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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Wild, Philipp S., et al. (författare)
  • A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease
  • 2011
  • Ingår i: Circulation: Cardiovascular Genetics. - : American Heart Association/Lippincott, Williams & Wilkins. - 1942-325X .- 1942-3268. ; 4:4, s. 203-403
  • Tidskriftsartikel (refereegranskat)abstract
    • Background-eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). Methods and Results-In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7 x 10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3 x 10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4 x 10(-3)). Conclusions-The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA, located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD. (Circ Cardiovasc Genet. 2011;4:403-412.)
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3.
  • Crespo, Ana, et al. (författare)
  • Phylogenetic generic classification of parmelioid lichens (Parmeliaceae,Ascomycota) based on molecular, morphological and chemical evidence.
  • 2010
  • Ingår i: Taxon. - : John Wiley & Sons. - 0040-0262 .- 1996-8175. ; 59:6, s. 1735-1753
  • Tidskriftsartikel (refereegranskat)abstract
    • Parmelioid lichens are a diverse and ubiquitous group of foliose lichens. Generic delimitation in parmelioid lichens has been in a state of flux since the late 1960s with the segregation of the large, heterogeneous genus Parmelia into numerous smaller genera. Recent molecular phylogenetic studies have demonstrated that some of these new genera were monophyletic, some were not, and others, previously believed to be unrelated, fell within single monophyletic groups, indicating the need for a revision of the generic delimitations. This study aims to give an overview of current knowledge of the major clades of all parmelioid lichens. For this, we assembled a dataset of 762 specimens, including 31 of 33 currently accepted parmelioid genera (and 63 of 84 accepted genera of Parmeliaceae). We performed maximum likelihood and Bayesian analyses of combined datasets including two, three and four loci. Based on these phylogenies and the correlation of morphological and chemical characters that characterize monophyletic groups, we accept 27 genera within nine main clades. We re-circumscribe several genera and reduce Parmelaria to synonymy with Parmotrema. Emodomelanelia Divakar & A. Crespo is described as a new genus (type: E. masonii). Nipponoparmelia (Kurok.) K.H. Moon, Y. Ohmura & Kashiw. ex A. Crespo & al. is elevated to generic rank and 15 new combinations are proposed (in the genera Flavoparmelia, Parmotrema, Myelochroa, Melanelixia and Nipponoparmelia). A short discussion of the accepted genera is provided and remaining challenges and areas requiring additional taxon sampling are identified.
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4.
  • Zamora, Juan Carlos, et al. (författare)
  • Considerations and consequences of allowing DNA sequence data as types of fungal taxa
  • 2018
  • Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
  • Tidskriftsartikel (refereegranskat)abstract
    • Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
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5.
  • Astrup, Arne, et al. (författare)
  • The role of reducing intakes of saturated fat in the prevention of cardiovascular disease : where does the evidence stand in 2010?
  • 2011
  • Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 93:4, s. 684-688
  • Tidskriftsartikel (refereegranskat)abstract
    • Current dietary recommendations advise reducing the intake of saturated fatty acids (SFAs) to reduce coronary heart disease (CHD) risk, but recent findings question the role of SFAs. This expert panel reviewed the evidence and reached the following conclusions: the evidence from epidemiologic, clinical, and mechanistic studies is consistent in finding that the risk of CHD is reduced when SFAs are replaced with polyunsaturated fatty acids (PUFAs). In populations who consume a Western diet, the replacement of 1% of energy from SFAs with PUFAs lowers LDL cholesterol and is likely to produce a reduction in CHD incidence of >= 2-3%. No clear benefit of substituting carbohydrates for SFAs has been shown, although there might be a benefit if the carbohydrate is unrefined and has a low glycemic index. Insufficient evidence exists to judge the effect on CHD risk of replacing SFAs with MUFAs. No clear association between SFA intake relative to refined carbohydrates and the risk of insulin resistance and diabetes has been shown. The effect of diet on a single biomarker is insufficient evidence to assess CHD risk. The combination of multiple biomarkers and the use of clinical end-points could help substantiate the effects on CHD. Furthermore, the effect of particular foods on CHD cannot be predicted solely by their content of total SFAs because individual SFAs may have different cardiovascular effects and major SFA food sources contain other constituents that could influence CHD risk. Research is needed to clarify the role of SFAs compared with specific forms of carbohydrates in CHD risk and to compare specific foods with appropriate alternatives.
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6.
  • Bauer, Michael, et al. (författare)
  • Association between solar insolation and a history of suicide attempts in bipolar I disorder.
  • 2019
  • Ingår i: Journal of psychiatric research. - : Elsevier BV. - 1879-1379 .- 0022-3956. ; 113, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • In many international studies, rates of completed suicide and suicide attempts have a seasonal pattern that peaks in spring or summer. This exploratory study investigated the association between solar insolation and a history of suicide attempt in patients with bipolar I disorder. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area on Earth. Data were collected previously from 5536 patients with bipolar I disorder at 50 collection sites in 32 countries at a wide range of latitudes in both hemispheres. Suicide related data were available for 3365 patients from 310 onset locations in 51 countries. 1047 (31.1%) had a history of suicide attempt. There was a significant inverse association between a history of suicide attempt and the ratio of mean winter solar insolation/mean summer solar insolation. This ratio is smallest near the poles where the winter insolation is very small compared to the summer insolation. This ratio is largest near the equator where there is relatively little variation in the insolation over the year. Other variables in the model that were positively associated with suicide attempt were being female, a history of alcohol or substance abuse, and being in a younger birth cohort. Living in a country with a state-sponsored religion decreased the association. (All estimated coefficients p<0.01). In summary, living in locations with large changes in solar insolation between winter and summer may be associated with increased suicide attempts in patients with bipolar disorder. Further investigation of the impacts of solar insolation on the course of bipolar disorder is needed.
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7.
  • Bleiker, Simon J., et al. (författare)
  • Device with a waveguide supported on a substrate and method for its fabrication
  • 2020
  • Patent (populärvet., debatt m.m.)abstract
    • ABSTRACT A device (1) and a method for fabricating such a device is described. The device (1) comprises a device layer (4), a substrate (2) defining a substrate plane (3). A device layer plane (5) is defined on the side of the device layer (4) facing the substrate (2). The device also comprises a waveguide (7) for guiding an electromagnetic wave. The waveguide (7) is supported on the substrate (2) via a support structure (6) extending from the substrate (2) to the device layer (4). The ratio of the largest distance (D1), perpendicular to the substrate plane (3), between a free surface of the waveguide (7) facing the substrate and any solid material to the height (h) of the waveguide (7) is more than 6, i.e. D1/h \textgreater 6. The ratio of the distance (D2), perpendicular to the substrate plane (3), between the device layer plane (5) and the substrate plane (3) to the height (h) of the waveguide (7) is more than 6, i.e. D2/h \textgreater 6.
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8.
  • Bornholdt, Dorothea, et al. (författare)
  • Genotype-Phenotype Correlations Emerging from the Identification of Missense Mutations in MBTPS2
  • 2013
  • Ingår i: Human Mutation. - : Hindawi Limited. - 1059-7794 .- 1098-1004. ; 34:4, s. 587-594
  • Tidskriftsartikel (refereegranskat)abstract
    • Missense mutations affecting membrane-bound transcription factor protease site 2 (MBTPS2) have been associated with Ichthyosis Follicularis with Atrichia and Photophobia (IFAP) syndrome with or without BRESHECK syndrome, with keratosis follicularis spinulosa decalvans, and Olmsted syndrome. This metalloprotease activates, by intramembranous trimming in conjunction with the protease MBTPS1, regulatory factors involved in sterol control of transcription and in cellular stress response. In this study, 11 different MBTPS2 missense mutations detected in patients from 13 unrelated families were correlated with the clinical phenotype, with their effect on cellular growth in media without lipids, and their potential role for sterol control of transcription. Seven variants were novel [c.774C>G (p.I258M); c.758G>C (p.G253A); c.686T>C (p.F229S); c.1427T>C (p.L476S); c.1430A>T (p.D477V); c.1499G>A (p.G500D); c.1538T>C (p.L513P)], four had previously been reported in unrelated sibships [c.261G>A (p.M87I); c.1286G>A (p.R429H); c.1424T>C (p.F475S); c.1523A>G (p.N508S)]. In the enzyme, the mutations cluster in transmembrane domains. Amino-acid exchanges near the active site are more detrimental to functionality of the enzyme and, clinically, associated with more severe phenotypes. In male patients, a genotypephenotype correlation begins to emerge, linking the site of the mutation in MBTPS2 with the clinical outcome described as IFAP syndrome with or without BRESHECK syndrome, keratosis follicularis spinulosa decalvans, X-linked, Olmsted syndrome, or possibly further X-linked traits with an oculocutaneous component.
