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Sökning: WFRF:(Nawaz R.)

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1.
  • 2017
  • swepub:Mat__t
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  • Ederle, Joerg, et al. (författare)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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  • Lozano, Rafael, et al. (författare)
  • 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
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)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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  • Murray, Christopher J. L., et al. (författare)
  • 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
  • Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 392:10159, s. 1995-2051
  • Tidskriftsartikel (refereegranskat)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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  • Wang, Haidong, et al. (författare)
  • Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2015 : the Global Burden of Disease Study 2015.
  • 2016
  • Ingår i: The lancet. HIV. - : Elsevier. - 2352-3018. ; 3:8, s. e361-e387
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.METHODS: For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.FINDINGS: Global HIV incidence reached its peak in 1997, at 3·3 million new infections (95% uncertainty interval [UI] 3·1-3·4 million). Annual incidence has stayed relatively constant at about 2·6 million per year (range 2·5-2·8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38·8 million (95% UI 37·6-40·4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1·8 million deaths (95% UI 1·7-1·9 million) in 2005, to 1·2 million deaths (1·1-1·3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.INTERPRETATION: Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030.
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  • Ahmed, S., et al. (författare)
  • Annealing characteristics of electrically isolated InGaAsP devices
  • 2007
  • Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 91:6, s. 062112-
  • Tidskriftsartikel (refereegranskat)abstract
    • The authors report on the effects of fluorine implants on the sheet resistivity of n-type InGaAsP layers grown lattice matched to InP by metal organic molecular beam epitaxy. Projected range matched fluorine ions are implanted at multiple energies and single MeV energy at room temperature (RT) and 77 K in both cases. Hall and resistivity measurements are carried out for the van der Pauw samples and the evolution of sheet resistivity (R-s) as a function of annealing temperature was studied in both cases. Fluorine multienergy implantation at 77 K produces higher as-implanted resistivity layers of similar to 10(7) Omega/square compared to RT implants. It is further observed that RT and 77 K implants recover to their preimplanted sheet resistivity values as soon as they are annealed at temperatures higher than 500 degrees C. Substrate temperature and collision cascade density due to multiple energy implants are found to play an important role to optimize the isolation process.
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  • Karwen, T., et al. (författare)
  • Platelet-derived lipids promote insulin secretion of pancreatic beta cells
  • 2023
  • Ingår i: Embo Molecular Medicine. - 1757-4676. ; 15:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyperreactive platelets are commonly observed in diabetic patients indicating a potential link between glucose homeostasis and platelet reactivity. This raises the possibility that platelets may play a role in the regulation of metabolism. Pancreatic beta cells are the central regulators of systemic glucose homeostasis. Here, we show that factor(s) derived from beta cells stimulate platelet activity and platelets selectively localize to the vascular endothelium of pancreatic islets. Both depletion of platelets and ablation of major platelet adhesion or activation pathways consistently resulted in impaired glucose tolerance and decreased circulating insulin levels. Furthermore, we found platelet-derived lipid classes to promote insulin secretion and identified 20-Hydroxyeicosatetraenoic acid (20-HETE) as the main factor promoting beta cells function. Finally, we demonstrate that the levels of platelet-derived 20-HETE decline with age and that this parallels with reduced impact of platelets on beta cell function. Our findings identify an unexpected function of platelets in the regulation of insulin secretion and glucose metabolism, which promotes metabolic fitness in young individuals.
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  • Nawaz, Muhammad, et al. (författare)
  • Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair
  • 2018
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 7:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.
