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I remove some descriptions about hydrothermal environments from Abstract and Conclusions.
| 2 | 1 |
If so, can RNA control the growth and division of the membrane?
| null | null |
life6030029_makarova
| 0 |
This comment is in relation to the thrid comment by reviewer 1. But, reviewer 1 agrees this part. So, I shorten this part.
| 2 | 1 |
There may be a link from one gene to one protein, but one protein is not really a phenotype.
| null | null |
life6030029_makarova
| 0 |
I remove the reference 11 from this part, and moved to line 108. I changed “soft molecules” to “organic molecules”, and changed to “formation and degradation”. The statement was changed to a sentence “… to focus …” shown in line 227.
| 2 | 1 |
line 73 - the point is made that current RNA World theories do not seem compatible with a hydrothermal origin of life.
| null | null |
life6030029_makarova
| 0 |
8. This is related to the comments about Fig. I added ref 74, 75. In addition, for the size of ribozyme, I added description at line 565 – 566 and ref 67 – 69.
| 2 | 1 |
There are many quantitative traits affected by many genes.
| null | null |
life6030029_makarova
| 0 |
I added a description at line 38 – 39.
| 2 | 1 |
This links to the introductory section about hydrothermal conditions etc.
| null | null |
life6030029_perova
| 0 |
I added a description at line 73 – 74.
| 2 | 1 |
However, I find the manuscript contains a number of weaknesses: One of the main issues is that paper suffers from trying to cover too many ideas, and because of this is quite long and unfocused.
| null | null |
life6030029_perova
| 0 |
This comment is in relation to the first comment by reviewer 2. Thus, I added description in lines 99 – 101 and 111 – 112. And I shorten this part to appreciate the comment by reviewer 2.
| 2 | 1 |
The idea in caption to Fig 4 that building blocks do not interact directly with the environment seems interesting and plausible, but not very well defined.
| null | null |
life6030029_perova
| 0 |
Actually, the comparison was made for cell-based life-like systems. So, I removed 2 references regarding civilization from this part, and add words at line 243 and 276 – 277. And, I simplify descriptions as shown in line 272.
| 2 | 1 |
However, I find the manuscript contains a number of weaknesses: One of the main issues is that paper suffers from trying to cover too many ideas, and because of this is quite long and unfocused.
| null | null |
life6030029_perova
| 0 |
This part is important. While it was difficult to simplify, but I tried to simplify section 2.3 as possible and added some descriptions.
| 2 | 1 |
I think there is some room for improvement in this diagram.
| null | null |
life6030029_perova
| 0 |
It is not essential that the whole circular network to be incorporated in a life-like system. A part of the network is accelerate by a newly evolved ribozyme is important. I tried to describe this, but it seems not sufficient. So I added carefully descriptions at lines 455 – 457, 466 – 471, 483 – 48
| 2 | 1 |
Statements such as in line 232: "the first step is to limit the characteristics of life-like systems into life on Earth" leave one scratching ones head.
| null | null |
life6030029_perova
| 0 |
I added a description at lines 538 – 540.
| 2 | 1 |
Fig 5 - drawing parallels between systems of different levels of complexity (from prokaryotes up to civilizations) is interesting, but it is a bit distracting at this point.
| null | null |
life6030029_perova
| 0 |
As I mentioned above, I added carefully descriptions at lines 455 – 457, 466 – 471, 483 – 488.
| 2 | 1 |
The input and output would not necessarily need to be controlled by another gene.
| null | null |
life6030029_perova
| 0 |
Formation of membrane is very important as reviewer 1 mentioned. I added a description at lines 542 – 544, 483 – 488, 544 – 548. line 554 - The case that two genes were essential initially is not made.
| 2 | 1 |
Fig 5 - drawing parallels between systems of different levels of complexity (from prokaryotes up to civilizations) is interesting, but it is a bit distracting at this point.
| null | null |
life6030029_perova
| 0 |
Polymerase can only amplify the population of RNA molecules. So, the population of RNA molecules would become of a population consisting of most rapid molecules for replication and then further evolution will struggle. Thus, connection of CCSI with CMIO is essential process to escape from such a non-living state.
| 2 | 1 |
There are a number of interesting points raised along the way, such as the generally one-to-one correspondence between DNA gene -> mRNA transcript -> protein enzyme -> single reaction (although many enzymes are often involved in a single pathway which transforms/produces a single substrate/product).
| null | null |
life6030029_perova
| 0 |
As I agree the reviewer 1, this is important point. And it should be evaluate to identify what process was accelerated at the beginning.
| 2 | 1 |
In summary, I think there are a lot of interesting points here, but the article could use some streamlining to emphasize the key new ideas.
| null | null |
life6030029_perova
| 0 |
I remove some descriptions about hydrothermal environments from Abstract and Conclusions.
| 2 | 1 |
Fig 8 is very reminiscent of Fig 1 of Wu and Higgs (2009) J Mol Evol 69:541-554 and Fig 1 of Wu and Higgs (2011) Astrobiology 11:895-906.
| null | null |
life6030029_perova
| 0 |
This comment is in relation to the thrid comment by reviewer 1. But, reviewer 1 agrees this part. So, I shorten this part.