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9.
  • Brådvik, Louise, et al. (författare)
  • Clinical prediction of suicide and undetermined death : A pseudo-prospective clinical and medico-legal study of substance abusers
  • 2017
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 14:3
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examines aspects of prediction of suicide and death of undetermined intent. We investigated all consecutive, autopsied patients between 1993 and 1997 who had been in contact with the Addiction Centre in Malmö from 1968 onwards. The staff was asked, shortly after autopsy but before they knew of the manner of death, if they thought the patient had committed suicide. The case records were blindly evaluated, and toxicological autopsy findings for alcohol in blood samples investigated. The specificity of prediction was 83% and significantly more often correct than the sensitivity, which was only 45% for suicide and for suicide/death of undetermined intent (93% versus 39%). Suicidal communication was more often considered non-serious before death of undetermined intent than before suicide. The former could be predicted by ideation but not by suicide attempt reported in case records, unlike suicide, which was predicted by both. The undetermined group also showed higher levels of alcohol in the blood at autopsy. We concluded that more serious clinical investigation of suicidal feelings, which may be hidden and not taken seriously, and treatment of alcohol use disorders with active follow-up appear urgent in the efforts to prevent suicide.
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10.
  • Brådvik, Louise, et al. (författare)
  • From Substance Use Disorders in Life to Autopsy Findings : A Combined Case-Record and Medico-Legal Study
  • 2019
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 16:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Several studies have shown mortality and suicide risk in substance use disorders, and autopsy findings with respect to the used substances. However, there seems to be a gap in the knowledge about substances misused in life and at death at the within-person level. Methods: All consecutive, autopsied patients during 1993 to 1997, who had been in contact with the Addiction Centre in Malmö from 1968, were investigated (365 subjects). Drug misuse in the long-term course noted in case records was related to autopsy findings. Self-inflicted death (suicide/undetermined suicide/accidental overdose) was compared with natural death. Results: Benzodiazepine misuse was associated with a high risk of autopsy findings of the substance in suicide and death of undetermined intent. It was also associated among non-misusers, but less so. An alcohol level above 1‰ was found more often in self-inflicted death. Prescription opioids at autopsy were mainly found in self-inflicted death among non-misusers. Heroin misuse was related to overdose. Central nervous system stimulants (CNS-S) and cannabis were rarely found in self-inflicted death among previous misusers. The overlap between depression in life and antidepressants at death was low. Conclusions: Benzodiazepines and alcohol seem to disinhibit suicidal tendencies. Suicide risk among users of cannabis and CNS-S may be related to other risk factors than acute use. Implications for suicide prevention are discussed.
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11.
  • Brådvik, Louise, et al. (författare)
  • Heroin addicts reporting previous heroin overdoses also report suicide attempts
  • 2007
  • Ingår i: Suicide & Life-Threatening Behavior. - : Wiley. - 0363-0234. ; 37:4, s. 475-481
  • Tidskriftsartikel (refereegranskat)abstract
    • Nonfatal heroin overdoses and suicide attempts are both common among heroin addicts, but there is limited knowledge about the association between them. The sample in the present study consisted of 149 regular heroin users in Malmo, Sweden. Out of these 98 had taken an unintentional heroin overdose at some time and 51 had made at least one attempt to commit suicide (but not using heroin). Suicide attempts were significantly more common among those who had taken unintentional overdoses as compared with those who had never taken any overdose (p < 0.01). The more overdoses, the greater the risk of suicide attempt.
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12.
  • Brådvik, Louise, et al. (författare)
  • Number of addictive substances used related to increased risk of unnatural death: a combined medico-legal and case-record study.
  • 2009
  • Ingår i: BMC Psychiatry. - 1471-244X. ; 9:Aug 4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Substance use disorders have repeatedly been found to lead to premature death, i.e. drug-related death by disease, fatal intoxications, or trauma (accidents, suicide, undetermined suicide, and homicide). The present study examined the relationship between multi-drug substance use and natural and unnatural death. METHODS: All consecutive, autopsied patients who had been in contact with the Addiction Centre in Malmö University Hospital from 1993 to 1997 inclusive were investigated. Drug abuse was investigated blindly in the case records and related to the cause of death in 387 subjects. RESULTS: Every substance apart from alcohol used previously in life added to the risk of unnatural death in a linear way. There were independent increased risks of fatal heroin overdoses or undetermined suicide. Death by suicide and violent death were unrelated to additional abuse. CONCLUSION: The number of drugs used was related to an increased risk of unnatural death by undetermined suicide (mainly fatal intoxications) and heroin overdose.
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13.
  • Brådvik, Louise, et al. (författare)
  • Self-reported and observed heroin overdoses in Malmoe
  • 2007
  • Ingår i: Journal of Substance Use. - : Informa UK Limited. - 1465-9891 .- 1475-9942. ; 12:2, s. 119-126
  • Tidskriftsartikel (refereegranskat)abstract
    • Object: The aim of the present study was to investigate the pattern of non-fatal heroin overdoses for men and women in Sweden, a country with late onset of heroin use. Material: Subjects were recruited through the Syringe Programme and the Addiction Centre in Malmoe. A total of 149 subjects were interviewed, 108 men and 41 women. They were asked about their social situation, experienced and observed overdoses and circumstances around them. Results: Overdoses were very common; 74% of the subjects had experienced at least one overdose. Almost all, 96%, had observed at least one overdose in others and 32% had witnessed a fatal overdose. Actions taken were often insufficient. A combination with other drugs, mainly benzodiazepine and alcohol and/or a lowered tolerance for heroin after visits in institutions contributed to the overdose in a majority of the cases. Men and women differed in that men used concomitant drugs more often and women more often took heroin alone. Conclusion: Self-reported and observed non-fatal heroin overdoses were more common than expected. Contributing factors were found in the majority of the cases. Pure overdoses were more common in women.
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14.
  • Culina, Antica, et al. (författare)
  • Connecting the data landscape of long-term ecological studies : The SPI-Birds data hub
  • 2021
  • Ingår i: Journal of Animal Ecology. - : John Wiley & Sons. - 0021-8790 .- 1365-2656. ; 90:9, s. 2147-2160
  • Tidskriftsartikel (refereegranskat)abstract
    • The integration and synthesis of the data in different areas of science is drastically slowed and hindered by a lack of standards and networking programmes. Long-term studies of individually marked animals are not an exception. These studies are especially important as instrumental for understanding evolutionary and ecological processes in the wild. Furthermore, their number and global distribution provides a unique opportunity to assess the generality of patterns and to address broad-scale global issues (e.g. climate change). To solve data integration issues and enable a new scale of ecological and evolutionary research based on long-term studies of birds, we have created the SPI-Birds Network and Database ()-a large-scale initiative that connects data from, and researchers working on, studies of wild populations of individually recognizable (usually ringed) birds. Within year and a half since the establishment, SPI-Birds has recruited over 120 members, and currently hosts data on almost 1.5 million individual birds collected in 80 populations over 2,000 cumulative years, and counting. SPI-Birds acts as a data hub and a catalogue of studied populations. It prevents data loss, secures easy data finding, use and integration and thus facilitates collaboration and synthesis. We provide community-derived data and meta-data standards and improve data integrity guided by the principles of Findable, Accessible, Interoperable and Reusable (FAIR), and aligned with the existing metadata languages (e.g. ecological meta-data language). The encouraging community involvement stems from SPI-Bird's decentralized approach: research groups retain full control over data use and their way of data management, while SPI-Birds creates tailored pipelines to convert each unique data format into a standard format. We outline the lessons learned, so that other communities (e.g. those working on other taxa) can adapt our successful model. Creating community-specific hubs (such as ours, COMADRE for animal demography, etc.) will aid much-needed large-scale ecological data integration.
