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1.
  • Thomas, HS, et al. (author)
  • 2019
  • swepub:Mat__t
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  • Mishra, A., et al. (author)
  • Stroke genetics informs drug discovery and risk prediction across ancestries
  • 2022
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
  • Journal article (peer-reviewed)abstract
    • Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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  • Delios, A., et al. (author)
  • Examining the generalizability of research findings from archival data
  • 2022
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:30
  • Journal article (peer-reviewed)abstract
    • This initiative examined systematically the extent to which a large set of archival research findings generalizes across contexts. We repeated the key analyses for 29 original strategic management effects in the same context (direct reproduction) as well as in 52 novel time periods and geographies; 45% of the reproductions returned results matching the original reports together with 55% of tests in different spans of years and 40% of tests in novel geographies. Some original findings were associated with multiple new tests. Reproducibility was the best predictor of generalizability-for the findings that proved directly reproducible, 84% emerged in other available time periods and 57% emerged in other geographies. Overall, only limited empirical evidence emerged for context sensitivity. In a forecasting survey, independent scientists were able to anticipate which effects would find support in tests in new samples. 
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  • de las Fuentes, Lisa, et al. (author)
  • Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
  • 2021
  • In: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
  • Journal article (peer-reviewed)abstract
    • Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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  • Kilpelainen, TO, et al. (author)
  • Multi-ancestry study of blood lipid levels identifies four loci interacting with physical activity
  • 2019
  • In: Nature communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 376-
  • Journal article (peer-reviewed)abstract
    • Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL cholesterol-increasing effects of the CLASP1, LHX1, and SNTA1 loci and attenuate the LDL cholesterol-increasing effect of the CNTNAP2 locus. The CLASP1, LHX1, and SNTA1 regions harbor genes linked to muscle function and lipid metabolism. Our results elucidate the role of physical activity interactions in the genetic contribution to blood lipid levels.
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15.
  • Feitosa, Mary F., et al. (author)
  • Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
  • 2018
  • In: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
  • Journal article (peer-reviewed)abstract
    • Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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  • de Vries, Paul S., et al. (author)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • In: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Journal article (peer-reviewed)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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  • Micah, Angela E., et al. (author)
  • Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
  • 2021
  • In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
  • Research review (peer-reviewed)abstract
    • Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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  • Kraja, Aldi T., et al. (author)
  • New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
  • 2017
  • In: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
  • Journal article (peer-reviewed)abstract
    • Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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  • Ntalla, Ioanna, et al. (author)
  • Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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  • Ademuyiwa, Adesoji O., et al. (author)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Journal article (peer-reviewed)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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  • Pinese, Mark, et al. (author)
  • The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly
  • 2020
  • In: Nature Communications. - : Springer Nature. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing. Healthspan and healthy aging are areas of research with potential socioeconomic impact. Here, the authors present the Medical Genome Reference Bank (MGRB) which consist of over 4,000 individuals aged 70 years and older without a history of the major age-related diseases and report on results from whole-genome sequencing and association analyses.
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  • Usman, M., et al. (author)
  • Refining and reuse of waste lube oil in si engines : A novel approach for a sustainable environment
  • 2021
  • In: Energies. - : MDPI AG. - 1996-1073. ; 14:10
  • Journal article (peer-reviewed)abstract
    • The protection of the environment and pollution control are issues of paramount impor-tance. Researchers today are engrossed in mitigating the harmful impacts of petroleum waste on the environment. Lubricating oils, which are essential for the smooth operation of engines, are often disposed of improperly after completing their life. In the experimental work presented in this paper, deteriorated engine oil was regenerated using the acid treatment method and was reused in the engine. The comparison of the properties of reused oil, the engine’s performance, and the emissions from the engine are presented. The reuse of regenerated oil, the evaluation of performance, and emissions establish the usefulness of the regeneration of waste lubricating oil. For the used oil, total acid number (TAN), specific gravity, flash point, ash content, and kinematic viscosity changed by 60.7%, 6.7%, 4.4%, 96%, and 15.5%, respectively, compared with fresh oil. The regeneration partially restored all the lost lubricating oil properties. The performance parameters, brake power (BP), brake specific fuel consumption (BSFC), and exhaust gas temperature (EGT) improved with regenerated oil in use compared with used oil. The emissions CO and NOX contents for acid-treated oil were 9.7% and 17.3% less in comparison with used oil, respectively. Thus, regenerated oil showed improved performance and oil properties along with significantly reduced emissions when employed in an SI engine. 
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  • Coimbra, M, et al. (author)
  • Segmentation for classification of gastroenterology images
  • 2010
  • In: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference. - 2375-7477. ; 2010, s. 4744-7
  • Journal article (peer-reviewed)
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  • Hussain, Fida, et al. (author)
  • A modeling approach for low-temperature SOFC-based micro-combined heat and power systems
  • 2019
  • In: International Journal of Modern Physics B. - : WORLD SCIENTIFIC PUBL CO PTE LTD. - 0217-9792. ; 33:4
  • Journal article (peer-reviewed)abstract
    • The world's challenge is to determine a more efficient, economical and environmental-friendly energy source to compete and replace the ongoing conventional energy resources. Solid oxide fuel cells (SOFCs) provide a highly efficient system to use divergent energy resources and have proved to provide the cleanest energy, least energy use, and lowest emissions. A techno-economic study is required to investigate the model design for SOFC-based micro-combined heat and power (m-CHP) systems for applications in terms of educational and commercial buildings. This work models and explores the optimized application of hydrogen gas-fueled SOFC-based m-CHP systems in educational buildings. Two educational departments' loads are presented and model of SOFC-based m-CHP system against the different electric power demands is performed, in order to provide a techno-economic assessment of the technology. For successful development of the technology, results are related to system rightsizing, operating strategies, thermal to electric ratios, and match between end-use, with an aim towards classifying the overall feasibility and essential application requirements.
