| 1. |
- Fitzmauric, C., et al.
(author)
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Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 : A Systematic Analysis for the Global Burden of Disease Study
- 2019
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In: JAMA Oncology. - : American Medical Association. - 2374-2437 .- 2374-2445. ; 5:12, s. 1749-1768
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Journal article (peer-reviewed)abstract
- Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs).Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
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| 2. |
- Frank, TD, et al.
(author)
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Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017
- 2019
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In: The lancet. HIV. - 2352-3018. ; 6:12, s. E831-E859
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Journal article (peer-reviewed)
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| 3. |
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| 4. |
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| 5. |
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| 6. |
- Sepanlou, Sadaf G., et al.
(author)
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The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017
- 2020
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In: The Lancet Gastroenterology & Hepatology. - 2468-1253. ; 5:3, s. 245-266
-
Journal article (peer-reviewed)abstract
- Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH.
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| 7. |
- Lam, MT, et al.
(author)
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A novel disorder involving dyshematopoiesis, inflammation, and HLH due to aberrant CDC42 function
- 2019
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 216:12, s. 2778-2799
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Journal article (peer-reviewed)abstract
- Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival.
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| 8. |
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| 9. |
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| 10. |
- Lembrechts, Jonas J., et al.
(author)
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Global maps of soil temperature
- 2022
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 28:9, s. 3110-3144
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Journal article (peer-reviewed)abstract
- Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world's major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean=3.0±2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6±2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7±2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications.
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| 11. |
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| 12. |
- Ehdaie, M., et al.
(author)
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Key splitting for random key distribution schemes
- 2012
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In: Network Protocols (ICNP), 2012 20th IEEE International Conference on. - : IEEE. - 9781467324472 ; , s. 6459951-
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Conference paper (peer-reviewed)abstract
- A large number of Wireless Sensor Network (WSN) security schemes have been proposed in the literature, relying primarily on symmetric key cryptography. To enable those, Random Key pre-Distribution (RKD) systems have been widely accepted. However, WSN nodes are vulnerable to physical compromise. Capturing one or more nodes operating with RKD would give the adversary keys to compromise communication of other benign nodes. Thus the challenge is to enhance resilience of WSN to node capture, while maintaining the flexibility and low-cost features of RKD. We address this problem, without any special-purpose hardware, proposing a new and simple idea: key splitting. Our scheme does not increase per-node storage, and computation and communication overheads, and it can increase connectivity. More important, it achieves a significant increase in resilience to compromise compared to the state of the art, notably when the adversary does not have overwhelming computational power.
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| 13. |
- Ahmadian-Moghaddam, M., et al.
(author)
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A facile method for regioselective synthesis of new N-acetyl/thioacetyl-(E)-stilbene benzenesulfonamide derivatives via N-acetyl/thioacetyl sulfonamide formation
- 2017
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In: Phosphorus Sulfur and Silicon and the Related Elements. - : Informa UK Limited. - 1042-6507 .- 1563-5325. ; 192:5, s. 481-484
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Journal article (peer-reviewed)abstract
- A series of new N-acetyl/thioacetyl-(E)-stilbene benzenesulfonamide derivatives were synthesized regioselectively in moderate to high yields by following a convenient, three-step procedure. The procedure consists of the direct oxidative conversion of a thiol compound to the corresponding sulfonyl chloride using TMSCl/KNO3, followed by a room temperature reaction in a one-pot transformation of the resultant sulfonyl chloride into N-acetyl/thioacetyl sulfonamide, which undergoes a further Pd-catalyzed coupling reaction, giving rise to the stilbene compounds reported for the first time.
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| 14. |
- Flex, Elisabetta, et al.
