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2.
  • Middha, Pooja K., et al. (author)
  • A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry
  • 2023
  • In: Breast Cancer Research. - : BioMed Central (BMC). - 1465-5411 .- 1465-542X. ; 25:1
  • Journal article (peer-reviewed)abstract
    • Background Genome-wide studies of gene-environment interactions (GxE) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide GxE analysis of similar to 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 x 10(-5) prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). Conclusions Overall, the contribution of GxE interactions to the heritability of breast cancer is very small. At the population level, multiplicative GxE interactions do not make an important contribution to risk prediction in breast cancer.
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3.
  • Wang, Hong, et al. (author)
  • Ambient Electrosynthesis of Ammonia : Electrode Porosity and Composition Engineering
  • 2018
  • In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 57:38, s. 12360-12364
  • Journal article (peer-reviewed)abstract
    • Ammonia, a key precursor for fertilizer production, convenient hydrogen carrier, and emerging clean fuel, plays a pivotal role in sustaining life on Earth. Currently, the main route for NH3 synthesis is by the heterogeneous catalytic Haber-Bosch process (N-2+ 3H(2) -> 2NH(3)), which proceeds under extreme conditions of temperature and pressure with a very large carbon footprint. Herein we report that a pristine nitrogen-doped nanoporous graphitic carbon membrane (NCM) can electrochemically convert N-2 into NH3 in an acidic aqueous solution under ambient conditions. The Faradaic efficiency and rate of production of NH3 on the NCM electrode reach 5.2% and 0.08 gm(-2) h(-1), respectively. Functionalization of the NCM with Au nanoparticles dramatically enhances these performance metrics to 22% and 0.36 gm(-2) h(-1), respectively. As this system offers the potential to be scaled to industrial levels it is highly likely that it might displace the century-old Haber-Bosch process.
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4.
  • Xu, Changdan, et al. (author)
  • CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules
  • 2023
  • In: Chinese Journal of Lung Cancer. - 1009-3419. ; 26:6, s. 449-460
  • Journal article (peer-reviewed)abstract
    • Background and objective Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. Materials and methods 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. Results Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. Conclusion CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
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5.
  • Zhang, Yinping, et al. (author)
  • Ten cities cross-sectional questionnaire survey of children asthma and other allergies in China
  • 2013
  • In: Chinese Science Bulletin. - : Springer Science and Business Media LLC. - 1001-6538 .- 1861-9541. ; 58:34, s. 4182-4189
  • Journal article (peer-reviewed)abstract
    • Asthma, rhinitis and eczema (allergic or non-allergic) have increased throughout the world during the last decades, especially among children. Changes in the indoor environment are suspected to be important causes. China has experienced a dramatic change in indoor environmental exposures during the past two decades. However, such changes and their associations with children's asthma and other health aspects have not been thoroughly studied. China, Children, Homes, Health (CCHH), Phase I, was a cross-sectional questionnaire survey of 48219 children 1-8 years old in 10 Chinese cities during 2010-2012. The questionnaire includes the International Study of Asthma and Allergies in Childhood (ISAAC) core health questions and additional questions regarding housing, life habits and outdoor environment. In health analyses, children aged 3-6 years old were included. The prevalences of doctor diagnosed asthma varied from 1.7% to 9.8% (mean 6.8%), a large increase from 0.91% in 1999 and 1.50% in 2000. The prevalence of wheeze, rhinitis and atopic eczema (last 12 months) varied from 13.9% to 23.7%, 24.0% to 50.8% and 4.8% to 15.8%, respectively. Taiyuan had the lowest prevalences of all illnesses and Shanghai the highest, except for wheezewhere the highest value was for Urumqi. We found (1) no obvious association between disease prevalences and ambient PM10 concentrations and (2) higher prevalences of disease in humid climates with hot summers and cold winters, but with no centrally heated buildings. Associations between the diseases and economic status as indexed by Gross Domestic Product (GDP) requires further study.
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6.
  • Binbin, Song, et al. (author)
  • Oxidation properties of self-propagating high temperature synthesized niobium disilicide
  • 2014
  • In: Corrosion Science. - : Elsevier BV. - 0010-938X .- 1879-0496. ; 85, s. 311-317
  • Journal article (peer-reviewed)abstract
    • NbSi2 monoliths were prepared by self-propagating high temperature synthesis (SHS) and hot pressing (HP) and their oxidation behavior was investigated at various temperatures (823-1123 K) in air. The combustion mode of SHS reaction was steady state combustion, and the combustion product was single-phase NbSi2. Oxidation studies show that the highest mass gain was 0.95675 kg m(-2) at 1023 K. In cyclic oxidation, the oxidation rate was reduced and the mass gain was only 0.15507 kg m(-2). A dense protective amorphous SiO2 scale formed at 823 K and 923 K whereas a porous multilayer SiO2 and alpha/beta-Nb2O5 oxide scales formed at and above 1023 K and spalled off. Pest oxidation of NbSi2 monoliths was not observed in hot pressed NbSi2 monoliths.
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7.
  • Cai, Xiaoping, et al. (author)
  • Fabrication of Highly Porous CuAl Intermetallic by Thermal Explosion Using NaCl Space Holder
  • 2018
  • In: JOM. - : The Minerals, Metals, and Materials Society. - 1047-4838 .- 1543-1851. ; 70:10, s. 2173-2178
  • Journal article (peer-reviewed)abstract
    • A high-porosity CuAl-based intermetallic compound with composition Cu-50 at.% Al has been successfully prepared by thermal explosion (TE) using NaCl as space holder. The results showed that the NaCl particles were completely removed from the green compact by water leaching. The temperature of the specimen during the TE and the evolution of the porous microstructure were investigated. The TE was ignited at 560°C, and the specimen temperature increased to 775°C in 3 s, resulting in formation of intermetallic CuAl and CuAl2 phases in the final product. A porous CuAl-based intermetallic compound with up to 62 vol.% open porosity was produced when adding 60 vol.% NaCl. The compound exhibited a bimodal pore size structure, including large pores (200 μm to 300 μm) that replicated the NaCl particles and small pores (5 μm to 10 μm) interspersed in the pore walls. Moreover, the large pores were interconnected by channels and formed an open CuAl-based intermetallic cellular structure, having great potential for use in heat exchange and filtration applications.
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8.