| 2 | 1 |
There are a number of interesting points raised along the way, such as the generally one-to-one correspondence between DNA gene -> mRNA transcript -> protein enzyme -> single reaction (although many enzymes are often involved in a single pathway which transforms/produces a single substrate/product).
| null | null |
life6030029_perova
| 0 |
I remove the reference 11 from this part, and moved to line 108. I changed “soft molecules” to “organic molecules”, and changed to “formation and degradation”. The statement was changed to a sentence “… to focus …” shown in line 227.
| 2 | 1 |
This section seems to mix up two important questions.
| null | null |
life6030029_perova
| 0 |
8. This is related to the comments about Fig. I added ref 74, 75. In addition, for the size of ribozyme, I added description at line 565 – 566 and ref 67 – 69.
| 2 | 1 |
The input and output would not necessarily need to be controlled by another gene.
| null | null |
life6030029_perova
| 0 |
To the best of our knowledge, rare earth doped yttrium iron garnet is still the main material used for magneto-optical devices. They include bismuth doped YIG, bismuth, terbium doped YIG and cerium doped YIG. Other materials such as Wely semimatels are still under theoretical study[1]. We have added comments to these materials in the manuscript. Revisions: Page 1, line 21, added “At present, rare earth doped yttrium iron garnet (RIG) is the most widely used magneto-optical material in integrated MO devices.” Point 2:
| 2 | 1 |
By replacing Y3+ ions with Dy3+ ions in Ce:YIG, authors demonstrate less than ±5% variation of the thin film Faraday rotation from the temperature of 25 ℃ to 70 ℃, compared to ~20% in Ce:YIG.
| null | null |
ma15051691_makarova
| 0 |
Absoultly there is also temperature dependence of the Faraday rotation when shift to other wavelengths. However, the transparency window of this material is in the 1550 nm wavelength range. When moving to shorter wavelengths, the absorption of this material increases sharply, making them less practical for photonic device applications.
| 2 | 1 |
demonstrate a temperature stable magneto-optical material Dy2Ce1Fe5O12 for silicon integrated nonreciprocal photonic device applications.
| null | null |
ma15051691_makarova
| 0 |
previously reported that the compensation temperature of DyIG is Tcomp = 225 K [2,3], which could decrease the Faraday rotation angle of Dy:CeIG in this work at the temperature below 300 K. Therefore, a higher Faraday rotation may be related to the increase of the saturation magnetization of this material in this temperature range. Revisions:Page 5, line 170-173, added “The increase of the Faraday rotation below 40 ℃ is possibly due to the increase of the magnetization of this material at this temperature range, considering a compensation temperature of 225 K in Dy3Fe5O12 [19,20].”. References: Okamura, Y.; Minami, S.; Kato, Y.; Fujishiro, Y.; Kaneko, Y.; Ikeda, J.; Muramoto, J.; Kaneko, R.; Ueda, K.; Kocsis, V.; et al. Giant magneto-optical responses in magnetic Weyl semimetal Co3Sn2S2. Nat Commun 2020, 11, 4619, doi:10.1038/s41467-020-18470-0. Sayetat, F. Huge magnetostriction in Tb3Fe5O12, Dy3Fe5O12, Ho3Fe5O12, Er3Fe5O12 garnets. Journal of magnetism and magnetic materials 1986, 58, 334-346.
| 2 | 1 |
This manuscript relates to the effect of dysprosium substitution in Ce:YIG thin films and in particular to the temperature dependance of their Faraday rotation.
| null | null |
ma15051691_makarova
| 0 |
We have updated the references and revised this in the context. Revisions: Page 1, line 21, revised to “for silicon integrated photonic circuits (PICs) [1-3].”. Page 1, line 24, revised to “including optical isolators [4-6]”. Page 1, line 41, revised to “which results in reduced bandwidth and isolation ratio [13].”. Page 1, line 45, revised to “in a temperature range of 20-60 ℃ [10].”. Page 5, line 148, revised to “measure the temperature stability of Dy:CeIG and Ce:YIG films[11].”.
| 2 | 1 |
Author Response Reviewer #1 (Comments to the Author): The article "Dysprosium substituted Ce:YIG thin films for temperature in-2 sensitive integrated optical isolator applications contains the results" presents a temperature stable magneto-optical material Dy2Ce1Fe5O12 for silicon integrated nonreciprocal photonic device applications.
| null | null |
ma15051691_makarova
| 0 |
We have revised this in the context. Revisions: Page 3, line 98, revised to “where is the Faraday rotation angle of MO films at room temperature. is the NRPS at room temperature.” Point 3:
| 2 | 1 |
Ostorero, J.; Escorne, M.; Pecheron‐Guegan, A.; Soulette, F.; Le Gall, H. Dy3Fe5O12 garnet thin films grown from sputtering of metallic targets.
| null | null |
ma15051691_makarova
| 0 |
Thanks for correcting this. “X-ray diffraction spectra” has been revised into “X-ray diffraction patterns”. Revisions: Page 3, line 109, revised to “X-ray diffraction patterns”.