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  • Körber, R., et al. (author)
  • SQUIDs in biomagnetism: A roadmap towards improved healthcare
  • 2016
  • In: Superconductors Science and Technology. - : IOP Publishing. - 0953-2048 .- 1361-6668. ; 29:11
  • Journal article (peer-reviewed)abstract
    • Globally, the demand for improved health care delivery while managing escalating costs is a major challenge. Measuring the biomagnetic fields that emanate from the human brain already impacts the treatment of epilepsy, brain tumours and other brain disorders. This roadmap explores how superconducting technologies are poised to impact health care. Biomagnetism is the study of magnetic fields of biological origin. Biomagnetic fields are typically very weak, often in the femtotesla range, making their measurement challenging. The earliest in vivo human measurements were made with room-temperature coils. In 1963, Baule and McFee (1963 Am. Heart J. 55 95-6) reported the magnetic field produced by electric currents in the heart ('magnetocardiography'), and in 1968, Cohen (1968 Science 161 784-6) described the magnetic field generated by alpha-rhythm currents in the brain ('magnetoencephalography'). Subsequently, in 1970, Cohen et al (1970 Appl. Phys. Lett. 16 278-80) reported the recording of a magnetocardiogram using a Superconducting QUantum Interference Device (SQUID). Just two years later, in 1972, Cohen (1972 Science 175 664-6) described the use of a SQUID in magnetoencephalography. These last two papers set the scene for applications of SQUIDs in biomagnetism, the subject of this roadmap. The SQUID is a combination of two fundamental properties of superconductors. The first is flux quantization - the fact that the magnetic flux Φ in a closed superconducting loop is quantized in units of the magnetic flux quantum, Φ0 ≡ h/2e, ≈ 2.07 × 10-15 Tm2 (Deaver and Fairbank 1961 Phys. Rev. Lett. 7 43-6, Doll R and Nabauer M 1961 Phys. Rev. Lett. 7 51-2). Here, h is the Planck constant and e the elementary charge. The second property is the Josephson effect, predicted in 1962 by Josephson (1962 Phys. Lett. 1 251-3) and observed by Anderson and Rowell (1963 Phys. Rev. Lett. 10 230-2) in 1963. The Josephson junction consists of two weakly coupled superconductors separated by a tunnel barrier or other weak link. A tiny electric current is able to flow between the superconductors as a supercurrent, without developing a voltage across them. At currents above the 'critical current' (maximum supercurrent), however, a voltage is developed. In 1964, Jaklevic et al (1964 Phys. Rev. Lett. 12 159-60) observed quantum interference between two Josephson junctions connected in series on a superconducting loop, giving birth to the dc SQUID. The essential property of the SQUID is that a steady increase in the magnetic flux threading the loop causes the critical current to oscillate with a period of one flux quantum. In today's SQUIDs, using conventional semiconductor readout electronics, one can typically detect a change in Φ corresponding to 10-6 Φ0 in one second. Although early practical SQUIDs were usually made from bulk superconductors, for example, niobium or Pb-Sn solder blobs, today's devices are invariably made from thin superconducting films patterned with photolithography or even electron lithography. An extensive description of SQUIDs and their applications can be found in the SQUID Handbooks (Clarke and Braginski 2004 Fundamentals and Technology of SQUIDs and SQUID Systems vol I (Weinheim, Germany: Wiley-VCH), Clarke and Braginski 2006 Applications of SQUIDs and SQUID Systems vol II (Weinheim, Germany: Wiley-VCH)). The roadmap begins (chapter 1) with a brief review of the state-of-the-art of SQUID-based magnetometers and gradiometers for biomagnetic measurements. The magnetic field noise referred to the pick-up loop is typically a few fT Hz-1/2, often limited by noise in the metallized thermal insulation of the dewar rather than by intrinsic SQUID noise. The authors describe a pathway to achieve an intrinsic magnetic field noise as low as 0.1 fT Hz-1/2, approximately the Nyquist noise of the human body. They also descibe a technology to defeat dewar noise. Chapter 2 reviews the neuroscientific and clinical use of magnetoencephalography (MEG), by far the most widespread application of biomagnetism with systems containing ty ically 300 sensors cooled to liquid-helium temperature, 4.2 K. Two important clinical applications are presurgical mapping of focal epilepsy and of eloquent cortex in brain-tumor patients. Reducing the sensor-to-brain separation and the system noise level would both improve spatial resolution. The very recent commercial innovation that replaces the need for frequent manual transfer of liquid helium with an automated system that collects and liquefies the gas and transfers the liquid to the dewar will make MEG systems more accessible. A highly promising means of placing the sensors substantially closer to the scalp for MEG is to use high-transition-temperature (high-T c) SQUID sensors and flux transformers (chapter 3). Operation of these devices at liquid-nitrogen temperature, 77 K, enables one to minimize or even omit metallic thermal insulation between the sensors and the dewar. Noise levels of a few fT Hz-1/2 have already been achieved, and lower values are likely. The dewars can be made relatively flexible, and thus able to be placed close to the skull irrespective of the size of the head, potentially providing higher spatial resolution than liquid-helium based systems. The successful realization of a commercial high-T c MEG system would have a major commercial impact. Chapter 4 introduces the concept of SQUID-based ultra-low-field magnetic resonance imaging (ULF MRI) operating at typically several kHz, some four orders of magnitude lower than conventional, clinical MRI machines. Potential advantages of ULF MRI include higher image contrast than for conventional MRI, enabling methodologies not currently available. Examples include screening for cancer without a contrast agent, imaging traumatic brain injury (TBI) and degenerative diseases such as Alzheimer's, and