(author)
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Activating mutations in RRAS underlie a phenotype within the RASopathy spectrum and contribute to leukaemogenesis
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:16, s. 4315-4327
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Journal article (peer-reviewed)abstract
- RASopathies, a family of disorders characterized by cardiac defects, defective growth, facial dysmorphism, variable cognitive deficits and predisposition to certain malignancies, are caused by constitutional dysregulation of RAS signalling predominantly through the RAF/MEK/ERK (MAPK) cascade. We report on two germline mutations (p.Gly39dup and p.Val55Met) in RRAS, a gene encoding a small monomeric GTPase controlling cell adhesion, spreading and migration, underlying a rare (2 subjects among 504 individuals analysed) and variable phenotype with features partially overlapping Noonan syndrome, the most common RASopathy. We also identified somatic RRAS mutations (p.Gly39dup and p.Gln87Leu) in 2 of 110 cases of non-syndromic juvenile myelomonocytic leukaemia, a childhood myeloproliferative/myelodysplastic disease caused by upregulated RAS signalling, defining an atypical form of this haematological disorder rapidly progressing to acute myeloid leukaemia. Two of the three identified mutations affected known oncogenic hotspots of RAS genes and conferred variably enhanced RRAS function and stimulus-dependent MAPK activation. Expression of an RRAS mutant homolog in Caenorhabditis elegans enhanced RAS signalling and engendered protruding vulva, a phenotype previously linked to the RASopathy-causing SHOC2(S2G) mutant. Overall, these findings provide evidence of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease.
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| 15. |
- Irannezhad, M., et al.
(author)
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Impacts of changes in climate and land cover-land use on flood characteristics in Gorganrood Watershed (Northeastern Iran) during recent decades
- 2018
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In: Geografiska Annaler Series a-Physical Geography. - : Informa UK Limited. - 0435-3676 .- 1468-0459. ; 100:4, s. 340-350
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Journal article (peer-reviewed)abstract
- This study evaluated the effects of changes in climate and land cover-land use (LCLU) on flood intensity and frequency in the Gorganrood Watershed (GW) located in the northeast of Iran during recent decades. For this purpose, hydroclimatic (precipitation, temperature, and river discharge) time series recorded at nine stations placed in the GW during 1973-2014 were used. Flood characteristics in terms of mean, maximum and number of peaks at five discharge stations (Galikash, Gonbad, Huji Ghushan, Tamar, and Tangrah) sited in the outlet of GW sub-basins were determined applying the Peak-Over-Threshold (POT) method to daily specific discharges. This is designed to remove the effect of the different size of sub-basins. The whole study period was divided into three 14-years segments (1973-1986, 1987-2000 and 2001-2014) based on satellite LCLU maps produced for 1973, 1986, 2000 and 2014. In the GW and its sub-basins during recent decades, both flood intensity and frequency increased, the climate became wetter and warmer, and LCLU mostly converted from rangeland to farmland. The partial correlation analyses identified that flood frequency in GW was primarily connected to the LCLU conversions, but moderately to observed wetter and warmer climate. Similarly, the Tamar sub-basin experienced effects of LCLU and climate on the maximum and the number of peaks. In Haji Ghushan, wetter and warmer climate resulted in more intense and frequent floods. Increases in precipitation appear to have played the most important role in the higher flood frequency in Galikash.
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| 16. |
- Ishaq, I., et al.
(author)
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Work in progress - establishing a master program in cyber physical systems : Basic findings and future perspectives
- 2019
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In: Proceedings - 2019 International Conference on Promising Electronic Technologies, ICPET 2019. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 4-9
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Conference paper (peer-reviewed)abstract
- This paper reports on the basic findings and future perspectives of a capacity building project funded by the European Union. The International Master of Science on Cyber Physical Systems (MS@CPS) is a collaborative project that aims to establish a master program in cyber physical systems (CPS). A consortium composed of nine partners proposed the project. Three partners are European and from Germany, UK and Sweden; while the other six partners are from the South Mediterranean region and include: Palestine, Jordan and Tunisia. The consortium is led by the University of Siegen in Germany who also manages the implementation of the work packages. CPS is an emerging engineering subject with significant economic and societal implications, which motivated the consortium to propose the establishment of a master program to offer educational and training opportunities at graduate level in the fields of CPS. In this paper, CPS as a field of study is presented with an emphasis on its importance, especially with regard to meeting local needs. A brief description of the project is presented in conjunction with the methodology for developing the courses and their learning outcomes.
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| 17. |
- Pontén, F, et al.
(author)
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Genomic analysis of single cells from human basal cell cancer using laser-assisted capture microscopy.