  • Cai, Xiaoping, et al. (author)
  • Oxidation Resistance of Highly Porous Fe-Al Foams Prepared by Thermal Explosion
  • 2018
  • In: Metallurgical and Materials Transactions. A. - : Springer. - 1073-5623 .- 1543-1940. ; 49A:8, s. 3683-3691
  • Journal article (peer-reviewed)abstract
    • Open-cell Fe-Al intermetallic foams were successfully prepared by a simple and energy-saving thermal explosion (TE) process. The effects of the Fe/Al molar ratio (Fe-(40–50) at. pct Al) and thermal treatment temperature on the TE temperature profile, phase composition, pore characteristics, and oxidation resistance of the prepared foams were investigated. The results showed that the Al content significantly influenced the ignition (Tig) and combustion (Tc) temperatures of the TE process; in particular, as the Al content decreased, Tig increased gradually from 623 °C to 636 °C and Tc decreased from 1059 °C to 981 °C. FeAl was identified as the dominant phase in the thermally treated foams. The Fe-Al intermetallic foams displayed an open porosity of 60 vol pct, with pores connected with each other to form an open pore structure. The formation of the pores was attributed to the expansion of interparticle pores in the pressed body during the TE reaction. X-ray photoelectron spectroscopy analysis of the Fe-50Al foam showed that the Al 2p and O 1s binding energies were 74.5 eV and at 531.4 eV, respectively. The formation of a surface alumina layer in the early stages of the oxidation process resulted in the parabolic oxidation rate law, and the Fe-50Al foams exhibited an excellent resistance to oxidation at 650 °C in air. These results suggest that the synthesized Fe-Al foams represent promising materials for applications involving an oxidizing environment and high temperatures.
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9.
  • Couch, Fergus J., et al. (author)
  • Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
  • 2016
  • In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
  • Journal article (peer-reviewed)abstract
    • Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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10.
  • Jiao, Xinjang, et al. (author)
  • Hierarchical porous TiAl3 intermetallics synthesized by thermal explosion with a leachable space-holder material
  • 2016
  • In: Materials letters (General ed.). - : Elsevier BV. - 0167-577X .- 1873-4979. ; 181, s. 261-264
  • Journal article (peer-reviewed)abstract
    • Porous TiAl3 intermetallics were synthesized by thermal explosion (TE) reaction with NaCl as space holder material, from Ti-75Al at.% elemental powders. Results showed that the actual temperature of specimen climbed rapidly from 667 °C to 1106 °C. As a consequence, porous TiAl3 intermetallics with high open porosity (>80%) can be easily achieved when adding NaCl particles above 50 vol%. XRD patterns showed that only single-phase TiAl3 compound was synthesized via TE. Hierarchical porous TiAl3 materials displayed three pore structures, including large pores replicating from original NaCl particles, small pores among the skeletons, and tiny pores precipitated from particle skeletons. Moreover, porous TiAl3 intermetallics exhibited a uniform pore size distribution and formed an open-cellular structures allowing for the liquid-gas separation and filtration applications
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11.
  • Jung, Audrey Y, et al. (author)
  • Distinct reproductive risk profiles for intrinsic-like breast cancer subtypes : pooled analysis of population-based studies
  • 2022
  • In: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 114:12, s. 1706-1719
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Reproductive factors have been shown to be differentially associated with risk of estrogen receptor (ER) positive and ER-negative breast cancer. However, their associations with intrinsic-like subtypes are less clear.METHODS: Analyses included up to 23,353 cases, and 71,072 controls pooled from 31 population-based case-control or cohort studies in the Breast Cancer Association Consortium across 16 countries on 4 continents. Polytomous logistic regression was used to estimate the association between reproductive factors and risk of breast cancer by intrinsic-like subtypes (luminal A-like, luminal B-like, luminal B-HER2-like, HER2-enriched-like, and triple-negative) and by invasiveness. All statistical tests were 2-sided.RESULTS: Compared to nulliparous women, parous women had a lower risk of luminal A-like, luminal B-like, luminal B-HER2-like and HER2-enriched-like disease. This association was apparent only after approximately 10 years since last birth and became stronger with increasing time (odds ratio [OR] = 0.59, 95% confidence interval [CI] = 0.49 to 0.71; and OR = 0.36, 95% CI = 0.28 to 0.46; for multiparous women with luminal A-like tumors 20-<25 years after last birth and 45-<50 years after last birth, respectively). In contrast, parous women had a higher risk of triple-negative breast cancer right after their last birth (for multiparous women: OR = 3.12, 95%CI = 2.02 to 4.83) that was attenuated with time but persisted for decades (OR = 1.03, 95%CI = 0.79 to 1.34, for multiparous women 25 to < 30 years after last birth). Older age at first birth (P-heterogeneity<.001 for triple-negative compared to luminal-A like) and breastfeeding (P-heterogeneity<.001 for triple-negative compared to luminal-A like) were associated with lower risk of triple-negative but not with other disease subtypes. Younger age at menarche was associated with higher risk of all subtypes; older age at menopause was associated with higher risk of luminal A-like but not triple-negative breast cancer. Associations for in situ tumors were similar to luminal A-like.CONCLUSION: This large and comprehensive study demonstrates a distinct reproductive risk factor profile for triple-negative breast cancer compared to other subtypes, with implications for the understanding of disease etiology and risk prediction.
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12.
  • Kapoor, Pooja Middha, et al. (author)
  • Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
  • 2021
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
  • Journal article (peer-reviewed)abstract
    • We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer. 
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13.
  • Lozano, Rafael, et al. (author)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Journal article (peer-reviewed)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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14.
  • Murray, Christopher J. L., et al. (author)
  • Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • In: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Journal article (peer-reviewed)abstract
    • Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49·4% (95% uncertainty interval [UI] 46·4–52·0). The TFR decreased from 4·7 livebirths (4·5–4·9) to 2·4 livebirths (2·2–2·5), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83·8 million people per year since 1985. The global population increased by 197·2% (193·3–200·8) since 1950, from 2·6 billion (2·5–2·6) to 7·6 billion (7·4–7·9) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2·0%; this rate then remained nearly constant until 1970 and then decreased to 1·1% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2·5% in 1963 to 0·7% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2·7%. The global average age increased from 26·6 years in 1950 to 32·1 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59·9% to 65·3%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1·0 livebirths (95% UI 0·9–1·2) in Cyprus to a high of 7·1 livebirths (6·8–7·4) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0·08 livebirths (0·07–0·09) in South Korea to 2·4 livebirths (2·2–2·6) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0·3 livebirths (0·3–0·4) in Puerto Rico to a high of 3·1 livebirths (3·0–3·2) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2·0% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation.
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15.
  • Ran, Huashen, et al. (author)
  • Microstructure and properties of Ti5Si3-based porous intermetallic compounds fabricated via combustion synthesis
  • 2014
  • In: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 612, s. 337-342
  • Journal article (peer-reviewed)abstract
    • Porous titanium silicides (Ti5Si3-based) were produced by combustion synthesis process from reaction mixtures of titanium to silicon in varying molar ratios. The effects of combustion characteristics of the reaction mixtures on the phase formation, microstructure, porosity, pore size and compressive strength of porous titanium silicide intermetallic compounds were investigated. The results showed that the flame-front propagation velocity and temperature of the combustion reaction were the maximum for the reaction mixture containing Ti and Si in the ratio of 5 to 3 (Ti5Si3), 32.7 mm/s and 2205 K, respectively. X-ray diffraction analysis confirmed that the dominant phase formed was Ti5Si3 in all combustion synthesized porous intermetallic compounds. Ti5Si3-based intermetallic compounds were highly porous. The porosity and pore size of these intermetallics were dependent on the initial composition of the reaction mixture. The total and open porosities of Ti5Si3-based intermetallics varied from 33 to 61% and 17 to 55%, respectively. The porous titanium silicide intermetallic materials displayed high mechanical strength, in the range of 6-35 MPa, duly required for their use as filters.
