TASK DEFINITION: In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
PROBLEM: Background: The HIV-1 RNA genome has a biased nucleotide composition with a surplus of As. Several hypotheses have been put forward to explain this striking phenomenon, but the A-count of the HIV-1 genome has thus far not been systematically manipulated. The reason for this reservation is the likelihood that known and unknown sequence motifs will be affected by such a massive mutational approach, thus resulting in replication-impaired virus mutants. We present the first attempt to increase and decrease the A-count in a relatively small polymerase (pol) gene segment of HIV-1 RNA. To minimize the mutational impact, a new mutational approach was developed that is inspired by natural sequence variation as present in HIV-1 isolates. This phylogeny-instructed mutagenesis allowed us to create replication-competent HIV-1 mutants with a significantly increased or decreased local A-count. The local A-count of the wild-type (wt) virus (40.2%) was further increased to 46.9% or reduced to 31.7 and 26.3%. These HIV-1 variants replicate efficiently in vitro, despite the fact that the pol changes cause a quite profound move in HIV-SIV sequence space. Extrapolating these results to the complete 9 kb RNA genome, we may cautiously suggest that the A-rich signature does not have to be maintained. This survey also provided clues that silent codon changes, in particular from G-to-A, determine the subtype-specific sequence signatures.

SOLUTION: HIV-1 tolerates changes in A-count in a small segment of the pol gene

PROBLEM: This paper attempts to understand optimal ventilation rates at the national level across 26 European countries and to contrast the benefits of optimizing ventilation with filtration of outdoor air pollution and control of indoor sources. This is an important topic given the key role of the housing sector in tackling both air pollution and climate change. Although the methods used are relatively simplistic, they are appropriate for analyses performed at the scale presented in the paper. The findings and conclusions are well supported by the results. I would therefore support publication. However, I believe the manuscript would benefit from a stronger statement of the aims of the work and some clarifications regarding the methods (see below). My main concern relates to the assumption made by the authors that indoor-generated PM2.5 is equally as harmful to health as outdoor-generated PM2.5. There is little evidence to support this (though it is quite a commonly made assumption). I would like to see some form of sensitivity analysis in relation to this assumption, since it may have an impact on the final results (though probably not on the ultimate conclusions). More detailed comments can be found below. I consider the suggested revisions to be relatively minor. 1. Is the question posed original, important and well defined? The research question posed by the paper is important and I believe the methods used are appropriate to answer it. However, the aims of the paper are not currently well stated (in both the main text and in the abstract). The main statement of the aims comes towards the end of page 5, which states "This work aims to summarize the current understanding of the sources of health risks in indoor environments and their relationship to ventilation requirements". This doesn't really capture what the authors have actually done. There is a slightly better statement of the aims hidden in the Methods (top of page 7) but even this doesn't quite feel sufficient. 2. Are the data sound and well controlled? Yes, although the source of some of the input data can be made clearer in the text, especially in relation to Table 2 (see below) . 3. Is the interpretation (discussion and conclusion) well balanced and supported by the data? Yes. 4. Are the methods appropriate and well described, and are sufficient details provided to allow others to evaluate and/or replicate the work? The methods are generally well described. However, I have a few specific issues (see the additional comments below). The methods are based on relatively simplistic tools (both the mass-balance exposure model and the risk/health impact model). However, I think they are appropriate for the type of analysis presented in the paper. My main concern relates to the assumption of equal health risk associated with both outdoor-and indoor-generated PM2.5. The authors discuss this briefly in the Discussion section but this assumption is highly uncertain since almost all of the published epidemiology is based on outdoor PM2.5. The paper would benefit from greater emphasis on the sensitivity of the results to this assumption. Perhaps, the analysis (or part of it) could be repeated without the effects of indoorgenerated PM2.5 or with a reduced exposure-response coefficient? 6. Can the writing, organization, tables and figures be improved? Although the manuscript is generally well written, there are reoccurring problems, most importantly missing articles throughout the paper (e.g. a, the). For instance, in the abstract, "Based on measurements of the European Environment Agency (EEA),…" and "A framework for developing European health-based ventilation guidelines…" would be preferable. I realise that English is not the authors' first language (and, again, I should stress that most of the language used is very good). However, I think the paper would benefit from a thorough edit by a native English speaker. Also, the figures appear to be quite pixelated and may not be in an appropriate format for publication. 7. When revisions are requested. No preference. 8. Are there any ethical or competing interests issues you would like to raise? None. • I believe the abstract would benefit from a little editing. At present, the Background section feels unnecessarily long and there isn't enough detail in either the Methods or Results sections. The methods used for the health impact calculations aren't mentioned at all, despite being key to the paper. At the moment, I don't feel the main results are clearly stated in the abstract. • The paper refers throughout to "optimization". I think a mathematician might object to the use of the term because the method doesn't actually use a formal optimization process. I don't think this is too much of a problem but I do think a clear statement of what the authors mean by optimization would be helpful (e.g. in the Methods). As I understand it, the "optimal" ventilation rate is just taken to be the one for which the health burden is smallest.

SOLUTION: Reducing burden of disease from residential indoor air exposures in Europe (HEALTHVENT project) Reducing burden of disease from residential indoor air exposures in Europe (HEALTHVENT project)

PROBLEM: In three successive experiments, the immune functions of pigs persistently infected with the Ž . porcine reproductive and respiratory syndrome virus PRRSV have been evaluated. Non-specific Ž . immune responses were analyzed over a period of 12 weeks post-infection PI . In addition, the capacity of PRRSV-infected pigs to develop an efficient immune response against pseudorabies Ž . virus PRV glycoproteins and to resist to a subsequent virulent challenge was investigated. Our results demonstrate that PRRSV produced minor effects on the immune system of pigs. The skin Ž . delayed type hypersensitivity DTH in response to phytohemagglutinine injection was slightly diminished one week after challenge, but was restored thereafter. However, three weeks after the infection, the total white blood cell count, and the number of CD2 q , CD8 q and IgM q cells were enhanced. The increase in numbers of CD8 q cells persisted for three consecutive weeks. Serum immunoglobulins in infected pigs also increased by week 3 PI and up to 8 weeks PI. These results show that PRRSV may have stimulating effects on the pig immune system during the phase of 0165-2427r98r$19.00 q 1998 Elsevier Science B.V. All rights reserved. Ž . PII S 0 1 6 5 -2 4 2 7 9 7 0 0 1 3 4 -7 ( ) E. Albina et al.r Veterinary Immunology and Immunopathology 61 1998 49-66 50 long-lasting infection. After immunization with PRV glycoproteins, the production of anti-PRV antibodies and skin DTH response against PRV glycoproteins were not affected. On the contrary, following a virulent PRV challenge, PRRSV-infected pigs developed a better secondary antibody response and their resistance to the infection was as effective as in control pigs. Taken together, our data do not support a systemic immunosuppressive effect of PRRSV, during the persistent phase of infection. Other mechanisms may therefore apply to explain the emergence of secondary infections in endemically infected herds. q 1998 Elsevier Science B.V.

SOLUTION:
Immune responses in pigs infected with porcine reproductive and respiratory syndrome virus ž / PRRSV