- 1997
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In: Mutation research. - 0027-5107 .- 1873-135X. ; 382:1-2
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Journal article (peer-reviewed)abstract
- In this study, we show that direct mutational analysis of genomic DNA can be performed on single somatic cells extracted from a frozen, immunohistochemically stained tissue section using laser-assisted capture microscopy. Eighty-nine single tumor cells were separately dissected from one case of human basal cell cancer (BCC) and p53 mutations were analyzed by direct semi-automated sequencing of PCR fragments. Amplification was obtained for at least one of the two analyzed exons from approximately 50% of the single tumor cells. Identical p53 mutations were found in widely spread areas of the tumor, suggesting a clonal proliferation originating from one cell. Interestingly, comparison between results of immunohistochemistry and genetic analysis of the single cells revealed the same p53 mutations irrespective of the p53 immunoreactivity. We propose that this approach has a great potential to allow investigation of genotypic differences in single cells and more specifically to resolve important and fundamental questions determining cancer heterogeneity.
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| 18. |
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| 19. |
- Pontén, F, et al.
(author)
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Molecular pathology in basal cell cancer with p53 as a genetic marker.
- 1997
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In: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 15:9
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Journal article (peer-reviewed)abstract
- Human basal cell cancer (BCC) has unique growth characteristics with virtual inability to metastasize. We investigated clonality and genetic progression using p53 mutations as marker. Sampling was done through microdissection of frozen immunohistochemically stained 16 microm slices of tumors. From 11 BCC tumors 78 samples were analysed. Direct DNA sequencing of exons 5-8 was performed, haplotypes were determined after cloning of p53 exons and loss of heterozygosity (LOH) ascertained by microsatellite analysis. All tumors had p53 mutations and in a majority both p53 alleles were affected, commonly through missense mutations. Microdissection of small parts (50-100 cells) of individual tumors showed BCC to be composed of a dominant cell clone and prone to genetic progression with appearance of subclones with a second and even third p53 mutation. Samples from normal immunohistochemically negative epidermis always showed wild type sequence, except for a case of previously unknown germline p53 mutation. Our analysis also included p53 immunoreactive patches i.e. morphologically normal epidermis with a compact pattern of p53 immunoreactivity. Mutations within those were never the same as in the adjacent BCC. This detailed study of only one gene thus uncovered a remarkable heterogeneity within a tumor category famous for its benign clinical behavior.
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| 20. |
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| 21. |
- Ren, Z. P., et al.
(author)
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Benign clonal keratinocyte patches with p53 mutations show no genetic link to synchronous squamous cell precancer or cancer in human skin
- 1997
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In: American Journal of Pathology. - : American Society for Investigative Pathology and the Association for Molecular Pathology. - 0002-9440 .- 1525-2191. ; 150:5, s. 1791-803
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Journal article (peer-reviewed)abstract
- Ultraviolet light, which is the major etiology of human skin cancer, will cause mutations in the p53 gene. We and others have found that such mutations occur in more than one-half of non-melanoma squamous cell cancer and precancer. Immunostaining for p53 has disclosed a characteristic compact pattern not only in cancer/precancer but also in areas of microscopically normal epidermis termed p53 patches. By microdissection, sequence analysis of the p53 gene, and analysis of loss of heterozygosity (LOH) at the site of this gene, we have now extended previous data to ascertain whether these p53 patches are precursors of simultaneously present squamous cell cancer or its morphologically recognized precancerous stages (dysplasia, carcinoma in situ). In none of 11 instances with co-existence of a p53 patch with dysplasia or in situ or invasive cancer were the mutations identical. We conclude that p53 patches, estimated to be approximately 100,000 times as common as dysplasia, have a very small or even no precancerous potential. Their common presence demonstrates that human epidermis contains a large number of p53 mutations apparently without detrimental effect. The only result of the mutation may be a clandestine benign clonal keratinocyte proliferation. The importance of p53 mutations for such benign cell multiplication on one band and malignant transformation on the other is unclear. Although the spectrum, type, and multiplicity of mutations were similar in both types of proliferative responses, there was a clear difference with respect to LOH. No LOH was found in 17 p53 patches. By contrast 11 of 30 precancers/cancers had LOH.
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| 22. |
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| 23. |
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| 24. |
- Williams, Cecilia, 1969-, et al.
(author)
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Assessment of sequence-based p53 gene analysis in human breast cancer : messenger RNA in comparison with genomic DNA targets.