| 2 | 1 |
Author Response Reviewer #1 (Comments to the Author): The article "Dysprosium substituted Ce:YIG thin films for temperature in-2 sensitive integrated optical isolator applications contains the results" presents a temperature stable magneto-optical material Dy2Ce1Fe5O12 for silicon integrated nonreciprocal photonic device applications.
| null | null |
ma15051691_makarova
| 0 |
Thanks for the commerts. The saturation magnetization of rare-earth doped YIG affects the Faraday rotation angle. Sayetat et al. and Ostorero et al. previously reported that the compensation temperature of DyIG is Tcomp = 225 K [1,2], which could decrease the Faraday rotation angle of Dy:CeIG in this work at the temperature below 300 K. Therefore, a higher Faraday rotation may be related to the increase of the saturation magnetization of this material in this temperature range. Revisions: Page 5, line 170-173, added “The increase of the Faraday rotation below 40 ℃ is possibly due to the increase of the magnetization of this material at this temperature range, considering a compensation temperature of 225 K in Dy3Fe5O12 [19,20].”.
| 2 | 1 |
It is in general well written and the work deserves publication.
| null | null |
ma15051691_makarova
| 0 |
Ostorero, J.; Escorne, M.; Pecheron‐Guegan, A.; Soulette, F.; Le Gall, H. Dy3Fe5O12 garnet thin films grown from sputtering of metallic targets. Journal of Applied Physics 1994, 75, 6103-6105. Thanks for pointing this out. We have revised the Figure 3. Revisions: Page 6, revised the horizontal scale of Figure 3 (c) and updated Figure 3 (c). References: Sayetat, F. Huge magnetostriction in Tb3Fe5O12, Dy3Fe5O12, Ho3Fe5O12, Er3Fe5O12 Journal of magnetism and magnetic materials 1986, 58, 334-346.
| 2 | 1 |
We answer the reviewer’s questions as follows.
| null | null |
ma15051691_makarova
| 0 |
Wide Angle X-ray Scattering (WAXS) and Small Angle X-ray Scattering (SAXS) obey the same Bragg's Law (2dsinθ=nλ), but with different distance from sample to detector. With a distance about 384 mm in this work, the WAXS can measure the structure from 0.12 nm to 0.45 nm, which correspond to the crystal lattice, while SAXS can measure the structure from 10 nm to 80 nm, with a distance of 2484 mm. In a SAXS curve, the strength reflect the number of defects, while the q range reflect the size of the defects.
| 2 | 1 |
), we described in detail how to calculate the specific surface area and volume fraction.
| null | null |
ma15124258_makarova
| 0 |
Thanks for your question, we looked up several literature and couldn't find a fixed usage of cracks and voids, and in this article, we think that using pores would completely cover our research objectives, so we deleted the cracks in this paper. Computed microtomography is usually used to confirm the voids in micron-scale but this paper focuses on nano-scale voids.
| 2 | 1 |
Do you have another proof for your conclusions.
| null | null |
ma15124258_makarova
| 0 |
Yes, the pores are assumed to be spherical in the fitting of SAXS data, because the spherical model is the simplest and widely used model in the SAXS fitting. The voids are cylindrical that is close to a spherical, so we can get a relatively accurate size distribution by assuming to spherical.
| 2 | 1 |
The manuscript is devoted to research on the phase transformations of CL-20 at various temperatures.
| null | null |
ma15124258_makarova
| 0 |
Yes, we had an experiment of differential scanning calorimetry (DSC) to characterize the process, as shown in Figure 1. According to the result from DSC, there were an endothermic peak of phase transformation between the temperature range of 151~172 ℃, which are not exactly consistent with the results from in this paper. We think the difference in temperature is result from the different sample amount and heating rate. As with X-ray diffraction (XRD), the WAXS can be used to characterize the content of different phase in the phase transformation. So, we think the results in our paper is reasonable.
| 2 | 1 |
Could you use X-ray microtomography on your samples?
| null | null |
ma15124258_makarova
| 0 |
SAXS can be used to measure the defect size and number of defects with rational theory and adequate validation in many
| 2 | 1 |
Some changes in propagation of pores caused by both the phase transitions and temperature were observed by an appropriate experimental technique.
| null | null |
ma15124258_makarova
| 0 |
The colors in figure 1 and 3 represent the strength of scattering, while the colors in other figures just represent different date.
| 2 | 1 |
As you can tell by these questions, my main issue is related to the specific form of the thermal damage.
| null | null |
ma15124258_makarova
| 0 |
The result of SAXS is a reflection of two-phase with different electron density. In our paper, the CL-20 powders are immersed in GPL107 with a approximately equal electron density with CL-20 crystals, so the SAXS reflects the nano-scale pores inside CL-20 powders. Thereby, the increase of strength in SAXS curve reflects the increase in number of internal nano-scale pores. According to the principle of SAXS, the scale of defects is correlated with the q range, so the growth into larger defects will appear in other q range. X-ray microtomography is usually used to confirm the voids in micron-scale but this paper focuses on nano-scale voids.
| 2 | 1 |
It indeed the case, but I could not find any discussion on this issue.
| null | null |
ma15124258_makarova
| 0 |
The GPL107 is resistant to high temperatures about 400 ℃, and we used the SAXS patterns of GPL107 at different temperature as the background to correct any bias at different temperature.