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  • Alyami, Mana, et al. (författare)
  • Estimating compressive strength of concrete containing rice husk ash using interpretable machine learning-based models
  • 2024
  • Ingår i: Case Studies in Construction Materials. - : Elsevier. - 2214-5095. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • The construction sector is a major contributor to global greenhouse gas emissions. Using recycled and waste materials in concrete is a practical solution to address environmental challenges. Currently, agricultural waste is widely used as a substitute for cement in the production of eco-friendly concrete. However, traditional methods for assessing the strength of such materials are both expensive and time-consuming. Therefore, this study uses machine learning techniques to develop prediction models for the compressive strength (CS) of rice husk ash (RHA) concrete. The ML techniques used in the present study include random forest (RF), light gradient boosting machine (LightGBM), ridge regression, and extreme gradient boosting (XGBoost). A total of 348 values of CS were collected from the experimental studies, and five characteristics of RHA concrete were taken as input variables. For the performance assessment of the models, multiple statistical metrics were used. During the training phase, the correlation coefficients (R) obtained for ridge regression, RF, XGBoost, and LightGBM were 0.943, 0.981, 0.985, and 0.996, respectively. In the testing set, the developed models demonstrated even higher performance, with correlation coefficients of 0.971, 0.993, 0.992, and 0.998 for ridge regression, RF, XGBoost, and LightGBM, respectively. The statistical analysis revealed that the LightGBM model outperformed other models, whereas the ridge regression model exhibited comparatively lower accuracy. SHapley Additive exPlanation (SHAP) method was employed for the interpretability of the developed model. The SHAP analysis revealed that water-to-cement is a controlling parameter in estimating the CS of RHA concrete. In conclusion, this study provides valuable guidance for builders and researchers to estimate the CS of RHA concrete. However, it is suggested that more input variables be incorporated and hybrid models utilized to further enhance the reliability and precision of the models.
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  • Alyami, Mana, et al. (författare)
  • Predictive modeling for compressive strength of 3D printed fiber-reinforced concrete using machine learning algorithms
  • 2024
  • Ingår i: Case Studies in Construction Materials. - : Elsevier. - 2214-5095. ; 20
  • Tidskriftsartikel (refereegranskat)abstract
    • Three-dimensional (3D) printing in the construction industry is growing rapidly due to its inherent advantages, including intricate geometries, reduced waste, accelerated construction, cost-effectiveness, eco-friendliness, and improved safety. However, optimizing the mixture composition for 3D-printed concrete remains a formidable task, encompassing multiple variables and requiring a comprehensive trial-and-error experimentation process. Accordingly, this study used seven machine learning (ML) algorithms, including support vector regression (SVR), decision tree (DT), SVR-Bagging, SVR-Boosting, random forest (RF), gradient boosting (GB), and gene expression programming (GEP) for forecasting the compressive strength (CS) of 3D printed fiber-reinforced concrete (3DP-FRC). For model development, 299 data points were collected from experimental studies and split into two portions: 70% for model training and 30% for model validation. Various statistical metrics were employed to examine the accuracy and generalizability of the established models. The DT, RF, GB, and GEP models demonstrated higher accuracy in the validation set, achieving correlation (R) values of 0.987, 0.986, 0.986, and 0.98, respectively. The DT, RF, GB, and GEP models exhibited mean absolute error (MAE) scores of 4.644, 3.989, 3.90, and 5.691, respectively. Furthermore, the combination of SVR with boosting and bagging techniques slightly improved the accuracy compared to the individual SVR model. Additionally, the SHapley Additive exPlanations (SHAP) approach unveils the proportional significance of parameters in influencing the CS of 3DP-FRC. The SHAP technique revealed that water, silica fume, superplasticizer, sand content, and loading directions are the dominant parameters in estimating the CS of 3DP-FRC. The SHAP local interpretability unveils the intrinsic relationship between diverse input variables and their impacts on the strength of 3DP-FRC. The SHAP interpretability offers significant insights into the optimum mix proportion of 3DP-FRC.
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  • Arpaia, Riccardo, 1985, et al. (författare)
  • Highly homogeneous YBCO/LSMO nanowires for photoresponse experiments
  • 2014
  • Ingår i: Superconductor Science and Technology. - : IOP Publishing. - 0953-2048 .- 1361-6668. ; 27:4
  • Tidskriftsartikel (refereegranskat)abstract
    • By using nanolithography and a soft etching procedure, we have realized YBa2Cu3O7-x/La0.7Sr0.3MnO3 (YBCO/LSMO) nanowires, with cross sections down to 100 x 50 nm(2) that ensure the cover age of areas up to 10 x 30 mu m(2). The LSMO layer acts as a capping for YBCO, minimizing the degradation of the superconducting properties taking place during the patterning; moreover, as a ferromagnetic manganite, it is expected to accelerate the relaxation dynamics of quasiparticles in YBCO, making such a system potentially attractive for applications in superconducting ultrafast optoelectronics. The reproducibility of the values of the critical current densities measured in different devices with the same geometry makes our nanowires ideal candidates for photoresponse experiments. First measurements have shown a satisfactory photoresponse from YBCO/LSMO devices.