- 1998
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 44:3
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Journal article (peer-reviewed)abstract
- The high prevalence of p53 mutations in human cancers and the suggestion from several groups that the presence or absence of p53 mutations might have both prognostic and therapeutic consequences point to the importance of optimal methods for p53 determination. Several strategies exploring this have been described, based either on mRNA or genomic DNA as a template. However, no comparative study on the reliability of the two templates has been performed. The principal aim of this study was to study the concordance of RNA- and DNA-based direct sequencing methods in detecting p53 mutations in breast tumors. In 100 tumors, 22 mutations were detected by both methods. Furthermore, one stop mutation, two splice-site mutations, and one intron alteration were found only by genomic sequencing. In addition, the comparative study suggests that cells with missense mutations have increased steady-state concentrations of p53-specific mRNA, in contrast to cells with a gene encoding a truncated protein.
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| 25. |
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| 26. |
- Ahmadian, Afshin, et al.
(author)
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Analysis of the p53 tumor suppressor gene by pyrosequencing
- 2000
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In: BioTechniques. - : Future Science Ltd. - 0736-6205 .- 1940-9818. ; 28:1, s. 140-
-
Journal article (peer-reviewed)abstract
- Tumor suppressor genes are implicated in cell cycle progression. Inactivation of these genes predominantly occurs through mutations and/or allelic loss that involves both alleles. With inactivation by multiple mutations in a single gene, cloning of the amplified gene is necessary to determine whether the mutations reside on one ol both alleles. Using pyrosequencing, a recently developed approach based on sequencing-by-synthesis, we studied genetic variability in the p53 tumor suppressor gene and could quantify the ratio between the mutated and wild-type amplified fragments. Further-more, this sequencing technique also allows allelic determination of adjacent mutations with no cloning of amplified fragments.
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| 27. |
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| 28. |
- Ahmadian, Amir M., et al.
(author)
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Dynamic Policies Revisited
- 2022
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In: Proceedings - 7th IEEE European Symposium on Security and Privacy, Euro S and P 2022. - : Institute of Electrical and Electronics Engineers (IEEE). ; , s. 448-466
-
Conference paper (peer-reviewed)abstract
- Information flow control and dynamic policies is a difficult relationship yet to be fully understood. While dynamic policies are a natural choice in many real-world applications that downgrade and upgrade the sensitivity of information, understanding the meaning of security in this setting is challenging. In this paper we revisit the knowledge-based security conditions to reinstate a simple and intuitive security condition for dynamic policies: A program is secure if at any point during the execution the attacker's knowledge is in accordance with the active security policy at that execution point. Our key observation is the new notion of policy consistency to prevent policy changes whenever an attacker is already in possession of the information that the new policy intends to protect. We use this notion to study a range of realistic attackers including the perfect recall attacker, bounded attackers, and forgetful attackers, and their relationship. Importantly, our new security condition provides a clean connection between the dynamic policy and the underlying attacker model independently of the specific use case. We illustrate this by considering the different facets of dynamic policies in our framework. On the verification side, we design and implement DynCoVer, a tool for checking dynamic information-flow policies for Java programs via symbolic execution and SMT solving. Our verification operates by first extracting a graph of program dependencies and then visiting the graph to check dynamic policies for a range of attackers. We evaluate the effectiveness and efficiency of DyncoVeron a benchmark of use cases from the literature and designed by ourselves, as well as the case study of a social network. The results show that DynCoVer can analyze small but intricate programs indicating that it can help verify security-critical parts of Java applications. We release Dyncover publicly to support open science and encourage researchers to explore the topic further.
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| 29. |
- Ahmadian, Afshin, et al.
(author)
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Pyrosequencing : History, biochemistry and future
- 2006
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In: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 363:02-jan, s. 83-94
-
Research review (peer-reviewed)abstract
- Background: Pyrosequencing is a DNA sequencing technology based on the sequencing-by-synthesis principle. Methods: The technique is built on a 4-enzyme real-time monitoring of DNA synthesis by bioluminescence using a cascade that upon nucleotide incorporation ends in a detectable light signal (bioluminescence). The detection system is based on the pyrophosphate released when a nucleotide is introduced in the DNA-strand. Thereby, the signal can be quantitatively connected to the number of bases added. Currently, the technique is limited to analysis of short DNA sequences exemplified by single-nucleotide polymorphism analysis and genotyping. Mutation detection and single-nucleotide polymorphisin genotyping require screening of large samples of materials and therefore the importance of high-throughput DNA analysis techniques is significant. In order to expand the field for pyrosequencing, the read length needs to be improved. Conclusions: Th pyrosequencing system is based on an enzymatic system. There are different current and future applications of this technique.