determining the elapsed time since a stroke. The major current problem with ULF MRI is that its signal-to-noise ratio (SNR) is low compared with high-field MRI. Realistic solutions to this problem are proposed, including implementing sensors with a noise level of 0.1 fT Hz-1/2. A logical and exciting prospect (chapter 5) is to combine MEG and ULF MRI into a single system in which both signal sources are detected with the same array of SQUIDs. A prototype system is described. The combination of MEG and ULF MRI allows one to obtain structural images of the head concurrently with the recording of brain activity. Since all MEG images require an MRI to determine source locations underlying the MEG signal, the combined modality would give a precise registration of the two images; the combination of MEG with high-field MRI can produce registration errors as large as 5 mm. The use of multiple sensors for ULF MRI increases both the SNR and the field of view. Chapter 6 describes another potentially far-reaching application of ULF MRI, namely neuronal current imaging (NCI) of the brain. Currently available neuronal imaging techniques include MEG, which is fast but has relatively poor spatial resolution, perhaps 10 mm, and functional MRI (fMRI) which has a millimeter resolution but is slow, on the order of seconds, and furthermore does not directly measure neuronal signals. NCI combines the ability of direct measurement of MEG with the spatial precision of MRI. In essence, the magnetic fields generated by neural currents shift the frequency of the magnetic resonance signal at a location that is imaged by the three-dimensional magnetic field gradients that form the basis of MRI. The currently achieved sensitivity of NCI is not quite sufficient to realize its goal, but it is close. The realization of NCI would represent a revolution in functional brain imaging. Improved techniques for immunoassay are always being sought, and chapter 7 introduces an entirely new topic, magnetic nanoparticles for immunoassay. These particles are bio-funtionalized, for example with a specific antibody which binds to its corresponding antigen, if it is present. Any resulting changes in the properties of the nanoparticles are detected with a SQUID. For liquid-phase detection, there are three ba ic methods: AC susceptibility, magnetic relaxation and remanence measurement. These methods, which have been successfully implemented for both in vivo and ex vivo applications, are highly sensitive and, although further development is required, it appears highly likely that at least some of them will be commercialized. © 2016 IOP Publishing Ltd.
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29.
  • Masrur Hossain, M., et al. (author)
  • Analysis and optimization of a modified Kalina cycle system for low-grade heat utilization
  • 2021
  • In: Energy Conversion and Management. - : Elsevier Ltd. - 2590-1745. ; 12
  • Journal article (peer-reviewed)abstract
    • Kalina cycle system (KCS) offers an attractive prospect to produce power by utilizing low-grade heat sources where traditional power cycles cannot be implemented. Intending to explore the potential of exploiting low-grade heat sources for conversion to electrical energy, this study proposes two modified power generation cycles based on KCS-34. A multi-phase expander is positioned between the Kalina separator and the second heat regenerator in the proposed X-modification. In contrast, it is located between the mixer and second regenerator for Y-modification. To explore the potential benefits and limitations of the proposed modifications contrasted with the KCS-34, thermodynamic modeling and optimization have been conducted. The influence of critical decision parameters on overall cycle performance is analyzed. The result elucidates that by implementing an additional multi-phase expander, a significant amount of energy can be extracted from a lean ammonia water loop and X-modification can deliver superior thermodynamic performance compared with the Y-modification and the original KCS-34. With a reduced turbine inlet pressure of 58 bar and an ammonia concentration of 80%, the X-modified cycle's efficiency reaches a peak value of 17% and a net power yield of 1015 kW. An increase of 6.35% can be achieved compared with the conventional KCS-34 operating at the same conditions. Maximum exergy destruction of the working substance was observed in the condenser. 
  •  
30.
  • Yang, W., et al. (author)
  • Immunogenic neoantigens derived from gene fusions stimulate T cell responses
  • 2019
  • In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 25:5
  • Journal article (peer-reviewed)abstract
    • Anti-tumor immunity is driven by self versus non-self discrimination. Many immunotherapeutic approaches to cancer have taken advantage of tumor neoantigens derived from somatic mutations. Here, we demonstrate that gene fusions are a source of immunogenic neoantigens that can mediate responses to immunotherapy. We identified an exceptional responder with metastatic head and neck cancer who experienced a complete response to immune checkpoint inhibitor therapy, despite a low mutational load and minimal pre-treatment immune infiltration in the tumor. Using whole-genome sequencing and RNA sequencing, we identified a novel gene fusion and demonstrated that it produces a neoantigen that can specifically elicit a host cytotoxic T cell response. In a cohort of head and neck tumors with low mutation burden, minimal immune infiltration and prevalent gene fusions, we also identified gene fusion-derived neoantigens that generate cytotoxic T cell responses. Finally, analyzing additional datasets of fusion-positive cancers, including checkpoint-inhibitor-treated tumors, we found evidence of immune surveillance resulting in negative selective pressure against gene fusion-derived neoantigens. These findings highlight an important class of tumor-specific antigens and have implications for targeting gene fusion events in cancers that would otherwise be less poised for response to immunotherapy, including cancers with low mutational load and minimal immune infiltration.
  •  
31.