| 2 | 1 |
199-198 “The specific surface area and volume fraction of pores are calculated, and the results are shown in figure 7.” From the text of the manuscript it is not clear what method was used to obtain the calculated data on the specific surface area and volume fraction of pores.
| null | null |
ma15124258_makarova
| 0 |
According to the principle of SAXS, the scale of defects is correlated with the q range, so the increase in scattering intensity in lager q range can be explained into the increase in more small voids. And also, our fitting result can provide more obvious display.
| 2 | 1 |
Thus, I can recommend it for publication after a minor revision.
| null | null |
ma15124258_makarova
| 0 |
In our paper, spherical model was just a choice in the SAXS date fitting, so we did not provide more illustrate, but a reference (L A Feigin and D I Svergun, Structure Analysis by Small-Angle X-Ray and Neutron Scattering, Plenum Press, New York, 1987) was provide in the manuscript. On line 173, we gave a conclusion “the number of pores increased, but the size distribution did not change.” We did not consider the pore volume, but we can deduce that the pores volume increase as the increase of the number of pores.
| 2 | 1 |
Can you explain why an increase in scattering intensity indicates increase in more small voids rather than an increase in existing void sizes?
| null | null |
ma15124258_makarova
| 0 |
Thanks again for your attention, According to the principle of SAXS, the scale of defects is correlated with the q range, so the increase in scattering intensity without the change of q range can be explained into the number of pores increasing, while the existing pores increasing in volume would result into an change of q to low range.
| 2 | 1 |
Review of the manuscript Investigation on the Evolution of Nano-scale Defects of CL-20 Crystals under Thermal Treatment by Wide/Small-Angle X-ray Scattering, Haobin Zhang, Hongfan Wang … The manuscript is devoted to research on the phase transformations of CL-20 at various temperatures.
| null | null |
ma15124258_makarova
| 0 |
Thanks for your comments, we added three reference about recent work published in 2021 and 2022.
| 2 | 1 |
Could computed microtomography be used to confirm some of the experimental results?
| null | null |
ma15124258_makarova
| 0 |
Thanks for you comment, I have supplemented with a forecast about the change in the performance of the CL-20 in terms of safety after thermal treatment in the conclusion.
| 2 | 1 |
199-198 “The specific surface area and volume fraction of pores are calculated, and the results are shown in figure 7.”From the text of the manuscript it is not clear what method was used to obtain the calculated data on the specific surface area and volume fraction of pores.
| null | null |
ma15124258_makarova
| 0 |
Thanks for you comments, and I have added the particle size in the manuscript.
| 2 | 1 |
Is the temperature high enough to cause decomposition effects?
| null | null |
ma15124258_makarova
| 0 |
The electron density of CL-20 and GPL107 are calculated according to the classical electron radius ( with a size of 2.818 E-13 cm) and the electron number per volume, the detailed information can refer to our previous work (Molecules 2020, 25 , 443.)
| 2 | 1 |
Every available suggestion has been answered carefully and corrected in the article.
| null | null |
ma15124258_makarova
| 0 |
In our previous work (Molecules 2020, 25, 443. ), we described in detail how to calculate the specific surface area and volume fraction. In this paper, the same method was used to calculate the specific surface area and volume fraction, so we did not repeat how to calculator, just added the reference in the manuscript.
| 2 | 1 |
Some changes in propagation of pores caused by both the phase transitions and temperature were observed by an appropriate experimental technique.
| null | null |
ma15124258_makarova
| 0 |
“During the thermal treatment, the nano-scale pores increase obviously, which will seriously increase the sensitivity of CL-20, and make a dangerous to the explosive charges with CL-20. To improve the application performance of CL-20, we should try to avoid the increase of such defects, such as storing in an constant low temperature to avoid the thermal expansion, and avoid any phase transition.” We have supplemented with a forecast about the change in the performance of the CL-20 in terms of safety and suitability for use after thermal treatment in the conclusion.
| 2 | 1 |
Could you use X-ray microtomography on your samples?
| null | null |
ma15124258_makarova
| 0 |
Wide Angle X-ray Scattering (WAXS) and Small Angle X-ray Scattering (SAXS) obey the same Bragg's Law (2dsinθ=nλ), but with different distance from sample to detector. With a distance about 384 mm in this work, the WAXS can measure the structure from 0.12 nm to 0.45 nm, which correspond to the crystal lattice, while SAXS can measure the structure from 10 nm to 80 nm, with a distance of 2484 mm. In a SAXS curve, the strength reflect the number of defects, while the q range reflect the size of the defects.
| 2 | 1 |
Response to Reviewer' Comments Dear Reviewer, We sincerely appreciate your comments and suggestions on the manuscript!
| null | null |
ma15124258_perova
| 0 |
Thanks for your question, we looked up several literature and couldn't find a fixed usage of cracks and voids, and in this article, we think that using pores would completely cover our research objectives, so we deleted the cracks in this paper. Computed microtomography is usually used to confirm the voids in micron-scale but this paper focuses on nano-scale voids.
| 2 | 1 |
Response: In our previous work (Molecules 2020, 25, 443.