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| 30. |
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| 31. |
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| 32. |
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| 33. |
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| 34. |
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| 35. |
- Dezfouli, Mahya, et al.
(author)
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Magnetic bead assisted labeling of antibodies at nanogram scale
- 2014
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 14:1, s. 14-18
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Journal article (peer-reviewed)abstract
- There are currently several initiatives that aim to produce binding reagents for proteome-wide analysis. To enable protein detection, visualization, and target quantification, covalent coupling of reporter molecules to antibodies is essential. However, current labeling protocols recommend considerable amount of antibodies, require antibody purity and are not designed for automation. Given that small amounts of antibodies are often sufficient for downstream analysis, we developed a labeling protocol that combines purification and modification of antibodies at submicrogram quantities. With the support of magnetic microspheres, automated labeling of antibodies in parallel using biotin or fluorescent dyes was achieved.
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| 36. |
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| 37. |
- Dezfouli, Mahya, et al.
(author)
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Parallel barcoding of antibodies for DNA-assisted proteomics
- 2014
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 14:21-22, s. 2432-2436
-
Journal article (peer-reviewed)abstract
- DNA-assisted proteomics technologies enable ultra-sensitive measurements in multiplex format using DNA-barcoded affinity reagents. Although numerous antibodies are available, nowadays targeting nearly the complete human proteome, the majority is not accessible at the quantity, concentration, or purity recommended for most bio-conjugation protocols. Here, we introduce a magnetic bead-assisted DNA-barcoding approach, applicable for several antibodies in parallel, as well as reducing required reagents quantities up to a thousand-fold. The success of DNA-barcoding and retained functionality of antibodies were demonstrated in sandwich immunoassays and standard quantitative Immuno-PCR assays. Specific DNA-barcoding of antibodies for multiplex applications was presented on suspension bead arrays with read-out on a massively parallel sequencing platform in a procedure denoted Immuno-Sequencing. Conclusively, human plasma samples were analyzed to indicate the functionality of barcoded antibodies in intended proteomics applications.
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| 38. |
- Ehn, M., et al.
(author)
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Escherichia coli single-stranded DNA-binding a molecular tool for improved sequence protein quality in pyrosequencing
- 2002
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In: Electrophoresis. - 0173-0835 .- 1522-2683. ; 23:19, s. 3289-3299
-
Journal article (peer-reviewed)abstract
- Pyrosequencing is a four-enzyme bioluminometric DNA sequencing technique based on a DNA sequencing by synthesis principle. Currently, the technique is limited to analysis of short DNA sequences exemplified by single-nucleotide polymorphism analysis. In order to expand the field for pyrosequencing, the read length needs to be improved and efforts have been made to purify reaction components as well as add single-stranded DNA-binding protein (SSB) to the pyrosequencing reaction. In this study, we have performed a systematic effort to analyze the effects of SSB by comparing the pyrosequencing result of 103 independent complementary DNA (cDNA) clones. More detailed information about the cause of low quality sequences on templates with different characteristics was achieved by thorough analysis of the pyrograms. Also, real-time biosensor analysis was performed on individual cDNA clones for investigation of primer annealing and SSB binding on these templates. Results from these studies indicate that templates with high performance in pyrosequencing without SSB possess efficient primer annealing and low SSB affinity. Alternative strategies to improve the performance in pyrosequencing by increasing the primer-annealing efficiency have also been evaluated.
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| 39. |
- Garcia, C. A., et al.
(author)
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Mutation detection by pyrosequencing : sequencing of exons 5-8 of the p53 tumor suppressor gene
- 2000
-
In: Gene. - 0378-1119 .- 1879-0038. ; 253:2, s. 249-257
-
Journal article (peer-reviewed)abstract
- The ability to sequence a large number of DNA samples rapidly and accurately for detection of all possible mutations is a critical goal for the future application of DNA sequencing in routine medical diagnostics. Pyrosequencing(TM) is a non-electrophoretic real-time DNA sequencing method that uses the luciferase-luciferin light release as the detection signal for nucleotide incorporation into target DNA. For pyrosequencing of the human p53 gene, a nested multiplex PCR method for amplification of exons 5-8 was prepared. In order to investigate the use of pyrosequencing in mutation detection, DNA samples from skin-cancer patients were used. Two forms of nucleotide dispensation strategy were used, cyclic and programmed. Bi-directional pyrosequencing was performed and the overlapping sequence data produced were assembled to determine the sequence of the gene. Reliable sequencing data were obtained with both dispensation strategies, but some advantages were obtained using the programmed nucleotide dispensation approach, such as longer and faster reads, and fewer out-of-phase problems. The accuracy of pyrosequencing for detection of p53 mutations and allele distribution was demonstrated.
