With the development of laser technology, laser-driven proton acceleration provides a new method for proton tumor therapy. However, it has not been applied in practice because of the wide and decreasing energy spectrum of laser-accelerated proton beams. In this paper, we propose an analytical model to reconstruct the spread-out Bragg peak (SOBP) using laser-accelerated proton beams. Firstly, we present a modified weighting formula for protons of different energies. Secondly, a theoretical model for the reconstruction of SOBPs with laser-accelerated proton beams has been built. It can quickly calculate the number of laser shots needed for each energy interval of the laser-accelerated protons. Finally, we show the 2D reconstruction results of SOBPs for laser-accelerated proton beams and the ideal situation. The final results show that our analytical model can give an SOBP reconstruction scheme that can be used for actual tumor therapy.
Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning. The biomarkers for blood coagulation, particularly vWF and sCD62p, were most consistently associated with oil combustion. Systemic oxidative stress biomarker (8-OHdG) was most consistently associated with vehicle and industrial combustion. The associations of the biomarkers were generally not significant or consistent with secondary formation of pollutants and with the aldehydes. The findings support policies to control anthropogenic pollution sources rather than natural soil or road dust from a cardio-respiratory health standpoint.
Importance: Exposure to ozone has been associated with cardiovascular mortality, but the underlying biological mechanisms are not yet understood. Objective: To examine the association between ozone exposure and cardiopulmonary pathophysiologic mechanisms. Design, Setting, and Participants: A longitudinal study involving 89 healthy adult participants living on a work campus in Changsha City, China, was conducted from December 1, 2014, to January 31, 2015. This unique quasiexperimental setting allowed for better characterization of air pollutant exposure effects because the participants spent most of their time in controlled indoor environments. Concentrations of indoor and outdoor ozone, along with the copollutants particulate matter, nitrogen dioxide, and sulfur dioxide, were monitored throughout the study period and then combined with time-activity information and filtration conditions of each residence and office to estimate 24-hour and 2-week combined indoor and outdoor mean exposure concentrations. Associations between each exposure measure and outcome measure were analyzed using single-pollutant and 2-pollutant linear mixed models controlling for ambient temperature, secondhand smoke exposure, and personal-level time-varying covariates. Main Outcomes and Measures: Biomarkers indicative of inflammation and oxidative stress, arterial stiffness, blood pressure, thrombotic factors, and spirometry were measured at 4 sessions. Results: Of the 89 participants, 25 (28%) were women and the mean (SD) age was 31.5 (7.6) years. The 24-hour ozone exposure concentrations ranged from 1.4 to 19.4 parts per billion (ppb), corresponding to outdoor concentrations ranging from 4.3 to 47.9 ppb. Within this range, in models controlling for a second copollutant and other potential confounders, a 10-ppb increase in 24-hour ozone was associated with mean increases of 36.3% (95% CI, 29.9%-43.0%) in the level of platelet activation marker soluble P-selectin, 2.8% (95% CI, 0.6%-5.1%) in diastolic blood pressure, 18.1% (95% CI, 4.5%-33.5%) in pulmonary inflammation markers fractional exhaled nitric oxide, and 31.0% (95% CI, 0.2%-71.1%) in exhaled breath condensate nitrite and nitrate as well as a -9.5% (95% CI, -17.7% to -1.4%) decrease in arterial stiffness marker augmentation index. A 10-ppb increase in 2-week ozone was associated with increases of 61.1% (95% CI, 37.8%-88.2%) in soluble P-selectin level and 126.2% (95% CI, 12.1%-356.2%) in exhaled breath condensate nitrite and nitrate level. Other measured biomarkers, including spirometry, showed no significant associations with either 24-hour ozone or 2-week ozone exposures. Conclusions and Relevance: Short-term ozone exposure at levels not associated with lung function changes was associated with platelet activation and blood pressure increases, suggesting a possible mechanism by which ozone may affect cardiovascular health.
Carotid intima-media thickness (CIMT) is a good surrogate for atherosclerosis. Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases. We aim to investigate the relationships between homocysteine (Hcy) related biochemical indexes and CIMT, the associations between Hcy related SNPs and CIMT, as well as the potential gene-gene interactions. The present study recruited full siblings (186 eligible families with 424 individuals) with no history of cardiovascular events from a rural area of Beijing. We examined CIMT, intima-media thickness for common carotid artery (CCA-IMT) and carotid bifurcation, tested plasma levels for Hcy, vitamin B6 (VB6), vitamin B12 (VB12) and folic acid (FA), and genotyped 9 SNPs on MTHFR, MTR, MTRR, BHMT, SHMT1, CBS genes. Associations between SNPs and biochemical indexes and CIMT indexes were analyzed using family-based association test analysis. We used multi-level mixed-effects regression model to verify SNP-CIMT associations and to explore the potential genegene interactions. VB6, VB12 and FA were negatively correlated with CIMT indexes (p < 0.05). rs2851391 T allele was associated with decreased plasma VB12 levels (p = 0.036). In FABT, CBS rs2851391 was significantly associated with CCA-IMT (p = 0.021) and CIMT (p = 0.019). In multi-level mixed-effects regression model, CBS rs2851391 was positively significantly associated with CCA-IMT (Coef = 0.032, se = 0.009, raw p < 0.001) after Bonferoni correction (corrected a = 0.0056). Genegene interactions were found between CBS rs2851391 and BHMT rs10037045 for CCA-IMT (p = 0.011), as well as between CBS rs2851391 and MTR rs1805087 for CCA-IMT (p = 0.007) and CIMT (p = 0.022). Significant associations are found between Hcy metabolism related genetic polymorphisms, biochemical indexes and CIMT indexes. There are complex interactions between genetic polymorphisms for CCA-IMT and CIMT.