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17.
  • Enrico, Alessandro, et al. (författare)
  • Ultrafast and Resist-Free Nanopatterning of 2D Materials by Femtosecond Laser Irradiation
  • 2023
  • Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 17:9, s. 8041-8052
  • Tidskriftsartikel (refereegranskat)abstract
    • The performance of two-dimensional (2D) materials is promising for electronic, photonic, and sensing devices since they possess large surface-to-volume ratios, high mechanical strength, and broadband light sensitivity. While significant advances have been made in synthesizing and transferring 2D materials onto different substrates, there is still the need for scalable patterning of 2D materials with nanoscale precision. Conventional lithography methods require protective layers such as resist or metals that can contaminate or degrade the 2D materials and deteriorate the final device performance. Current resist-free patterning methods are limited in throughput and typically require custom-made equipment. To address these limitations, we demonstrate the noncontact and resist-free patterning of platinum diselenide (PtSe2), molybdenum disulfide (MoS2), and graphene layers with nanoscale precision at high processing speed while preserving the integrity of the surrounding material. We use a commercial, off-the-shelf two-photon 3D printer to directly write patterns in the 2D materials with features down to 100 nm at a maximum writing speed of 50 mm/s. We successfully remove a continuous film of 2D material from a 200 μm × 200 μm substrate area in less than 3 s. Since two-photon 3D printers are becoming increasingly available in research laboratories and industrial facilities, we expect this method to enable fast prototyping of devices based on 2D materials across various research areas.
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18.
  • Fielding, Christopher, et al. (författare)
  • Age and pattern of the southern high-latitude continental end-Permian extinction constrained by multiproxy analysis
  • 2019
  • Ingår i: Nature Communications. - London : Springer Science and Business Media LLC. - 2041-1723. ; 10:385, s. 1-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Past studies of the end-Permian extinction (EPE), the largest biotic crisis of the Phanerozoic, have not resolved the timing of events in southern high-latitudes. Here we use palynology coupled with high-precision CA-ID-TIMS dating of euhedral zircons from continental sequences of the Sydney Basin, Australia, to show that the collapse of the austral Permian Glossopteris flora occurred prior to 252.3 Ma (~370 kyrs before the main marine extinction). Weathering proxies indicate that floristic changes occurred during a brief climate perturbation in a regional alluvial landscape that otherwise experienced insubstantial change in fluvial style, insignificant reorganization of the depositional surface, and no abrupt aridification. Palaeoclimate modelling suggests a moderate shift to warmer summer temperatures and amplified seasonality in temperature across the EPE, and warmer and wetter conditions for all seasons into the Early Triassic. The terrestrial EPE and a succeeding peak in Ni concentration in the Sydney Basin correlate, respectively, to the onset of the primary extrusive and intrusive phases of the Siberian Traps Large Igneous Province.
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19.
  • Fielding, Christopher R., et al. (författare)
  • A multidisciplinary approach to resolving the end-Guadalupian extinction
  • 2023
  • Ingår i: Evolving Earth. - : Elsevier. - 2950-1172. ; 1
  • Tidskriftsartikel (refereegranskat)abstract
    • The transition from the middle to late Permian (Guadalupian–Lopingian) is claimed to record one or more extinction events that rival the ‘Big Five’ in terms of depletion of biological diversity and reorganization of ecosystem structure. Yet many questions remain as to whether the events recorded in separate regions were synchronous, causally related, or were of a magnitude rivaling other major crises in Earth’s history. In this paper, we survey some major unresolved issues related to the Guadalupian–Lopingian transition and offer a multidisciplinary approach to advance understanding of this under-appreciated biotic crisis by utilizing records in Southern Hemisphere high-palaeolatitude settings. We focus on the Bowen-Gunnedah-Sydney Basin System (BGSBS) as a prime site for analyses of biotic and physical environmental change at high palaeolatitudes in the middle and terminal Capitanian. Preliminary data suggest the likely position of the mid-Capitanian event is recorded in regressive deposits at the base of the Tomago Coal Measures (northern Sydney Basin) and around the contact between the Broughton Formation and the disconformably overlying Pheasants Nest Formation (southern Sydney Basin). Initial data suggest that the end-Capitanian event roughly correlates to the transgressive “Kulnura Marine Tongue” in the middle of the Tomago Coal Measures (northern Sydney Basin) and strata bearing dispersed, ice-rafted gravel in the Erins Vale Formation (southern Sydney Basin). Preliminary observations suggest that few plant genera or species disappeared in the transition from the Guadalupian to Lopingian, and the latter interval saw an increase in floristic diversity.
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20.
  • Gabre, Jonatan L., 1988, et al. (författare)
  • Preclinical exploration of the DNA damage response pathway using the interactive neuroblastoma cell line explorer CLEAN
  • 2024
  • Ingår i: NAR Cancer. - 2632-8674. ; 6:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuroblastoma (NB) is the most common cancer in infancy with an urgent need for more efficient targeted therapies. The development of novel (combinatorial) treatment strategies relies on extensive explorations of signaling perturbations in neuroblastoma cell lines, using RNA-Seq or other high throughput technologies (e.g. phosphoproteomics). This typically requires dedicated bioinformatics support, which is not always available. Additionally, while data from published studies are highly valuable and raw data (e.g. fastq files) are nowadays released in public repositories, data processing is time-consuming and again difficult without bioinformatics support. To facilitate NB research, more user-friendly and immediately accessible platforms are needed to explore newly generated as well as existing high throughput data. To make this possible, we developed an interactive data centralization and visualization web application, called CLEAN (the Cell Line Explorer web Application of Neuroblastoma data; https://ccgg.ugent.be/shiny/clean/). By focusing on the regulation of the DNA damage response, a therapeutic target of major interest in neuroblastoma, we demonstrate how CLEAN can be used to gain novel mechanistic insights and identify putative drug targets in neuroblastoma.
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21.
  • Gazit, Aviv, et al. (författare)
  • Tricyclic quinoxalines as potent kinase inhibitors of PDGFR kinase, Flt3 and Kit
  • 2003
  • Ingår i: Bioorganic & Medicinal Chemistry. - 0968-0896 .- 1464-3391. ; 11:9, s. 2007-2018
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we report on novel quinoxalines as highly potent and selective inhibitors of the type III receptor tyrosine kinases PDGFR, FLT3, and KIT. These compounds, tricyclic quinoxalines, were generated in order to improve bioavailability over the highly hydrophobic bicyclic quinoxalines. Four of the highly active compounds were characterized in detail and are shown to inhibit PDGFR kinase activity of the isolated receptor as well as in intact cells in the sub-micromolar concentration range. We show that the most active inhibitor (compound 13, AGL 2043) is approximately 15-20 times more potent than its isomer (compound 14, AGL 2044). We therefore compared the three dimensional structures of the two compounds by X-ray crystallography. These compounds are also highly effective in blocking the kinase activity of FLT3, KIT, and the oncogenic protein Tel-PDGFR in intact cells. These compounds are potent inhibitors of the proliferation of pig heart smooth muscle cells. They fully arrest the growth of these cells and the effect is fully reversible. The chemical, biochemical and cellular properties of these compounds as well as the solubility properties make them suitable for development as anti-restenosis and anti-cancer agents.
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22.