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| 40. |
- Gharizadeh, B., et al.
(author)
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Long-read pyrosequencing using pure 2 '-deoxyadenosine-5 '-O '-(1-thiotriphosphate) Sp-isomer
- 2002
-
In: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 301:1, s. 82-90
-
Journal article (peer-reviewed)abstract
- Pyrosequencing, a nonelectrophoretic DNA sequencing method that uses a luciferase-based enzymatic system to monitor DNA synthesis in real time, has so far been limited to sequencing of short stretches of DNA. To increase the signal-to-noise ratio in pyrosequencing the natural dATP was replaced by dATPalphaS (M. Ronaghi et al., 1996, Anal. Biochem. 242, 84-89). The applied dATPaS was a mixture of two isomers (Sp and Rp). We show here that by the introduction of pure 2'-deoxyadenosine-5'-O'-(1-thiotriphosphate) Sp-isomer in pyrosequencing substantial longer reads could be obtained. The pure Sp-isomer allowed lower nucleotide concentration to be used and improved the possibility to read through poly(T) regions. In general, a doubling of the read length could be obtained by the use of pure Sp-isomer. Pyrosequencing data for 50 to 100 bases could be generated on different types of template. The longer read will enable numerous new applications, such as identification and typing of medically important microorganisms as well as resequencing of DNA fragments for mutation screening and clone checking.
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| 41. |
- Gharizadeh, B., et al.
(author)
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Type-specific multiple sequencing primers - A novel strategy for reliable and rapid genotyping of human papilloma viruses by pyrosequencing technology
- 2005
-
In: Journal of Molecular Diagnostics. - 1525-1578 .- 1943-7811. ; 7:2, s. 198-205
-
Journal article (peer-reviewed)abstract
- DNA sequencing is the gold standard method for accurate microbial and viral typing. However, DNA sequencing techniques have been facing limitations in typing of human papillomaviruses when the specimen harbors multiple genotypes and yields nonspecific amplification products, resulting in nonspecific and noninterpretable sequence data. To address these limitations we have developed a type-specific multiple sequencing primer DNA-sequencing method. This new strategy is suitable for sequencing and typing of samples harboring different genotypes (co-infections with multiple genotypes) and yielding nonspecific amplifications, thus eliminating the need for nested polymerase chain reaction (PCR), stringent PCR conditions, and cloning. The new approach has also proved useful for amplicons containing low PCR yield or subdominant types, avoiding reperforming of amplifications. We have applied the multiple sequencing primer method for genotyping of clinically relevant human papillomaviruses in a clinical test panel by using a combined pool of seven type-specific sequencing primers for HPV-6, -11, -16, -18, -31, -33, and -45. Furthermore, we introduced a sequence pattern recognition approach when there was a plurality of genotypes in the sample to facilitate typing of more than one target DNA in the sample. The multiple sequencing primer method has proved to be a multifaceted approach for typing of human papillomaviruses by DNA sequencing technologies.
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| 42. |
- Gustafsson, A. C., et al.
(author)
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HPV-related cancer susceptibility and p53 codon 72 polymorphism
- 2001
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In: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 81, s. 125-
-
Journal article (peer-reviewed)abstract
- Conflicting results regarding the association of a polymorphism at codon 72 of the p53 tumour suppressor gene and susceptibility to develop human papilloma virus (HPV)-associated cervical cancer have been published over the last year, implicating differences in ethnic background, sample origin, sample size and/or detection assay, The material for this study was collected in the identical geographical region as for 2 previous reports with contradictory results regarding the association of codon 72 genotype with squamous cell cancer (SCC), We have used an alternative detection assay, based on pyrosequencing technology, that interrogates the variable position by the accuracy of DNA polymerase. In addition to cervical clinical specimens from SCC, HPV16- and HPV18-infected adenocarcinoma cases as well as cervical intraepithelial neoplasia (CM) were investigated. No significant association was found between p53 codon 72 genotype and the risk to develop adenocarcinoma, SCC or CIN in the Swedish population.