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21.
  • Bedard, J., et al. (författare)
  • Suppressors of the Chloroplast Protein Import Mutant tic40 Reveal a Genetic Link between Protein Import and Thylakoid Biogenesis
  • 2017
  • Ingår i: Plant Cell. - : Oxford University Press (OUP). - 1040-4651 .- 1532-298X. ; 29:7
  • Tidskriftsartikel (refereegranskat)abstract
    • To extend our understanding of chloroplast protein import and the role played by the import machinery component Tic40, we performed a genetic screen for suppressors of chlorotic tic40 knockout mutant Arabidopsis thaliana plants. As a result, two suppressor of tic40 loci, stic1 and stic2, were identified and characterized. The stic1 locus corresponds to the gene ALBINO4 (ALB4), which encodes a paralog of the well-known thylakoid protein targeting factor ALB3. The stic2 locus identified a previously unknown stromal protein that interacts physically with both ALB4 and ALB3. Genetic studies showed that ALB4 and STIC2 act together in a common pathway that also involves cpSRP54 and cpFtsY. Thus, we conclude that ALB4 and STIC2 both participate in thylakoid protein targeting, potentially for a specific subset of thylakoidal proteins, and that this targeting pathway becomes disadvantageous to the plant in the absence of Tic40. As the stic1 and stic2 mutants both suppressed tic40 specifically (other TIC-related mutants were not suppressed), we hypothesize that Tic40 is a multifunctional protein that, in addition to its originally described role in protein import, is able to influence downstream processes leading to thylakoid biogenesis.
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  • Gudmundsson, O. O., et al. (författare)
  • Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder
  • 2019
  • Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9
  • Tidskriftsartikel (refereegranskat)abstract
    • Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR=2.43, P=1.6×10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.
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  • Hu, Jiaxin, et al. (författare)
  • Allele-selective inhibition of ataxin-3 (ATX3) expression by antisense oligomers and duplex RNAs
  • 2011
  • Ingår i: Biological chemistry (Print). - 1431-6730 .- 1437-4315. ; 392:4, s. 315-325
  • Tidskriftsartikel (refereegranskat)abstract
    • Spinocerebellar ataxia-3 (also known as Machado-Joseph disease) is an incurable neurodegenerative disorder caused by expression of a mutant variant of ataxin-3 (ATX3) protein. Inhibiting expression of ATX3 would provide a therapeutic strategy, but indiscriminant inhibition of both wild-type and mutant ATX3 might lead to undesirable side effects. An ideal silencing agent would block expression of mutant ATX3 while leaving expression of wild-type ATX3 intact. We have previously observed that peptide nucleic acid (PNA) conjugates targeting the expanded CAG repeat within ATX3 mRNA block expression of both alleles. We have now identified additional PNAs capable of inhibiting ATX3 expression that vary in length and in the nature of the conjugated cation chain. We can also achieve potent and selective inhibition using duplex RNAs containing one or more mismatches relative to the CAG repeat. Anti-CAG antisense bridged nucleic acid oligonucleotides that lack a cationic domain are potent inhibitors but are not allele-selective. Allele-selective inhibitors of ATX3 expression provide insights into the mechanism of selectivity and promising lead compounds for further development and in vivo investigation.
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25.