  • Hart, Robert G., et al. (författare)
  • Rivaroxaban for secondary stroke prevention in patients with embolic strokes of undetermined source : Design of the NAVIGATE ESUS randomized trial
  • 2016
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 1:3, s. 146-154
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Embolic strokes of undetermined source comprise up to 20% of ischemic strokes. The stroke recurrence rate is substantial with aspirin, widely used for secondary prevention. The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source international trial will compare the efficacy and safety of rivaroxaban, an oral factor Xa inhibitor, versus aspirin for secondary prevention in patients with recent embolic strokes of undetermined source. Main hypothesis: In patients with recent embolic strokes of undetermined source, rivaroxaban 15 mg once daily will reduce the risk of recurrent stroke (both ischemic and hemorrhagic) and systemic embolism (primary efficacy outcome) compared with aspirin 100 mg once daily. Design: Double-blind, randomized trial in patients with embolic strokes of undetermined source, defined as nonlacunar cryptogenic ischemic stroke, enrolled between seven days and six months from the qualifying stroke. The planned sample size of 7000 participants will be recruited from approximately 480 sites in 31 countries between 2014 and 2017 and followed for a mean of about two years until at least 450 primary efficacy outcome events have occurred. The primary safety outcome is major bleeding. Two substudies assess (1) the relative effect of treatments on MRI-determined covert brain infarcts and (2) the biological underpinnings of embolic strokes of undetermined source using genomic and biomarker approaches. Summary: The New Approach riVaroxaban Inhibition of Factor Xa in a Global trial versus ASA to prevenT Embolism in Embolic Stroke of Undetermined Source trial is evaluating the benefits and risks of rivaroxaban for secondary stroke prevention in embolic strokes of undetermined source patients. Main results are anticipated in 2018.
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23.
  • Ilinca, Andreea, et al. (författare)
  • Updated Stroke Gene Panels : Rapid evolution of knowledge on monogenic causes of stroke
  • 2023
  • Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1476-5438 .- 1018-4813. ; 31:2, s. 239-242
  • Tidskriftsartikel (refereegranskat)abstract
    • This article updates our previous Stroke Gene Panels (SGP) from 2017. Online Mendelian Inheritance in Man and PubMed were searched. We divided detected genes into two SGP groups, SGP1: genes reported in at least one person with stroke and associated with one or more clinical subgroups: large artery atherosclerotic, large artery non-atherosclerotic (tortuosity, dolichoectasia, aneurysm, non-atherosclerotic dissection or occlusion), cerebral small vessel diseases, cardio-embolic (arrhythmia, heart defect, cardiomyopathy), coagulation dysfunctions (venous thrombosis, arterial thrombosis, bleeding tendency), intracerebral hemorrhage, vascular malformations (cavernoma, arteriovenous malformations) and metabolism disorders; and SGP2: genes related to diseases that may predispose to stroke. We identified 168 SGP1 genes, 70 of these were validated for clinical practice. We also detected 72 SGP2 genes. Nine genes were removed because of conflicting evidence. The number of genes increased from 168 to 240 during 4.5-years, reflecting a dynamic evolution and the need for regular updates for research and clinical use.
  •  
24.
  • Jandt, Enrico, et al. (författare)
  • The protein-tyrosine phosphatase DEP-1 modulates growth factor-stimulated cell migration and cell-matrix adhesion
  • 2003
  • Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 0950-9232 .- 1476-5594. ; 22:27, s. 4175-4185
  • Tidskriftsartikel (refereegranskat)abstract
    • Density-enhanced protein-tyrosine phosphatase-1 (DEP-1 also CD148) is a transmembrane molecule with a single intracellular PTP domain. It has recently been proposed to function as a tumor suppressor. We have previously shown that DEP-1 dephosphorylates the activated platelet-derived growth factor (PDGF) beta-receptor in a site-selective manner (Kovalenko et al. (2000). J. Biol. Chem. 275, 16219-16226). We analysed cell lines with inducible DEP-1 expression for cellular functions of DEP-1. Several aspects of PDGFbeta-receptor signaling were negatively affected by DEP-1 expression. These include PDGF-stimulated activation of inositol trisphosphate formation, Erk1/2, p21Ras, and Src. Activation of receptor-associated phosphoinositide-3 kinase activity and of Akt/PKB were weakly attenuated at early time points of stimulation. Inhibition of PDGF-stimulated signaling depended on DEP-1 catalytic activity. Importantly, DEP-1 inhibited PDGF-stimulated cell migration. The catalytically inactive DEP-1 C1239S variant enhanced cell migration and PDGF-stimulated Erk1/2 activation, suggesting a dominant negative interference with endogenous DEP-1. In contrast to cell migration, cell-substrate adhesion was promoted by active DEP-1 and delayed or suppressed by DEP-1 C1239S, correlating with positive effects of DEP-1 on adhesion-stimulated Src kinase. We propose that negative regulation of growth-factor stimulated cell migration and promotion of cell-matrix adhesion may be related to the function of DEP-1 as tumor suppressor.
  •  
25.
  • Kasner, Scott E., et al. (författare)
  • Characterization of Patients with Embolic Strokes of Undetermined Source in the NAVIGATE ESUS Randomized Trial
  • 2018
  • Ingår i: Journal of Stroke and Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 27:6, s. 1673-1682
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial vs. ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial is a randomized phase-III trial comparing rivaroxaban versus aspirin in patients with recent ESUS. Aims: We aimed to describe the baseline characteristics of this large ESUS cohort to explore relationships among key subgroups. Methods: We enrolled 7213 patients at 459 sites in 31 countries. Prespecified subgroups for primary safety and efficacy analyses included age, sex, race, global region, stroke or transient ischemic attack prior to qualifying event, time to randomization, hypertension, and diabetes mellitus. Results: Mean age was 66.9 ± 9.8 years; 24% were under 60 years. Older patients had more hypertension, coronary disease, and cancer. Strokes in older subjects were more frequently cortical and accompanied by radiographic evidence of prior infarction. Women comprised 38% of participants and were older than men. Patients from East Asia were oldest whereas those from Latin America were youngest. Patients in the Americas more frequently were on aspirin prior to the qualifying stroke. Acute cortical infarction was more common in the United States, Canada, and Western Europe, whereas prior radiographic infarctions were most common in East Asia. Approximately forty-five percent of subjects were enrolled within 30 days of the qualifying stroke, with earliest enrollments in Asia and Eastern Europe. Conclusions: NAVIGATE-ESUS is the largest randomized trial comparing antithrombotic strategies for secondary stroke prevention in patients with ESUS. The study population encompasses a broad array of patients across multiple continents and these subgroups provide ample opportunities for future research.
  •  
26.
  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
  •  
27.
  • Kondratyuk, Sergey Y., et al. (författare)
  • Four new Caloplaca species with depsidones from Australia.
  • 2011
  • Ingår i: Bibiotheca Lichenologica 106. Biomonitoring, ecology, and systematics of lichens. Recognizing the lichenological legacy of Thomas H. Nash III on his 65th birthday.. - 1436-1698. - 9783443580858 ; 106, s. 179-186
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • Four new Caloplaca species with depsidones are described, C. ochrolechioides S.Y. Kondr., Kärnefelt & Elix, with variolaric and isosubnotatic acids, C. phaeocincta S.Y. Kondr. & Elix, C. sconensis S.Y.Kondr., Kärnefelt & A.Thell, and C. tomnashii S.Y. Kondr., Elix & Kärnefelt, with caloploicin, vicanicin, diploicin, fulgidin, and isofulgidin. The new combination Crocynia glaucescens (F. Wilson) S.Y. Kondr., Elix & Kärnefelt, containing atranorin, is proposed for Amphiloma glaucescens F.Wilson.
  •  
28.