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| 43. |
- Oak, Aditya, et al.
(author)
-
Enclave-Based Secure Programming with JE
- 2021
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In: 2021 IEEE SECURE DEVELOPMENT CONFERENCE (SECDEV 2021). - : Institute of Electrical and Electronics Engineers (IEEE).
-
Conference paper (peer-reviewed)abstract
- Over the past few years, major hardware vendors have started offering processors that support Trusted Execution Environments (TEEs) allowing confidential computations over sensitive data on untrusted hosts. Unfortunately, developing applications that use TEEs remains challenging. Current solutions require using low-level languages (e.g., C/C++) to handle the TEE management process manually a complex and error-prone task. Worse, the separation of the application into components that run inside and outside the TEE may lead to information leaks. In summary, TEEs are a powerful means to design secure applications, but there is still a long way to building secure software with TEEs alone. In this work, we present J(E), a programming model for developing TEE-enabled applications where developers only need to annotate Java programs to define application-level security policies and run them securely inside enclaves.
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| 44. |
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| 45. |
- Odeberg, Jacob, et al.
(author)
-
Cloning and characterization of ZNF189, a novel human Krüppel-like zinc finger gene localized to chromosome 9q22-q31.
- 1998
-
In: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 50, s. 233-
-
Journal article (peer-reviewed)abstract
- A 3-kb-long cDNA encoding a Krüppel-like human zinc finger protein was isolated and mapped to chromosome 9q22-q31. The ZNF189 gene encodes a protein with 16 zinc fingers at its C-terminus and belongs to the Krüppel-associated box (KRAB)-containing group of zinc finger proteins. Four differently spliced cDNA transcripts, differing at the 5' coding region where a KRAB A repressor domain is encoded, were isolated. In addition, Northern blot analysis indicates the presence of two additional unidentified splice variants. Comparison of cDNA and genomic sequences shows that the ZNF189 gene spans approximately 11 kb and is organized into at least four exons, the large 3'-end exon coding for the complete zinc finger domain and the 3' untranslated region. ZNF189 is expressed in all tissues and cell types currently investigated, at varying levels, but with a tissue- or cell-type-restricted expression pattern for the different splice variants. ZNF189 is conserved in the genome of several mammalian species. Direct sequencing of the ZNF189 gene in microdissected tumor biopsies of sporadic basal cell carcinoma and squamous cell carcinoma reveals no mutations in the coding sequence or at exon/intron boundaries.
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| 46. |
- Odeberg, J, et al.
(author)
-
Context-dependent Taq-polymerase-mediated nucleotide alterations, as revealed by direct sequencing of the ZNF189 gene : implications for mutation detection.
- 1999
-
In: Gene. - 0378-1119 .- 1879-0038. ; 235:1-2
-
Journal article (peer-reviewed)abstract
- We have recently reported on the genetic organisation of a novel Krüppel-like zinc finger, ZNF189, located to 9q22-q31. In that study we found no mutations in the coding sequence when using ZNF189 as a candidate gene for sporadic basal cell cancer and squamous cell cancer. Here, by direct sequencing of the proximal promotor of ZNF189, mutations were found to appear in a small hot-spot region in over 50% of analysed tumour samples, the majority being G to A substitutions. The hot-spot region spans a 24bp G-rich region. Repeated analyses of the original sample lysates fail to confirm each of these mutations; and frequently new mutations appear at neighbouring positions. Subsequent analysis with serial dilutions of genomic DNA and a cosmid harbouring the wild-type ZNF189 gene demonstrate that these sequence-specific alterations arise in the outer PCR-amplification when 50 copies or less of template are used. Although the mechanism of how these context-specific alterations arise is not proven, the results demonstrate a previously unreported type of PCR-mediated sequence-specific alteration that easily could have been interpreted as being of clinical relevance. The phenomena observed show that mutations detected by direct sequencing can be caused by PCR-introduced alterations. Consequently, this should be of general caution in mutation analysis of disease gene candidates when using small amounts of template, such as microdissected biopsies.
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| 47. |
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| 48. |
- Ostergaard, Henrik, et al.
