services
Role of the Reviewer Introduction
Comment on effectiveness, clarity and organization
Comment on motivation for what follows
Suggest changes in organization
Point authors to appropriate citations
Dont just write authors have done a poor job in citing
relevant research
Role of the Reviewer Methods
Can an interested colleague repeat the experiments and
get similar outcomes?
Proper reference to previously published methodology?
Accurate description of new methodology?
Proper use of Supplementary material?
Role of Reviewer
Results and Discussion (I)
Suggest improvements in the data presented, in presentation,
and in style
Comment on logic, and justification of conclusions and
interpretations
Detail concisely and precisely the changes you recommend
remember that authors must respond to, and be able to implement or to
rebut your comments
List, separately under one header, suggested changes in style,
grammar, and other small changes
Role of Reviewer
Results and Discussion (II)
Comment on number of figures, tables, schemes, their
need and their quality
Require or suggest other experiments or analyses
make clear the need for such, but defer to the Editor if you
are not sure whether new experiments are essential, or
would be more appropriate for future studies
Before you propose additional work, first ask yourself
whether the current manuscript is worth to be published
Role of Reviewer - Conclusions
Comment on importance, validity, and generality of
conclusions
Request toning down unjustified claims to generality
Request removal of redundancies and summaries
Summary should be in the abstract, not in the conclusions
Role of Reviewer
References, Tables, Figures
Check, if possible, accuracy of citations, and also comment on
number and suitability
Comment on any footnotes (text or tables) and whether those
used should have been included in the body of the text
Comment on the need for figures, their quality, legibility
consider their likely size on the typeset journal page
Assess legends, headers, and axis labels
completeness
Check for consistency of presentation
font, size, etc.
Comment on need for colour in figures
References Tool for reviewers
Editors view - What makes a good
Reviewer?
Provides review that is thorough and comprehensive
Provides review on time
Cites appropriate evidence to support comments made
to author
Provides constructive criticism
Demonstrates objectivity
Provides a clear recommendation to the Editor as to the
appropriateness and relevance of the research
Outline
Brazil, UNICAMP and Elsevier

How to Review an article

Why Peer Review
Reviewer, author and editor
Structure

Cases

49
Example Journal of Molecular Biology
Title:
Article Type: Communication
Section/Category: Protein and RNA folding
Keywords: unfolded proteins; NMR spectroscopy; amyloid diseases; protein folding
Corresponding Author's Institution: Johann Wolfgang Goethe Universitat Frankfurt

Abstract:
Lorem ipsum tempor laboramus persecuti qui te, dicat iisque mel no. Has eu eros mutat perpetua. Eam lorem gloriatur no, cu mei
gloriatur persequeris. Usu ridens vocent docendi ad, ut mei sumo quot definitionem, ne modo postea accusam vis. Suscipit honestatis in
vis, mea in error consectetuer. Id sea modus posse accusata, est no zzril convenire salutatus, ne vim mucius ceteros facilisis. Ea aliquip
albucius inimicus mea, te qui modus dolorem quaerendum. Te vel pericula periculis. Per facer mentitum consequat ut. Eos et consul
omnium, et hinc pertinacia vim. Pri id quando eripuit, summo detraxit pri at. Vidit audiam sensibus sea an, qui et tamquam quaeque, ut
usu dicant inciderint contentiones. Id prima explicari pri, eu cum minimum deserunt. Vel mutat petentium eu, an eos corpora nominati,
fuisset reprimique ea sit. Omittam luptatum delicatissimi an mel. Duo id justo utamur alienum. Nostro nostrud deseruisse vis ad, ad
nusquam ponderum conclusionemque vix. Mea te meis torquatos efficiendi, sea ei novum sensibus elaboraret. At cum adhuc sanctus
splendide, ut enim placerat sed. Eos oportere conceptam comprehensam ea, duo recusabo facilisis pertinacia at, an civibus corrumpit
vel. Malis tollit volumus usu no, blandit fabellas iracundia ei mei, amet dicit an cum.
Cover letter of the author
Dear Editor,

We would like to submit the manuscript entitled:

Lorem ipsum tempor laboramus persecuti qui "
by XXXX et al. for publication as correspondence in the Journal of Molecular Biology.