  • Köttgen, Anna, et al. (författare)
  • New loci associated with kidney function and chronic kidney disease
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:5, s. 376-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea < 60 ml/min/1.73 m2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide–significant loci (P < 5 × 10−8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or near LASS2, GCKR, ALMS1, TFDP2, DAB2, SLC34A1, VEGFA, PRKAG2, PIP5K1B, ATXN2, DACH1, UBE2Q2 and SLC7A9) and 7 loci suspected to affect creatinine production and secretion (CPS1, SLC22A2, TMEM60, WDR37, SLC6A13, WDR72 and BCAS3). These results further our understanding of the biologic mechanisms of kidney function by identifying loci that potentially influence nephrogenesis, podocyte function, angiogenesis, solute transport and metabolic functions of the kidney.
  •  
29.
  • Lin, Pen-Sheng, et al. (författare)
  • Low-concentration detection of CO2 using suspended silicon waveguides in the mid-IR
  • 2022
  • Ingår i: 2022 Conference on Lasers and Electro-Optics, CLEO 2022. - : Institute of Electrical and Electronics Engineers Inc..
  • Konferensbidrag (refereegranskat)abstract
    • We show detection of CO2 concentrations as low as 500 ppm using a suspended silicon photonic mid-IR waveguide. The performance is enabled by the low propagation loss (2.35 ±0.25) dB/cm permitting sensing with waveguides up to 7 cm in length. 
  •  
30.
  • Livingstone, Katherine M., et al. (författare)
  • FTO genotype and weight loss : systematic review and meta-analysis of 9563 individual participant data from eight randomised controlled trials
  • 2016
  • Ingår i: BMJ: British Medical Journal. - : BMJ. - 1756-1833. ; 354
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual participant data from all studies included in this review, using allele dose coding for genetic effects and a common set of covariates. Study level interactions were combined using random effect models. Metaregression and subgroup analysis were used to assess sources of study heterogeneity.RESULTS: We identified eight eligible randomised controlled trials for the systematic review and meta-analysis (n=9563). Overall, differential changes in body mass index, body weight, and waist circumference in response to weight loss intervention were not significantly different between FTO genotypes. Sensitivity analyses indicated that differential changes in body mass index, body weight, and waist circumference by FTO genotype did not differ by intervention type, intervention length, ethnicity, sample size, sex, and baseline body mass index and age category.CONCLUSIONS: We have observed that carriage of the FTO minor allele was not associated with differential change in adiposity after weight loss interventions. These findings show that individuals carrying the minor allele respond equally well to dietary, physical activity, or drug based weight loss interventions and thus genetic predisposition to obesity associated with the FTO minor allele can be at least partly counteracted through such interventions.SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015969.
  •  
31.
  • McCarthy, Randy J., et al. (författare)
  • Registered Replication Report on Srull and Wyer (1979)
  • 2018
  • Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications Inc. - 2515-2459 .- 2515-2467. ; 1:3, s. 321-336
  • Tidskriftsartikel (refereegranskat)abstract
    • Srull and Wyer (1979) demonstrated that exposing participants to more hostility-related stimuli caused them subsequently to interpret ambiguous behaviors as more hostile. In their Experiment 1, participants descrambled sets of words to form sentences. In one condition, 80% of the descrambled sentences described hostile behaviors, and in another condition, 20% described hostile behaviors. Following the descrambling task, all participants read a vignette about a man named Donald who behaved in an ambiguously hostile manner and then rated him on a set of personality traits. Next, participants rated the hostility of various ambiguously hostile behaviors (all ratings on scales from 0 to 10). Participants who descrambled mostly hostile sentences rated Donald and the ambiguous behaviors as approximately 3 scale points more hostile than did those who descrambled mostly neutral sentences. This Registered Replication Report describes the results of 26 independent replications (N = 7,373 in the total sample; k = 22 labs and N = 5,610 in the primary analyses) of Srull and Wyer?s Experiment 1, each of which followed a preregistered and vetted protocol. A random-effects meta-analysis showed that the protagonist was seen as 0.08 scale points more hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% confidence interval, CI = [0.004, 0.16]). The ambiguously hostile behaviors were seen as 0.08 points less hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% CI = [?0.18, 0.01]). Although the confidence interval for one outcome excluded zero and the observed effect was in the predicted direction, these results suggest that the currently used methods do not produce an assimilative priming effect that is practically and routinely detectable.
  •  
32.
  • Miadlikowska, Jolanta, et al. (författare)
  • A multigene phylogenetic synthesis for the class Lecanoromycetes (Ascomycota): 1307 fungi representing 1139 infrageneric taxa, 317 genera and 66 families.
  • 2014
  • Ingår i: Molecular Phylogenetics and Evolution. - : Elsevier BV. - 1095-9513 .- 1055-7903. ; 79:Online 18 April 2014, s. 132-168
  • Tidskriftsartikel (refereegranskat)abstract
    • The Lecanoromycetes is the largest class of lichenized Fungi, and one of the most species-rich classes in the kingdom. Here we provide a multigene phylogenetic synthesis (using three ribosomal RNA-coding and two protein-coding genes) of the Lecanoromycetes based on 635 newly generated and 3307 publicly available sequences representing 1139 taxa, 317 genera, 66 families, 17 orders and five subclasses (four currently recognized: Acarosporomycetidae, Lecanoromycetidae, Ostropomycetidae, Umbilicariomycetidae; and one provisionarily recognized, 'Candelariomycetidae'). Maximum likelihood phylogenetic analyses on four multigene datasets assembled using a cumulative supermatrix approach with a progressively higher number of species and missing data (5-gene, 5+4-gene, 5+4+3-gene and 5+4+3+2-gene datasets) show that the current classification includes non-monophyletic taxa at various ranks, which need to be recircumscribed and require revisionary treatments based on denser taxon sampling and more loci. Two newly circumscribed orders (Arctomiales and Hymeneliales in the Ostropomycetidae) and three families (Ramboldiaceae and Psilolechiaceae in the Lecanorales, and Strangosporaceae in the Lecanoromycetes inc. sed.) are introduced. The potential resurrection of the families Eigleraceae and Lopadiaceae is considered here to alleviate phylogenetic and classification disparities. An overview of the photobionts associated with the main fungal lineages in the Lecanoromycetes based on available published records is provided. A revised schematic classification at the family level in the phylogenetic context of widely accepted and newly revealed relationships across Lecanoromycetes is included. The cumulative addition of taxa with an increasing amount of missing data (i.e., a cumulative supermatrix approach, starting with taxa for which sequences were available for all five targeted genes and ending with the addition of taxa for which only two genes have been sequenced) revealed relatively stable relationships for many families and orders. However, the increasing number of taxa without the addition of more loci also resulted in an expected substantial loss of phylogenetic resolving power and support (especially for deep phylogenetic relationships), potentially including the misplacements of several taxa. Future phylogenetic analyses should include additional single copy protein-coding markers in order to improve the tree of the Lecanoromycetes. As part of this study, a new module ("Hypha") of the freely available Mesquite software was developed to compare and display the internodal support values derived from this cumulative supermatrix approach.
  •  
33.
  • Middleton, Matthew J., et al. (författare)
  • Bright radio emission from an ultraluminous stellar-mass microquasar in M 31
  • 2013
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 493:7431, s. 187-190
  • Tidskriftsartikel (refereegranskat)abstract
    • A subset of ultraluminous X-ray sources (those with luminosities of less than 10(40) erg s(-1); ref. 1) are thought to be powered by the accretion of gas onto black holes with masses of similar to 5-20M(circle dot), probably by means of an accretion disk(2,3). The X-ray and radio emission are coupled in such Galactic sources; the radio emission originates in a relativistic jet thought to be launched from the innermost regions near the black hole(4,5), with the most powerful emission occurring when the rate of infalling matter approaches a theoretical maximum (the Eddington limit). Only four such maximal sources are known in the Milky Way(6), and the absorption of soft X-rays in the interstellar medium hinders the determination of the causal sequence of events that leads to the ejection of the jet. Here we report radio and X-ray observations of a bright new X-ray source in the nearby galaxy M 31, whose peak luminosity exceeded 10(39) erg s(-1). The radio luminosity is extremely high and shows variability on a timescale of tens of minutes, arguing that the source is highly compact and powered by accretion close to the Eddington limit onto a black hole of stellar mass. Continued radio and X-ray monitoring of such sources should reveal the causal relationship between the accretion flow and the powerful jet emission.