| null | null |
ma15124258_perova
| 0 |
Yes, the pores are assumed to be spherical in the fitting of SAXS data, because the spherical model is the simplest and widely used model in the SAXS fitting. The voids are cylindrical that is close to a spherical, so we can get a relatively accurate size distribution by assuming to spherical.
| 2 | 1 |
“During the thermal treatment, the nano-scale pores increase obviously, which will seriously increase the sensitivity of CL-20, and make a dangerous to the explosive charges with CL-20.
| null | null |
ma15124258_perova
| 0 |
Yes, we had an experiment of differential scanning calorimetry (DSC) to characterize the process, as shown in Figure 1. According to the result from DSC, there were an endothermic peak of phase transformation between the temperature range of 151~172 ℃, which are not exactly consistent with the results from in this paper. We think the difference in temperature is result from the different sample amount and heating rate. As with X-ray diffraction (XRD), the WAXS can be used to characterize the content of different phase in the phase transformation. So, we think the results in our paper is reasonable.
| 2 | 1 |
Materials and instruments, you need to specify the particle size of the initial CL-20 powders.
| null | null |
ma15124258_perova
| 0 |
SAXS can be used to measure the defect size and number of defects with rational theory and adequate validation in many field.
| 2 | 1 |
Materials and instruments, you need to specify the particle size of the initial CL-20 powders.
| null | null |
ma15124258_perova
| 0 |
The colors in figure 1 and 3 represent the strength of scattering, while the colors in other figures just represent different date.
| 2 | 1 |
It indeed the case, but I could not find any discussion on this issue.
| null | null |
ma15124258_perova
| 0 |
The result of SAXS is a reflection of two-phase with different electron density. In our paper, the CL-20 powders are immersed in GPL107 with a approximately equal electron density with CL-20 crystals, so the SAXS reflects the nano-scale pores inside CL-20 powders. Thereby, the increase of strength in SAXS curve reflects the increase in number of internal nano-scale pores. According to the principle of SAXS, the scale of defects is correlated with the q range, so the growth into larger defects will appear in other q range. X-ray microtomography is usually used to confirm the voids in micron-scale but this paper focuses on nano-scale voids.
| 2 | 1 |
The nano-scale defects were studied by using Wide Angle X-ray Scattering (WAXS) and Small Angle X-ray Scattering (SAXS), during the temperature range from 30 °C to 200 °C .
| null | null |
ma15124258_perova
| 0 |
The GPL107 is resistant to high temperatures about 400 ℃, and we used the SAXS patterns of GPL107 at different temperature as the background to correct any bias at different temperature.
| 2 | 1 |
I recommend publishing the manuscript after minor the revision.
| null | null |
ma15124258_perova
| 0 |
According to the principle of SAXS, the scale of defects is correlated with the q range, so the increase in scattering intensity in lager q range can be explained into the increase in more small voids. And also, our fitting result can provide more obvious display.
| 2 | 1 |
How do you results compare to phase transformation measured using DSC?
| null | null |
ma15124258_perova
| 0 |
In our paper, spherical model was just a choice in the SAXS date fitting, so we did not provide more illustrate, but a reference (L A Feigin and D I Svergun, Structure Analysis by Small-Angle X-Ray and Neutron Scattering, Plenum Press, New York, 1987) was provide in the manuscript. On line 173, we gave a conclusion “the number of pores increased, but the size distribution did not change.” We did not consider the pore volume, but we can deduce that the pores volume increase as the increase of the number of pores.
| 2 | 1 |
), we described in detail how to calculate the specific surface area and volume fraction.
| null | null |
ma15124258_perova
| 0 |
Thanks again for your attention, According to the principle of SAXS, the scale of defects is correlated with the q range, so the increase in scattering intensity without the change of q range can be explained into the number of pores increasing, while the existing pores increasing in volume would result into an change of q to low range.
| 2 | 1 |
How do you results compare to phase transformation measured using DSC?
| null | null |
ma15124258_perova
| 0 |
Thanks for your comments, we added three reference about recent work published in 2021 and 2022.
| 2 | 1 |
Materials and instruments, you need to specify the particle size of the initial CL-20 powders.
| null | null |
ma15124258_perova
| 0 |
Thanks for you comment, I have supplemented with a forecast about the change in the performance of the CL-20 in terms of safety after thermal treatment in the conclusion.
| 2 | 1 |
To improve the application performance of CL-20, we should try to avoid the increase of such defects, such as storing in an constant low temperature to avoid the thermal expansion, and avoid any phase transition.”
| null | null |
ma15124258_perova
| 0 |
Thanks for you comments, and I have added the particle size in the manuscript.
| 2 | 1 |
Review of the manuscript Investigation on the Evolution of Nano-scale Defects of CL-20 Crystals under Thermal Treatment by Wide/Small-Angle X-ray Scattering, Haobin Zhang, Hongfan Wang … The manuscript is devoted to research on the phase transformations of CL-20 at various temperatures.
| null | null |
ma15124258_perova
| 0 |
The electron density of CL-20 and GPL107 are calculated according to the classical electron radius ( with a size of 2.818 E-13 cm) and the electron number per volume, the detailed information can refer to our previous work (Molecules 2020, 25 , 443.)