  • Jonsson, Lina, 1982, et al. (författare)
  • Rare and Common Variants Conferring Risk of Tooth Agenesis
  • 2018
  • Ingår i: Journal of Dental Research. - : SAGE Publications. - 0022-0345 .- 1544-0591. ; 97:5, s. 515-522
  • Tidskriftsartikel (refereegranskat)abstract
    • We present association results from a large genome-wide association study of tooth agenesis (TA) as well as selective TA, including 1,944 subjects with congenitally missing teeth, excluding third molars, and 338,554 controls, all of European ancestry. We also tested the association of previously identified risk variants, for timing of tooth eruption and orofacial clefts, with TA. We report associations between TA and 9 novel risk variants. Five of these variants associate with selective TA, including a variant conferring risk of orofacial clefts. These results contribute to a deeper understanding of the genetic architecture of tooth development and disease. The few variants previously associated with TA were uncovered through candidate gene studies guided by mouse knockouts. Knowing the etiology and clinical features of TA is important for planning oral rehabilitation that often involves an interdisciplinary approach.
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26.
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27.
  • Nawaz, Imran, et al. (författare)
  • Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma
  • 2015
  • Ingår i: Oncotarget. - Albany, NY, United States : Impact Journals LLC. - 1949-2553. ; 6:31, s. 31493-31507
  • Tidskriftsartikel (refereegranskat)abstract
    • Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5-aza-2 deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines. Immunostaining showed strong expression of these genes in the membrane and cytoplasm of adjacent control nasopharyngeal epithelium cells, while they were weakly expressed in NPC tumor cells. The ITGA9 promoter showed marked differentially methylation between tumor and control tissue, whereas no differentially methylation could be detected for the WNT7A promoter. The expression level of ITGA9 in NPC tumors was downregulated 4.9-fold, compared to the expression in control. ITGA9 methylation was detected by methylation specific PCR (MSP) in 56% of EBV positive NPC-cases with 100% specificity. Taken together, this suggests that ITGA9 might be a TSG in NPC that is involved in tumor cell biology. The possibility of using ITGA9 methylation as a marker for early detection of NPC should further be explored.
  •  
28.
  • Nawaz, S., et al. (författare)
  • Explainable machine learning for diffraction patterns
  • 2023
  • Ingår i: Journal of applied crystallography. - : International Union of Crystallography (IUCr). - 0021-8898 .- 1600-5767. ; 56:5, s. 1494-1504
  • Tidskriftsartikel (refereegranskat)abstract
    • Serial crystallography experiments at X-ray free-electron laser facilities produce massive amounts of data but only a fraction of these data are useful for downstream analysis. Thus, it is essential to differentiate between acceptable and unacceptable data, generally known as 'hit' and 'miss', respectively. Image classification methods from artificial intelligence, or more specifically convolutional neural networks (CNNs), classify the data into hit and miss categories in order to achieve data reduction. The quantitative performance established in previous work indicates that CNNs successfully classify serial crystallography data into desired categories [Ke, Brewster, Yu, Ushizima, Yang & Sauter (2018). J. Synchrotron Rad. 25, 655-670], but no qualitative evidence on the internal workings of these networks has been provided. For example, there are no visualization methods that highlight the features contributing to a specific prediction while classifying data in serial crystallography experiments. Therefore, existing deep learning methods, including CNNs classifying serial crystallography data, are like a 'black box'. To this end, presented here is a qualitative study to unpack the internal workings of CNNs with the aim of visualizing information in the fundamental blocks of a standard network with serial crystallography data. The region(s) or part(s) of an image that mostly contribute to a hit or miss prediction are visualized. 
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29.
  • Paolini, Lucia, et al. (författare)
  • Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop
  • 2022
  • Ingår i: Journal of Extracellular Biology. - : Wiley. - 2768-2811. ; 1:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field.
  •  
30.