  •  
34.
  • Moller, Anders Pape, et al. (författare)
  • Clutch-size variation in Western Palaearctic secondary hole-nesting passerine birds in relation to nest box design
  • 2014
  • Ingår i: Methods in Ecology and Evolution. - 2041-210X. ; 5:4, s. 353-362
  • Tidskriftsartikel (refereegranskat)abstract
    • Secondary hole-nesting birds that do not construct nest holes themselves and hence regularly breed in nest boxes constitute important model systems for field studies in many biological disciplines with hundreds of scientists and amateurs involved. Those research groups are spread over wide geographic areas that experience considerable variation in environmental conditions, and researchers provide nest boxes of varying designs that may inadvertently introduce spatial and temporal variation in reproductive parameters. We quantified the relationship between mean clutch size and nest box size and material after controlling for a range of environmental variables in four of the most widely used model species in the Western Palaearctic: great tit Parus major, blue tit Cyanistes caeruleus, pied flycatcher Ficedula hypoleuca and collared flycatcher F.albicollis from 365 populations and 79610 clutches. Nest floor area and nest box material varied non-randomly across latitudes and longitudes, showing that scientists did not adopt a random box design. Clutch size increased with nest floor area in great tits, but not in blue tits and flycatchers. Clutch size of blue tits was larger in wooden than in concrete nest boxes. These findings demonstrate that the size of nest boxes and material used to construct nest boxes can differentially affect clutch size in different species. The findings also suggest that the nest box design may affect not only focal species, but also indirectly other species through the effects of nest box design on productivity and therefore potentially population density and hence interspecific competition.
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35.
  • Moller, Anders P., et al. (författare)
  • Variation in clutch size in relation to nest size in birds
  • 2014
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:18, s. 3583-3595
  • Tidskriftsartikel (refereegranskat)abstract
    • Nests are structures built to support and protect eggs and/or offspring from predators, parasites, and adverse weather conditions. Nests are mainly constructed prior to egg laying, meaning that parent birds must make decisions about nest site choice and nest building behavior before the start of egg-laying. Parent birds should be selected to choose nest sites and to build optimally sized nests, yet our current understanding of clutch size-nest size relationships is limited to small-scale studies performed over short time periods. Here, we quantified the relationship between clutch size and nest size, using an exhaustive database of 116 slope estimates based on 17,472 nests of 21 species of hole and non-hole-nesting birds. There was a significant, positive relationship between clutch size and the base area of the nest box or the nest, and this relationship did not differ significantly between open nesting and hole-nesting species. The slope of the relationship showed significant intraspecific and interspecific heterogeneity among four species of secondary hole-nesting species, but also among all 116 slope estimates. The estimated relationship between clutch size and nest box base area in study sites with more than a single size of nest box was not significantly different from the relationship using studies with only a single size of nest box. The slope of the relationship between clutch size and nest base area in different species of birds was significantly negatively related to minimum base area, and less so to maximum base area in a given study. These findings are consistent with the hypothesis that bird species have a general reaction norm reflecting the relationship between nest size and clutch size. Further, they suggest that scientists may influence the clutch size decisions of hole-nesting birds through the provisioning of nest boxes of varying sizes.
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36.
  • Mulder, Eric, et al. (författare)
  • Case Studies in Physiology : Is blackout in breath-hold diving related to cardiac arrhythmias?
  • 2023
  • Ingår i: Journal of applied physiology. - : American Physiological Society. - 8750-7587 .- 1522-1601. ; 134:4, s. 951-956
  • Tidskriftsartikel (refereegranskat)abstract
    • Syncope or "blackout" (BO) in breath-hold diving (freediving) is generally considered to be caused by hypoxia. However, it has been suggested that cardiac arrhythmias affecting the pumping effectivity could contribute to BO. BO is fairly common in competitive freediving, where athletes aim for maximal performance. We recorded heart rate (HR) during a static apnea (STA) competition, to reveal if arrhythmias occur. Four male freedivers with STA personal best (PB) of 349 ± 43 s, volunteered during national championships, where they performed STA floating face down in a shallow indoor pool. A non-coded Polar T31 chest strap recorded R-R intervals and a water- and pressure-proof pulse oximeter arterial oxygen saturation. Three divers produced STA near their PB without problems, whereas one diver ended with BO at 5 min 17s, which was 12 s beyond his PB. He was immediately brought up by safety divers and resumed breathing within 10 s. All divers attained similar lowest diving HR (47 ± 4 beats/min), but HR recordings displayed a different pattern for the diver ending with BO. After a short tachycardia, the three successful divers developed bradycardia, which became more pronounced during the second half of the apnea. The fourth diver developed pronounced bradycardia earlier, and at 2.5 min into the apnea, HR started alternating between approximately 50 and 140 beats/min, until the diver lost consciousness. At resumed breathing, HR returned to baseline. Nadir oxygen saturation was similar for all divers. We speculate that arrhythmia could have contributed to BO, by lowering stroke volume leading to a systolic blood pressure drop, affecting brain perfusion.NEW & NOTEWORTHY Heart rate during prolonged breath-holding until the point of loss of consciousness has not previously been published. The recordings show that blackout was preceded by a period of persistent alterations in R-R intervals, whereby an ectopic beat followed every normal heartbeat. Explanations for this deviating heart rate pattern could be either premature atrial contractions or premature ventricular contractions following every atrial beat, i.e., bigeminy, which could have compromised cardiac pumping function and caused/contributed to blackout.
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37.
  • Myhre, Peder L., et al. (författare)
  • Cardiac troponin T and NT-proBNP for detecting myocardial ischemia in suspected chronic coronary syndrome
  • 2022
  • Ingår i: International Journal of Cardiology. - : Elsevier Ireland Ltd. - 0167-5273 .- 1874-1754. ; 361, s. 14-17
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Elevated N-terminal pro-B-type natriuretic peptides (NT-proBNP) and cardiac troponin T (cTnT) are associated with poor outcome in patients with chronic coronary syndrome (CCS). The performance of these biomarkers in diagnosing ischemia, and their association with myocardial hypoperfusion and hypokinesis is unclear. Methods: Patients with suspected CCS (history of angina, estimated cardiovascular risk >15% or a positive stress test) were included in the prospective, multi-center DOPPLER-CIP study. Patients underwent Single Positron Emission Computed Tomography for assessment of ischemia and NT-proBNP and cTnT were measured in venous blood samples. Results: We included 430 patients (25% female) aged 64 +/- 8 years. Reversible hypoperfusion and hypokinesis were present in 139 (32%) and 89 (21%), respectively. Concentrations of NT-proBNP and cTnT correlated moderately (rho = 0.50, p < 0.001). NT-proBNP and cTnT concentrations (median [IQR]) were higher in patients with versus without reversible ischemia: 150 (73-294) versus 87 (44-192) ng/L and 10 (6-13) versus 7 (4-11) ng/L, respectively (p < 0.001 for both), and the associations persisted after adjusting for possible confounders. The C-statistics to discriminate ischemia ranged from 63%-73%, were comparable for cTnT and NT-proBNP, and higher for hypokinesis than hypoperfusion, and both were superior to exercise electrocardiography and stress echocardiography. Very low concentrations (<= 5 ng/L cTnT and <= 60 ng/L NT-proBNP) ruled out reversible hypokinesis with negative predictive value >90%. Conclusion: cTnT and NT-proBNP are associated with irreversible and reversible ischemia in patients with suspected CCS, particularly hypokinesis. The diagnostic performance was comparable between the biomarkers, and very low concentrations may reliably rule out ischemia.
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38.