We have investigated the unfolded states of human lysozyme and two disease-related single point
mutants (I56T, D67H) using liquid-state NMR-spectroscopy and compare it with our previous
investigations of hen lysozyme.

We show that residual structure and rigidity is conserved in sequence in all investigated proteins.
However, the extent of transient structure propensity varies: hen lysozyme exhibits the least residual
structure and human lysozyme mutants show the largest, with the largest differences at the interface
between the - and the -domain. Up to now, such comparison has only been carried out for the
native states of the proteins. Fibril formation, however, involves at least partially unstructured states.
The results shown here suggest a correlation of residual structure and dynamics in the unfolded state
with the ability to form amyloids. Our investigations are thus important to increase our understanding
about the mechanism of fibril formation which is crucial for the understanding of the disease, a first
step towards finding measures to prevent the disease.

We feel that the broad audience of JMB is the best place to publish our results.
Yours sincerely,
Reviewer #1: Accept with Minor Revisions
The manuscript by XXX et al. reports on an NMR study of the unfolded state ensemble of
human lysozyme and two single-point mutants (I56T and D67H) that are found in amyloid
deposits. What is being
Since lysozyme is stable under physiological conditions, the wild type and mutants were
investigated in their reduced variants (i.e., replacement of eight Cys residues by Ala) and at reported
pH 2, which represent unfolding conditions even in the absence of chemical denaturant and
at low temperature (293 K was used in this study). Chemical shift and relaxation
measurements were performed to investigate secondary structure propensity and flexibility,
respectively. The main results is that the single-point mutations seem to change the
ruggedness of the free energy surface in the unfolded state. The topic is interesting and the
Why it is
results seem to be new.
relevant
Remarks:
1) The reduced variant of lysozyme at pH 2 does not reflect physiological conditions. The
authors should mention the possible differences in the unfolded state and its flexibility with
respect to the wild type (or single-point mutants) in physiological milieu. Also, has the
denatured state of the original lysozyme sequence (i.e., with disulfide bridges) been
Specifics
investigated previously at (very) low denaturant concentration (even at elevated
temperature)?

2) The authors should compare their results with simulation studies (mainly of structured Quality of report?
peptides) that have shown changes in the topography of the denatured state ensemble
upon single-point mutations.

3) A ribbon structure of lysozyme should be presented next to Scheme 1 to illustrate the

individual elements of secondary structure. Moreover, cylinders and arrow could be added
below the x-axes in Figures 2 and 3 to illustrate helices and strands, respectively.
 Reviewer #2: Reject
This manuscript describes conformational features of the unfolded states of two mutants of
human lysozyme and compare them with those of the homologous hen egg white protein. The What is being
unfolded state are obtained by substituting alanines to the endogenous cysteines and by
working at pH 2. I find the manuscript very difficult to follow, poorly written and not giving reported
enough information on the protocol used. In addition, I feel that its content is strongly out of
date: it was more than 20 years ago that Alan Fersht and his group exploited molecular biology
to show the effect of point mutations on protein stability. Here, it seems to have gone back at
that stage. The only possible novelty could be that we are now able to afford a more detailed Why it is NOT
study of the unfolded state but this looks to me not enough to grant publication of this relevant
manuscript.

