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Atmospheric test of the J(BrONO<sub>2</sub>)/<i>k</i><sub>BrO+NO<sub>2</sub></sub> ratio: implications for total stratospheric Br<sub>y</sub> and bromine-mediated ozone loss

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Atmospheric Chemistry and Physics Discussions 3 1 4 S. Kreycy , C. Camy-Peyret , M. P. Chipperfield , M. Dorf , W. Feng , 3 5 1 1 R. Hossaini , L. Kritten , B. Werner , and K. Pfeilsticker 1 Correspondence to: S. Kreycy (sebastian.kreycy@iup.uni-heidelberg.de) Published by Copernicus Publications on behalf of the European Geosciences Union. | 27821 Discussion Paper Received: 26 September 2012 – Accepted: 8 October 2012 – Published: 23 October 2012 | Institute of Environmental Physics, University of Heidelberg, Heidelberg, Germany Laboratoire de Physique Moléculaire pour l’Atmosphère et l’Astrophysique (LPMAA), Université Pierre et Marie Curie, Paris, France 3 Institute for Climate and Atmospheric Science, School of Earth and Environment, University of Leeds, Leeds, UK 4 National Centre for Atmospheric Science, School of Earth and Environment, University of Leeds, Leeds, UK 5 Institute for Space Sciences, Free University Berlin, Berlin, Germany 2 Discussion Paper 2 ACPD 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Abstract Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | 1 Discussion Paper Atmospheric test of the J(BrONO2)/kBrO+NO2 ratio: implications for total stratospheric Bry and bromine-mediated ozone loss | This discussion paper is/has been under review for the journal Atmospheric Chemistry and Physics (ACP). Please refer to the corresponding final paper in ACP if available. Discussion Paper Atmos. Chem. Phys. Discuss., 12, 27821–27845, 2012 www.atmos-chem-phys-discuss.net/12/27821/2012/ doi:10.5194/acpd-12-27821-2012 © Author(s) 2012. CC Attribution 3.0 License. Full Screen / Esc Printer-friendly Version Interactive Discussion 5 | Discussion Paper | 27822 Discussion Paper 25 ACPD 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Abstract Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | 20 Discussion Paper 15 | 10 We report on time-dependent O3 , NO2 and BrO profile measurements taken in the stratosphere by limb observations of scattered skylight at high-latitudes during autumn circulation turn-over. The observations are complemented by simultaneous direct solar occultation measurements around sunset and sunrise performed aboard the same stratospheric balloon payload. Supporting radiative transfer and photochemical modelling indicates that, the measurements can be used to constrain the ratio J(BrONO2 )/kBrO+NO2 , for which overall a 1.69 ± 0.04 larger ratio is found than indicated by the most recent JPL compilation (Sander et al., 2011). Sensitivity studies reveal the major reasons likely to be (1) a larger BrONO2 absorption cross-section σBrONO2 , primarily for wavelengths larger than 300 nm, and (2) a smaller kBrO+NO2 at 220 K than given by Sander et al. (2011). Other factors, e.g. the actinic flux and quantum yield for the dissociation of BrONO2 , can be ruled out. The observations also have consequences for total inorganic stratospheric bromine (Bry ) estimated from stratospheric BrO measurements at high NOx loadings, since the J(BrONO2 )/kBrO+NO2 ratio largely determines the stratospheric BrO/Bry ratio during daylight. Using the revised J(BrONO2 )/kBrO+NO2 ratio, total stratospheric Bry is likely to be 1.4 ppt smaller than previously estimated from BrO profile measurements at high NOx loadings. This brings estimates of total stratospheric bromine inferred from organic source gas measurements (i.e. CH3 Br, the halons, CH2 Br2 , CHBr3 , .) into closer agreement with estimates based on BrO observations (inorganic method). The consequences for stratospheric ozone due to the revised J(BrONO2 )/kBrO+NO2 ratio are small (maximum −0.8 %), since at high NOx (for which most Bry assessments are made) an overestimated Bry using the inorganic method would in return almost cancel out with the amount of reactive bromine calculated in the photochemical models. Discussion Paper Abstract Full Screen / Esc Printer-friendly Version Interactive Discussion (1) Discussion Paper 1 Introduction The effect reactive bromine has on stratospheric ozone is largely dominated by the Reactions (1), (2a), and (2b) (Spencer and Rowland, 1977) 5 (2a) BrONO2 + h · ν −→ Br + NO3 (0.85) (2b) BrONO2 + O( P) −→ BrO + NO3 Nevertheless, Reaction (3) has a negligible effect on the lifetime of BrONO2 below about 25 km (Sinnhuber et al., 2005), where the bulk of BrONO2 resides during our measurements. Discussion Paper 