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16.
  • Shi, Haonan, et al. (author)
  • Prevalence, risk factors, impact and management of pneumonia among preschool children in Chinese seven cities : a cross-sectional study with interrupted time series analysis
  • 2023
  • In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21
  • Journal article (peer-reviewed)abstract
    • Background: Pneumonia is a common disease worldwide in preschool children. Despite its large population size, China has had no comprehensive study of the national prevalence, risk factors, and management of pneumonia among preschool children. We therefore investigated the prevalence of pneumonia among preschool children in Chinese seven representative cities, and explore the possible risk factors of pneumonia on children, with a view to calling the world's attention to childhood pneumonia to reduce the prevalence of childhood pneumonia.Methods: Two group samples of 63,663 and 52,812 preschool children were recruited from 2011 and 2019 surveys, respectively. Which were derived from the cross-sectional China, Children, Homes, Health (CCHH) study using a multi-stage stratified sampling method. This survey was conducted in kindergartens in seven representative cities. Exclusion criteria were younger than 2 years old or older than 8 years old, non-permanent population, basic information such as gender, date of birth and breast feeding is incomplete. Pneumonia was determined on the basis of parents reported history of clearly diagnosed by the physician. All participants were assessed with a standard questionnaire. Risk factors for pneumonia, and association between pneumonia and other respiratory diseases were examined by multivariable-adjusted analyses done in all participants for whom data on the variables of interest were available. Disease management was evaluated by the parents' reported history of physician diagnosis, longitudinal comparison of risk factors in 2011 and 2019.Results: In 2011 and 2019, 31,277 (16,152 boys and 15,125 girls) and 32,016 (16,621 boys and 15,395 girls) preschool children aged at 2-8 of permanent population completed the questionnaire, respectively, and were thus included in the final analysis. The findings showed that the age-adjusted prevalence of pneumonia in children was 32.7% in 2011 and 26.4% in 2019. In 2011, girls (odds ratio [OR] 0.91, 95%CI [confidence interval]0.87-0.96; p = 0.0002), rural (0.85, 0.73-0.99; p = 0.0387), duration of breastfeeding & GE; 6 months(0.83, 0.79-0.88; p < 0.0001), birth weight (g) & GE; 4000 (0.88, 0.80-0.97; p = 0.0125), frequency of putting bedding to sunshine (Often) (0.82, 0.71-0.94; p = 0.0049), cooking fuel type (electricity) (0.87, 0.80-0.94; p = 0.0005), indoor use air-conditioning (0.85, 0.80-0.90; p < 0.0001) were associated with a reduced risk of childhood pneumonia. Age (4-6) (1.11, 1.03-1.20; p = 0.0052), parental smoking (one) (1.12, 1.07-1.18; p < 0.0001), used antibiotics (2.71, 2.52-2.90; p < 0.0001), history of parental allergy (one and two) (1.21, 1.12-1.32; p < 0.0001 and 1.33, 1.04-1.69; p = 0.0203), indoor dampness (1.24, 1.15-1.33; p < 0.0001), home interior decoration (1.11, 1.04-1.19; p = 0.0013), Wall painting materials (Paint) (1.16, 1.04-1.29; p = 0.0084), flooring materials (Laminate / Composite wood) (1.08, 1.02-1.16; p = 0.0126), indoor heating mode(Central heating)(1.18, 1.07-1.30, p = 0.0090), asthma (2.38, 2.17-2.61; p < 0.0001), allergic rhinitis (1.36, 1.25-1.47; p < 0.0001), wheezing (1.64, 1.55-1.74; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (2.53, 2.31-2.78; p < 0.0001), allergic rhinitis (1.41, 1.29-1.53; p < 0.0001) and wheezing (1.64, 1.55-1.74; p < 0.0001). In 2019, girls (0.92, 0. 87-0.97; p = 0.0019), duration of breastfeeding & GE; 6 months (0.92, 0.87-0.97; p = 0.0031), used antibiotics (0.22, 0.21-0.24; p < 0.0001), cooking fuel type (Other) (0.40, 0.23-0.63; p = 0.0003), indoor use air-conditioning (0.89, 0.83-0.95; p = 0.0009) were associated with a reduced risk of childhood pneumonia. Urbanisation (Suburb) (1.10, 1.02-1.18; p = 0.0093), premature birth (1.29, 1.08-1.55; p = 0.0051), birth weight (g) < 2500 (1.17, 1.02-1.35; p = 0.0284), parental smoking (1.30, 1.23-1.38; p < 0.0001), history of parental asthma (One) (1.23, 1.03-1.46; p = 0.0202), history of parental allergy (one and two) (1.20, 1.13-1.27; p < 0.0001 and 1.22, 1.08-1.37; p = 0.0014), cooking fuel type (Coal) (1.58, 1.02-2.52; p = 0.0356), indoor dampness (1.16, 1.08-1.24; p < 0.0001), asthma (1.88, 1.64-2.15; p < 0.0001), allergic rhinitis (1.57, 1.45-1.69; p < 0.0001), wheezing (2.43, 2.20-2.68; p < 0.0001) were associated with an elevated risk of childhood pneumonia; pneumonia was associated with an elevated risk of childhood asthma (1.96, 1.72-2.25; p < 0.0001), allergic rhinitis (1.60, 1.48-1.73; p < 0.0001) and wheezing (2.49, 2.25-2.75; p < 0.0001).Conclusions: Pneumonia is prevalent among preschool children in China, and it affects other childhood respiratory diseases. Although the prevalence of pneumonia in Chinese children shows a decreasing trend in 2019 compared to 2011, a well-established management system is still needed to further reduce the prevalence of pneumonia and reduce the burden of disease in children.
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17.
  • Shu, Xiang, et al. (author)
  • Associations of obesity and circulating insulin and glucose with breast cancer risk : a Mendelian randomization analysis
  • 2019
  • In: International Journal of Epidemiology. - : OXFORD UNIV PRESS. - 0300-5771 .- 1464-3685. ; 48:3, s. 795-806
  • Journal article (peer-reviewed)abstract
    • Background: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p = 5.09 x 10(-4)], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p = 4.02 x 10(-4)), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p = 5.05 x 10(-19)) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p = 9.22 x 10(-6)). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.
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18.
  • Wang, Faming, et al. (author)
  • Development Processes and Property Measurements of Moisture Absorption and Quick Dry Fabrics
  • 2009
  • In: Fibres & Textiles in Eastern Europe. - 1230-3666. ; 17:2, s. 46-49
  • Journal article (peer-reviewed)abstract
    • In this study a new type of honeycomb-patterned micro-porous polyester fibre was used to develop good moisture absorption and quick drying properties of woven fabrics. Details of the development and after-finish processes of the fabrics were illustrated. The water transport, vapour transmission and quick dry properties of the seven different end products were also investigated. It was evident that weaving parameters and after-finish processes are crucial factors in the fabric production process. The final products can also have good water transport and quick dry properties without additive treatment.
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19.