| 2 | 1 |
Every available suggestion has been answered carefully and corrected in the article.
| null | null |
ma15124258_perova
| 0 |
In our previous work (Molecules 2020, 25, 443. ), we described in detail how to calculate the specific surface area and volume fraction. In this paper, the same method was used to calculate the specific surface area and volume fraction, so we did not repeat how to calculator, just added the reference in the manuscript.
| 2 | 1 |
Every available suggestion has been answered carefully and corrected in the article.
| null | null |
ma15124258_perova
| 0 |
We have supplemented with a forecast about the change in the performance of the CL-20 in terms of safety and suitability for use after thermal treatment in the conclusion. “During the thermal treatment, the nano-scale pores increase obviously, which will seriously increase the sensitivity of CL-20, and make a dangerous to the explosive charges with CL-20. To improve the application performance of CL-20, we should try to avoid the increase of such defects, such as storing in an constant low temperature to avoid the thermal expansion, and avoid any phase transition.”
| 2 | 1 |
Do you have another proof for your conclusions.
| null | null |
ma15124258_perova
| 0 |
There was a question related to electronic devices (eCigarettes) but we missed to add this data. Only 0.5% of participants used eCigaretes or similar devices. We added this sentence in the section Results.
| 2 | 1 |
Please provide a conclusion based on obtained findings and please avoid overwhelming conclusions Response 8.
| null | null |
medicina58040502_makarova
| 0 |
It has been showed that higher exposure to secondhand smoking increased the risk of smoking. The multivariable logistic regression analysis showed that variables such as secondhand smoke at home, secondhand smoke at faculty, and secondhand smoke at public spaces can determine whether students smoke or not. It is also obvious that non-smokers avoid being in closed smoking places, but this was not subject of this study.
| 2 | 1 |
This is contrary to accepted public health policy internationally.
| null | null |
medicina58040502_makarova
| 0 |
Your comment is very logical. Cigarette smoking, sedentary life-style and obesity are the major public health concerns, particularly in the Balkan region. This was a reason that we have provided some additional comments and recommendations for further actions at the very end of the Discussion section.
| 2 | 1 |
Tables 6 and 7 are unclear and should be more precise (Especially confidence intervals) Response 6.
| null | null |
medicina58040502_makarova
| 0 |
The “Aim of the study” has been changed completely.
| 2 | 1 |
This is a well-designed and executed survey of university cigarette smoking in a country with above-average poverty.
| null | null |
medicina58040502_makarova
| 0 |
To reply on this comment and to provide readers with more precise data we made some changes in two sections. In the subsection “Sample size” of the section “Materials and methods” we emphasized that “students from 16 faculties of the University of Banja Luka were participants in our study”. In section “Results” we have added a new sentence that “Majority of study participants were medical students (41.4%) and the rest were students from other faculties (58.6%).” Comment 3.
| 2 | 1 |
Medicina 2021, 57, x. https://doi.org/10.3390/xxxxx Academic Editor: Firstname Lastname Received: date Accepted: date Published: date Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.
| null | null |
medicina58040502_makarova
| 0 |
This has been already presented in Table 2. and explained by asterisks (**) below the table: * Students who smoked at least one day in 30 days prior to the survey. ** Students who smoke every day and desired to smoke always or sometimes upon waking up, and where smoking time after waking up was within one day. If necessary the English version of the Questionnaire could be provided as Supplementary material.
| 2 | 1 |
In Table 5 please provide thr number of subjects (n=.....) Response 5.
| null | null |
medicina58040502_makarova
| 0 |
We have made some changes in the section “Results” to avoid data duplication.
| 2 | 1 |
In Table 5 please provide thr number of subjects (n=.....) Response 5.
| null | null |
medicina58040502_makarova
| 0 |
The number of subjects (N) has been added.
| 2 | 1 |
Response to Reviewer 2 I would like to thank Reviewer 2 for very detailed and useful comments which will definitely improve our manuscript.
| null | null |
medicina58040502_makarova
| 0 |
The contents of Table 6 and Table 7 have been rearranged and comprised into one table which is now Table 6.
| 2 | 1 |
Is the omission of any items referring to experience/use of eCigarette/vaping.
| null | null |
medicina58040502_makarova
| 0 |
In the last paragraph of the section “Discussion” we have proposed some practical implications and recommendations for further actions.
| 2 | 1 |
In Table 5 please provide thr number of subjects (n=.....) Response 5.
| null | null |
medicina58040502_makarova
| 0 |
The section “Conclusion” has been completely revised and rearranged according to the reviewer’s comment.
| 2 | 1 |
Healthcare providers who smoke provide a bad example to their patients - giving the impression that smoking is not dangerous.
| null | null |
medicina58040502_makarova
| 0 |
There was a question related to electronic devices (eCigarettes) but we missed to add this data. Only 0.5% of participants used eCigaretes or similar devices. We added this sentence in the section Results.
| 2 | 1 |
Is the omission of any items referring to experience/use of eCigarette/vaping.