27823 | 25 (3) | 3 Discussion Paper (the brackets give the recommended quantum yields Φ for λ > 300 nm), since they determine the amount of reactive bromine (BrO) and thus the bromine-mediated ozone loss in almost the whole global lower stratosphere in daytime, except in the chlorineactivated polar ozone hole regions. Sander et al. (2011) report for the termolecular Reaction (1) a 1σ uncertainty of 1.465 (at 220 K) and for the BrONO2 absorption crosssection, σ(BrONO2 ) (Eqs. 2a and 2b) and hence for J(BrONO2 ) an overall uncertainty of about 1.4 (e.g. taken from Table 4.2 in JPL-2011). The former uncertainty mostly arises from the extrapolation of the laboratory measurements of kBrO+NO2 from high to low temperatures. The uncertainty of σ(BrONO2 ) though is due to its large decrease by 3.5 orders of magnitude with wavelength, when going from the extreme UV (λ = 200 nm) to λ > 300 nm, where the actinic fluxes, and thus the spectral contribution to J(BrONO2 ) strongly increases. BrONO2 can also be destroyed by reaction (Soller et al., 2002) 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Abstract Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | 20 (0.15) Discussion Paper 15 BrONO2 + h · ν −→ BrO + NO2 | 10 BrO + NO2 + M −→ BrONO2 + M ACPD Full Screen / Esc Printer-friendly Version Interactive Discussion 5 | Discussion Paper | 27824 Discussion Paper 25 ACPD 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Abstract Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | 20 Discussion Paper 15 | 10 We report on spectroscopic measurements taken during a balloon flight of the LPMA/DOAS (Limb Profile Monitor of the Atmosphere/Differential Optical Absorption Spectroscopy) payload at Kiruna, Sweden (67.9 N, 22.1 E) on 7 and 8 September 2009. The payload accommodated three spectrometers: (a) a near-IR (LPMA) spectrometer that is suitable for the detection of O3 , NO2 , CH4 , N2 O, HNO3 , and other trace-gases (e.g. Camy-Peyret et al., 1995; Payan et al., 1998), (b) a UV/vis spectrometer for the high precision detection of O3 , NO2 , BrO, IO, O4 , . in direct sunlight (e.g. Harder et al., 1998; Ferlemann et al., 2000), and (c) a UV/vis mini-DOAS instrument primarily for the detection of O3 , NO2 , and BrO in limb scattered skylight (e.g. Weidner et al., 2005; Kritten et al., 2010). While spectrometers (a) and (b) measure in direct sun during balloon ascent, solar occultation at sunset and sunrise, the mini-DOAS instrument records the atmosphere in limb geometry, with the azimuth angle being clock-wise perpendicular (α = 90 ) to o the sun’s azimuth direction. Viewing elevation angles are held constant (+0.05 ) during balloon ascent and but subsequently changed from +0.6 to −4.88 elevation angle in steps of 0.39 for the limb observations at balloon float altitude. The balloon was launched at 14:50 UT and a solar zenith angle (SZA) of 75 on 7 September 2009 and balloon float altitude (≈ 33.5 km) was reached around 16:45 UT (SZA = 86 ). The solar occultation and limb observations during sunset on 7 September 2009 lasted until 18:15 UT (SZA = 94 ), and were resumed at 02:30 UT during sunrise on 8 September 2009 (SZA = 94 ). They lasted until 06:00 UT (SZA = 75 ), when the payload was separated from the balloon. Due to the low stratospheric winds at high-latitudes during summer/winter circulation turn-over, the balloon payload gently drifted from Kiruna to the Finish-Russian border (at around 350 km distance) within the 16-h long flight. Accordingly, due to the low shear winds the azimuth stabilisation of the balloon gondola and therefore the sun and limb pointing was extremely stable as compared to previous balloon flights (e.g. see Table 1 in Dorf et al., 2006a; Kritten et al., Discussion Paper 2 Methods Full Screen / Esc Printer-friendly Version Interactive Discussion 27825 | Discussion Paper | Discussion Paper 25 ACPD 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Abstract Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | 20 Discussion Paper 15 | 10 Discussion Paper 5 2010). Here we primarily report on the data obtained from the spectrometers (b), and (c) obtained during sunset and of spectrometer (c) during sunrise. For both instruments the spectral retrieval is based on the DOAS method (Platt and Stutz, 2008). Since in previous studies, they have been described at length (e.g. Weidner et al., 2005; Dorf et al., 2006a; Butz et al., 2006; Kritten et al., 2010), here only those details are described which depart from our previous work. The retrieval of O3 , NO2 , and BrO from the solar occultation and the mini-DOAS measurements is performed along the parameters as given