  • Wang, Xiaohong, et al. (author)
  • Effects of tungsten and aluminum additions on the formation of molybdenum disilicide by mechanically-induced self-propagating reaction
  • 2010
  • In: Journal of Alloys and Compounds. - : Elsevier BV. - 0925-8388 .- 1873-4669. ; 490:1, s. 388-392
  • Journal article (peer-reviewed)abstract
    • The effects of tungsten and aluminum additions to Mo–Si system on the formation of MoSi2 by mechanically-induced self-propagating reaction in a high-energy ball mill were investigated by X-ray diffraction. The incubation time for mechanically-induced self-propagating reaction to form MoSi2 was 90 min in Mo–Si system. With the addition of tungsten to Mo–Si system, the incubation time of mechanically-induced self-propagating reaction of (Wx,Mo1−x)Si2 system was prolonged. It was due to the decrease of adiabatic temperature with increase in x, and the mechanically-induced self-propagating reaction was not observed until 150 min of high-energy milling in (Wx,Mo1−x)Si2 powder sample with x equals to 0.4. Conversely, the minor aluminum (y < 0.2 in Mo(Si1−y,Aly)2 system) substituting for silicon had shorten the incubation period and accelerated the reaction. When tungsten and aluminium were added simultaneously to Mo–Si system, the mechanically-induced self-propagating reaction was observed in (W0.1,Mo0.9)(Si0.9,Al0.1)2 sample, but it was not observed in (W0.2,Mo0.8)(Si0.8,Al0.2)2 and (W0.3,Mo0.7)(Si0.7,Al0.3)2 samples.
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20.
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21.
  • Wang, Zhang, et al. (author)
  • Fabrication and properties of freeze-cast mullite foams derived from coal-series kaolin
  • 2016
  • In: Ceramics International. - : Elsevier BV. - 0272-8842 .- 1873-3956. ; 42:10, s. 12414-12421
  • Journal article (peer-reviewed)abstract
    • Hierarchically porous mullite foams were fabricated from coal-series kaolin and Al2O3 slurries by freeze-casting using tert-butyl alcohol (TBA) and water as templates. TBA developed unidirectionally aligned pore channels along the freezing direction and water developed lamellar pores. The total porosity (60.2–83.4%), density (0.49–1.23 g/cm3) and macro-pore size (10–50 µm) of mullite foams were tailored by controlling the solid content of the slurries. The mullitization reaction was completed at the sintering temperature of 1500 °C. The compressive strength of mullite foams along the freezing direction was 3.8–49.4 MPa. Lower porosity and higher compressive strength of sintered mullite foams were obtained using TBA as solvent compared to water. The thermal conductivity of low density and mechanically stable TBA templated porous mullite with 80.2% porosity was 0.18 W/m K, indicting that the freeze-cast porous mullite was a promising refractory material for applications in thermal insulation
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22.
  • Wang, Zhang, et al. (author)
  • Highly porous open cellular TiAl-based intermetallics fabricated by thermal explosion with space holder process
  • 2016
  • In: Intermetallics (Barking). - : Elsevier BV. - 0966-9795 .- 1879-0216. ; 68, s. 95-100
  • Journal article (peer-reviewed)abstract
    • High porosity TiAl-based intermetallics were prepared through thermal explosion (TE) from Ti–50Al at.% powders with NaCl as soluble template. The results showed that the space holder particles of NaCl were removed completely in green compacts, and porous Ti–Al materials were synthesized via a low-energy consumption method of TE at a temperature of 600 °C. TiAl was evolved as dominant phase in sintered materials at 1100 °C. With adding 80 vol.% NaCl to Ti–50Al at.% powders, the open porosity was significantly elevated up to 84%. Moreover, the porous materials exhibited a bimodal pore size distribution: large pores (200–500 μm) replicating NaCl particles and small pores (<50 μm) embedded in pore walls. The interconnected small and large pores make open cellular porous TiAl materials, which prescribe them promising for a wide range of applications in separation, heat insulation and catalysis.
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23.
  • Xiaoping, Cai, et al. (author)
  • Preparation of Porous NiAl Intermetallic with Controllable Shape and Pore Structure by Rapid Thermal Explosion with Space Holder
  • 2021
  • In: Metals and Materials International. - : Springer. - 1598-9623 .- 2005-4149. ; 27:10, s. 4216-4224
  • Journal article (peer-reviewed)abstract
    • Due to the high exothermic characteristic of NiAl during the reaction synthesis process from Ni–Al elemental powders, the NiAl intermetallic melts frequently, and the specimens are difficult to maintain their original shape, which leads to the inhomogeneity of the pore size and morphology. To tackle this problem, porous NiAl intermetallic monolith with controllable shape and pore structure was prepared through thermal explosion (TE) using NaCl as space holder. The TE behavior was recorded, and the effect of the volume fraction of NaCl on the phase composition, macroscopic feature, pore morphology and open porosity were investigated. The results showed that NiAl was the main phase in the products, and the specimen was free from cracking or deforming when NaCl content reached 30 vol%. The interconnected channel and pore windows were formed, and the open porosity was improved greatly to 63% by adding 50 vol% NaCl. The leachable space holder route provides a simple way to control the shape, pore structure and open porosity of the synthesized porous NiAl intermetallic.
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24.
  • Yang, Liu, et al. (author)
  • Prenatal and postnatal early life exposure to greenness and particulate matter of different size fractions in relation to childhood rhinitis : A multi-center study in China
  • 2024
  • In: Science of the Total Environment. - : Elsevier. - 0048-9697 .- 1879-1026. ; 938
  • Journal article (peer-reviewed)abstract
    • The impact of early life exposure to residential greenness on childhood rhinitis and its interaction with particulate matter (PM) of different size fractions remain inconsistent. Herein, we recruited 40,486 preschool children from randomly selected daycare centers in 7 cities in China from 2019 to 2020, and estimated exposure to residential greenness by the normalized difference vegetation index (NDVI) with a 500 m buffer. Exposure to ambient PM (PM1, PM2.5, and PM10) was evaluated using a satellite-based prediction model (daily, at a resolution of 1 km × 1 km). By mixed-effect logistic regression, NDVI values during pregnancy, in the first (0–1 year old) and the second (1–2 years old) year of life were negatively associated with lifetime rhinitis (LR) and current rhinitis (CR) (P < 0.001). PM in the same time windows was associated with increased risks of LR and CR in children, with smaller size fraction of PM showing greater associations. The negative associations between prenatal and postnatal NDVI and LR and CR in preschool children remained robust after adjusting for concomitant exposure to PM, whereas the associations of postnatal NDVI and rhinitis showed significant interactions with PM. At lower levels of PM, postnatal NDVI remained negatively associated with rhinitis and was partly mediated by PM (10.0–40.9 %), while at higher levels of PM, the negative associations disappeared or even turned positive. The cut-off levels of PM were identified for each size fraction of PM. In conclusion, prenatal exposure to greenness had robust impacts in lowering the risk of childhood rhinitis, while postnatal exposure to greenness depended on the co-exposure levels to PM. This study revealed the complex interplay of greenness and PM on rhinitis in children. The exposure time window in prenatal or postnatal period and postnatal concomitant PM levels played important roles in influencing the associations between greenness, PM and rhinitis.
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25.