Specific criticisms:
1. Introduction: 'Typically, the single point mutations do not significantly change the structure
of the native state9.' This sentence is written as its content was generally true which is not.
The citation refers to the specific case of lysozyme. It is very confusing and conceptually Specifics
wrong.
2. Bottom of p. 4: RMSD are given in Hz?
3. No information is given on the buffer or on the experimental conditions used. This is bad.
4. p. 7: the authors talk about clusters. Which clusters? how have these residues been Quality of report?
clustered? according to which property?
5. Figure 1: the position of the secondary structure elements must be indicated in teh figure.
Frankly, I would say that there is a very fair chance that the spectra have been incorrectly
referenced. I would be VERY surprised if there was really such a general tendency towards a
helical structure. It is simply too much and these results can have a much simpler and trivial
explanation: wrong referencing.
6. Figure 3: the structures are hardly visible. As it is, this figure does not properly convey any
useful information.
Reviewer #3: Major Revision Required
The manuscript describes a NMR study of the unfolded forms of human and hen
egg white lysozyme. In order to unfold the proteins all of cysteine residues have
What is being
been mutated to alanyl residues in both proteins. This results in a polypeptide reported
chain which is unfolded at pH 2.0 in the absence of other denaturant both for
human and hen lysozyme. A secondary chemical shift analysis is presented for
three types of nuclei HN , C?, and C? , Figure 1a. An order parameter study
including measurements of 15N R1 and R2 relaxation rates and H- 15N NOEs is
presented in Figure 1b including a spectral density analysis.
Two mutations I56T and D67H of human lysozyme, which are disease relevant,
have been built into the "all Cys to Ala" variant of human lysozyme and
the 15N R2 relaxation times have been measured for the two mutant proteins and
compared to the "all Cys to Ala" wild type human lysozyme. The difference in R2
throughout the amino acid sequence is presented. Why it is NOT
acceptable in its
The manuscript has a number of minor but still serious problems, which have to
be resolved prior to any further consideration of the manuscript. Firstly, the current form
comparison of the hen and human "all Cys to Ala" variants does not seem to
have much relevance to the disease related mutant studies. Secondly, the
interesting effects on the R2 of the mutations are not really analyzed very well. It
is not clear whether the differences between wild type and mutant relaxation Specifics
times are indeed significant, no error bars for the differences. A reference to a
chemical shift analysis in the supplementary material Figure S4 is not what would
to be expected, showing just another annotated HSQC spectrum of one of the
mutant proteins but no analysis of chemical shift perturbations.
Quality of report?
Decision by editor
Major revision
Sent all three referee reports to the author
All reports had suggestions
Give the author the chance to respond to the negative
criticisms
Resubmitted and sent to the reviewers

Dear Peter,
Thank you very much for sending us the comments of the reviewers. They
have helped us improving the quality of our manuscript. We hope we have
adequately addressed the concerns by the reviewers. Please find below our
detailed response. We hope that the manuscript can then be published in the
Journal of Molecular Biology.
With very best wishes
Example: Journal of Molecular Biology
Title: : Lorem ipsum tempor laboramus persecuti qui te, dicat iisque mel no
Section/Category: Protein and RNA folding
Keywords: Protein design; protein symmetry; protein evolution; top-down symmetric deconstruction;
-trefoil
Corresponding Author: Dr. XXX
Corresponding Author's Institution: Florida State University, USA