in Butz et al. (2006) and Aliwell et al. (2002), with updates as recently described in Dorf et al. (2008), and Kritten et al. (2010). Also, the errors and uncertainties the DOAS retrievals have already been discussed in length in previous studies (e.g. Harder et al., 1998; Aliwell et al., 2002; Weidner et al., 2005; Dorf et al., 2006a; Butz et al., 2006), they are only referred to when necessary. The limb radiances are modelled using version 2.1 of the Monte Carlo radiative transfer (RT) model McArtim (Deutschmann et al., 2011). The model’s input is chosen according to measured atmospheric temperatures and pressures, including a climatological high-latitude summer aerosol profile inferred from SAGE III (http://eosweb.larc. nasa.gov/PRODOCS/sage3/table_sage3.html) and confirmed with the direct sun measurement of spectrometer (b), the balloon altitude and the geolocation, SZAs as encountered during each measurement, the azimuth and elevation angles, as well as the field of view (FOV) of the mini-DOAS telescopes. Since the mini-DOAS spectrometer is not radio-metrically calibrated, all simulations are performed relative to the first limb spectrum (elevation angle +0.6 ) of each limb sequence. It is noteworthy that the radiometric calibration does not change between the individual limb sequences, except for very high SZAs ≥ 93 , when spectrometer straylight becomes important. This finding is in agreement with the small mismatch between measured and modelled limb radiances also found by Deutschmann et al. (2011) (see Figs. 5 and 6 therein). Figure 2 indicates how well the modelled and measured relative radiances are reproduced for the limb observations at λ = 350, 450, and 495 nm, where BrO, NO2 and O3 are evaluated. The good agreement indicates that both, the relevant observation parameters (e.g. balloon Full Screen / Esc Printer-friendly Version Interactive Discussion 27826 | Discussion Paper | Discussion Paper 25 ACPD 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Abstract Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | 20 Discussion Paper 15 | 10 Discussion Paper 5 altitude, SZA, elevation and azimuth angles, FOV), and the atmospheric parameters (T , p, aerosol concentration, and their optical properties) are well represented in the RT model. For the interpretation of the direct sun observations, our group’s raytracing model (DAMF) is used that was extensively tested in the profile retrievals of past balloon flights (e.g. Harder et al., 2000, see Fig. 1 therein). For the photochemical modelling the output from the most recent simulations of the 3-D CTM SLIMCAT (Chipperfield, 1999) at Kiruna for 6 September 2009 is used to initialise our lab-owned 1-D Facsimile code Labmos (e.g. Bösch et al., 2003). This approach is neccessary here because the output from global SLIMCAT run is only available every 48 h. This time resolution is too coarse to be used for comparisons with measurements. On the other hand using a 1-D photochemical model for the model vs measurement inter-comparison appears justified, since during the balloon flight stratospheric winds were low, and thus very likely the same air masses were probed throughout our observations. However, both photochemical models use the most recent version of the JPL kinetics and thermochemical data for all relevant gas-phase and heterogeneous reactions (Sander et al., 2011). Finally, the Labmos simulations are constrained to the measured N2 O and CH4 from spectrometer (a) to correct for small mismatches in the profiles of the source gases due to a small bias in the diabatic heating rate of SLIMCAT. Total stratospheric bromine (Bry ) is set to 20.3 ppt, derived from BrO observations of spectrometer (b), and the Bry mixing ratio profile are accordingly vertically shifted (about 2 km) until the modelled and measured N2 O and CH4 profiles matched. The initialisation is further constrained to O3 and NO2 obtained from the direct sun observations of spectrometer (b). As an example of the simulations, Fig. 3 shows the simulated 2-D fields of BrO, BrONO2 , and HOBr over Kiruna for 7 and 8 September 2009. Here, the simulation indicates that balloon soundings are well suited to study the Reactions (1), (2a), and (2b) at northern high-latitudes during the summer to winter circulation turn-over, mostly because NOx concentrations are large and the profiles of both targeted gases (NO2 , Full Screen / Esc Printer-friendly Version Interactive Discussion at night. Therefore, our high-latitude sunrise solar occultation measurements are not considered any further here but they will be discussed in a separate study addressing the HOBr photochemistry. In