| null | null |
medicina58040502_perova
| 0 |
It has been showed that higher exposure to secondhand smoking increased the risk of smoking. The multivariable logistic regression analysis showed that variables such as secondhand smoke at home, secondhand smoke at faculty, and secondhand smoke at public spaces can determine whether students smoke or not. It is also obvious that non-smokers avoid being in closed smoking places, but this was not subject of this study.
| 2 | 1 |
Thus it is unclear if students may be nicotine addicting by alternative means to tobacco smoking.
| null | null |
medicina58040502_perova
| 0 |
Your comment is very logical. Cigarette smoking, sedentary life-style and obesity are the major public health concerns, particularly in the Balkan region. This was a reason that we have provided some additional comments and recommendations for further actions at the very end of the Discussion section.
| 2 | 1 |
Please provide the most important results in the text, and the rest of them are present in Tables.
| null | null |
medicina58040502_perova
| 0 |
The “Aim of the study” has been changed completely.
| 2 | 1 |
Results were consistent with previous studies of similar target populations.
| null | null |
medicina58040502_perova
| 0 |
To reply on this comment and to provide readers with more precise data we made some changes in two sections. In the subsection “Sample size” of the section “Materials and methods” we emphasized that “students from 16 faculties of the University of Banja Luka were participants in our study”. In section “Results” we have added a new sentence that “Majority of study participants were medical students (41.4%) and the rest were students from other faculties (58.6%).” Comment 3.
| 2 | 1 |
Response to Reviewer 1 I would like to thank Reviewer 1 for very detailed and useful comments which will definitely improve our manuscript.
| null | null |
medicina58040502_perova
| 0 |
Response 3. This has been already presented in Table 2. and explained by asterisks (**) below the table: * Students who smoked at least one day in 30 days prior to the survey. ** Students who smoke every day and desired to smoke always or sometimes upon waking up, and where smoking time after waking up was within one day. If necessary the English version of the Questionnaire could be provided as Supplementary material.
| 2 | 1 |
Response to Reviewer 1 I would like to thank Reviewer 1 for very detailed and useful comments which will definitely improve our manuscript.
| null | null |
medicina58040502_perova
| 0 |
We have made some changes in the section “Results” to avoid data duplication.
| 2 | 1 |
Healthcare providers who smoke provide a bad example to their patients - giving the impression that smoking is not dangerous.
| null | null |
medicina58040502_perova
| 0 |
The number of subjects (N) has been added.
| 2 | 1 |
Is the omission of any items referring to experience/use of eCigarette/vaping.
| null | null |
medicina58040502_perova
| 0 |
The contents of Table 6 and Table 7 have been rearranged and comprised into one table which is now Table 6.
| 2 | 1 |
Results were consistent with previous studies of similar target populations.
| null | null |
medicina58040502_perova
| 0 |
In the last paragraph of the section “Discussion” we have proposed some practical implications and recommendations for further actions.
| 2 | 1 |
This is the opposite of health promotion one expects from all healthcare providers - especially physicians.
| null | null |
medicina58040502_perova
| 0 |
The section “Conclusion” has been completely revised and rearranged according to the reviewer’s comment.
| 2 | 1 |
Recommendations did not go beyond the data and human subjects protections were adequate.
| null | null |
medicina58040502_perova
| 0 |
thank you for reviewer’s comments, we made changes accordingly. We added statistical analysis for CNA association between case and reference groups (please see page 5).
| 2 | 1 |
The authors claim that they observed statistical differences between case and reference groups yet they do not preform a statistical test, nor give any p-value.
| null | null |
medsci4030012_makarova
| 0 |
For the questions of “is the deletion burden observed really exceptional in a population sample of similar ancestry”, we agree with the reviewer’s comment. We did the analysis a couple of years ago, at that time, there is no CNV data from the 1000 genome for Mexicans, Colombians, Puerto Ricans and Peruvians, however, there is data for the admixed populations, thus we used this for this study. There might be some difficulty to do more analysis since our statistician and bioinformatics person left the department and we are in the process of hiring somebody for this role. At the same, we continue in recruiting more subjects with cervical cancers to further confirm our findings. Moreover, in the discussion, we have list this as one of the limitations in page 8 “2) there might be bias of the CNA identified in cervical cancer for the Mexican Americans since we used the 1000 Genome admixed populations, not Mexican Americans, thus, we current recruit more subjects with cervical cancer from the same population and plan to validate the findings in more samples;” 2)
| 2 | 1 |
It is not clear which statistical method is used for the significant results in Table 2.
| null | null |
medsci4030012_makarova
| 0 |
For the question of “is the deletion burden observed similar to those for other cancers? Then again there must be estimates of deletion burden for different types of cancers from TCGA studies”, our response is that we did search of CNAs observed in other cancer based on TCGA studies, although there are limited studies, we addressed this issue in the discussion section (page 8) “…Using the TCGA data, a recent study identified nine regions of deletion that were unique to ER+ post menopause tumors in patients with breast cancer, including deletion in 7p22.3 where our newly identified deletion in cases only located and it contains known tumor suppressor gene”.
| 2 | 1 |
I think that these finding are indeed intriguing and deserve to be pursued in a larger study.