  • Qureshi, Hisham Jahangir, et al. (författare)
  • Prediction of compressive strength of two-stage (preplaced aggregate) concrete using gene expression programming and random forest
  • 2023
  • Ingår i: Case Studies in Construction Materials. - : Elsevier Ltd. - 2214-5095. ; 19
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this research is to predict preplaced-aggregate concrete (PAC) compressive strength (CS) by using machine learning approaches such as gene expression programming (GEP) and random forest (RF). PAC requires injecting a portland cement-sand grout with admixtures into a mold after coarse aggregate has been deposited, making CS prediction complicated and requiring substantial study. Machine learning methods were used to cut down on the time and money needed for extensive experimental testing. The database includes 135 values for CS with eleven input variables. There is an acceptable degree of agreement between predicted and experimental values, as shown by the CS R2 values of 0.94 for GEP and 0.96 for RF. When comparing RF with GEP, RF performed better as measured by R2. The lower values displayed by the statistical error also showed that RF performed better than GEP. To compare, the GEP model's COV, MAE, RSME, and RMSLE were 0.527, 1.569, 2.706, and 0.133, whereas those for RF were 0.450, 1.648, 2.17, and 0.092. The SHAP analysis showed the effects of each input parameter, illuminating the positive effect of increasing the superplasticizer content on strength and the negative effect of raising the water-to-binder ratio. Using machine learning approaches to forecast the CS of PAC, this study has the potential to boost environmental protection and economic advantage.
  •  
31.
  • Rahmani, V., et al. (författare)
  • Data reduction for X-ray serial crystallography using machine learning
  • 2023
  • Ingår i: Journal of applied crystallography. - 0021-8898 .- 1600-5767. ; 56, s. 200-213
  • Tidskriftsartikel (refereegranskat)abstract
    • Serial crystallography experiments produce massive amounts of experimental data. Yet in spite of these large-scale data sets, only a small percentage of the data are useful for downstream analysis. Thus, it is essential to differentiate reliably between acceptable data (hits) and unacceptable data (misses). To this end, a novel pipeline is proposed to categorize the data, which extracts features from the images, summarizes these features with the 'bag of visual words' method and then classifies the images using machine learning. In addition, a novel study of various feature extractors and machine learning classifiers is presented, with the aim of finding the best feature extractor and machine learning classifier for serial crystallography data. The study reveals that the oriented FAST and rotated BRIEF (ORB) feature extractor with a multilayer perceptron classifier gives the best results. Finally, the ORB feature extractor with multilayer perceptron is evaluated on various data sets including both synthetic and experimental data, demonstrating superior performance compared with other feature extractors and classifiers. 
  •  
32.
  • Ramirez, M. I., et al. (författare)
  • Technical challenges of working with extracellular vesicles
  • 2018
  • Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 10:3, s. 881-906
  • Tidskriftsartikel (refereegranskat)abstract
    • Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review. © 2018 The Royal Society of Chemistry.
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33.
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34.
  • Yu, Wenbin, et al. (författare)
  • Assessing the Long-­term Performance of Polyethylene Stabilised WithPhenolic Antioxidants Exposed to Water Containing Chlorine Dioxide
  • 2013
  • Ingår i: Polymer testing. - : Elsevier BV. - 0142-9418 .- 1873-2348. ; 32:2, s. 359-365
  • Tidskriftsartikel (refereegranskat)abstract
    • The addition of chlorine dioxide disinfectant to tap water prevents the spread of infection but has a serious drawback in that it degrades materials used in piping, including pipes made of polyethylene. Efficient methods are required to assess the long-term performance of different combinations of antioxidants and polyethylene grades. We have previously presented a screening method which exposes solutions of phenolic antioxidants in squalane (a liquid, low molar mass analogue of polyethylene) to 70 °C water containing either chlorine dioxide or chlorine. This method assesses the stability of the antioxidants towards these aqueous chlorinated media by determining the oxidation induction time through differential scanning calorimetry. The same experimental set-up with two modifications was used in developing a new method. A 0.3 mm thick polyethylene tape replaced the squalane phase and the supply of fresh water containing chlorine dioxide (10 ppm at pH = 6.8) was continuous; this required minimum attention from the operator over the longer exposure time periods used. Tapes of medium-density polyethylene containing 0.1 wt.% of six different phenolic antioxidants were studied. A linear relationship was established between the times to reach antioxidant depletion in the polyethylene tape samples and the times in the squalane samples (with the same antioxidants at the same concentration). A linear relationship was also found between the initial antioxidant consumption rates in polyethylene and squalane. Infrared spectroscopy and scanning electron microscopy of drawn samples revealed the onset of surface oxidation and surface embrittlement in tape samples exposed beyond the time for antioxidant depletion.
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