| 1. |
- Repetto, Linda, et al.
(författare)
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Genetic mechanisms of 184 neuro-related proteins in human plasma.
- 2023
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.
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| 2. |
- Repetto, Linda, et al.
(författare)
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Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders.
- 2023
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Ingår i: Nature Portfolio. - : Research Square Platform LLC.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.
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| 3. |
- Yang, Zhijian, et al.
(författare)
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Genetic Landscape of the ACE2 Coronavirus Receptor
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 30:SUPPL 1, s. 36-36
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Tidskriftsartikel (refereegranskat)abstract
- Background: SARS-CoV-2, the causal agent of COVID-19, enters human cells using the ACE2 (angiotensin-converting enzyme 2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart and respiratory and gastrointestinal tracts, playing important regulatory roles in the cardiovascular and other biological systems. However, the genetic basis of the ACE2 protein levels is not well understood.Methods: We have conducted the largest genome-wide association meta-analysis of plasma ACE2 levels in >28 000 individuals of the SCALLOP Consortium (Systematic and Combined Analysis of Olink Proteins). We summarize the cross-sectional epidemiological correlates of circulating ACE2. Using the summary statistics-based high-definition likelihood method, we estimate relevant genetic correlations with cardiometabolic phenotypes, COVID-19, and other human complex traits and diseases. We perform causal inference of soluble ACE2 on vascular disease outcomes and COVID-19 severity using mendelian randomization. We also perform in silico functional analysis by integrating with other types of omics data.Results: We identified 10 loci, including 8 novel, capturing 30% of the heritability of the protein. We detected that plasma ACE2 was genetically correlated with vascular diseases, severe COVID-19, and a wide range of human complex diseases and medications. An X-chromosome cis-protein quantitative trait loci-based mendelian randomization analysis suggested a causal effect of elevated ACE2 levels on COVID-19 severity (odds ratio, 1.63 [95% CI, 1.10-2.42]; P=0.01), hospitalization (odds ratio, 1.52 [95% CI, 1.05-2.21]; P=0.03), and infection (odds ratio, 1.60 [95% CI, 1.08-2.37]; P=0.02). Tissue- and cell type-specific transcriptomic and epigenomic analysis revealed that the ACE2 regulatory variants were enriched for DNA methylation sites in blood immune cells.Conclusions: Human plasma ACE2 shares a genetic basis with cardiovascular disease, COVID-19, and other related diseases. The genetic architecture of the ACE2 protein is mapped, providing a useful resource for further biological and clinical studies on this coronavirus receptor.
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| 4. |
- Abram, Emese, et al.
(författare)
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Spectrophotometric examination of the optical effects of monolithic multilayered zirconia with different substrates
- 2020
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Ingår i: Advances in Applied Ceramics. - : Informa UK Limited. - 1743-6753 .- 1743-6761. ; 119:5-6, s. 261-266
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Tidskriftsartikel (refereegranskat)abstract
- The goal of this study is to examine specific optical effects of multilayered and coloured monolithic zirconia considering thickness and substrates of different colours using one of the most advanced spectrophotometers of the world. Multilayered zirconia specimens were used for the study with the thickness range of 0.5-2.5 mm and six types of substrate materials and three types of metal substrates. Measurements were carried out at Budapest Technical University with a PerkinElmer (R) Lambda1050UV/Vis/NIR spectrophotometer. The substrate colour and the thickness of zirconia affects the optical results, with special regard to colour perceptibility and acceptability. Monochromatic and multilayer zirconia show both similarities and discrepancies in behaviour, i.e. spectral reflectance and Delta E. Owing to the multi-coloured characteristics of multilayered zirconia the optical effect of the substrate less predictable than in the case of monochromatic zirconia thus requiring more detailed planning and implementation.
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| 5. |
- Abram, Emese, et al.
(författare)
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The colour of monolithic zirconia restorations determined by spectrophotometric examination
- 2019
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Ingår i: Advances in Applied Ceramics. - : Informa UK Limited. - 1743-6753 .- 1743-6761. ; 118:1-2, s. 3-8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this in vitro study is to examine the optical effects of monolithic zirconia of different translucency and thickness, combined with substrates of different colours. Materials and methods: Zirconia specimens of two colours (A2P1, WHITE) were used for the study, three try-in pastes (Variolink Esthetic); substrates were prepared from nine types of materials (six VITA SIMULATE, three metals). Measurements were carried out at the Faculty of Atomic Physics of the Technical University of Budapest with the state-of-the-art PerkinElmer (R) Lambda 1050 spectrophotometer. Results: The colouring of zirconia has a major effect on dE values resulting in different colour perceptibility and acceptability. Try-in pastes, however, have no significant effects overall. Conclusion: Applying coloured zirconia is highly eligible for preparing aesthetic crowns as their substrate-covering effect makes it possible to reproduce the desired colour. Uncoloured zirconia nonetheless is unaffected by the substrate material, especially above a certain layer thickness.
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| 6. |
- Adolfsson, Erik, et al.