BACKGROUND: Helicobacter pylori (HP) infection and chronic atrophic gastritis (CAG) have shown strong associations with the development of gastric cancer. This study aimed to examine whether both risk factors are associated with accelerated epigenetic ageing, as determined by the 'DNA methylation age', in a population-based study of older adults (n=1477). METHODS: Serological measurements of HP antibodies and pepsinogen I and II for CAG definition were obtained by ELISA kits. Whole blood DNA methylation profiles were measured by Illumina Human Methylation450K Beadchip. DNA methylation ages were calculated by two algorithms proposed by Horvath and Hannum et al. RESULTS: After adjusting for potential covariates in linear regression models, we found that HP infection, infection with virulent HP strains (CagA+) and severe CAG were significantly associated with an increase in DNA methylation age by approximately 0.4, 0.6 and 1 year (all P-values <0.05), respectively. CONCLUSIONS: Our study indicates that both CagA+ HP infection and CAG go along with accelerated epigenetic ageing.
Tobacco smoking and oxidative stress (OS) are both related to a wide spectrum of adverse age-related health outcomes, but their association is not yet well-established. We examined the associations of self-reported smoking indicators, serum cotinine levels and smoking-related DNA methylation biomarkers with two urinary proxy markers of OS, 8-isoprostane (8-iso) and 8-hydroxy-2'-deoxyguanosine (8-oxodG), in two independent subsets of older adults recruited in Germany (discovery set: n = 978, validation set: n = 531). We obtained DNA methylation profiles in whole blood samples by Illumina Human Methylation450K Beadchip and measured the urinary levels of both OS markers using commercial ELISA kits. After controlling for potential confounders, current smoking, cumulative smoking exposure (pack-years) and serum cotinine levels (ng/ml) were strongly associated with 8-iso levels (p values <0.0001, 0.004 and 0.001, respectively). Of 151 previously identified smoking-related CpG sites, 71 loci were associated with 8-iso levels after correction for multiple testing (FDR < 0.05) in the validation phase and were designated as loci related to 8-iso levels defined OS. In addition, serum cotinine levels, cumulative smoking exposure and a smoking index (SI) based on the 71 identified loci manifested monotonic associations with 8-iso levels. However, we did not observe any associations between these smoking indicators and 8-oxodG levels. In conclusion, this study suggests that smoking-related epigenetic alterations are closely correlated with smoking-induced OS. The identified CpG sites could potentially be prognostic epigenetic markers of OS and OS-related health outcomes. Our findings and the underlying mechanisms should be followed up in further, preferably longitudinal studies.
A practical approach to achieve strong coherent synchrotron emissions (CSE) in relativistic laser-plasma interaction is proposed, where a plane target with its electron density satisfying the self-similar parameter S similar or equal to n(e0)/a(0)n(c) = 1 is obliquely irradiated by a P-polarized laser pulse. In this case, electrons at the target surface are periodically dragged out into the vacuum by the laser field component perpendicular to the target surface, resulting in the formation of a series of dense electron bunches propagating along the target surface. Intense CSE is generated by these electron bunches under acceleration by the laser field component parallel to the target surface. Two-dimensional particle-in-cell simulations show that an intense attosecond light pulse at intensity 9.1 x 10(20) W/cm(2) (electric field strength similar to 41% as that of the drive laser) can be obtained through such CSE. In the high-order harmonics with 15 omega(0) < omega(n) < 500 omega(0) (omega(0) is the laser frequency), the power spectrum of the emission scales as I(n) similar to n(-1.8) and the conversion efficiency from laser to emission reaches similar to 10(-2). Published by AIP Publishing.
A balanced RF rectifier is proposed to replace terminations in microwave circuits and thus to recycle the otherwise dissipated power in resistances. In order not to degrade the performance of the original circuits, a balanced configuration is adopted because it minimizes the variation of input impedance of the rectification circuitry. This approach achieves good input reflection coefficient over a large dynamic range and operating frequencies. The highly efficient energy recycler is composed of a 3 dB quadrature coupler and two identical RF rectifiers. The impact of amplitude and phase imbalances of the transfer characteristics of the coupler is discussed. Furthermore, an arbitrary-port-resistance coupler is studied to replace non-50- Ω terminations. The experimental verification demonstrates that the proposed circuit provides an input reflection coefficient of better than −15 dB from 2.2 to 2.5GHz over different input power levels. The measured peak RF-to-dc efficiency is 74.9% at 2.34 GHz with S11=−24dB . The proposed balanced rectifier thus significantly improves S11 over existing rectifiers and is therefore suitable for replacing resistive terminations in a large variety of circuits.