order to support an inter-comparison of measured and modelled slant column densities (SCDs) of O3 , NO2 and BrO, the simulated photochemical fields are fed into the RT models McArtim and DAMF, where path integrals through the simulated photochemical fields are calculated and then compared with the measured SCDs. Discussion Paper 10 (4) | BrONO2 + H2 O|aqueous −→ HOBr + HNO3 Discussion Paper 5 and BrO) nicely overlap as well, thus providing a good sensitivity for Reaction (1) during sunset. However, the Bry partitioning at early dawn during the solar occultation measurements (the period of the red dashed lines in Fig. 3), is largely given by the efficiency of the heterogenous reaction of ACPD 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | Abstract 15 Discussion Paper 25 | 20 | Figure 4 displays the inter-comparison of the measured and modelled limb SCDs of O3 , NO2 and BrO. While for O3 and NO2 the agreement is close to perfect for all elevation angles and tangent heights, measured limb BrO is in general larger than obtained from the simulations for the standard run (i.e. [Bry ] = 20.3 ppt, σ(BrONO2 ) and kBrO+NO2 from JPL-2011). This is in particular true for the high BrO SCDs values, which are obtained for large negative elevation angles (low tangent heights, or much lower altitudes than the balloon float altitude), where the bulk of BrO and BrONO2 resides. In short, our observations indicate that during dusk BrO tends to react later (or at higher SZAs) into its major nighttime reservoir gas BrONO2 , while at dawn limb BrO tends to appear more rapidly than the standard simulation suggests. A similar finding is obtained from the solar occultation measurements during sunset using the direct sun instrument (b) (Ferlemann et al., 2000) even though they are 27827 Discussion Paper 3 Results Full Screen / Esc Printer-friendly Version Interactive Discussion Discussion Paper | 27828 | 25 In order to investigate potential causes for the deviation of the measured vs. modelled BrO SCDs, a sensitivity test for the size of the parameters J(BrONO2 ), kBrO+NO2 , and Bry is performed for limb and solar occultation measurements (Figs. 6 and 7). In both cases the best agreement between measurements and simulations is found by increasing J(BrONO2 ), and decreasing kBrO+NO2 , when forcing the regression line measured vs. modelled BrO SCDs through 0. Figure 8 illustrates the situation, when varying J(BrONO2 ), and kBrO+NO2 for both, the limb (dusk and dawn) and the solar occulation measurements (dusk), whereby the colour coding denotes the slope Discussion Paper 20 ACPD 12, 27821–27845, 2012 In-situ test of the J(BrONO2 )/kBrO+NO2 ratio S. Kreycy et al. Title Page Abstract Introduction Conclusions References Tables Figures ◭ ◮ ◭ ◮ Back Close | 4 Discussion Discussion Paper 15 | 10 Discussion Paper 5 less sensitive to Reactions (1), (2a), and (2b), since by definition the samples are al ways taken at SZA = 90 , i.e. at the tangent height from where most of the absorption (signal) comes from (Fig. 5). Hence, our solar occultation observations mostly probe the atmosphere for a more-or-less constant J(BrONO2 ), but at the same time the effectively probed air masses (i.e. tangent points) move more and more away from the payload (up to 1200 km), i.e. towards the northwest during sunset. An inspection of the assimilation maps of the MIMOSA model’s (http://ether.ipsl.jussieu.fr/ether/pubipsl/ mimosa_2009_uk.jsp) potential vorticity (PV) indicate a negligible PV equilibrium value of MeCpG steps (,+14 deg.) [31,44]. In comparison, methylation has a significantly lower stability cost when happening at major groove positions, such as 211 and 21 base pair from dyad (mutations 9 and 12), where the roll of the nucleosome bound conformation (+10 deg.) is more compatible with the equilibrium geometry of MeCpG steps. The nucleosome destabilizing effect of cytosine methylation increases with the number of methylated cytosines, following the same position dependence as the single methylations. The multiple-methylation case reveals that each major groove meth- PLOS Computational Biology | www.ploscompbiol.org 3 November 2013 | Volume 9 | Issue 11 | e1003354 DNA Methylation and Nucleosome Positioning ylation destabilizes the nucleosome by around 1 kJ/mol (close to the average estimate of 2 kJ/mol obtained for from individual methylation studies), while each minor groove methylation destabilizes it by up to 5 kJ/mol (average free energy as single mutation is around 6 kJ/mol). This energetic position-dependence is the reverse of what was observed in a recent FRET/SAXS study [30]. The differences can be attributed