  • Ahearn, Thomas U., et al. (author)
  • Common variants in breast cancer risk loci predispose to distinct tumor subtypes
  • 2022
  • In: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
  • Journal article (peer-reviewed)abstract
    • BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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26.
  • Chen, Huihui, et al. (author)
  • Molecular, behavioral, and growth responses of juvenile yellow catfish ( Tachysurus fulvidraco ) exposed to carbamazepine
  • 2024
  • In: Aquatic Toxicology. - : Elsevier. - 0166-445X .- 1879-1514. ; 271
  • Journal article (peer-reviewed)abstract
    • Carbamazepine (CBZ) is an anticonvulsant medication used to treat epilepsy and bipolar disorder. Due to its persistence and low removal rate in wastewater treatment plants, it is frequently detected in the environment, raising concerns regarding its potential adverse effects on aquatic organisms and ecosystems. In this study, we aimed to assess the impact of CBZ on the behavior and growth of juvenile yellow catfish Tachysurus fulvidraco , a native and economically important species in China. Fish were exposed to CBZ at three concentrations of 1, 10, or 100 mu g/L for 14 days. The fish exposed to 10 and 100 mu g/L of CBZ exhibited decreased feeding, and a significant increase in cannibalistic tendencies was observed in fish exposed to 100 mu g/L CBZ. Acetylcholinesterase activity was increased in the brain of fish exposed to 100 mu g/L CBZ. CBZ also inhibited the growth of yellow catfish. To better elucidate mechanisms of toxicity, transcriptomics was conducted in both the brain and liver. In the brain, gene networks associated with neurotransmitter dysfunction were altered by CBZ, as well as networks associated with mitochondrial dysfunction and metabolism. In the liver, gene networks associated with the immune system were altered by CBZ. The current study improves comprehension of the sub-lethal effects of CBZ and reveals novel insight into molecular and biochemical pathways disrupted by CBZ, identifying putative key events associated with reduced growth and altered behavior. This study emphasizes the necessity for improved comprehension of the effects of pharmaceutical contaminants on fish at environmentally relevant levels.
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27.
  • Clark, Andrew G., et al. (author)
  • Evolution of genes and genomes on the Drosophila phylogeny
  • 2007
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
  • Journal article (peer-reviewed)abstract
    • Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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28.
  • Du, Chenqiu, et al. (author)
  • Home dampness/mold(D/M) improvement in children's residences over the past decade in China-a comparison of repeated surveys in 2010 and 2019
  • 2021
  • In: Building and Environment. - : Elsevier. - 0360-1323 .- 1873-684X. ; 205
  • Journal article (peer-reviewed)abstract
    • There is mounting evidence that exposure to household dampness/mold (D/M) is the cause of respiratory, allergic diseases for children. While few research focuses on the effects caused by building environment changes, from a longitudinal investigation perspective, especially for China experiencing a rapid development in recent years. This study aimed to explore the changes of D/M in Chinese homes over the past 10 years and identify the impacts of climate, building energy efficiency and residents' behaviors. The cross-sectional surveys were repeatedly conducted in children' residences in 2010 (Period I) and 2019 (Period II), among Taiyuan, Urumqi in northern China, and Nanjing, Shanghai, Wuhan, Changsha, Chongqing in southern China. Finally, 23465 children in Period I and 34720 children in Period II were involved, with no changes of residences since birth. The results showed that the proportions for reported D/M indicators were significantly reduced in Period II: e.g., 93.8% and 84.1% residents respectively answered no visible mold spots and damp stains in current residences, compared to only 78.3% and 62.2% in Period I. Southern homes accounted for high proportions for D/M indicator occurrences; warm-humid climate, annual higher precipitation and lower sunshine hours, etc., exacerbated the indoor D/M exposure risks. While residents' behaviors like ventilation, airing quilt/beddings, regular cleaning ameliorated the reported D/M significantly. The findings, from a temporal and spacious dimension perspective, advance our understanding of indoor D/M changes, precisely improvement in children' homes over the past 10 years, benefiting to promote indoor air quality standards in China.
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29.
  • Escala-Garcia, Maria, et al. (author)
  • A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
  • 2020
  • In: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
  •  
30.
  • Fanourgakis, George S., et al. (author)
  • Evaluation of global simulations of aerosol particle and cloud condensation nuclei number, with implications for cloud droplet formation
  • 2019
  • In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:13, s. 8591-8617
  • Journal article (peer-reviewed)abstract
    • A total of 16 global chemistry transport models and general circulation models have participated in this study; 14 models have been evaluated with regard to their ability to reproduce the near-surface observed number concentration of aerosol particles and cloud condensation nuclei (CCN), as well as derived cloud droplet number concentration (CDNC). Model results for the period 2011-2015 are compared with aerosol measurements (aerosol particle number, CCN and aerosol particle composition in the submicron fraction) from nine surface stations located in Europe and Japan. The evaluation focuses on the ability of models to simulate the average across time state in diverse environments and on the seasonal and short-term variability in the aerosol properties. There is no single model that systematically performs best across all environments represented by the observations. Models tend to underestimate the observed aerosol particle and CCN number concentrations, with average normalized mean bias (NMB) of all models and for all stations, where data are available, of -24% and -35% for particles with dry diameters >50 and >120nm, as well as -36% and -34% for CCN at supersaturations of 0.2% and 1.0%, respectively. However, they seem to behave differently for particles activating at very low supersaturations (<0.1%) than at higher ones. A total of 15 models have been used to produce ensemble annual median distributions of relevant parameters. The model diversity (defined as the ratio of standard deviation to mean) is up to about 3 for simulated N3 (number concentration of particles with dry diameters larger than 3nm) and up to about 1 for simulated CCN in the extra-polar regions. A global mean reduction of a factor of about 2 is found in the model diversity for CCN at a supersaturation of 0.2% (CCN0.2) compared to that for N3, maximizing over regions where new particle formation is important. An additional model has been used to investigate potential causes of model diversity in CCN and bias compared to the observations by performing a perturbed parameter ensemble (PPE) accounting for uncertainties in 26 aerosol-related model input parameters. This PPE suggests that biogenic secondary organic aerosol formation and the hygroscopic properties of the organic material are likely to be the major sources of CCN uncertainty in summer, with dry deposition and cloud processing being dominant in winter. Models capture the relative amplitude of the seasonal variability of the aerosol particle number concentration for all studied particle sizes with available observations (dry diameters larger than 50, 80 and 120nm). The short-term persistence time (on the order of a few days) of CCN concentrations, which is a measure of aerosol dynamic behavior in the models, is underestimated on average by the models by 40% during winter and 20% in summer. In contrast to the large spread in simulated aerosol particle and CCN number concentrations, the CDNC derived from simulated CCN spectra is less diverse and in better agreement with CDNC estimates consistently derived from the observations (average NMB -13% and -22% for updraft velocities 0.3 and 0.6ms-1, respectively). In addition, simulated CDNC is in slightly better agreement with observationally derived values at lower than at higher updraft velocities (index of agreement 0.64 vs. 0.65). The reduced spread of CDNC compared to that of CCN is attributed to the sublinear response of CDNC to aerosol particle number variations and the negative correlation between the sensitivities of CDNC to aerosol particle number concentration (Nd=Na) and to updraft velocity (Nd=w). Overall, we find that while CCN is controlled by both aerosol particle number and composition, CDNC is sensitive to CCN at low and moderate CCN concentrations and to the updraft velocity when CCN levels are high. Discrepancies are found in sensitivities Nd=Na and Nd=w; models may be predisposed to be too "aerosol sensitive" or "aerosol insensitive" in aerosol-cloud-climate interaction studies, even if they may capture average droplet numbers well. This is a subtle but profound finding that only the sensitivities can clearly reveal and may explain intermodel biases on the aerosol indirect effect.