  • Beasley, W., et al. (author)
  • Image-based Data Mining to Probe Dosimetric Correlates of Radiation-induced Trismus
  • 2018
  • In: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 102:4, s. 1330-1338
  • Journal article (peer-reviewed)abstract
    • Purpose: To identify imaged regions in which dose is associated with radiation-induced trismus after head and neck cancer radiation therapy (HNRT) using a novel image-based data mining (IBDM) framework. Methods and Materials: A cohort of 86 HNRT patients were analyzed for region identification. Trismus was characterized as a continuous variable by the maximum incisor-to-incisor opening distance (MID) at 6 months after radiation therapy. Patient anatomies and dose distributions were spatially normalized to a common frame of reference using deformable image registration. IBDM was used to identify clusters of voxels associated with MID (P <= .05 based on permutation testing). The result was externally tested on a cohort of 35 patients with head and neck cancer. Internally, we also performed a dose-volume histogram-based analysis by comparing the magnitude of the correlation between MID and the mean dose for the IBDM-identified cluster in comparison with 5 delineated masticatory structures. Results: A single cluster was identified with the IBDM approach (P < .01), partially overlapping with the ipsilateral masseter. The dose-volume histogram-based analysis confirmed that the IBDM cluster had the strongest association with MID, followed by the ipsilateral masseter and the ipsilateral medial pterygoid (Spearman's rank correlation coefficients: R-s = -0.36, -0.35, -0.32; P = .001, .001, .002, respectively). External validation confirmed an association between mean dose to the IBDM cluster and MID (R-s = -0.45; P = .007). Conclusions: IBDM bypasses the common assumption that dose patterns within structures are unimportant. Our novel IBDM approach for continuous outcome variables successfully identified a cluster of voxels that are highly associated with trismus, overlapping partially with the ipsilateral masseter. Tests on an external validation cohort showed an even stronger correlation with trismus. These results support use of the region in HNRT treatment planning to potentially reduce trismus. (C) 2018 Elsevier Inc. All rights reserved.
  •  
32.
  • Dent, W. R. F., et al. (author)
  • GASPS-A Herschel Survey of Gas and Dust in Protoplanetary Disks: Summary and Initial Statistics
  • 2013
  • In: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 125:927, s. 477-505
  • Journal article (peer-reviewed)abstract
    • We describe a large-scale far-infrared line and continuum survey of protoplanetary disk through to young debris disk systems carried out using the ACS instrument on the Herschel Space Observatory. This Open Time Key program, known as GASPS (Gas Survey of Protoplanetary Systems), targeted similar to 250 young stars in narrow wavelength regions covering the [OI] fine structure line at 63 mu m the brightest far-infrared line in such objects. A subset of the brightest targets were also surveyed in [OI]145 mu m, [CII] at 157 mu m, as well as several transitions of H2O and high-excitation CO lines at selected wavelengths between 78 and 180 mu m. Additionally, GASPS included continuum photometry at 70, 100 and 160 mu m, around the peak of the dust emission. The targets were SED Class II-III T Tauri stars and debris disks from seven nearby young associations, along with a comparable sample of isolated Herbig AeBe stars. The aim was to study the global gas and dust content in a wide sample of circumstellar disks, combining the results with models in a systematic way. In this overview paper we review the scientific aims, target selection and observing strategy of the program. We summarise some of the initial results, showing line identifications, listing the detections, and giving a first statistical study of line detectability. The [OI] line at 63 mu m was the brightest line seen in almost all objects, by a factor of similar to 10. Overall [OI]63 mu m detection rates were 49%, with 100% of HAeBe stars and 43% of T Tauri stars detected. A comparison with published disk dust masses (derived mainly from sub-mm continuum, assuming standard values of the mm mass opacity) shows a dust mass threshold for [OI] 63 mu m detection of similar to 10(-5) M-circle dot. Normalising to a distance of 140 pc, 84% of objects with dust masses >= 10(-5) M-circle dot can be detected in this line in the present survey; 32% of those of mass 10(-6)-10(-5) M-circle dot, and only a very small number of unusual objects with lower masses can be detected. This is consistent with models with a moderate UV excess and disk flaring. For a given disk mass, [OI] detectability is lower for M stars compared with earlier spectral types. Both the continuum and line emission was, in most systems, spatially and spectrally unresolved and centred on the star, suggesting that emission in most cases was from the disk. Approximately 10 objects showed resolved emission, most likely from outflows. In the GASPS sample, [OI] detection rates in T Tauri associations in the 0.3-4 Myr age range were similar to 50%. For each association in the 5-20 Myr age range, similar to 2 stars remain detectable in [OI]63 mu m, and no systems were detected in associations with age >20 Myr. Comparing with the total number of young stars in each association, and assuming a ISM-like gas/dust ratio, this indicates that similar to 18% of stars retain a gas-rich disk of total mass similar to 1 M-Jupiter for 1-4 Myr, 1-7% keep such disks for 5-10 Myr, but none are detected beyond 10-20 Myr. The brightest [OI] objects from GASPS were also observed in [OI]145 mu m, [CII]157 mu m and CO J = 18 - 17, with detection rates of 20-40%. Detection of the [CII] line was not correlated with disk mass, suggesting it arises more commonly from a compact remnant envelope.
  •  
33.