(author)
-
Prolonged half-life and preserved enzymatic properties of factor IX selectively PEGylated on native N-glycans in the activation peptide
- 2011
-
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 118:8, s. 2333-2341
-
Journal article (peer-reviewed)abstract
- Current management of hemophilia B entails multiple weekly infusions of factor IX (FIX) to prevent bleeding episodes. In an attempt to make a longer acting recombinant FIX (rFIX), we have explored a new releasable protraction concept using the native N-glycans in the activation peptide as sites for attachment of polyethylene glycol (PEG). Release of the activation peptide by physiologic activators converted glycoPEGylated rFIX (N9-GP) to native rFIXa and proceeded with normal kinetics for FXIa, while the Km for activation by FVIIa-tissue factor (TF) was increased by 2-fold. Consistent with minimal perturbation of rFIX by the attached PEG, N9-GP retained 73%-100% specific activity in plasma and whole-blood-based assays and showed efficacy comparable with rFIX in stopping acute bleeds in hemophilia B mice. In animal models N9-GP exhibited up to 2-fold increased in vivo recovery and a markedly prolonged half-life in mini-pig (76 hours) and hemophilia B dog (113 hours) compared with rFIX (16 hours). The extended circulation time of N9-GP was reflected in prolonged correction of coagulation parameters in hemophilia B dog and duration of effect in hemophilia B mice. Collectively, these results suggest that N9-GP has the potential to offer efficacious prophylactic and acute treatment of hemophilia B patients at a reduced dosing frequency. (Blood. 2011; 118(8): 2333-2341)
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| 49. |
- Vahed, M., et al.
(author)
-
Molecular dynamics simulation and experimental study of the surface-display of SPA protein via Lpp-OmpA system for screening of IgG
- 2020
-
In: AMB Express. - : Springer Nature. - 2191-0855. ; 10:1
-
Journal article (peer-reviewed)abstract
- Staphylococcal protein A (SpA) is a major virulence factor of Staphylococcus aureus. S. aureus is able to escape detection by the immune system by the surface display of protein A. The SpA protein is broadly used to purify immunoglobulin G (IgG) antibodies. This study investigates the fusion ability of Lpp′-OmpA (46–159) to anchor and display five replicate domains of protein A with 295 residues length (SpA295) of S. aureus on the surface of Escherichia coli to develop a novel bioadsorbent. First, the binding between Lpp’-OmpA-SPA295 and IgGFc and the three-dimensional structure was investigated using molecular dynamics simulation. Then high IgG recovery from human serum by the surface-displayed system of Lpp′-OmpA-SPA295 performed experimentally. In silico analysis was demonstrated the binding potential of SPA295 to IgG after expression on LPP-OmpA surface. Surface-engineered E. coli displaying SpA protein and IgG-binding assay with SDS-PAGE analysis exhibited high potential of the expressed complex on the E. coli surface for IgG capture from human serum which is applicable to conventional immune precipitation.
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| 50. |
- Williams, Cecilia, 1969-, et al.
(author)
-
Clones of normal keratinocytes and a variety of simultaneously present epidermal neoplastic lesions contain a multitude of p53 gene mutations in a xeroderma pigmentosum patient.
- 1998
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 58:11
-
Journal article (peer-reviewed)abstract
- A patient with xeroderma pigmentosum group C was extensively examined for mutations in the p53 gene in normal skin exposed to varying degrees of sunlight and in excisional biopsies of basal cell cancer, squamous cell cancer, and squamous cell dysplasia. Seventy-three samples were analyzed by microdissection of small cell clusters, followed by PCR and direct DNA sequencing. In skin taken from areas that most likely had never been exposed to the sun, no mutations were found. However, in skin exposed to the sun, we observed a multitude of mutations in the p53 gene. UV light-induced mutations were found in all types of lesions, as well as in clusters of morphologically normal epidermal cells. Twenty-nine distinct mutations were found in exons 5-8, all missense or nonsense, of which 27 (93%) were UV-specific C --> T or CC --> TT transitions at dipyrimidine sites of the nontranscribed strand. Two types of normal skin areas containing p53 mutations were observed: areas that stain strongly with p53 antibody (p53 patches) and those that do not stain. Because no silent or intron mutations were found in these cell clusters, the alterations in the p53 gene of morphologically normal cells are likely to have resulted in a selective growth advantage. The poor correlation between mutations and morphological phenotypes demonstrates that p53 mutations alone do not determine the phenotypes observed.
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