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31.
  • Feng, Peizhong, et al. (author)
  • Combustion synthesis of (Mo1-xCrx)Si-2 (x=0.00-0.30) alloys in SHS mode
  • 2012
  • In: Advanced Powder Technology. - : Elsevier BV. - 0921-8831 .- 1568-5527. ; 23:2, s. 133-138
  • Journal article (peer-reviewed)abstract
    • Combustion synthesis was adopted to successfully synthesize molybdenum-silicon-chromium (Mo-Si-Cr) alloys by the mode of self-propagating high-temperature synthesis (SHS). The experimental study of combustion synthesis of Mo-Si-Cr alloys was conducted on elemental powder compacts. Powder compacts with nominal compositions including MoSi2, (Mo0.95Cr0.05)Si-2, (Mo0.90Cr0.10)Si-2, (Mo0.85Cr0.15)Si-2, (Mo0.80Cr0.20)Si-2, (Mo0.75Cr0.25)Si-2 and (Mo0.20Cr0.30)Si-2 were employed in combustion synthesis experiments. The combustion mode, combustion temperature, flame-front propagation velocity and product structure were investigated. The results showed that Mo-Si-Cr alloys were synthesized by an unsteady state combustion mode with a spiral-trajectory reaction front. The peak combustion temperature reduced with the addition of Cr to Mo-Si system. The flame-front propagation velocity decreased with an increase in Cr content of the powder compact. The X-ray diffraction (XRD) results showed that the crystal structure of the combustion product changed from CIIb-type structure (Mo0.90Cr0.10)Si-2 to C40-type structure (Mo0.80Cr0.15)Si-2 with increase in Cr content of Mo-Cr-Si alloys. The intensities of diffraction peaks of the C40-type phase gradually increased with increase in Cr content.
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32.
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33.
  • Feng, Peizhong, et al. (author)
  • Mechanically activated reactive synthesis of refractory molybdenum and tungsten silicides
  • 2008
  • In: International journal of refractory metals & hard materials. - : Elsevier BV. - 0263-4368. ; 26:3, s. 173-178
  • Journal article (peer-reviewed)abstract
    • In this study, processing of elemental powders mixtures was carried out by mechanical alloying (MA) and heat treatment in vacuum at 700–1000 °C for 1 h. The phase transformation of the powders was investigated by X-ray diffractometer (XRD). The results showed that mechanical alloying promoted the formation of a solid solution of elemental powders. The energy stored in the powders was increased as a result of exterior energy and the barrier energy of the formation of the compound could be exceeded easily. Intermetallics of MoSi2, WSi2, Mo5Si3, Mo3Si and SiC/MoSi2 composite powders were synthesized by mechanically activated reactive synthesis (MARS). The mechanically induced self-sustaining reaction was observed in MoSi2 and MoSi2 + 10 wt%SiC stoichiometry system. It has concluded that mechanically activated reactive synthesis is an effective method for the preparation of high melting-point refractory compounds.
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34.
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35.
  • Han, Guang, et al. (author)
  • Porous titania surfaces on titanium with hierarchical macro- and mesoporosities for enhancing cell adhesion, proliferation and mineralization
  • 2015
  • In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 47, s. 376-383
  • Journal article (peer-reviewed)abstract
    • Titanium received a macroporous titania surface layer by anodization, which contains open pores with average pore diameter around 5 gm. An additional mesoporous titania top layer following the contour of the macropores, of 100-200 nm thickness and with a pore diameter of 10 nm, was formed by using the evaporation-induced self-assembly (EISA) method with titanium (IV) tetraethoxide as the precursor. A coherent laminar titania surface layer was thus obtained, creating a hierarchical macro- and mesoporous surface that was characterized by high-resolution electron microscopy. The interfacial bonding between the surface layers and the titanium matrix was characterized by the scratch test that confirmed a stable and strong bonding of titania surface layers on titanium. The wettability to water and the effects on the osteosarcoma cell line (SaOS-2) proliferation and mineralization of the formed titania surface layers were studied systematically by cell culture and scanning electron microscopy. The results proved that the porous titania surface with hierarchical macro- and mesoporosities was hydrophilic that significantly promoted cell attachment and spreading. A synergistic role of the hierarchical macro- and mesoporosities was revealed in terms of enhancing cell adhesion, proliferation and mineralization, compared with the titania surface with solo scale topography.
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36.
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37.
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38.
  • Jiang, Yi, et al. (author)
  • Promoting the Activity of Catalysts for the Oxidation of Water with Bridged Dinuclear Ruthenium Complexes
  • 2013
  • In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 52:12, s. 3398-3401
  • Journal article (peer-reviewed)abstract
    • Solar fuels: Dinuclear ruthenium catalysts prepared from two covalently bridged monomeric catalytic units show outstanding activities towards the oxidation of water with high turnover numbers up to 43 000 and turnover frequencies up to 40 s-1 (see picture). Direct comparison of the performance parameters indicates that the dimers are significantly more active as catalysts than the monomers.
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39.
  • Jiang, Zhiwu, et al. (author)
  • Combustion synthesis and mechanical properties of MoSi2­-ZrB2­-SiC ceramics
  • 2018
  • In: Journal of the Ceramic Society of Japan. - : Ceramic Society of Japan. - 1882-0743 .- 1348-6535. ; 126:7, s. 504-509
  • Journal article (peer-reviewed)abstract
    • MoSi2ZrB2SiC ceramics were synthesized using Mo, Zr, Si and B4C powders by self-propagating high-temperature synthesis and densifying by spark plasma sintering. The effects of MoSi2 content on the combustion synthesis process, microstructure, and mechanical properties of the ceramics were investigated. The results showed that combustion synthesis is an unstable mode, spiral combustion. The Gibbs calculations and combustion temperature curves indicate there are two reactions occurring at the same time. The volume fraction of the four different phases and their relative densities were also measured and calculated. Compared to pure MoSi2, the 1.0MoSi20.2ZrB20.1SiC (M10) ceramic exhibits excellent mechanical properties with its maximum Vickers hardness and fracture toughness being 14.0 GPa and of 5.5 MPa m1/2, respectively. The hardness is in agreement with the rule of mixture. The morphology of indentation cracks reveals that the fracture toughness improves as a result of toughening mechanisms such as crack bridge, crack deflection, and microcracks.
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40.