  • Hussain, Fida, et al. (author)
  • Comparative electrochemical investigation of zinc based nano-composite anode materials for solid oxide fuel cell
  • 2019
  • In: Ceramics International. - : Elsevier. - 0272-8842 .- 1873-3956. ; 45:1, s. 1077-1083
  • Journal article (peer-reviewed)abstract
    • The structural and electrochemical properties of zinc based nano-composites anode materials with a composition of X0.25Ti0.5Zn0.70 (where X = Cu, Mn, Ag) have been investigated in this present study. The proposed Xo.zsTiousZno.70 oxide materials have been synthesized through sol-gel method. The doping effect of Cu, Mn, and Ag on TiZn oxides were analyzed in terms of electronic conduction and power density in hydrogen atmosphere at comparatively low temperature in the range of 650 degrees C. The crystal structure and surface morphology were examined by X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis techniques. The XRD patterns of composites depict that the average crystalline sizes lie in the range of 20-100 nm. Four -probe DC conductivity technique was used to measure the conductivity of the materials and maximum electrical conductivity of Ag0.25Ti0.05Zn0.70 oxide was found to be 7.81 S/cm at 650 degrees C. The band gap and absorption spectra were determined by ultra-violet visible (UV-Vis) and Fourier Transform Infrared spectroscopy (FTIR) techniques respectively. The maximum power density was achieved to be 354 mW/cm(2) at 650 degrees C by Ag0.25Ti0.05Zn0.70 oxide anode with SDC (electrolyte) and BSCF (conventional cathode) materials.
  •  
34.
  • Hussain, F., et al. (author)
  • Electrochemical investigation of multi-fuel based low temperature nano-composite anode for solid oxide fuel cell
  • 2019
  • In: Journal of Power Sources. - : Elsevier B.V.. - 0378-7753 .- 1873-2755. ; 425, s. 147-152
  • Journal article (peer-reviewed)abstract
    • Extensive efforts have been made in order to develop multi-fuel-based low temperature solid oxide fuel cell for direct conversion of hydrocarbons to electric power. It is extremely difficult to operate due to the C–H activation and its tremendously sluggish oxidation reduction in the low temperature range from 300 to 600 °C. The structural and electrochemical properties of novel anode material Ni 0.6 (Ba 0.3 Ce 0.2 Zn 0.5 ) 0.4 have been investigated in the presence of hydrogen, natural gas, ethanol, glucose, and sugar-cane at low temperature of 600 °C. Through sol-gel method the proposed oxide material is synthesized. The composite average crystalline size has been found 25–90 nm by both scanning electron microscopy and X-ray diffraction techniques. The ultraviolet– visible and Fourier transform infrared techniques are used to determine band gap and absorption spectrum respectively. The power density of the cell at various fuels has been observed and measurements indicate that it varies from 57 to 315 mWcm −2 at 600 °C among different fuels at anode side. The current study reveals that proposed anode Ni 0.6 (Ba 0.3 Ce 0.2 Zn 0.5 ) 0.4 is promising multi-fuel anode material for low-temperature solid oxide fuel cell, and it does not need to reform hydrocarbon fuels in order to fully utilize the advantage of these cells.
  •  
35.
  • Iqbal, M. S., et al. (author)
  • FSS inspired polarization insensitive chipless RFID tag
  • 2017
  • In: IEICE Electronics Express. - : Institute of Electronics Information Communication Engineers. - 1349-2543. ; 14:10
  • Journal article (peer-reviewed)abstract
    • A polarization insensitive, compact, fully-passive bit encoding structure exhibiting 1 : 1 resonator-to-bit correspondence is presented. Inspired by frequency selective surface (FSS) based microwave absorbers, the structure readily operates as a chipless radio frequency identification (RFID) tag. The unit cell is composed of several concentric hexagonal loops. Finite repetitions of the unit cell constitute the proposed RFID tag in its entirety. The required bit sequence is encoded in the frequency domain by addition or omission of corresponding nested resonant elements. A functional prototype is fabricated on a commercial-grade grounded FR4 substrate, occupying a physical footprint of 23 × 10mm2 while offering a capacity of 14 bits. The proposed tag boasts a minuscule profile, and demonstrates polarization insensitivity as well as stable oblique angular performance.
  •  
36.
  • Mathews, G. S., et al. (author)
  • GAS in Protoplanetary Systems (GASPS) I. First results
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L127
  • Journal article (peer-reviewed)abstract
    • Context. Circumstellar discs are ubiquitous around young stars, but rapidly dissipate their gas and dust on timescales of a few Myr. The Herschel Space Observatory allows for the study of the warm disc atmosphere, using far-infrared spectroscopy to measure gas content and excitation conditions, and far-IR photometry to constrain the dust distribution. Aims. We aim to detect and characterize the gas content of circumstellar discs in four targets as part of the Herschel science demonstration phase. Methods. We carried out sensitive medium resolution spectroscopy and high sensitivity photometry at gimel similar to 60-190 mu m using the Photodetector Array Camera and Spectrometer instrument on the Herschel Space Observatory. Results. We detect [OI] 63 mu m emission from the young stars HD 169142, TW Hydrae, and RECX 15, but not HD 181327. No other lines, including [CII] 158 and [OI] 145, are significantly detected. All four stars are detected in photometry at 70 and 160 mu m. Extensive models are presented in associated papers.
  •  
37.