  • Myhre, Peder L., et al. (författare)
  • Cardiac Troponin T Concentrations, Reversible Myocardial Ischemia, and Indices of Left Ventricular Remodeling in Patients with Suspected Stable Angina Pectoris: a DOPPLER-CIP Substudy
  • 2018
  • Ingår i: Clinical Chemistry. - : AMER ASSOC CLINICAL CHEMISTRY. - 0009-9147 .- 1530-8561. ; 64:9, s. 1370-1379
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cardiac troponin T concentrations measured with high-sensitivity assays (hs-cTnT) provide important prognostic information for patients with stable coronary artery disease (CAD). However, whether hsc-TnT concentrations mainly reflect left ventricular (LV) remodeling or recurrent myocardial ischemia in this population is not known. METHODS: We measured hs-cTnT concentrations in 619 subjects with suspected stable CAD in a prospectively designed multicenter study. We identified associations with indices of LV remodeling, as assessed by cardiac MRI and echocardiography, and evidence of myocardial ischemia diagnosed by single positron emission computed tomography. RESULTS: Median hs-cTnT concentration was 7.8 ng/L (interquartile range, 4.8 -11.6 ng/L), and 111 patients (18%) had hs-cTnT concentrations above the upper reference limit (amp;gt; 14 ng/L). Patients with hs-cTnT amp;gt; 14 ng/L had increased LV mass (144 +/- 40 g vs 116 +/- 34 g; P amp;lt; 0.001) and volume (179 +/- 80 mL vs 158 +/- 44 mL; P = 0.006), lower LV ejection fraction (LVEF) (59 +/- 14 vs 62 +/- 11; P = 0.006) and global longitudinal strain (14.1 +/- 3.4% vs 16.9 +/- 3.2%; P amp;lt; 0.001), and more reversible perfusion defects (P amp;lt; 0.001) and reversible wall motion abnormalities (P = 0.008). Age (P = 0.009), estimated glomerular filtration rate (P = 0.01), LV mass (P = 0.003), LVEF (P = 0.03), and evidence of reversible myocardial ischemia (P = 0.004 for perfusion defects and P = 0.02 for LV wall motion) were all associated with increasing hs-cTnT concentrations in multivariate analysis. We found analogous results when using the revised US upper reference limit of 19 ng/L. CONCLUSIONS: hs-cTnT concentrations reflect both LV mass and reversible myocardial ischemia in patients with suspected stable CAD. (c) 2018 American Association for Clinical Chemistry
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39.
  • Negm, N., et al. (författare)
  • Graphene waveguide-integrated thermal infrared emitter
  • 2022
  • Ingår i: Device Research Conference - Conference Digest, DRC. - : Institute of Electrical and Electronics Engineers (IEEE).
  • Konferensbidrag (refereegranskat)abstract
    • Low-cost and easily integrable mid-infrared (MIR) sources are highly desired for photonic integrated circuits. Thermal incandescent MIR sources are widely used. They work by Joule heating, i.e. an electrical current through the emitter causes thermal emission according to Planck's law. Their simple design with only two contact pads makes them integrable with typical optoelectronic components in high-volume production flows. Graphene's emissivity is comparable to common metallic emitters. In contrast to the latter, graphene is transparent at MIR wavelengths, which enables placing large area graphene emitters in the evanescent field of integrated waveguides [1]-[2]. This enhances emission by near-field coupling directly into the waveguide mode, avoiding the mode-mismatch to free space. Here, we present the first experimental demonstration of a graphene emitter placed directly on a photonic waveguide, hence emitting directly into the waveguide mode. 
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40.
  • Nicholson, Andrew G., et al. (författare)
  • Interobserver Variation among Pathologists and Refinement of Criteria in Distinguishing Separate Primary Tumors from Intrapulmonary Metastases in Lung
  • 2018
  • Ingår i: Journal of Thoracic Oncology. - : ELSEVIER SCIENCE INC. - 1556-0864 .- 1556-1380. ; 13:2, s. 205-217
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple tumor nodules are seen with increasing frequency in clinical practice. On the basis of the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment to distinguish second primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs), looking for the most distinctive histologic features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients and recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM, or a combination thereof. Cohen kappa statistics of 0.60 on overall assessment of SPLC or IPM indicated a good agreement. Likewise, there was good agreement (kappa score 0.64, p < 0.0001) between WHO histologic pattern in individual cases and SPLC or IPM status, but the proportions diversified for histologic pattern and SPLC or IPM status (McNemar test, p < 0.0001). The strongest associations for distinguishing between SPLC and IPM were observed for nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intraalveolar clusters, and necrosis. Conversely, the associations for lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization, and emperipolesis did not reach significance with tumor extent. Comprehensive histologic assessment is recommended for distinguishing SPLC from IPM with good reproducibility among lung pathologists. In addition to main histologic type and predominant patterns of histologic subtypes, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate strongly correlate with pathologic staging status.
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41.
  • Nordström, Göran, et al. (författare)
  • Stability of successful long-term adjustment in alcohol dependence: a follow-up study 15 years after the first long-term follow-up.
  • 2004
  • Ingår i: European Addiction Research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 10:3, s. 126-132
  • Tidskriftsartikel (refereegranskat)abstract
    • From a large consecutive sample (n = 1,312) of hospital-treated alcoholics with multiaxial ratings, 105 were chosen for personal examination two decades after the subjects’ first admission (1949–1969) for alcohol problems. To study patterns of successful adjustment, 70 were chosen on the basis of a good social adjustment (health insurance data) at follow-up, whereas the control subjects had been granted a disability pension. The first follow-up was carried through in 1982–1983. In 1998–1999, the same 105 subjects were studied concerning mortality rate and adjustment patterns. In the good social adjustment group, 33% had deceased as compared with 63% in the control group (p < 0.01). Twenty-three out of 44 surviving subjects accepted a personal interview. Favourable adjustment was generally reported as being stable over the follow-up period. Several subjects reported stable non-problem drinking and others a change between abstinent and non-abstinent adjustment patterns.
  •  
42.
  • Persson, Camilla, et al. (författare)
  • Site-selective regulation of platelet-derived growth factor beta receptor tyrosine phosphorylation by T-cell protein tyrosine phosphatase
  • 2004
  • Ingår i: Molecular and Cellular Biology. - 0270-7306 .- 1098-5549. ; 24:5, s. 2190-2201
  • Tidskriftsartikel (refereegranskat)abstract
    • The platelet-derived growth factor (PDGF) beta receptor mediates mitogenic and chemotactic signals. Like other tyrosine kinase receptors, the PDGF beta receptor is negatively regulated by protein tyrosine phosphatases (PTPs). To explore whether T-cell PTP (TC-PTP) negatively regulates the PDGF beta receptor, we compared PDGF beta receptor tyrosine phosphorylation in wild-type and TC-PTP knockout (ko) mouse embryos. PDGF beta receptors were hyperphosphorylated in TC-PTP ko embryos. Fivefold-higher ligand-induced receptor phosphorylation was observed in TC-PTP ko mouse embryo fibroblasts (MEFs) as well. Reexpression of TC-PTP partly abolished this difference. As determined with site-specific phosphotyrosine antibodies, the extent of hyperphosphorylation varied among different autophosphorylation sites. The phospholipase Cgamma1 binding site Y1021, previously implicated in chemotaxis, displayed the largest increase in phosphorylation. The increase in Y1021 phosphorylation was accompanied by increased phospholipase Cgamma1 activity and migratory hyperresponsiveness to PDGF. PDGF beta receptor tyrosine phosphorylation in PTP-1B ko MEFs but not in PTPepsilon ko MEFs was also higher than that in control cells. This increase occurred with a site distribution different from that seen after TC-PTP depletion. PDGF-induced migration was not increased in PTP-1B ko cells. In summary, our findings identify TC-PTP as a previously unrecognized negative regulator of PDGF beta receptor signaling and support the general notion that PTPs display site selectivity in their action on tyrosine kinase receptors.
  •  
43.