  • Jiao, Xinyang, et al. (author)
  • Effect of heating rate on porous TiAl-based intermetallics synthesized by thermal explosion
  • 2017
  • In: Materials and Manufacturing Processes. - : Taylor & Francis. - 1042-6914 .- 1532-2475. ; 32:5, s. 489-494
  • Journal article (peer-reviewed)abstract
    • TiAl-based porous materials were synthesized by a novel process of thermal explosion (TE) reaction. The effect of heating rate on expansion behavior of powder assemblies, phase compositions and pore structures were investigated. Results showed that the actual temperature of specimen increased rapidly from 655-661 °C (furnace temperature) to 1018–1136 °C (combustion temperature) in a short time interval of 25–55 s, indicating that an obvious TE reaction occurred at different heating rates (1, 2, 5 and 10°C · min−1). TE reaction in Ti/Al powder assemblies resulted in formation of open-celled TiAl-based intermetallics. When the heating rate was set at 5 °C · min−1, the maximum open porosity of 59% was obtained in Ti-Al bodies, which experienced the highest combustion temperature (1136°C) and underwent maximum volume expansion (48%). The pore size distribution was uniform and pores were interconnected in TE products.
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41.
  • Jiao, Xinyang, et al. (author)
  • Microstructure Evolution and Pore Formation Mechanism of Porous TiAl3 Intermetallics via Reactive Sintering
  • 2018
  • In: Acta Metallurgica Sinica (English Letters). - : Springer. - 1006-7191 .- 2194-1289. ; 31:4, s. 440-448
  • Journal article (peer-reviewed)abstract
    • Porous TiAl3 intermetallics were fabricated through vacuum reactive sintering from Ti–75Al at.% elemental powder mixture. The phase compositions, expansion behaviors, pore characteristics and microstructure evolution of TiAl3 intermetallics were investigated, and the pore formation mechanism was also proposed. It was found that the actual temperature of compacts showed an acute climb from 668 to 1244 °C in 166s, while the furnace temperature maintained the linear growth of 5 °C/min, which indicated that an obvious thermal explosion (TE) reaction occurred during sintering, and only single-phase TiAl3 intermetallic was synthesized in TE products. The open porosity increased from 22.2 (green compact) to 32.8% after reactive diffusion sintering at 600 °C and rised to 58.7% after TE, then decreased to 51.2% after high-temperature homogenization at 1100 °C. Therefore, TE reaction is the dominated pore formation mechanism of porous TiAl3 intermetallics. The pore evolution in porous TiAl3 intermetallics occurred by the following mechanisms: certain intergranular pores remained among powder particles of green compact, then low-temperature sintering resulted in a further increase in porosity due to the Kirkendall effect. Moreover, TE reaction gave rise to a dramatic volume expansion because of the rapid increase in temperature, and high-temperature sintering caused densification and a slight shrinkage.
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42.
  • Kong, Ge, et al. (author)
  • Recycling Molybdenum Oxides from Waste Molybdenum Disilicides: Oxidation Experimental Study and Photocatalytic Properties
  • 2019
  • In: Oxidation of Metals. - : Springer. - 0030-770X .- 1573-4889. ; 92:1-2, s. 1-12
  • Journal article (peer-reviewed)abstract
    • To recycle elemental molybdenum from waste molybdenum disilicide (MoSi2) heating elements, the MoSi2 was first disintegrated to MoO3 and SiO2 powders in air at a pest oxidation temperature of 500 °C. X-ray diffraction (XRD) patterns confirmed the completion of the pest oxidation reaction. The mixture of MoO3 and SiO2 powders were heated to 950 °C in a tube furnace to evaporate MoO3, and the XRD patterns of the residue showed that only SiO2 was left in the crucible, confirming that the MoO3 was removed through thermal evaporation. The collected MoO3 crystals had a striped morphology. Photocatalytic performance of MoO3 showed superior activity in comparison with commercial MoO3 and P25 for the degradation of methylene blue under visible light irradiation. The photocatalytic degradation activity of MoO3 synthesized by thermal evaporation at 950 °C was 99.25% in 60 min.
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43.
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44.
  • Lee, Dung-Fang, et al. (author)
  • Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling.
  • 2012
  • In: Cell Stem Cell. - : Elsevier BV. - 1934-5909 .- 1875-9777. ; 11:2
  • Journal article (peer-reviewed)abstract
    • Many signals must be integrated to maintain self-renewal and pluripotency in embryonic stem cells (ESCs) and to enable induced pluripotent stem cell (iPSC) reprogramming. However, the exact molecular regulatory mechanisms remain elusive. To unravel the essential internal and external signals required for sustaining the ESC state, we conducted a short hairpin (sh) RNA screen of 104 ESC-associated phosphoregulators. Depletion of one such molecule, aurora kinase A (Aurka), resulted in compromised self-renewal and consequent differentiation. By integrating global gene expression and computational analyses, we discovered that loss of Aurka leads to upregulated p53 activity that triggers ESC differentiation. Specifically, Aurka regulates pluripotency through phosphorylation-mediated inhibition of p53-directed ectodermal and mesodermal gene expression. Phosphorylation of p53 not only impairs p53-induced ESC differentiation but also p53-mediated suppression of iPSC reprogramming. Our studies demonstrate an essential role for Aurka-p53 signaling in the regulation of self-renewal, differentiation, and somatic cell reprogramming.
  •  
45.
  • Li, Shuo, et al. (author)
  • Economic, energy and environmental performance assessment on wheat production under water-saving cultivation strategies
  • 2022
  • In: Energy. - : Elsevier BV. - 0360-5442 .- 1873-6785. ; , s. 125330-125330
  • Journal article (peer-reviewed)abstract
    • Improvements in economic profit, energy-use efficiency and environmental friendliness are critical for the sustainability of wheat production. The present study was aimed at evaluating the suitability of wheat production shifting conventional flat planting (CFH) and supplemental irrigation (SIH) with water-saving cultivation strategies [straw mulching (SML) and plastic film mulching (PFL) with 50% less N fertilizer] from economic, energy, and environmental perspectives on the Loess Plateau of China. Results showed that the PFL exhibited ∼18.5% and 12.7% higher grain yields, and 74.0% and 59.9% higher economic profit over the CFH and SML, while reduced grain yields by 9.6% retative to the SIH. Meanwhile, the economic profit and the ratio of income to cost remained consistent between the PFL and SIH. The PFL had the highest net energy out, energy use efficiency and energy productivity, but had the lowest specific energy. Compared with the SIH, the total environmental emissions final score increased by 36.6% under SML, while decreased by 24.8% under PFL. Overall, the strategy of plastic film mulching with 50% less N fertilizer has great potential to cater to the demands of wheat production with environmental sustainability on the Loess Plateau of China.
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46.