  • Meeus, G., et al. (author)
  • Gas in the protoplanetary disc of HD 169142: Herschel's view
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L124
  • Journal article (peer-reviewed)abstract
    • In an effort to simultaneously study the gas and dust components of the disc surrounding the young Herbig Ae star HD 169142, we present far-IR observations obtained with the PACS instrument onboard the Herschel Space Observatory. This work is part of the open time key program GASPS, which is aimed at studying the evolution of protoplanetary discs. To constrain the gas properties in the outer disc, we observed the star at several key gas-lines, including [OI] 63.2 and 145.5 mu m, [CII] 157.7 mu m, CO 72.8 and 90.2 mu m, and o-H2O 78.7 and 179.5 mu m. We only detect the [OI] 63.2 mu m line in our spectra, and derive upper limits for the other lines. We complement our data set with PACS photometry and (CO)-C-12/13 data obtained with the Submillimeter Array. Furthermore, we derive accurate stellar parameters from optical spectra and UV to mm photometry. We model the dust continuum with the 3D radiative transfer code MCFOST and use this model as an input to analyse the gas lines with the thermo-chemical code ProDIMo. Our dataset is consistent with a simple model in which the gas and dust are well-mixed in a disc with a continuous structure between 20 and 200 AU, but this is not a unique solution. Our modelling effort allows us to constrain the gas-to-dust mass ratio as well as the relative abundance of the PAHs in the disc by simultaneously fitting the lines of several species that originate in different regions. Our results are inconsistent with a gas-poor disc with a large UV excess; a gas mass of 5.0 +/- 2.0 x 10(-3) M-circle dot is still present in this disc, in agreement with earlier CO observations.
  •  
38.
  • Pinte, C., et al. (author)
  • The Herschel view of GAS in Protoplanetary Systems (GASPS) First comparisons with a large grid of models
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L126
  • Journal article (peer-reviewed)abstract
    • The Herschel GASPS key program is a survey of the gas phase of protoplanetary discs, targeting 240 objects which cover a large range of ages, spectral types, and disc properties. To interpret this large quantity of data and initiate self-consistent analyses of the gas and dust properties of protoplanetary discs, we have combined the capabilities of the radiative transfer code MCFOST with the gas thermal balance and chemistry code ProDiMo to compute a grid of approximate to 300 000 disc models (DENT). We present a comparison of the first Herschel/GASPS line and continuum data with the predictions from the DENT grid of models. Our objective is to test some of the main trends already identified in the DENT grid, as well as to define better empirical diagnostics to estimate the total gas mass of protoplanetary discs. Photospheric UV radiation appears to be the dominant gas-heating mechanism for Herbig stars, whereas UV excess and/or X-rays emission dominates for T Tauri stars. The DENT grid reveals the complexity in the analysis of far-IR lines and the difficulty to invert these observations into physical quantities. The combination of Herschel line observations with continuum data and/or with rotational lines in the (sub-)millimetre regime, in particular CO lines, is required for a detailed characterisation of the physical and chemical properties of circumstellar discs.
  •  
39.
  • Raihan Uddin, M., et al. (author)
  • Energy analysis of a solar driven vaccine refrigerator using environment-friendly refrigerants for off-grid locations
  • 2021
  • In: Energy Conversion and Management. - : Elsevier Ltd. - 2590-1745. ; 11
  • Journal article (peer-reviewed)abstract
    • In many remote localities, one of the underlying reasons for not receiving life-saving vaccines is the lack of electricity to store the vaccines in the required refrigerated conditions. Solar Photovoltaic (PV) refrigerators have been considered as a viable and green solution to store the vaccines in remote localities having no access to electricity. In this paper, a detailed methodology has been presented for the performance evaluation of a solar PV powered vaccine refrigerator for remote locations. Thermal modelling with hourly cooling load calculations and refrigeration cycle simulations were carried out. The performance parameters for three environment-friendly refrigerants: R152a, R1234yf, and R1234ze(E) has been compared against the commonly used R134a for two remote, off-grid locations in Bangladesh and South Sudan. The energy systems comprising of solar PV panels and batteries to run the refrigerator were modelled in HOMER software for techno-economic optimizations. For both the locations, R152a was found to be the best performing refrigerant exhibiting higher COP (2%−5.29%) as compared to the other refrigerants throughout the year, while R1234ze(E) exhibited COPs on par with R134a, and R1234yf had the least performance. Techno-economic analysis showed an energy system providing electricity to the refrigerator with R152a also had lower levelized cost of electricity (0.48%−2.54%) than the systems having other refrigerants in these locations.
  •  
40.
  •  
41.
  • Riaz, Muhammad, et al. (author)
  • Construction of efficient classes of circular balanced repeated measurements designs with R
  • 2024
  • In: Communications in Statistics - Theory and Methods. - 0361-0926 .- 1532-415X.
  • Journal article (peer-reviewed)abstract
    • Pharmacology, medicine, psychology, and the animal sciences all employ repeated measurement designs (RMDs). However, RMDs may experience carryover effects, which are the primary cause of bias in treatment effect estimation. In order to eliminate the carryover effects for odd v (the number of treatments), minimal circular balanced and strongly balanced repeated measurement designs (RMDs) are the ones that should be used. The minimal circular partially balanced and weakly balanced RMDs are used for even v. In order to obtain these important classes of minimal circular RMDs in periods of equal, two, and three different sizes, an R-based algorithm is developed in this article. The newly developed algorithm has made so simple the construction of balanced RMDs and their generalized classes. As a result, it is a novel piece of research.
  •  
42.
  • Tariq, N., et al. (author)
  • A Novel Kite-Shaped Chipless RFID Tag for Low-Profile Applications
  • 2019
  • In: IETE Journal of Research. - : Informa UK Limited. - 0377-2063 .- 0974-780X. ; , s. 1-8
  • Journal article (peer-reviewed)abstract
    • In this paper a novel, compact 10-bit chipless radio frequency identification (RFID) tag with stable readable characteristics is proposed. The tag is composed of several concentric novel kite-shaped loop resonators. The desired data sequence is obtained by the insertion or removal of nested elements, offering a 1:1 data bit to resonance correspondence. Each data sequence is encoded in the spectral domain of the tag. The proposed tag shows operability at different polarizations and incident angles of the impinging electromagnetic waves. Operating within the ultra-wideband (UWB), the tag is realized on the Roger RT/duroid® 5880 substrate having physical dimensions of 13.55 × 13.55 mm2. The measurement results of the design reveal a high code density and spectral efficiency of 5.44 bits/cm2 and 2 bits/GHz, respectively. The compact and robust passive chipless RFID tag having scalable data storage potential can be deployed in numerous low-profile applications such as those of wearable and healthcare.