(författare)
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Defect Minimization in Prosthetic Ceramics
- 2014
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Ingår i: Advanced Ceramics for Dentistry. - : Elsevier Inc.. - 9780123946195 ; , s. 359-373
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Bokkapitel (refereegranskat)abstract
- The mechanical reliability and aesthetic appearance of ceramic dental prostheses are strongly influenced by the presence of defects. When several processes are used during fabrication of ceramic dental prostheses, additional defects are unavoidably introduced in each process step; these are in addition to the ones that already exist in raw materials. To avoid the degeneration of material performance by the accumulated defect population, process optimization is needed to minimize the defects introduced. Standardized mechanical evaluations are usually performed on samples with carefully prepared surfaces in order to minimize the influence from the defects usually induced by fabrication processes. The results from such mechanical evaluation indicate the strength level that is achievable by the material with the given population of bulk defects. In order to avoid a reduction in the performance of the ceramic material by the additional defects normally induced by the fabrication process, it must be understood how these defects are introduced, and solutions must be found to reduce their size and frequency through modifications of the material and processes. The aim of this chapter is to elucidate the sources of defects that are common for ceramic dental prostheses and to determine how to minimize them.
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| 7. |
- Ahmed, Shafique, et al.
(författare)
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Terahertz probing of low-temperature degradation in zirconia bioceramics
- 2022
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Ingår i: Journal of The American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 105:2, s. 1106-1115
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Tidskriftsartikel (refereegranskat)abstract
- ZrO2-based ceramics are widely used in biomedical applications due to its color, biocompatibility, and excellent mechanical properties. However, low-temperature degradation (LTD) introduces a potential risk for long-term reliability of these materials. The development of innovative nondestructive techniques, which can explore LTD in zirconia-derived compounds, is strongly required. Yttria stabilized zirconia, 3Y-TZP, is one of the well-developed ZrO2-based ceramics with improved resistance to LTD for dental crown and implant applications. Here, 3Y-TZP ceramic powders were pressed and sintered to study the LTD phenomenon by phase transition behavior. The LTD-driven tetragonal-to-monoclinic phase transition was confirmed by XRD. XPS analysis demonstrated that induced LTD reduced the oxygen vacancies which supports these findings. It is proved that after the degradation, the 3Y-TZP ceramics show the decreased dielectric permittivity at terahertz frequencies due to the crystallographic phase transformation. Terahertz nondestructive probe is a promising method to investigate LTD in zirconia ceramics.
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| 8. |
- Chaim, R., et al.
(författare)
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Densification and preservation of ceramic nanocrystalline character by spark plasma sintering
- 2012
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Ingår i: Advances in Applied Ceramics. - 1743-6753 .- 1743-6761. ; 111:5-6, s. 280-285
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Tidskriftsartikel (refereegranskat)abstract
- Spark plasma sintering is a hot pressing technique where rapid heating by dc electric pulses is used simultaneously with applied pressure. Thus, spark plasma sintering is highly suitable for rapid densification of ceramic nanoparticles and preservation of the final nanostructure. A considerable portion of the shrinkage during densification of the green compact of nanoparticles in the first and intermediate stages of sintering occurs during heating by particle rearrangement by sliding and rotation. Further densification to the final stage of sintering takes place by either plastic yield or diffusional processes. Full densification in the final stage of sintering is associated with diffusional processes only. Nanoparticle sliding and rotation during heating may also lead to grain coalescence, with much faster kinetics than normal grain growth at higher temperatures. Based on existing models for particle rearrangement and sliding, the contributions of these processes in conjunction with nanoparticle properties and process parameters were highlighted.
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| 9. |
- Eriksson, Mirva, et al.
(författare)
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Spark plasma sintering of wc, cemented carbide and functional graded materials
- 2013
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Ingår i: International journal of refractory metals & hard materials. - : Elsevier BV. - 0263-4368. ; 36, s. 31-37
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Tidskriftsartikel (refereegranskat)abstract
- Spark plasma sintering (SPS) is an extremely fast solidification technique for compounds that are difficult to sinter within the material group's metals, ceramics, or composites thereof. SPS uses a uniaxial pressure and a very rapid heating cycle to consolidate these materials. The heating is generated by Joule effect when a strong, pulsed electric current passes the conductive graphite die and also through the sample, if conductive. Cemented carbides (hard metals) are mostly used for metal cutting and drilling, wood cutting or rock drilling tools and are consolidated either by pressureless sintering (PLS), hot pressing (HP), or hot isostatic pressing (HIP). With SPS the main benefit is the ability to control the WC grain size due to the short sintering times at high temperature. In addition, unwished reactions between WC and cobalt to form other phases are minimized. By SPS the amount of cobalt can be reduced towards zero in fully dense WC materials. With this technique it is easy to prepare gradient materials where a ductile weldable metal can be joined with the cemented carbide part.
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| 10. |
- Eriksson, Mirva, et al.
(författare)
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Transparent hydroxyapatite ceramics with nanograin structure prepared by high pressure spark plasma sintering at the minimized sintering temperature
- 2011
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Ingår i: Journal of the European Ceramic Society. - : Elsevier BV. - 0955-2219 .- 1873-619X. ; 31:9, s. 1533-1540
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Tidskriftsartikel (refereegranskat)abstract
- A hydrothermally processed bulky powder composed of loosely aggregated nano-sized rods was consolidated by spark plasma sintering. The use of a high pressure cell allows the application of pressure up to 500 MPa. It was found that applying of high pressure is beneficial for widening up the kinetic window for attaining dense HAp nanoceramics. The high transparency of HAp nanoceramics obtained in this study is ascribed to the high density and homogeneous nano-grained structure achieved besides the unique intrinsic optical properties of the HAp crystal itself, i.e. its low refractive index and very small birefringence. Achieving full densification at the minimized sintering temperature allows for the first time the preparation of transparent HAp nanoceramics with stoichiometric composition, i.e. avoiding the loss of structural water that commonly takes place during the conventional ways of sintering.
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