| null | null |
medsci4030012_makarova
| 0 |
great suggestions, thank the reviewer. Now we added a sentence of “Moreover, the pathway analysis revealed endometrial cancer and estrogen signaling pathways associated with this cancer (P < 0.05) using the KEGG” in the abstract as the reviewer’s suggestion. In addition, in the introduction section, we added “We are aware of the limited number of cases and lack of control group. Thus future a large study with a control sample and more cases as methodological alternative is needed”. (Please see page 3) Minor comments: 1-
| 2 | 1 |
Therefore, the authors pointed out that validation and confirmation of the results in a large sample size will be needed in the future.
| null | null |
medsci4030012_makarova
| 0 |
as the reviewer’s suggestion, we changed “Latino” to “Mexican American” in the text of the manuscript and table
| 2 | 1 |
7) Lines 238-242 are replicated in discussion lines 376-380.
| null | null |
medsci4030012_makarova
| 0 |
now we change “Latino population” to “Mexican American” as the reviewer’s suggestion
| 2 | 1 |
The authors need to define “pre-cancer” in materials.
| null | null |
medsci4030012_makarova
| 0 |
thank you for the comments. We also realized this issue which is due to that the color green overlaps with the other colors, thus it cannot be distinguished, and we have tried different color combinations without help. Now we made changes of the figure and legend.
| 2 | 1 |
My suggestion is to offer a better background for these results by trying to answer two main questions: 1) is the deletion burden observed really exceptional in a population sample of similar ancestry?
| null | null |
medsci4030012_makarova
| 0 |
thanks, we removed the % sign in table cells in Table 2b
| 2 | 1 |
You can refer to it as methodological alternative, in the introduction, for the limited number of cases and lack of control group; issues that must be tackle in a larger study.
| null | null |
medsci4030012_makarova
| 0 |
thank you, reviewer, this is a typo, we corrected it.
| 2 | 1 |
It is not clear if there is one or two groups but just one percentage.
| null | null |
medsci4030012_makarova
| 0 |
yes, we added up to six key words now
| 2 | 1 |
However if the ancestry is only self reported as latino, then I would write latino in the title and mention the issue of genetic variability between latinos in the discussion.
| null | null |
medsci4030012_makarova
| 0 |
we made changes based on the reviewer’s suggestion, please see statistical method in page 5 and result in page 6
| 2 | 1 |
The ancestry of HapMap is not latino so therefore any test between cases and references will be confounded by ancestry.
| null | null |
medsci4030012_makarova
| 0 |
thanks, we provided definition for pre-cancer in materials, which include patients with CIN I, II, and III.
| 2 | 1 |
I think that these finding are indeed intriguing and deserve to be pursued in a larger study.
| null | null |
medsci4030012_makarova
| 0 |
thanks, we added “…using statistical analyses described in the method section”
| 2 | 1 |
It is not clear which statistical method is used for the significant results.
| null | null |
medsci4030012_makarova
| 0 |
thanks, the reviewer. Now we removed redundancy statement.
| 2 | 1 |
The PCA they show is probably capturing those differences instead of real differences given by disease status and, by the way, I question the usefulness of this PCA.
| null | null |
medsci4030012_makarova
| 0 |
thank you for reviewer’s comments, we made changes accordingly. We added statistical analysis for CNA association between case and reference groups (please see page 5).
| 2 | 1 |
My suggestion is to offer a better background for these results by trying to answer two main questions: 1) is the deletion burden observed really exceptional in a population sample of similar ancestry?
| null | null |
medsci4030012_perova
| 0 |
For the questions of “is the deletion burden observed really exceptional in a population sample of similar ancestry”, we agree with the reviewer’s comment. We did the analysis a couple of years ago, at that time, there is no CNV data from the 1000 genome for Mexicans, Colombians, Puerto Ricans and Peruvians, however, there is data for the admixed populations, thus we used this for this study. There might be some difficulty to do more analysis since our statistician and bioinformatics person left the department and we are in the process of hiring somebody for this role. At the same, we continue in recruiting more subjects with cervical cancers to further confirm our findings. Moreover, in the discussion, we have list this as one of the limitations in page 8 “2) there might be bias of the CNA identified in cervical cancer for the Mexican Americans since we used the 1000 Genome admixed populations, not Mexican Americans, thus, we current recruit more subjects with cervical cancer from the same population and plan to validate the findings in more samples;” 2)
| 2 | 1 |
Therefore, the authors pointed out that validation and confirmation of the results in a large sample size will be needed in the future.
| null | null |
medsci4030012_perova
| 0 |
For the question of “is the deletion burden observed similar to those for other cancers? Then again there must be estimates of deletion burden for different types of cancers from TCGA studies”, our response is that we did search of CNAs observed in other cancer based on TCGA studies, although there are limited studies, we addressed this issue in the discussion section (page 8) “…Using the TCGA data, a recent study identified nine regions of deletion that were unique to ER+ post menopause tumors in patients with breast cancer, including deletion in 7p22.3 where our newly identified deletion in cases only located and it contains known tumor suppressor gene”.
| 2 | 1 |
The experimental design is adequate and the statistical methods are updated.
| null | null |
medsci4030012_perova
| 0 |
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