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43.
  •  
44.
  • Thi, W. F., et al. (author)
  • Herschel-PACS observation of the 10 Myr old T Tauri disk TW Hya Constraining the disk gas mass
  • 2010
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 518:Article Number: L125
  • Journal article (peer-reviewed)abstract
    • Planets are formed in disks around young stars. With an age of similar to 10 Myr, TW Hya is one of the nearest T Tauri stars that is still surrounded by a relatively massive disk. In addition a large number of molecules has been found in the TW Hya disk, making TW Hya the perfect test case in a large survey of disks with Herschel-PACS to directly study their gaseous component. We aim to constrain the gas and dust mass of the circumstellar disk around TW Hya. We observed the fine-structure lines of [OI] and [CII] as part of the open-time large program GASPS. We complement this with continuum data and ground-based (12) CO 3-2 and (CO)-C-13 3-2 observations. We simultaneously model the continuum and the line fluxes with the 3D Monte-Carlo code MCFOST and the thermo-chemical code ProDiMo to derive the gas and dust masses. We detect the [OI] line at 63 mu m. The other lines that were observed, [OI] at 145 mu m and [CII] at 157 mu m, are not detected. No extended emission has been found. Preliminary modeling of the photometric and line data assuming [(CO)-C-12]/[(CO)-C-13] = 69 suggests a dust mass for grains with radius
  •  
45.
  • Andersen, L. M., et al. (author)
  • On-scalp MEG SQUIDs are sensitive to early somatosensory activity unseen by conventional MEG
  • 2020
  • In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 221
  • Journal article (peer-reviewed)abstract
    • Magnetoencephalography (MEG) has a unique capacity to resolve the spatio-temporal development of brain activity from non-invasive measurements. Conventional MEG, however, relies on sensors that sample from a distance (20–40 mm) to the head due to thermal insulation requirements (the MEG sensors function at 4 K in a helmet). A gain in signal strength and spatial resolution may be achieved if sensors are moved closer to the head. Here, we report a study comparing measurements from a seven-channel on-scalp SQUID MEG system to those from a conventional (in-helmet) SQUID MEG system. We compared the spatio-temporal resolution between on-scalp and conventional MEG by comparing the discrimination accuracy for neural activity patterns resulting from stimulating five different phalanges of the right hand. Because of proximity and sensor density differences between on-scalp and conventional MEG, we hypothesized that on-scalp MEG would allow for a more high-resolved assessment of these activity patterns, and therefore also a better classification performance in discriminating between neural activations from the different phalanges. We observed that on-scalp MEG provided better classification performance during an early post-stimulus period (10–20 ms). This corresponded to the electroencephalographic (EEG) component P16/N16 and was an unexpected observation as this component is usually not observed in conventional MEG. This finding shows that on-scalp MEG enables a richer registration of the cortical signal, indicating a sensitivity to what are potentially sources in the thalamo-cortical radiation. We had originally expected that on-scalp MEG would provide better classification accuracy based on activity in proximity to the P60m component compared to conventional MEG. This component indeed allowed for the best classification performance for both MEG systems (60–75%, chance 50%). However, we did not find that on-scalp MEG allowed for better classification than conventional MEG at this latency. We suggest that this absence of differences is due to the limited sensor coverage in the recording, in combination with our strategy for positioning the on-scalp MEG sensors. We show how the current sensor coverage may have limited our chances to register the necessary between-phalange source field dissimilarities for fair hypothesis testing, an approach we otherwise believe to be useful for future benchmarking measurements. © 2020 The Authors
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46.
  • Bilal, Muhammad Sajjad, et al. (author)
  • Computational Investigation of 1, 3, 4 Oxadiazole Derivatives as Lead Inhibitors of VEGFR 2 in Comparison with EGFR : Density Functional Theory, Molecular Docking and Molecular Dynamics Simulation Studies
  • 2022
  • In: Biomolecules. - : MDPI. - 2218-273X. ; 12:11
  • Journal article (peer-reviewed)abstract
    • Vascular endothelial growth factor (VEGF) is an angiogenic factor involved in tumor growth and metastasis. Gremlin has been proposed as a novel therapeutic pathway for the treatment of renal inflammatory diseases, acting via VEGFR 2 receptor. To date, most FDA-approved tyrosine kinase (TK) inhibitors have been reported as dual inhibitors of EGFR and VEGFR 2. The aim of the present study was to find the potent and selective inhibitor of VEGFR 2 specifically for the treatment of renal cancer. Fourteen previously identified anti-inflammatory compounds i.e., 1, 3, 4 oxadiazoles derivatives by our own group were selected for their anti-cancer potential, targeting the tyrosine kinase (TK) domain of VEGFR2 and EGFR. A detailed virtual screening-based study was designed viz density functional theory (DFT) study to find the compounds stability and reactivity, molecular docking for estimating binding affinity, SeeSAR analysis and molecular dynamic simulations to confirm protein ligand complex stability and ADMET properties to find the pharmacokinetic profile of all compounds. The DFT results suggested that among all the derivatives, the 7g, 7j, and 7l were chemically reactive and stable derivatives. The optimized structures obtained from the DFTs were further selected for molecular docking, and the results suggested that 7g, 7j and 7l derivatives as the best inhibitors of VEGFR 2 with binding energy values -46.32, -48.89 and -45.01 kJ/mol. The Estimated inhibition constant (IC50) of hit compound 7j (0.009 mu M) and simulation studies of its complexes confirms its high potency and best inhibitor of VEGFR2. All the derivatives were also docked with EGFR, where they showed weak binding energies and poor interactions, important compound 7g, 7j and 7i exhibited binding energy of -31.01, -33.23 and -34.19 kJ/mol respectively. Furthermore, the anticancer potential of the derivatives was confirmed by cell viability (MTT) assay using breast cancer and cervical cancer cell lines. At the end, the results of ADMET studies confirmed these derivatives as drug like candidates. Conclusively, the current study suggested substituted oxadiazoles as the potential anticancer compounds which exhibited more selectivity towards VEGFR2 in comparison to EGFR. Therefore, the identified lead molecules can be used for the synthesis of more potent derivatives of VEGFR2, along with extensive in vitro and in vivo experiments, that can be used to treat various cancers, especially renal cancers, and to prevent angiogenesis due to aberrant expression of VEGFR2.