to the use of different ionic conditions and different sequences: a modified Widom-601 sequence of 157 bp, which already contains multiple CpG steps in mixed orientations, and which could assume different positioning due to the introduction of new CpG steps and by effect of the methylation. The analysis of our trajectories reveals a larger root mean square deviation (RMSD) and fluctuation (RMSF; see Figures S2– S3 in Text S1) for the methylated nucleosomes, but failed to detect any systematic change in DNA geometry or in intermolecular DNA-histone energy related to methylation (Fig. S1B, S1C, S4–S6 in Text S1). The hydrophobic effect should favor orientation of the methyl group out from the solvent but this effect alone is not likely to justify the positional dependent stability changes in Figure 2, as the differential solvation of the methyl groups in the bound and unbound states is only in the order of a fraction of a water molecule (Figure S5 in Text S1). We find however, a reasonable correlation between methylation-induced changes in hydrogen bond and stacking interactions of the bases and the change in nucleosome stability (see Figure S6 in Text S1). This finding suggests that methylation-induced nucleosome destabilization is related to the poorer ability of methylated DNA to fit into the required conformation for DNA in a nucleosome. Changes in the elastic deformation energy between methylated and un-methylated DNA correlate with nucleosomal differential binding free energies To further analyze the idea that methylation-induced nucleosome destabilization is connected to a worse fit of methylated DNA into the required nucleosome-bound conformation, we computed the elastic energy of the nucleosomal DNA using a harmonic deformation method [36,37,44]. This method provides a rough estimate of the energy required to deform a DNA fiber to adopt the super helical conformation in the nucleosome (full details in Suppl. Information Text S1). As shown in Figure 2, there is an evident correlation between the increase that methylation produces in the elastic deformation energy (DDE def.) and the free energy variation (DDG bind.) computed from MD/TI calculations. Clearly, methylation increases the stiffness of the CpG step [31], raising the energy cost required to wrap DNA around the histone octamers. This extra energy cost will be smaller in regions of high positive roll (naked DNA MeCpG steps have a higher roll than CpG steps [31]) than in regions of high negative roll. Thus, simple elastic considerations explain why methylation is better tolerated when the DNA faces the histones through the major groove (where positive roll is required) that when it faces histones through the minor groove (where negative roll is required). Nucleosome methylation can give rise to nucleosome repositioning We have established that methylation affects the wrapping of DNA in nucleosomes, but how does this translate into chromatin structure? As noted above, accumulation of minor groove methylations strongly destabilizes the nucleosome, and could trigger nucleosome unfolding, or notable changes in positioning or phasing of DNA around the histone core. While accumulation of methylations might be well tolerated if placed in favorable positions, accumulation in unfavorable positions would destabilize the nucleosome, which might trigger changes in chromatin structure. Chromatin could in fact react in two different ways in response to significant levels of methylation in unfavorable positions: i) the DNA could either detach from the histone core, leading to nucleosome eviction or nucleosome repositioning, or ii) the DNA could rotate around the histone core, changing its phase to place MeCpG steps in favorable positions. Both effects are anticipated to alter DNA accessibility and impact gene expression regulation. The sub-microsecond time scale of our MD trajectories of methylated DNAs bound to nucleosomes is not large enough to capture these effects, but clear trends are visible in cases of multiple mutations occurring in unfavorable positions, where unmethylated and methylated DNA sequences are out of phase by around 28 degrees (Figure S7 in Text S1). Due to this repositioning, large or small, DNA could move and the nucleosome structure could assume a more compact and distorted conformation, as detected by Lee and Lee [29], or a slightly open conformation as found in Jimenez-Useche et al. [30]. Using the harmonic deformation method, we additionally predicted the change in stability induced by cytosine methylation for millions of different nucleosomal DNA sequences. Consistently with our calculations, we