  • Li, Yachen, et al. (author)
  • Intrauterine and early postnatal exposures to submicron particulate matter and childhood allergic rhinitis : A multicity cross-sectional study in China
  • 2024
  • In: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 247
  • Journal article (peer-reviewed)abstract
    • Background: Airborne particulate matter pollution has been linked to occurrence of childhood allergic rhinitis (AR). However, the relationships between exposure to particulate matter with an aerodynamic diameter <= 1 µm (PM1) during early life (in utero and first year of life) and the onset of childhood AR remain largely unknown. This study aims to investigate potential associations of in utero and first-year exposures to size-segregated PMs, including PM1, PM1-2.5, PM2.5, PM2.5-10, and PM10, with childhood AR.Methods: We investigated 29286 preschool children aged 3-6 years in 7 Chinese major cities during 2019-2020 as the Phase II of the China Children, Families, Health Study. Machine learning-based space-time models were utilized to estimate early-life residential exposure to PM1, PM2.5, and PM10 at 1 x 1-km resolutions. The concentrations of PM1-2.5 and PM2.5-10 were calculated by subtracting PM1 from PM2.5 and PM2.5 from PM10, respectively. Multiple mixed-effects logistic models were used to assess the odds ratios (ORs) and 95% confidence intervals (CIs) of childhood AR associated with per 10-µg/m3 increase in exposure to particulate air pollution during in utero period and the first year of life.Results: Among the 29286 children surveyed (mean +/- standard deviation, 4.9 +/- 0.9 years), 3652 (12.5%) were reported to be diagnosed with AR. Average PM1 concentrations during in utero period and the first year since birth were 36.3 +/- 8.6 µg/m3 and 33.1 +/- 6.9 µg/m3, respectively. Exposure to PM1 and PM2.5 during pregnancy and the first year of life was associated with an increased risk of AR in children, and the OR estimates were higher for each 10-µg/m3 increase in PM1 than for PM2.5 (e.g., 1.132 [95% CI: 1.022-1.254] vs. 1.079 [95% CI: 1.014-1.149] in pregnancy; 1.151 [95% CI: 1.014-1.306] vs. 1.095 [95% CI: 1.008-1.189] in the first year of life). No associations were observed between AR and both pre- and post-natal exposure to PM1-2.5, indicating that PM1 rather than PM1-2.5 contributed to the association between PM2.5 and childhood AR. In trimester-stratified analysis, childhood AR was only found to be associated with exposure to PM1 (OR = 1.077, 95% CI: 1.027-1.128), PM2.5 (OR = 1.048, 95% CI: 1.018-1.078), and PM10 (OR = 1.032, 95% CI: 1.007-1.058) during the third trimester of pregnancy. Subgroup analysis suggested stronger PM-AR associations among younger (<5 years old) and winter-born children.Conclusions: Prenatal and postnatal exposures to ambient PM1 and PM2.5 were associated with an increased risk of childhood AR, and PM2.5-related hazards could be predominantly attributed to PM1. These findings highlighted public health significance of formulating air quality guideline for ambient PM1 in mitigating children's AR burden caused by particulate air pollution.
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47.
  • Liu, Zhiyong, et al. (author)
  • Compensating Effects Between Climate and Underlying Characteristics on Watershed Water Loss
  • 2023
  • In: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 128:6
  • Journal article (peer-reviewed)abstract
    • Identifying climate impacts on watershed water loss (evapotranspiration) generally involves the interactions with land surface change (e.g., vegetation dynamics and anthropogenic disturbances). Here, we seek to understand the compensating effects of climate and underlying characteristics on watershed evapotranspiration. In this regard, an analytical solution was derived by using a simple water-energy partitioning framework for separating the individual contributions of climate and underlying characteristics to changes in watershed actual evapotranspiration between 1930-1970 and 1971-2008 over global 87 basins. We found that for the basins with larger increases in the total evapotranspiration, a positive underlying characteristic-related contribution is dominant, rather than the climate-related contribution. Tradeoffs (i.e., the compensating effects) between the contributions of climate and underlying characteristics to evaporative water loss were also identified in a few basins where there were relatively large changes in the underlying characteristic-related evapotranspiration but only a slight change in the total evapotranspiration. This suggests that the climate contribution in evapotranspiration may offset the effect of underlying characteristic-related changes over these basins, associated with stronger hydrological resilience under the double impacts of both climate and underlying factors. The results also indicate that the underlying characteristics exert greater contributions to the changes in the total evapotranspiration rather than the climate variation, and the underlying characteristic-related evapotranspiration variations are closely related to the changes in reservoirs and land-use types of the basins. The presented findings may provide an insightful understanding of interactions among climate, water, and underlying characteristics over global basins.
  •  
48.
  • Mueller, Stefanie H., et al. (author)
  • Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry
  • 2023
  • In: Genome Medicine. - : BioMed Central (BMC). - 1756-994X. ; 15
  • Journal article (peer-reviewed)abstract
    • Background: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes.Methods: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry.Results: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 x 10(-6)) and AC058822.1 (P = 1.47 x 10(-4)), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C.Conclusions: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 x 10(-5)), demonstrating the importance of diversifying study cohorts.
  •  
49.
  • Nyman, Elin, et al. (author)
  • Perturbation biology links temporal protein changes to drug responses in a melanoma cell line
  • 2020
  • In: PloS Computational Biology. - : PUBLIC LIBRARY SCIENCE. - 1553-734X .- 1553-7358. ; 16:7
  • Journal article (peer-reviewed)abstract
    • Cancer cells have genetic alterations that often directly affect intracellular protein signaling processes allowing them to bypass control mechanisms for cell death, growth and division. Cancer drugs targeting these alterations often work initially, but resistance is common. Combinations of targeted drugs may overcome or prevent resistance, but their selection requires context-specific knowledge of signaling pathways including complex interactions such as feedback loops and crosstalk. To infer quantitative pathway models, we collected a rich dataset on a melanoma cell line: Following perturbation with 54 drug combinations, we measured 124 (phospho-)protein levels and phenotypic response (cell growth, apoptosis) in a time series from 10 minutes to 67 hours. From these data, we trained time-resolved mathematical models that capture molecular interactions and the coupling of molecular levels to cellular phenotype, which in turn reveal the main direct or indirect molecular responses to each drug. Systematic model simulations identified novel combinations of drugs predicted to reduce the survival of melanoma cells, with partial experimental verification. This particular application of perturbation biology demonstrates the potential impact of combining time-resolved data with modeling for the discovery of new combinations of cancer drugs.
  •  
50.
  • Rommel, O, et al. (author)
  • Heparan sulfate proteoglycans interact exclusively with conformationally intact HPV L1 assemblies: Basis for a virus-like particle ELISA
  • 2005
  • In: Journal of Medical Virology. - : Wiley. - 1096-9071 .- 0146-6615. ; 75:1, s. 114-121
  • Journal article (peer-reviewed)abstract
    • In this article, we demonstrate that interaction of human papillomavirus-like particles (HPV-VLPs) with the putative glucosaminoglycan binding receptor is strictly dependent on conformational integrity. Such conformations are present on VLPs and capsomeres but not on monomers of the major capsid protein, L1, confirming reports that capsomeres can induce virus-neutralizing antibodies. Furthermore, we show the suitability of this specific interaction for development of VLP-based enzyme-linked immunosorbent assays (ELISAs), using heparin for indirect coupling of VLPs to microtiter plates, which may add an intrinsic quality control. This avoids presentation of linear, often highly cross-reactive epitopes of L1. In addition, heparin specifically interacts with a wide variety of HPV types, making it a prime candidate for a universal capture molecule.
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