  •  
47.
  • Epp, L. S., et al. (author)
  • New environmental metabarcodes for analysing soil DNA: potential for studying past and present ecosystems
  • 2012
  • In: Molecular Ecology. - 0962-1083. ; 21:8, s. 1821-1833
  • Journal article (peer-reviewed)abstract
    • Metabarcoding approaches use total and typically degraded DNA from environmental samples to analyse biotic assemblages and can potentially be carried out for any kinds of organisms in an ecosystem. These analyses rely on specific markers, here called metabarcodes, which should be optimized for taxonomic resolution, minimal bias in amplification of the target organism group and short sequence length. Using bioinformatic tools, we developed metabarcodes for several groups of organisms: fungi, bryophytes, enchytraeids, beetles and birds. The ability of these metabarcodes to amplify the target groups was systematically evaluated by (i) in silico PCRs using all standard sequences in the EMBL public database as templates, (ii) in vitro PCRs of DNA extracts from surface soil samples from a site in Varanger, northern Norway and (iii) in vitro PCRs of DNA extracts from permanently frozen sediment samples of late-Pleistocene age (similar to 16 00050 000 years bp) from two Siberian sites, Duvanny Yar and Main River. Comparison of the results from the in silico PCR with those obtained in vitro showed that the in silico approach offered a reliable estimate of the suitability of a marker. All target groups were detected in the environmental DNA, but we found large variation in the level of detection among the groups and between modern and ancient samples. Success rates for the Pleistocene samples were highest for fungal DNA, whereas bryophyte, beetle and bird sequences could also be retrieved, but to a much lesser degree. The metabarcoding approach has considerable potential for biodiversity screening of modern samples and also as a palaeoecological tool.
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48.
  • Ercan, Ayse Bahar, et al. (author)
  • Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
  • 2024
  • In: The Lancet. Oncology. - 1474-5488. ; 25:5, s. 668-682
  • Journal article (peer-reviewed)abstract
    • Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
  •  
49.
  • Fulati, Alimujiang, et al. (author)
  • Miniaturized pH Sensors Based on Zinc Oxide Nanotubes/Nanorods
  • 2009
  • In: SENSORS. - : MDPI AG. - 1424-8220. ; 9:11, s. 8911-8923
  • Journal article (peer-reviewed)abstract
    • ZnO nanotubes and nanorods grown on gold thin film were used to create pH sensor devices. The developed ZnO nanotube and nanorod pH sensors display good reproducibility, repeatability and long-term stability and exhibit a pH-dependent electrochemical potential difference versus an Ag/AgCl reference electrode over a large dynamic pH range. We found the ZnO nanotubes provide sensitivity as high as twice that of the ZnO nanorods, which can be ascribed to the fact that small dimensional ZnO nanotubes have a higher level of surface and subsurface oxygen vacancies and provide a larger effective surface area with higher surface-to-volume ratio as compared to ZnO nanorods, thus affording the ZnO nanotube pH sensor a higher sensitivity. Experimental results indicate ZnO nanotubes can be used in pH sensor applications with improved performance. Moreover, the ZnO nanotube arrays may find potential application as a novel material for measurements of intracellular biochemical species within single living cells.
  •  
50.
  • Khan, K., et al. (author)
  • Requirement development life cycle : The industry practices
  • 2011
  • Conference paper (peer-reviewed)abstract
    • Requirements engineering activities act as a backbone of software development. The more efforts devoted during requirements engineering activities guarantee a better software product. Appropriate selection of requirements has been a challenge for software industry. This selection will increase the probability of success of the software product. Each year many cases are registered against companies for not fulfilling product requirements appropriately. The product failure mostly depends on, either by missing important requirements or capturing irrelevant requirements. SDLC consists of stages where software starts from scratch to a refined product. Requirements Development Life cycle (RDLC) consists of stages where requirements gets initiated, raised, refined, forcefully changed, implemented and validated. The processes to capture requirements vary industry to industry. This paper presents several requirements engineering processes used during the development of requirements, in industry. These processes will identify appropriate requirements and develop a quality product within budget on time. These practices are captured within the Pakistan software industry. This paper also explains the motivations for selecting particular methods, within company, during requirements development and the results associated with it. The processes captured in this paper, from different companies, can be an education for software industry.
  •  
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