  • Przewoski, Barbara, et al. (författare)
  • Spin Exchange in Polarized Deuterium
  • 2003
  • Ingår i: Physical Review A: covering atomic, molecular, and optical physics and quantum information. - : American Physical Society. - 2469-9926 .- 2469-9934. ; 68:042705, s. 4-
  • Tidskriftsartikel (refereegranskat)abstract
    • We have measured the vector and tensor polarization of an atomic deuterium targte as a function of the target density. Th epolarized deuterium was produced in an atomic beam source and injected into a storage cell. For this experiment, the atomic beam sou
  •  
44.
  • Putaala, Jukka, et al. (författare)
  • Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design
  • 2017
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:2, s. 116-125
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
  •  
45.
  • Quadri, Marialuisa, et al. (författare)
  • LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies : a genome-wide linkage and sequencing study
  • 2018
  • Ingår i: The Lancet Neurology. - 1474-4422. ; 17:7, s. 597-608
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Methods: Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells. Findings: Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent—albeit limited—evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism. Interpretation: Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets. Funding: Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw—Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Läkarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands–Ligue Européene Contre la Maladie d'Alzheimer (LECMA).
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46.
  • Quellmalz, Arne, et al. (författare)
  • Influence of Humidity on Contact Resistance in Graphene Devices
  • 2018
  • Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 10:48, s. 41738-41746
  • Tidskriftsartikel (refereegranskat)abstract
    • The electrical contact resistance at metal–graphene interfaces can significantly degrade the properties of graphene devices and is currently hindering the full exploitation of graphene’s potential. Therefore, the influence of environmental factors, such as humidity, on the metal–graphene contact resistance is of interest for all graphene devices that operate without hermetic packaging. We experimentally studied the influence of humidity on bottom-contacted chemical-vapor-deposited (CVD) graphene–gold contacts, by extracting the contact resistance from transmission line model (TLM) test structures. Our results indicate that the contact resistance is not significantly affected by changes in relative humidity (RH). This behavior is in contrast to the measured humidity sensitivity  of graphene’s sheet resistance. In addition, we employ density functional theory (DFT) simulations to support our experimental observations. Our DFT simulation results demonstrate that the electronic structure of the graphene sheet on top of silica is much more sensitive to adsorbed water molecules than the charge density at the interface between gold and graphene. Thus, we predict no degradation of device performance by alterations in contact resistance when such contacts are exposed to humidity. This knowledge underlines that bottom-contacting of graphene is a viable approach for a variety of graphene devices and the back end of the line integration on top of conventional integrated circuits.
  •  
47.
  • Quellmalz, Arne (författare)
  • Integration of Two-Dimensional Materials for Electronics and Photonics
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Two-dimensional (2D) materials with a thickness on the atomic scale promise to continue the trend of increasing performance in electronics, photonics, and sensing. However, despite record-breaking demonstrations of individual devices, the commercial exploitation of 2D materials is still limited. This constraint is partly because of challenges in integration technologies for manufacturing devices.This thesis presents manufacturing methods of transferring and patterning 2D materials. On the device level, it investigates the influence of environmental factors on electrical contacts and material properties. Finally, it demonstrates the integration of photodetectors for integrated photonic circuits.The synthesis of 2D materials requires high process temperatures to obtain high material quality, which precludes the direct synthesis on top of device wafers. Thus, manufacturing requires a transfer of the 2D material from a dedicated growth substrate to the device wafer.This thesis introduces a universal method of transferring 2D materials by wafer bonding. The method targets the integration on top of electronic circuits at the back-end of the line in semiconductor foundries. A variation of the approach suspends free-hanging membranes of 2D materials and stacks layers to 2D material heterostructures. The patterning of 2D materials is a fundamental step in device fabrication. However, standard lithographic methods cause residues of protective resists that degrade the device performance. This thesis presents a non-contact and resist-free method of patterning 2D materials with nanoscale precision by laser direct writing with an off-the-shelf system.The electrical contact resistance between metal electrodes and 2D materials significantly affects the performance of devices. This thesis investigates the influence of humidity on the contact resistance and sheet resistance of graphene. This insight is essential for operation in ambient environments without encapsulation or hermetic packaging.Multilayered platinum diselenide (PtSe2) is a semimetallic 2D material that can be synthesized below 450 degree Celsius. This thesis demonstrates the integration of PtSe2 photodetectors with silicon waveguides by direct growth on the device substrate. The photodetectors operate at infrared wavelength, which is promising for integrated photonic circuits.
  •  
48.
  • Quellmalz, Arne, et al. (författare)
  • Large-area integration of two-dimensional materials and their heterostructures by wafer bonding
  • 2021
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrating two-dimensional (2D) materials into semiconductor manufacturing lines is essential to exploit their material properties in a wide range of application areas. However, current approaches are not compatible with high-volume manufacturing on wafer level. Here, we report a generic methodology for large-area integration of 2D materials by adhesive wafer bonding. Our approach avoids manual handling and uses equipment, processes, and materials that are readily available in large-scale semiconductor manufacturing lines. We demonstrate the transfer of CVD graphene from copper foils (100-mm diameter) and molybdenum disulfide (MoS2) from SiO2/Si chips (centimeter-sized) to silicon wafers (100-mm diameter). Furthermore, we stack graphene with CVD hexagonal boron nitride and MoS2 layers to heterostructures, and fabricate encapsulated field-effect graphene devices, with high carrier mobilities of up to 4520 cm2V-1s-1. Thus, our approach is suited for backend of the line integration of 2D materials on top of integrated circuits, with potential to accelerate progress in electronics, photonics, and sensing. The existing integration approaches for 2D materials often degrade material properties and are not compatible with industrial processing. Here, the authors devise an adhesive wafer bonding strategy to transfer and stack monolayers, suitable for back end of the line integration of 2D materials.
  •  
49.
  • Quellmalz, Arne, et al. (författare)
  • Large-Area Integration of Two-Dimensional Materials and Their Heterostructures Using Wafer Bonding
  • 2021
  • Ingår i: Nature Communications. - 2041-1723. ; 12, s. 917-
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrating two-dimensional (2D) materials into semiconductor manufacturing lines is essential to exploit their material properties in a wide range of application areas. However, current approaches are not compatible with high-volume manufacturing on wafer level. Here, we report a generic methodology for large-area integration of 2D materials by adhesive wafer bonding. Our approach avoids manual handling and uses equipment, processes, and materials that are readily available in large-scale semiconductor manufacturing lines. We demonstrate the transfer of CVD graphene from copper foils (100-mm diameter) and molybdenum disulfide (MoS2) from SiO2/Si chips (centimeter-sized) to silicon wafers (100-mm diameter). Furthermore, we stack graphene with CVD hexagonal boron nitride and MoS2 layers to heterostructures, and fabricate encapsulated field-effect graphene devices, with high carrier mobilities of up to 4520cm2V−1s−14520cm2V−1s−1. Thus, our approach is suited for backend of the line integration of 2D materials on top of integrated circuits, with potential to accelerate progress in electronics, photonics, and sensing.
  •  
50.
  • Quellmalz, Arne, et al. (författare)
  • Large-scale Integration of 2D Material Heterostructures by Adhesive Bonding
  • 2020
  • Ingår i: 2020 IEEE 33rd International Conference on Micro Electro Mechanical Systems.
  • Konferensbidrag (refereegranskat)abstract
    • We report the integration of graphene/hexagonal boron nitride (hBN) heterostructure devices on large-areas by adhesive wafer bonding, a method suitable for industrial mass-production. In this new approach, we stack graphene and hBN by two consecutive bond transfers whereby the graphene and its interface to hBN is not in contact with potentially contaminating polymers or adhesives at any time. To show the feasibility of our approach for back end of the line (BEOL) integration of two-dimensional (2D) material heterostructures on standard silicon substrates, we fabricated graphene/hBN devices with electrical bottom contacts using only established semiconductor manufacturing tools, processes and materials.
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