Abstract: Lorem ipsum tempor laboramus persecuti qui te, dicat iisque mel no. Has eu eros mutat perpetua. Eam lorem gloriatur no, cu
mei gloriatur persequeris. Usu ridens vocent docendi ad, ut mei sumo quot definitionem, ne modo postea accusam vis. Suscipit
honestatis in vis, mea in error consectetuer. Id sea modus posse accusata, est no zzril convenire salutatus, ne vim mucius ceteros
facilisis. Ea aliquip albucius inimicus mea, te qui modus dolorem quaerendum. Te vel pericula periculis. Per facer mentitum consequat ut.
Eos et consul omnium, et hinc pertinacia vim. Pri id quando eripuit, summo detraxit pri at. Vidit audiam sensibus sea an, qui et tamquam
quaeque, ut usu dicant inciderint contentiones. Id prima explicari pri, eu cum minimum deserunt. Vel mutat petentium eu, an eos corpora
nominati, fuisset reprimique ea sit. Omittam luptatum delicatissimi an mel. Duo id justo utamur alienum. Nostro nostrud deseruisse vis ad,
ad nusquam ponderum conclusionemque vix. Mea te meis torquatos efficiendi, sea ei novum sensibus elaboraret. At cum adhuc sanctus
splendide, ut enim placerat sed. Eos oportere conceptam comprehensam ea, duo recusabo facilisis pertinacia at, an civibus corrumpit
vel. Malis tollit volumus usu no, blandit fabellas iracundia ei mei, amet dicit an cum. The topdown symmetric deconstruction approach
provides a novel alternative means to successfully identify a useful polypeptide "building block" for subsequent "bottom-up" de novo
design of the target architecture.
Reviewer #1: Reject
Much of the paper, including the abstract, gives the impression
that new results on protein design are being presented. But it Structure of report?
seems that most of the important findings, all the way from
designed sequences to final structures, have been published in a
string of earlier papers and a new one in PNAS. It is hard to tell
from this manuscript what new is being presented. Whatever is Quality of report?
new is not properly placed in the context of what was already
done. Perhaps the design strategy itself has not been discussed
previously in much detail. But the description of the designs in
this manuscript is confusing and not well organized. The results
section begins with a discussion of the "hydrophobic core-packing
group", but no figure of the structure shows up until Figure 4, and
then only as an unnumbered ribbon diagram. In fact, no figure
showing side chains appears anywhere in the paper, which is
very strange if the goal is to explain a structure-based design
strategy. Even if things were clarified, there is a worry that not
much insight would be gained. The design approach appears to
have been highly heuristic and based on human interpretation,
with little computational or quantitative components to the
strategy. This obviously limits the ease with which
generalizations can be made.
 Reviewer #2: Accept with Minor Revision
XXX et al. present a novel "top-down symmetric deconstruction" approach to find What is being
the building block of constructing a symmetric protein by beginning from a known
protein. The proteins constructed by this approach can exhibit much better stability reported
and folding properties and can also avoid the misfolding or aggregating problem
encountered by polypeptides with exact sequence symmetry in bottom-up de novo
design. The author successfully used their approach to find a building block of Why it is
three-fold symmetric beta-trefoil fold from Fibroblast growth factor-1 (FGF-1). This
approach seems to be applicable to find the building blocks of other symmetric
proteins. This paper is well written.
relevant
Pages 9-10 show "no detectable monomer form present with either protein"
(Monofoil-4P or Difoil-4P) and "The molecular mass of the Monofoil-4P (6.4 kDa) Specifics
and Difoil-4P (11.2 kDa) polypeptides therefore indicated a homo-trimer oligomer in
solution for both polypeptides with no evidence of monomeric or higher-order
oligomeric forms." Does this suggest that the Monofoil-4P is not foldable by itself or
has not pre-folded before forming oligomer? If yes, this will relax some constraints
for the building block in the bottom-up de novo design of symmetric proteins.
Therefore it is interesting to know how three Monofoil-4P polypeptides fold into a
homo-trimer oligomer cooperatively. Is there any information about this?
Furthermore, the building block identified by the present top-down approach can
only form an oligomer with the same degree of symmetry as the original protein. It Quality of report?
is better to give an explanation to this. Finally, can Monofoil-4P be considered as
ancestor of beta-trefoil fold from a view of evolution?

Other minor issues:

(1)Page 5, line 2: The full name of the abbreviation "SD" should be firstly indicated
here .
(2) For convenience for readers, it is better to give the PDB ID of FGF-1 directly in
this paper.
Reviewer #3: Accept with Minor Revision
I very much like this paper. I like
the description of design Structure of report?
considerations and the thorough
characterization of all intermediate
designs, and not just the 'final' Quality of report?
one. A nice paper. I don't think we
necessarily need the Figure of m-
values i.e. Figure 10, because x-
axis is just 'number of the design' Was it useful?
so it is not very meaningful. Noting
these values in the table will
suffice.

Quality of report?
Decision by editor
Major revision
Sent only two reports to the author
All reports had suggestions
Give the author the chance to respond to the negative
criticisms
Resubmitted and was accepted.