used two extreme scenarios to prepare our DNA sequences (see Fig. 3): i) all positions where the minor grooves contact the histone core are occupied by CpG steps, and ii) all positions where the major grooves contact the histone core are occupied by CpG steps. We then computed the elastic energy required to wrap the DNA around the histone proteins in unmethylated and methylated states, and, as expected, observed that methylation disfavors DNA wrapping (Figure 3A). We have rescaled the elastic energy differences with a factor of 0.23 to match the DDG prediction in figure 2B. In agreement with the rest of our results, our analysis confirms that the effect of methylation is position-dependent. In fact, the overall difference between the two extreme methylation scenarios (all-in-minor vs all-in-major) is larger than 60 kJ/mol, the average difference being around 15 kJ/ mol. We have also computed the elastic energy differences for a million sequences with CpG/MeCpG steps positioned at all possible intermediate locations with respect to the position (figure 3B). The large differences between the extreme cases can induce rotations of DNA around the histone core, shifting its phase to allow the placement of the methylated CpG steps facing the histones through the major groove. It is illustrative to compare the magnitude of CpG methylation penalty with sequence dependent differences. Since there are roughly 1.5e88 possible 147 base pairs long sequence combinations (i.e., (4n+4(n/2))/2, n = 147), it is unfeasible to calculate all the possible sequence effects. However, using our elastic model we can provide a range of values based on a reasonably large number of samples. If we consider all possible nucleosomal sequences in the yeast genome (around 12 Mbp), the energy difference between the best and the worst sequence that could form a nucleosome is 0.7 kj/mol per base (a minimum of 1 kJ/mol and maximum of around 1.7 kJ/mol per base, the first best and the last worst sequences are displayed in Table S3 in Text S1). We repeated the same calculation for one million random sequences and we obtained equivalent results. Placing one CpG step every helical turn gives an average energetic difference between minor groove and major groove methylation of 15 kJ/ mol, which translates into ,0.5 kJ/mol per methyl group, 2 kJ/ mol per base for the largest effects. Considering that not all nucleosome base pair steps are likely to be CpG steps, we can conclude that the balance between the destabilization due to CpG methylation and sequence repositioning will depend on the PLOS Computational Biology | www.ploscompbiol.org 4 November 2013 | Volume 9 | Issue 11 | e1003354 DNA Methylation and Nucleosome Positioning Figure 3. Methylated and non-methylated DNA elastic deformation energies. (A) Distribution of deformation energies for 147 bplong random DNA sequences with CpG steps positioned every 10 base steps (one helical turn) in minor (red and dark red) and major (light and dark blue) grooves respectively. The energy values were rescaled by the slope of a best-fit straight line of figure 2, which is 0.23, to source of circulating FGF-21. The lack of association between circulating and muscle-expressed FGF-21 also suggests that muscle FGF-21 primarily works in a local manner regulating glucose metabolism in the muscle and/or signals to the adipose tissue in close contact to the muscle. Our study has some limitations. The number of subjects is small and some correlations could have been significant with greater statistical power. Another aspect is that protein levels of FGF-21 were not determined in the muscles extracts, consequently we cannot be sure the increase in FGF-21 mRNA is followed by increased protein expression. In conclusion, we show that FGF-21 mRNA is increased in skeletal muscle in HIV patients and that FGF-21 mRNA in muscle correlates to whole-body (primarily reflecting muscle) insulin resistance. These findings add to the evidence that FGF-21 is a myokine and that muscle FGF-21 might primarily work in an autocrine manner. Acknowledgments We thank the subjects for their participation in this study. 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Atmospheric test of the J(BrONO<sub>2</sub>)/<i>k</i><sub>BrO+NO<sub>2</sub></sub> ratio: implications for total stratospheric Br<sub>y</sub> and bromine-mediated ozone loss
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Atmospheric test of the J(BrONO<sub>2</sub>)/<i>k</i><sub>BrO+NO<sub>2</sub></sub> ratio: implications for total stratospheric Br<sub>y</sub> and bromine-mediated ozone loss

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