The revised version ended up as the cover article for JMB

The NSF peer review panel declined to fund the project, saying it was unlikely
to succeed.
Example Chemical Engineering Journal
Title: Synthesis and characterization of hydrophobically associating cationic polyacrylamide
Keywords: Hydrophobic association, Cationic polyacrylamide flocculant, Oily wastewater, Synergistic effect
Corresponding Author's Institution: Shandong Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental
Science and Engineering, Shandong University

Abstract: P(AM-DMDAAC-BA), one kind of hydrophobically associating cationic polyacrylamide, was synthesized with acrylamide (AM),
dimethyldiallyammonium chloride (DMDAAC) and butylacrylate (BA) by the micellar free radical copolymerization technique. The
copolymer was characterized by means of Nuclear Magnetic Resonance Hydrogen Spectroscopy (1H NMR), Transmission Electron
Microscopy (TEM) and Thermal Gravimetric Analysis (TGA). The effect of flocculant dosage on oil removal efficiency and synergistic
effect of the copolymer with other reagents were studied with respect to oily wastewater treatment. 1H NMR results proved the formation
of the hydrophobically associating cationic copolymers. TEM showed that adsorption bridging property of P(AM-DMDAAC-BA) was
significantly enhanced along with the increase of hydrophobic group content in the copolymer. TGA results indicated that the copolymer
has favorable thermal stability. It was found that the oil removal efficiency of P(AM-DMDAAC-BA) could reach 93.4% at dosage of 50
mg/L. P(AM-DMDAAC-BA) had good synergistic effect with soluble starch and Al2(SO4)3. The oil removal efficiency could be improved if
Al2(SO4)3 was added prior to P(AM-DMDAAC-BA).
Reviewer #1: Accept
The manuscript can be published in the CEJ.
Regards

Quality of report?
 Reviewer #2: Accept with major revision
Due to continuous interest to waste utilization technologies, it is of great importance to develop new
flocculants for wastewater treatments. The reviewed manuscript is intended to prepare flocculating
polymer systems to enhance oil removal efficiency, thus the paper is topical for the Chemical Engineering
Journal. What is being
The authors have synthesized a hydrophobically associating cationic copolymer of polyacrylamide,
dimethyldiallylammonium chloride and butylacrylate, using micellar free radical polymerization. The oil
reported
removal efficiency of the synthesized copolymer solo and its synergistic effect with soluble starch or
Al2(SO4)3 is discussed. The authors have shown that a small starch addition can decrease a
concentration of the copolymer from 50 to 30 mg/L to ensure the same oil removal efficiency. The
Al2(SO4)3 aids also acts synergistically with the synthesized copolymer to treat oily wastewaters.
Why it is relevant
However, some points should be revised to suit the manuscript to the high CEJ standards.

1. It would be probably desirable to give a chemical structure or a scheme of the copolymer synthesis, if it is new. <>
2. Unfortunately the authors do not give us an idea about such important characteristic of polymer flocculating agent as molar mass,
only intrinsic viscosity is cited. Probably it was measured in water, but could you kindly precise this point.
3. The conditions of TEM experiments and the sample preparation should be described to understand the results.
4. The interpretation of TEM analysis is unclear. What are "particles" (Page 9, line 13 - fig.3(a))? <.>
Specifics
5. There is a contradiction on page 6 (lines 6 -17). <>
6. It is questionable to discuss a maximum in Fig.5. <.>
7. The experimental error of oil removal efficiency measurements is a separate question <.>
8.
9.
In connection with the mentioned above, it is surprising that when discussing < .>
The instrument for TGA measurements is not described.
Quality of report?
10. To my opinion, the word combination "synergistically added <.>.
11. Page 3, lines 4-9. The sentence is too difficult to understand. Kindly revise it to divide in several simple sentences.
12. There are some typing errors in the text. For example:
* Page 6, line 14. Probably instead of "power" it should be written "powder".
* page 9, line 4. Probably "images" should be writted instead of "image".
* Page 3, line 13. probably the authors meant the word "below" instead of "bellow".

The reviewed paper can be published after a revision.

Ultimate decision by editor
Major revision
After the revision was sent back, the article was
accepted

Dear Editors,
Our revised manuscript and the responses to the comments from the
reviewers have been submitted on line. Thank you very much for your
strong support and great help. I am also grateful to the reviewers for their
constructive comments and suggestions that definitely improved the
presentation of the material. We have read all the comments carefully and
revised the manuscript accordingly. If you have any questions, please write
me at the above address.

Thank you again and look forward to hearing from you.

Sincerely,
The published article
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Thank you!

Questions?

Carl Schwarz
c.schwarz@elsevier.com

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